Safety Guided Design Based on Stamp/STPA for Manned Vehicle in Concept Design Phase

NASA Astrophysics Data System (ADS)

Ujiie, Ryo; Katahira, Masafumi; Miyamoto, Yuko; Umeda, Hiroki; Leveson, Nancy; Hoshino, Nobuyuki

2013-09-01

In manned vehicles, such as the Soyuz and the Space Shuttle, the crew and computer system cooperate to succeed in returning to the earth. While computers increase the functionality of system, they also increase the complexity of the interaction between the controllers (human and computer) and the target dynamics. In some cases, the complexity can produce a serious accident. To prevent such losses, traditional hazard analysis such as FTA has been applied to system development, however it can be used after creating a detailed system because it focuses on detailed component failures. As a result, it's more difficult to eliminate hazard cause early in the process when it is most feasible.STAMP/STPA is a new hazard analysis that can be applied from the early development phase, with the analysis being refined as more detailed decisions are made. In essence, the analysis and design decisions are intertwined and go hand-in-hand. We have applied STAMP/STPA to a concept design of a new JAXA manned vehicle and tried safety guided design of the vehicle. As a result of this trial, it has been shown that STAMP/STPA can be accepted easily by system engineers and the design has been made more sophisticated from a safety viewpoint. The result also shows that the consequences of human errors on system safety can be analysed in the early development phase and the system designed to prevent them. Finally, the paper will discuss an effective way to harmonize this safety guided design approach with system engineering process based on the result of this experience in this project.

Phase IV of Early Restoration | NOAA Gulf Spill Restoration

Science.gov Websites

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

Gene expression profiles of Vibrio parahaemolyticus in the early stationary phase.

PubMed

Meng, L; Alter, T; Aho, T; Huehn, S

2015-09-01

Vibrio (V.) parahaemolyticus is an aquatic bacterium capable of causing foodborne gastroenteritis. In the environment or the food chain, V. parahaemolyticus cells are usually forced into the stationary phase, the common phase for bacterial survival in the environment. So far, little is known about whole genomic expression of V. parahaemolyticus in the early stationary phase compared with the exponential growth phase. We performed whole transcriptomic profiling of V. parahaemolyticus cells in both phases (exponential and early stationary phase). Our data showed in total that 172 genes were induced in early stationary phase, while 61 genes were repressed in early stationary phase compared with the exponential phase. Three functional categories showed stable gene expression in the early stationary phase. Eleven functional categories showed that up-regulation of genes was dominant over down-regulation in the early stationary phase. Although genes related to endogenous metabolism were repressed in the early stationary phase, massive regulation of gene expression occurred in the early stationary phase, indicating the expressed gene set of V. parahaemolyticus in the early stationary phase impacts environmental survival. Vibrio (V.) parahaemolyticus is one of the main bacterial causes of foodborne intestinal infections. This bacterium usually is forced into stationary phase in the environment, which includes, e.g. seafood. When bacteria are in stationary phase, physiological changes can lead to a resistance to many stresses, including physical and chemical challenges during food processing. To the best of our knowledge, highlighting the whole genome expression changes in the early stationary phase compared with exponential phase, as well as the investigation of physiological changes of V. parahaemolyticus such as the survival mechanism in the stationary phase has been the very first study in this field. © 2015 The Society for Applied Microbiology.

Two-stage phase II oncology designs using short-term endpoints for early stopping.

PubMed

Kunz, Cornelia U; Wason, James Ms; Kieser, Meinhard

2017-08-01

Phase II oncology trials are conducted to evaluate whether the tumour activity of a new treatment is promising enough to warrant further investigation. The most commonly used approach in this context is a two-stage single-arm design with binary endpoint. As for all designs with interim analysis, its efficiency strongly depends on the relation between recruitment rate and follow-up time required to measure the patients' outcomes. Usually, recruitment is postponed after the sample size of the first stage is achieved up until the outcomes of all patients are available. This may lead to a considerable increase of the trial length and with it to a delay in the drug development process. We propose a design where an intermediate endpoint is used in the interim analysis to decide whether or not the study is continued with a second stage. Optimal and minimax versions of this design are derived. The characteristics of the proposed design in terms of type I error rate, power, maximum and expected sample size as well as trial duration are investigated. Guidance is given on how to select the most appropriate design. Application is illustrated by a phase II oncology trial in patients with advanced angiosarcoma, which motivated this research.

Evolutionary Design of a Phased Array Antenna Element

NASA Technical Reports Server (NTRS)

Globus, Al; Linden, Derek; Lohn, Jason

2006-01-01

We present an evolved S-band phased array antenna element design that meets the requirements of NASA's TDRS-C communications satellite scheduled for launch early next decade. The original specification called for two types of elements, one for receive only and one for transmit/receive. We were able to evolve a single element design that meets both specifications thereby simplifying the antenna and reducing testing and integration costs. The highest performance antenna found using a genetic algorithm and stochastic hill-climbing has been fabricated and tested. Laboratory results are largely consistent with simulation. Researchers have been investigating evolutionary antenna design and optimization since the early 1990s, and the field has grown in recent years its computer speed has increased and electromagnetic simulators have improved. Many antenna types have been investigated, including wire antennas, antenna arrays and quadrifilar helical antennas. In particular, our laboratory evolved a wire antenna design for NASA's Space Technology 5 (ST5) spacecraft. This antenna has been fabricated, tested, and is scheduled for launch on the three spacecraft in 2006.

Early phase clinical trials with human immunodeficiency virus-1 and malaria vectored vaccines in The Gambia: frontline challenges in study design and implementation.

PubMed

Afolabi, Muhammed O; Adetifa, Jane U; Imoukhuede, Egeruan B; Viebig, Nicola K; Kampmann, Beate; Bojang, Kalifa

2014-05-01

Human immunodeficiency virus/acquired immune deficiency syndrome (HIV/AIDS) and malaria are among the most important infectious diseases in developing countries. Existing control strategies are unlikely to curtail these diseases in the absence of efficacious vaccines. Testing of HIV and malaria vaccines candidates start with early phase trials that are increasingly being conducted in developing countries where the burden of the diseases is high. Unique challenges, which affect planning and implementation of vaccine trials according to internationally accepted standards have thus been identified. In this review, we highlight specific challenges encountered during two early phase trials of novel HIV-1 and malaria vectored vaccine candidates conducted in The Gambia and how some of these issues were pragmatically addressed. We hope our experience will be useful for key study personnel involved in day-to-day running of similar clinical trials. It may also guide future design and implementation of vaccine trials in resource-constrained settings.

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.

Maximizing Launch Vehicle and Payload Design Via Early Communications

NASA Technical Reports Server (NTRS)

Morris, Bruce

2010-01-01

The United States? current fleet of launch vehicles is largely derived from decades-old designs originally made for payloads that no longer exist. They were built primarily for national security or human exploration missions. Today that fleet can be divided roughly into small-, medium-, and large-payload classes based on mass and volume capability. But no vehicle in the U.S. fleet is designed to accommodate modern payloads. It is usually the payloads that must accommodate the capabilities of the launch vehicles. This is perhaps most true of science payloads. It was this paradigm that the organizers of two weekend workshops in 2008 at NASA's Ames Research Center sought to alter. The workshops brought together designers of NASA's Ares V cargo launch vehicle (CLV) with scientists and payload designers in the astronomy and planetary sciences communities. Ares V was still in a pre-concept development phase as part of NASA?s Constellation Program for exploration beyond low Earth orbit (LEO). The space science community was early in a Decadal Survey that would determine future priorities for research areas, observations, and notional missions to make those observations. The primary purpose of the meetings in April and August of 2008, including the novel format, was to bring vehicle designers together with space scientists to discuss the feasibility of using a heavy lift capability to launch large observatories and explore the Solar System. A key question put to the science community was whether this heavy lift capability enabled or enhanced breakthrough science. The meetings also raised the question of whether some trade-off between mass/volume and technical complexity existed that could reduce technical and programmatic risk. By engaging the scientific community early in the vehicle design process, vehicle engineers sought to better understand potential limitations and requirements that could be added to the Ares V from the mission planning community. From the vehicle

Accelerating clinical development of HIV vaccine strategies: methodological challenges and considerations in constructing an optimised multi-arm phase I/II trial design.

PubMed

Richert, Laura; Doussau, Adélaïde; Lelièvre, Jean-Daniel; Arnold, Vincent; Rieux, Véronique; Bouakane, Amel; Lévy, Yves; Chêne, Geneviève; Thiébaut, Rodolphe

2014-02-26

Many candidate vaccine strategies against human immunodeficiency virus (HIV) infection are under study, but their clinical development is lengthy and iterative. To accelerate HIV vaccine development optimised trial designs are needed. We propose a randomised multi-arm phase I/II design for early stage development of several vaccine strategies, aiming at rapidly discarding those that are unsafe or non-immunogenic. We explored early stage designs to evaluate both the safety and the immunogenicity of four heterologous prime-boost HIV vaccine strategies in parallel. One of the vaccines used as a prime and boost in the different strategies (vaccine 1) has yet to be tested in humans, thus requiring a phase I safety evaluation. However, its toxicity risk is considered minimal based on data from similar vaccines. We newly adapted a randomised phase II trial by integrating an early safety decision rule, emulating that of a phase I study. We evaluated the operating characteristics of the proposed design in simulation studies with either a fixed-sample frequentist or a continuous Bayesian safety decision rule and projected timelines for the trial. We propose a randomised four-arm phase I/II design with two independent binary endpoints for safety and immunogenicity. Immunogenicity evaluation at trial end is based on a single-stage Fleming design per arm, comparing the observed proportion of responders in an immunogenicity screening assay to an unacceptably low proportion, without direct comparisons between arms. Randomisation limits heterogeneity in volunteer characteristics between arms. To avoid exposure of additional participants to an unsafe vaccine during the vaccine boost phase, an early safety decision rule is imposed on the arm starting with vaccine 1 injections. In simulations of the design with either decision rule, the risks of erroneous conclusions were controlled <15%. Flexibility in trial conduct is greater with the continuous Bayesian rule. A 12-month gain in

Wide-field phase imaging for the endoscopic detection of dysplasia and early-stage esophageal cancer

NASA Astrophysics Data System (ADS)

Fitzpatrick, C. R. M.; Gordon, G. S. D.; Sawyer, T. W.; Wilkinson, T. D.; Bohndiek, S. E.

2018-02-01

Esophageal cancer has a 5-year survival rate below 20%, but can be curatively resected if it is detected early. At present, poor contrast for early lesions in white light imaging leads to a high miss rate in standard-of- care endoscopic surveillance. Early lesions in the esophagus, referred to as dysplasia, are characterized by an abundance of abnormal cells with enlarged nuclei. This tissue has a different refractive index profile to healthy tissue, which results in different light scattering properties and provides a source of endogenous contrast that can be exploited for advanced endoscopic imaging. For example, point measurements of such contrast can be made with scattering spectroscopy, while optical coherence tomography generates volumetric data. However, both require specialist interpretation for diagnostic decision making. We propose combining wide-field phase imaging with existing white light endoscopy in order to provide enhanced contrast for dysplasia and early-stage cancer in an image format that is familiar to endoscopists. Wide-field phase imaging in endoscopy can be achieved using coherent illumination combined with phase retrieval algorithms. Here, we present the design and simulation of a benchtop phase imaging system that is compatible with capsule endoscopy. We have undertaken preliminary optical modelling of the phase imaging setup, including aberration correction simulations and an investigation into distinguishing between different tissue phantom scattering coefficients. As our approach is based on phase retrieval rather than interferometry, it is feasible to realize a device with low-cost components for future clinical implementation.

Early Intervention Services for Early-Phase Psychosis - Centre for integrative psychiatry in Psychiatric Hospital "Sveti Ivan", Croatia.

PubMed

Matić, Katarina; Gereš, Natko; Gerlach, Josefina; Prskalo-Čule, Diana; Zadravec Vrbanc, Tihana; Lovretić, Vanja; Librenjak, Dina; Vuk Pisk, Sandra; Ivezić, Ena; Šimunović Filipčić, Ivona; Jeleč, Vjekoslav; Filipčić, Igor

2018-06-01

There is a growing body of evidence suggesting that early and effective management in the critical early years of schizophrenia can improve long-term outcomes. The objective of this study was to evaluate time to relapse of the patients with early-phase psychosis treated in the Centre for integrative psychiatry (CIP). We performed a retrospective cohort study on the sample of 373 early-phase psychosis patients admitted to Psychiatric Hospital "Sveti Ivan", Zagreb Croatia: from January 1, 2015 to December 31, 2017. The primary outcome was time to relapse. Patients who were admitted to group psychotherapeutic program after the end of acute treatment had 70% lower hazard for relapse (HR=0.30; 95% CI 0.16-0.58). Patients who were included first in the psychotherapeutic program and then treated and controlled in the daily hospital had 74% lower hazard for relapse (HR=0.26; 95% CI 0.10-0.67). In early-phase psychosis, integrative early intervention service has relevant beneficial effects compare to treatment as usual. These results justified the implementation of multimodal early intervention services in treatment of patients with early-phase psychosis.

A Bayesian-frequentist two-stage single-arm phase II clinical trial design.

PubMed

Dong, Gaohong; Shih, Weichung Joe; Moore, Dirk; Quan, Hui; Marcella, Stephen

2012-08-30

It is well-known that both frequentist and Bayesian clinical trial designs have their own advantages and disadvantages. To have better properties inherited from these two types of designs, we developed a Bayesian-frequentist two-stage single-arm phase II clinical trial design. This design allows both early acceptance and rejection of the null hypothesis ( H(0) ). The measures (for example probability of trial early termination, expected sample size, etc.) of the design properties under both frequentist and Bayesian settings are derived. Moreover, under the Bayesian setting, the upper and lower boundaries are determined with predictive probability of trial success outcome. Given a beta prior and a sample size for stage I, based on the marginal distribution of the responses at stage I, we derived Bayesian Type I and Type II error rates. By controlling both frequentist and Bayesian error rates, the Bayesian-frequentist two-stage design has special features compared with other two-stage designs. Copyright © 2012 John Wiley & Sons, Ltd.

Dispositional Optimism and Therapeutic Expectations in Early Phase Oncology Trials

PubMed Central

Jansen, Lynn A.; Mahadevan, Daruka; Appelbaum, Paul S.; Klein, William MP; Weinstein, Neil D.; Mori, Motomi; Daffé, Racky; Sulmasy, Daniel P.

2016-01-01

Purpose Prior research has identified unrealistic optimism as a bias that might impair informed consent among patient-subjects in early phase oncology trials. Optimism, however, is not a unitary construct – it can also be defined as a general disposition, or what is called dispositional optimism. We assessed whether dispositional optimism would be related to high expectations for personal therapeutic benefit reported by patient-subjects in these trials but not to the therapeutic misconception. We also assessed how dispositional optimism related to unrealistic optimism. Methods Patient-subjects completed questionnaires designed to measure expectations for therapeutic benefit, dispositional optimism, unrealistic optimism, and the therapeutic misconception. Results Dispositional optimism was significantly associated with higher expectations for personal therapeutic benefit (Spearman r=0.333, p<0.0001), but was not associated with the therapeutic misconception. (Spearman r=−0.075, p=0.329). Dispositional optimism was weakly associated with unrealistic optimism (Spearman r=0.215, p=0.005). In multivariate analysis, both dispositional optimism (p=0.02) and unrealistic optimism (p<0.0001) were independently associated with high expectations for personal therapeutic benefit. Unrealistic optimism (p=.0001), but not dispositional optimism, was independently associated with the therapeutic misconception. Conclusion High expectations for therapeutic benefit among patient-subjects in early phase oncology trials should not be assumed to result from misunderstanding of specific information about the trials. Our data reveal that these expectations are associated with either a dispositionally positive outlook on life or biased expectations about specific aspects of trial participation. Not all manifestations of optimism are the same, and different types of optimism likely have different consequences for informed consent in early phase oncology research. PMID:26882017

Three steps to writing adaptive study protocols in the early phase clinical development of new medicines

PubMed Central

2014-01-01

This article attempts to define terminology and to describe a process for writing adaptive, early phase study protocols which are transparent, self-intuitive and uniform. It provides a step by step guide, giving templates from projects which received regulatory authorisation and were successfully performed in the UK. During adaptive studies evolving data is used to modify the trial design and conduct within the protocol-defined remit. Adaptations within that remit are documented using non-substantial protocol amendments which do not require regulatory or ethical review. This concept is efficient in gathering relevant data in exploratory early phase studies, ethical and time- and cost-effective. PMID:24980283

Results from conceptual design study of potential early commercial MHD/steam power plants

NASA Technical Reports Server (NTRS)

Hals, F.; Kessler, R.; Swallom, D.; Westra, L.; Zar, J.; Morgan, W.; Bozzuto, C.

1981-01-01

This paper presents conceptual design information for a potential early MHD power plant developed in the second phase of a joint study of such plants. Conceptual designs of plant components and equipment with performance, operational characteristics and costs are reported on. Plant economics and overall performance including full and part load operation are reviewed. Environmental aspects and the methods incorporated in plant design for emission control of sulfur and nitrogen oxides are reviewed. Results from reliability/availability analysis conducted are also included.

Study design and early result of a phase I study of SABR for early-stage glottic cancer.

PubMed

Yu, Tosol; Wee, Chan Woo; Choi, Noorie; Wu, Hong-Gyun; Kang, Hyun-Cheol; Park, Jong Min; Kim, Jung-In; Kim, Jin Ho; Kwon, Tack-Kyun; Chung, Eun-Jae

2018-05-14

Avoidance of organs at risk has become possible with advances in image-guided volumetric-modulated arc therapy (VMAT) techniques. This study was designed to evaluate the safety and feasibility of stereotactic ablative radiotherapy (SABR) for early stage glottic cancer. This report presents the preliminary result of the first and second dose level. Fraction size was increased from 3.5 gray (Gy) (total dose 59.5 Gy) to 9 Gy (total dose 45 Gy). Dose-limiting toxicities were defined as grade 3 or higher treatment-related toxicities. Voice outcome was assessed with electroglottography, and quality of life (QoL) was measured with the Head and Neck Cancer Inventory (HNCI). Seven patients received 59.5 Gy at 3.5 Gy per fraction as the first dose level, and five patients received 55 Gy at 5 Gy per fraction as the second dose level. None of the patients developed grade 3+ toxicity throughout a median follow-up of 17.5 months (range, 1.7-30.6 months). One patient in the second dose level recurred in the primary site at 4 months after radiotherapy (RT) and received total laryngectomy. The rest of participants were disease-free at locoregional and distant sites. Jitter, shimmer, mean phonation time, and noise-to-harmony ratio did not change significantly at 6 months after RT. HNCI scores between pretreatment and posttreatment were not significantly different (P = 0.221). This study revealed acceptable toxicity, voice outcome, and QoL in patients treated with hypofractionated VMAT of 3.5 Gy and 5 Gy per fraction. This phase I study is currently ongoing with a dose of 55 Gy in 11 fractions and 45 Gy in five fractions. 2b. Laryngoscope, 2018. © 2018 The American Laryngological, Rhinological and Otological Society, Inc.

Phase III Early Restoration Meeting | NOAA Gulf Spill Restoration

Science.gov Websites

Louisiana Mississippi Texas Region-wide Open Ocean Data Media & News Publications Press Releases Story programmatic approach to early restoration planning for Phase III and future early restoration plans. Open

Phase III Early Restoration Meeting - Pensacola, FL (rescheduled) | NOAA

Science.gov Websites

Restoration Areas Alabama Florida Louisiana Mississippi Texas Region-wide Open Ocean Data Media & News programmatic approach to early restoration planning for Phase III and future early restoration plans. Open

Use of Probabilistic Engineering Methods in the Detailed Design and Development Phases of the NASA Ares Launch Vehicle

NASA Technical Reports Server (NTRS)

Fayssal, Safie; Weldon, Danny

2008-01-01

The United States National Aeronautics and Space Administration (NASA) is in the midst of a space exploration program called Constellation to send crew and cargo to the international Space Station, to the moon, and beyond. As part of the Constellation program, a new launch vehicle, Ares I, is being developed by NASA Marshall Space Flight Center. Designing a launch vehicle with high reliability and increased safety requires a significant effort in understanding design variability and design uncertainty at the various levels of the design (system, element, subsystem, component, etc.) and throughout the various design phases (conceptual, preliminary design, etc.). In a previous paper [1] we discussed a probabilistic functional failure analysis approach intended mainly to support system requirements definition, system design, and element design during the early design phases. This paper provides an overview of the application of probabilistic engineering methods to support the detailed subsystem/component design and development as part of the "Design for Reliability and Safety" approach for the new Ares I Launch Vehicle. Specifically, the paper discusses probabilistic engineering design analysis cases that had major impact on the design and manufacturing of the Space Shuttle hardware. The cases represent important lessons learned from the Space Shuttle Program and clearly demonstrate the significance of probabilistic engineering analysis in better understanding design deficiencies and identifying potential design improvement for Ares I. The paper also discusses the probabilistic functional failure analysis approach applied during the early design phases of Ares I and the forward plans for probabilistic design analysis in the detailed design and development phases.

Dispositional optimism and therapeutic expectations in early-phase oncology trials.

PubMed

Jansen, Lynn A; Mahadevan, Daruka; Appelbaum, Paul S; Klein, William M P; Weinstein, Neil D; Mori, Motomi; Daffé, Racky; Sulmasy, Daniel P

2016-04-15

Prior research has identified unrealistic optimism as a bias that might impair informed consent among patient-subjects in early-phase oncology trials. However, optimism is not a unitary construct; it also can be defined as a general disposition, or what is called dispositional optimism. The authors assessed whether dispositional optimism would be related to high expectations for personal therapeutic benefit reported by patient-subjects in these trials but not to the therapeutic misconception. The authors also assessed how dispositional optimism related to unrealistic optimism. Patient-subjects completed questionnaires designed to measure expectations for therapeutic benefit, dispositional optimism, unrealistic optimism, and the therapeutic misconception. Dispositional optimism was found to be significantly associated with higher expectations for personal therapeutic benefit (Spearman rank correlation coefficient [r], 0.333; P<.0001), but was not associated with the therapeutic misconception (Spearman r, -0.075; P = .329). Dispositional optimism was found to be weakly associated with unrealistic optimism (Spearman r, 0.215; P = .005). On multivariate analysis, both dispositional optimism (P = .02) and unrealistic optimism (P<.0001) were found to be independently associated with high expectations for personal therapeutic benefit. Unrealistic optimism (P = .0001), but not dispositional optimism, was found to be independently associated with the therapeutic misconception. High expectations for therapeutic benefit among patient-subjects in early-phase oncology trials should not be assumed to result from misunderstanding of specific information regarding the trials. The data from the current study indicate that these expectations are associated with either a dispositionally positive outlook on life or biased expectations concerning specific aspects of trial participation. Not all manifestations of optimism are the same, and different types of optimism likely have

Metacognition in Early Phase Psychosis: Toward Understanding Neural Substrates

PubMed Central

Vohs, Jenifer L.; Hummer, Tom A.; Yung, Matthew G.; Francis, Michael M.; Lysaker, Paul H.; Breier, Alan

2015-01-01

Individuals in the early phases of psychotic illness have disturbed metacognitive capacity, which has been linked to a number of poor outcomes. Little is known, however, about the neural systems associated with metacognition in this population. The purpose of this study was to elucidate the neuroanatomical correlates of metacognition. We anticipated that higher levels of metacognition may be dependent upon gray matter density (GMD) of regions within the prefrontal cortex. Examining whole-brain structure in 25 individuals with early phase psychosis, we found positive correlations between increased medial prefrontal cortex and ventral striatum GMD and higher metacognition. These findings represent an important step in understanding the path through which the biological correlates of psychotic illness may culminate into poor metacognition and, ultimately, disrupted functioning. Such a path will serve to validate and promote metacognition as a viable treatment target in early phase psychosis. PMID:26132568

Early Phase Contingency Trajectory Design for the Failure of the First Lunar Orbit Insertion Maneuver: Direct Recovery Options

NASA Astrophysics Data System (ADS)

Song, Young-Joo; Bae, Jonghee; Kim, Young-Rok; Kim, Bang-Yeop

2017-12-01

To ensure the successful launch of the Korea pathfinder lunar orbiter (KPLO) mission, the Korea Aerospace Research Institute (KARI) is now performing extensive trajectory design and analysis studies. From the trajectory design perspective, it is crucial to prepare contingency trajectory options for the failure of the first lunar brake or the failure of the first lunar orbit insertion (LOI) maneuver. As part of the early phase trajectory design and analysis activities, the required time of flight (TOF) and associated delta-V magnitudes for each recovery maneuver (RM) to recover the KPLO mission trajectory are analyzed. There are two typical trajectory recovery options, direct recovery and low energy recovery. The current work is focused on the direct recovery option. Results indicate that a quicker execution of the first RM after the failure of the first LOI plays a significant role in saving the magnitudes of the RMs. Under the conditions of the extremely tight delta-V budget that is currently allocated for the KPLO mission, it is found that the recovery of the KPLO without altering the originally planned mission orbit (a 100 km circular orbit) cannot be achieved via direct recovery options. However, feasible recovery options are suggested within the boundaries of the currently planned delta-V budget. By changing the shape and orientation of the recovered final mission orbit, it is expected that the KPLO mission may partially pursue its scientific mission after successful recovery, though it will be limited.

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.

Design of an ammonia two-phase Prototype Thermal Bus for Space Station

NASA Technical Reports Server (NTRS)

Brown, Richard F.; Gustafson, Eric; Parish, Richard

1987-01-01

The feasibility of two-phase heat transport systems for use on Space Station was demonstrated by testing the Thermal Bus Technology Demonstrator (TBTD) as part of the Integrated Two-Phase System Test in NASA-JSC's Thermal Test Bed. Under contract to NASA-JSC, Grumman is currently developing the successor to the TBTD, the Prototype Thermal Bus System (TBS). The TBS design, which uses ammonia as the working fluid, is intended to achieve a higher fidelity level than the TBTD by incorporating both improvements based on TBTD testing and realistic design margins, and by addressing Space Station issues such as redundancy and maintenance. The TBS is currently being fabricated, with testing scheduled for late 1987/early 1988. This paper describes the TBS design which features fully redundant plumbing loops, five evaporators designed to represent different heat acquisition interfaces, 14 condensers which mate with either space radiators or facility heat exchangers, and several modular components.

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.

Graphical method to design multilayer phase retarders.

PubMed

Apfel, J H

1981-03-15

When multilayer reflectors are used at nonnormal incidence, the two planes of polarization generally have different phase shifts. This difference, known as phase retardance, depends on the multilayer design, the incidence angle, and the wavelength. Heretofore, the design of reflectors with specific phase retardance has been carried out by computer optimization except for the case of a single layer on a metal substrate. A graph of phase retardance D vs the average phase shift A as a function of layer thickness provides a means for visualization that is useful in reflector designs. A D-A graph predicts the phase properties of a reflector as a function of the index and thickness of an added layer. Graphs of phase retardance vs average phase for two different materials can be superposed to predict the composite performance of a multilayer reflector. This graphical technique is employed to design and analyze reflectors with specified phase retardance.

Fluctuation-driven electroweak phase transition. [in early universe

NASA Technical Reports Server (NTRS)

Gleiser, Marcelo; Kolb, Edward W.

1992-01-01

We examine the dynamics of the electroweak phase transition in the early Universe. For Higgs masses in the range 46 less than or = M sub H less than or = 150 GeV and top quark masses less than 200 GeV, regions of symmetric and asymmetric vacuum coexist to below the critical temperature, with thermal equilibrium between the two phases maintained by fluctuations of both phases. We propose that the transition to the asymmetric vacuum is completed by percolation of these subcritical fluctuations. Our results are relevant to scenarios of baryogenesis that invoke a weakly first-order phase transition at the electroweak scale.

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

PubMed Central

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

2016-01-01

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 (CAPs) received for slow-accruing Phase 1 and 2 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 1 trials and 66 for Phase 2 trials. Primary reasons cited for slow accrual were safety/toxicity (Phase 1: 48%), design/protocol concerns (Phase 1: 42%, Phase 2: 33%), and eligibility criteria (Phase 1: 41%, Phase 2: 35%). The most commonly proposed corrective actions were adding institutions (Phase 1: 43%, Phase 2: 85%) and amending the trial to change eligibility or design (Phase 1: 55%, Phase 2: 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 1=48; Phase 2=46). Of these, 67% of Phase 1 and 70% of Phase 2 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 lifecycles, but it may be more beneficial to invest in earlier accrual planning. PMID:27401246

Optimum design of hybrid phase locked loops

NASA Technical Reports Server (NTRS)

Lee, P.; Yan, T.

1981-01-01

The design procedure of phase locked loops is described in which the analog loop filter is replaced by a digital computer. Specific design curves are given for the step and ramp input changes in phase. It is shown that the designed digital filter depends explicitly on the product of the sampling time and the noise bandwidth of the phase locked loop. This technique of optimization can be applied to the design of digital analog loops for other applications.

Conceptual Design of Simulation Models in an Early Development Phase of Lunar Spacecraft Simulator Using SMP2 Standard

NASA Astrophysics Data System (ADS)

Lee, Hoon Hee; Koo, Cheol Hea; Moon, Sung Tae; Han, Sang Hyuck; Ju, Gwang Hyeok

2013-08-01

The conceptual study for Korean lunar orbiter/lander prototype has been performed in Korea Aerospace Research Institute (KARI). Across diverse space programs around European countries, a variety of simulation application has been developed using SMP2 (Simulation Modelling Platform) standard related to portability and reuse of simulation models by various model users. KARI has not only first-hand experience of a development of SMP compatible simulation environment but also an ongoing study to apply the SMP2 development process of simulation model to a simulator development project for lunar missions. KARI has tried to extend the coverage of the development domain based on SMP2 standard across the whole simulation model life-cycle from software design to its validation through a lunar exploration project. Figure. 1 shows a snapshot from a visualization tool for the simulation of lunar lander motion. In reality, a demonstrator prototype on the right-hand side of image was made and tested in 2012. In an early phase of simulator development prior to a kick-off start in the near future, targeted hardware to be modelled has been investigated and indentified at the end of 2012. The architectural breakdown of the lunar simulator at system level was performed and the architecture with a hierarchical tree of models from the system to parts at lower level has been established. Finally, SMP Documents such as Catalogue, Assembly, Schedule and so on were converted using a XML(eXtensible Mark-up Language) converter. To obtain benefits of the suggested approaches and design mechanisms in SMP2 standard as far as possible, the object-oriented and component-based design concepts were strictly chosen throughout a whole model development process.

Practical characteristics of adaptive design in phase 2 and 3 clinical trials.

PubMed

Sato, A; Shimura, M; Gosho, M

2018-04-01

Adaptive design methods are expected to be ethical, reflect real medical practice, increase the likelihood of research and development success and reduce the allocation of patients into ineffective treatment groups by the early termination of clinical trials. However, the comprehensive details regarding which types of clinical trials will include adaptive designs remain unclear. We examined the practical characteristics of adaptive design used in clinical trials. We conducted a literature search of adaptive design clinical trials published from 2012 to 2015 using PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials, with common search terms related to adaptive design. We systematically assessed the types and characteristics of adaptive designs and disease areas employed in the adaptive design trials. Our survey identified 245 adaptive design clinical trials. The number of trials by the publication year increased from 2012 to 2013 and did not greatly change afterwards. The most frequently used adaptive design was group sequential design (n = 222, 90.6%), especially for neoplasm or cardiovascular disease trials. Among the other types of adaptive design, adaptive dose/treatment group selection (n = 21, 8.6%) and adaptive sample-size adjustment (n = 19, 7.8%) were frequently used. The adaptive randomization (n = 8, 3.3%) and adaptive seamless design (n = 6, 2.4%) were less frequent. Adaptive dose/treatment group selection and adaptive sample-size adjustment were frequently used (up to 23%) in "certain infectious and parasitic diseases," "diseases of nervous system," and "mental and behavioural disorders" in comparison with "neoplasms" (<6.6%). For "mental and behavioural disorders," adaptive randomization was used in two trials of eight trials in total (25%). Group sequential design and adaptive sample-size adjustment were used frequently in phase 3 trials or in trials where study phase was not specified, whereas the other types of adaptive

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

Volunteering for early phase gene transfer research in Parkinson disease.

PubMed

Kim, S Y H; Holloway, R G; Frank, S; Beck, C A; Zimmerman, C; Wilson, R; Kieburtz, K

2006-04-11

For early phase trials of novel interventions-such as gene transfer for Parkinson disease (PD)--whose focus is primarily on safety and tolerability, it is important that participants have a realistic understanding of the goals of such research. Recently, some have expressed concern that patients with PD may have unrealistic expectations. The authors examined why patients with PD might volunteer for invasive early phase research by interviewing 92 patients with PD and comparing those who would (n = 46) and those who would not (n = 46) participate in a hypothetical phase I gene-transfer study. The two groups' demographic, clinical, functional, and quality of life measures, as well as their understanding of the research protocol, were similar. The groups did not differ on their perception of potential for personal benefit nor on the level of likelihood of benefit they saw as a precondition for volunteering. However, those willing to participate tended to perceive lower probability of risk, were tolerant of greater probability of risk, and were more optimistic about the phase I study's potential benefits to society. They also appeared more decisive and action-oriented than the unwilling group. It is likely that the decision whether to participate in early phase PD gene transfer studies will depend mostly on patients' attitudes regarding risk, optimism about science, and an action orientation, rather than on their clinical, functional, or demographic characteristics.

DESIGNING PHASE 0 CANCER CLINICAL TRIALS

PubMed Central

Murgo, Anthony J.; Kummar, Shivaani; Rubinstein, Larry; Gutierrez, Martin; Collins, Jerry; Kinders, Robert; Parchment, Ralph E.; Ji, Jiuping; Steinberg, Seth M.; Yang, Sherry X.; Hollingshead, Melinda; Chen, Alice; Helman, Lee; Wiltrout, Robert; Tomaszewski, Joseph E.; Doroshow, James H.

2008-01-01

Phase 0 trials are designed primarily to evaluate the pharmacodynamic and/or pharmacokinetic properties of selected investigational agents prior to initiating more traditional phase 1 testing. One of the major objectives of phase 0 trials is to interrogate and refine a target or biomarker assay for drug effect in human samples implementing procedures developed and validated in preclinical models. Thus, close collaboration between laboratory scientists and clinical investigators is essential to the design and conduct of phase 0 trials. Given the relatively small number of patients and tissue samples, demonstrating a significant drug effect in phase 0 trials requires precise and reproducible assay procedures and innovative statistical methodology. Furthermore, phase 0 trials involving limited exposure of study agent administered at low doses and/or for a short period allows them to be initiated under the FDA Exploratory IND Guidance with less preclinical toxicity data than usually required for traditional first-in-human studies. Because of the very limited drug exposure, phase 0 trials offer no chance of therapeutic benefit, which can impede patient enrollment, particularly if invasive tumor biopsies are required. However, the challenges to accrual are not insurmountable, and well-designed and executed phase 0 trials are feasible and have great potential for improving the efficiency and success of subsequent trials, particularly those evaluating molecularly targeted agents. PMID:18559582

Statistical controversies in clinical research: requiem for the 3 + 3 design for phase I trials.

PubMed

Paoletti, X; Ezzalfani, M; Le Tourneau, C

2015-09-01

More than 95% of published phase I trials have used the 3 + 3 design to identify the dose to be recommended for phase II trials. However, the statistical community agrees on the limitations of the 3 + 3 design compared with model-based approaches. Moreover, the mechanisms of action of targeted agents strongly challenge the hypothesis that the maximum tolerated dose constitutes the optimal dose, and more outcomes including clinical and biological activity increasingly need to be taken into account to identify the optimal dose. We review key elements from clinical publications and from the statistical literature to show that the 3 + 3 design lacks the necessary flexibility to address the challenges of targeted agents. The design issues raised by expansion cohorts, new definitions of dose-limiting toxicity and trials of combinations are not easily addressed by the 3 + 3 design or its extensions. Alternative statistical proposals have been developed to make a better use of the complex data generated by phase I trials. Their applications require a close collaboration between all actors of early phase clinical trials. © The Author 2015. 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.

40 CFR 76.8 - Early election for Group 1, Phase II boilers.

Code of Federal Regulations, 2010 CFR

2010-07-01

... PROGRAMS (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.8 Early election for Group 1... plan and: (i) If a Phase I Acid Rain permit governing the source at which the unit is located has been... chapter to include the early election plan; or (ii) If a Phase I Acid Rain permit governing the source at...

40 CFR 76.8 - Early election for Group 1, Phase II boilers.

Code of Federal Regulations, 2014 CFR

2014-07-01

... PROGRAMS (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.8 Early election for Group 1... plan and: (i) If a Phase I Acid Rain permit governing the source at which the unit is located has been... chapter to include the early election plan; or (ii) If a Phase I Acid Rain permit governing the source at...

40 CFR 76.8 - Early election for Group 1, Phase II boilers.

Code of Federal Regulations, 2011 CFR

2011-07-01

... PROGRAMS (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.8 Early election for Group 1... plan and: (i) If a Phase I Acid Rain permit governing the source at which the unit is located has been... chapter to include the early election plan; or (ii) If a Phase I Acid Rain permit governing the source at...

40 CFR 76.8 - Early election for Group 1, Phase II boilers.

Code of Federal Regulations, 2012 CFR

2012-07-01

... PROGRAMS (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.8 Early election for Group 1... plan and: (i) If a Phase I Acid Rain permit governing the source at which the unit is located has been... chapter to include the early election plan; or (ii) If a Phase I Acid Rain permit governing the source at...

40 CFR 76.8 - Early election for Group 1, Phase II boilers.

Code of Federal Regulations, 2013 CFR

2013-07-01

... PROGRAMS (CONTINUED) ACID RAIN NITROGEN OXIDES EMISSION REDUCTION PROGRAM § 76.8 Early election for Group 1... plan and: (i) If a Phase I Acid Rain permit governing the source at which the unit is located has been... chapter to include the early election plan; or (ii) If a Phase I Acid Rain permit governing the source at...

Phase III Early Restoration Meeting - Corpus Christi, TX | NOAA Gulf Spill

Science.gov Websites

Areas Alabama Florida Louisiana Mississippi Texas Region-wide Open Ocean Data Media & News programmatic approach to early restoration planning for Phase III and future early restoration plans. Open

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.

Phase III Early Restoration Meeting - Lake Charles, LA | NOAA Gulf Spill

Science.gov Websites

Areas Alabama Florida Louisiana Mississippi Texas Region-wide Open Ocean Data Media & News early restoration planning for Phase III and future early restoration plans. Open House: 5:30pm Public

Early visual processing is enhanced in the midluteal phase of the menstrual cycle.

PubMed

Lusk, Bethany R; Carr, Andrea R; Ranson, Valerie A; Bryant, Richard A; Felmingham, Kim L

2015-12-01

Event-related potential (ERP) studies have revealed an early attentional bias in processing unpleasant emotional images in women. Recent neuroimaging data suggests there are significant differences in cortical emotional processing according to menstrual phase. This study examined the impact of menstrual phase on visual emotional processing in women compared to men. ERPs were recorded from 28 early follicular women, 29 midluteal women, and 27 men while they completed a passive viewing task of neutral and low- and high- arousing pleasant and unpleasant images. There was a significant effect of menstrual phase in early visual processing, as midluteal women displayed significantly greater P1 amplitude at occipital regions to all visual images compared to men. Both midluteal and early follicular women displayed larger N1 amplitudes than men (although this only reached significance for the midluteal group) to the visual images. No sex or menstrual phase differences were apparent in later N2, P3, or LPP. A condition effect demonstrated greater P3 and LPP amplitude to highly-arousing unpleasant images relative to all other stimuli conditions. These results indicate that women have greater early automatic visual processing compared to men, and suggests that this effect is particularly strong in women in the midluteal phase at the earliest stage of visual attention processing. Our findings highlight the importance of considering menstrual phase when examining sex differences in the cortical processing of visual stimuli. Copyright © 2015 Elsevier Ltd. All rights reserved.

The Langley Research Center CSI phase-0 evolutionary model testbed-design and experimental results

NASA Technical Reports Server (NTRS)

Belvin, W. K.; Horta, Lucas G.; Elliott, K. B.

1991-01-01

A testbed for the development of Controls Structures Interaction (CSI) technology is described. The design philosophy, capabilities, and early experimental results are presented to introduce some of the ongoing CSI research at NASA-Langley. The testbed, referred to as the Phase 0 version of the CSI Evolutionary model (CEM), is the first stage of model complexity designed to show the benefits of CSI technology and to identify weaknesses in current capabilities. Early closed loop test results have shown non-model based controllers can provide an order of magnitude increase in damping in the first few flexible vibration modes. Model based controllers for higher performance will need to be robust to model uncertainty as verified by System ID tests. Data are presented that show finite element model predictions of frequency differ from those obtained from tests. Plans are also presented for evolution of the CEM to study integrated controller and structure design as well as multiple payload dynamics.

Proactive Integration of Planetary Protection Needs Into Early Design Phases of Human Exploration Missions

NASA Astrophysics Data System (ADS)

Race, Margaret; Conley, Catharine

discussed by the study participants to date have set the agenda for additional work that will continue for at least another year, culminating in a final report that should be useful to current and new nations and partnerships in planning human missions beyond LEO. In addition, over the past two years, NASA has made progress in integrating planetary protection considerations into mission designs along with other important human, environmental and science needs. Details about planetary protection have also been incorporated into the latest Addendum of the Design Reference Architecture (DRA) for human missions to Mars. Other ongoing studies of Mars human mission architecture, technologies and operations have likewise been integrating PP requirements and guidelines into cross-cutting measures of various types. An important objective of all these studies is to proactively gather and communicate PP information to the broad community of planners, engineers and assorted partners who are facing the challenges of future human exploration missions. By analyzing ways to integrate PP provisions effectively into early mission phases in synergism with other needs, these projects and studies will help ensure that all institutions and organizations avoid releasing harmful contamination on bodies with biological potential, thereby ensuring protection of the Earth and astronauts throughout their missions and safeguarding the integrity of science exploration—all in compliance with the 1967 Outer Space Treaty.

Proteomic analysis of early phase of conidia germination in Aspergillus nidulans.

PubMed

Oh, Young Taek; Ahn, Chun-Seob; Kim, Jeong Geun; Ro, Hyeon-Su; Lee, Chang-Won; Kim, Jae Won

2010-03-01

In order to investigate proteins involved in early phase of conidia germination, proteomic analysis was performed using two-dimensional gel electrophoresis (2D-GE) in conjunction with MALDI-TOF mass spectrometry (MS). The expression levels of 241 proteins varied quantitatively with statistical significance (P<0.05) at the early phase of the germination stage. Out of these 57 were identified by MALDI-TOF MS. Through classification of physiological functions from Conserved Domain Database analysis, among the identified proteins, 21, 13, and 6 proteins were associated with energy metabolism, protein synthesis, and protein folding process, respectively. Interestingly, eight proteins, which are involved in detoxification of reactive oxygen species (ROS) including catalase A, thioredoxin reductase, and mitochondrial peroxiredoxin, were also identified. The expression levels of the genes were further confirmed using Northern blot and reverse transcriptase (RT)-PCR analyses. This study represents the first proteomic analysis of early phase of conidia germination and will contribute to a better understanding of the molecular events involved in conidia germination process. Copyright (c) 2009 Elsevier Inc. All rights reserved.

A phase one AR/C system design

NASA Technical Reports Server (NTRS)

Kachmar, Peter M.; Polutchko, Robert J.; Matusky, Martin; Chu, William; Jackson, William; Montez, Moises

1991-01-01

The Phase One AR&C System Design integrates an evolutionary design based on the legacy of previous mission successes, flight tested components from manned Rendezvous and Proximity Operations (RPO) space programs, and additional AR&C components validated using proven methods. The Phase One system has a modular, open architecture with the standardized interfaces proposed for Space Station Freedom system architecture.

Challenges and perspective of drug repurposing strategies in early phase clinical trials.

PubMed

Kato, Shumei; Moulder, Stacy L; Ueno, Naoto T; Wheler, Jennifer J; Meric-Bernstam, Funda; Kurzrock, Razelle; Janku, Filip

2015-01-01

Despite significant investments in the development of new agents only 5% of cancer drugs entering Phase I clinical trials are ultimately approved for routine clinical cancer care. Drug repurposing strategies using novel combinations of previously tested anticancer agents could reduce the cost and improve treatment outcomes. At MD Anderson Cancer Center, early phase clinical trials with drug repurposing strategies demonstrated promising outcomes in patients with both rare and common treatment refractory advanced cancers. Despite clinical efficacy advancing drug repurposing strategies in the clinical trial trajectory beyond early phase studies has been challenging mainly due to lack of funding and interest from the pharmaceutical industry. In this review, we delineate our experience and challenges with drug repurposing strategies.

Identifying Effective Design Approaches to Allocate Genotypes in Two-Phase Designs: A Case Study in Pelargonium zonale.

PubMed

Molenaar, Heike; Boehm, Robert; Piepho, Hans-Peter

2017-01-01

Robust phenotypic data allow adequate statistical analysis and are crucial for any breeding purpose. Such data is obtained from experiments laid out to best control local variation. Additionally, experiments frequently involve two phases, each contributing environmental sources of variation. For example, in a former experiment we conducted to evaluate production related traits in Pelargonium zonale , there were two consecutive phases, each performed in a different greenhouse. Phase one involved the propagation of the breeding strains to obtain the stem cutting count, and phase two involved the assessment of root formation. The evaluation of the former study raised questions regarding options for improving the experimental layout: (i) Is there a disadvantage to using exactly the same design in both phases? (ii) Instead of generating a separate layout for each phase, can the design be optimized across both phases, such that the mean variance of a pair-wise treatment difference (MVD) can be decreased? To answer these questions, alternative approaches were explored to generate two-phase designs either in phase-wise order (Option 1) or across phases (Option 2). In Option 1 we considered the scenarios (i) using in both phases the same experimental design and (ii) randomizing each phase separately. In Option 2, we considered the scenarios (iii) generating a single design with eight replicates and splitting these among the two phases, (iv) separating the block structure across phases by dummy coding, and (v) design generation with optimal alignment of block units in the two phases. In both options, we considered the same or different block structures in each phase. The designs were evaluated by the MVD obtained by the intra-block analysis and the joint inter-block-intra-block analysis. The smallest MVD was most frequently obtained for designs generated across phases rather than for each phase separately, in particular when both phases of the design were separated with a

Identifying Effective Design Approaches to Allocate Genotypes in Two-Phase Designs: A Case Study in Pelargonium zonale

PubMed Central

Molenaar, Heike; Boehm, Robert; Piepho, Hans-Peter

2018-01-01

Robust phenotypic data allow adequate statistical analysis and are crucial for any breeding purpose. Such data is obtained from experiments laid out to best control local variation. Additionally, experiments frequently involve two phases, each contributing environmental sources of variation. For example, in a former experiment we conducted to evaluate production related traits in Pelargonium zonale, there were two consecutive phases, each performed in a different greenhouse. Phase one involved the propagation of the breeding strains to obtain the stem cutting count, and phase two involved the assessment of root formation. The evaluation of the former study raised questions regarding options for improving the experimental layout: (i) Is there a disadvantage to using exactly the same design in both phases? (ii) Instead of generating a separate layout for each phase, can the design be optimized across both phases, such that the mean variance of a pair-wise treatment difference (MVD) can be decreased? To answer these questions, alternative approaches were explored to generate two-phase designs either in phase-wise order (Option 1) or across phases (Option 2). In Option 1 we considered the scenarios (i) using in both phases the same experimental design and (ii) randomizing each phase separately. In Option 2, we considered the scenarios (iii) generating a single design with eight replicates and splitting these among the two phases, (iv) separating the block structure across phases by dummy coding, and (v) design generation with optimal alignment of block units in the two phases. In both options, we considered the same or different block structures in each phase. The designs were evaluated by the MVD obtained by the intra-block analysis and the joint inter-block–intra-block analysis. The smallest MVD was most frequently obtained for designs generated across phases rather than for each phase separately, in particular when both phases of the design were separated with a

48 CFR 570.305 - Two-phase design-build selection procedures.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 4 2012-10-01 2012-10-01 false Two-phase design-build...-phase design-build selection procedures. (a) These procedures apply to acquisitions of leasehold interests if the contracting officer uses the two-phase design-build selection procedures authorized by 570...

48 CFR 570.305 - Two-phase design-build selection procedures.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 4 2014-10-01 2014-10-01 false Two-phase design-build...-phase design-build selection procedures. (a) These procedures apply to acquisitions of leasehold interests if the contracting officer uses the two-phase design-build selection procedures authorized by 570...

48 CFR 570.305 - Two-phase design-build selection procedures.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 4 2013-10-01 2013-10-01 false Two-phase design-build...-phase design-build selection procedures. (a) These procedures apply to acquisitions of leasehold interests if the contracting officer uses the two-phase design-build selection procedures authorized by 570...

48 CFR 570.305 - Two-phase design-build selection procedures.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 48 Federal Acquisition Regulations System 4 2011-10-01 2011-10-01 false Two-phase design-build...-phase design-build selection procedures. (a) These procedures apply to acquisitions of leasehold interests if the contracting officer uses the two-phase design-build selection procedures authorized by 570...

Cytokine expression during early and late phase of acute Puumala hantavirus infection

PubMed Central

2011-01-01

Background Hantaviruses of the family Bunyaviridae are emerging zoonotic pathogens which cause hemorrhagic fever with renal syndrome (HFRS) in the Old World and hantavirus pulmonary syndrome (HPS) in the New World. An immune-mediated pathogenesis is discussed for both syndromes. The aim of our study was to investigate cytokine expression during the course of acute Puumala hantavirus infection. Results We retrospectively studied 64 patients hospitalised with acute Puumala hantavirus infection in 2010 during a hantavirus epidemic in Germany. Hantavirus infection was confirmed by positive anti-hantavirus IgG/IgM. Cytokine expression of IL-2, IL-5, IL-6, IL-8, IL-10, IFN-γ, TNF-α and TGF-β1 was analysed by ELISA during the early and late phase of acute hantavirus infection (average 6 and 12 days after onset of symptoms, respectively). A detailed description of the demographic and clinical presentation of severe hantavirus infection requiring hospitalization during the 2010 hantavirus epidemic in Germany is given. Acute hantavirus infection was characterized by significantly elevated levels of IL-2, IL-6, IL-8, TGF-β1 and TNF-α in both early and late phase compared to healthy controls. From early to late phase of disease, IL-6, IL-10 and TNF-α significantly decreased whereas TGF-β1 levels increased. Disease severity characterized by elevated creatinine and low platelet counts was correlated with high pro-inflammatory IL-6 and TNF-α but low immunosuppressive TGF-β1 levels and vice versa . Conclusion High expression of cytokines activating T-lymphocytes, monocytes and macrophages in the early phase of disease supports the hypothesis of an immune-mediated pathogenesis. In the late phase of disease, immunosuppressive TGF-β1 level increase significantly. We suggest that delayed induction of a protective immune mechanism to downregulate a massive early pro-inflammatory immune response might contribute to the pathologies characteristic of human hantavirus infection

Design principles for enhancing phase sensitivity and suppressing phase fluctuations simultaneously in biochemical oscillatory systems.

PubMed

Fei, Chenyi; Cao, Yuansheng; Ouyang, Qi; Tu, Yuhai

2018-04-12

Biological systems need to function accurately in the presence of strong noise and at the same time respond sensitively to subtle external cues. Here we study design principles in biochemical oscillatory circuits to achieve these two seemingly incompatible goals. We show that energy dissipation can enhance phase sensitivity linearly by driving the phase-amplitude coupling and increase timing accuracy by suppressing phase diffusion. Two general design principles in the key underlying reaction loop formed by two antiparallel pathways are found to optimize oscillation performance with a given energy budget: balancing the forward-to-backward flux ratio between the two pathways to reduce phase diffusion and maximizing the net flux of the phase-advancing pathway relative to that of the phase-retreating pathway to enhance phase sensitivity. Experimental evidences consistent with these design principles are found in the circadian clock of cyanobacteria. Future experiments to test the predicted dependence of phase sensitivity on energy dissipation are proposed.

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

NASA Technical Reports Server (NTRS)

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

1992-01-01

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

48 CFR 570.305 - Two-phase design-build selection procedures.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 48 Federal Acquisition Regulations System 4 2010-10-01 2010-10-01 false Two-phase design-build... for Leasehold Interests in Real Property 570.305 Two-phase design-build selection procedures. (a) These procedures apply to acquisitions of leasehold interests if you use the two-phase design-build...

The Early Years: Integrating Design

ERIC Educational Resources Information Center

Ashbrook, Peggy; Nellor, Sue

2015-01-01

Engineering is such a common part of children's work in early childhood programs that teachers can simply look around the room to identify examples where students have engaged in engineering practices. This article presents a classroom activity that integrates engineering design by building on the everyday problems that young children encounter in…

Safety Guided Design of Crew Return Vehicle in Concept Design Phase Using STAMP/STPA

NASA Astrophysics Data System (ADS)

Nakao, H.; Katahira, M.; Miyamoto, Y.; Leveson, N.

2012-01-01

In the concept development and design phase of a new space system, such as a Crew Vehicle, designers tend to focus on how to implement new technology. Designers also consider the difficulty of using the new technology and trade off several system design candidates. Then they choose an optimal design from the candidates. Safety should be a key aspect driving optimal concept design. However, in past concept design activities, safety analysis such as FTA has not used to drive the design because such analysis techniques focus on component failure and component failure cannot be considered in the concept design phase. The solution to these problems is to apply a new hazard analysis technique, called STAMP/STPA. STAMP/STPA defines safety as a control problem rather than a failure problem and identifies hazardous scenarios and their causes. Defining control flow is the essential in concept design phase. Therefore STAMP/STPA could be a useful tool to assess the safety of system candidates and to be part of the rationale for choosing a design as the baseline of the system. In this paper, we explain our case study of safety guided concept design using STPA, the new hazard analysis technique, and model-based specification technique on Crew Return Vehicle design and evaluate benefits of using STAMP/STPA in concept development phase.

Phase III Early Restoration Meeting - Galveston, TX | NOAA Gulf Spill

Science.gov Websites

Areas Alabama Florida Louisiana Mississippi Texas Region-wide Open Ocean Data Media & News planning for Phase III and future early restoration plans. Open House: 6:00pm Public Meeting: 6:30pm

Impact of incretin on early-phase insulin secretion and glucose excursion.

PubMed

Shen, Jie; Chen, Zhi; Chen, Chaofeng; Zhu, Xiao; Han, Yajuan

2013-10-01

This study investigated the impact of incretin on early-phase insulin secretion and glucose excursion. The normal glucose tolerance (NGT), impaired glucose tolerance (IGT), and type 2 diabetes mellitus (T2DM) groups included 16, 8, and 19 subjects, respectively. Subjects underwent continuous glucose monitoring for 3 days, followed by an oral glucose tolerance test. Plasma glucose, insulin, glucagon, total glucose-dependent insulinotropic polypeptide (GIP), and glucagon-like peptide-l (GLP-1) levels were measured at 30-min increments for 2 h after glucose intake. Differences with P < 0.05 were considered statistically significant. The area under the curve (AUC) of total GIP (120-min GIP-AUC) of the T2DM group was significantly lower than those of the NGT and IGT groups. The 120-min GLP-1-AUC of the NGT group was significantly larger than those of the T2DM and IGT groups. The early-phase insulin secretion index (ΔI30/ΔG30) of the T2DM group was significantly lower than those of the NGT and IGT groups. Mean amplitudes of glycemic excursions (MAGEs) went in the order of NGT < IGT < T2DM (P < 0.01, IGT vs. NGT; P < 0.001, T2DM vs. IGT). The 120-min GIP-AUC was negatively correlated with MAGE (r = -0.464), but uncorrelated with ΔI30/ΔG30. The 120-min GLP-1-AUC was positively correlated with ΔI30/ΔG30 (r = 0.580), but negatively correlated with MAGE (r = -0.606). Incretin may ameliorate glucose excursions, and GLP-1 may exert them by promoting early-phase insulin secretion. No correlation was observed between GIP secretion and early-phase insulin secretion.

A Bayesian pick-the-winner design in a randomized phase II clinical trial.

PubMed

Chen, Dung-Tsa; Huang, Po-Yu; Lin, Hui-Yi; Chiappori, Alberto A; Gabrilovich, Dmitry I; Haura, Eric B; Antonia, Scott J; Gray, Jhanelle E

2017-10-24

Many phase II clinical trials evaluate unique experimental drugs/combinations through multi-arm design to expedite the screening process (early termination of ineffective drugs) and to identify the most effective drug (pick the winner) to warrant a phase III trial. Various statistical approaches have been developed for the pick-the-winner design but have been criticized for lack of objective comparison among the drug agents. We developed a Bayesian pick-the-winner design by integrating a Bayesian posterior probability with Simon two-stage design in a randomized two-arm clinical trial. The Bayesian posterior probability, as the rule to pick the winner, is defined as probability of the response rate in one arm higher than in the other arm. The posterior probability aims to determine the winner when both arms pass the second stage of the Simon two-stage design. When both arms are competitive (i.e., both passing the second stage), the Bayesian posterior probability performs better to correctly identify the winner compared with the Fisher exact test in the simulation study. In comparison to a standard two-arm randomized design, the Bayesian pick-the-winner design has a higher power to determine a clear winner. In application to two studies, the approach is able to perform statistical comparison of two treatment arms and provides a winner probability (Bayesian posterior probability) to statistically justify the winning arm. We developed an integrated design that utilizes Bayesian posterior probability, Simon two-stage design, and randomization into a unique setting. It gives objective comparisons between the arms to determine the winner.

Early-Phase 11C-PiB PET in Amyloid Angiopathy-Related Symptomatic Cerebral Hemorrhage: Potential Diagnostic Value?

PubMed Central

Aigbirhio, Franklin I.; Fryer, Tim D.; Menon, David K.; Warburton, Elizabeth A.; Baron, Jean-Claude

2015-01-01

Although late-phase (>35min post-administration) 11C-PiB-PET has good sensitivity in cerebral amyloid angiopathy (CAA), its specificity is poor due to frequently high uptake in healthy aged subjects. By detecting perfusion-like abnormalities, early-phase 11C-PiB-PET might add diagnostic value. Early-frame (1–6min) 11C-PiB-PET was obtained in 11 non-demented patients with probable CAA-related symptomatic lobar intracerebral haemorrhage (70±7yrs), 9 age-matched healthy controls (HCs) and 10 HCs <55yrs. There was a significant decrease in early-phase atrophy-corrected whole-cortex SUV relative to cerebellar vermis (SUVR) in the CAA vs age-matched HC group. None of the age-matched controls fell below the lower 95% confidence limit derived from the young HCs, while 6/11 CAA patients did (sensitivity = 55%, specificity = 100%). Combining both early- and late-phase 11C-PiB data did not change the sensitivity and specificity of late-phase PiB, but combined early- and late-phase positivity entails a very high suspicion of underlying Aβ-related clinical disorder, i.e., CAA or Alzheimer disease (AD). In order to clarify this ambiguity, we then show that the occipital/posterior cingulate ratio is markedly lower in CAA than in AD (N = 7). These pilot data suggest that early-phase 11C-PiB-PET may not only add to late-phase PiB-PET with respect to the unclear situation of late-phase positivity, but also help differentiate CAA from AD. PMID:26439113

Design of Training Systems Phase I Summary Report.

ERIC Educational Resources Information Center

Lindahl, William H.; And Others

A summary is provided of the status of Phase I of the three-stage project, "Design of Training Systems" (DOTS). The purpose of the overall project is described as being to introduce the technologies of education, psychology, management and operations research into the management of Navy training. Phase I of the effort is designed to…

Project 8, Phase III Design: Placing an eV-Scale Limit on the Neutrino Mass using Cyclotron Radiation Emission Spectroscopy

NASA Astrophysics Data System (ADS)

Oblath, Noah; Project 8 Collaboration

2016-09-01

We report on the design concept for Phase III of the Project 8 experiment. In the third phase of Project 8 we aim to place a limit on the neutrino mass that is similar to the current limits set by tritium beta-decay experiments, mν < 2eV . From the first two phases of Project 8 we move to a novel design consisting of a 100cm3 cylindrical volume of tritium gas instrumented with two 30-element rings of inward-facing antennas. Beam-forming techniques similar to those used in radioastronomy will be employed to search for and track electron signals in the fiducial volume. This talk will present the quantitative design concept for the phased-array receiver, and illustrate how we are progressing towards the Phase IV experiment, which will have sensitivity to the neutrino mass scale allowed by the inverted mass hierarchy. This work is supported by the DOE Office of Science Early Career Research Program, and the Laboratory Directed Research and Development Program at Pacific Northwest National Laboratory.

Psychotropic and Anticonvulsant Drug Usage in Early Childhood Special Education Programs I. Phase One: A Preliminary Report: Prevalence, Attitude, Training, and Problems.

ERIC Educational Resources Information Center

Gadow, Kenneth D.

As part of a three phase study designed to survey the teachers and parents of children receiving psychotropic and anticonvulsant drugs, 208 teachers of preschool special education children on medication were mailed questionnaires. The Early Childhood Medication Questionnaire used in the survey included items relating to teacher, program, and…

Designing Estimator/Predictor Digital Phase-Locked Loops

NASA Technical Reports Server (NTRS)

Statman, J. I.; Hurd, W. J.

1988-01-01

Signal delays in equipment compensated automatically. New approach to design of digital phase-locked loop (DPLL) incorporates concepts from estimation theory and involves decomposition of closed-loop transfer function into estimator and predictor. Estimator provides recursive estimates of phase, frequency, and higher order derivatives of phase with respect to time, while predictor compensates for delay, called "transport lag," caused by PLL equipment and by DPLL computations.

Early Detection of Amyloid Plaque in Alzheimer’s Disease via X-ray Phase CT

DTIC Science & Technology

2016-08-01

AWARD NUMBER: W81XWH-12-1-0138 TITLE: Early Detection of Amyloid Plaque in Alzheimer’s Disease via X-ray Phase CT PRINCIPAL INVESTIGATOR...NUMBER W81XWH-12-1-0138 Early Detection of Amyloid Plaque in Alzheimer’s Disease via X-ray Phase CT 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6...method for early detection of amyloid plaque in Alzheimer’s disease , with three Specific Aims: #1 Develop and optimize an x-ray PCCT to explore the

A Phase I/II adaptive design for heterogeneous groups with application to a stereotactic body radiation therapy trial.

PubMed

Wages, Nolan A; Read, Paul W; Petroni, Gina R

2015-01-01

Dose-finding studies that aim to evaluate the safety of single agents are becoming less common, and advances in clinical research have complicated the paradigm of dose finding in oncology. A class of more complex problems, such as targeted agents, combination therapies and stratification of patients by clinical or genetic characteristics, has created the need to adapt early-phase trial design to the specific type of drug being investigated and the corresponding endpoints. In this article, we describe the implementation of an adaptive design based on a continual reassessment method for heterogeneous groups, modified to coincide with the objectives of a Phase I/II trial of stereotactic body radiation therapy in patients with painful osseous metastatic disease. Operating characteristics of the Institutional Review Board approved design are demonstrated under various possible true scenarios via simulation studies. Copyright © 2015 John Wiley & Sons, Ltd.

Modified Toxicity Probability Interval Design: A Safer and More Reliable Method Than the 3 + 3 Design for Practical Phase I Trials

PubMed Central

Ji, Yuan; Wang, Sue-Jane

2013-01-01

The 3 + 3 design is the most common choice among clinicians for phase I dose-escalation oncology trials. In recent reviews, more than 95% of phase I trials have been based on the 3 + 3 design. Given that it is intuitive and its implementation does not require a computer program, clinicians can conduct 3 + 3 dose escalations in practice with virtually no logistic cost, and trial protocols based on the 3 + 3 design pass institutional review board and biostatistics reviews quickly. However, the performance of the 3 + 3 design has rarely been compared with model-based designs in simulation studies with matched sample sizes. In the vast majority of statistical literature, the 3 + 3 design has been shown to be inferior in identifying true maximum-tolerated doses (MTDs), although the sample size required by the 3 + 3 design is often orders-of-magnitude smaller than model-based designs. In this article, through comparative simulation studies with matched sample sizes, we demonstrate that the 3 + 3 design has higher risks of exposing patients to toxic doses above the MTD than the modified toxicity probability interval (mTPI) design, a newly developed adaptive method. In addition, compared with the mTPI design, the 3 + 3 design does not yield higher probabilities in identifying the correct MTD, even when the sample size is matched. Given that the mTPI design is equally transparent, costless to implement with free software, and more flexible in practical situations, we highly encourage its adoption in early dose-escalation studies whenever the 3 + 3 design is also considered. We provide free software to allow direct comparisons of the 3 + 3 design with other model-based designs in simulation studies with matched sample sizes. PMID:23569307

Optimizing the early phase development of new analgesics by human pain biomarkers.

PubMed

Arendt-Nielsen, Lars; Hoeck, Hans Christian

2011-11-01

Human pain biomarkers are based on standardized acute activation of pain pathways/mechanisms and quantitative assessment of the evoked responses. This approach can be applied to healthy volunteers, to pain patients, and before and after pharmacological interventions to help understanding and profile the mode of action (proof-of-concept) of new and existing analgesic compounds. Standardized stimuli of different modalities can be applied to different tissues (multimodal and multi-tissue) for profiling analgesic compounds with respect to modulation of pain transduction, transmission, specific mechanisms and processing. This approach substantiates which specific compounds may work in particular clinical pain conditions. Human pain biomarkers can be translational and may bridge animal findings in clinical pain conditions, which in turn can provide new possibilities for designing more successful clinical trials. Biomarker based proof-of-concept drug studies in either volunteers or selected patient populations provide inexpensive, fast and reliable mechanism-based information about dose-efficacy relationships. This is important information in the early drug development phase and for designing large expensive clinical trials.

LST phase A design update study

NASA Technical Reports Server (NTRS)

1973-01-01

An update is presented of the Phase A study of the Large Space Telescope (LST), based on changes in guidelines and new data developed subsequent to the Phase A study. The study defines an LST concept based on the broad mission guidelines provided by the Office of Space Science (OSS), the scientific requirements developed by OSS with the scientific community, and an understanding of long range NASA planning current at the time the study was performed. A low cost design approach was followed. This resulted in the use of standard spacecraft hardware, the provision for maintenance at the black box level, growth potential in systems designs, and sharing of shuttle maintenance flights with other payloads (See N73-18449 through N73-18453)

Accumulation of unsaturated lipids in monocytes during early phase pyrogen tolerance.

PubMed

Szewczenko-Pawlikowski, M; Kozak, W

2000-04-12

This paper presents data that inspired a new explanation for the mechanism of early phase endotoxin tolerance. Rabbits injected intravenously with LPS from Salmonella abortus developed a two-phase fever (6 h) and monophasic hyperlipidemia of very low density lipoproteins (two consecutive days). If during these days rabbits were injected with the same dose of LPS at 24-h intervals, the second phase of fever disappeared, i.e. early phase pyrogenic tolerance was obtained. This was correlated with a decrease of lipoprotein hyperlipidemia (measured 1.5 h after LPS injection) and an accumulation of lipids rich in double bonds in monocytes (measured 3.5 h after LPS injection). Results showed that the degree of unsaturation of acyl chains (AC) in monocytes (AC/DB, DB=double bonds) is negatively correlated (r=-0.72) with fever response (fever index). The authors maintain that a gradual increase in monocyte membrane fluidity is an adaptation to repeated exposure of monocytes to lipid A and is responsible for the progressive desensitization of monocytes to endotoxin. It is suggested that disorders of this mechanism lead to an accumulation of abnormal quantities of saturated lipids and cholesterol within macrophages, which, as foam cells, are the starting point for atherosclerosis pathology.

Phase III Early Restoration Meeting - Port Arthur, TX | NOAA Gulf Spill

Science.gov Websites

Areas Alabama Florida Louisiana Mississippi Texas Region-wide Open Ocean Data Media & News planning for Phase III and future early restoration plans. Open House: 6:00pm Public Meeting: 6:30pm

Phase III Early Restoration Meeting - Panama City, FL | NOAA Gulf Spill

Science.gov Websites

Areas Alabama Florida Louisiana Mississippi Texas Region-wide Open Ocean Data Media & News planning for Phase III and future early restoration plans. Open House: 6:00pm Public Meeting: 6:30pm

Overcoming ecologic bias using the two-phase study design.

PubMed

Wakefield, Jon; Haneuse, Sebastien J-P A

2008-04-15

Ecologic (aggregate) data are widely available and widely utilized in epidemiologic studies. However, ecologic bias, which arises because aggregate data cannot characterize within-group variability in exposure and confounder variables, can only be removed by supplementing ecologic data with individual-level data. Here the authors describe the two-phase study design as a framework for achieving this objective. In phase 1, outcomes are stratified by any combination of area, confounders, and error-prone (or discretized) versions of exposures of interest. Phase 2 data, sampled within each phase 1 stratum, provide accurate measures of exposure and possibly of additional confounders. The phase 1 aggregate-level data provide a high level of statistical power and a cross-classification by which individuals may be efficiently sampled in phase 2. The phase 2 individual-level data then provide a control for ecologic bias by characterizing the within-area variability in exposures and confounders. In this paper, the authors illustrate the two-phase study design by estimating the association between infant mortality and birth weight in several regions of North Carolina for 2000-2004, controlling for gender and race. This example shows that the two-phase design removes ecologic bias and produces gains in efficiency over the use of case-control data alone. The authors discuss the advantages and disadvantages of the approach.

Beryllium and boron constraints on an early Galactic bright phase

NASA Technical Reports Server (NTRS)

Fields, Brian D.; Schramm, David N.; Truran, James W.

1993-01-01

The recent observations of Be and B in metal-deficient halo dwarfs are used to constrain a 'bright phase' of enhanced cosmic-ray flux in the early Galaxy. Assuming that this Be and B arises from cosmic-ray spallation in the early Galaxy, limits are placed on the intensity of the early (Population II) cosmic-ray flux relative to the present (Population I) flux. A simple estimate of bounds on the flux ratio is 1 - 40. This upper bound would restrict galaxies like our own from producing neutrino fluxes that would be detectable in any currently proposed detectors. It is found that the relative enhancement of the early flux varies inversely with the relative time of enhancement. It is noted that associated gamma-ray production via pp - pi sup 0 pp may be a significant contribution to the gamma-ray background above 100 MeV.

Early Childhood Technology Integrated Instructional System (EC-TIIS) Phase 1: A Final Report

ERIC Educational Resources Information Center

Hutinger, Patricia; Robinson, Linda; Schneider, Carol

2004-01-01

The Early Childhood Technology Integrated Instructional System (EC-TIIS), a Steppingstones of Technology Innovation Phase 1--Development project, was developed by the Center for Best Practices in Early Childhood (the Center) at Western Illinois University as an online instructional system. EC-TIIS' ultimate goal was to improve technology services…

Architects and Design-Phase Cost Estimates: Design Professionals Should Reconsider the Value of Third-Party Estimates

ERIC Educational Resources Information Center

Coakley, John

2010-01-01

Professional cost estimators are widely used by architects during the design phases of a project to provide preliminary cost estimates. These estimates may begin at the conceptual design phase and are prepared at regular intervals through the construction document phase. Estimating professionals are frequently tasked with "selling" the importance…

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

PubMed

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

2017-12-15

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

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.

Numerical investigation of the early flight phase in ski-jumping.

PubMed

Gardan, N; Schneider, A; Polidori, G; Trenchard, H; Seigneur, J M; Beaumont, F; Fourchet, F; Taiar, R

2017-07-05

The purpose of this study is to develop a numerical methodology based on real data from wind tunnel experiments to investigate the effect of the ski jumper's posture and speed on aerodynamic forces in a wide range of angles of attack. To improve our knowledge of the aerodynamic behavior of the ski jumper and his equipment during the early flight phase of the ski jump, we applied CFD methodology to evaluate the influence of angle of attack (α=14°, 21.5°, 29°, 36.5° and 44°) and speed (u=23, 26 and 29m/s) on aerodynamic forces in the situation of stable attitude of the ski jumper's body and skis. The standard k-ω turbulence model was used to investigate both the influence of the ski jumper's posture and speed on aerodynamic performance during the early flight phase. Numerical results show that the ski jumper's speed has very little impact on the lift and drag coefficients. Conversely, the lift and drag forces acting on the ski jumper's body during the early flight phase of the jump are strongly influenced by the variations of the angle of attack. The present results suggest that the greater the ski jumper's angle of inclination, with respect to the relative flow, the greater the pressure difference between the lower and upper parts of the skier. Further studies will focus on the dependency of the parameters with both the angle of attack α and the body-ski angle β as control variables. It will be possible to test and optimize different ski jumping styles in different ski jumping hills and investigate different environmental conditions such as temperature, altitude or crosswinds. Copyright © 2017 Elsevier Ltd. All rights reserved.

Alternating phase-shifted mask for logic gate levels, design, and mask manufacturing

NASA Astrophysics Data System (ADS)

Liebmann, Lars W.; Graur, Ioana C.; Leipold, William C.; Oberschmidt, James M.; O'Grady, David S.; Regaill, Denis

1999-07-01

While the benefits of alternating phase shifted masks in improving lithographic process windows at increased resolution are well known throughout the lithography community, broad implementation of this potentially powerful technique has been slow due to the inherent complexity of the layout design and mask manufacturing process. This paper will review a project undertaken at IBM's Semiconductor Research and Development Center and Mask Manufacturing and Development facility to understand the technical and logistical issues associated with the application of alternating phase shifted mask technology to the gate level of a full microprocessor chip. The work presented here depicts an important milestone toward integration of alternating phase shifted masks into the manufacturing process by demonstrating an automated design solution and yielding a functional alternating phase shifted mask. The design conversion of the microprocessor gate level to a conjugate twin shifter alternating phase shift layout was accomplished with IBM's internal design system that automatically scaled the design, added required phase regions, and resolved phase conflicts. The subsequent fabrication of a nearly defect free phase shifted mask, as verified by SEM based die to die inspection, highlights the maturity of the alternating phase shifted mask manufacturing process in IBM's internal mask facility. Well defined and recognized challenges in mask inspection and repair remain and the layout of alternating phase shifted masks present a design and data preparation overhead, but the data presented here demonstrate the feasibility of designing and building manufacturing quality alternating phase shifted masks for the gate level of a microprocessor.

Heliogyro Preliminary Design, Phase 2

NASA Technical Reports Server (NTRS)

1978-01-01

There are 12 blades in the Heliogyro design, and each blade is envisioned to be 8 meters in width and 7,500 meters in length. The blades are expected to be composed primarily of a thin membrane constructed of material such as Kapton film with an aluminum reflective coating on one side and an infrared emissive coating on the other. The present Phase 2 Final Report covers work done on the following six topics: (1) Design and analysis of a stowable circular lattice batten for the Heliogyro blade. (2) Design and analysis of a biaxially tensioned blade panel. (3) Definition of a research program for micrometeoroid damage to tendons. (4) A conceptual design for a flight test model of the Heliogyro. (5) Definition of modifications to the NASTRAN computer program required to provide improved analysis of the Heliogyro. (6) A User's Manual covering applications of NASTRAN to the Heliogyro.

Imaging of early acceleration phase of the 2013-2014 Boso slow slip event

NASA Astrophysics Data System (ADS)

Fukuda, J.; Kato, A.; Obara, K.; Miura, S.; Kato, T.

2014-12-01

Based on GPS and seismic data, we examine the spatiotemporal evolution of a slow slip event (SSE) and associated seismic activity that occurred off the Boso peninsula, central Japan, from December 2013 to January 2014. We use GPS data from 71 stations of the GEONET and 6 stations operated by Earthquake Research Institute of the University of Tokyo and Tohoku University around the Boso peninsula. We apply a modified version of the Network Inversion Filter to the GPS time series at the 77 stations to estimate the spatiotemporal evolution of daily cumulative slip and slip rate on the subducting Philippine Sea plate. In addition, we create an improved earthquake catalog by applying a matched filter technique to continuous seismograms and examine the spatiotemporal relations between slow slip and seismicity. We find that the SSE started in early December 2013. The spatiotemporal evolution of slow slip and seismicity is divided into two distinct phases, an earlier slow phase from early to 30 December 2013 (Phase I) and a subsequent faster phase from 30 December 2013 to 9 January 2014 (Phase II). During Phase I, slip accelerated slowly up to a maximum rate of 1.6 m/yr with potentially accelerating　along-strike propagation at speeds on the order of 1 km/day or less and no accompanying seismicity. On the other hand, during Phase II, slip accelerated rapidly up to a maximum rate of 4.5 m/yr and then rapidly decelerated. The slip front propagated along strike at a constant speed of ~10 km/day. During the Phase II, slow slip was accompanied by seismic swarm activity that was highly correlated in space and time with slip rate, suggesting that the swarm activity was triggered by stress loading due to slow slip. Early slow acceleration of slip has not been identified in the past Boso SSEs in 1996, 2002, 2007, and 2011. It is not clear at this point whether the past Boso SSEs started with slow acceleration similarly to the 2013-2014 SSE. The transition from the slow to the

Perspectives and Open Problems in the Early Phases of Left-Right Patterning

PubMed Central

Vandenberg, Laura N.; Levin, Michael

2009-01-01

Summary Embryonic left-right (LR) patterning is a fascinating aspect of embryogenesis. The field currently faces important questions about the origin of LR asymmetry, the mechanisms by which consistent asymmetry is imposed on the scale of the whole embryo, and the degree of conservation of early phases of LR patterning among model systems. Recent progress on planar cell polarity and cellular asymmetry in a variety of tissues and species provides a new perspective on the early phases of LR patterning. Despite the huge diversity in body-plans over which consistent LR asymmetry is imposed, and the apparent divergence in molecular pathways that underlie laterality, the data reveal conservation of physiological modules among phyla and a basic scheme of cellular chirality amplified by a planar cell polarity-like pathway over large cell fields. PMID:19084609

14 CFR 33.201 - Design and test requirements for Early ETOPS eligibility.

Code of Federal Regulations, 2014 CFR

2014-01-01

... 14 Aeronautics and Space 1 2014-01-01 2014-01-01 false Design and test requirements for Early... Aircraft Engines § 33.201 Design and test requirements for Early ETOPS eligibility. An applicant seeking type design approval for an engine to be installed on a two-engine airplane approved for ETOPS without...

Ultra-Early Phase pathologies of Alzheimer's disease and other neurodegenerative diseases.

PubMed

Okazawa, Hitoshi

2017-01-01

The concept of neurodegenerative diseases and the therapeutics targeting these intractable diseases are changing rapidly. Protein aggregation as the top of pathological cascade is now challenged, and many alternative ideas are proposed. Early molecular pathologies before microscopic detection of diseases protein aggregates, which I propose to call "Ultra-Early Phase pathologies or phase 0 pathologies", are the focus of research that might explain the failures of clinical trials with anti-Aβ antibodies against Alzheimer's disease. In this review article, I summarize the critical issues that should be successfully and consistently answered by a new concept of neurodegeneration. For reevaluating old concepts and reconstructing a new concept of neurodegeneration that will replace the old ones, non-biased comprehensive approaches including proteome combined with systems biology analyses will be a powerful tool. I introduce our recent efforts in this orientation that have reached to the stage of non-clinical proof of concept applicable to clinical trials.

Design of recursive digital filters having specified phase and magnitude characteristics

NASA Technical Reports Server (NTRS)

King, R. E.; Condon, G. W.

1972-01-01

A method for a computer-aided design of a class of optimum filters, having specifications in the frequency domain of both magnitude and phase, is described. The method, an extension to the work of Steiglitz, uses the Fletcher-Powell algorithm to minimize a weighted squared magnitude and phase criterion. Results using the algorithm for the design of filters having specified phase as well as specified magnitude and phase compromise are presented.

Pilot study assessing the feasibility of applying bilateral subthalamic nucleus deep brain stimulation in very early stage Parkinson's disease: study design and rationale.

PubMed

Charles, David; Tolleson, Christopher; Davis, Thomas L; Gill, Chandler E; Molinari, Anna L; Bliton, Mark J; Tramontana, Michael G; Salomon, Ronald M; Kao, Chris; Wang, Lily; Hedera, Peter; Phibbs, Fenna T; Neimat, Joseph S; Konrad, Peter E

2012-01-01

Deep brain stimulation provides significant symptomatic benefit for people with advanced Parkinson's disease whose symptoms are no longer adequately controlled with medication. Preliminary evidence suggests that subthalamic nucleus stimulation may also be efficacious in early Parkinson's disease, and results of animal studies suggest that it may spare dopaminergic neurons in the substantia nigra. We report the methodology and design of a novel Phase I clinical trial testing the safety and tolerability of deep brain stimulation in early Parkinson's disease and discuss previous failed attempts at neuroprotection. We recently conducted a prospective, randomized, parallel-group, single-blind pilot clinical trial of deep brain stimulation in early Parkinson's disease. Subjects were randomized to receive either optimal drug therapy or deep brain stimulation plus optimal drug therapy. Follow-up visits occurred every six months for a period of two years and included week-long therapy washouts. Thirty subjects with Hoehn & Yahr Stage II idiopathic Parkinson's disease were enrolled over a period of 32 months. Twenty-nine subjects completed all follow-up visits; one patient in the optimal drug therapy group withdrew from the study after baseline. Baseline characteristics for all thirty patients were not significantly different. This study demonstrates that it is possible to recruit and retain subjects in a clinical trial testing deep brain stimulation in early Parkinson's disease. The results of this trial will be used to support the design of a Phase III, multicenter trial investigating the efficacy of deep brain stimulation in early Parkinson's disease.

Local phase method for designing and optimizing metasurface devices.

PubMed

Hsu, Liyi; Dupré, Matthieu; Ndao, Abdoulaye; Yellowhair, Julius; Kanté, Boubacar

2017-10-16

Metasurfaces have attracted significant attention due to their novel designs for flat optics. However, the approach usually used to engineer metasurface devices assumes that neighboring elements are identical, by extracting the phase information from simulations with periodic boundaries, or that near-field coupling between particles is negligible, by extracting the phase from single particle simulations. This is not the case most of the time and the approach thus prevents the optimization of devices that operate away from their optimum. Here, we propose a versatile numerical method to obtain the phase of each element within the metasurface (meta-atoms) while accounting for near-field coupling. Quantifying the phase error of each element of the metasurfaces with the proposed local phase method paves the way to the design of highly efficient metasurface devices including, but not limited to, deflectors, high numerical aperture metasurface concentrators, lenses, cloaks, and modulators.

Design of multi-phase dynamic chemical networks

NASA Astrophysics Data System (ADS)

Chen, Chenrui; Tan, Junjun; Hsieh, Ming-Chien; Pan, Ting; Goodwin, Jay T.; Mehta, Anil K.; Grover, Martha A.; Lynn, David G.

2017-08-01

Template-directed polymerization reactions enable the accurate storage and processing of nature's biopolymer information. This mutualistic relationship of nucleic acids and proteins, a network known as life's central dogma, is now marvellously complex, and the progressive steps necessary for creating the initial sequence and chain-length-specific polymer templates are lost to time. Here we design and construct dynamic polymerization networks that exploit metastable prion cross-β phases. Mixed-phase environments have been used for constructing synthetic polymers, but these dynamic phases emerge naturally from the growing peptide oligomers and create environments suitable both to nucleate assembly and select for ordered templates. The resulting templates direct the amplification of a phase containing only chain-length-specific peptide-like oligomers. Such multi-phase biopolymer dynamics reveal pathways for the emergence, self-selection and amplification of chain-length- and possibly sequence-specific biopolymers.

Application of Design of Experiments and Surrogate Modeling within the NASA Advanced Concepts Office, Earth-to-Orbit Design Process

NASA Technical Reports Server (NTRS)

Zwack, Matthew R.; Dees, Patrick D.; Holt, James B.

2016-01-01

Decisions made during early conceptual design can have a profound impact on life-cycle cost (LCC). Widely accepted that nearly 80% of LCC is committed. Decisions made during early design must be well informed. Advanced Concepts Office (ACO) at Marshall Space Flight Center aids in decision making for launch vehicles. Provides rapid turnaround pre-phase A and phase A studies. Provides customer with preliminary vehicle sizing information, vehicle feasibility, and expected performance.

Design Techniques for Uniform-DFT, Linear Phase Filter Banks

NASA Technical Reports Server (NTRS)

Sun, Honglin; DeLeon, Phillip

1999-01-01

Uniform-DFT filter banks are an important class of filter banks and their theory is well known. One notable characteristic is their very efficient implementation when using polyphase filters and the FFT. Separately, linear phase filter banks, i.e. filter banks in which the analysis filters have a linear phase are also an important class of filter banks and desired in many applications. Unfortunately, it has been proved that one cannot design critically-sampled, uniform-DFT, linear phase filter banks and achieve perfect reconstruction. In this paper, we present a least-squares solution to this problem and in addition prove that oversampled, uniform-DFT, linear phase filter banks (which are also useful in many applications) can be constructed for perfect reconstruction. Design examples are included illustrate the methods.

Inhibition of Late and Early Phases of Cancer Metastasis by the NF-κB Inhibitor DHMEQ Derived from Microbial Bioactive Metabolite Epoxyquinomicin: A Review.

PubMed

Lin, Yinzhi; Ukaji, Tamami; Koide, Naoki; Umezawa, Kazuo

2018-03-03

We previously designed and synthesized dehydroxyepoxyquinomicin (DHMEQ) as an inhibitor of NF-κB based on the structure of microbial secondary metabolite epoxyquinomicin C. DHMEQ showed anti-inflammatory and anticancer activity in various in vivo disease models without toxicity. On the other hand, the process of cancer metastasis consists of cell detachment from the primary tumor, invasion, transportation by blood or lymphatic vessels, invasion, attachment, and formation of secondary tumor. Cell detachment from the primary tumor and subsequent invasion are considered to be early phases of metastasis, while tumor cell attachment to the tissue and secondary tumor formation the late phases. The assay system for the latter phase was set up with intra-portal-vein injection of pancreatic cancer cells. Intraperitoneal administration of DHMEQ was found to inhibit liver metastasis possibly by decreasing the expression of MMP-9 and IL-8. Also, when the pancreatic cancer cells treated with DHMEQ were inoculated into the peritoneal cavity of mice, the metastatic foci formation was inhibited. These results indicate that DHMEQ is likely to inhibit the late phase of metastasis. Meanwhile, we have recently employed three-dimensional (3D) culture of breast cancer cells for the model of early phase metastasis, since the 3D invasion just includes cell detachment and invasion into the matrix. DHMEQ inhibited the 3D invasion of breast cancer cells at 3D-nontoxic concentrations. In this way, DHMEQ was shown to inhibit the late and early phases of metastasis. Thus, DHMEQ is likely to be useful for the suppression of cancer metastasis.

Early follicular phase hormone levels in relation to patterns of alcohol, tobacco, and coffee use.

PubMed

Lucero, J; Harlow, B L; Barbieri, R L; Sluss, P; Cramer, D W

2001-10-01

To examine the effects of alcohol, caffeine, and tobacco use on early follicular phase FSH, LH, E2, and sex hormone-binding globulin (SHBG). Cross-sectional study. Academic medical center. Four hundred ninety-eight women selected from the general population, ages 36-45, who were not currently pregnant, breast feeding, or using exogenous hormones. A general questionnaire assessing demography, anthropometry, and smoking habits and a standardized dietary questionnaire assessing food and beverage frequencies, including sources of alcohol and caffeine. FSH, LH, E2, and SHBG levels measured during the early follicular phase of the menstrual cycle. Significant associations observed in a univariate analysis included age > or =40 and current smoking associated with higher FSH; higher body mass index (BMI) associated with lower SHBG levels; and daily alcohol use, cholesterol consumption greater than the median, and coffee use >1 cup/d associated with higher E2 levels. In a multivariate model, total caffeine use was significantly associated with E2 levels after adjustment for age, BMI, total calories, current smoking, alcohol, cholesterol consumption, and day of sampling. Early follicular phase E2 increased from 28.2 pg/mL for women consuming < or =100 mg of caffeine to 45.2 pg/mL for women consuming > or =500 mg of caffeine per day, about a 70% increase. Coffee consumption and total caffeine use may increase early follicular phase E2 levels independent of related habits of alcohol or tobacco use.

Towards Risk Based Design for NASA's Missions

NASA Technical Reports Server (NTRS)

Tumer, Irem Y.; Barrientos, Francesca; Meshkat, Leila

2004-01-01

This paper describes the concept of Risk Based Design in the context of NASA s low volume, high cost missions. The concept of accounting for risk in the design lifecycle has been discussed and proposed under several research topics, including reliability, risk analysis, optimization, uncertainty, decision-based design, and robust design. This work aims to identify and develop methods to enable and automate a means to characterize and optimize risk, and use risk as a tradeable resource to make robust and reliable decisions, in the context of the uncertain and ambiguous stage of early conceptual design. This paper first presents a survey of the related topics explored in the design research community as they relate to risk based design. Then, a summary of the topics from the NASA-led Risk Colloquium is presented, followed by current efforts within NASA to account for risk in early design. Finally, a list of "risk elements", identified for early-phase conceptual design at NASA, is presented. The purpose is to lay the foundation and develop a roadmap for future work and collaborations for research to eliminate and mitigate these risk elements in early phase design.

Development and application of a biorelevant dissolution method using USP apparatus 4 in early phase formulation development.

PubMed

Fang, Jiang B; Robertson, Vivian K; Rawat, Archana; Flick, Tawnya; Tang, Zhe J; Cauchon, Nina S; McElvain, James S

2010-10-04

Dissolution testing is frequently used to determine the rate and extent at which a drug is released from a dosage form, and it plays many important roles throughout drug product development. However, the traditional dissolution approach often emphasizes its application in quality control testing and usually strives to obtain 100% drug release. As a result, dissolution methods are not necessarily biorelevant and meaningful application of traditional dissolution methods in the early phases of drug product development can be very limited. This article will describe the development of a biorelevant in vitro dissolution method using USP apparatus 4, biorelevant media, and real-time online UV analysis. Several case studies in the areas of formulation selection, lot-to-lot variability, and food effect will be presented to demonstrate the application of this method in early phase formulation development. This biorelevant dissolution method using USP apparatus 4 provides a valuable tool to predict certain aspects of the in vivo drug release. It can be used to facilitate the formulation development/selection for pharmacokinetic (PK) and clinical studies. It may also potentially be used to minimize the number of PK studies, and to aid in the design of more efficient PK and clinical studies.

Pedagogy and Space: Design Inspirations for Early Childhood Classrooms

ERIC Educational Resources Information Center

Zane, Linda M.

2015-01-01

The intersection of design and learning is a new and burgeoning area of interest in all levels of education. "Pedagogy and Space" combines architectural design information with early childhood theory to enhance children's learning and educators' experience within the space. Filled with colorful, inspiring photographs of intentionally…

The Advanced Technology Solar Telescope: design and early construction

NASA Astrophysics Data System (ADS)

McMullin, Joseph P.; Rimmele, Thomas R.; Keil, Stephen L.; Warner, Mark; Barden, Samuel; Bulau, Scott; Craig, Simon; Goodrich, Bret; Hansen, Eric; Hegwer, Steve; Hubbard, Robert; McBride, William; Shimko, Steve; Wöger, Friedrich; Ditsler, Jennifer

2012-09-01

The National Solar Observatory’s (NSO) Advanced Technology Solar Telescope (ATST) is the first large U.S. solar telescope accessible to the worldwide solar physics community to be constructed in more than 30 years. The 4-meter diameter facility will operate over a broad wavelength range (0.35 to 28 μm ), employing adaptive optics systems to achieve diffraction limited imaging and resolve features approximately 20 km on the Sun; the key observational parameters (collecting area, spatial resolution, spectral coverage, polarization accuracy, low scattered light) enable resolution of the theoretically-predicted, fine-scale magnetic features and their dynamics which modulate the radiative output of the sun and drive the release of magnetic energy from the Sun’s atmosphere in the form of flares and coronal mass ejections. In 2010, the ATST received a significant fraction of its funding for construction. In the subsequent two years, the project has hired staff and opened an office on Maui. A number of large industrial contracts have been placed throughout the world to complete the detailed designs and begin constructing the major telescope subsystems. These contracts have included the site development, AandE designs, mirrors, polishing, optic support assemblies, telescope mount and coudé rotator structures, enclosure, thermal and mechanical systems, and high-level software and controls. In addition, design development work on the instrument suite has undergone significant progress; this has included the completion of preliminary design reviews (PDR) for all five facility instruments. Permitting required for physically starting construction on the mountaintop of Haleakalā, Maui has also progressed. This paper will review the ATST goals and specifications, describe each of the major subsystems under construction, and review the contracts and lessons learned during the contracting and early construction phases. Schedules for site construction, key factory testing of

Iteration in Early-Elementary Engineering Design

NASA Astrophysics Data System (ADS)

McFarland Kendall, Amber Leigh

K-12 standards and curricula are beginning to include engineering design as a key practice within Science Technology Engineering and Mathematics (STEM) education. However, there is little research on how the youngest students engage in engineering design within the elementary classroom. This dissertation focuses on iteration as an essential aspect of engineering design, and because research at the college and professional level suggests iteration improves the designer's understanding of problems and the quality of design solutions. My research presents qualitative case studies of students in kindergarten and third-grade as they engage in classroom engineering design challenges which integrate with traditional curricula standards in mathematics, science, and literature. I discuss my results through the lens of activity theory, emphasizing practices, goals, and mediating resources. Through three chapters, I provide insight into how early-elementary students iterate upon their designs by characterizing the ways in which lesson design impacts testing and revision, by analyzing the plan-driven and experimentation-driven approaches that student groups use when solving engineering design challenges, and by investigating how students attend to constraints within the challenge. I connect these findings to teacher practices and curriculum design in order to suggest methods of promoting iteration within open-ended, classroom-based engineering design challenges. This dissertation contributes to the field of engineering education by providing evidence of productive engineering practices in young students and support for the value of engineering design challenges in developing students' participation and agency in these practices.

Statistical aspects of the TNK-S2B trial of tenecteplase versus alteplase in acute ischemic stroke: an efficient, dose-adaptive, seamless phase II/III design.

PubMed

Levin, Bruce; Thompson, John L P; Chakraborty, Bibhas; Levy, Gilberto; MacArthur, Robert; Haley, E Clarke

2011-08-01

TNK-S2B, an innovative, randomized, seamless phase II/III trial of tenecteplase versus rt-PA for acute ischemic stroke, terminated for slow enrollment before regulatory approval of use of phase II patients in phase III. (1) To review the trial design and comprehensive type I error rate simulations and (2) to discuss issues raised during regulatory review, to facilitate future approval of similar designs. In phase II, an early (24-h) outcome and adaptive sequential procedure selected one of three tenecteplase doses for phase III comparison with rt-PA. Decision rules comparing this dose to rt-PA would cause stopping for futility at phase II end, or continuation to phase III. Phase III incorporated two co-primary hypotheses, allowing for a treatment effect at either end of the trichotomized Rankin scale. Assuming no early termination, four interim analyses and one final analysis of 1908 patients provided an experiment-wise type I error rate of <0.05. Over 1,000 distribution scenarios, each involving 40,000 replications, the maximum type I error in phase III was 0.038. Inflation from the dose selection was more than offset by the one-half continuity correction in the test statistics. Inflation from repeated interim analyses was more than offset by the reduction from the clinical stopping rules for futility at the first interim analysis. Design complexity and evolving regulatory requirements lengthened the review process. (1) The design was innovative and efficient. Per protocol, type I error was well controlled for the co-primary phase III hypothesis tests, and experiment-wise. (2a) Time must be allowed for communications with regulatory reviewers from first design stages. (2b) Adequate type I error control must be demonstrated. (2c) Greater clarity is needed on (i) whether this includes demonstration of type I error control if the protocol is violated and (ii) whether simulations of type I error control are acceptable. (2d) Regulatory agency concerns that protocols

Test Design Optimization in CAT Early Stage with the Nominal Response Model

ERIC Educational Resources Information Center

Passos, Valeria Lima; Berger, Martijn P. F.; Tan, Frans E.

2007-01-01

The early stage of computerized adaptive testing (CAT) refers to the phase of the trait estimation during the administration of only a few items. This phase can be characterized by bias and instability of estimation. In this study, an item selection criterion is introduced in an attempt to lessen this instability: the D-optimality criterion. A…

A Path to Successful Energy Retrofits: Early Collaboration through Integrated Project Delivery Teams

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

Parrish, Kristen

2012-10-01

This document guides you through a process for the early design phases of retrofit projects to help you mitigate frustrations commonly experienced by building owners and designers. It outlines the value of forming an integrated project delivery team and developing a communication and information-sharing infrastructure that fosters collaboration. This guide does not present a complete process for designing an energy retrofit for a building. Instead, it focuses on the early design phase tasks related to developing and selecting energy efficiency measures (EEMs) that benefit from collaboration, and highlights the resulting advantages.

A phase I/II trial of AT9283, a selective inhibitor of aurora kinase in children with relapsed or refractory acute leukemia: challenges to run early phase clinical trials for children with leukemia.

PubMed

Vormoor, B; Veal, G J; Griffin, M J; Boddy, A V; Irving, J; Minto, L; Case, M; Banerji, U; Swales, K E; Tall, J R; Moore, A S; Toguchi, M; Acton, G; Dyer, K; Schwab, C; Harrison, C J; Grainger, J D; Lancaster, D; Kearns, P; Hargrave, D; Vormoor, J

2017-06-01

Aurora kinases regulate mitosis and are commonly overexpressed in leukemia. This phase I/IIa study of AT9283, a multikinase inhibitor, was designed to identify maximal tolerated doses, safety, pharmacokinetics, and pharmacodynamic activity in children with relapsed/refractory acute leukemia. The trial suffered from poor recruitment and terminated early, therefore failing to identify its primary endpoints. AT9283 caused tolerable toxicity, but failed to show clinical responses. Future trials should be based on robust preclinical data that provide an indication of which patients may benefit from the experimental agent, and recruitment should be improved through international collaborations and early combination with established treatment strategies. © 2016 Wiley Periodicals, Inc.

Functional neuroanatomical correlates of episodic memory impairment in early phase psychosis

PubMed Central

Hummer, Tom A.; Vohs, Jenifer L.; Yung, Matthew G.; Liffick, Emily; Mehdiyoun, Nicole F.; Radnovich, Alexander J.; McDonald, Brenna C.; Saykin, Andrew J.; Breier, Alan

2015-01-01

Studies have demonstrated that episodic memory (EM) is often preferentially disrupted in schizophrenia. The neural substrates that mediate EM impairment in this illness are not fully understood. Several functional magnetic resonance imaging (fMRI) studies have employed EM probe tasks to elucidate the neural underpinnings of impairment, though results have been inconsistent. The majority of EM imaging studies have been conducted in chronic forms of schizophrenia with relatively few studies in early phase patients. Early phase schizophrenia studies are important because they may provide information regarding when EM deficits occur and address potential confounds more frequently observed in chronic populations. In this study, we assessed brain activation during the performance of visual scene encoding and recognition fMRI tasks in patients with earlyphase psychosis (n=35) and age, sex, and race matched healthy control subjects (n = 20). Patients demonstrated significantly lower activation than controls in the right hippocampus and left fusiform gyrus during scene encoding and lower activation in the posterior cingulate, precuneus, and left middle temporal cortex during recognition of target scenes. Symptom levels were not related to the imaging findings, though better cognitive performance in patients was associated with greater right hippocampal activation during encoding. These results provide evidence of altered function in neuroanatomical circuitry subserving EM early in the course of psychotic illness, which may have implications for pathophysiological models of this illness. PMID:25749917

Early cytokine modulation after the rapid induction phase of sublingual immunotherapy with mite monomeric allergoids.

PubMed

Di Gioacchino, M; Perrone, A; Petrarca, C; Di Claudio, F; Mistrello, G; Falagiani, P; Dadorante, V; Verna, N; Braga, M; Ballone, E; Cavallucci, E

2008-01-01

The influence of different treatment schedules of sublingual immunotherapy (SLIT) in activating IL-10-producing T-cells, crucial in inducing allergen-specific tolerance, is not completely understood. The present work was designed to evaluate allergen driven interleukin release by mononuclear cells in the early phase of SLIT, after application of different induction schemes. Twenty mite-allergic patients were enrolled, 10 (group A) treated with a traditional 98 day induction scheme and 10 (group B) with a 16 day scheme with monomeric allergoid vaccine. At the end of the induction phase, the cumulative doses taken by group A and group B patients were equivalent to 50.5 and 50.3 microg of mite group 1 allergens, respectively. The release of Th1-, Th2- and Treg-related interleukins was assessed in culture supernatants of 5 microg/ml Der-p1-stimulated mononuclear cells, isolated before and after the induction phases. No relevant treatment-related side effects were observed. Interleukin release was similar in the two groups at the enrolment. Non-stimulated and Der p 1 stimulated release of studied cytokines was similar in the two groups at enrolment. Der p 1 stimulation significantly increased IL-10 release (p<0.0002) after treatment in group B patients, and this effect was higher (p=0.05) compared to group A patients. Furthermore, at the end of SLIT induction TNF-alpha, IL-4 and IFN-gamma production were reduced in group B patients (p<0.05, p=0.062 and p=0.060, respectively). The rapid induction scheme of sublingual immunotherapy induces an early immune suppression more effectively than the slower one. The rapid induction scheme should be the preferential way to start sublingual immunotherapy, particularly when monomeric allergoids are utilized.

Cabling design for phased arrays

NASA Technical Reports Server (NTRS)

Kruger, I. D.; Turkiewicz, L.

1972-01-01

The ribbon-cabling system used for the AEGIS phased array which provides minimum cable bulk, complete EMI shielding, rugged mechanical design, repeatable electrical characteristics, and ease of assembly and maintenance is described. The ribbon cables are 0.040-inch thick, and in widths up to 2 1/2 inches. Their terminations are molded connectors that can be grouped in a three-tier arrangement, with cable branching accomplished by a matrix-welding technique.

Treatment of Early-Onset Schizophrenia Spectrum Disorders (TEOSS): Rationale, Design, and Methods

ERIC Educational Resources Information Center

McClellan, Jon; Sikich, Linmarie; Findling, Robert L.; Frazier, Jean A.; Vitiello, Benedetto; Hlastala, Stefanie A.; Williams, Emily; Ambler, Denisse; Hunt-Harrison, Tyehimba; Maloney, Ann E.; Ritz, Louise; Anderson, Robert; Hamer, Robert M.; Lieberman, Jeffrey A.

2007-01-01

Objective: The Treatment of Early Onset Schizophrenia Spectrum Disorders Study is a publicly funded clinical trial designed to compare the therapeutic benefits, safety, and tolerability of risperidone, olanzapine, and molindone in youths with early-onset schizophrenia spectrum disorders. The rationale, design, and methods of the Treatment of Early…

Design definition of the Laser Atmospheric Wind Sounder (LAWS), phase 2. Volume 1: Executive summary

NASA Technical Reports Server (NTRS)

1992-01-01

recommends a 6-1/2 year phase C/D program for LAWS to provide adequate feedback from the engineering unit and the qualification unit to the final flight unit. Assuming a one year period for LAWS integration to the spacecraft, followed by a six-month period for launch vehicle integration, LAWS could be successfully developed and launched in eight years. Our baseline design or downsized design can be accommodated by either the Atlas 2AS or the Delta launch vehicles. Lockheed's recommendation is that, based on the successful phase 2 design study and breadboard program, a follow-on 18 month extended breadboard testing program and additional system engineering studies, primarily in interfacing with a to be defined platform, be initiated. This should be immediately followed by the phase C/D program, leading to a LAWS launch in late 2001 or early 2002.

Pilot Study Assessing the Feasibility of Applying Bilateral Subthalamic Nucleus Deep Brain Stimulation in Very Early Stage Parkinson's Disease: Study design and rationale

PubMed Central

Charles, David; Tolleson, Christopher; Davis, Thomas L.; Gill, Chandler E.; Molinari, Anna L.; Bliton, Mark J.; Tramontana, Michael G.; Salomon, Ronald M.; Kao, Chris; Wang, Lily; Hedera, Peter; Phibbs, Fenna T.; Neimat, Joseph S.; Konrad, Peter E.

2014-01-01

Background Deep brain stimulation provides significant symptomatic benefit for people with advanced Parkinson's disease whose symptoms are no longer adequately controlled with medication. Preliminary evidence suggests that subthalamic nucleus stimulation may also be efficacious in early Parkinson's disease, and results of animal studies suggest that it may spare dopaminergic neurons in the substantia nigra. Objective We report the methodology and design of a novel Phase I clinical trial testing the safety and tolerability of deep brain stimulation in early Parkinson's disease and discuss previous failed attempts at neuroprotection. Methods We recently conducted a prospective, randomized, parallel-group, single-blind pilot clinical trial of deep brain stimulation in early Parkinson's disease. Subjects were randomized to receive either optimal drug therapy or deep brain stimulation plus optimal drug therapy. Follow-up visits occurred every six months for a period of two years and included week-long therapy washouts. Results Thirty subjects with Hoehn & Yahr Stage II idiopathic Parkinson's disease were enrolled over a period of 32 months. Twenty-nine subjects completed all follow-up visits; one patient in the optimal drug therapy group withdrew from the study after baseline. Baseline characteristics for all thirty patients were not significantly different. Conclusions This study demonstrates that it is possible to recruit and retain subjects in a clinical trial testing deep brain stimulation in early Parkinson's disease. The results of this trial will be used to support the design of a Phase III, multicenter trial investigating the efficacy of deep brain stimulation in early Parkinson's disease. PMID:23938229

78 FR 5816 - Guidance for Industry on Clinical Pharmacogenomics: Premarket Evaluation in Early-Phase Clinical...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-28

.... The guidance provides recommendations on when and how genomic principles should be considered and... recommendations on when and how genomic principles should be considered and applied in early-phase clinical... the larger, later adequate, and well-controlled trials (phase 3) that are needed to support marketing...

Best practices of Building Information Modelling (BIM) implementation in design phase for construction project

NASA Astrophysics Data System (ADS)

Kasim, N.; Zainal Abidin, N. A.; Zainal, R.; Sarpin, N.; Rahim, M. H. I. Abd; Saikah, M.

2017-11-01

Implementation of Building Information Modelling (BIM) was expected to bring improvement in current practices of Malaysian construction industry. In the design phase, there is a lack of a ready pool of skilled workers who are able to develop BIM strategic plan and effectively utilise it. These create boundaries for BIM nature in Malaysian construction industry specifically in the design phase to achieve its best practices. Therefore, the objectives of this research are to investigate the current practices of BIM implementation in the design phase as well as the best practices factors of BIM implementation in the design phase. The qualitative research approach is carried out through semi-structured interviews with the designers of different organisations which adopt BIM in the design phase. Data collection is analysed by executing content analysis method. From the findings, the best practices factors of BIM implementation in design phase such as the incentive for BIM training, formal approach to monitoring automated Level of Detailing (LOD), run a virtual meeting and improve Industry Foundation Class (IFC). Thus, best practices factors which lead to practices improvements in the design phase of project development which subsequently improves the implementation of BIM in the design phase of Malaysian construction industry.

Formal Verification Toolkit for Requirements and Early Design Stages

NASA Technical Reports Server (NTRS)

Badger, Julia M.; Miller, Sheena Judson

2011-01-01

Efficient flight software development from natural language requirements needs an effective way to test designs earlier in the software design cycle. A method to automatically derive logical safety constraints and the design state space from natural language requirements is described. The constraints can then be checked using a logical consistency checker and also be used in a symbolic model checker to verify the early design of the system. This method was used to verify a hybrid control design for the suit ports on NASA Johnson Space Center's Space Exploration Vehicle against safety requirements.

Evaluation of HiPHES convective reformer design alternatives. Phase 2, Final issue

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

Not Available

1991-08-01

Phase I Stone & Webster presented three potential design configurations for a ceramic-tubed steam-methane reformer. These were the Tube-Within-a-Tube (TWIT) design, the Once-Through design, and the Monolith design. Although the TWIT design configuration appeared to be the most viable, the inclusion of a more detailed examination of design alternatives for the HiPHES reformer was deemed appropriate for the Phase II program. Of particular concern was the length of the ceramic tubes required for the TWIT design. To assist in this evaluation, Stone & Webster established a Development Team consisting of specialists in the areas of heat transfer, ceramic materials, exchangermore » design, vessel design, and potential users. Stone & Webster reviewed the critical areas of concern for a ceramic convective reformer, evaluated competing design configurations, and presented the results to the Development Team. This report presents Stone & Webster`s evaluations and the comments and recommendations of the Development Team. This effort comprised the majority of Task 1 of Phase II of Stone & Webster`s HiPHES project. The design review was executed in parallel with the material coupon screening tests at BP America. The goal of both tasks was to confirm the materials selection and reformer design configuration so that the conditions for the tube and joint tests to be conducted at Oak Ridge National Laboratory (ORNL) could be specified. The ORNL tests are intended to evaluate the reformer design configuration and materials of construction used for the reformer design in Phase II, and to be used in the demonstration unit in Phase III. The Task 1 (Evaluation of Alternative Reformer Designs) effort has identified a preferred design configuration for the proposed ceramic reformer. Additional engineering and material evaluation work is necessary before an operating prototype can be designed.« less

Satellite Systems Design/Simulation Environment: A Systems Approach to Pre-Phase A Design

NASA Technical Reports Server (NTRS)

Ferebee, Melvin J., Jr.; Troutman, Patrick A.; Monell, Donald W.

1997-01-01

A toolset for the rapid development of small satellite systems has been created. The objective of this tool is to support the definition of spacecraft mission concepts to satisfy a given set of mission and instrument requirements. The objective of this report is to provide an introduction to understanding and using the SMALLSAT Model. SMALLSAT is a computer-aided Phase A design and technology evaluation tool for small satellites. SMALLSAT enables satellite designers, mission planners, and technology program managers to observe the likely consequences of their decisions in terms of satellite configuration, non-recurring and recurring cost, and mission life cycle costs and availability statistics. It was developed by Princeton Synergetic, Inc. and User Systems, Inc. as a revision of the previous TECHSAT Phase A design tool, which modeled medium-sized Earth observation satellites. Both TECHSAT and SMALLSAT were developed for NASA.

Geoeffectiveness during the early phase of Solar Cycle 24

NASA Astrophysics Data System (ADS)

Pande, Bimal

Geoeffectiveness during the early phase of Solar Cycle 24 \\underline{} Abstract\\underline{} It is very important and interesting to understand the solar eruptions because it produces the geoeffectiveness in our Earth environment. In the rise phase of the solar cycle, geoeffective events are less frequent, thus this provide us better opportunity to study these events including the detection of their source regions. Keeping this in mind, we have analysed the data of rise phase of current solar cycle 24 ( 2009-2012). During above time period, we have selected 59 geoeffective events having Disturbance Storm Time (Dst) index < -50 nT. Based on the Dst index, we divided the events into two categories i.e. moderate (< -50 nT > -100 nT ) and intense ( <-100 nT). To locate the solar source regions of geoeffective and SEPs associated events, we have used available images, movies and Solar Geophysical data (SGD) list: for example movies from SOHO/EIT, images and movies from the Solar Dynamic Observatory (SDO). In this study, we will discuss and compare the different properties of associated CMEs, flares and their relation with geoeffectiveness.

Bayesian Optimal Interval Design: A Simple and Well-Performing Design for Phase I Oncology Trials

PubMed Central

Yuan, Ying; Hess, Kenneth R.; Hilsenbeck, Susan G.; Gilbert, Mark R.

2016-01-01

Despite more than two decades of publications that offer more innovative model-based designs, the classical 3+3 design remains the most dominant phase I trial design in practice. In this article, we introduce a new trial design, the Bayesian optimal interval (BOIN) design. The BOIN design is easy to implement in a way similar to the 3+3 design, but is more flexible for choosing the target toxicity rate and cohort size and yields a substantially better performance that is comparable to that of more complex model-based designs. The BOIN design contains the 3+3 design and the accelerated titration design as special cases, thus linking it to established phase I approaches. A numerical study shows that the BOIN design generally outperforms the 3+3 design and the modified toxicity probability interval (mTPI) design. The BOIN design is more likely than the 3+3 design to correctly select the maximum tolerated dose (MTD) and allocate more patients to the MTD. Compared to the mTPI design, the BOIN design has a substantially lower risk of overdosing patients and generally a higher probability of correctly selecting the MTD. User-friendly software is freely available to facilitate the application of the BOIN design. PMID:27407096

Phase A design study of microgravity fluoride fiber puller

NASA Technical Reports Server (NTRS)

Workman, Gary L.; Smith, Guy A.; Kosten, Susan

1994-01-01

Improved transmission properties for fluoride fibers due to space processing has great potential for commercial benefits. Phase A design study will determine conceptual feasibility and provide initial definition of the technical requirements and design issues for space.

Early Validation of Failure Detection, Isolation, and Recovery Design Using Heterogeneous Modelling and Simulation

NASA Astrophysics Data System (ADS)

van der Plas, Peter; Guerriero, Suzanne; Cristiano, Leorato; Rugina, Ana

2012-08-01

Modelling and simulation can support a number of use cases across the spacecraft development life-cycle. Given the increasing complexity of space missions, the observed general trend is for a more extensive usage of simulation already in the early phases. A major perceived advantage is that modelling and simulation can enable the validation of critical aspects of the spacecraft design before the actual development is started, as such reducing the risk in later phases.Failure Detection, Isolation, and Recovery (FDIR) is one of the areas with a high potential to benefit from early modelling and simulation. With the increasing level of required spacecraft autonomy, FDIR specifications can grow in such a way that the traditional document-based review process soon becomes inadequate.This paper shows that FDIR modelling and simulation in a system context can provide a powerful tool to support the FDIR verification process. It is highlighted that FDIR modelling at this early stage requires heterogeneous modelling tools and languages, in order to provide an adequate functional description of the different components (i.e. FDIR functions, environment, equipment, etc.) to be modelled.For this reason, an FDIR simulation framework is proposed in this paper. This framework is based on a number of tools already available in the Avionics Systems Laboratory at ESTEC, which are the Avionics Test Bench Functional Engineering Simulator (ATB FES), Matlab/Simulink, TASTE, and Real Time Developer Studio (RTDS).The paper then discusses the application of the proposed simulation framework to a real case-study, i.e. the FDIR modelling of a satellite in support of actual ESA mission. Challenges and benefits of the approach are described. Finally, lessons learned and the generality of the proposed approach are discussed.

Biomarker-Guided Adaptive Trial Designs in Phase II and Phase III: A Methodological Review

PubMed Central

Antoniou, Miranta; Jorgensen, Andrea L; Kolamunnage-Dona, Ruwanthi

2016-01-01

Background Personalized medicine is a growing area of research which aims to tailor the treatment given to a patient according to one or more personal characteristics. These characteristics can be demographic such as age or gender, or biological such as a genetic or other biomarker. Prior to utilizing a patient’s biomarker information in clinical practice, robust testing in terms of analytical validity, clinical validity and clinical utility is necessary. A number of clinical trial designs have been proposed for testing a biomarker’s clinical utility, including Phase II and Phase III clinical trials which aim to test the effectiveness of a biomarker-guided approach to treatment; these designs can be broadly classified into adaptive and non-adaptive. While adaptive designs allow planned modifications based on accumulating information during a trial, non-adaptive designs are typically simpler but less flexible. Methods and Findings We have undertaken a comprehensive review of biomarker-guided adaptive trial designs proposed in the past decade. We have identified eight distinct biomarker-guided adaptive designs and nine variations from 107 studies. Substantial variability has been observed in terms of how trial designs are described and particularly in the terminology used by different authors. We have graphically displayed the current biomarker-guided adaptive trial designs and summarised the characteristics of each design. Conclusions Our in-depth overview provides future researchers with clarity in definition, methodology and terminology for biomarker-guided adaptive trial designs. PMID:26910238

Vestibular Function Research (VFR) experiment. Phase B: Design definition study

NASA Technical Reports Server (NTRS)

1978-01-01

The Vestibular Functions Research (VFR) Experiment was established to investigate the neurosensory and related physiological processes believed to be associated with the space flight nausea syndrome and to develop logical means for its prediction, prevention and treatment. The VFR Project consists of ground and spaceflight experimentation using frogs as specimens. The phase B Preliminary Design Study provided for the preliminary design of the experiment hardware, preparation of performance and hardware specification and a Phase C/D development plan, establishment of STS (Space Transportation System) interfaces and mission operations, and the study of a variety of hardware, experiment and mission options. The study consist of three major tasks: (1) mission mode trade-off; (2) conceptual design; and (3) preliminary design.

Bayesian Optimal Interval Design: A Simple and Well-Performing Design for Phase I Oncology Trials.

PubMed

Yuan, Ying; Hess, Kenneth R; Hilsenbeck, Susan G; Gilbert, Mark R

2016-09-01

Despite more than two decades of publications that offer more innovative model-based designs, the classical 3 + 3 design remains the most dominant phase I trial design in practice. In this article, we introduce a new trial design, the Bayesian optimal interval (BOIN) design. The BOIN design is easy to implement in a way similar to the 3 + 3 design, but is more flexible for choosing the target toxicity rate and cohort size and yields a substantially better performance that is comparable with that of more complex model-based designs. The BOIN design contains the 3 + 3 design and the accelerated titration design as special cases, thus linking it to established phase I approaches. A numerical study shows that the BOIN design generally outperforms the 3 + 3 design and the modified toxicity probability interval (mTPI) design. The BOIN design is more likely than the 3 + 3 design to correctly select the MTD and allocate more patients to the MTD. Compared with the mTPI design, the BOIN design has a substantially lower risk of overdosing patients and generally a higher probability of correctly selecting the MTD. User-friendly software is freely available to facilitate the application of the BOIN design. Clin Cancer Res; 22(17); 4291-301. ©2016 AACR. ©2016 American Association for Cancer Research.

A design concept for an MMIC (Monolithic Microwave Integrated Circuit) microstrip phased array

NASA Technical Reports Server (NTRS)

Lee, Richard Q.; Smetana, Jerry; Acosta, Roberto

1987-01-01

A conceptual design for a microstrip phased array with monolithic microwave integrated circuit (MMIC) amplitude and phase controls is described. The MMIC devices used are 20 GHz variable power amplifiers and variable phase shifters recently developed by NASA contractors for applications in future Ka proposed design, which concept is for a general NxN element array of rectangular lattice geometry. Subarray excitation is incorporated in the MMIC phased array design to reduce the complexity of the beam forming network and the number of MMIC components required.

Bayesian adaptive phase II screening design for combination trials.

PubMed

Cai, Chunyan; Yuan, Ying; Johnson, Valen E

2013-01-01

Trials of combination therapies for the treatment of cancer are playing an increasingly important role in the battle against this disease. To more efficiently handle the large number of combination therapies that must be tested, we propose a novel Bayesian phase II adaptive screening design to simultaneously select among possible treatment combinations involving multiple agents. Our design is based on formulating the selection procedure as a Bayesian hypothesis testing problem in which the superiority of each treatment combination is equated to a single hypothesis. During the trial conduct, we use the current values of the posterior probabilities of all hypotheses to adaptively allocate patients to treatment combinations. Simulation studies show that the proposed design substantially outperforms the conventional multiarm balanced factorial trial design. The proposed design yields a significantly higher probability for selecting the best treatment while allocating substantially more patients to efficacious treatments. The proposed design is most appropriate for the trials combining multiple agents and screening out the efficacious combination to be further investigated. The proposed Bayesian adaptive phase II screening design substantially outperformed the conventional complete factorial design. Our design allocates more patients to better treatments while providing higher power to identify the best treatment at the end of the trial.

Bayesian adaptive phase II screening design for combination trials

PubMed Central

Cai, Chunyan; Yuan, Ying; Johnson, Valen E

2013-01-01

Background Trials of combination therapies for the treatment of cancer are playing an increasingly important role in the battle against this disease. To more efficiently handle the large number of combination therapies that must be tested, we propose a novel Bayesian phase II adaptive screening design to simultaneously select among possible treatment combinations involving multiple agents. Methods Our design is based on formulating the selection procedure as a Bayesian hypothesis testing problem in which the superiority of each treatment combination is equated to a single hypothesis. During the trial conduct, we use the current values of the posterior probabilities of all hypotheses to adaptively allocate patients to treatment combinations. Results Simulation studies show that the proposed design substantially outperforms the conventional multiarm balanced factorial trial design. The proposed design yields a significantly higher probability for selecting the best treatment while allocating substantially more patients to efficacious treatments. Limitations The proposed design is most appropriate for the trials combining multiple agents and screening out the efficacious combination to be further investigated. Conclusions The proposed Bayesian adaptive phase II screening design substantially outperformed the conventional complete factorial design. Our design allocates more patients to better treatments while providing higher power to identify the best treatment at the end of the trial. PMID:23359875

Early Design Energy Analysis Using Building Information Modeling Technology

DTIC Science & Technology

2011-11-01

building, (a) floor plan and (b) 3D image. ....................................... 50 Figure 28. Comparison of different energy estimates...when they make the biggest impact on building life-cycle costs. Traditionally, most building energy analyses have been conducted late in design, by...complete energy analysis. This method enables project teams to make energy conscious decisions early in design when they impact building life-cycle

Designing of a small wearable conformal phased array antenna for wireless communications

NASA Astrophysics Data System (ADS)

Roy, Sayan

In this thesis, a unique design of a self-adapting conformal phased-array antenna system for wireless communications is presented. The antenna system is comprised of one microstrip antenna array and a sensor circuit. A 1x4 printed microstrip patch antenna array was designed on a flexible substrate with a resonant frequency of 2.47 GHz. However, the performance of the antenna starts to degrade as the curvature of the surface of the substrate changes. To recover the performance of the system, a flexible sensor circuitry was designed. This sensor circuitry uses analog phase shifters, a flexible resistor and operational-amplifier circuitry to compensate the phase of each array element of the antenna. The proposed analytical method for phase compensation has been first verified by designing an RF test platform consisting of a microstrip antenna array, commercially available analog phase shifters, analog voltage attenuators, 4-port power dividers and amplifiers. The platform can be operated through a LabVIEW GUI interface using a 12-bit digital-to-analog converter. This test board was used to design and calibrate the sensor circuitry by observing the behavior of the antenna array system on surfaces with different curvatures. In particular, this phased array antenna system was designed to be used on the surface of a spacesuit or any other flexible prototype. This work was supported in part by the Defense Miroelectronics Activity (DMEA), NASA ND EPSCoR and DARPA/MTO.

Numerical analysis of nonminimum phase zero for nonuniform link design

NASA Technical Reports Server (NTRS)

Girvin, Douglas L.; Book, Wayne J.

1991-01-01

As the demand for light-weight robots that can operate in a large workspace increases, the structural flexibility of the links becomes more of an issue in control. When the objective is to accurately position the tip while the robot is actuated at the base, the system is nonminimum phase. One important characteristic of nonminimum phase systems is system zeros in the right half of the Laplace plane. The ability to pick the location of these nonminimum phase zeros would give the designer a new freedom similar to pole placement. This research targets a single-link manipulator operating in the horizontal plane and modeled as a Euler-Bernoulli beam with pinned-free end conditions. Using transfer matrix theory, one can consider link designs that have variable cross-sections along the length of the beam. A FORTRAN program was developed to determine the location of poles and zeros given the system model. The program was used to confirm previous research on nonminimum phase systems, and develop a relationship for designing linearly tapered links. The method allows the designer to choose the location of the first pole and zero and then defines the appropriate taper to match the desired locations. With the pole and zero location fixed, the designer can independently change the link's moment of inertia about its axis of rotation by adjusting the height of the beam. These results can be applied to the inverse dynamic algorithms that are currently under development.

Numerical analysis of nonminimum phase zero for nonuniform link design

NASA Astrophysics Data System (ADS)

Girvin, Douglas L.; Book, Wayne J.

1991-11-01

As the demand for light-weight robots that can operate in a large workspace increases, the structural flexibility of the links becomes more of an issue in control. When the objective is to accurately position the tip while the robot is actuated at the base, the system is nonminimum phase. One important characteristic of nonminimum phase systems is system zeros in the right half of the Laplace plane. The ability to pick the location of these nonminimum phase zeros would give the designer a new freedom similar to pole placement. This research targets a single-link manipulator operating in the horizontal plane and modeled as a Euler-Bernoulli beam with pinned-free end conditions. Using transfer matrix theory, one can consider link designs that have variable cross-sections along the length of the beam. A FORTRAN program was developed to determine the location of poles and zeros given the system model. The program was used to confirm previous research on nonminimum phase systems, and develop a relationship for designing linearly tapered links. The method allows the designer to choose the location of the first pole and zero and then defines the appropriate taper to match the desired locations. With the pole and zero location fixed, the designer can independently change the link's moment of inertia about its axis of rotation by adjusting the height of the beam. These results can be applied to the inverse dynamic algorithms that are currently under development.

Decreased endometrial vascularity and receptivity in unexplained recurrent miscarriage patients during midluteal and early pregnancy phases.

PubMed

Tan, Shu-Yin; Hang, Fu; Purvarshi, Gowreesunkur; Li, Min-Qing; Meng, Da-Hua; Huang, Ling-Ling

2015-10-01

To evaluate the predictive value of three-dimensional (3D)-power Doppler sonography on recurrent miscarriage. The study patients were divided into a recurrent miscarriage group (30 cases) and a normal pregnancy group (21 cases). Measurement of endometrial thickness was performed using two-dimensional transvaginal ultrasound in the midluteal phase. The endometrial volume, vascularization index (VI), flow index (FI), and vascularization-flow index (VFI) in midluteal and placenta volume, as well as the VI, FI, and VFI of early pregnancy were measured using Virtual Organ Computer-aided Analysis of 3D-power Doppler ultrasound. Endometrial thickness, endometrial volume, endometrial vascular data, VI, FI, and VFI of the midluteal phase were lower in the recurrent miscarriage group compared with the normal pregnancy group (p < 0.05). Placental volume, VI, and VFI during early pregnancy were lower in the miscarriage group compared with the normal pregnancy group (p < 0.05). There was no significant change in FI between the recurrent miscarriage and control groups during early pregnancy (p > 0.05). The predictive accuracy of endometrial thickness, endometrial volume, VI, FI, and VFI in the midluteal phase, and placenta volume, VI, FI, and VFI in early pregnancy as measured by the receiver operating characteristic curve to predict miscarriage before 12 gestational weeks in participants was 0.681, 0.876, 0.770, 0.720, 0.879, 0.771, 0.907, 0.592, respectively. The 3D-power Doppler ultrasound is a more comprehensive and sensitive method for evaluating endometrial receptivity. Endometrial volume, VI, FI, and VFI in the midluteal phase, as well as VI in early pregnancy, can be considered as predictive factors for recurrent miscarriage. Copyright © 2015. Published by Elsevier B.V.

Conceptual design study for a teleoperator visual system, phase 1

NASA Technical Reports Server (NTRS)

Adams, D.; Grant, C.; Johnson, C.; Meirick, R.; Polhemus, C.; Ray, A.; Rittenhouse, D.; Skidmore, R.

1972-01-01

Results are reported for work performed during the first phase of the conceptual design study for a teleoperator visual system. This phase consists of four tasks: General requirements, concept development, subsystem requirements and analysis, and concept evaluation.

SARCOPENIA: DESIGNING PHASE IIB TRIALS

PubMed Central

CHUMLEA, WM.C.; CESARI, M.; EVANS, W.J.; FERRUCCI, L.; FIELDING, R.A.; PAHOR, M.; STUDENSKI, S.; VELLAS, B.

2012-01-01

Sarcopenia is the age-related involuntary loss of skeletal muscle mass and functionality that can lead to the development of disability, frailty and increased health care costs. The development of interventions aimed at preventing and/or treating sarcopenia is complex, requiring the adoption of assumptions and standards that are not well established scientifically or clinically. A number of investigators and clinicians (both from academia and industry) met in Rome (Italy) in 2009 to develop a consensus definition of sarcopenia. Subsequently, in Albuquerque (New Mexico, USA) in 2010, the same group met again to consider the complex issues necessary for designing Phase II clinical trials for sarcopenia. Current clinical trial data indicate that fat-free mass (FFM) parameters are responsive to physical activity/nutritional treatment modalities over short time periods, but pharmacological trials of sarcopenia have yet to show significant efficacy. In order to conduct a clinical trial within a reasonable time frame, groups that model or display accelerated aging and loss of FFM are necessary. Few studies have used acceptable designs for testing treatment effects, sample sizes or primary outcomes that could provide interpretable findings or effects across studies. Dual energy x ray absorptiometry (DXA) is the measure of choice for assessing FFM, but sufficient time is needed for changes to be detected accurately and reliably. A tool set that would allow clinical, basic and epidemiological research on sarcopenia to advance rapidly toward diagnosis and treatment phases should be those reflecting function and strength. PMID:21623466

Safety and effectiveness of stem cell therapies in early-phase clinical trials in stroke: a systematic review and meta-analysis.

PubMed

Nagpal, Anjali; Choy, Fong Chan; Howell, Stuart; Hillier, Susan; Chan, Fiona; Hamilton-Bruce, Monica A; Koblar, Simon A

2017-08-30

Stem cells have demonstrated encouraging potential as reparative therapy for patients suffering from post-stroke disability. Reperfusion interventions in the acute phase of stroke have shown significant benefit but are limited by a narrow window of opportunity in which they are beneficial. Thereafter, rehabilitation is the only intervention available. The current review summarises the current evidence for use of stem cell therapies in stroke from early-phase clinical trials. The safety and feasibility of administering different types of stem cell therapies in stroke seem to be reasonably proven. However, the effectiveness needs still to be established through bigger clinical trials with more pragmatic clinical trial designs that address the challenges raised by the heterogeneous nature of stroke per se, as well those due to unique characteristics of stem cells as therapeutic agents.

Design of Digital Phase-Locked Loops For Advanced Digital Transponders

NASA Technical Reports Server (NTRS)

Nguyen, Tien M.

1994-01-01

For advanced digital space transponders, the Digital Phased-Locked Loops (DPLLs) can be designed using the available analog loops. DPLLs considered in this paper are derived from the Analog Phase-Locked Loop (APLL) using S-domain mapping techniques.

Effects of temperature on early-phase transmission of Yersina pestis by the flea, Xenopsylla cheopis.

PubMed

Schotthoefer, Anna M; Bearden, Scott W; Vetter, Sara M; Holmes, Jennifer; Montenieri, John A; Graham, Christine B; Woods, Michael E; Eisen, Rebecca J; Gage, Kenneth L

2011-03-01

Sharp declines in human and animal cases of plague, caused by the bacterium Yersinia pestis (Yersin), have been observed when outbreaks coincide with hot weather. Failure of biofilm production, or blockage, to occur in the flea, as temperatures reach 30 degrees C has been suggested as an explanation for these declines. Recent work demonstrating efficient flea transmission during the first few days after fleas have taken an infectious blood meal, in the absence of blockage (e.g., early-phase transmission), however, has called this hypothesis into question. To explore the potential effects of temperature on early-phase transmission, we infected colony-reared Xenopsylla cheopis (Rothchild) fleas with a wild-type strain of plague bacteria using an artificial feeding system, and held groups of fleas at 10, 23, 27, and 30 degrees C. Naive Swiss Webster mice were exposed to fleas from each of these temperatures on days 1-4 postinfection, and monitored for signs of infection for 21 d. Temperature did not significantly influence the rates of transmission observed for fleas held at 23, 27, and 30 degrees C. Estimated per flea transmission efficiencies for these higher temperatures ranged from 2.32 to 4.96% (95% confidence interval [CI]: 0.96-8.74). In contrast, no transmission was observed in mice challenged by fleas held at 10 degrees C (per flea transmission efficiency estimates, 0-1.68%). These results suggest that declines in human and animal cases during hot weather are not related to changes in the abilities of X. cheopis fleas to transmit Y. pestis infections during the early-phase period. By contrast, transmission may be delayed or inhibited at low temperatures, indicating that epizootic spread of Y. pestis by X. cheopis via early-phase transmission is unlikely during colder periods of the year.

Early phase drugs and biologicals clinical trials on worldwide leading causes of death: a descriptive analysis.

PubMed

Dal-Ré, Rafael

2011-06-01

To describe the global effort targeting the major causes of mortality in terms of "open" early phase clinical trials with drugs and biologicals. Sixteen of the 20 leading causes of death were chosen; 9 of these were also amongst the top 10 causes of death in low-income countries. Studies were identified from the ClinicalTrials.gov database and included phase 1 and/or 2 "interventional" "open" trials, i.e. those recruiting or about to start recruitment. Trials were considered in terms of sponsorship [industry, universities and other organisations (UNO), and US federal agencies (NIH included)], genders and age groups included, and whether they were conducted with drugs and/or biologicals. The search was performed in March 2010. A total of 2,298 (824 phase 1; 1,474 phase 2) trials were retrieved. Of these, 67% were on trachea, bronchus, and lung cancers (25%); diabetes mellitus (15%); colon and rectum cancers (14%); and HIV/AIDS (12%). In contrast, only 4% were trials on diarrhoeal disease, nephrosis and nephritis, liver cirrhosis, and prematurity and low birth weight. UNO were the first source of funding. Fifty-two percent of phase 1 non-cancer trials were on healthy volunteers. Twenty-nine percent of all trials were co-funded. There were 4.6 times as many drug trials as those with biologicals. Only 7% were conducted with a combination of drugs and biologicals, the majority (78%) on cancers. Discrimination in terms of gender or age group was not observed. Four of the 16 diseases considered represented 2/3 of early phase trials. Cancers were a top priority for all sponsors. Increasing attention should be given to conditions with current and projected global high mortality rates that had few "open" early phase trials.

Optical Design of the WFIRST Phase-A Integral Field Channel

NASA Technical Reports Server (NTRS)

Gao, Guangjun; Pasquale, Bert A.; Marx, Catherine T.; Chambers, Victor

2017-01-01

WFIRST is one of NASA's Decadal Survey Missions and is currently in Phase-A development. The optical design of the WFIRST Integral Field Channel (IFC), one of three main optical channels of WFIRST, is presented, and the evolution of the IFC channel since Mission Concept Review (MCR, end of Pre-Phase A) is discussed. The IFC has two sub-channels: Supernova (IFC-S) and Galaxy (IFC-G) channels, with Fields of View of 3"x4.5" and 4.2"x9" respectively, and approximately R 75 spectral analysis over waveband 0.42 approximately 2.0 micrometers. The Phase-A IFC optical design meets image quality requirements over the FOV areas while balancing cost and volume constraints.

Design, analysis, and testing of the Phase 1 CSI Evolutionary Model erectable truss

NASA Technical Reports Server (NTRS)

Gronet, M. J.; Davis, D. A.; Kintis, D. H.; Brillhart, R. D.; Atkins, E. M.

1992-01-01

This report addressed the design, analysis, and testing of the erectable truss structure for the Phase 1 CSI Evolutionary Model (CEM) testbed. The Phase 1 CEM testbed is the second testbed to form part of an ongoing program of focused research at NASA/LaRC in the development of Controls-Structures Integration (CSI) technology. The Phase 1 CEM contains the same overall geometry, weight, and sensor locations as the Phase 0 CEM, but is based in an integrated controller and structure design, whereby both structure and controller design variables are sized simultaneously. The Phase 1 CEM design features seven truss sections composed of struts with tailored mass and stiffness properties. A common erectable joint is used and the strut stiffness is tailored by varying the cross-sectional area. To characterize the structure, static tests were conducted on individual struts and 10-bay truss assemblies. Dynamic tests were conducted on 10-bay truss assemblies as well as the fully-assembled CEM truss. The results indicate that the static and dynamic properties of the structure are predictable, well-characterized, and within the performance requirements established during the Phase 1 CEM integrated controller/structure design analysis.

An Expert System-Driven Method for Parametric Trajectory Optimization During Conceptual Design

NASA Technical Reports Server (NTRS)

Dees, Patrick D.; Zwack, Mathew R.; Steffens, Michael; Edwards, Stephen; Diaz, Manuel J.; Holt, James B.

2015-01-01

During the early phases of engineering design, the costs committed are high, costs incurred are low, and the design freedom is high. It is well documented that decisions made in these early design phases drive the entire design's life cycle cost. In a traditional paradigm, key design decisions are made when little is known about the design. As the design matures, design changes become more difficult in both cost and schedule to enact. The current capability-based paradigm, which has emerged because of the constrained economic environment, calls for the infusion of knowledge usually acquired during later design phases into earlier design phases, i.e. bringing knowledge acquired during preliminary and detailed design into pre-conceptual and conceptual design. An area of critical importance to launch vehicle design is the optimization of its ascent trajectory, as the optimal trajectory will be able to take full advantage of the launch vehicle's capability to deliver a maximum amount of payload into orbit. Hence, the optimal ascent trajectory plays an important role in the vehicle's affordability posture yet little of the information required to successfully optimize a trajectory is known early in the design phase. Thus, the current paradigm of optimizing ascent trajectories involves generating point solutions for every change in a vehicle's design parameters. This is often a very tedious, manual, and time-consuming task for the analysts. Moreover, the trajectory design space is highly non-linear and multi-modal due to the interaction of various constraints. When these obstacles are coupled with the Program to Optimize Simulated Trajectories (POST), an industry standard program to optimize ascent trajectories that is difficult to use, expert trajectory analysts are required to effectively optimize a vehicle's ascent trajectory. Over the course of this paper, the authors discuss a methodology developed at NASA Marshall's Advanced Concepts Office to address these issues

Worldwide isotope ratios of the Fukushima release and early-phase external dose reconstruction

PubMed Central

Chaisan, Kittisak; Smith, Jim T.; Bossew, Peter; Kirchner, Gerald; Laptev, Gennady V.

2013-01-01

Measurements of radionuclides (RNs) in air made worldwide following the Fukushima accident are quantitatively compared with air and soil measurements made in Japan. Isotopic ratios RN:137Cs of 131I, 132Te, 134,136Cs, are correlated with distance from release. It is shown, for the first time, that both within Japan and globally, ratios RN:137Cs in air were relatively constant for primarily particle associated radionuclides (134,136Cs; 132Te) but that 131I shows much lower local (<80 km) isotope ratios in soils relative to 137Cs. Derived isotope ratios are used to reconstruct external dose rate during the early phase post-accident. Model “blind” tests show more than 95% of predictions within a factor of two of measurements from 15 sites to the north, northwest and west of the power station. It is demonstrated that generic isotope ratios provide a sound basis for reconstruction of early-phase external dose rates in these most contaminated areas. PMID:24018776

Dietary Soy Supplement on Fibromyalgia Symptoms: A Randomized, Double-Blind, Placebo-Controlled, Early Phase Trial

PubMed Central

Wahner-Roedler, Dietlind L.; Thompson, Jeffrey M.; Luedtke, Connie A.; King, Susan M.; Cha, Stephen S.; Elkin, Peter L.; Bruce, Barbara K.; Townsend, Cynthia O.; Bergeson, Jody R.; Eickhoff, Andrea L.; Loehrer, Laura L.; Sood, Amit; Bauer, Brent A.

2011-01-01

Most patients with fibromyalgia use complementary and alternative medicine (CAM). Properly designed controlled trials are necessary to assess the effectiveness of these practices. This study was a randomized, double-blind, placebo-controlled, early phase trial. Fifty patients seen at a fibromyalgia outpatient treatment program were randomly assigned to a daily soy or placebo (casein) shake. Outcome measures were scores of the Fibromyalgia Impact Questionnaire (FIQ) and the Center for Epidemiologic Studies Depression Scale (CES-D) at baseline and after 6 weeks of intervention. Analysis was with standard statistics based on the null hypothesis, and separation test for early phase CAM comparative trials. Twenty-eight patients completed the study. Use of standard statistics with intent-to-treat analysis showed that total FIQ scores decreased by 14% in the soy group (P = .02) and by 18% in the placebo group (P < .001). The difference in change in scores between the groups was not significant (P = .16). With the same analysis, CES-D scores decreased in the soy group by 16% (P = .004) and in the placebo group by 15% (P = .05). The change in scores was similar in the groups (P = .83). Results of statistical analysis using the separation test and intent-to-treat analysis revealed no benefit of soy compared with placebo. Shakes that contain soy and shakes that contain casein, when combined with a multidisciplinary fibromyalgia treatment program, provide a decrease in fibromyalgia symptoms. Separation between the effects of soy and casein (control) shakes did not favor the intervention. Therefore, large-sample studies using soy for patients with fibromyalgia are probably not indicated. PMID:18990724

Gathering Design References from Nature

ERIC Educational Resources Information Center

Debs, Luciana; Kelley, Todd

2015-01-01

Teaching design to middle and high school students can be challenging. One of the first procedures in teaching design is to help students gather information that will be useful in the design phase. An early stage of engineering design as described by Lewis (2005), calls for the designer to establish the state of the art of the problem. During this…

23 CFR 636.202 - When are two-phase design-build selection procedures appropriate?

Code of Federal Regulations, 2011 CFR

2011-04-01

... 23 Highways 1 2011-04-01 2011-04-01 false When are two-phase design-build selection procedures appropriate? 636.202 Section 636.202 Highways FEDERAL HIGHWAY ADMINISTRATION, DEPARTMENT OF TRANSPORTATION ENGINEERING AND TRAFFIC OPERATIONS DESIGN-BUILD CONTRACTING Selection Procedures, Award Criteria § 636.202 When are two-phase design-build...

Review of hardware cost estimation methods, models and tools applied to early phases of space mission planning

NASA Astrophysics Data System (ADS)

Trivailo, O.; Sippel, M.; Şekercioğlu, Y. A.

2012-08-01

The primary purpose of this paper is to review currently existing cost estimation methods, models, tools and resources applicable to the space sector. While key space sector methods are outlined, a specific focus is placed on hardware cost estimation on a system level, particularly for early mission phases during which specifications and requirements are not yet crystallised, and information is limited. For the space industry, cost engineering within the systems engineering framework is an integral discipline. The cost of any space program now constitutes a stringent design criterion, which must be considered and carefully controlled during the entire program life cycle. A first step to any program budget is a representative cost estimate which usually hinges on a particular estimation approach, or methodology. Therefore appropriate selection of specific cost models, methods and tools is paramount, a difficult task given the highly variable nature, scope as well as scientific and technical requirements applicable to each program. Numerous methods, models and tools exist. However new ways are needed to address very early, pre-Phase 0 cost estimation during the initial program research and establishment phase when system specifications are limited, but the available research budget needs to be established and defined. Due to their specificity, for vehicles such as reusable launchers with a manned capability, a lack of historical data implies that using either the classic heuristic approach such as parametric cost estimation based on underlying CERs, or the analogy approach, is therefore, by definition, limited. This review identifies prominent cost estimation models applied to the space sector, and their underlying cost driving parameters and factors. Strengths, weaknesses, and suitability to specific mission types and classes are also highlighted. Current approaches which strategically amalgamate various cost estimation strategies both for formulation and validation

TRAVELLERS: a school-based early intervention programme helping young people manage and process change, loss and transition. Pilot phase findings.

PubMed

Dickinson, Pauline; Coggan, Carolyn; Bennett, Sara

2003-06-01

This paper outlines the conceptual background and findings from the pilot phase of TRAVELLERS--an early intervention programme designed to enhance protective factors for young people experiencing change, loss and transition events and early signs of emotional distress. The pilot study aimed to determine whether TRAVELLERS was a feasible, acceptable and promising intervention for young people within secondary schools in Aotearoa/New Zealand. The conceptual origins of the TRAVELLERS programme are described in terms of: adolescent mental health concerns; emerging mental health promotion theory and practice; and prevention and early intervention models. The key elements of the TRAVELLERS programme are described. The programme was piloted in two secondary schools, one rural and one urban with 34 participants (females n = 24, males n = 10). Evaluation methods included: review of programme materials; identification of potential selection tools appropriate to Year 9 students; analysis of selection questionnaire; and conduct of feedback from participants, facilitators and parents/caregivers. The TRAVELLERS programme provides a means of identifying and selecting young people who may benefit from participating in an early intervention programme. The programme has achieved a statistically significant reduction in participants' distress (p < 0.01). Young people were overwhelmingly enthusiastic about most aspects of TRAVELLERS. School personnel reported that TRAVELLERS was an appropriate and acceptable programme to the school. Targeted interventions provided within a supportive school environment can contribute to enhancing protective factors such as personal and interpersonal coping strategies, increased help-seeking behaviour, and young people feeling more positive about themselves and their lives. The pilot programme has been amended and prepared for a two year trial phase in 10 secondary schools during 2002-2003.

Cosmological QCD phase transition in steady non-equilibrium dissipative Hořava–Lifshitz early universe

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

Khodadi, M., E-mail: M.Khodadi@sbu.ac.ir; Sepangi, H.R., E-mail: hr-sepangi@sbu.ac.ir

We study the phase transition from quark–gluon plasma to hadrons in the early universe in the context of non-equilibrium thermodynamics. According to the standard model of cosmology, a phase transition associated with chiral symmetry breaking after the electro-weak transition has occurred when the universe was about 1–10 μs old. We focus attention on such a phase transition in the presence of a viscous relativistic cosmological background fluid in the framework of non-detailed balance Hořava–Lifshitz cosmology within an effective model of QCD. We consider a flat Friedmann–Robertson–Walker universe filled with a non-causal and a causal bulk viscous cosmological fluid respectively and investigatemore » the effects of the running coupling constants of Hořava–Lifshitz gravity, λ, on the evolution of the physical quantities relevant to a description of the early universe, namely, the temperature T, scale factor a, deceleration parameter q and dimensionless ratio of the bulk viscosity coefficient to entropy density (ξ)/s . We assume that the bulk viscosity cosmological background fluid obeys the evolution equation of the steady truncated (Eckart) and full version of the Israel–Stewart fluid, respectively. -- Highlights: •In this paper we have studied quark–hadron phase transition in the early universe in the context of the Hořava–Lifshitz model. •We use a flat FRW universe with the bulk viscosity cosmological background fluid obeying the evolution equation of the steady truncated (Eckart) and full version of the Israel–Stewart fluid, respectively.« less

Changes in neural circuitry associated with depression at pre-clinical, pre-motor and early motor phases of Parkinson's disease.

PubMed

Borgonovo, Janina; Allende-Castro, Camilo; Laliena, Almudena; Guerrero, Néstor; Silva, Hernán; Concha, Miguel L

2017-02-01

Although Parkinson's Disease (PD) is mostly considered a motor disorder, it can present at early stages as a non-motor pathology. Among the non-motor clinical manifestations, depression shows a high prevalence and can be one of the first clinical signs to appear, even a decade before the onset of motor symptoms. Here, we review the evidence of early dysfunction in neural circuitry associated with depression in the context of PD, focusing on pre-clinical, pre-motor and early motor phases of the disease. In the pre-clinical phase, structural and functional changes in the substantia nigra, basal ganglia and limbic structures are already observed. Some of these changes are linked to motor compensation mechanisms while others correspond to pathological processes common to PD and depression and thus could underlie the appearance of depressive symptoms during the pre-motor phase. Studies of the early motor phase (less than five years post diagnosis) reveal an association between the extent of damage in different monoaminergic systems and the appearance of emotional disorders. We propose that the limbic loop of the basal ganglia and the lateral habenula play key roles in the early genesis of depression in PD. Alterations in the neural circuitry linked with emotional control might be sensitive markers of the ongoing neurodegenerative process and thus may serve to facilitate an early diagnosis of this disease. To take advantage of this, we need to improve the clinical criteria and develop biomarkers to identify depression, which could be used to determine individuals at risk to develop PD. Copyright © 2016 Elsevier Ltd. All rights reserved.

48 CFR 36.301 - Use of two-phase design-build selection procedures.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 1 2013-10-01 2013-10-01 false Use of two-phase design-build selection procedures. 36.301 Section 36.301 Federal Acquisition Regulations System FEDERAL ACQUISITION REGULATION SPECIAL CATEGORIES OF CONTRACTING CONSTRUCTION AND ARCHITECT-ENGINEER CONTRACTS Two-Phase Design-Build Selection Procedures 36.301...

Endothelial gaps and adherent leukocytes in allergen-induced early- and late-phase plasma leakage in rat airways.

PubMed Central

Baluk, P.; Bolton, P.; Hirata, A.; Thurston, G.; McDonald, D. M.

1998-01-01

Exposure of sensitized individuals to antigen can induce allergic responses in the respiratory tract, manifested by early and late phases of vasodilatation, plasma leakage, leukocyte influx, and bronchoconstriction. Similar responses can occur in the skin, eye, and gastrointestinal tract. The early-phase response involves mast cell mediators and the late-phase response is leukocyte dependent, but the mechanism of leakage is not understood. We sought to identify the leaky blood vessels, to determine whether these vessels contained endothelial gaps, and to analyze the relationship of the gaps to adherent leukocytes, using biotinylated lectins or silver nitrate to stain the cells in situ and Monastral blue as a tracer to quantify plasma leakage. Most of the leakage occurred in postcapillary venules (< 40-microns diameter), whereas most of the leukocyte migration (predominantly neutrophils) occurred in collecting venules. Capillaries and arterioles did not leak. Endothelial gaps were found in the leaky venules, both by silver nitrate staining and by scanning electron microscopy, and 94% of the gaps were distinct from sites of leukocyte adhesion or migration. We conclude that endothelial gaps contribute to both early and late phases of plasma leakage induced by antigen, but most leakage occurs upstream to sites of leukocyte adhesion. Images Figure 3 Figure 5 Figure 6 Figure 7 PMID:9626051

Early phase drug discovery: cheminformatics and computational techniques in identifying lead series.

PubMed

Duffy, Bryan C; Zhu, Lei; Decornez, Hélène; Kitchen, Douglas B

2012-09-15

Early drug discovery processes rely on hit finding procedures followed by extensive experimental confirmation in order to select high priority hit series which then undergo further scrutiny in hit-to-lead studies. The experimental cost and the risk associated with poor selection of lead series can be greatly reduced by the use of many different computational and cheminformatic techniques to sort and prioritize compounds. We describe the steps in typical hit identification and hit-to-lead programs and then describe how cheminformatic analysis assists this process. In particular, scaffold analysis, clustering and property calculations assist in the design of high-throughput screening libraries, the early analysis of hits and then organizing compounds into series for their progression from hits to leads. Additionally, these computational tools can be used in virtual screening to design hit-finding libraries and as procedures to help with early SAR exploration. Copyright © 2012 Elsevier Ltd. All rights reserved.

Investigating Analytic Tools for e-Book Design in Early Literacy Learning

ERIC Educational Resources Information Center

Roskos, Kathleen; Brueck, Jeremy; Widman, Sarah

2009-01-01

Toward the goal of better e-book design to support early literacy learning, this study investigates analytic tools for examining design qualities of e-books for young children. Three research-based analytic tools related to e-book design were applied to a mixed genre collection of 50 e-books from popular online sites. Tool performance varied…

Seamless Phase IIa/IIb and enhanced dose-finding adaptive design.

PubMed

Yuan, Jiacheng; Pang, Herbert; Tong, Tiejun; Xi, Dong; Guo, Wenzhao; Mesenbrink, Peter

2016-01-01

In drug development, when the drug class has a relatively well-defined path to regulatory approval and the enrollment is slow with certain patient populations, one may want to consider combining studies of different phases. This article considers combining a proof of concept (POC) study and a dose-finding (DF) study with a control treatment. Conventional DF study designs sometimes are not efficient, or do not have a high probability to find the optimal dose(s) for Phase III trials. This article seeks more efficient DF strategies that allow the economical testing of more doses. Hypothetical examples are simulated to compare the proposed adaptive design vs. the conventional design based on different models of the overall quantitative representation of efficacy, safety, and tolerability. The results show that the proposed adaptive design tests more active doses with higher power and comparable or smaller sample size in a shorter overall study duration for POC and DF, compared with a conventional design.

Contribution of economic evaluation to decision making in early phases of product development: a methodological and empirical review.

PubMed

Hartz, Susanne; John, Jürgen

2008-01-01

Economic evaluation as an integral part of health technology assessment is today mostly applied to established technologies. Evaluating healthcare innovations in their early states of development has recently attracted attention. Although it offers several benefits, it also holds methodological challenges. The aim of our study was to investigate the possible contributions of economic evaluation to industry's decision making early in product development and to confront the results with the actual use of early data in economic assessments. We conducted a literature research to detect methodological contributions as well as economic evaluations that used data from early phases of product development. Economic analysis can be beneficially used in early phases of product development for various purposes including early market assessment, R&D portfolio management, and first estimations of pricing and reimbursement scenarios. Analytical tools available for these purposes have been identified. Numerous empirical works were detected, but most do not disclose any concrete decision context and could not be directly matched with the suggested applications. Industry can benefit from starting economic evaluation early in product development in several ways. Empirical evidence suggests that there is still potential left unused.

Hemoglobin phase of oxygenation and deoxygenation in early brain development measured using fNIRS

PubMed Central

Watanabe, Hama; Shitara, Yoshihiko; Aoki, Yoshinori; Inoue, Takanobu; Tsuchida, Shinya; Takahashi, Naoto; Taga, Gentaro

2017-01-01

A crucial issue in neonatal medicine is the impact of preterm birth on the developmental trajectory of the brain. Although a growing number of studies have shown alterations in the structure and function of the brain in preterm-born infants, we propose a method to detect subtle differences in neurovascular and metabolic functions in neonates and infants. Functional near-infrared spectroscopy (fNIRS) was used to obtain time-averaged phase differences between spontaneous low-frequency (less than 0.1 Hz) oscillatory changes in oxygenated hemoglobin (oxy-Hb) and those in deoxygenated hemoglobin (deoxy-Hb). This phase difference was referred to as hemoglobin phase of oxygenation and deoxygenation (hPod) in the cerebral tissue of sleeping neonates and infants. We examined hPod in term, late preterm, and early preterm infants with no evidence of clinical issues and found that all groups of infants showed developmental changes in the values of hPod from an in-phase to an antiphase pattern. Comparison of hPod among the groups revealed that developmental changes in hPod in early preterm infants precede those in late preterm and term infants at term equivalent age but then, progress at a slower pace. This study suggests that hPod measured using fNIRS is sensitive to the developmental stage of the integration of circular, neurovascular, and metabolic functions in the brains of neonates and infants. PMID:28196885

Critical early mission design considerations for lunar data systems architecture

NASA Technical Reports Server (NTRS)

Hei, Donald J., Jr.; Stephens, Elaine

1992-01-01

This paper outlines recent early mission design activites for a lunar data systems architecture. Each major functional element is shown to be strikingly similar when viewed in a common reference system. While this similarity probably deviates with lower levels of decomposition, the sub-functions can always be arranged into similar and dissimilar categories. Similar functions can be implemented as objects - implemented once and reused several times like today's advanced integrated circuits. This approach to mission data systems, applied to other NASA programs, may result in substantial agency implementation and maintenance savings. In today's zero-sum-game budgetary environment, this approach could help to enable a lunar exploration program in the next decade. Several early mission studies leading to such an object-oriented data systems design are recommended.

Design and calibration of zero-additional-phase SPIDER

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

Baum, Peter; Riedle, Eberhard

2005-09-01

Zero-additional-phase spectral phase interferometry for direct electric field reconstruction (ZAP-SPIDER) is a novel technique for measuring the temporal shape and phase of ultrashort optical pulses directly at the interaction point of a spectroscopic experiment. The scheme is suitable for an extremely wide wavelength region from the ultraviolet to the near infrared. We present a comprehensive description of the experimental setup and design guidelines to effectively apply the technique to various wavelengths and pulse durations. The calibration of the setup and procedures to check the consistency of the measurement are discussed in detail. We show experimental data for various center wavelengthsmore » and pulse durations down to 7 fs to verify the applicability to a wide range of pulse parameters.« less

Earthquake Early Warning: User Education and Designing Effective Messages

NASA Astrophysics Data System (ADS)

Burkett, E. R.; Sellnow, D. D.; Jones, L.; Sellnow, T. L.

2014-12-01

The U.S. Geological Survey (USGS) and partners are transitioning from test-user trials of a demonstration earthquake early warning system (ShakeAlert) to deciding and preparing how to implement the release of earthquake early warning information, alert messages, and products to the public and other stakeholders. An earthquake early warning system uses seismic station networks to rapidly gather information about an occurring earthquake and send notifications to user devices ahead of the arrival of potentially damaging ground shaking at their locations. Earthquake early warning alerts can thereby allow time for actions to protect lives and property before arrival of damaging shaking, if users are properly educated on how to use and react to such notifications. A collaboration team of risk communications researchers and earth scientists is researching the effectiveness of a chosen subset of potential earthquake early warning interface designs and messages, which could be displayed on a device such as a smartphone. Preliminary results indicate, for instance, that users prefer alerts that include 1) a map to relate their location to the earthquake and 2) instructions for what to do in response to the expected level of shaking. A number of important factors must be considered to design a message that will promote appropriate self-protective behavior. While users prefer to see a map, how much information can be processed in limited time? Are graphical representations of wavefronts helpful or confusing? The most important factor to promote a helpful response is the predicted earthquake intensity, or how strong the expected shaking will be at the user's location. Unlike Japanese users of early warning, few Californians are familiar with the earthquake intensity scale, so we are exploring how differentiating instructions between intensity levels (e.g., "Be aware" for lower shaking levels and "Drop, cover, hold on" at high levels) can be paired with self-directed supplemental

Inside information: Financial conflicts of interest for research subjects in early phase clinical trials.

PubMed

Helft, Paul R; Ratain, Mark J; Epstein, Richard A; Siegler, Mark

2004-05-05

In recent years, several research subjects have told us that they had bought or intended to buy stock in the companies sponsoring the clinical trials in which they were enrolled. This situation has led us to ask what, if any, are physician-investigators' scientific, ethical, and legal responsibilities concerning research subjects who choose to buy stock in the companies sponsoring the clinical trials in which they are participating. Although the scope of this problem is unknown and is likely to be small, this commentary examines the scientific, ethical, and legal concerns raised by such activities on the part of research subjects enrolled in early phase clinical trials. In addition, this commentary also outlines the basis for our opinion that research subjects involved in an early phase clinical trial should avoid the financial conflicts of interest created by trading stock in the company sponsoring the clinical trial.

Divided attention can enhance early-phase memory encoding: the attentional boost effect and study trial duration.

PubMed

Mulligan, Neil W; Spataro, Pietro

2015-07-01

Divided attention during encoding typically produces marked reductions in later memory. The attentional boost effect (ABE) is a surprising variation on this phenomenon. In this paradigm, each study stimulus (e.g., a word) is presented along with a target or a distractor (e.g., different colored circles) in a detection task. Later memory is better for stimuli co-occurring with targets. The present experiments indicate that the ABE arises during an early phase of memory encoding that involves initial stimulus perception and comprehension rather than at a later phase entailing controlled, elaborative rehearsal. Experiment 1 demonstrated that the ABE was robust at a short study duration (700 ms) and did not increase with increasing study trial durations (1,500 ms and 4,000 ms). Furthermore, the target condition is boosted to the level of memory performance in a full-attention condition for the short duration but not the long duration. Both results followed from the early-phase account. This account also predicts that for very short study times (limiting the influence of late-phase controlled encoding and thus minimizing the usual negative effect of divided attention), the target condition will produce better memory than will the full-attention condition. Experiment 2 used a study time of 400 ms and found that words presented with targets lead to greater recognition accuracy than do either words presented with distractors or words in the full-attention condition. Consistent with the early-phase account, a divided attention condition actually produced superior memory than did the full-attention condition, a very unusual but theoretically predicted result. (c) 2015 APA, all rights reserved.

Brain responses to food images during the early and late follicular phase of the menstrual cycle in healthy young women: relation to fasting and feeding1234

PubMed Central

Ziemke, Florencia; Magkos, Faidon; Barrios, Fernando A; Brinkoetter, Mary; Boyd, Ingrid; Rifkin-Graboi, Anne; Yannakoulia, Mary; Rojas, Rafael; Pascual-Leone, Alvaro; Mantzoros, Christos S

2011-01-01

Background: Food intake fluctuates throughout the menstrual cycle; it is greater during the early follicular and luteal phases than in the late follicular (periovulatory) phase. Ovarian steroids can influence brain areas that process food-related information, but the specific contribution of individual hormones and the importance of the prandial state remain unknown. Objective: The objective was to examine whether brain activation during food visualization is affected by changes in estradiol concentration in the fasted and fed conditions. Design: Nine eumenorrheic, lean young women [mean (±SD) age: 26.2 ± 3.2 y; body mass index (in kg/m2): 22.4 ± 1.2] completed 2 visits, one in the early (low estradiol) and one in the late (high estradiol) follicular phase of their menstrual cycle. At each visit, subjects underwent functional magnetic resonance imaging while they viewed food and nonfood images, before and after a standardized meal. Region-of-interest analysis was used to examine the effect of follicular phase and prandial state on brain activation (food > nonfood contrast) and its association with estradiol concentration. Results: Differences were identified in the inferior frontal and fusiform gyri. In these areas, visualization of food elicited greater activation in the fed state than during fasting but only in the late follicular phase, when estradiol concentration was high. The change in estradiol concentration across the follicular phase (late minus early) was inversely correlated with the change in fusiform gyrus activation in the fasted state but not in the fed state. Conclusion: Our findings suggest that estradiol may reduce food intake by decreasing sensitivity to food cues in the ventral visual pathway under conditions of energy deprivation. This trial was registered at clinicaltrials.gov as NCT00130117. PMID:21593494

Early Childhood Settings in 15 Countries: What Are Their Structural Characteristics? The IEA Preprimary Project, Phase 2.

ERIC Educational Resources Information Center

Olmsted, Patricia P., Ed.; Montie, Jeanne, Ed.

This is the second of four monographs reporting the findings of Phase 2 of the International Association for the Evaluation of Educational Achievement (IEA) Preprimary Project, which presents data on the physical characteristics of children's early childhood settings. Early childhood settings were documented in the following 15 countries: (1)…

Learning to Be: The Modelling of Art and Design Practice in University Art and Design Teaching

ERIC Educational Resources Information Center

Budge, Kylie

2016-01-01

Learning to be an artist or designer is a complex process of becoming. Much of the early phase of "learning to be" occurs during the time emerging artists and designers are students in university art/design programmes, both undergraduate and postgraduate. Recent research reveals that a critical role in assisting students in their…

Characterization of Early-Phase Neutrophil Extracellular Traps in Urinary Tract Infections

PubMed Central

Yu, Yanbao; Kwon, Keehwan; Tsitrin, Tamara; Sikorski, Patricia; Nelson, Karen E.; Pieper, Rembert

2017-01-01

Neutrophils have an important role in the antimicrobial defense and resolution of urinary tract infections (UTIs). Our research suggests that a mechanism known as neutrophil extracellular trap (NET) formation is a defense strategy to combat pathogens that have invaded the urinary tract. A set of human urine specimens with very high neutrophil counts had microscopic evidence of cellular aggregation and lysis. Deoxyribonuclease I (DNase) treatment resulted in disaggregation of such structures, release of DNA fragments and a proteome enriched in histones and azurophilic granule effectors whose quantitative composition was similar to that of previously described in vitro-formed NETs. The effector proteins were further enriched in DNA-protein complexes isolated in native PAGE gels. Immunofluorescence microscopy revealed a flattened morphology of neutrophils associated with decondensed chromatin, remnants of granules in the cell periphery, and myeloperoxidase co-localized with extracellular DNA, features consistent with early-phase NETs. Nuclear staining revealed that a considerable fraction of bacterial cells in these structures were dead. The proteomes of two pathogens, Staphylococcus aureus and Escherichia coli, were indicative of adaptive responses to early-phase NETs, specifically the release of virulence factors and arrest of ribosomal protein synthesis. Finally, we discovered patterns of proteolysis consistent with widespread cleavage of proteins by neutrophil elastase, proteinase 3 and cathepsin G and evidence of citrullination in many nuclear proteins. PMID:28129394

Sustained attention is favored by progesterone during early luteal phase and visuo-spatial memory by estrogens during ovulatory phase in young women.

PubMed

Solís-Ortiz, S; Corsi-Cabrera, M

2008-08-01

Studies examining the influence of the menstrual cycle on cognitive function have been highly contradictory. The maintenance of attention is key to successful information processing, however how it co-vary with other cognitive functions and mood in function of phases of the menstrual cycle is not well know. Therefore, neuropsychological performance of nine healthy women with regular menstrual cycles was assessed during ovulation (OVU), early luteal (EL), late luteal (LL) and menstrual (MEN) phases. Neuropsychological test scores of sustained attention, executive functions, manual coordination, visuo-spatial memory, verbal fluency, spatial ability, anxiety and depression were obtained and submitted to a principal components analysis (PCA). Five eigenvectors that accounted the 68.31% of the total variance were identified. Performance of the sustained attention was grouped in an independent eigenvector (component 1), and the scores on verbal fluency and visuo-spatial memory were grouped together in an eigenvector (component 5), which explained 17.69% and 12.03% of the total variance, respectively. The component 1 (p<0.034) and the component 5 (p<0.003) showed significant variations during the menstrual cycle. Sustained attention showed an increase in the EL phase, when the progesterone is high. Visuo-spatial memory was increased, while that verbal fluency was decreased during the OVU phase, when the estrogens levels are high. These results indicate that sustained attention is favored by early luteal phase progesterone and do not covaried with any other neuropsychological variables studied. The influence of the estrogens on visuo-spatial memory was corroborated, and covaried inversely with verbal fluency.

DESIGN OF A TRAP GREASE UPGRADER FOR BIOFUEL PROCESSING - PHASE I

EPA Science Inventory

This project provides capstone senior design experience to several teams of engineering undergraduates at Drexel University through the technical and economic evaluation of a trap grease to biodiesel conversion process. The project incorporates two phases: Phase I characteri...

Early Human Testing Initiative Phase 1 Regenerative Life Support Systems

NASA Image and Video Library

1995-08-08

Early Human Testing (EHT) Initiative Phase 1 Regenerative Life Support Systems Laboratory (RLSSL). Nigel Packham activities in the Variable Pressure Growth Chamber which he lived inside for 15 days. A crowd of well-wishers outside the test chamber, at the console are John Lewis, Ed Mohr and Marybeth Edeen (15577). Packham exiting the chamber (15578-81). Packham is the focus of television cameras and reporters (15582-3). Don Henninger interviewed by reporters (15584). Packham is presented with a jacket after his stay in the chamber (15585). Packham inside the wheat growth chamber checking the condition of the plants (15586-7, 15597). Packham exercising on a recumbant bicycle (15588, 15592). Packham, through the window into the growth chamber, displays a handful of wheat plants to console monitor Dan Barta (15589-90). Group portrait of the team conducting the Early Human Testing Initiative Phase 1 Regenerative Life Support Systems test and include, front row, from left: Jeff Dominick and Don Overton and back row, from left, unidentified member, Marybeth Edeen, Nigel Packham, John Lewis, Ed Mohr, Dan Barta and Tim Monk (15591). Harry Halford prepares to send a package through the airlock to Packham (15593). Packham displays a handful of wheat plants (15594). Packham fixes himself a bowl of cereal (15595) and retrieves a carton of milk from the refrigerator (15596). Packham retrieves a package from the airlock (15598). Packham packs up trash in plastic bag (15599-600) and sends it back through the airlock (15601). Packham gets a cup of water (15602) and heats it in the microwave (15603).

Flexibility in Early Stage Design of U. S. Navy Ships: An Analysis of Options

DTIC Science & Technology

2011-01-01

Flexibility in Early Stage Design of US Navy Ships: An Analysis of Options by Jonathan Page B.S., Systems Engineering, US Naval Academy, 2002...8217C/ v = (;!;!: ;: Pat Hale Director, Systems Design and Ma~ement Fellows Program E~i_yfering.S~~pivi~i~ Acceptedby...2. REPORT TYPE 3. DATES COVERED 00-00-2012 to 00-00-2012 4. TITLE AND SUBTITLE Flexibility in Early Stage Design of U. S. Navy Ships: An

Measurement Matrix Design for Phase Retrieval Based on Mutual Information

NASA Astrophysics Data System (ADS)

Shlezinger, Nir; Dabora, Ron; Eldar, Yonina C.

2018-01-01

In phase retrieval problems, a signal of interest (SOI) is reconstructed based on the magnitude of a linear transformation of the SOI observed with additive noise. The linear transform is typically referred to as a measurement matrix. Many works on phase retrieval assume that the measurement matrix is a random Gaussian matrix, which, in the noiseless scenario with sufficiently many measurements, guarantees invertability of the transformation between the SOI and the observations, up to an inherent phase ambiguity. However, in many practical applications, the measurement matrix corresponds to an underlying physical setup, and is therefore deterministic, possibly with structural constraints. In this work we study the design of deterministic measurement matrices, based on maximizing the mutual information between the SOI and the observations. We characterize necessary conditions for the optimality of a measurement matrix, and analytically obtain the optimal matrix in the low signal-to-noise ratio regime. Practical methods for designing general measurement matrices and masked Fourier measurements are proposed. Simulation tests demonstrate the performance gain achieved by the proposed techniques compared to random Gaussian measurements for various phase recovery algorithms.

Design rules for phase-change materials in data storage applications.

PubMed

Lencer, Dominic; Salinga, Martin; Wuttig, Matthias

2011-05-10

Phase-change materials can rapidly and reversibly be switched between an amorphous and a crystalline phase. Since both phases are characterized by very different optical and electrical properties, these materials can be employed for rewritable optical and electrical data storage. Hence, there are considerable efforts to identify suitable materials, and to optimize them with respect to specific applications. Design rules that can explain why the materials identified so far enable phase-change based devices would hence be very beneficial. This article describes materials that have been successfully employed and dicusses common features regarding both typical structures and bonding mechanisms. It is shown that typical structural motifs and electronic properties can be found in the crystalline state that are indicative for resonant bonding, from which the employed contrast originates. The occurence of resonance is linked to the composition, thus providing a design rule for phase-change materials. This understanding helps to unravel characteristic properties such as electrical and thermal conductivity which are discussed in the subsequent section. Then, turning to the transition kinetics between the phases, the current understanding and modeling of the processes of amorphization and crystallization are discussed. Finally, present approaches for improved high-capacity optical discs and fast non-volatile electrical memories, that hold the potential to succeed present-day's Flash memory, are presented. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Design and early performance of IGRINS (Immersion Grating Infrared Spectrometer)

NASA Astrophysics Data System (ADS)

Park, Chan; Jaffe, Daniel T.; Yuk, In-Soo; Chun, Moo-Young; Pak, Soojong; Kim, Kang-Min; Pavel, Michael; Lee, Hanshin; Oh, Heeyoung; Jeong, Ueejeong; Sim, Chae Kyung; Lee, Hye-In; Nguyen Le, Huynh Anh; Strubhar, Joseph; Gully-Santiago, Michael; Oh, Jae Sok; Cha, Sang-Mok; Moon, Bongkon; Park, Kwijong; Brooks, Cynthia; Ko, Kyeongyeon; Han, Jeong-Yeol; Nah, Jakyoung; Hill, Peter C.; Lee, Sungho; Barnes, Stuart; Yu, Young Sam; Kaplan, Kyle; Mace, Gregory; Kim, Hwihyun; Lee, Jae-Joon; Hwang, Narae; Park, Byeong-Gon

2014-07-01

The Immersion Grating Infrared Spectrometer (IGRINS) is a compact high-resolution near-infrared cross-dispersed spectrograph whose primary disperser is a silicon immersion grating. IGRINS covers the entire portion of the wavelength range between 1.45 and 2.45μm that is accessible from the ground and does so in a single exposure with a resolving power of 40,000. Individual volume phase holographic (VPH) gratings serve as cross-dispersing elements for separate spectrograph arms covering the H and K bands. On the 2.7m Harlan J. Smith telescope at the McDonald Observatory, the slit size is 1ʺ x 15ʺ and the plate scale is 0.27ʺ pixel. The spectrograph employs two 2048 x 2048 pixel Teledyne Scientific and Imaging HAWAII-2RG detectors with SIDECAR ASIC cryogenic controllers. The instrument includes four subsystems; a calibration unit, an input relay optics module, a slit-viewing camera, and nearly identical H and K spectrograph modules. The use of a silicon immersion grating and a compact white pupil design allows the spectrograph collimated beam size to be only 25mm, which permits a moderately sized (0.96m x 0.6m x 0.38m) rectangular cryostat to contain the entire spectrograph. The fabrication and assembly of the optical and mechanical components were completed in 2013. We describe the major design characteristics of the instrument including the system requirements and the technical strategy to meet them. We also present early performance test results obtained from the commissioning runs at the McDonald Observatory.

[The correlation between serum uric acid level and early-phase insulin secretion in subjects with normal glucose regulation].

PubMed

Lu, L; Zheng, F P; Li, H

2016-05-01

To investigate the correlation between serum uric acid (SUA) level and early-phase insulin secretion in subjects with normal glucose regulation (NGR). Totally 367 community NGR residents confirmed by a 75g oral glucose tolerance test were enrolled. The insulin resistance index (HOMA-IR) and the early-phase insulin secretion index after a glucose load (ΔI30/ΔG30) were used to estimate the insulin sensitivity and the early-phase insulin secretion, respectively. The subjects were divided into 4 groups according to the SUA level quartiles. Differences in early-phase insulin levels, ΔI30/ΔG30, and HOMA-IR were compared among the 4 groups. Age, BMI, waist circumference, systolic blood pressure, diastolic blood pressure, fasting insulin (FINS), 30 minutes postprandial insulin(30 minINS), 2 hours postprandial insulin(2hINS), HOMA-IR and TG levels increased across the rising categories of SUA levels, while the HDL-C was decreased across the SUA groups (P<0.01). The SUA level was positively correlated with age(r=0.157, P<0.01), BMI(r=0.262, P<0.01), waist circumference(r=0.372, P<0.01), systolic blood pressure(r=0.200, P<0.01), diastolic blood pressure(r=0.254, P<0.01), 30 minutes postprandial plasma glucose(r=0.118, P=0.023), FINS(r=0.249, P<0.01), 30minINS(r=0.189, P<0.01), 2hINS(r=0.206, P<0.01), glycosylated hemoglobin(HbA1c, r=0.106, P=0.042), HOMA-IR(r=0.244, P<0.01), TG(r=0.350, P<0.01), ΔI30/ΔG30(r=0.144, P<0.01), and negatively correlated with HDL-C level(r=-0.321, P<0.01). Multiple stepwise regression analysis showed that SUA(β=0.292, P<0.01) and HOMA-IR(β=29.821, P<0.01) were positively associated with ΔI30/ΔG30. SUA level is closely related with the early-phase insulin secretion in NGR subjects.

77 FR 36958 - Proposed Requirements-Race to the Top-Early Learning Challenge; Phase 2

Federal Register 2010, 2011, 2012, 2013, 2014

2012-06-20

... DEPARTMENT OF EDUCATION 34 CFR Chapter II DEPARTMENT OF HEALTH AND HUMAN SERVICES 45 CFR Subtitle... Requirements--Race to the Top--Early Learning Challenge; Phase 2 AGENCY: Department of Education and Department of Health and Human Services. ACTION: Proposed requirements. SUMMARY: The Secretary of Education and...

Design of photonic phased array switches using nano electromechanical systems on silicon-on-insulator integration platform

NASA Astrophysics Data System (ADS)

Hussein, Ali Abdulsattar

This thesis presents an introduction to the design and simulation of a novel class of integrated photonic phased array switch elements. The main objective is to use nano-electromechanical (NEMS) based phase shifters of cascaded under-etched slot nanowires that are compact in size and require a small amount of power to operate them. The structure of the switch elements is organized such that it brings the phase shifting elements to the exterior sides of the photonic circuits. The transition slot couplers, used to interconnect the phase shifters, are designed to enable biasing one of the silicon beams of each phase shifter from an electrode located at the side of the phase shifter. The other silicon beam of each phase shifter is biased through the rest of the silicon structure of the switch element, which is taken as a ground. Phased array switch elements ranging from 2x2 up to 8x8 multiple-inputs/multiple-outputs (MIMO) are conveniently designed within reasonable footprints native to the current fabrication technologies. Chapter one presents the general layout of the various designs of the switch elements and demonstrates their novel features. This demonstration will show how waveguide disturbances in the interconnecting network from conventional switch elements can be avoided by adopting an innovative design. Some possible applications for the designed switch elements of different sizes and topologies are indicated throughout the chapter. Chapter two presents the design of the multimode interference (MMI) couplers used in the switch elements as splitters, combiners and waveguide crossovers. Simulation data and design methodologies for the multimode couplers of interest are detailed in this chapter. Chapter three presents the design and analysis of the NEMS-operated phase shifters. Both simulations and numerical analysis are utilized in the design of a 0°-180° capable NEMS-operated phase shifter. Additionally, the response of some of the designed photonic phased

Exploring a Comprehensive Model for Early Childhood Vocabulary Instruction: A Design Experiment

ERIC Educational Resources Information Center

Wang, X. Christine; Christ, Tanya; Chiu, Ming Ming

2014-01-01

Addressing a critical need for effective vocabulary practices in early childhood classrooms, we conducted a design experiment to achieve three goals: (1) developing a comprehensive model for early childhood vocabulary instruction, (2) examining the effectiveness of this model, and (3) discerning the contextual conditions that hinder or facilitate…

The Single-Phase ProtoDUNE Technical Design Report

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

Abi, B.

2017-06-21

ProtoDUNE-SP is the single-phase DUNE Far Detector prototype that is under construction and will be operated at the CERN Neutrino Platform (NP) starting in 2018. ProtoDUNE-SP, a crucial part of the DUNE effort towards the construction of the first DUNE 10-kt fiducial mass far detector module (17 kt total LAr mass), is a significant experiment in its own right. With a total liquid argon (LAr) mass of 0.77 kt, it represents the largest monolithic single-phase LArTPC detector to be built to date. It's technical design is given in this report.

Antigravity treadmill training during the early rehabilitation phase following unicompartmental knee arthroplasty: A case series.

PubMed

Huang, Chun-Hao; Schroeder, E Todd; Powers, Christopher

2018-02-26

Patients who have undergone unicompartmental knee arthroplasty (UKA) have been reported to exhibit altered gait 19-25 months post-surgery. The most common gait impairment in this population is inadequate knee flexion and a corresponding decrease in the knee extensor moment during loading response (i.e., quadriceps avoidance). The purpose of this case series was to determine whether incorporation of antigravity treadmill training into a standard physical therapy program can eliminate quadriceps avoidance gait during the early rehabilitation phase following UKA. Four females who underwent UKA were recruited for this study. Participants completed antigravity treadmill training three times per week for 12 weeks in addition to their standard physical therapy program. Instrumented gait analysis was performed at baseline (pre-intervention), week 6 (mid-intervention), and week 12 (post-intervention). We found that peak knee flexion and the peak knee extensor moment during the weight acceptance phase of gait increased to normal values following the 12-week intervention period (14.1 ± 6.5° to 20.6 ± 1.5° and 0.4 ± 0.3 to 0.7 ± 0.2 Nm/kg respectively). The findings of this case series suggest that a standard physical therapy program that incorporates early gait training using an antigravity treadmill may be beneficial in eliminating "quadriceps avoidance" during the early rehabilitation phase following UKA.

Adaptive multibeam phased array design for a Spacelab experiment

NASA Technical Reports Server (NTRS)

Noji, T. T.; Fass, S.; Fuoco, A. M.; Wang, C. D.

1977-01-01

The parametric tradeoff analyses and design for an Adaptive Multibeam Phased Array (AMPA) for a Spacelab experiment are described. This AMPA Experiment System was designed with particular emphasis to maximize channel capacity and minimize implementation and cost impacts for future austere maritime and aeronautical users, operating with a low gain hemispherical coverage antenna element, low effective radiated power, and low antenna gain-to-system noise temperature ratio.

Mars Rover/Sample Return - Phase A cost estimation

NASA Technical Reports Server (NTRS)

Stancati, Michael L.; Spadoni, Daniel J.

1990-01-01

This paper presents a preliminary cost estimate for the design and development of the Mars Rover/Sample Return (MRSR) mission. The estimate was generated using a modeling tool specifically built to provide useful cost estimates from design parameters of the type and fidelity usually available during early phases of mission design. The model approach and its application to MRSR are described.

White matter changes in early phase schizophrenia and cannabis use: an update and systematic review of diffusion tensor imaging studies.

PubMed

Cookey, Jacob; Bernier, Denise; Tibbo, Philip G

2014-07-01

The impact of cannabis use on the brain tissue is still unclear, both in the healthy developing brain and in people with schizophrenia. The focus of this review is on white matter, the primary connective infrastructure of the brain. We systematically reviewed diffusion tensor imaging (DTI) studies of early phase schizophrenia (illness effect), of cannabis use in otherwise healthy brains (drug effect), and of early phase schizophrenia with cannabis use (combined effects). Studies had to include a healthy, non-cannabis using, control group as well as report on fractional anisotropy as it is the most commonly used DTI index. We excluded cohorts with heavy alcohol or illicit drug use and studies with a sample size of less than 20 in the clinical group. We retained 17 studies of early phase schizophrenia, which together indicate deficits in white matter integrity observed in all fiber tract families, but most frequently in association, callosal and projection fibers. In otherwise healthy cannabis users (2 studies), deficits in white matter tracts were reported mainly in callosal fibers, but also in projection and limbic fibers. In cannabis users with early phase schizophrenia (1 study), deficits in white matter integrity were also observed in all fiber tract families, except for limbic fibers. The current literature points to several families of white matter tracts being differentially affected in early phase schizophrenia. Further work is required to reveal the impact of cannabis use in otherwise healthy people as well as those with schizophrenia. Paucity of available studies as well as restricting analysis to FA values represent the main limitations of this review. Copyright © 2014 Elsevier B.V. All rights reserved.

An NAFP Project: Use of Object Oriented Methodologies and Design Patterns to Refactor Software Design

NASA Technical Reports Server (NTRS)

Shaykhian, Gholam Ali; Baggs, Rhoda

2007-01-01

In the early problem-solution era of software programming, functional decompositions were mainly used to design and implement software solutions. In functional decompositions, functions and data are introduced as two separate entities during the design phase, and are followed as such in the implementation phase. Functional decompositions make use of refactoring through optimizing the algorithms, grouping similar functionalities into common reusable functions, and using abstract representations of data where possible; all these are done during the implementation phase. This paper advocates the usage of object-oriented methodologies and design patterns as the centerpieces of refactoring software solutions. Refactoring software is a method of changing software design while explicitly preserving its external functionalities. The combined usage of object-oriented methodologies and design patterns to refactor should also benefit the overall software life cycle cost with improved software.

Enhancing Research and Practice in Early Childhood through Formative and Design Experiments

ERIC Educational Resources Information Center

Bradley, Barbara A.; Reinking, David

2011-01-01

This article describes formative and design experiments and how they can advance research and instructional practices in early childhood education. We argue that this relatively new approach to education research closes the gap between research and practice, and it addresses limitations that have been identified in early childhood research. We…

Definition of two-phase flow behaviors for spacecraft design

NASA Technical Reports Server (NTRS)

Reinarts, Thomas R.; Best, Frederick R.; Miller, Katherine M.; Hill, Wayne S.

1991-01-01

Data for complete models of two-phase flow in microgravity are taken from in-flight experiments and applied to an adiabatic flow-regime analysis to study the feasibility of two-phase systems for spacecraft. The data are taken from five in-flight experiments by Hill et al. (1990) in which a two-phase pump circulates a freon mixture and vapor and liquid flow streams are measured. Adiabatic flow regimes are analyzed based on the experimental superficial velocities of liquid and vapor, and comparisons are made with the results of two-phase flow regimes at 1 g. A motion analyzer records the flow characteristics at a rate of 1000 frames/sec, and stratified flow regimes are reported at 1 g. The flow regimes observed under microgravitational conditions are primarily annular and include slug and bubbly-slug regimes. The present data are of interest to the design and analysis of two-phase thermal-management systems for use in space missions.

Designing Studies to Test Causal Questions About Early Math: The Development of Making Pre-K Count.

PubMed

Mattera, Shira K; Morris, Pamela A; Jacob, Robin; Maier, Michelle; Rojas, Natalia

2017-01-01

A growing literature has demonstrated that early math skills are associated with later outcomes for children. This research has generated interest in improving children's early math competencies as a pathway to improved outcomes for children in elementary school. The Making Pre-K Count study was designed to test the effects of an early math intervention for preschoolers. Its design was unique in that, in addition to causally testing the effects of early math skills, it also allowed for the examination of a number of additional questions about scale-up, the influence of contextual factors and the counterfactual environment, the mechanism of long-term fade-out, and the role of measurement in early childhood intervention findings. This chapter outlines some of the design considerations and decisions put in place to create a rigorous test of the causal effects of early math skills that is also able to answer these questions in early childhood mathematics and intervention. The study serves as a potential model for how to advance science in the fields of preschool intervention and early mathematics. © 2017 Elsevier Inc. All rights reserved.

The Role of Early-Phase Transmission in the Spread of Yersinia pestis

PubMed Central

EISEN, REBECCA J.; DENNIS, DAVID T.; GAGE, KENNETH L.

2015-01-01

Early-phase transmission (EPT) of Yersinia pestis by unblocked fleas is a well-documented, replicable phenomenon with poorly defined mechanisms. We review evidence demonstrating EPT and current knowledge on its biological and biomechanical processes. We discuss the importance of EPT in the epizootic spread of Y. pestis and its role in the maintenance of plague bacteria in nature. We further address the role of EPT in the epidemiology of plague. PMID:26336267

Definition of technology development missions for early space stations. Large space structures, phase 2, midterm review

NASA Technical Reports Server (NTRS)

1984-01-01

The large space structures technology development missions to be performed on an early manned space station was studied and defined and the resources needed and the design implications to an early space station to carry out these large space structures technology development missions were determined. Emphasis is being placed on more detail in mission designs and space station resource requirements.

Treatment of early-onset schizophrenia spectrum disorders (TEOSS): rationale, design, and methods.

PubMed

McClellan, Jon; Sikich, Linmarie; Findling, Robert L; Frazier, Jean A; Vitiello, Benedetto; Hlastala, Stefanie A; Williams, Emily; Ambler, Denisse; Hunt-Harrison, Tyehimba; Maloney, Ann E; Ritz, Louise; Anderson, Robert; Hamer, Robert M; Lieberman, Jeffrey A

2007-08-01

The Treatment of Early Onset Schizophrenia Spectrum Disorders Study is a publicly funded clinical trial designed to compare the therapeutic benefits, safety, and tolerability of risperidone, olanzapine, and molindone in youths with early-onset schizophrenia spectrum disorders. The rationale, design, and methods of the Treatment of Early Onset Schizophrenia Spectrum Disorders Study are described. Using a randomized, double-blind, parallel-group design at four sites, youths with EOSS (ages 8-19 years) were assigned to an 8-week acute trial of risperidone (0.5-6.0 mg/day), olanzapine (2.5-20 mg/day), or molindone (10-140 mg/day). Responders continued double-blind treatment for 44 weeks. The primary outcome measure was responder status at 8 weeks, defined by a 20% reduction in baseline Positive and Negative Symptom Scale scores plus ratings of significant improvement on the Clinical Global Impressions. Secondary outcome measures included assessments of psychopathology, functional impairment, quality of life, and medication safety. An intent-to-treat analytic plan was used. From February 2002 to May 2006, 476 youths were screened, 173 were further evaluated, and 119 were randomized. Several significant study modifications were required to address safety, the use of adjunctive medications, and the termination of the olanzapine treatment arm due to weight gain. The Treatment of Early Onset Schizophrenia Spectrum Disorders Study will inform clinical practice regarding the use of antipsychotic medications for youths with early-onset schizophrenia spectrum disorders. Important safety concerns emerged during the study, including higher than anticipated rates of suicidality and problems tapering thymoleptic agents before randomization.

Design, delivery, and evaluation of early interventions for children exposed to acute trauma

PubMed Central

Kassam-Adams, Nancy

2014-01-01

Background Exposure to acute, potentially traumatic events is an unfortunately common experience for children and adolescents. Posttraumatic stress (PTS) responses following acute trauma can have an ongoing impact on child development and well-being. Early intervention to prevent or reduce PTS responses holds promise but requires careful development and empirical evaluation. Objectives The aims of this review paper are to present a framework for thinking about the design, delivery, and evaluation of early interventions for children who have been exposed to acute trauma; highlight targets for early intervention; and describe next steps for research and practice. Results and conclusions Proposed early intervention methods must (1) have a firm theoretical grounding that guides the design of intervention components; (2) be practical for delivery in peri-trauma or early post-trauma contexts, which may require creative models that go outside of traditional means of providing services to children; and (3) be ready for evaluation of both outcomes and mechanisms of action. This paper describes three potential targets for early intervention—maladaptive trauma-related appraisals, excessive early avoidance, and social/interpersonal processes—for which there is theory and evidence suggesting an etiological role in the development or persistence of PTS symptoms in children. PMID:25018860

Real-time dynamic modelling for the design of a cluster-randomized phase 3 Ebola vaccine trial in Sierra Leone.

PubMed

Camacho, A; Eggo, R M; Goeyvaerts, N; Vandebosch, A; Mogg, R; Funk, S; Kucharski, A J; Watson, C H; Vangeneugden, T; Edmunds, W J

2017-01-23

Declining incidence and spatial heterogeneity complicated the design of phase 3 Ebola vaccine trials during the tail of the 2013-16 Ebola virus disease (EVD) epidemic in West Africa. Mathematical models can provide forecasts of expected incidence through time and can account for both vaccine efficacy in participants and effectiveness in populations. Determining expected disease incidence was critical to calculating power and determining trial sample size. In real-time, we fitted, forecasted, and simulated a proposed phase 3 cluster-randomized vaccine trial for a prime-boost EVD vaccine in three candidate regions in Sierra Leone. The aim was to forecast trial feasibility in these areas through time and guide study design planning. EVD incidence was highly variable during the epidemic, especially in the declining phase. Delays in trial start date were expected to greatly reduce the ability to discern an effect, particularly as a trial with an effective vaccine would cause the epidemic to go extinct more quickly in the vaccine arm. Real-time updates of the model allowed decision-makers to determine how trial feasibility changed with time. This analysis was useful for vaccine trial planning because we simulated effectiveness as well as efficacy, which is possible with a dynamic transmission model. It contributed to decisions on choice of trial location and feasibility of the trial. Transmission models should be utilised as early as possible in the design process to provide mechanistic estimates of expected incidence, with which decisions about sample size, location, timing, and feasibility can be determined. Copyright © 2016. Published by Elsevier Ltd.

Design of a fiber-optic transmitter for microwave analog transmission with high phase stability

NASA Technical Reports Server (NTRS)

Logan, R. T., Jr.; Lutes, G. F.; Primas, L. E.; Maleki, L.

1990-01-01

The principal considerations in the design of fiber-optic transmitters for highly phase-stable radio frequency and microwave analog transmission are discussed. Criteria for a fiber-optic transmitter design with improved amplitude and phase-noise performance are developed through consideration of factors affecting the phase noise, including low-frequency laser-bias supply noise, the magnitude and proximity of external reflections into the laser, and temperature excursions of the laser-transmitter package.

Concurrent Design used in the Design of Space Instruments

NASA Technical Reports Server (NTRS)

Oxnevad, Knut I.

1998-01-01

At the Project Design Center at the Jet Propulsion Laboratory, a concurrent design environment is under development for supporting development and analyses of space instruments in the early, conceptual design phases. This environment is being utilized by a Team I, a multidisciplinary group of experts. Team I is providing study and proposal support. To provide the required support, the Team I concurrent design environment features effectively interconnected high-end optics, CAD, and thermal design and analysis tools. Innovative approaches for linking tools, and for transferring files between applications have been implemented. These approaches together with effective sharing of geometry between the optics, CAD, and thermal tools are already showing significant timesavings.

Webcam Delivery of the Lidcombe Program for Early Stuttering: A Phase I Clinical Trial

ERIC Educational Resources Information Center

O'Brian, Sue; Smith, Kylie; Onslow, Mark

2014-01-01

Purpose: The Lidcombe Program is an operant treatment for early stuttering shown with meta-analysis to have a favorable odds ratio. However, many clients are unable to access the treatment because of distance and lifestyle factors. In this Phase I trial, we explored the potential efficacy, practicality, and viability of an Internet webcam Lidcombe…

Diffusion-weighted MR imaging findings of kidneys in patients with early phase of obstruction.

PubMed

Bozgeyik, Zulkif; Kocakoc, Ercan; Sonmezgoz, Fitnet

2009-04-01

Diffusion-weighted (DW) magnetic resonance (MR) imaging is an MR technique used to show molecular diffusion. The apparent diffusion coefficient (ADC), as a quantitative parameter calculated from the DW MR images. The purpose of this study is to evaluate the ability of DW MR imaging in early phase of obstruction due to urolithiasis. Twenty-six patients with acute dilatation of the pelvicalyceal system detected by intravenous urography were included in this study. MR imaging was performed using a 1.5 T whole-body superconducting MR scanner. DW imaging can be performed using single-shot spin-echo, echo-planar imaging (EPI) sequences with the following diffusion gradient b values: 100, 600, 1000 s/mm(2). Circular region of interest (ROI) was placed in the renal parenchyma for the measurement of ADC values in the normal and obstructed kidney. For statistical analyses, Paired t test were used. In spite of obstructed kidneys had the lower ADC values compared to normal kidneys, these alterations were statistically insignificant. We did not observe significantly different ADC values of early phase of obstructed kidneys compared to normal kidneys.

Kentucky's Individualized Kindergartens: A State Network Design for Early Intervention.

ERIC Educational Resources Information Center

Bright, B.; Cansler, D. P.

The KIK (Kentucky Individualized Kindergartens) project, a collaborative project between Kentucky's Department of Education and the Chapel Hill (NC) Training-Outreach project, is designed to serve high risk children. KIK provides early identification of high risk kindergarteners, development of individualized education programs, and implementation…

Design for Safety - The Ares Launch Vehicles Paradigm Change

NASA Technical Reports Server (NTRS)

Safie, Fayssal M.; Maggio, Gaspare

2010-01-01

The lessons learned from the S&MA early involvement in the Ares I launch vehicle design phases proved that performing an in-line function jointly with engineering is critical for S&MA to have an effective role in supporting the system, element, and component design. These lessons learned were used to effectively support the Ares V conceptual design phase and planning for post conceptual design phases. The Top level Conceptual LOM assessment for Ares V performed by the S&MA community jointly with the engineering Advanced Concept Office (ACO) was influential in the final selection of the Ares V system configuration. Post conceptual phase, extensive reliability effort should be planned to support future Heavy Lift Launch Vehicles (HLLV) design. In-depth reliability analysis involving the design, manufacturing, and system engineering communities is critical to understand design and process uncertainties and system integrated failures.

Design of Chern insulating phases in honeycomb lattices

NASA Astrophysics Data System (ADS)

Pickett, Warren E.; Lee, Kwan-Woo; Pentcheva, Rossitza

2018-06-01

The search for robust examples of the magnetic version of topological insulators, referred to as quantum anomalous Hall insulators or simply Chern insulators, so far lacks success. Our groups have explored two distinct possibilities based on multiorbital 3d oxide honeycomb lattices. Each has a Chern insulating phase near the ground state, but materials parameters were not appropriate to produce a viable Chern insulator. Further exploration of one of these classes, by substituting open shell 3d with 4d and 5d counterparts, has led to realistic prediction of Chern insulating ground states. Here we recount the design process, discussing the many energy scales that are active in participating (or resisting) the desired Chern insulator phase.

Reducing Work Content in Early Stage Naval Ship Designs (Briefing Charts)

DTIC Science & Technology

2014-05-14

criticizes US naval ships for: • early design decisions that lock in density • poor arrangements of piping and ventilation 8 An overly dense ship with...Thresholds Update Save As Exit T45 #1 T45 #2 T45 #3 HPC Enables Exhaustive Exploration by: and Visualization Exploring The Space Evaluating The Space From...design points such as traditional design spiral method 30 SHIP AVG Weighted Qty (Qty) by Cost 1980s Reagan Build-up 14 10% 1% 1990/2000s Low Rate

EARLY ENTRANCE COPRODUCTION PLANT

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

David Storm; Govanon Nongbri; Steve Decanio

2004-01-12

The overall objective of this project is the three phase development of an Early Entrance Coproduction Plant (EECP) which uses petroleum coke to produce at least one product from at least two of the following three categories: (1) electric power (or heat), (2) fuels, and (3) chemicals using ChevronTexaco's proprietary gasification technology. The objective of Phase I is to determine the feasibility and define the concept for the EECP located at a specific site; develop a Research, Development, and Testing (RD&T) Plan to mitigate technical risks and barriers; and prepare a Preliminary Project Financing Plan. The objective of Phase IImore » is to implement the work as outlined in the Phase I RD&T Plan to enhance the development and commercial acceptance of coproduction technology. The objective of Phase III is to develop an engineering design package and a financing and testing plan for an EECP located at a specific site. The project's intended result is to provide the necessary technical, economic, and environmental information needed by industry to move the EECP forward to detailed design, construction, and operation. The partners in this project are Texaco Energy Systems LLC or TES (a subsidiary of ChevronTexaco), General Electric (GE), Praxair, and Kellogg Brown & Root (KBR) in addition to the U.S. Department of Energy (DOE). TES is providing gasification technology and Fischer-Tropsch (F-T) technology developed by Rentech, Inc., GE is providing combustion turbine technology, Praxair is providing air separation technology, and KBR is providing engineering. During Phase I, a design basis for the Fischer-Tropsch Synthesis section was developed based on limited experience with the specified feed gas and operating conditions. The objective of this Task in Phase II RD&T work was to confirm the performance of the F-T reactor at the set design conditions. Although much of the research, development, and testing work were done by TES outside of this project, several

Phase Transitions in the Early Universe: The Cosmology of Non-Minimal Scalar Sectors

NASA Astrophysics Data System (ADS)

Kost, Jeffrey D.

Light scalar fields such as axions and string moduli can play an important role in early-universe cosmology. However, many factors can significantly impact their late-time cosmological abundances. For example, in cases where the potentials for these fields are generated dynamically--such as during cosmological mass-generating phase transitions--the duration of the time interval required for these potentials to fully develop can have significant repercussions. Likewise, in scenarios with multiple scalars, mixing amongst the fields can also give rise to an effective timescale that modifies the resulting late-time abundances. Previous studies have focused on the effects of either the first or the second timescale in isolation. In this thesis, by contrast, we examine the new features that arise from the interplay between these two timescales when both mixing and time-dependent phase transitions are introduced together. First, we find that the effects of these timescales can conspire to alter not only the total late-time abundance of the system--often by many orders of magnitude--but also its distribution across the different fields. Second, we find that these effects can produce large parametric resonances which render the energy densities of the fields highly sensitive to the degree of mixing as well as the duration of the time interval over which the phase transition unfolds. Finally, we find that these effects can even give rise to a "re-overdamping" phenomenon which causes the total energy density of the system to behave in novel ways that differ from those exhibited by pure dark matter or vacuum energy. All of these features therefore give rise to new possibilities for early-universe phenomenology and cosmological evolution. They also highlight the importance of taking into account the time dependence associated with phase transitions in cosmological settings. In the second part of this thesis, we proceed to study the early-universe cosmology of a Kaluza-Klein (KK

Cognitive function in early clinical phase huntington disease after rivastigmine treatment.

PubMed

Sešok, Sanja; Bolle, Nika; Kobal, Jan; Bucik, Valentin; Vodušek, David B

2014-09-01

In Huntington disease (HD) patients receiving rivastigmine treatment improvement of behavioral symptoms and of cognitive function (assessed with screening diagnostic instruments) has been reported. The aim of the present study was to verify such improvement in cognitive function by cognitive function assessment with a detailed neuropsychological battery covering all relevant cognitive systems expected to be impaired in early phase HD. Eighteen (18) HD patients entered the study and were randomly allocated to the rivastigmine and placebo group. All subjects underwent neuropsychological assessment at baseline. Follow-up neuropsychological assessment was applied after 6 months of rivastigmine or placebo treatment. Eighteen (18) healthy controls entered the study to control for practice effect and underwent neuropsychological assessment at baseline and after 6 months, without treatment. The neuropsychological battery consisted of assessment tools that are sensitive to cognitive impairment seen in early phase HD: CTMT, SDMT, Stroop (attention and information control), RFFT, TOL, Verbal fluency (executive functioning), CVLT-II, RCFT (learning and memory). Effect of rivastigmine and possible effect of practice was assessed using the mixed ANOVA model. No statistically significant effect of rivastigmine treatment on cognitive function in HD patients was detected. There was no evidence for practice or placebo effect. Detailed neuropsychological assessment did not confirm previously reported effect of rivastigmine treatment on cognitive function in HD patients. The limitations of our study are, in particular, small sample size and the lack of a single measure of relevant cognitive functioning in HD patients. Instead of focusing solely on statistical significance, a clinical relevance study is proposed to clarify the issue of rivastigmine effects in HD.

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.

Natural environment design criteria for the space station program definition phase

NASA Technical Reports Server (NTRS)

Vaughan, W. W.

1984-01-01

The natural environment design criteria requirements for use in the Space Station and its Elements (SSPE) definition phase studies are presented. The atmospheric dynamic and thermodynamic environments, meteoroids, radiation, physical constants are addressed. It is intended to enable all groups involved in the definition phase studies to proceed with a common and consistent set of natural environment criteria requirements.

Conceptual design of two-phase fluid mechanics and heat transfer facility for spacelab

NASA Technical Reports Server (NTRS)

North, B. F.; Hill, M. E.

1980-01-01

Five specific experiments were analyzed to provide definition of experiments designed to evaluate two phase fluid behavior in low gravity. The conceptual design represents a fluid mechanics and heat transfer facility for a double rack in Spacelab. The five experiments are two phase flow patterns and pressure drop, flow boiling, liquid reorientation, and interface bubble dynamics. Hardware was sized, instrumentation and data recording requirements defined, and the five experiments were installed as an integrated experimental package. Applicable available hardware was selected in the experiment design and total experiment program costs were defined.

Phase-shifting point diffraction interferometer mask designs

DOEpatents

Goldberg, Kenneth Alan

2001-01-01

In a phase-shifting point diffraction interferometer, different image-plane mask designs can improve the operation of the interferometer. By keeping the test beam window of the mask small compared to the separation distance between the beams, the problem of energy from the reference beam leaking through the test beam window is reduced. By rotating the grating and mask 45.degree., only a single one-dimensional translation stage is required for phase-shifting. By keeping two reference pinholes in the same orientation about the test beam window, only a single grating orientation, and thus a single one-dimensional translation stage, is required. The use of a two-dimensional grating allows for a multiplicity of pinholes to be used about the pattern of diffracted orders of the grating at the mask. Orientation marks on the mask can be used to orient the device and indicate the position of the reference pinholes.

SOME DESIGN ISSUES IN PHASE 2B VERSUS PHASE 3 PREVENTION TRIALS FOR TESTING EFFICACY OF PRODUCTS OR CONCEPTS

PubMed Central

Gilbert, Peter B.

2009-01-01

SUMMARY After one or more Phase 2 trials show that a candidate preventive vaccine induces immune responses that putatively protect against an infectious disease for which there is no licensed vaccine, the next step is to evaluate the efficacy of the candidate. The trial-designer faces the question of what is the optimal size of the initial efficacy trial? Part of the answer will entail deciding between a large Phase 3 licensure trial or an intermediate-sized Phase 2b screening trial, the latter of which may be designed to directly contribute to the evidence-base for licensing the candidate, or, to test a scientific concept for moving the vaccine field forward, acknowledging that the particular candidate will never be licensable. Using the HIV vaccine field as a case study, we describe distinguishing marks of Phase 2b and Phase 3 prevention efficacy trials, and compare the expected utility of these trial types using Pascal’s decision-theoretic framework. By integrating values/utilities on (1) Correct or incorrect conclusions resulting from the trial; (2) Timeliness of obtaining the trial results; (3) Precision for estimating the intervention effect; and (4) Resources expended; this decision framework provides a more complete approach to selecting the optimal efficacy trial size than a traditional approach that is based primarily on power calculations. Our objective is to help inform the decision-process for planning an initial efficacy trial design. PMID:20419758

Designing scattering-free isotropic index profiles using phase-amplitude equations

NASA Astrophysics Data System (ADS)

King, C. G.; Horsley, S. A. R.; Philbin, T. G.

2018-05-01

The Helmholtz equation can be written as coupled equations for the amplitude and phase. By considering spatial phase distributions corresponding to reflectionless wave propagation in the plane and solving for the amplitude in terms of this phase, we designed two-dimensional graded-index media which do not scatter light. We give two illustrative examples, the first of which is a periodic grating for which diffraction is completely suppressed at a single frequency at normal incidence to the periodicity. The second example is a medium which behaves as a "beam shifter" at a single frequency; acting to laterally shift a plane wave, or sufficiently wide beam, without reflection.

Progress and prospects of silicon-based design for optical phased array

NASA Astrophysics Data System (ADS)

Hu, Weiwei; Peng, Chao; Chang-Hasnain, Connie

2016-03-01

The high-speed, high-efficient, compact phase modulator array is indispensable in the Optical-phased array (OPA) which has been considered as a promising technology for realizing flexible and efficient beam steering. In our research, two methods are presented to utilize high-contrast grating (HCG) as high-efficient phase modulator. One is that HCG possesses high-Q resonances that origins from the cancellation of leaky waves. As a result, sharp resonance peaks appear on the reflection spectrum thus HCGs can be utilized as efficient phase shifters. Another is that low-Q mode HCG is utilized as ultra-lightweight mirror. With MEMS technology, small HCG displacement (~50 nm) leads to large phase change (~1.7π). Effective beam steering is achieved in Connie Chang-Hasnian's group. On the other hand, we theoretically and experimentally investigate the system design for silicon-based optical phased array, including the star coupler, phased array, emission elements and far-field patterns. Further, the non-uniform optical phased array is presented.

Structures and Design Phase I Summary for the NASA Composite Cryotank Technology Demonstration Project

NASA Technical Reports Server (NTRS)

Johnson, Ted; Sleight, David W.; Martin, Robert A.

2013-01-01

A description of the Phase I structures and design work of the Composite Cryotank Technology Demonstration (CCTD) Project is in this paper. The goal of the CCTD Project in the Game Changing Development (GCD) Program is to design and build a composite liquid-hydrogen cryogenic tank that can save 30% in weight and 25% in cost compared to state-of-the-art aluminum metallic cryogenic tank technology when the wetted composite skin wall is at an allowable strain of 5000 in/in. Three Industry teams developed composite cryogenic tank concepts that are compared for weight to an aluminum-lithium (Al-Li) cryogenic tank designed by NASA in Phase I of the CCTD Project. The requirements used to design all of the cryogenic tanks in Phase I will be discussed and the resulting designs, analyses, and weight of the concepts developed by NASA and Industry will be reviewed and compared.

Specifications of a continual reassessment method design for phase I trials of combined drugs†

PubMed Central

Wages, Nolan A.; Conaway, Mark R.

2013-01-01

In studies of combinations of agents in phase I oncology trials, the dose–toxicity relationship may not be monotone for all combinations, in which case the toxicity probabilities follow a partial order. The continual reassessment method for partial orders (PO-CRM) is a design for phase I trials of combinations that leans upon identifying possible complete orders associated with the partial order. This article addresses some practical design considerations not previously undertaken when describing the PO-CRM. We describe an approach in choosing a proper subset of possible orderings, formulated according to the known toxicity relationships within a matrix of combination therapies. Other design issues, such as working model selection and stopping rules, are also discussed. We demonstrate the practical ability of PO-CRM as a phase I design for combinations through its use in a recent trial designed at the University of Virginia Cancer Center. PMID:23729323

Unknown loads affect force production capacity in early phases of bench press throws.

PubMed

Hernández Davó, J L; Sabido Solana, R; Sarabia Marínm, J M; Sánchez Martos, Á; Moya Ramón, M

2015-10-01

Explosive strength training aims to improve force generation in early phases of movement due to its importance in sport performance. The present study examined the influence of lack of knowledge about the load lifted in explosive parameters during bench press throws. Thirteen healthy young men (22.8±2.0 years) participated in the study. Participants performed bench press throws with three different loads (30, 50 and 70% of 1 repetition maximum) in two different conditions (known and unknown loads). In unknown condition, loads were changed within sets in each repetition and participants did not know the load, whereas in known condition the load did not change within sets and participants had knowledge about the load lifted. Results of repeated-measures ANOVA revealed that unknown conditions involves higher power in the first 30, 50, 100 and 150 ms with the three loads, higher values of ratio of force development in those first instants, and differences in time to reach maximal rate of force development with 50 and 70% of 1 repetition maximum. This study showed that unknown conditions elicit higher values of explosive parameters in early phases of bench press throws, thereby this kind of methodology could be considered in explosive strength training.

Analysis of Loss-of-Coolant Accidents in the NIST Research Reactor - Early Phase

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

Baek, Joo S.; Diamond, David

A study of the fuel temperature during the early phase of a loss-of-coolant accident (LOCA) in the NIST research reactor (NBSR) was completed. Previous studies had been reported in the preliminary safety analysis report for the conversion of the NBSR from high-enriched uranium (HEU) fuel to low-enriched (LEU) fuel. Those studies had focused on the most vulnerable LOCA situation, namely, a double-ended guillotine break in the time period after reactor trip when water is drained from either the coolant channels inside the fuel elements or the region outside the fuel elements. The current study fills in a gap in themore » analysis which is the early phase of the event when there may still be water present but the reactor is at power or immediately after reactor trip and pumps have tripped. The calculations were done, for both the current HEU-fueled core and the proposed LEU core, with the TRACE thermal-hydraulic systems code. Several break locations and different break sizes were considered. In all cases the increase in the clad (or fuel meat) temperature was relatively small so that a large margin to the temperature threshold for blistering (the Safety Limit for the NBSR) remained.« less

Design space exploration for early identification of yield limiting patterns

NASA Astrophysics Data System (ADS)

Li, Helen; Zou, Elain; Lee, Robben; Hong, Sid; Liu, Square; Wang, JinYan; Du, Chunshan; Zhang, Recco; Madkour, Kareem; Ali, Hussein; Hsu, Danny; Kabeel, Aliaa; ElManhawy, Wael; Kwan, Joe

2016-03-01

In order to resolve the causality dilemma of which comes first, accurate design rules or real designs, this paper presents a flow for exploration of the layout design space to early identify problematic patterns that will negatively affect the yield. A new random layout generating method called Layout Schema Generator (LSG) is reported in this paper, this method generates realistic design-like layouts without any design rule violation. Lithography simulation is then used on the generated layout to discover the potentially problematic patterns (hotspots). These hotspot patterns are further explored by randomly inducing feature and context variations to these identified hotspots through a flow called Hotspot variation Flow (HSV). Simulation is then performed on these expanded set of layout clips to further identify more problematic patterns. These patterns are then classified into design forbidden patterns that should be included in the design rule checker and legal patterns that need better handling in the RET recipes and processes.

Toward a clinically useful method of predicting early breast-feeding attrition.

PubMed

Lewallen, Lynne Porter; Dick, Margaret J; Wall, Yolanda; Zickefoose, Kimberly Taylor; Hannah, Susan Hensley; Flowers, Janet; Powell, Wanda

2006-08-01

The overall purpose of this study was to revise and test an instrument to identify, during the early postpartum period, women at risk for early breast-feeding attrition. This study was completed in two phases: the first phase tested a revision of the Breast-Feeding Attrition Prediction Tool (BAPT); the second, a new instrument, the Breast-Feeding Attitude Scale (BrAS), which was adapted from the BAPT. The two phases of this study involved 415 pregnant and postpartum women. Women answered questions either by phone (pregnant women) or in their hospital rooms after delivery (postpartum women). Data were analyzed using t tests and reliability analysis. The BAPT did not predict early breast-feeding attrition; however, the BrAS did differentiate between the attitudes of breast-feeding women and those of formula-feeding women and had adequate reliability. Women at risk for early breast-feeding attrition should be identified early so nursing interventions can be directed toward preventing early unintended weaning. Although the BrAS did not reliably identify women at risk in this sample, it did highlight important differences between breast-feeding and formula-feeding women that can be used in designing preconceptional or prenatal educational assessments and interventions.

Extinct radioactivities - A three-phase mixing model. [for early solar system abundances

NASA Technical Reports Server (NTRS)

Clayton, D. D.

1983-01-01

A new class of models is advanced for interpreting the relationship of radioactive abundances in the early solar system to their average concentration in the interstellar medium. The model assumes that fresh radioactivities are ejected from supernovae into the hot interstellar medium, and that the time scales for changes of phase into molecular clouds determine how much survives for formation therein of the solar system. A more realistic and physically motivated understanding of the low observed concentrations of I-129, Pu-244, and Pd-107 may result.

Examination of a modified cell cycle synchronization method and bovine nuclear transfer using synchronized early G1 phase fibroblast cells.

PubMed

Urakawa, Manami; Ideta, Atsushi; Sawada, Tokihiko; Aoyagi, Yoshito

2004-08-01

Somatic cell nuclear transfer has a low success rate, due to a high incidence of fetal loss and increased perinatal morbidity/mortality. One factor that may affect the successful development of nuclear transfer embryos is the cell cycle stage of the donor cell. In order to establish a cell cycle synchronization method that can consistently produce cloned embryos and offspring, we examined the effects of different combinations of three cell treatments on the recovery rate of mitotic phase cells using bovine fetal fibroblasts. In the first experiment, we examined the recovery rate of mitotic phase cells by a combination of treatment with a metaphase arrestant (1 microM 2-methoxyestradiol), shaking the plate and selecting cells with a diameter of 20 microns. As a result, 99% of mitotic phase cells were recovered by repeating the combined treatment of metaphase arrestant and shaking, and collection of cells with a specific diameter. In the second experiment, nuclear transfer was carried out using early G1 phase cells by choosing pairs of bridged cells derived from mitotic phase cells recovered by the combined treatment of 1 microM 2-methoxyestradiol and shaking, and collection of cells with a diameter of 20 microns. The reconstructed embryos were transferred to recipient heifers to determine post-implantation development. Development of embryos reconstructed from early G1 phase cells from the >/=6 cells stage on Day 3 to the morula-blastocyst stage on Day 6 was 100%. Ten blastocysts constructed from two cell lines were transferred into 10 recipient heifers. Nine of the 10 recipients delivered single live calves. In conclusion, mitotic phase bovine fibroblast cells were easily recovered by the combined treatments of 1 microM 2-methoxyestradiol, shaking, and selecting cells of the appropriate diameter. Furthermore, nuclear transfer using cells in the early G1 phase as donor cells gave a high rate of offspring production.

ART/Ada design project, phase 1: Project plan

NASA Technical Reports Server (NTRS)

Allen, Bradley P.

1988-01-01

The plan and schedule for Phase 1 of the Ada based ESBT Design Research Project is described. The main platform for the project is a DEC Ada compiler on VAX mini-computers and VAXstations running the Virtual Memory System (VMS) operating system. The Ada effort and lines of code are given in tabular form. A chart is given of the entire project life cycle.

Auto-inhibitory regulation of angiotensin II functionality in hamster aorta during the early phases of dyslipidemia.

PubMed

Pereira, Priscila Cristina; Pernomian, Larissa; Côco, Hariane; Gomes, Mayara Santos; Franco, João José; Marchi, Kátia Colombo; Hipólito, Ulisses Vilela; Uyemura, Sergio Akira; Tirapelli, Carlos Renato; de Oliveira, Ana Maria

2016-06-15

Emerging data point the crosstalk between dyslipidemia and renin-angiotensin system (RAS). Advanced dyslipidemia is described to induce RAS activation in the vasculature. However, the interplay between early dyslipidemia and the RAS remains unexplored. Knowing that hamsters and humans have a similar lipid profile, we investigated the effects of early and advanced dyslipidemia on angiotensin II-induced contraction. Cumulative concentration-response curves for angiotensin II (1.0pmol/l to 1.0µmol/l) were obtained in the hamster thoracic aorta. We also investigated the modulatory action of NAD(P)H oxidase on angiotensin II-induced contraction using ML171 (Nox-1 inhibitor, 0.5µmol/l) and VAS2870 (Nox-4 inhibitor, 5µmol/l). Early dyslipidemia was detected in hamsters treated with a cholesterol-rich diet for 15 days. Early dyslipidemia decreased the contraction induced by angiotensin II and the concentration of Nox-4-derived hydrogen peroxide. Advanced dyslipidemia, observed in hamsters treated with cholesterol-rich diet for 30 days, restored the contractile response induced by angiotensin II by compensatory mechanism that involves Nox-4-mediated oxidative stress. The hyporresponsiveness to angiotensin II may be an auto-inhibitory regulation of the angiotensinergic function during early dyslipidemia in an attempt to reduce the effects of the upregulation of the vascular RAS during the advanced stages of atherogenesis. The recovery of vascular angiotensin II functionality during the advanced phases of dyslipidemia is the result of the upregulation of redox-pro-inflammatory pathway that might be most likely involved in atherogenesis progression rather than in the recovery of vascular function. Taken together, our findings show the early phase of dyslipidemia may be the most favorable moment for effective atheroprotective therapeutic interventions. Copyright © 2016 Elsevier B.V. All rights reserved.

An Analysis of Risk and Function Information in Early Stage Design

NASA Technical Reports Server (NTRS)

Barrientos, Francesca; Tumer, Irem; Grantham, Katie; VanWie, Michael; Stone, Robert

2005-01-01

The concept of function offers a high potential for thinking and reasoning about designs as well as providing a common thread for relating together other design information. This paper focuses specifically on the relation between function and risk by examining how this information is addressed for a design team conducting early stage design for space missions. Risk information is decomposed into a set of key attributes which are then used to scrutinize the risk information using three approaches from the pragmatics sub-field of linguistics: i) Gricean, ii) Relevance Theory, and Functional Analysis. Results of this linguistics-based approach descriptively account for the context of designer communication with respect to function and risk, and offer prescriptive guidelines for improving designer communication.

The cortical damage, early relapses, and onset of the progressive phase in multiple sclerosis.

PubMed

Scalfari, Antonio; Romualdi, Chiara; Nicholas, Richard S; Mattoscio, Miriam; Magliozzi, Roberta; Morra, Aldo; Monaco, Salvatore; Muraro, Paolo A; Calabrese, Massimiliano

2018-05-16

To investigate the relationship among cortical radiologic changes, the number of early relapses (ERs), and the long-term course of multiple sclerosis (MS). In this cohort study, we assessed the number of cortical lesions (CLs) and white matter (WM) lesions and the cortical thickness (Cth) at clinical onset and after 7.9 mean years among 219 patients with relapsing remitting (RR) MS with 1 (Low-ER), 2 (Mid-ER), and ≥3 (High-ER) ERs during the first 2 years. Kaplan-Meier and Cox regression analyses investigated early factors influencing the risk of secondary progressive (SP) MS. Fifty-nine patients (27%) converted to SPMS in 6.1 mean years. A larger number of CLs at onset predicted a higher risk of SPMS (hazard ratio [HR] 2.16, 4.79, and 12.3 for 2, 5, and 7 CLs, respectively, p < 0.001) and shorter latency to progression. The High-ER compared to the Low-ER and Mid-ER groups had a larger volume of WM lesions and CLs at onset, accrued more CLs, experienced more severe cortical atrophy over time, and entered the SP phase more rapidly. In the multivariate model, older age at onset (HR 1.97, p < 0.001), a larger baseline CL (HR 2.21, p = 0.005) and WM lesion (HR 1.32, p = 0.03) volume, early changes of global Cth (HR 1.36, p = 0.03), and ≥3 ERs (HR 6.08, p < 0.001) independently predicted a higher probability of SP. Extensive cortical damage at onset is associated with florid inflammatory clinical activity and predisposes to a rapid occurrence of the progressive phase. Age at onset, the number of early attacks, and the extent of baseline focal cortical damage can identify groups at high risk of progression who may benefit from more active therapy. © 2018 American Academy of Neurology.

MSFC Sortie Laboratory Environmental Control System (ECS) phase B design study results

NASA Technical Reports Server (NTRS)

Ignatonis, A. J.; Mitchell, K. L.

1974-01-01

Phase B effort of the Sortie Lab program has concluded. Results of that effort are presented which pertain to the definitions of the environmental control system (ECS). Numerous design studies were performed in Phase B to investigate system feasibility, complexity, weight, and cost. The results and methods employed for these design studies are included. An autonomous Sortie Lab ECS was developed which utilizes a deployed space radiator. Total system weight was projected to be 1814.4 kg including the radiator and fluids. ECS power requirements were estimated at 950 watts.

Tucson Diversion Channel. Phase I. Sport Fields & Picnic Area. Feature Design Memorandum Number 3.

DTIC Science & Technology

1983-04-01

opportunities for picnicking, a variety of field sports and court games , archery, jogging, and bicycling. d. Rapid urban growth in the Tucson metropolitan area...AD’A136 927 TUCSON DIVERSION CHANNEL PHASE I SPORT FIELDS A PICNI IC J AREA FEATURE DESIGN MEMORANDUM NUMBER 3(U) ARMY ENGINEER DISTRICT LOS ANGELES...TUCSON DIVERSION CHMNEL DESIGN EIORANDUK NO. 3 FEATURE DESIGN MNRORANDIJ PHASE I SPORT FIELDS & PICNIC AREA APRIL 1983 t1 US AM CORPS OF

Integrating nutrition and early child-development interventions among infants and preschoolers in rural India.

PubMed

Fernandez-Rao, Sylvia; Hurley, Kristen M; Nair, Krishnapillai Madhavan; Balakrishna, Nagalla; Radhakrishna, Kankipati V; Ravinder, Punjal; Tilton, Nicholas; Harding, Kimberly B; Reinhart, Greg A; Black, Maureen M

2014-01-01

This article describes the development, design, and implementation of an integrated randomized double-masked placebo-controlled trial (Project Grow Smart) that examines how home/preschool fortification with multiple micronutrient powder (MNP) combined with an early child-development intervention affects child development, growth, and micronutrient status among infants and preschoolers in rural India. The 1-year trial has an infant phase (enrollment age: 6-12 months) and a preschool phase (enrollment age: 36-48 months). Infants are individually randomized into one of four groups: placebo, placebo plus early learning, MNP alone, and MNP plus early learning (integrated intervention), conducted through home visits. The preschool phase is a cluster-randomized trial conducted in Anganwadi centers (AWCs), government-run preschools sponsored by the Integrated Child Development System of India. AWCs are randomized into MNP or placebo, with the MNP or placebo mixed into the children's food. The evaluation examines whether the effects of the MNP intervention vary by the quality of the early learning opportunities and communication within the AWCs. Study outcomes include child development, growth, and micronutrient status. Lessons learned during the development, design, and implementation of the integrated trial can be used to guide large-scale policy and programs designed to promote the developmental, educational, and economic potential of children in developing countries. © 2013 New York Academy of Sciences.

A Policymaker's Guide to Early College Designs: Expanding a Strategy for Achieving College Readiness for All

ERIC Educational Resources Information Center

Hoffman, Nancy; Vargas, Joel

2010-01-01

Today, states and the federal government recognize the potential of early college designs to improve the economic prospects of future generations. But individuals are just beginning to put in place public policies that promote and support early college designs on a significant scale. Jobs for the Future (JFF) prepared this guide to help…

Feasibility study for early removal of HEU from CPP-651-Phase II

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

Smith, C.V.; Henry, R.; Milligan, C.

1997-09-01

A two-phase feasibility study was initiated in late 1996 to identify a way to expedite the removal of SNM from the CPP-651 vault. The first phase of this study provided preliminary information that appeared promising, but needed additional detailed planning and evaluate to validate the concepts and conclusions. The focus of Phase 2 was to provide the validation via resource-loaded schedules and more detailed cost estimates. Section 1 describes the purpose and objectives of the Phase 2 tasks and the programmatic drivers that influence related CPP-651 high-enriched uranium (HEU) management issues. Section 2 identifies the evaluation criteria and methodology andmore » the transfer issues and barriers preventing shipment. Section 3 provides site-specific background information for the CPP-651 facility and the Idaho National Engineering and Environmental Laboratory (INEEL) and describes the development of the basic material removal schedule, the proposed base case plan for removal of SNM, and the proposed HEU material management/shipping issues and strategies. Section 4 identifies the proposed options for accelerated removal of SNM and how they were evaluated via detailed scheduling, resource histograms, and cost analysis. Section 5 summarizes principal tasks for implementing this plan and other related HEU CPP-651 management issues that require continued planning efforts to assure successful implementation of this proposed early removal strategy.« less

Fast optimization method of designing a wideband metasurface without using the Pancharatnam-Berry phase.

PubMed

Sui, Sai; Ma, Hua; Lv, Yueguang; Wang, Jiafu; Li, Zhiqiang; Zhang, Jieqiu; Xu, Zhuo; Qu, Shaobo

2018-01-22

Arbitrary control of electromagnetic waves remains a significant challenge although it promises many important applications. Here, we proposed a fast optimization method of designing a wideband metasurface without using the Pancharatnam-Berry (PB) phase, of which the elements are non-absorptive and capable of predicting the wideband and smooth phase-shift. In our design method, the metasurface is composed of low-Q-factor resonant elements without using the PB phase, and is optimized by the genetic algorithm and nonlinear fitting method, having the advantages that the far field scattering patterns can be quickly synthesized by the hybrid array patterns. To validate the design method, a wideband low radar cross section metasurface is demonstrated, showing good feasibility and performance of wideband RCS reduction. This work reveals an opportunity arising from a metasurface in effective manipulation of microwave and flexible fast optimal design method.

10 CFR 2.110 - Filing and administrative action on submittals for standard design approval or early review of...

Code of Federal Regulations, 2011 CFR

2011-01-01

... standard design approval or early review of site suitability issues. 2.110 Section 2.110 Energy NUCLEAR... or early review of site suitability issues. (a)(1) A submittal for a standard design approval under... provisions of appendix Q to parts 50 of this chapter, a submittal for early review of site suitability issues...

10 CFR 2.110 - Filing and administrative action on submittals for standard design approval or early review of...

Code of Federal Regulations, 2010 CFR

2010-01-01

... standard design approval or early review of site suitability issues. 2.110 Section 2.110 Energy NUCLEAR... or early review of site suitability issues. (a)(1) A submittal for a standard design approval under... provisions of appendix Q to parts 50 of this chapter, a submittal for early review of site suitability issues...

Definition of two-phase flow behaviors for spacecraft design

NASA Technical Reports Server (NTRS)

Reinarts, Thomas R.; Best, Frederick R.; Miller, Katherine M.; Hill, Wayne S.

1991-01-01

Two-phase flow, thermal management systems are currently being considered as an alternative to conventional, single phase systems for future space missions because of their potential to reduce overall system mass, size, and pumping power requirements. Knowledge of flow regime transitions, heat transfer characteristics, and pressure drop correlations is necessary to design and develop two-phase systems. A boiling and condensing experiment was built in which R-12 was used as the working fluid. A two-phase pump was used to circulate a freon mixture and allow separate measurements of the vapor and liquid flow streams. The experimental package was flown five times aboard the NASA KC-135 aircraft which simulates zero-g conditions by its parabolic flight trajectory. Test conditions included stratified and annual flow regimes in 1-g which became bubbly, slug, or annular flow regimes on 0-g. A portion of this work is the analysis of adiabatic flow regimes. The superficial velocities of liquid and vapor have been obtained from the measured flow rates and are presented along with the observed flow regimes.

National accident sampling system sample design, phases 2 and 3 : executive summary

DOT National Transportation Integrated Search

1979-11-01

This report describes the Phase 2 and 3 sample design for the : National Accident Sampling System (NASS). It recommends a procedure : for the first-stage selection of Primary Sampling Units (PSU's) and : the second-stage design for the selection of a...

Design and development of high frequency matrix phased-array ultrasonic probes

NASA Astrophysics Data System (ADS)

Na, Jeong K.; Spencer, Roger L.

2012-05-01

High frequency matrix phased-array (MPA) probes have been designed and developed for more accurate and repeatable assessment of weld conditions of thin sheet metals commonly used in the auto industry. Unlike the line focused ultrasonic beam generated by a linear phased-array (LPA) probe, a MPA probe can form a circular shaped focused beam in addition to the typical beam steering capabilities of phased-array probes. A CIVA based modeling and simulation method has been used to design the probes in terms of various probe parameters such as number of elements, element size, overall dimensions, frequency etc. Challenges associated with the thicknesses of thin sheet metals have been resolved by optimizing these probe design parameters. A further improvement made on the design of the MPA probe proved that a three-dimensionally shaped matrix element can provide a better performing probe at a much lower probe manufacturing cost by reducing the total number of elements and lowering the operational frequency. This three dimensional probe naturally matches to the indentation shape of the weld on the thin sheet metals and hence a wider inspection area with the same level of spatial resolution obtained by a twodimensional flat MPA probe operating at a higher frequency. The two aspects, a wider inspection area and a lower probe manufacturing cost, make this three-dimensional MPA sensor more attractive to auto manufacturers demanding a quantitative nondestructive inspection method.

Early-phase prandial insulin secretion: its role in the pathogenesis of type 2 diabetes mellitus and its modulation by repaglinide.

PubMed

Owens, D R; Cozma, L S; Luzio, S D

2002-12-01

The major contributory factor to increasing hyperglycaemia in established Type 2 diabetes mellitus (T2DM) appears to be the progressive delay and attenuation of the prandial insulin response. An important consequence of this derangement is that hepatic glucose production is no longer suppressed during times of prandial glucose intake. Together with a relative impairment in the rate of peripheral glucose disposal, this leads to supra-physiological plasma glucose excursions, which may damage the vasculature. An obvious therapeutic strategy, therefore, would be to increase insulin availability when most needed--in the early prandial phase. In experiments with exogenous insulin interventions, peak post-prandial blood glucose increments were curtailed without undue increases in total insulin exposure. However, available evidence suggests that the sulphonylurea glibenclamide does not effectively alter early-phase prandial insulin release but predominately increases late-phase and basal insulin output, thus incurring the risk of hypoglycaemia. The novel insulin secretagogue repaglinide, by contrast, augments early-phase prandial insulin secretion when taken before meals, as shown by studies in non-diabetic people and patients with newly diagnosed, previously untreated T2DM. Repaglinide exerts its greatest effect on the insulin secretion rate during the first 30 min after a meal is started, thereby going some way to restoring the early insulin secretion curve seen after a meal in non-diabetic people. No residual secretagogue activity is seen 4 hr after taking a single dose of up to 2 mg. Prandial glucose regulation with repaglinide could be associated with lower post-prandial glucose excursions and less risk of post-prandial hypoglycaemia than glibenclamide.

Mechanisms of the early phases of plant gravitropism

NASA Technical Reports Server (NTRS)

Kiss, J. Z.

2000-01-01

Gravitropism is directed growth of a plant or plant organ in response to gravity and can be divided into the following temporal sequence: perception, transduction, and response. This article is a review of the research on the early events of gravitropism (i.e., phenomena associated with the perception and transduction phases). The two major hypotheses for graviperception are the protoplast-pressure and starch-statolith models. While most researchers support the concept of statoliths, there are suggestions that plants have multiple mechanisms of perception. Evidence supports the hypothesis that the actin cytoskeleton is involved in graviperception/transduction, but the details of these mechanisms remain elusive. A number of recent developments, such as increased use of the molecular genetic approach, magnetophoresis, and laser ablation, have facilitated research in graviperception and have allowed for refinement of the current models. In addition, the entire continuum of acceleration forces from hypo- to hyper-gravity have been useful in studying perception mechanisms. Future interdisciplinary molecular approaches and the availability of sophisticated laboratories on the International Space Station should help to develop new insights into mechanisms of gravitropism in plants.

Multi-band phase shifter design using modified slotline configuration

NASA Astrophysics Data System (ADS)

Kulandhaisamy, Indhumathi; Rajendran, Dinesh Babu; Kanagasabai, Malathi; Gurusamy, Gunasekaran; Moorthy, Balaji; George, Jithila V.; Lawrance, Livya

2017-01-01

In this paper, an analog multiband phase shifter using slotline configuration is proposed. To implement the design, a pair of modified Split Ring Resonator (SRR) is employed. The periodic property of SRR provides multiband characteristics, whether the coupling slot gives the phase variations over the bands. The operation is well explained with an equivalent circuit model and its characteristics have been studied both in simulation and measurement. The prototype operates in 1.77-2.16, 3.5-3.97, 5.08-5.33, 6.43-6.93, and 8.01-8.59 GHz frequency bands which can be utilized for GSM, GPS, WLAN, C-band, and X-band applications, respectively.

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 &

Phase II design with sequential testing of hypotheses within each stage.

PubMed

Poulopoulou, Stavroula; Karlis, Dimitris; Yiannoutsos, Constantin T; Dafni, Urania

2014-01-01

The main goal of a Phase II clinical trial is to decide, whether a particular therapeutic regimen is effective enough to warrant further study. The hypothesis tested by Fleming's Phase II design (Fleming, 1982) is [Formula: see text] versus [Formula: see text], with level [Formula: see text] and with a power [Formula: see text] at [Formula: see text], where [Formula: see text] is chosen to represent the response probability achievable with standard treatment and [Formula: see text] is chosen such that the difference [Formula: see text] represents a targeted improvement with the new treatment. This hypothesis creates a misinterpretation mainly among clinicians that rejection of the null hypothesis is tantamount to accepting the alternative, and vice versa. As mentioned by Storer (1992), this introduces ambiguity in the evaluation of type I and II errors and the choice of the appropriate decision at the end of the study. Instead of testing this hypothesis, an alternative class of designs is proposed in which two hypotheses are tested sequentially. The hypothesis [Formula: see text] versus [Formula: see text] is tested first. If this null hypothesis is rejected, the hypothesis [Formula: see text] versus [Formula: see text] is tested next, in order to examine whether the therapy is effective enough to consider further testing in a Phase III study. For the derivation of the proposed design the exact binomial distribution is used to calculate the decision cut-points. The optimal design parameters are chosen, so as to minimize the average sample number (ASN) under specific upper bounds for error levels. The optimal values for the design were found using a simulated annealing method.

Current status of amorphous formulation and other special dosage forms as formulations for early clinical phases.

PubMed

Kawakami, Kohsaku

2009-09-01

Although most chemists in the pharmaceutical industry have a good understanding on favorable physicochemical properties for drug candidates, formulators must still deal with many challenging candidates. On the other hand, formulators are not allowed to spend much time on formulation development for early phases of the clinical studies. Thus, it is basically difficult to apply special dosage form technologies to the candidates for the first-in-human formulations. Despite the availability of numerous reviews on oral special dosage forms, information on their applicability as the early phase formulation has been limited. This article describes quick review on the oral special dosage forms that may be applied to the early clinical formulations, followed by discussion focused on the amorphous formulations, which still has relatively many issues to be proved for the general use. The major problems that inhibit the use of the amorphous formulation are difficulty in the manufacturing and the poor chemical/physical stability. Notably, the poor physical stability can be critical, because of not the poor stability itself but the difficulty in the timely evaluation in the preclinical developmental timeframes. Research directions of the amorphous formulations are suggested to utilize this promising technology without disturbing the preclinical developmental timelines.

Men Managing, Not Teaching Foundation Phase: Teachers, Masculinity and the Early Years of Primary Schooling

ERIC Educational Resources Information Center

Moosa, Shaaista; Bhana, Deevia

2017-01-01

In this article we argue that eliminating the divisions of labour between men and women could work towards counteracting gender inequality within professions. Globally women are over-represented in the teaching of young children in the early years of primary school, or Foundation Phase (FP), as it is known in South Africa. We are concerned to go…

ART/Ada design project, phase 1. Task 3 report: Test plan

NASA Technical Reports Server (NTRS)

Allen, Bradley P.

1988-01-01

The plan is described for the integrated testing and benchmark of Phase Ada based ESBT Design Research Project. The integration testing is divided into two phases: (1) the modules that do not rely on the Ada code generated by the Ada Generator are tested before the Ada Generator is implemented; and (2) all modules are integrated and tested with the Ada code generated by the Ada Generator. Its performance and size as well as its functionality is verified in this phase. The target platform is a DEC Ada compiler on VAX mini-computers and VAX stations running the VMS operating system.

Evolution of Ada technology in the flight dynamics area: Design phase analysis

NASA Technical Reports Server (NTRS)

Quimby, Kelvin L.; Esker, Linda

1988-01-01

The software engineering issues related to the use of the Ada programming language during the design phase of an Ada project are analyzed. Discussion shows how an evolving understanding of these issues is reflected in the design processes of three generations of Ada projects.

Sustainability in the Architectural Design Studio: A Case Study of Designing On-Campus Academic Staff Housing in Konya and Izmir, Turkey

ERIC Educational Resources Information Center

Bala, Havva Alkan

2010-01-01

It is important to engender a "sustainable" architectural consciousness in the students who will be the next generation architects. In architectural education, design decisions taken during the early phases of the design process play an important role in ensuring concern for the sustainability issue. But, in general, all discussions…

77 FR 58359 - Applications for New Awards; Race to the Top-Early Learning Challenge; Phase 2

Federal Register 2010, 2011, 2012, 2013, 2014

2012-09-20

... amended by section 1832(b) of Division B of Pub. L. 112-10, the Department of Defense and Full-Year... DEPARTMENT OF EDUCATION DEPARTMENT OF HEALTH AND HUMAN SERVICES Applications for New Awards; Race to the Top--Early Learning Challenge; Phase 2 AGENCY: Department of Education and Department of...

Early stage design decisions: the way to achieve sustainable buildings at lower costs.

PubMed

Bragança, Luís; Vieira, Susana M; Andrade, Joana B

2014-01-01

The construction industry attempts to produce buildings with as lower environmental impact as possible. However, construction activities still greatly affect environment; therefore, it is necessary to consider a sustainable project approach based on its performance. Sustainability is an important issue to consider in design, not only due to environmental concerns but also due to economic and social matters, promoting architectural quality and economic advantages. This paper aims to identify the phases through which a design project should be developed, emphasising the importance and ability of earlier stages to influence sustainability, performance, and life cycle cost. Then, a selection of sustainability key indicators, able to be used at the design conceptual phase and able to start predicting environmental sustainability performance of buildings is presented. The output of this paper aimed to enable designers to compare and evaluate the consequences of different design solutions, based on preliminary data, and facilitate the collaboration between stakeholders and clients and eventually yield a sustainable and high performance building throughout its life cycle.

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

Phase Response Design of Recursive All-Pass Digital Filters Using a Modified PSO Algorithm

PubMed Central

2015-01-01

This paper develops a new design scheme for the phase response of an all-pass recursive digital filter. A variant of particle swarm optimization (PSO) algorithm will be utilized for solving this kind of filter design problem. It is here called the modified PSO (MPSO) algorithm in which another adjusting factor is more introduced in the velocity updating formula of the algorithm in order to improve the searching ability. In the proposed method, all of the designed filter coefficients are firstly collected to be a parameter vector and this vector is regarded as a particle of the algorithm. The MPSO with a modified velocity formula will force all particles into moving toward the optimal or near optimal solution by minimizing some defined objective function of the optimization problem. To show the effectiveness of the proposed method, two different kinds of linear phase response design examples are illustrated and the general PSO algorithm is compared as well. The obtained results show that the MPSO is superior to the general PSO for the phase response design of digital recursive all-pass filter. PMID:26366168

The Low-luminosity Type IIP Supernova 2016bkv with Early-phase Circumstellar Interaction

NASA Astrophysics Data System (ADS)

Nakaoka, Tatsuya; Kawabata, Koji S.; Maeda, Keiichi; Tanaka, Masaomi; Yamanaka, Masayuki; Moriya, Takashi J.; Tominaga, Nozomu; Morokuma, Tomoki; Takaki, Katsutoshi; Kawabata, Miho; Kawahara, Naoki; Itoh, Ryosuke; Shiki, Kensei; Mori, Hiroki; Hirochi, Jun; Abe, Taisei; Uemura, Makoto; Yoshida, Michitoshi; Akitaya, Hiroshi; Moritani, Yuki; Ueno, Issei; Urano, Takeshi; Isogai, Mizuki; Hanayama, Hidekazu; Nagayama, Takahiro

2018-06-01

We present optical and near-infrared observations of a low-luminosity (LL) Type IIP supernova (SN) 2016bkv from the initial rising phase to the plateau phase. Our observations show that the end of the plateau is extended to ≳140 days since the explosion, indicating that this SN takes one of the longest times to finish the plateau phase among Type IIP SNe (SNe IIP), including LL SNe IIP. The line velocities of various ions at the middle of the plateau phase are as low as 1000–1500 km s‑1, which is the lowest even among LL SNe IIP. These measurements imply that the ejecta mass in SN 2016bkv is larger than that of the well-studied LL IIP SN 2003Z. In the early phase, SN 2016bkv shows a strong bump in the light curve. In addition, the optical spectra in this bump phase exhibit a blue continuum accompanied by a narrow Hα emission line. These features indicate an interaction between the SN ejecta and the circumstellar matter (CSM) as in SNe IIn. Assuming the ejecta–CSM interaction scenario, the mass loss rate is estimated to be ∼ 1.7× {10}-2 {M}ȯ yr‑1 within a few years before the SN explosion. This is comparable to or even larger than the largest mass loss rate observed for the Galactic red supergiants (∼ {10}-3 {M}ȯ yr‑1 for VY CMa). We suggest that the progenitor star of SN 2016bkv experienced a violent mass loss just before the SN explosion.

Novel phase diagram behavior and materials design in heterostructural semiconductor alloys

PubMed Central

Holder, Aaron M.; Siol, Sebastian; Ndione, Paul F.; Peng, Haowei; Deml, Ann M.; Matthews, Bethany E.; Schelhas, Laura T.; Toney, Michael F.; Gordon, Roy G.; Tumas, William; Perkins, John D.; Ginley, David S.; Gorman, Brian P.; Tate, Janet; Zakutayev, Andriy; Lany, Stephan

2017-01-01

Structure and composition control the behavior of materials. Isostructural alloying is historically an extremely successful approach for tuning materials properties, but it is often limited by binodal and spinodal decomposition, which correspond to the thermodynamic solubility limit and the stability against composition fluctuations, respectively. We show that heterostructural alloys can exhibit a markedly increased range of metastable alloy compositions between the binodal and spinodal lines, thereby opening up a vast phase space for novel homogeneous single-phase alloys. We distinguish two types of heterostructural alloys, that is, those between commensurate and incommensurate phases. Because of the structural transition around the critical composition, the properties change in a highly nonlinear or even discontinuous fashion, providing a mechanism for materials design that does not exist in conventional isostructural alloys. The novel phase diagram behavior follows from standard alloy models using mixing enthalpies from first-principles calculations. Thin-film deposition demonstrates the viability of the synthesis of these metastable single-phase domains and validates the computationally predicted phase separation mechanism above the upper temperature bound of the nonequilibrium single-phase region. PMID:28630928

Novel phase diagram behavior and materials design in heterostructural semiconductor alloys.

PubMed

Holder, Aaron M; Siol, Sebastian; Ndione, Paul F; Peng, Haowei; Deml, Ann M; Matthews, Bethany E; Schelhas, Laura T; Toney, Michael F; Gordon, Roy G; Tumas, William; Perkins, John D; Ginley, David S; Gorman, Brian P; Tate, Janet; Zakutayev, Andriy; Lany, Stephan

2017-06-01

Structure and composition control the behavior of materials. Isostructural alloying is historically an extremely successful approach for tuning materials properties, but it is often limited by binodal and spinodal decomposition, which correspond to the thermodynamic solubility limit and the stability against composition fluctuations, respectively. We show that heterostructural alloys can exhibit a markedly increased range of metastable alloy compositions between the binodal and spinodal lines, thereby opening up a vast phase space for novel homogeneous single-phase alloys. We distinguish two types of heterostructural alloys, that is, those between commensurate and incommensurate phases. Because of the structural transition around the critical composition, the properties change in a highly nonlinear or even discontinuous fashion, providing a mechanism for materials design that does not exist in conventional isostructural alloys. The novel phase diagram behavior follows from standard alloy models using mixing enthalpies from first-principles calculations. Thin-film deposition demonstrates the viability of the synthesis of these metastable single-phase domains and validates the computationally predicted phase separation mechanism above the upper temperature bound of the nonequilibrium single-phase region.

Logistical challenges and design considerations for studies using acute anterior cruciate ligament injury as a potential model for early posttraumatic osteoarthritis.

PubMed

Lattermann, Christian; Jacobs, Cale A; Bunnell, Mary Proffitt; Jochimsen, Kate N; Abt, John P; Reinke, Emily K; Gammon, Lee G; Huebner, Janet L; Kraus, Virginia B; Spindler, Kurt P

2017-03-01

Anterior cruciate ligament (ACL) injuries are common and lead to posttraumatic osteoarthritis (PTOA) in a high percentage of patients. Research has been ineffective in identifying successful treatment options for people suffering from symptomatic PTOA resulting in a shift of focus toward the young, ACL injured patients at risk of developing PTOA. Randomized clinical trials examining the very early phase after ACL injury are ideal to study this population; however, these trials face significant challenges regarding recruitment as well as reproducibility of patient-reported outcomes (PROs) and inflammatory and/or chondrodegenerative biomarkers associated with early PTOA. The aim of this work was to develop an approach to allow for early recruitment into an RCT for early treatment following ACL injury and to analyze the variability of commonly used measures and biomarkers at various time points after injury. This paper reports the study design and data related to the first month of treatment for the placebo group of an ongoing 2-year clinical trial to evaluate the effect of an early intra-articular intervention after ACL injury. The results of this study suggest that acute ACL injury results in early changes of both inflammatory and chondrodegenerative biomarkers. These results also provide vital information for researchers to consider when developing future protocols, both related to the logistics of early patient enrollment as well as the appropriate timing of biomarker and patient-reported outcome collection. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:641-650, 2017. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.

Phase 2 design study of the electronic assembly for the HRUV spectrometer/polarimeter intended for the solar maximum mission. Implementation phase program plan, revision A

NASA Technical Reports Server (NTRS)

1977-01-01

The primary function of the implementation phase is to convert the ERA design of the design study phase into deliverable flight hardware. The development aspects of the experiment logic unit, the dual power converter, the junction box and the cables are considered.

Phased-array radar for airborne systems

NASA Astrophysics Data System (ADS)

Tahim, Raghbir S.; Foshee, James J.; Chang, Kai

2003-09-01

Phased array antenna systems, which support high pulse rates and high transmit power, are well suited for radar and large-scale surveillance. Sensors and communication systems can function as the eyes and ears for ballistic missile defense applications, providing early warning of attack, target detection and identification, target tracking, and countermeasure decision. In such applications, active array radar systems that contain solid-state transmitter sources and low-noise preamplifiers for transmission and reception are preferred over the conventional radar antennas, because the phased array radar offers the advantages of power management and efficiency, reliability, signal reception, beam steering target detection. The current phased array radar designs are very large, complex and expensive and less efficient because of high RF losses in the phase control circuits used for beam scan. Several thousands of phase shifters and drivers may be required for a single system thus making the system very complex and expensive. This paper describes the phased array radar system based on high power T/R modules, wide-band radiating planar antenna elements and very low loss wide-band phase control circuits (requiring reduced power levels) for beam scan. The phase shifter design is based on micro-strip feed lines perturbed by the proximity of voltage controlled piezoelectric transducer (PET). Measured results have shown an added insertion loss of less than 1 dB for a phase shift of 450 degrees from 2 to 20 GHz. The new wideband phased array radar design provides significant reduction in size cost and weight. Compared to the conventional phased array systems, the cost saving is more than 15 to 1.

The progamic phase of an early-divergent angiosperm, Annona cherimola (Annonaceae)

PubMed Central

Lora, J.; Hormaza, J. I.; Herrero, M.

2010-01-01

Background and Aims Recent studies of reproductive biology in ancient angiosperm lineages are beginning to shed light on the early evolution of flowering plants, but comparative studies are restricted by fragmented and meagre species representation in these angiosperm clades. In the present study, the progamic phase, from pollination to fertilization, is characterized in Annona cherimola, which is a member of the Annonaceae, the largest extant family among early-divergent angiosperms. Beside interest due to its phylogenetic position, this species is also an ancient crop with a clear niche for expansion in subtropical climates. Methods The kinetics of the reproductive process was established following controlled pollinations and sequential fixation. Gynoecium anatomy, pollen tube pathway, embryo sac and early post-fertilization events were characterized histochemically. Key Results A plesiomorphic gynoecium with a semi-open carpel shows a continuous secretory papillar surface along the carpel margins, which run from the stigma down to the obturator in the ovary. The pollen grains germinate in the stigma and compete in the stigma-style interface to reach the narrow secretory area that lines the margins of the semi-open stylar canal and is able to host just one to three pollen tubes. The embryo sac has eight nuclei and is well provisioned with large starch grains that are used during early cellular endosperm development. Conclusions A plesiomorphic simple gynoecium hosts a simple pollen–pistil interaction, based on a support–control system of pollen tube growth. Support is provided through basipetal secretory activity in the cells that line the pollen tube pathway. Spatial constraints, favouring pollen tube competition, are mediated by a dramatic reduction in the secretory surface available for pollen tube growth at the stigma–style interface. This extramural pollen tube competition contrasts with the intrastylar competition predominant in more recently derived

Learning from Experts: Fostering Extended Thinking in the Early Phases of the Design Process

ERIC Educational Resources Information Center

Haupt, Grietjie

2015-01-01

Empirical evidence on the way in which expert designers from different domains cognitively connect their internal processes with external resources is presented in the context of an extended cognition model. The article focuses briefly on the main trends in the extended design cognition theory and in particular on recent trends in information…

Operator Station Design System - A computer aided design approach to work station layout

NASA Technical Reports Server (NTRS)

Lewis, J. L.

1979-01-01

The Operator Station Design System is resident in NASA's Johnson Space Center Spacecraft Design Division Performance Laboratory. It includes stand-alone minicomputer hardware and Panel Layout Automated Interactive Design and Crew Station Assessment of Reach software. The data base consists of the Shuttle Transportation System Orbiter Crew Compartment (in part), the Orbiter payload bay and remote manipulator (in part), and various anthropometric populations. The system is utilized to provide panel layouts, assess reach and vision, determine interference and fit problems early in the design phase, study design applications as a function of anthropometric and mission requirements, and to accomplish conceptual design to support advanced study efforts.

Liverpool Telescope 2: beginning the design phase

NASA Astrophysics Data System (ADS)

Copperwheat, Christopher M.; Steele, Iain A.; Barnsley, Robert M.; Bates, Stuart D.; Bode, Mike F.; Clay, Neil R.; Collins, Chris A.; Jermak, Helen E.; Knapen, Johan H.; Marchant, Jon M.; Mottram, Chris J.; Piascik, Andrzej S.; Smith, Robert J.

2016-07-01

The Liverpool Telescope is a fully robotic 2-metre telescope located at the Observatorio del Roque de los Muchachos on the Canary Island of La Palma. The telescope began routine science operations in 2004, and currently seven simultaneously mounted instruments support a broad science programme, with a focus on transient followup and other time domain topics well suited to the characteristics of robotic observing. Work has begun on a successor facility with the working title `Liverpool Telescope 2'. We are entering a new era of time domain astronomy with new discovery facilities across the electromagnetic spectrum, and the next generation of optical survey facilities such as LSST are set to revolutionise the field of transient science in particular. The fully robotic Liverpool Telescope 2 will have a 4-metre aperture and an improved response time, and will be designed to meet the challenges of this new era. Following a conceptual design phase, we are about to begin the detailed design which will lead towards the start of construction in 2018, for first light ˜2022. In this paper we provide an overview of the facility and an update on progress.

Conceptual design study of potential early commercial MHD powerplant. Report of task 2 results

NASA Astrophysics Data System (ADS)

Hals, F. A.

1981-03-01

The conceptual design of one of the potential early commercial MHD power plants was studied. The plant employs oxygen enrichment of the combustion air and preheating of this oxygen enriched air to an intermediate temperature of 1200 F attainable with a tubular type recuperative heat exchanger. Conceptual designs of plant componets and equipment with performance, operational characteristics, and costs are reported. Plant economics and overall performance including full and part load operation are reviewed. The projected performance and estimated cost of this early MHD plant are compared to conventional power plants, although it does not offer the same high efficiency and low costs as the mature MHD power plant. Environmental aspects and the methods incorporated in plant design for emission control of sulfur and nitrogen are reviewed.

Conceptual design study of potential early commercial MHD powerplant. Report of task 2 results

NASA Technical Reports Server (NTRS)

Hals, F. A.

1981-01-01

The conceptual design of one of the potential early commercial MHD power plants was studied. The plant employs oxygen enrichment of the combustion air and preheating of this oxygen enriched air to an intermediate temperature of 1200 F attainable with a tubular type recuperative heat exchanger. Conceptual designs of plant componets and equipment with performance, operational characteristics, and costs are reported. Plant economics and overall performance including full and part load operation are reviewed. The projected performance and estimated cost of this early MHD plant are compared to conventional power plants, although it does not offer the same high efficiency and low costs as the mature MHD power plant. Environmental aspects and the methods incorporated in plant design for emission control of sulfur and nitrogen are reviewed.

The early phase of /see symbol/ production development in adult Japanese learners of English.

PubMed

Saito, Kazuya; Munro, Murray J

2014-12-01

Although previous research indicates that Japanese speakers' second language (L2) perception and production of English /see symbol/ may improve with increased L2 experience, relatively little is known about the fine phonetic details of their /see symbol/ productions, especially during the early phase of L2 speech learning. This cross-sectional study examined acoustic properties of word-initial /see symbol/ from 60 Japanese learners with a length of residence of between one month and one year in Canada. Their performance was compared to that of 15 native speakers of English and 15 low-proficiency Japanese learners of English. Formant frequencies (F2 and F3) and F1 transition durations were evaluated under three task conditions--word reading, sentence reading, and timed picture description. Learners with as little as two to three months of residence demonstrated target-like F2 frequencies. In addition, increased LOR was predictive of more target-like transition durations. Although the learners showed some improvement in F3 as a function of LOR, they did so mainly at a controlled level of speech production. The findings suggest that during the early phase of L2 segmental development, production accuracy is task-dependent and is influenced by the availability of L1 phonetic cues for redeployment in L2.

Restoration of energy level in the early phase of acute pediatric pancreatitis.

PubMed

Mosztbacher, Dóra; Farkas, Nelli; Solymár, Margit; Pár, Gabriella; Bajor, Judit; Szűcs, Ákos; Czimmer, József; Márta, Katalin; Mikó, Alexandra; Rumbus, Zoltán; Varjú, Péter; Hegyi, Péter; Párniczky, Andrea

2017-02-14

Acute pancreatitis (AP) is a serious inflammatory disease with rising incidence both in the adult and pediatric populations. It has been shown that mitochondrial injury and energy depletion are the earliest intracellular events in the early phase of AP. Moreover, it has been revealed that restoration of intracellular ATP level restores cellular functions and defends the cells from death. We have recently shown in a systematic review and meta-analysis that early enteral feeding is beneficial in adults; however, no reviews are available concerning the effect of early enteral feeding in pediatric AP. In this minireview, our aim was to systematically analyse the literature on the treatment of acute pediatric pancreatitis. The preferred reporting items for systematic review (PRISMA-P) were followed, and the question was drafted based on participants, intervention, comparison and outcomes: P: patients under the age of twenty-one suffering from acute pancreatitis; I: early enteral nutrition (per os and nasogastric- or nasojejunal tube started within 48 h); C: nil per os therapy; O: length of hospitalization, need for treatment at an intensive care unit, development of severe AP, lung injury (including lung oedema and pleural effusion), white blood cell count and pain score on admission. Altogether, 632 articles (PubMed: 131; EMBASE: 501) were found. After detailed screening of eligible papers, five of them met inclusion criteria. Only retrospective clinical trials were available. Due to insufficient information from the authors, it was only possible to address length of hospitalization as an outcome of the study. Our mini-meta-analysis showed that early enteral nutrition significantly (SD = 0.806, P = 0.034) decreases length of hospitalization compared with nil per os diet in acute pediatric pancreatitis. In this minireview, we clearly show that early enteral nutrition, started within 24-48 h, is beneficial in acute pediatric pancreatitis. Prospective studies and better

Restoration of energy level in the early phase of acute pediatric pancreatitis

PubMed Central

Mosztbacher, Dóra; Farkas, Nelli; Solymár, Margit; Pár, Gabriella; Bajor, Judit; Szűcs, Ákos; Czimmer, József; Márta, Katalin; Mikó, Alexandra; Rumbus, Zoltán; Varjú, Péter; Hegyi, Péter; Párniczky, Andrea

2017-01-01

Acute pancreatitis (AP) is a serious inflammatory disease with rising incidence both in the adult and pediatric populations. It has been shown that mitochondrial injury and energy depletion are the earliest intracellular events in the early phase of AP. Moreover, it has been revealed that restoration of intracellular ATP level restores cellular functions and defends the cells from death. We have recently shown in a systematic review and meta-analysis that early enteral feeding is beneficial in adults; however, no reviews are available concerning the effect of early enteral feeding in pediatric AP. In this minireview, our aim was to systematically analyse the literature on the treatment of acute pediatric pancreatitis. The preferred reporting items for systematic review (PRISMA-P) were followed, and the question was drafted based on participants, intervention, comparison and outcomes: P: patients under the age of twenty-one suffering from acute pancreatitis; I: early enteral nutrition (per os and nasogastric- or nasojejunal tube started within 48 h); C: nil per os therapy; O: length of hospitalization, need for treatment at an intensive care unit, development of severe AP, lung injury (including lung oedema and pleural effusion), white blood cell count and pain score on admission. Altogether, 632 articles (PubMed: 131; EMBASE: 501) were found. After detailed screening of eligible papers, five of them met inclusion criteria. Only retrospective clinical trials were available. Due to insufficient information from the authors, it was only possible to address length of hospitalization as an outcome of the study. Our mini-meta-analysis showed that early enteral nutrition significantly (SD = 0.806, P = 0.034) decreases length of hospitalization compared with nil per os diet in acute pediatric pancreatitis. In this minireview, we clearly show that early enteral nutrition, started within 24-48 h, is beneficial in acute pediatric pancreatitis. Prospective studies and better

Summary of the Advanced Reactor Design Criteria (ARDC) Phase 2 Activities

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

Holbrook, Mark Raymond

This report provides an end-of-year summary reflecting the progress and status of proposed regulatory design criteria for advanced non-LWR designs in accordance with the Level 3 milestone in M3AT-15IN2001017 in work package AT-15IN200101. These criteria have been designated as ARDC, and they provide guidance to future applicants for addressing the GDC that are currently applied specifically to LWR designs. The report provides a summary of Phase 2 activities related to the various tasks associated with ARDC development and the subsequent development of example adaptations of ARDC for Sodium Fast Reactor (SFR) and modular High Temperature Gas-cooled Reactor (HTGR) designs.

Welcome to the Twilight Zone: a forgotten early phase of human evolutionary studies.

PubMed

Delisle, Richard G

2012-06-01

The field of paleoanthropology arose out of a strange and unacknowledged early phase of development prior to about the 1930s. It is often assumed that a key pillar of the discipline, the unity of humankind--the notion that humans are clearly separated phylogenetically (genealogically) from other non-human primates--was widely accepted from the inception of paleoanthropology around 1860. However, a final consensus on this fundamental question only appeared later on in the 20th century. This paper will focus on two key areas of disagreement, which reveal the unsettled state of this question during this early period: the question of uncertainty with respect to the number, identity and boundary of primate species (including humans) which prevailed in the 18th, 19th and early 20th centuries; and the matter of uncertainty with respect to the nature of the phylogenetic relationships among the various human populations and the other primate species which prevailed between 1864 and 1931. Consideration of these matters reveals that the modern research structure that paleoanthropologists take for granted today is much more recent than believed. Copyright © 2012 Elsevier Ltd. All rights reserved.

Automatic Debugging Support for UML Designs

NASA Technical Reports Server (NTRS)

Schumann, Johann; Swanson, Keith (Technical Monitor)

2001-01-01

Design of large software systems requires rigorous application of software engineering methods covering all phases of the software process. Debugging during the early design phases is extremely important, because late bug-fixes are expensive. In this paper, we describe an approach which facilitates debugging of UML requirements and designs. The Unified Modeling Language (UML) is a set of notations for object-orient design of a software system. We have developed an algorithm which translates requirement specifications in the form of annotated sequence diagrams into structured statecharts. This algorithm detects conflicts between sequence diagrams and inconsistencies in the domain knowledge. After synthesizing statecharts from sequence diagrams, these statecharts usually are subject to manual modification and refinement. By using the "backward" direction of our synthesis algorithm. we are able to map modifications made to the statechart back into the requirements (sequence diagrams) and check for conflicts there. Fed back to the user conflicts detected by our algorithm are the basis for deductive-based debugging of requirements and domain theory in very early development stages. Our approach allows to generate explanations oil why there is a conflict and which parts of the specifications are affected.

Muscle contributions to knee extension in the early stance phase in patients with knee osteoarthritis.

PubMed

Ogaya, Shinya; Kubota, Ryo; Chujo, Yuta; Hirooka, Eiko; Kwang-Ho, Kim; Hase, Kimitaka

2017-10-01

The aim of this study was to analyze individual muscle contributions to knee angular acceleration using a musculoskeletal simulation analysis and evaluate knee extension mechanics in the early stance phase in patients with knee osteoarthritis (OA). The subjects comprised 15 patients with medial knee OA and 14 healthy elderly individuals. All participants underwent gait performance test using 8 infrared cameras and two force plates to measure the kinetic and kinematic data. The simulation was driven by 92 Hill-type muscle-tendon units of the lower extremities and a trunk with 23° of freedom. We analyzed each muscle contribution to knee angular acceleration in the 5%-15% and 15%-25% periods of the stance phase (% SP) using an induced acceleration analysis. We compared accelerations by individual muscles between the two groups using an analysis of covariance for controlling gait speed. Patients with knee OA had a significantly lesser knee extension acceleration by the vasti muscles and higher knee acceleration by hip adductors than those in controls in 5-15% SP. In addition, knee OA resulted in significantly lesser knee extension acceleration by the vasti muscles in 15-25% SP. These results indicate that patients with knee OA have decreased dependency on the vasti muscles to control knee movements during early stance phase. Hip adductor muscles, which mainly control mediolateral motion, partly compensate for the weak knee extension by the vasti muscles in patients with knee OA. Copyright © 2017 Elsevier B.V. All rights reserved.

Design and fabrication of a freeform phase plate for high-order ocular aberration correction

NASA Astrophysics Data System (ADS)

Yi, Allen Y.; Raasch, Thomas W.

2005-11-01

In recent years it has become possible to measure and in some instances to correct the high-order aberrations of human eyes. We have investigated the correction of wavefront error of human eyes by using phase plates designed to compensate for that error. The wavefront aberrations of the four eyes of two subjects were experimentally determined, and compensating phase plates were machined with an ultraprecision diamond-turning machine equipped with four independent axes. A slow-tool servo freeform trajectory was developed for the machine tool path. The machined phase-correction plates were measured and compared with the original design values to validate the process. The position of the phase-plate relative to the pupil is discussed. The practical utility of this mode of aberration correction was investigated with visual acuity testing. The results are consistent with the potential benefit of aberration correction but also underscore the critical positioning requirements of this mode of aberration correction. This process is described in detail from optical measurements, through machining process design and development, to final results.

Army-NASA aircrew/aircraft integration program (A3I) software detailed design document, phase 3

NASA Technical Reports Server (NTRS)

Banda, Carolyn; Chiu, Alex; Helms, Gretchen; Hsieh, Tehming; Lui, Andrew; Murray, Jerry; Shankar, Renuka

1990-01-01

The capabilities and design approach of the MIDAS (Man-machine Integration Design and Analysis System) computer-aided engineering (CAE) workstation under development by the Army-NASA Aircrew/Aircraft Integration Program is detailed. This workstation uses graphic, symbolic, and numeric prototyping tools and human performance models as part of an integrated design/analysis environment for crewstation human engineering. Developed incrementally, the requirements and design for Phase 3 (Dec. 1987 to Jun. 1989) are described. Software tools/models developed or significantly modified during this phase included: an interactive 3-D graphic cockpit design editor; multiple-perspective graphic views to observe simulation scenarios; symbolic methods to model the mission decomposition, equipment functions, pilot tasking and loading, as well as control the simulation; a 3-D dynamic anthropometric model; an intermachine communications package; and a training assessment component. These components were successfully used during Phase 3 to demonstrate the complex interactions and human engineering findings involved with a proposed cockpit communications design change in a simulated AH-64A Apache helicopter/mission that maps to empirical data from a similar study and AH-1 Cobra flight test.

Ultrastructural Complexity of Nuclear Components During Early Apoptotic Phases in Breast Cancer Cells

PubMed Central

Castelli, Christian; Losa, Gabriele A.

2001-01-01

Fractal morphometry was used to investigate the ultrastructural features of the plasma membrane, perinuclear membrane and nuclear chromatin in SK‐BR‐3 human breast cancer cells undergoing apoptosis. Cells were incubated with 1 μM calcimycin (A23187) for 24 h. Cells in the early stage of apoptosis had fractal dimension (FD) values indicating that their plasma membranes were less rough (lower FD) than those of control cells, while their perinuclear membranes were unaffected. Changes of the chromatin texture within the entire nucleus and in selected nuclear domains were more pronounced in treated cells. This confirms that the morphological reorganization imputable to a loss of structural complexity (reduced FD) occurs in the early stage of apoptosis, is accompanied by the inhibition of distinct enzymatic events and precedes the onset of conventional cellular markers, which can only be detected during the active phases of the apoptotic process. PMID:11790854

The hepatocyte phase of Gd-EOB-DTPA-enhanced MRI in the evaluation of hepatic fibrosis and early liver cirrhosis in a rat model: an experimental study.

PubMed

Ma, Chunmei; Liu, Ailian; Wang, Yuanyuan; Geng, Xiaoling; Hao, Li; Song, Qingwei; Sun, Bo; Wang, Heqing; Zhao, Gang

2014-07-17

To evaluate the hepatocyte phase of Gd-EOB-DTPA-enhanced MRI in the early diagnosis of hepatic fibrosis and cirrhosis and assessment of liver function in a rat model. In 2 groups of SD rats, liver fibrosis was induced in experimental animals by repetitive carbon tetrachloride injections, while the control group received saline injections. Five experimental rats and 2 control rats were randomly selected at weeks 4, 8, 12. One week after carbon tetrachloride administration, MRI (FIRM T1WI) scan was performed. Gd-EOB-DTPA (0.08mL) was injected into the rat's tail vein and hepatocyte phase images were obtained after 20min. The pre-enhanced phase and hepatocyte phase signal intensities (SI) were measured, and the relative contrast enhancement index (RCEI) was calculated. ANOVA analysis (LSD) of RCEI values in controls (n=6), hepatic fibrosis (n=7), and histopathologically-determined early cirrhosis group (n=6) was performed. RECI values showed a decreasing trend in the control group, hepatic fibrosis and early cirrhosis groups (1.11±0.43, 0.96±0.22, and 0.57±0.33, respectively). While the difference between the control and early cirrhosis groups was statistically significant (p=0.013), there was no significant difference in the hepatic fibrosis group vs the control (p=0.416) and the hepatic fibrosis group vs the early cirrhosis group (p=0.054). Hepatocyte phase RCEI values obtained with Gd-EOB-DTPA-enhanced MRI scan indicate liver injury in hepatic fibrosis and early cirrhosis. RCEI values are helpful for early diagnosis of liver cirrhosis. Copyright © 2014 Elsevier Inc. All rights reserved.

Feed-pump hydraulic performance and design improvement, Phase I: research program design. Final report

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

Brown, W.H.; Gopalakrishnan, S.; Fehlau, R.

1982-03-01

As a result of prior EPRI-sponsored studies, it was concluded that a research program should be designed and implemented to provide an improved basis for the design, procurement, testing, and operation of large feed pumps with increased reliability and stability over the full range of operating conditions. This two-volume report contains a research plan which is based on a review of the present state of the art and which defines the necessary R and D program and estimates the benefits and costs of the program. The recommended research program consists of 30 interrelated tasks. It is designed to perform themore » needed research; to verify the results; to develop improved components; and to publish computer-aided design methods, pump specification guidelines, and a troubleshooting manual. Most of the technology proposed in the research plan is applicable to nuclear power plants as well as to fossil-fired plants. This volume contains appendixes on pump design, cavitation damage, performance testing, hydraulics, two-phase flow in pumps, flow stability, and rotor dynamics.« less

Direct manipulation of wave amplitude and phase through inverse design of isotropic media

NASA Astrophysics Data System (ADS)

Liu, Y.; Vial, B.; Horsley, S. A. R.; Philbin, T. G.; Hao, Y.

2017-07-01

In this article we propose a new design methodology allowing us to control both amplitude and phase of electromagnetic waves from a cylindrical incident wave. This results in isotropic materials and does not resort to transformation optics or its quasi-conformal approximations. Our method leads to two-dimensional isotropic, inhomogeneous material profiles of permittivity and permeability, to which a general class of scattering-free wave solutions arise. Our design is based on the separation of the complex wave solution into amplitude and phase. We give two types of examples to validate our methodology.

Maintenance phase in psoralen-ultraviolet A phototherapy of early-stage mycosis fungoides. A critically appraised topic.

PubMed

Grandi, V; Delfino, C; Pileri, A; Pimpinelli, N

2017-08-01

A 65-year-old patient affected by mycosis fungoides (MF) stage IB achieved complete remission (CR) after a cycle of PUVA phototherapy. The U.S. Cutaneous Lymphoma Consortium (USCLC) guidelines suggest that the patient should be kept in the maintenance phase, defined as a 'period of gradual decrease of frequency of UVL [ultraviolet light] while in clinical remission before discontinuation of phototherapy' by slowly tapering the number of psoralen-ultraviolet A (PUVA) applications over time up to clinical relapse. The USCLC guidelines also suggest a standardized schedule for the maintenance phase. Alternatively, the patient could end PUVA therapy and go straight to follow-up. The aim of this critically appraised topic (CAT) was to determine if a maintenance phase gives a significant benefit in terms of relapse rate (RR) and RFI in patients affected by early-stage MF who had achieved CR under PUVA phototherapy. Embase, PubMed and TRIP databases were searched for 'mycosis fungoides' AND [('photochemotherapy' OR 'puva') OR 'psoralen'] in June 2016. Three articles matched our inclusion criteria and are discussed in this CAT. In this field of research the literature is poor and the reported level of evidence is low. Only one of the studies was conducted prospectively, and none were randomized. No significant difference in terms of reduction in relapse rate or increase in RFI in patients who underwent a PUVA maintenance phase emerged when compared with those who went for simple follow-up. Further randomized clinical trials (RCTs) are required in order to evaluate maintenance phase vs. no treatment before it can be favoured as the standard protocol of treatment in early-stage MF. At the time of writing this paper, we report an ongoing Austrian multicentre RCT (Clinical Trial.gov identifier: NCT01686594) that will hopefully give useful results in this topic. © 2017 British Association of Dermatologists.

Warfighting Concepts to Future Weapon System Designs (WARCON)

DTIC Science & Technology

2003-09-12

34* Software design documents rise to litigation. "* A Material List "Cost information that may support, or may * Final Engineering Process Maps be...document may include design the system as derived from the engineering design, software development, SRD. MTS Technologies, Inc. 26 FOR OFFICIAL USE...document, early in the development phase. It is software engineers produce the vision of important to establish a standard, formal the design effort. As

Phytochrome-mediated germination and early development in spores of Dryopteris filix-mas L.: phase-specific and non phase-specific inhibition by staurosporine

NASA Technical Reports Server (NTRS)

Haas, C. J.; Scheuerlein, R.; Roux, S. J.

1991-01-01

The alkaloid staurosporine, currently known as the most potent inhibitor of protein kinase C, PKC, was tested for its ability to inhibit phytochrome-mediated spore germination in Dryopteris filix-mas L., evaluated by the induction of chlorophyll synthesis. Approximately half-maximal inhibition was obtained at a concentration of 10(-5) M. This effect of staurosporine was phase-specific and was found during the same period in which the presence of extracellular calcium is necessary for realization of the light signal. Furthermore, the ability of staurosporine to prevent progression of a germinated spore into early gametophyte development, evaluated by the accumulation of chlorophyll, was examined. Again, staurosporine (10(-5) M) significantly diminished chlorophyll accumulation, determined quantitatively in vivo by single-cell measurements, in a non-phase specific way. The fact that the phase-specific inhibitory effect of staurosporine in preventing germination was coincident with the phase-specific requirement of Ca2+ suggests that both Ca2+ and staurosporine affect the same step in the signal-transduction chain. A phosphorylation event catalysed by PKC or any Ca2+ -dependent protein kinase is proposed as the target of staurosporine and Ca2+.

Design versions of HTS three-phase cables with the minimized value of AC losses

NASA Astrophysics Data System (ADS)

Altov, V. A.; Balashov, N. N.; Degtyarenko, P. N.; Ivanov, S. S.; Kopylov, S. I.; Lipa, DA; Samoilenkov, S. V.; Sytnikov, V. E.; Zheltov, V. V.

2018-03-01

Design versions of HTS three-phase cables consisting of 2G HTS tapes have been investigated by the numerical simulation method with the aim of AC losses minimization. Two design versions of cables with the coaxial and extended rectangular cross-section shape are considered – the non-sectioned and sectioned one. In the latter each cable phase consists of sections connected in parallel. The optimal dimensions of sections and order of their alteration are chosen by appropriate calculations. The model used takes into account the current distribution between the sections and its non-uniformity within each single HTS tape as well. The following characteristics are varied: design version, dimension, positioning of extra copper layer in a cable, design of HTS tapes themselves and their mutual position. The dependence of AC losses on the latter two characteristics is considered in details, and the examples of cable designs optimized by the total set of characteristics for the medium class of voltages (10 – 60 kV) are given. At the critical current JC=5.1 кA per phase and current amplitudes lower than 0.85JC, the level of total AC losses does not exceed the natural cryostat heat losses.

Exploring the Role of Social Memory of Floods for Designing Flood Early Warning Operations

NASA Astrophysics Data System (ADS)

Girons Lopez, Marc; Di Baldassarre, Giuliano; Grabs, Thomas; Halldin, Sven; Seibert, Jan

2016-04-01

Early warning systems are an important tool for natural disaster mitigation practices, especially for flooding events. Warnings rely on near-future forecasts to provide time to take preventive actions before a flood occurs, thus reducing potential losses. However, on top of the technical capacities, successful warnings require an efficient coordination and communication among a range of different actors and stakeholders. The complexity of integrating the technical and social spheres of warning systems has, however, resulted in system designs neglecting a number of important aspects such as social awareness of floods thus leading to suboptimal results. A better understanding of the interactions and feedbacks among the different elements of early warning systems is therefore needed to improve their efficiency and therefore social resilience. When designing an early warning system two important decisions need to be made regarding (i) the hazard magnitude at and from which a warning should be issued and (ii) the degree of confidence required for issuing a warning. The first decision is usually taken based on the social vulnerability and climatic variability while the second one is related to the performance (i.e. accuracy) of the forecasting tools. Consequently, by estimating the vulnerability and the accuracy of the forecasts, these two variables can be optimized to minimize the costs and losses. Important parameters with a strong influence on the efficiency of warning systems such as social awareness are however not considered in their design. In this study we present a theoretical exploration of the impact of social awareness on the design of early warning systems. For this purpose we use a definition of social memory of flood events as a proxy for flood risk awareness and test its effect on the optimization of the warning system design variables. Understanding the impact of social awareness on warning system design is important to make more robust warnings that can

Novel phase diagram behavior and materials design in heterostructural semiconductor alloys

DOE PAGES

Holder, Aaron M.; Siol, Sebastian; Ndione, Paul F.; ...

2017-06-07

Structure and composition control the behavior of materials. Isostructural alloying is historically an extremely successful approach for tuning materials properties, but it is often limited by binodal and spinodal decomposition, which correspond to the thermodynamic solubility limit and the stability against composition fluctuations, respectively. We show that heterostructural alloys can exhibit a markedly increased range of metastable alloy compositions between the binodal and spinodal lines, thereby opening up a vast phase space for novel homogeneous single-phase alloys. We distinguish two types of heterostructural alloys, that is, those between commensurate and incommensurate phases. Because of the structural transition around the criticalmore » composition, the properties change in a highly nonlinear or even discontinuous fashion, providing a mechanism for materials design that does not exist in conventional isostructural alloys. The novel phase diagram behavior follows from standard alloy models using mixing enthalpies from first-principles calculations. Furthermore, thin-film deposition demonstrates the viability of the synthesis of these metastable single-phase domains and validates the computationally predicted phase separation mechanism above the upper temperature bound of the nonequilibrium single-phase region.« less

Methylene blue prevents surgery-induced peritoneal adhesions but impairs the early phase of anastomotic wound healing

PubMed Central

Dinc, Soykan; Ozaslan, Cihangir; Kuru, Bekir; Karaca, Sefa; Ustun, Huseyin; Alagol, Haluk; Renda, Nurten; Oz, Murat

2006-01-01

Objectives Adhesion formation continues to be an important problem in gastrointestinal surgery. In recent years, methylene blue (MB) has been reported to be an effective agent for preventing peritoneal adhesions. However, its effects on the wound healing process are unknown. In the present study, we investigated the effects of MB on the early and late phases of anastomotic wound healing and on adhesion formation. Methods We randomly categorized 92 rats into 2 groups in bursting pressure measurements and 50 rats into 3 groups in the adhesion model. We divided the animals into saline-treated (n = 46) or MB-treated (n = 46) groups. Bursting pressures of the anastomoses were measured on postoperative days 3 and 7. In biochemical studies, tissue hydroxyproline levels, total nitrite/nitrate levels and nitric oxide synthase activity were measured on postoperative days 3 and 7. In the adhesion model, we randomly categorized rats into sham (n = 10), saline-treated (n = 20) and MB-treated (n = 20) groups, and the formation of intraperitoneal adhesions was scored on postoperative day 14. We compared the measurement of bursting pressure and biochemical measurements of tissue hydroxyproline levels, total nitrite/nitrate levels and nitric oxide synthase activity. Histopathological findings of specimens were presented. Results During the early phase of wound healing (postoperative day 3), bursting pressures, tissue hydroxyproline, total nitrite/nitrate levels and nitric oxide synthase activity in the MB-treated group were significantly lower than those of the saline-treated group. On postoperative day 7, there was no significant difference in these parameters between MB and saline-treated groups. In the adhesion model, MB caused a significant reduction in the formation of peritoneal adhesions. Conclusion MB prevents peritoneal adhesions but causes a significant impairment of anastomotic bursting pressure during the early phase of the wound healing process by its transient

Early Stage Design Decisions: The Way to Achieve Sustainable Buildings at Lower Costs

PubMed Central

Bragança, Luís; Vieira, Susana M.; Andrade, Joana B.

2014-01-01

The construction industry attempts to produce buildings with as lower environmental impact as possible. However, construction activities still greatly affect environment; therefore, it is necessary to consider a sustainable project approach based on its performance. Sustainability is an important issue to consider in design, not only due to environmental concerns but also due to economic and social matters, promoting architectural quality and economic advantages. This paper aims to identify the phases through which a design project should be developed, emphasising the importance and ability of earlier stages to influence sustainability, performance, and life cycle cost. Then, a selection of sustainability key indicators, able to be used at the design conceptual phase and able to start predicting environmental sustainability performance of buildings is presented. The output of this paper aimed to enable designers to compare and evaluate the consequences of different design solutions, based on preliminary data, and facilitate the collaboration between stakeholders and clients and eventually yield a sustainable and high performance building throughout its life cycle. PMID:24578630

Teachers' Beliefs on Foreign Language Teaching Practices in Early Phases of Primary Education: A Case Study

ERIC Educational Resources Information Center

Caner, Mustafa; Subasi, Gonca; Kara, Selma

2010-01-01

The purpose of the study was to examine whether teacher beliefs would play a role in their actual practices while teaching target language in early phases of primary education, principally, in kindergarten and first grades in a state school. As it is a very broad research area, the researchers exclusively analyzed teaching practices and teaching…

A tale of two timescales: Mixing, mass generation, and phase transitions in the early universe

NASA Astrophysics Data System (ADS)

Dienes, Keith R.; Kost, Jeff; Thomas, Brooks

2016-02-01

Light scalar fields such as axions and string moduli can play an important role in early-universe cosmology. However, many factors can significantly impact their late-time cosmological abundances. For example, in cases where the potentials for these fields are generated dynamically—such as during cosmological mass-generating phase transitions—the duration of the time interval required for these potentials to fully develop can have significant repercussions. Likewise, in scenarios with multiple scalars, mixing amongst the fields can also give rise to an effective timescale that modifies the resulting late-time abundances. Previous studies have focused on the effects of either the first or the second timescale in isolation. In this paper, by contrast, we examine the new features that arise from the interplay between these two timescales when both mixing and time-dependent phase transitions are introduced together. First, we find that the effects of these timescales can conspire to alter not only the total late-time abundance of the system—often by many orders of magnitude—but also its distribution across the different fields. Second, we find that these effects can produce large parametric resonances which render the energy densities of the fields highly sensitive to the degree of mixing as well as the duration of the time interval over which the phase transition unfolds. Finally, we find that these effects can even give rise to a "reoverdamping" phenomenon which causes the total energy density of the system to behave in novel ways that differ from those exhibited by pure dark matter or vacuum energy. All of these features therefore give rise to new possibilities for early-universe phenomenology and cosmological evolution. They also highlight the importance of taking into account the time dependence associated with phase transitions in cosmological settings.

Proteomics analysis identified peroxiredoxin 2 involved in early-phase left ventricular impairment in hamsters with cardiomyopathy.

PubMed

Kuzuya, Kentaro; Ichihara, Sahoko; Suzuki, Yuka; Inoue, Chisa; Ichihara, Gaku; Kurimoto, Syota; Oikawa, Shinji

2018-01-01

Given the hypothesis that inflammation plays a critical role in the progression of cardiovascular diseases, the aim of the present study was to identify new diagnostic and prognostic biomarkers of myocardial proteins involved in early-phase cardiac impairment, using proteomics analysis. Using the two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) combined with MALDI-TOF/TOF tandem mass spectrometry, we compared differences in the expression of proteins in the whole left ventricles between control hamsters, dilated cardiomyopathic hamsters (TO-2), and hypertrophy cardiomyopathic hamsters (Bio14.6) at 6 weeks of age (n = 6, each group). Proteomic analysis identified 10 protein spots with significant alterations, with 7 up-regulated and 3 down-regulated proteins in the left ventricles of both TO-2 and Bio 14.6 hamsters, compared with control hamsters. Of the total alterations, peroxiredoxin 2 (PRDX2) showed significant upregulation in the left ventricles of TO-2 and Bio 14.6 hamsters. Our data suggest that PRDX2, a redox regulating molecule, is involved in early-phase left ventricular impairment in hamsters with cardiomyopathy.

ERIS: preliminary design phase overview

NASA Astrophysics Data System (ADS)

Kuntschner, Harald; Jochum, Lieselotte; Amico, Paola; Dekker, Johannes K.; Kerber, Florian; Marchetti, Enrico; Accardo, Matteo; Brast, Roland; Brinkmann, Martin; Conzelmann, Ralf D.; Delabre, Bernard A.; Duchateau, Michel; Fedrigo, Enrico; Finger, Gert; Frank, Christoph; Rodriguez, Fernando G.; Klein, Barbara; Knudstrup, Jens; Le Louarn, Miska; Lundin, Lars; Modigliani, Andrea; Müller, Michael; Neeser, Mark; Tordo, Sebastien; Valenti, Elena; Eisenhauer, Frank; Sturm, Eckhard; Feuchtgruber, Helmut; George, Elisabeth M.; Hartl, Michael; Hofmann, Reiner; Huber, Heinrich; Plattner, Markus P.; Schubert, Josef; Tarantik, Karl; Wiezorrek, Erich; Meyer, Michael R.; Quanz, Sascha P.; Glauser, Adrian M.; Weisz, Harald; Esposito, Simone; Xompero, Marco; Agapito, Guido; Antichi, Jacopo; Biliotti, Valdemaro; Bonaglia, Marco; Briguglio, Runa; Carbonaro, Luca; Cresci, Giovanni; Fini, Luca; Pinna, Enrico; Puglisi, Alfio T.; Quirós-Pacheco, Fernando; Riccardi, Armando; Di Rico, Gianluca; Arcidiacono, Carmelo; Dolci, Mauro

2014-07-01

The Enhanced Resolution Imager and Spectrograph (ERIS) is the next-generation adaptive optics near-IR imager and spectrograph for the Cassegrain focus of the Very Large Telescope (VLT) Unit Telescope 4, which will soon make full use of the Adaptive Optics Facility (AOF). It is a high-Strehl AO-assisted instrument that will use the Deformable Secondary Mirror (DSM) and the new Laser Guide Star Facility (4LGSF). The project has been approved for construction and has entered its preliminary design phase. ERIS will be constructed in a collaboration including the Max- Planck Institut für Extraterrestrische Physik, the Eidgenössische Technische Hochschule Zürich and the Osservatorio Astrofisico di Arcetri and will offer 1 - 5 μm imaging and 1 - 2.5 μm integral field spectroscopic capabilities with a high Strehl performance. Wavefront sensing can be carried out with an optical high-order NGS Pyramid wavefront sensor, or with a single laser in either an optical low-order NGS mode, or with a near-IR low-order mode sensor. Due to its highly sensitive visible wavefront sensor, and separate near-IR low-order mode, ERIS provides a large sky coverage with its 1' patrol field radius that can even include AO stars embedded in dust-enshrouded environments. As such it will replace, with a much improved single conjugated AO correction, the most scientifically important imaging modes offered by NACO (diffraction limited imaging in the J to M bands, Sparse Aperture Masking and Apodizing Phase Plate (APP) coronagraphy) and the integral field spectroscopy modes of SINFONI, whose instrumental module, SPIFFI, will be upgraded and re-used in ERIS. As part of the SPIFFI upgrade a new higher resolution grating and a science detector replacement are envisaged, as well as PLC driven motors. To accommodate ERIS at the Cassegrain focus, an extension of the telescope back focal length is required, with modifications of the guider arm assembly. In this paper we report on the status of the

30 CFR 250.916 - What are the CVA's primary duties during the design phase?

Code of Federal Regulations, 2014 CFR

2014-07-01

... the design phase? (a) The CVA must use good engineering judgment and practices in conducting an...; (iv) Load determinations; (v) Stress analyses; (vi) Material designations; (vii) Soil and foundation...

30 CFR 250.916 - What are the CVA's primary duties during the design phase?

Code of Federal Regulations, 2012 CFR

2012-07-01

... the design phase? (a) The CVA must use good engineering judgment and practices in conducting an...; (iv) Load determinations; (v) Stress analyses; (vi) Material designations; (vii) Soil and foundation...

30 CFR 250.916 - What are the CVA's primary duties during the design phase?

Code of Federal Regulations, 2013 CFR

2013-07-01

... the design phase? (a) The CVA must use good engineering judgment and practices in conducting an...; (iv) Load determinations; (v) Stress analyses; (vi) Material designations; (vii) Soil and foundation...

A seamless phase IIB/III adaptive outcome trial: design rationale and implementation challenges.

PubMed

Chen, Y H Joshua; Gesser, Richard; Luxembourg, Alain

2015-02-01

The licensed four-valent prophylactic human papillomavirus vaccine is highly efficacious in preventing cervical, vulvar, vaginal, and anal cancers and related precancers caused by human papillomavirus types 6, 11, 16, and 18. These four types account for approximately 70% of cervical cancers. A nine-valent human papillomavirus vaccine, including the four original types (6, 11, 16, and 18) plus the next five most prevalent types in cervical cancer (31, 33, 45, 52, and 58) could provide approximately 90% overall cervical cancer coverage. To expedite the nine-valent human papillomavirus vaccine clinical development, an adaptive, seamless Phase IIB/III outcome trial with ∼ 15,000 subjects was conducted to facilitate dose formulation selection and provide pivotal evidence of safety and efficacy for regulatory registrations. We discuss the design rationale and implementation challenges of the outcome trial, focusing on the adaptive feature of the seamless Phase IIB/III design. Subjects were enrolled in two parts (Part A and Part B). Approximately 1240 women, 16-26 years of age, were enrolled in Part A for Phase IIB evaluation and equally randomized to one of three dose formulations of the nine-valent human papillomavirus vaccine or the four-valent human papillomavirus vaccine (active control). Based on an interim analysis of immunogenicity and safety, one dose formulation of the nine-valent human papillomavirus vaccine was selected for evaluation in the Phase III part of the study. Subjects enrolled in Part A who received the selected dose formulation of the nine-valent human papillomavirus vaccine or four-valent human papillomavirus vaccine continued to be followed up and contributed to the final efficacy and safety analyses. In addition, ∼ 13,400 women 16-26 years of age were enrolled in Part B, randomized to nine-valent human papillomavirus vaccine at the selected dose formulation or four-valent human papillomavirus vaccine, and followed for immunogenicity

The coating design of phase-shifting reflector array with high reflectance and specified reflection phase shifts for static Michelson interferometer

NASA Astrophysics Data System (ADS)

Zhang, Xuanni; Zhang, Hui; Wang, Yijun

2016-02-01

The optical Doppler Michelson imaging interferometer is widely used for wind measurements. Four interferograms obtained simultaneously are needed to immune to environmental disturbances. Thus, a static and divided mirror Michelson interferometer is proposed. Its highlight is the phase-shifting reflector array, which divides one mirror into four quadrants coated by different multilayer films with high reflectance, specified phase steps π/2 and little polarization effects. By combining analytical and empirical method, four coatings are designed with software TFCalc. The simulated results showed good agreement with the desired optical properties. Due to the limitation of the optical material and function of the software TFCalc, there are some design errors within tolerance.

Wide gap Chern Mott insulating phases achieved by design

NASA Astrophysics Data System (ADS)

Guo, Hongli; Gangopadhyay, Shruba; Koeksal, Okan; Pentcheva, Rossitza; Pickett, Warren E.

Chern insulators are exciting both as a novel electronic phase and for their novel and potentially useful boundary transport properties. Honeycomb lattices occupied by heavy transition metal ions,have been proposed by Okamoto and coworkers as Chern insulators, but finding a concrete example has been challenging due to an assortment of broken symmetry phases that thwart the topological character. Building on accumulated knowledge of the behavior of the 3 d series, we tune spin-orbit and interaction strength together with strain to design two Chern insulator systems (one with Ru, one with Os) with bandgaps up to 130 meV and Chern numbers calC = - 1 and calC = 2 . We find, in this class, that a trade-off between larger spin-orbit coupling and strong interactions leads to a larger gap, whereas the stronger SOC correlates with the larger magnitude of the Hall conductivity. Symmetry lowering in the course of structural relaxation hampers retaining QAH character, as pointed out previously. Fortunately there is only mild structural symmetry breaking of the bilayer in these robust Chern phases.Recent (111) growth of insulating, magnetic phases in closely related materials with this orientation supports the likelihood that synthesis and exploitation will follow. Supported partially by the NSF DMREF program.

Advanced Envelope Research for Factory Built Housing, Phase 3. Design Development and Prototyping

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

Levy, E.; Kessler, B.; Mullens, M.

2014-01-01

The Advanced Envelope Research effort will provide factory homebuilders with high performance, cost-effective alternative envelope designs. In the near term, these technologies will play a central role in meeting stringent energy code requirements. For manufactured homes, the thermal requirements, last updated by statute in 1994, will move up to the more rigorous IECC 2012 levels in 2013, the requirements of which are consistent with site built and modular housing. This places added urgency on identifying envelope technologies that the industry can implement in the short timeframe. The primary goal of this research is to develop wall designs that meet themore » thermal requirements based on 2012 IECC standards. Given the affordable nature of manufactured homes, impact on first cost is a major consideration in developing the new envelope technologies. This work is part of a four-phase, multi-year effort. Phase 1 identified seven envelope technologies and provided a preliminary assessment of three selected methods for building high performance wall systems. Phase 2 focused on the development of viable product designs, manufacturing strategies, addressing code and structural issues, and cost analysis of the three selected options. An industry advisory committee helped critique and select the most viable solution to move further in the research -- stud walls with continuous exterior insulation. Phase 3, the subject of the current report, focused on the design development of the selected wall concept and explored variations on the use of exterior foam insulation. The scope also included material selection, manufacturing and cost analysis, and prototyping and testing.« less

Advanced Envelope Research for Factory Built Housing, Phase 3 -- Design Development and Prototyping

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

Levy, E.; Kessler, B.; Mullens, M.

2014-01-01

The Advanced Envelope Research effort will provide factory homebuilders with high performance, cost-effective alternative envelope designs. In the near term, these technologies will play a central role in meeting stringent energy code requirements. For manufactured homes, the thermal requirements, last updated by statute in 1994, will move up to the more rigorous IECC 2012 levels in 2013, the requirements of which are consistent with site built and modular housing. This places added urgency on identifying envelope technologies that the industry can implement in the short timeframe. The primary goal of this research is to develop wall designs that meet themore » thermal requirements based on 2012 IECC standards. Given the affordable nature of manufactured homes, impact on first cost is a major consideration in developing the new envelope technologies. This work is part of a four-phase, multi-year effort. Phase 1 identified seven envelope technologies and provided a preliminary assessment of three selected methods for building high performance wall systems. Phase 2 focused on the development of viable product designs, manufacturing strategies, addressing code and structural issues, and cost analysis of the three selected options. An industry advisory committee helped critique and select the most viable solution to move further in the research -- stud walls with continuous exterior insulation. Phase 3, the subject of the current report, focused on the design development of the selected wall concept and explored variations on the use of exterior foam insulation. The scope also included material selection, manufacturing and cost analysis, and prototyping and testing.« less

Serum Metabolomics Reveals Serotonin as a Predictor of Severe Dengue in the Early Phase of Dengue Fever

PubMed Central

Thein, Tun Linn; Fang, Jinling; Pang, Junxiong; Ooi, Eng Eong; Leo, Yee Sin; Ong, Choon Nam; Tannenbaum, Steven R.

2016-01-01

Effective triage of dengue patients early in the disease course for in- or out-patient management would be useful for optimal healthcare resource utilization while minimizing poor clinical outcome due to delayed intervention. Yet, early prognosis of severe dengue is hampered by the heterogeneity in clinical presentation and routine hematological and biochemical measurements in dengue patients that collectively correlates poorly with eventual clinical outcome. Herein, untargeted liquid-chromatography mass spectrometry metabolomics of serum from patients with dengue fever (DF) and dengue hemorrhagic fever (DHF) in the febrile phase (<96 h) was used to globally probe the serum metabolome to uncover early prognostic biomarkers of DHF. We identified 20 metabolites that are differentially enriched (p<0.05, fold change >1.5) in the serum, among which are two products of tryptophan metabolism–serotonin and kynurenine. Serotonin, involved in platelet aggregation and activation decreased significantly, whereas kynurenine, an immunomodulator, increased significantly in patients with DHF, consistent with thrombocytopenia and immunopathology in severe dengue. To sensitively and accurately evaluate serotonin levels as prognostic biomarkers, we implemented stable-isotope dilution mass spectrometry and used convalescence samples as their own controls. DHF serotonin was significantly 1.98 fold lower in febrile compared to convalescence phase, and significantly 1.76 fold lower compared to DF in the febrile phase of illness. Thus, serotonin alone provided good prognostic utility (Area Under Curve, AUC of serotonin = 0.8). Additionally, immune mediators associated with DHF may further increase the predictive ability than just serotonin alone. Nine cytokines, including IFN-γ, IL-1β, IL-4, IL-8, G-CSF, MIP-1β, FGF basic, TNFα and RANTES were significantly different between DF and DHF, among which IFN-γ ranked top by multivariate statistics. Combining serotonin and IFN-γ improved

Sampling design for aquatic invasive species early detection in Great Lakes ports

EPA Science Inventory

From 2006-2012, we evaluated a pilot aquatic invasive species (AIS) early detection monitoring program in Lake Superior that was designed to detect newly introduced fishes. We established survey protocols for three major ports (Duluth-Superior, Sault Ste. Marie, Thunder Bay) and ...

Designs for Living and Learning: Transforming Early Childhood Environments, Second Edition

ERIC Educational Resources Information Center

Carter, Margie; Curtis, Deb

2015-01-01

You likely have dreams for your early childhood environment that are greater than rating scales, regulations, and room arrangements. "Designs for Living and Learning" has been a favorite resource among educators and caregivers for more than a decade, and this new edition is packed with even more ideas that can be used as you create…

The Design of Phase II Clinical Trials Testing Cancer Therapeutics: Consensus Recommendations from the Clinical Trial Design Task Force of the National Cancer Institute Investigational Drug Steering Committee

PubMed Central

Seymour, Lesley; Ivy, S. Percy; Sargent, Daniel; Spriggs, David; Baker, Laurence; Rubinstein, Larry; Ratain, Mark J; Le Blanc, Michael; Stewart, David; Crowley, John; Groshen, Susan; Humphrey, Jeffrey S; West, Pamela; Berry, Donald

2010-01-01

The optimal design of phase II studies continues to be the subject of vigorous debate, especially with regards to studies of newer molecularly targeted agents. The observations that many new therapeutics ‘fail’ in definitive phase III studies, coupled with the numbers of new agents to be tested as well as the increasing costs and complexity of clinical trials further emphasizes the critical importance of robust and efficient phase II design. The Clinical Trial Design Task Force(CTD-TF)of the NCI Investigational Drug Steering Committee (IDSC) has published a series of discussion papers on Phase II trial design in Clinical Cancer Research. The IDSC has developed formal recommendations regarding aspects of phase II trial design which are the subject of frequent debate such as endpoints(response vs. progression free survival), randomization(single arm designs vs. randomization), inclusion of biomarkers, biomarker based patient enrichment strategies, and statistical design(e.g. two stage designs vs. multiple-group adaptive designs). While these recommendations in general encourage the use of progression-free survival as the primary endpoint, the use of randomization, the inclusion of biomarkers and the incorporation of newer designs, we acknowledge that objective response as an endpoint, and single arm designs, remain relevant in certain situations. The design of any clinical trial should always be carefully evaluated and justified based on the characteristic specific to the situation. PMID:20215557

The Third Year of the Brookline Early Education Project.

ERIC Educational Resources Information Center

Pierson, Donald E.

This is the third progress report of the Brookline Early Education Project (BEEP) which is a program designed to provide diagnostic and educational services to the family through their child's preschool years. This document provides information on (1) the BEEP center, (2) playgroups: transition phase of the education program, (3) dental screening…

Multi-Attribute Tradespace Exploration in Space System Design

NASA Astrophysics Data System (ADS)

Ross, A. M.; Hastings, D. E.

2002-01-01

The complexity inherent in space systems necessarily requires intense expenditures of resources both human and monetary. The high level of ambiguity present in the early design phases of these systems causes long, highly iterative, and costly design cycles. This paper looks at incorporating decision theory methods into the early design processes to streamline communication of wants and needs among stakeholders and between levels of design. Communication channeled through formal utility interviews and analysis enables engineers to better understand the key drivers for the system and allows a more thorough exploration of the design tradespace. Multi-Attribute Tradespace Exploration (MATE), an evolving process incorporating decision theory into model and simulation- based design, has been applied to several space system case studies at MIT. Preliminary results indicate that this process can improve the quality of communication to more quickly resolve project ambiguity, and enable the engineer to discover better value designs for multiple stakeholders. MATE is also being integrated into a concurrent design environment to facilitate the transfer knowledge of important drivers into higher fidelity design phases. Formal utility theory provides a mechanism to bridge the language barrier between experts of different backgrounds and differing needs (e.g. scientists, engineers, managers, etc). MATE with concurrent design couples decision makers more closely to the design, and most importantly, maintains their presence between formal reviews.

Early intervention for psychosis

PubMed Central

Marshall, Max; Rathbone, John

2014-01-01

Background Proponents of early intervention have argued that outcomes might be improved if more therapeutic efforts were focused on the early stages of schizophrenia or on people with prodromal symptoms. Early intervention in schizophrenia has two elements that are distinct from standard care: early detection, and phase-specific treatment (phase-specific treatment is a psychological, social or physical treatment developed, or modified, specifically for use with people at an early stage of the illness). Early detection and phase-specific treatment may both be offered as supplements to standard care, or may be provided through a specialised early intervention team. Early intervention is now well established as a therapeutic approach in America, Europe and Australasia. Objectives To evaluate the effects of: (a) early detection; (b) phase-specific treatments; and (c) specialised early intervention teams in the treatment of people with prodromal symptoms or first-episode psychosis. Search methods We searched the Cochrane Schizophrenia Group Trials Register (March 2009), inspected reference lists of all identified trials and reviews and contacted experts in the field. Selection criteria We included all randomised controlled trials (RCTs) designed to prevent progression to psychosis in people showing prodromal symptoms, or to improve outcome for people with first-episode psychosis. Eligible interventions, alone and in combination, included: early detection, phase-specific treatments, and care from specialised early intervention teams. We accepted cluster-randomised trials but excluded non-randomised trials. Data collection and analysis We reliably selected studies, quality rated them and extracted data. For dichotomous data, we estimated relative risks (RR), with the 95% confidence intervals (CI). Where possible, we calculated the number needed to treat/harm statistic (NNT/H) and used intention-to-treat analysis (ITT). Main results Studies were diverse, mostly small

Lunar Ultraviolet Telescope Experiment (LUTE), phase A

NASA Technical Reports Server (NTRS)

Mcbrayer, Robert O.

1994-01-01

The Lunar Ultraviolet Telescope Experiment (LUTE) is a 1-meter telescope for imaging from the lunar surface the ultraviolet spectrum between 1,000 and 3,500 angstroms. There have been several endorsements of the scientific value of a LUTE. In addition to the scientific value of LUTE, its educational value and the information it can provide on the design of operating hardware for long-term exposure in the lunar environment are important considerations. This report provides the results of the LUTE phase A activity begun at the George C. Marshall Space Flight Center in early 1992. It describes the objective of LUTE (science, engineering, and education), a feasible reference design concept that has evolved, and the subsystem trades that were accomplished during the phase A.

The Design of Software for Three-Phase Induction Motor Test System

NASA Astrophysics Data System (ADS)

Haixiang, Xu; Fengqi, Wu; Jiai, Xue

2017-11-01

The design and development of control system software is important to three-phase induction motor test equipment, which needs to be completely familiar with the test process and the control procedure of test equipment. In this paper, the software is developed according to the national standard (GB/T1032-2005) about three-phase induction motor test method by VB language. The control system and data analysis software and the implement about motor test system are described individually, which has the advantages of high automation and high accuracy.

Adaptation of the quality by design concept in early pharmaceutical development of an intranasal nanosized formulation.

PubMed

Pallagi, Edina; Ambrus, Rita; Szabó-Révész, Piroska; Csóka, Ildikó

2015-08-01

Regulatory science based pharmaceutical development and product manufacturing is highly recommended by the authorities nowadays. The aim of this study was to adapt regulatory science even in the nano-pharmaceutical early development. Authors applied the quality by design (QbD) concept in the early development phase of nano-systems, where the illustration material was meloxicam. The meloxicam nanoparticles produced by co-grinding method for nasal administration were studied according to the QbD policy and the QbD based risk assessment (RA) was performed. The steps were implemented according to the relevant regulatory guidelines (quality target product profile (QTPP) determination, selection of critical quality attributes (CQAs) and critical process parameters (CPPs)) and a special software (Lean QbD Software(®)) was used for the RA, which represents a novelty in this field. The RA was able to predict and identify theoretically the factors (e.g. sample composition, production method parameters, etc.) which have the highest impact on the desired meloxicam-product quality. The results of the practical research justified the theoretical prediction. This method can improve pharmaceutical nano-developments by achieving shorter development time, lower cost, saving human resource efforts and more effective target-orientation. It makes possible focusing the resources on the selected parameters and area during the practical product development. Copyright © 2015 Elsevier B.V. All rights reserved.

Strontium ranelate causes osteophytes overgrowth in a model of early phase osteoarthritis.

PubMed

Chu, Jian-Guo; Dai, Mu-Wei; Wang, Yu; Tian, Fa-Ming; Song, Hui-Ping; Xiao, Ya-Ping; Shao, Li-Tao; Zhang, Ying-Ze; Zhang, Liu

2017-02-10

Osteoarthritis (OA) involves cartilage changes as well as modifications of subchondral bone and synovial tissues. Strontium ranelate (SR), an anti-osteoporosis compound, which is currently in phase III clinical trial for treatment of OA. Evidences suggest that SR preferably deposited in osteophyte, other than in subchondral bone in early phase of OA. This phenomenon raises concern about its utility for OA treatment as a disease-modifying drug. To evaluate the effect of SR on cartilage, subchondral bone mass and subchondral trabecular bone structure in medial meniscectomized (MNX) guinea pigs. Thirty-six 3-month-old male Dunkin Hartley albino guinea pigs received either sham or medial meniscectomy operations. One week after the procedure, meniscectomized animals began 12 weeks of SR (625 mg/kg, daily) treatment by oral gavage for MNX + SR group, or normal saline for MNX + V group. All animals were euthanized 12 weeks later, cartilage degeneration and subchondral bone micro-architecture was analyzed. Both OARSI scores (P = 0.523 for marcoscopic scores, P = 0.297 for histological scores) and Cartilage thickness (P = 0.335) in MNX + SR group were comparable to MNX + V group. However, osteophyte sizes were larger in MNX + SR group (P = 0.014), and collapsed osteophytes in MNX + SR group (7 by 12) were significantly more than in MNX + V group (1 by 12) (P = 0.027), while immunohistochemistry indicates catabolic changes in osteophyte/plateau junction. Micro-CT analysis showed bone mineral density (BMD) (P = 0.001), bone volume fraction (BV/TV) (P = 0.008), trabecular spacing (Tb.Sp) (P = 0.020), trabecular thickness (Tb.Th) (P = 0.012) and structure model index (SMI) (P = 0.005) levels to be significantly higher in the MNX + SR group than in the MNX + V group. SR (625 mg/kg/day) did not protect cartilage from degeneration in MNX guinea pigs but subchondral bone was significantly enhanced. In early

A phase II flexible screening design allowing for interim analysis and comparison with historical control.

PubMed

Wu, Wenting; Bot, Brian; Hu, Yan; Geyer, Susan M; Sargent, Daniel J

2013-07-01

Sargent and Goldberg [1] proposed a randomized phase II flexible screening design (SG design) which took multiple characteristics of candidate regimens into consideration in selecting a regimen for further phase III testing. In this paper, we extend the SG design by including provisions for an interim analysis and/or a comparison to a historical control. By including a comparison with a historical control, a modified SG design not only identifies a more promising treatment but also assures that the regimen has a clinically meaningful level of efficacy as compared to a historical control. By including an interim analysis, a modified SG design could reduce the number of patients exposed to inferior treatment regimens. When compared to the original SG design, the modified designs increase the sample size moderately, but expand the utility of the flexible screening design substantially. Copyright © 2013 Elsevier Inc. All rights reserved.

Defining, Designing, Implementing, and Evaluating Phase 4 HIV Prevention Effectiveness Trials for Vulnerable Populations

PubMed Central

Kelly, Jeffrey A.; Spielberg, Freya; McAuliffe, Timothy L.

2008-01-01

Summary The efficacy of behavioral HIV prevention interventions has been convincingly demonstrated in a large number of randomized controlled phase 3 research outcome trials. Little research attention has been directed toward studying the effectiveness of the same interventions when delivered by providers to their own clients or community members, however. This article argues for the need to conduct phase 4 effectiveness trials of HIV prevention interventions that have been found efficacious in the research arena. Such trials can provide important information concerning the impact of interventions when applied in heterogeneous “real-world” circumstances. This article raises design issues and methodologic questions that need to be addressed in the conduct of phase 4 trials of behavioral interventions. These issues include the selection and training of service providers engaged in such trials, maintenance of fidelity to intervention protocol in provider-delivered interventions, determination of intervention core elements versus aspects that require tailoring, selection of relevant phase 4 study outcomes, interpretation of findings indicative of field effectiveness, sustainability, and other aspects of phase 4 trial design. PMID:18301131

Design and implementation of a low-cost multiple-range digital phase detector

NASA Astrophysics Data System (ADS)

Omran, Hesham; Albasha, Lutfi; Al-Ali, A. R.

2012-06-01

This article describes the design, simulation, implementation and testing of a novel low-cost multiple-range programmable digital phase detector. The detector receives two periodic signals and calculates the ratio of the time difference to the time period to measure and display the phase difference. The resulting output values are in integer form ranging from -180° to 180°. Users can select the detector pre-set operation frequency ranges using a three-bit pre-scalar. This enables to use the detector for various applications. The proposed detector can be programmed over a frequency range of 10 Hz to 25 kHz by configuring its clock divider circuit. Detector simulations were conducted and verified using ModelSim and the design was implemented and tested using an Altera Cyclone II field-programmable gate array board. Both the simulation and actual circuit testing results showed that the phase detector has a magnitude of error of only 1°. The detector is ideal for applications such as power factor measurement and correction, self-tuning resonant circuits and in metal detection systems. Unlike other stand-alone phase detection systems, the reported system has the ability to be programmed to several frequency ranges, hence expanding its bandwidth.

FPGA-based real-time phase measuring profilometry algorithm design and implementation

NASA Astrophysics Data System (ADS)

Zhan, Guomin; Tang, Hongwei; Zhong, Kai; Li, Zhongwei; Shi, Yusheng

2016-11-01

Phase measuring profilometry (PMP) has been widely used in many fields, like Computer Aided Verification (CAV), Flexible Manufacturing System (FMS) et al. High frame-rate (HFR) real-time vision-based feedback control will be a common demands in near future. However, the instruction time delay in the computer caused by numerous repetitive operations greatly limit the efficiency of data processing. FPGA has the advantages of pipeline architecture and parallel execution, and it fit for handling PMP algorithm. In this paper, we design a fully pipelined hardware architecture for PMP. The functions of hardware architecture includes rectification, phase calculation, phase shifting, and stereo matching. The experiment verified the performance of this method, and the factors that may influence the computation accuracy was analyzed.

Universal Design for Learning: Cognitive Theory into Practice for Facilitating Comprehension in Early Literacy

ERIC Educational Resources Information Center

Brand, Susan Trostle; Dalton, Elizabeth M.

2012-01-01

Addressing the unique needs of children of all ages and abilities, Universal Design for Learning (UDL) is gaining momentum in schools and preschools around the nation and the globe. This article explores Universal Design for Learning and its promising applications to a variety of reading and language arts experiences in the Early Childhood…

77 FR 7174 - Correction Notice for Deepwater Horizon Oil Spill; Draft Phase I Early Restoration Plan and...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-10

... DEPARTMENT OF THE INTERIOR Fish and Wildlife Service [FWS-R4-FHC-2012-N030; FVHC98130406900Y4-XXX-FF04G01000] Correction Notice for Deepwater Horizon Oil Spill; Draft Phase I Early Restoration Plan and Environmental Assessment AGENCY: Fish and Wildlife Service, Interior. ACTION: Notice of availability and request...

Evaluation of measles-rubella vaccination for mothers in early puerperal phase.

PubMed

Hisano, Michi; Kato, Tatsuo; Inoue, Eisuke; Sago, Haruhiko; Yamaguchi, Koushi

2016-02-24

The postpartum period is an ideal opportunity to vaccinate mothers with inadequate immunity to vaccine-preventable diseases including measles and rubella. A prospective study of measles-rubella (MR) vaccination in the early puerperal phase was conducted in 171 mothers, who had insufficient antibody titers when screened for immunity to measles (≤ 1:4 on the neutralization test [NT]) or rubella (≤ 1:16 on the hemagglutination inhibition [HI] test) during pregnancy. To evaluate the efficacy of MR vaccination in the postpartum period, we determined their post-vaccination antibody titers and immune responses to vaccination, and investigated the association between these and their prolactin (PRL) levels and Th1/Th2 ratios at the time of vaccination. We also examined the passage of viral RNA and antigen into breast milk. Of the 169 participants who completed the study schedule, 117 and 101 had low antibody titers against measles and rubella, respectively. In the measles-seronegative group, the antibody-positive rate was 87% on the NT assay, and the NT geometric mean antibody titer was 11.4 (95% confidence interval [CI], 10.0-13.0). In the rubella-seronegative group, the antibody-positive rate was 88% on the HI test assay, and the HI geometric mean antibody titer was 64.0 (95% CI, 53.9-76.0). There was no association between the post-vaccination antibody titers and the PRL levels or Th1/Th2 ratios at the time of vaccination. In the rubella-seronegative group, subjects with higher Th1/Th2 ratios showed higher rates of responsiveness than those with lower ratios (P=0.045). Although measles virus RNA was isolated from the breast milk of two vaccinated mothers, breastfeeding was not associated with clinical disease in any infants. MR vaccination in the early puerperal phase is considered an effective way to prevent the diseases, regardless of the mother's immunological status and hormonal milieu. Copyright © 2016 Elsevier Ltd. All rights reserved.

Bayesian enhancement two-stage design for single-arm phase II clinical trials with binary and time-to-event endpoints.

PubMed

Shi, Haolun; Yin, Guosheng

2018-02-21

Simon's two-stage design is one of the most commonly used methods in phase II clinical trials with binary endpoints. The design tests the null hypothesis that the response rate is less than an uninteresting level, versus the alternative hypothesis that the response rate is greater than a desirable target level. From a Bayesian perspective, we compute the posterior probabilities of the null and alternative hypotheses given that a promising result is declared in Simon's design. Our study reveals that because the frequentist hypothesis testing framework places its focus on the null hypothesis, a potentially efficacious treatment identified by rejecting the null under Simon's design could have only less than 10% posterior probability of attaining the desirable target level. Due to the indifference region between the null and alternative, rejecting the null does not necessarily mean that the drug achieves the desirable response level. To clarify such ambiguity, we propose a Bayesian enhancement two-stage (BET) design, which guarantees a high posterior probability of the response rate reaching the target level, while allowing for early termination and sample size saving in case that the drug's response rate is smaller than the clinically uninteresting level. Moreover, the BET design can be naturally adapted to accommodate survival endpoints. We conduct extensive simulation studies to examine the empirical performance of our design and present two trial examples as applications. © 2018, The International Biometric Society.

Temporal regulation of expression of immediate early and second phase transcripts by endothelin-1 in cardiomyocytes

PubMed Central

Cullingford, Timothy E; Markou, Thomais; Fuller, Stephen J; Giraldo, Alejandro; Pikkarainen, Sampsa; Zoumpoulidou, Georgia; Alsafi, Ali; Ekere, Collins; Kemp, Timothy J; Dennis, Jayne L; Game, Laurence; Sugden, Peter H; Clerk, Angela

2008-01-01

Background Endothelin-1 stimulates Gq protein-coupled receptors to promote proliferation in dividing cells or hypertrophy in terminally differentiated cardiomyocytes. In cardiomyocytes, endothelin-1 rapidly (within minutes) stimulates protein kinase signaling, including extracellular-signal regulated kinases 1/2 (ERK1/2; though not ERK5), with phenotypic/physiological changes developing from approximately 12 h. Hypertrophy is associated with changes in mRNA/protein expression, presumably consequent to protein kinase signaling, but the connections between early, transient signaling events and developed hypertrophy are unknown. Results Using microarrays, we defined the early transcriptional responses of neonatal rat cardiomyocytes to endothelin-1 over 4 h, differentiating between immediate early gene (IEG) and second phase RNAs with cycloheximide. IEGs exhibited differential temporal and transient regulation, with expression of second phase RNAs within 1 h. Of transcripts upregulated at 30 minutes encoding established proteins, 28 were inhibited >50% by U0126 (which inhibits ERK1/2/5 signaling), with 9 inhibited 25-50%. Expression of only four transcripts was not inhibited. At 1 h, most RNAs (approximately 67%) were equally changed in total and polysomal RNA with approximately 17% of transcripts increased to a greater extent in polysomes. Thus, changes in expression of most protein-coding RNAs should be reflected in protein synthesis. However, approximately 16% of transcripts were essentially excluded from the polysomes, including some protein-coding mRNAs, presumably inefficiently translated. Conclusion The phasic, temporal regulation of early transcriptional responses induced by endothelin-1 in cardiomyocytes indicates that, even in terminally differentiated cells, signals are propagated beyond the primary signaling pathways through transcriptional networks leading to phenotypic changes (that is, hypertrophy). Furthermore, ERK1/2 signaling plays a major role in

PAR-2-mediated control of barrier function and motility differs between early and late phases of postinfectious gut dysfunction in the rat.

PubMed

Fernández-Blanco, Joan Antoni; Fernández-Blanco, Juan A; Hollenberg, Morley D; Martínez, Vicente; Vergara, Patri

2013-02-15

Proteinase-activated receptor-2 (PAR-2) and mast cell (MC) mediators contribute to inflammatory and functional gastrointestinal disorders. We aimed to characterize jejunal PAR-2-mediated responses and the potential MC involvement in the early and late phases of a rat model of postinfectious gut dysfunction. Jejunal tissues of control and Trichinella spiralis-infected (14 and 30 days postinfection) rats, treated or not with the MC stabilizer, ketotifen, were used. Histopathology and immunostaining were used to characterize inflammation, PAR-2 expression, and mucosal and connective tissue MCs. Epithelial barrier function (hydroelectrolytic transport and permeability) and motility were assessed in vitro in basal conditions and after PAR-2 activation. Intestinal inflammation on day 14 postinfection (early phase) was significantly resolved by day 30 (late phase) although MC counts and epithelial permeability remained increased. PAR-2-mediated ion transport (Ussing chambers, in vitro) and epithelial surface PAR-2 expression were reduced in the early phase, with a trend toward normalization during the late phase. In control conditions, PAR-2 activation (organ bath) induced biphasic motor responses (relaxation followed by excitation). At 14 days postinfection, spontaneous contractility and PAR-2-mediated relaxations were enhanced; motor responses were normalized on day 30. Postinfectious changes in PAR-2 functions were not affected by ketotifen treatment. We concluded that, in the rat model of Trichinella spiralis infection, alterations of intestinal PAR-2 function and expression depend on the inflammatory phase considered. A lack of a ketotifen effect suggests no interplay between MCs and PAR-2-mediated motility and ion transport alterations. These observations question the role of MC mediators in PAR-2-modulating postinfectious gut dysfunction.

77 FR 14012 - Eligible Telecommunications Carrier Designation for Participation in Mobility Fund Phase I

Federal Register 2010, 2011, 2012, 2013, 2014

2012-03-08

...; DA 12-271] Eligible Telecommunications Carrier Designation for Participation in Mobility Fund Phase I... Wireless Telecommunications and Wireline Competition Bureaus describe the process and requirements for applicants seeking Eligible Telecommunications Carrier (ETC) Designation from the Commission for...

Phased Array Probe Optimization for the Inspection of Titanium Billets

NASA Astrophysics Data System (ADS)

Rasselkorde, E.; Cooper, I.; Wallace, P.; Lupien, V.

2010-02-01

The manufacturing process of titanium billets can produce multiple sub-surface defects that are particularly difficult to detect during the early stages of production. Failure to detect these defects can lead to subsequent in-service failure. A new and novel automated quality control system is being developed for the inspection of titanium billets destined for use in aerospace applications. The sensors will be deployed by an automated system to minimise the use of manual inspections, which should improve the quality and reliability of these critical inspections early on in the manufacturing process. This paper presents the first part of the work, which is the design and the simulation of the phased array ultrasonic inspection of the billets. A series of phased array transducers were designed to optimise the ultrasonic inspection of a ten inch diameter billet made from Titanium 6Al-4V. A comparison was performed between different probes including a 2D annular sectorial array.

Cognitive effects of bilateral high frequency repetitive transcranial magnetic stimulation in early phase psychosis: a pilot study.

PubMed

Francis, Michael M; Hummer, Tom A; Vohs, Jenifer L; Yung, Matthew G; Visco, Andrew C; Mehdiyoun, Nikki F; Kulig, Teresa C; Um, Miji; Yang, Ziyi; Motamed, Mehrdad; Liffick, Emily; Zhang, Ying; Breier, Alan

2018-05-31

Cognitive dysfunction is a core facet of schizophrenia that is present early in the course of the illness and contributes to diminished functioning and outcomes. Repetitive transcranial magnetic stimulation (rTMS) is a relatively new neuropsychiatric intervention. Initially used in treatment resistant depression, investigators are now studying rTMS for other psychiatric diseases such as schizophrenia. In this study we examined the effect of high frequency rTMS on cognitive function in a group of individuals with early phase psychosis. Twenty subjects were randomized (1:1) in double-blind fashion to rTMS or sham condition. Over two weeks subjects underwent ten sessions of high frequency, bilateral, sequential rTMS targeting the dorsolateral prefrontal cortex (DLPFC). Prior to beginning and following completion of study treatment, subjects completed a cognitive assessment and magnetic resonance imaging. Subjects receiving rTMS, compared to sham treatment, displayed improvement on a standardized cognitive battery both immediately following the course of study treatment and at follow-up two weeks later. Imaging results revealed that left frontal cortical thickness at baseline was correlated with treatment response. The study treatment was found to be safe and well tolerated. These results suggest that rTMS may hold promise for the treatment of cognitive dysfunction in the early phase of psychosis, and that MRI may provide biomarkers predicting response to the treatment.

Phase 1 Space Fission Propulsion System Design Considerations

NASA Technical Reports Server (NTRS)

Houts, Mike; VanDyke, Melissa; Godfroy, Tom; Pedersen, Kevin; Martin, James; Carter, Robert; Dickens, Ricky; Salvail, Pat; Hrbud, Ivana; Rodgers, Stephen L. (Technical Monitor)

2001-01-01

Fission technology can enable rapid, affordable access to any point in the solar system. If fission propulsion systems are to be developed to their full potential; however, near-term customers must be identified and initial fission systems successfully developed, launched, and operated. Studies conducted in fiscal year 2001 (IISTP, 2001) show that fission electric propulsion (FEP) systems operating at 80 kWe or above could enhance or enable numerous robotic outer solar system missions of interest. At these power levels it is possible to develop safe, affordable systems that meet mission performance requirements. In selecting the system design to pursue, seven evaluation criteria were identified: safety, reliability, testability, specific mass, cost, schedule, and programmatic risk. A top-level comparison of three potential concepts was performed: an SP-100 based pumped liquid lithium system, a direct gas cooled system, and a heatpipe cooled system. For power levels up to at least 500 kWt (enabling electric power levels of 125-175 kWe, given 25-35% power conversion efficiency) the heatpipe system has advantages related to several criteria and is competitive with respect to all. Hardware-based research and development has further increased confidence in the heatpipe approach. Successful development and utilization of a "Phase 1" fission electric propulsion system will enable advanced Phase 2 and Phase 3 systems capable of providing rapid, affordable access to any point in the solar system.

Phase 1 space fission propulsion system design considerations

NASA Astrophysics Data System (ADS)

Houts, Mike; van Dyke, Melissa; Godfroy, Tom; Pedersen, Kevin; Martin, James; Dickens, Ricky; Salvail, Pat; Hrbud, Ivana; Carter, Robert

2002-01-01

Fission technology can enable rapid, affordable access to any point in the solar system. If fission propulsion systems are to be developed to their full potential; however, near-term customers must be identified and initial fission systems successfully developed, launched, and operated. Studies conducted in fiscal year 2001 (IISTP, 2001) show that fission electric propulsion (FEP) systems operating at 80 kWe or above could enhance or enable numerous robotic outer solar system missions of interest. At these power levels it is possible to develop safe, affordable systems that meet mission performance requirements. In selecting the system design to pursue, seven evaluation criteria were identified: safety, reliability, testability, specific mass, cost, schedule, and programmatic risk. A top-level comparison of three potential concepts was performed: an SP-100 based pumped liquid lithium system, a direct gas cooled system, and a heatpipe cooled system. For power levels up to at least 500 kWt (enabling electric power levels of 125-175 kWe, given 25-35% power conversion efficiency) the heatpipe system has advantages related to several criteria and is competitive with respect to all. Hardware-based research and development has further increased confidence in the heatpipe approach. Successful development and utilization of a ``Phase 1'' fission electric propulsion system will enable advanced Phase 2 and Phase 3 systems capable of providing rapid, affordable access to any point in the solar system. .

The human early-life exposome (HELIX): project rationale and design.

PubMed

Vrijheid, Martine; Slama, Rémy; Robinson, Oliver; Chatzi, Leda; Coen, Muireann; van den Hazel, Peter; Thomsen, Cathrine; Wright, John; Athersuch, Toby J; Avellana, Narcis; Basagaña, Xavier; Brochot, Celine; Bucchini, Luca; Bustamante, Mariona; Carracedo, Angel; Casas, Maribel; Estivill, Xavier; Fairley, Lesley; van Gent, Diana; Gonzalez, Juan R; Granum, Berit; Gražulevičienė, Regina; Gutzkow, Kristine B; Julvez, Jordi; Keun, Hector C; Kogevinas, Manolis; McEachan, Rosemary R C; Meltzer, Helle Margrete; Sabidó, Eduard; Schwarze, Per E; Siroux, Valérie; Sunyer, Jordi; Want, Elizabeth J; Zeman, Florence; Nieuwenhuijsen, Mark J

2014-06-01

Developmental periods in early life may be particularly vulnerable to impacts of environmental exposures. Human research on this topic has generally focused on single exposure-health effect relationships. The "exposome" concept encompasses the totality of exposures from conception onward, complementing the genome. The Human Early-Life Exposome (HELIX) project is a new collaborative research project that aims to implement novel exposure assessment and biomarker methods to characterize early-life exposure to multiple environmental factors and associate these with omics biomarkers and child health outcomes, thus characterizing the "early-life exposome." Here we describe the general design of the project. In six existing birth cohort studies in Europe, HELIX will estimate prenatal and postnatal exposure to a broad range of chemical and physical exposures. Exposure models will be developed for the full cohorts totaling 32,000 mother-child pairs, and biomarkers will be measured in a subset of 1,200 mother-child pairs. Nested repeat-sampling panel studies (n = 150) will collect data on biomarker variability, use smartphones to assess mobility and physical activity, and perform personal exposure monitoring. Omics techniques will determine molecular profiles (metabolome, proteome, transcriptome, epigenome) associated with exposures. Statistical methods for multiple exposures will provide exposure-response estimates for fetal and child growth, obesity, neurodevelopment, and respiratory outcomes. A health impact assessment exercise will evaluate risks and benefits of combined exposures. HELIX is one of the first attempts to describe the early-life exposome of European populations and unravel its relation to omics markers and health in childhood. As proof of concept, it will form an important first step toward the life-course exposome.

Standardized Radiation Shield Design Methods: 2005 HZETRN

NASA Technical Reports Server (NTRS)

Wilson, John W.; Tripathi, Ram K.; Badavi, Francis F.; Cucinotta, Francis A.

2006-01-01

Research committed by the Langley Research Center through 1995 resulting in the HZETRN code provides the current basis for shield design methods according to NASA STD-3000 (2005). With this new prominence, the database, basic numerical procedures, and algorithms are being re-examined with new methods of verification and validation being implemented to capture a well defined algorithm for engineering design processes to be used in this early development phase of the Bush initiative. This process provides the methodology to transform the 1995 HZETRN research code into the 2005 HZETRN engineering code to be available for these early design processes. In this paper, we will review the basic derivations including new corrections to the codes to insure improved numerical stability and provide benchmarks for code verification.

Test results of a pumped two-phase mounting plate with ammonia. [designed for spacecraft thermal control

NASA Technical Reports Server (NTRS)

Swanson, T. D.; Mccabe, M. E., Jr.; Grote, M. G.

1987-01-01

The design, fabrication, and testing of full-scale prototype units of a two-phase mounting plate (TPMP), which will be used in a two-phase ammonia-based thermal control system for a large spacecraft, are described. The mounting plate uses an evaporator design in which liquid is mechanically pumped through porous feed tubes within the plate. The prototype TPMPs were tested with ammonia at heat loads over 3000 W (3.2 W/sq cm) and local heat fluxes of up to 4 W/sq cm. Calculated total heat transfer coefficients from these tests were between 0.8 and 1.0 W/sq cm per C. This represents a better than twenty-fold improvement over comparable single-phase heat transfer coefficients. Design diagrams are included.

Decrease in early right alpha band phase synchronization and late gamma band oscillations in processing syntax in music.

PubMed

Ruiz, María Herrojo; Koelsch, Stefan; Bhattacharya, Joydeep

2009-04-01

The present study investigated the neural correlates associated with the processing of music-syntactical irregularities as compared with regular syntactic structures in music. Previous studies reported an early ( approximately 200 ms) right anterior negative component (ERAN) by traditional event-related-potential analysis during music-syntactical irregularities, yet little is known about the underlying oscillatory and synchronization properties of brain responses which are supposed to play a crucial role in general cognition including music perception. First we showed that the ERAN was primarily represented by low frequency (<8 Hz) brain oscillations. Further, we found that music-syntactical irregularities as compared with music-syntactical regularities, were associated with (i) an early decrease in the alpha band (9-10 Hz) phase synchronization between right fronto-central and left temporal brain regions, and (ii) a late ( approximately 500 ms) decrease in gamma band (38-50 Hz) oscillations over fronto-central brain regions. These results indicate a weaker degree of long-range integration when the musical expectancy is violated. In summary, our results reveal neural mechanisms of music-syntactic processing that operate at different levels of cortical integration, ranging from early decrease in long-range alpha phase synchronization to late local gamma oscillations. 2008 Wiley-Liss, Inc.

Unified approach for extrapolation and bridging of adult information in early-phase dose-finding paediatric studies.

PubMed

Petit, Caroline; Samson, Adeline; Morita, Satoshi; Ursino, Moreno; Guedj, Jérémie; Jullien, Vincent; Comets, Emmanuelle; Zohar, Sarah

2018-06-01

The number of trials conducted and the number of patients per trial are typically small in paediatric clinical studies. This is due to ethical constraints and the complexity of the medical process for treating children. While incorporating prior knowledge from adults may be extremely valuable, this must be done carefully. In this paper, we propose a unified method for designing and analysing dose-finding trials in paediatrics, while bridging information from adults. The dose-range is calculated under three extrapolation options, linear, allometry and maturation adjustment, using adult pharmacokinetic data. To do this, it is assumed that target exposures are the same in both populations. The working model and prior distribution parameters of the dose-toxicity and dose-efficacy relationships are obtained using early-phase adult toxicity and efficacy data at several dose levels. Priors are integrated into the dose-finding process through Bayesian model selection or adaptive priors. This calibrates the model to adjust for misspecification, if the adult and pediatric data are very different. We performed a simulation study which indicates that incorporating prior adult information in this way may improve dose selection in children.

Design and fabrication of a high temperature leading edge heating array, phase 1

NASA Technical Reports Server (NTRS)

1972-01-01

Progress during a Phase 1 program to design a high temperature heating array is reported for environmentally testing full-scale shuttle leading edges (30 inch span, 6 to 15 inch radius) at flight heating rates and pressures. Heat transfer analyses of the heating array, individual modules, and the shuttle leading edge were performed, which influenced the array design, and the design, fabrication, and testing of a prototype heater module.

Design of a delayed XOR phase detector for an optical phase-locked loop toward high-speed coherent laser communication.

PubMed

Liu, Yang; Tong, Shoufeng; Chang, Shuai; Song, Yansong; Dong, Yan; Zhao, Xin; An, Zhe; Yu, Fuwan

2018-05-10

Optical phase-locked loops are an effective detection method in high-speed and long-distance laser communication. Although this method can detect weak signal light and maintain a small bit error rate, it is difficult to perform because identifying the phase difference between the signal light and the local oscillator accurately has always been a technical challenge. Thus, a series of studies is conducted to address this issue. First, a delayed exclusive or gate (XOR) phase detector with multi-level loop compound control is proposed. Then, a 50 ps delay line and relative signal-to-noise ratio control at 15 dB are produced through theoretical derivation and simulation. Thereafter, a phase discrimination module is designed on a 15  cm×5  cm printed circuit board board. Finally, the experiment platform is built for verification. Experimental results show that the phase discrimination range is -1.1 to 1.1 GHz, and the gain is 0.82 mV/MHz. Three times the standard deviation, that is, 0.064 V, is observed between the test and theoretical values. The accuracy of phase detection is better than 0.07 V, which meets the design standards. A coherent carrier recovery test system is established. The delayed XOR gate has good performance in this system. When the communication rate is 5 Gbps, the system realizes a bit error rate of 1.55×10 -8 when the optical power of the signal is -40.4  dBm. When the communication rate is increased to 10 Gbps, the detection sensitivity drops to -39.5  dBm and still shows good performance in high-speed communications. This work provides a reference for future high-speed coherent homodyne detection in space. Ideas for the next phase of this study are presented at the end of this paper.

Designing a Measurement Framework for Response to Intervention in Early Childhood Programs

ERIC Educational Resources Information Center

McConnell, Scott R.; Wackerle-Hollman, Alisha K.; Roloff, Tracy A.; Rodriguez, Michael

2014-01-01

The overall architecture and major components of a measurement system designed and evaluated to support Response to Intervention (RTI) in the areas of language and literacy in early childhood programs are described. Efficient and reliable measurement is essential for implementing any viable RTI system, and implementing such a system in early…

Preliminary design of flight hardware for two-phase fluid research

NASA Technical Reports Server (NTRS)

Hustvedt, D. C.; Oonk, R. L.

1982-01-01

This study defined the preliminary designs of flight software for the Space Shuttle Orbiter for three two-phase fluid research experiments: (1) liquid reorientation - to study the motion of liquid in tanks subjected to small accelerations; (2) pool boiling - to study low-gravity boiling from horizontal cylinders; and (3) flow boiling - to study low-gravity forced flow boiling heat transfer and flow phenomena in a heated horizontal tube. The study consisted of eight major tasks: reassessment of the existing experiment designs, assessment of the Spacelab facility approach, assessment of the individual carry-on approach, selection of the preferred approach, preliminary design of flight hardware, safety analysis, preparation of a development plan, estimates of detailed design, fabrication and ground testing costs. The most cost effective design approach for the experiments is individual carry-ons in the Orbiter middeck. The experiments were designed to fit into one or two middeck lockers. Development schedules for the detailed design, fabrication and ground testing ranged from 15 1/2 to 18 months. Minimum costs (in 1981 dollars) ranged from $463K for the liquid reorientation experiment to $998K for the pool boiling experiment.

Enhancing the Design Process for Complex Space Systems through Early Integration of Risk and Variable-Fidelity Modeling

NASA Technical Reports Server (NTRS)

Mavris, Dimitri; Osburg, Jan

2005-01-01

An important enabler of the new national Vision for Space Exploration is the ability to rapidly and efficiently develop optimized concepts for the manifold future space missions that this effort calls for. The design of such complex systems requires a tight integration of all the engineering disciplines involved, in an environment that fosters interaction and collaboration. The research performed under this grant explored areas where the space systems design process can be enhanced: by integrating risk models into the early stages of the design process, and by including rapid-turnaround variable-fidelity tools for key disciplines. Enabling early assessment of mission risk will allow designers to perform trades between risk and design performance during the initial design space exploration. Entry into planetary atmospheres will require an increased emphasis of the critical disciplines of aero- and thermodynamics. This necessitates the pulling forward of EDL disciplinary expertise into the early stage of the design process. Radiation can have a large potential impact on overall mission designs, in particular for the planned nuclear-powered robotic missions under Project Prometheus and for long-duration manned missions to the Moon, Mars and beyond under Project Constellation. This requires that radiation and associated risk and hazards be assessed and mitigated at the earliest stages of the design process. Hence, RPS is another discipline needed to enhance the engineering competencies of conceptual design teams. Researchers collaborated closely with NASA experts in those disciplines, and in overall space systems design, at Langley Research Center and at the Jet Propulsion Laboratory. This report documents the results of this initial effort.

Internal Dose from Food and Drink Ingestion in the Early Phase after the Accident

NASA Astrophysics Data System (ADS)

Kawai, Masaki; Yoshizawa, Nobuaki; Hirakawa, Sachiko; Murakami, Kana; Takizawa, Mari; Sato, Osamu; Takagi, Shunji; Miyatake, Hirokazu; Takahashi, Tomoyuki; Suzuki, Gen

2017-09-01

Activity concentrations in food and drink, represented by water and vegetables, have been monitored continuously since the Fukushima Daiichi Nuclear Power Plant accident, with a focus on radioactive cesium. On the other hand, iodine-131 was not measured systematically in the early phase after the accident. The activity concentrations of iodine-131 in food and drink are important to estimate internal exposure due to ingestion pathway. When the internal dose from ingestion in the evacuation areas is estimated, water is considered as the main ingestion pathway. In this study, we estimated the values of activity concentrations in water in the early phase after the accident, using a compartment model as an estimation method. The model uses measurement values of activity concentration and deposition rate of iodine-131 onto the ground, which is calculated from an atmospheric dispersion simulation. The model considers how drinking water would be affected by radionuclides deposited into water. We estimated the activity concentrations of water on Kawamata town and Minamisouma city during March of 2011 and the committed effective doses were 0.08 mSv and 0.06 mSv. We calculated the transfer parameters in the model for estimating the activity concentrations in the areas with a small amount of measurement data. In addition, we estimated the committed effective doses from vegetables using atmospheric dispersion simulation and FARMLAND model in case of eating certain vegetables as option information.

Conceptual design of an ascent-phase interceptor missile

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

Salguero, D E

1994-11-01

A conceptual design for an air-launched interceptor missile to defend against theater ballistic missiles is presented. The missile is designed to intercept the target while ascending, during Or just after the boost phase, before it reaches exo-atmospheric flight. The interceptor consists of a two-stage booster and a shrouded kinetic-kill vehicle. This report concentrates on the booster design required to achieve reasonable standoff ranges. The kinetic-kill vehicle and shroud (the payload) is assumed to weigh 80 lb{sub m} (36 kg) and assumed to contain guidance computers for both the kill vehicle and the booster. The interceptor missile is about 6 mmore » long, .48 m in diameter and weighs about 900 kg. Allowing 25 sec for target detection, trajectory estimation, and interceptor launch, it can intercept 90 sec after target launch from a 220 km stand-off range at an altitude of 60 km. Trade-off studies show that the interceptor performance is most sensitive to the stage mass fractions (with the first-stage mass fraction the most important), the first-stage burn time and the payload weight.« less

The design of composite monitoring scheme for multilevel information in crop early diseases

NASA Astrophysics Data System (ADS)

Zhang, Yan; Meng, Qinglong; Shang, Jing

2018-02-01

It is difficult to monitor and predict the crops early diseases in that the crop disease monitoring is usually monitored by visible light images and the availabilities in early warning are poor at present. The features of common nondestructive testing technology applied to the crop diseases were analyzed in this paper. Based on the changeable characteristics of the virus from the incubation period to the onset period of crop activities, the multilevel composite information monitoring scheme were designed by applying infrared thermal imaging, visible near infrared hyperspectral imaging, micro-imaging technology to the monitoring of multilevel information of crop disease infection comprehensively. The early warning process and key monitoring parameters of compound monitoring scheme are given by taking the temperature, color, structure and texture of crops as the key monitoring characteristics of disease. With overcoming the deficiency that the conventional monitoring scheme is only suitable for the observation of diseases with naked eyes, the monitoring and early warning of the incubation and early onset of the infection crops can be realized by the composite monitoring program as mentioned in this paper.

Virtual Design of a Controller for a Hydraulic Cam Phasing System

NASA Astrophysics Data System (ADS)

Schneider, Markus; Ulbrich, Heinz

2010-09-01

Hydraulic vane cam phasing systems are nowadays widely used for improving the performance of combustion engines. At stationary operation, these systems should achieve a constant phasing angle, which however is badly disturbed by the alternating torque generated by the valve actuation. As the hydraulic system shows a non-linear characteristic over the full operation range and the inductivity of the hydraulic pipes generates a significant time delay, a full model based control emerges very complex. Therefore a simple feed-forward controller is designed, bridging the time delay of the hydraulic system and improving the system behaviour significantly.

Design of electromagnetic refractor and phase transformer using coordinate transformation theory.

PubMed

Lin, Lan; Wang, Wei; Cui, Jianhua; Du, Chunlei; Luo, Xiangang

2008-05-12

We designed an electromagnetic refractor and a phase transformer using form-invariant coordinate transformation of Maxwell's equations. The propagation direction of electromagnetic energy in these devices can be modulated as desired. Unlike the conventional dielectric refractor, electromagnetic fields at our refraction boundary do not conform to the Snell's law in isotropic materials and the impedance at this boundary is matched which makes the reflection extremely low; and the transformation of the wave front from cylindrical to plane can be realized in the phase transformer with a slab structure. Two dimensional finite-element simulations were performed to confirm the theoretical results.

Masks as Self-Study. Challenging and Sustaining Teachers' Personal and Professional Personae in Early-Mid Career Life Phases

ERIC Educational Resources Information Center

Leitch, Ruth

2010-01-01

Drawing on previous research identifying how teachers' capacities to sustain their effectiveness in different phases of their professional lives are affected positively and/or negatively by their sense of identity, this paper illuminates three early-mid career teachers' self-study inquiries, centring on mask work. The creative development of…

Sampling design for early detection of aquatic invasive species in Great Lakes ports

EPA Science Inventory

We evaluated a pilot adaptive monitoring program for aquatic invasive species (AIS) early detection in Lake Superior. The monitoring program is designed to detect newly-introduced fishes, and encompasses the lake’s three major ports (Duluth-Superior, Sault Ste. Marie, Thund...

Q-band 4-state phase shifter in planar technology: Circuit design and performance analysis.

PubMed

Villa, E; Cagigas, J; Aja, B; de la Fuente, L; Artal, E

2016-09-01

A 30% bandwidth phase shifter with four phase states is designed to be integrated in a radio astronomy receiver. The circuit has two 90° out-of-phase microwave phase-shifting branches which are combined by Wilkinson power dividers. Each branch is composed of a 180° phase shifter and a band-pass filter. The 180° phase shifter is made of cascaded hybrid rings with microwave PIN diodes as switching devices. The 90° phase shift is achieved with the two band-pass filters. Experimental characterization has shown significant results, with average phase shift values of -90.7°, -181.7°, and 88.5° within the operation band, 35-47 GHz, and mean insertion loss of 7.4 dB. The performance of its integration in a polarimetric receiver for radio astronomy is analyzed, which validates the use of the presented phase shifter in such type of receiver.

Differential role of afferent and efferent renal nerves in the maintenance of early- and late-phase Dahl S hypertension

PubMed Central

Foss, Jason D.; Fink, Gregory D.

2015-01-01

Clinical data suggest that renal denervation (RDNX) may be an effective treatment for human hypertension; however, it is unclear whether this therapeutic effect is due to ablation of afferent or efferent renal nerves. We have previously shown that RDNX lowers arterial pressure in hypertensive Dahl salt-sensitive (S) rats to a similar degree observed in clinical trials. In addition, we have recently developed a method for selective ablation of afferent renal nerves (renal-CAP). In the present study, we tested the hypothesis that the antihypertensive effect of RDNX in the Dahl S rat is due to ablation of afferent renal nerves by comparing the effect of complete RDNX to renal-CAP during two phases of hypertension in the Dahl S rat. In the early phase, rats underwent treatment after 3 wk of high-NaCl feeding when mean arterial pressure (MAP) was ∼140 mmHg. In the late phase, rats underwent treatment after 9 wk of high NaCl feeding, when MAP was ∼170 mmHg. RDNX reduced MAP ∼10 mmHg compared with sham surgery in both the early and late phase, whereas renal-CAP had no antihypertensive effect. These results suggest that, in the Dahl S rat, the antihypertensive effect of RDNX is not dependent on pretreatment arterial pressure, nor is it due to ablation of afferent renal nerves. PMID:26661098

Rethinking Instructional Technology to Improve Pedagogy for Digital Literacy: A Design Case in a Graduate Early Childhood Education Course

ERIC Educational Resources Information Center

Langub, Lee Woodham; Lokey-Vega, Anissa

2017-01-01

Digital literacy is an important aspect to consider within teacher education as a way to address twenty-first century learner needs, particularly in early childhood contexts where developmental concerns should be paramount in making instructional design decisions. This article is a design case of a graduate level early childhood education…

Relationship between ADAMTS13 activity, von Willebrand factor antigen levels and platelet function in the early and late phases after TIA or ischaemic stroke.

PubMed

McCabe, Dominick J H; Murphy, Stephen J X; Starke, Richard; Harrison, Paul; Brown, Martin M; Sidhu, Paul S; Mackie, Ian J; Scully, Marie; Machin, Samuel J

2015-01-15

Reduced ADAMTS13 activity is seen in thrombotic thrombocytopenic purpura (TTP), and may lead to accumulation of prothrombotic ultra-large von Willebrand factor (ULVWF) multimers in vivo. ADAMTS13 activity and its relationship with VWF antigen (VWF:Ag) levels and platelet function in 'non-TTP related' TIA or ischaemic stroke has not been comprehensively studied. In this prospective pilot observational analytical case-control study, ADAMTS13 activity and VWF:Ag levels were quantified in platelet poor plasma in 53 patients in the early phase (≤ 4 weeks) and 34 of these patients in the late phase (≥ 3 months) after TIA or ischaemic stroke on aspirin. Data were compared with those from 22 controls not on aspirin. The impact of ADAMTS13 on platelet function in whole blood was quantified by measuring Collagen-ADP (C-ADP) and Collagen-Epinephrine closure times on a platelet function analyser (PFA-100(®)). Median ADAMTS13 activity was significantly reduced in the early phase (71.96% vs. 95.5%, P <0.01) but not in the late phase after TIA or stroke compared with controls (86.3% vs. 95.5%, P=0.19). There was a significant inverse relationship between ADAMTS13 activity and VWF:Ag levels in the early phase (r=-0.31; P=0.024), but not in the late phase after TIA or stroke (P=0.74). There was a positive correlation between ADAMTS13 activity and C-ADP closure times in early phase patients only, likely mediated via VWF:Ag levels. ADAMTS13 activity is reduced and VWF:Ag expression is increased within 4 weeks of TIA or ischaemic stroke onset, and can promote enhanced platelet adhesion and aggregation in response to stimulation with collagen and ADP via VWF-mediated pathways. These data improve our understanding of the dynamic haemostatic and thrombotic profiles of ischaemic cerebrovascular disease (CVD) patients, and are important in view of the potential future role that ADAMTS13 may have to play as an anti-thrombotic agent in CVD. Copyright © 2014 Elsevier B.V. All rights

Training Early Career Scientists in Flight Instrument Design Through Experiential Learning: NASA Goddard's Planetary Science Winter School.

NASA Technical Reports Server (NTRS)

Bleacher, L. V.; Lakew, B.; Bracken, J.; Brown, T.; Rivera, R.

2017-01-01

The NASA Goddard Planetary Science Winter School (PSWS) is a Goddard Space Flight Center-sponsored training program, managed by Goddard's Solar System Exploration Division (SSED), for Goddard-based postdoctoral fellows and early career planetary scientists. Currently in its third year, the PSWS is an experiential training program for scientists interested in participating on future planetary science instrument teams. Inspired by the NASA Planetary Science Summer School, Goddard's PSWS is unique in that participants learn the flight instrument lifecycle by designing a planetary flight instrument under actual consideration by Goddard for proposal and development. They work alongside the instrument Principal Investigator (PI) and engineers in Goddard's Instrument Design Laboratory (IDL; idc.nasa.gov), to develop a science traceability matrix and design the instrument, culminating in a conceptual design and presentation to the PI, the IDL team and Goddard management. By shadowing and working alongside IDL discipline engineers, participants experience firsthand the science and cost constraints, trade-offs, and teamwork that are required for optimal instrument design. Each PSWS is collaboratively designed with representatives from SSED, IDL, and the instrument PI, to ensure value added for all stakeholders. The pilot PSWS was held in early 2015, with a second implementation in early 2016. Feedback from past participants was used to design the 2017 PSWS, which is underway as of the writing of this abstract.

Wide gap Chern Mott insulating phases achieved by design

NASA Astrophysics Data System (ADS)

Guo, Hongli; Gangopadhyay, Shruba; Köksal, Okan; Pentcheva, Rossitza; Pickett, Warren E.

2017-12-01

Quantum anomalous Hall insulators, which display robust boundary charge and spin currents categorized in terms of a bulk topological invariant known as the Chern number (Thouless et al Phys. Rev. Lett. 49, 405-408 (1982)), provide the quantum Hall anomalous effect without an applied magnetic field. Chern insulators are attracting interest both as a novel electronic phase and for their novel and potentially useful boundary charge and spin currents. Honeycomb lattice systems such as we discuss here, occupied by heavy transition-metal ions, have been proposed as Chern insulators, but finding a concrete example has been challenging due to an assortment of broken symmetry phases that thwart the topological character. Building on accumulated knowledge of the behavior of the 3d series, we tune spin-orbit and interaction strength together with strain to design two Chern insulator systems with bandgaps up to 130 meV and Chern numbers C = -1 and C = 2. We find, in this class, that a trade-off between larger spin-orbit coupling and strong interactions leads to a larger gap, whereas the stronger spin-orbit coupling correlates with the larger magnitude of the Hall conductivity. Symmetry lowering in the course of structural relaxation hampers obtaining quantum anomalous Hall character, as pointed out previously; there is only mild structural symmetry breaking of the bilayer in these robust Chern phases. Recent growth of insulating, magnetic phases in closely related materials with this orientation supports the likelihood that synthesis and exploitation will follow.

[Spiral CT of the head-neck area: the advantages of the early arterial phase in the detection of squamous-cell carcinomas].

PubMed

Conrad, R; Pauleit, D; Layer, G; Kandyba, J; Kohlbecher, R; Hortling, N; Baselides, P; Schild, H

1999-07-01

To determine if scanning in the arterial phase improves detection of squamous cell carcinomas in the pharynx and larynx. In a prospective clinical study 20 patients with a pharyngeal or laryngeal carcinoma were examined with by spiral CT. 80 ml lopromid were intravenously injected as a bolus with a rate of 3 ml/sec. Two consecutive spiral CT scans were performed with start-delay times of 20 and 70 seconds respectively. Delineation and contrast enhancement of tumours, cervical lymph nodes and vessels were evaluated. The radiodensities (HU) of tumors, lymph nodes vessels, pharyngeal wall and muscle were measured. Comparing early and late start delay time scans tumor assessment in the early phase was better in 58%, less in 16% and equal in both scans in 26%. 82% of the pathologic lymph nodes had more peripheral enhancement than surrounding muscle tissue. During the arterial phase the measured radiodensities of the common carotid artery and jugular vein were significantly higher than in the second phase. Contrast-enhanced special CT permits accurate morphologic assessment (size, infiltration) of pharyngeal and supraglottic laryngeal squamous cell carcinoma, while pathologic lymph nodes already have a sufficient contrast enhancement for the detection.

A Taxonomy of Instructional Strategies in Early Childhood Education; Toward a Developmental Theory of Instructional Design.

ERIC Educational Resources Information Center

Vance, Barbara

This paper suggests two steps in instructional deisgn for early childhood that can be derived from a recent major paper on instructional strategy taxonomy. These steps, together with the instructional design variables involved in each step, are reviewed relative to current research in child development and early education. The variables reviewed…

Standards for Clinical Trials in Male and Female Sexual Dysfunction: I. Phase I to Phase IV Clinical Trial Design.

PubMed

Fisher, William A; Gruenwald, Ilan; Jannini, Emmanuele A; Lev-Sagie, Ahinoam; Lowenstein, Lior; Pyke, Robert E; Reisman, Yakov; Revicki, Dennis A; Rubio-Aurioles, Eusebio

2016-12-01

This series of articles outlines standards for clinical trials of treatments for male and female sexual dysfunctions, with a focus on research design and patient-reported outcome assessment. These articles consist of revision, updating, and integration of articles on standards for clinical trials in male and female sexual dysfunction from the 2010 International Consultation on Sexual Medicine developed by the authors as part of the 2015 International Consultation on Sexual Medicine. We are guided in this effort by several principles. In contrast to previous versions of these guidelines, we merge discussion of standards for clinical trials in male and female sexual dysfunction in an integrated approach that emphasizes the common foundational practices that underlie clinical trials in the two settings. We present a common expected standard for clinical trial design in male and female sexual dysfunction, a common rationale for the design of phase I to IV clinical trials, and common considerations for selection of study population and study duration in male and female sexual dysfunction. We present a focused discussion of fundamental principles in patient- (and partner-) reported outcome assessment and complete this series of articles with specific discussions of selected aspects of clinical trials that are unique to male and to female sexual dysfunction. Our consideration of standards for clinical trials in male and female sexual dysfunction attempts to embody sensitivity to existing and new regulatory guidance and to address implications of the evolution of the diagnosis of sexual dysfunction that have been brought forward in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition. The first article in this series focuses on phase I to phase IV clinical trial design considerations. Subsequent articles in this series focus on the measurement of patient-reported outcomes, unique aspects of clinical trial design for men, and unique aspects of clinical

Optical path design of phase contrast imaging on HL-2A tokamak

NASA Astrophysics Data System (ADS)

Qiyun, CHENG; Yi, YU; Shaobo, GONG; Min, XU; Tao, LAN; Wei, JIANG; Boda, YUAN; Yifan, WU; Lin, NIE; Rui, KE; Ting, LONG; Dong, GUO; Minyou, YE; Xuru, DUAN

2017-12-01

A phase contrast imaging (PCI) diagnostic has recently been developed on HL-2A tokamak. It can diagnose plasma density fluctuations with maximum wave number of 15 cm-1 and wave number resolution of 2 cm-1. The time resolution reaches 2 μs. A 10.6 μm CO2 laser is expanded to a beam with a diameter of 30 mm and injected into the plasma as an incident beam, injecting into plasma. The emerging scattered and unscattered beams are contrasted by a phase plate. The ideas of optical path design are presented in this paper, together with the parameters of the main optical components. The whole optical path of PCI is not only carefully designed, but also constructed on HL-2A. First calibration results show the ability of this system to catch plasma turbulence in a wide frequency domain.

Acute lipophilicity-dependent effect of intravascular simvastatin in the early phase of focal cerebral ischemia.

PubMed

Beretta, S; Pastori, C; Sala, G; Piazza, F; Ferrarese, C; Cattalini, A; de Curtis, M; Librizzi, L

2011-05-01

The acute effects of simvastatin lactone (lipophilic) and simvastatin acid (hydrophilic) on transient focal ischemia were assessed using the isolated guinea pig brain maintained in vitro by arterial perfusion. This new model of cerebral ischemia allows the assessment of the very early phase of the ischemic process, with the functional preservation of the vascular and neuronal compartments and the blood-brain barrier (bbb). The middle cerebral artery was transiently tied for 30 min followed by reperfusion for 60 min. Statins (nanomolar doses) were administered by intravascular continuous infusion starting 60 min before ischemia induction. Brain cortical activity and arterial vascular tone were continuously recorded. At the end of the experiment immunoreactivity for microtubule-associated protein 2 (MAP-2), expression of survival kinases (ERK and Akt) and total anti-oxidant capacity were assayed. Brains treated with simvastatin lactone showed i) reduced amplitude and delayed onset of ischemic depressions, ii) preservation of MAP-2 immunoreactivity, iii) activation of ERK signaling in the ischemic hemisphere and iv) increase in whole-brain anti-oxidant capacity. Treatment with the bbb-impermeable simvastatin acid was ineffective on the above-mentioned parameters. Vascular resistance recordings and Akt signaling were unchanged by any statin treatment. Our findings suggest that intravascular-delivered simvastatin exerts an acute lipophilicity-dependent protective effect in the early phase of cerebral ischemia. Copyright © 2011 Elsevier Ltd. All rights reserved.

A Bayesian predictive two-stage design for phase II clinical trials.

PubMed

Sambucini, Valeria

2008-04-15

In this paper, we propose a Bayesian two-stage design for phase II clinical trials, which represents a predictive version of the single threshold design (STD) recently introduced by Tan and Machin. The STD two-stage sample sizes are determined specifying a minimum threshold for the posterior probability that the true response rate exceeds a pre-specified target value and assuming that the observed response rate is slightly higher than the target. Unlike the STD, we do not refer to a fixed experimental outcome, but take into account the uncertainty about future data. In both stages, the design aims to control the probability of getting a large posterior probability that the true response rate exceeds the target value. Such a probability is expressed in terms of prior predictive distributions of the data. The performance of the design is based on the distinction between analysis and design priors, recently introduced in the literature. The properties of the method are studied when all the design parameters vary.

Evaluation of early efficacy endpoints for proof-of-concept trials.

PubMed

Chen, Cong; Sun, Linda; Li, Chih-Lin

2013-03-11

A Phase II proof-of-concept (POC) trial usually uses an early efficacy endpoint other than a clinical endpoint as the primary endpoint. Because of the advancement in bioscience and technology, which has yielded a number of new surrogate biomarkers, drug developers often have more candidate endpoints to choose from than they can handle. As a result, selection of endpoint and its effect size as well as choice of type I/II error rates are often at the center of heated debates in design of POC trials. While optimization of the trade-off between benefit and cost is the implicit objective in such a decision-making process, it is seldom explicitly accounted for in practice. In this research note, motivated by real examples from the oncology field, we provide practical measures for evaluation of early efficacy endpoints (E4) for POC trials. We further provide optimal design strategies for POC trials that include optimal Go-No Go decision criteria for initiation of Phase III and optimal resource allocation strategies for conducting multiple POC trials in a portfolio under fixed resources. Although oncology is used for illustration purpose, the same idea developed in this research note also applies to similar situations in other therapeutic areas or in early-stage drug development in that a Go-No Go decision has to rely on limited data from an early efficacy endpoint and cost-effectiveness is the main concern.

Design of early warning system for nuclear preparedness case study at Serpong

NASA Astrophysics Data System (ADS)

Farid, M. M.; Prawito, Susila, I. P.; Yuniarto, A.

2017-07-01

One effort to protect the environment from the increasing of potentially environmental radiation hazards as an impact of radiation discharge around nuclear facilities is by a continuous monitoring of the environmental radiation in real time It is important to disclose the dose rate information to public or authorities for radiological protection. In this research, we have designed a nuclear preparedness early warning system around the Serpong nuclear facility. The design is based on Arduino program, general packet radio service (GPRS) shield, and radio frequencies technology to transmit environmental radiation result of the measurement and meteorological data. Data was collected at a certain location at The Center for Informatics and Nuclear Strategic Zone Utilization BATAN Serpong. The system consistency models are defined by the quality of data and the level of radiation exposure in the deployed environment. Online users can access the website which displays the radiation dose on the environment marked on Google Map. This system is capable to issue an early warning emergency when the dose reaches three times of the background radiation exposure value, 250 nSv/hour.

Preliminary Two-Phase Terry Turbine Nozzle Models for RCIC Off-Design Operation Conditions

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

Zhao, Haihua; O'Brien, James

This report presents the effort to extend the single-phase analytical Terry turbine model to cover two-phase off-design conditions. The work includes: (1) adding well-established two-phase choking models – the Isentropic Homogenous Equilibrium Model (IHEM) and Moody’s model, and (2) theoretical development and implementation of a two-phase nozzle expansion model. The two choking models provide bounding cases for the two-phase choking mass flow rate. The new two-phase Terry turbine model uses the choking models to calculate the mass flow rate, the critical pressure at the nozzle throat, and steam quality. In the divergent stage, we only consider the vapor phase withmore » a similar model for the single-phase case by assuming that the liquid phase would slip along the wall with a much slower speed and will not contribute the impulse on the rotor. We also modify the stagnation conditions according to two-phase choking conditions at the throat and the cross-section areas for steam flow at the nozzle throat and at the nozzle exit. The new two-phase Terry turbine model was benchmarked with the same steam nozzle test as for the single-phase model. Better agreement with the experimental data is observed than from the single-phase model. We also repeated the Terry turbine nozzle benchmark work against the Sandia CFD simulation results with the two-phase model for the pure steam inlet nozzle case. The RCIC start-up tests were simulated and compared with the single-phase model. Similar results are obtained. Finally, we designed a new RCIC system test case to simulate the self-regulated Terry turbine behavior observed in Fukushima accidents. In this test, a period inlet condition for the steam quality varying from 1 to 0 is applied. For the high quality inlet period, the RCIC system behaves just like the normal operation condition with a high pump injection flow rate and a nominal steam release rate through the turbine, with the net addition of water to the primary

48 CFR 570.105-2 - Criteria for the use of two-phase design-build.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 48 Federal Acquisition Regulations System 4 2012-10-01 2012-10-01 false Criteria for the use of two-phase design-build. 570.105-2 Section 570.105-2 Federal Acquisition Regulations System GENERAL SERVICES ADMINISTRATION SPECIAL CONTRACTING PROGRAMS ACQUIRING LEASEHOLD INTERESTS IN REAL PROPERTY General 570.105-2 Criteria for the use of two-phase...

48 CFR 570.105-2 - Criteria for the use of two-phase design-build.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 48 Federal Acquisition Regulations System 4 2013-10-01 2013-10-01 false Criteria for the use of two-phase design-build. 570.105-2 Section 570.105-2 Federal Acquisition Regulations System GENERAL SERVICES ADMINISTRATION SPECIAL CONTRACTING PROGRAMS ACQUIRING LEASEHOLD INTERESTS IN REAL PROPERTY General 570.105-2 Criteria for the use of two-phase...

48 CFR 570.105-2 - Criteria for the use of two-phase design-build.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 48 Federal Acquisition Regulations System 4 2014-10-01 2014-10-01 false Criteria for the use of two-phase design-build. 570.105-2 Section 570.105-2 Federal Acquisition Regulations System GENERAL SERVICES ADMINISTRATION SPECIAL CONTRACTING PROGRAMS ACQUIRING LEASEHOLD INTERESTS IN REAL PROPERTY General 570.105-2 Criteria for the use of two-phase...

30 CFR 250.916 - What are the CVA's primary duties during the design phase?

Code of Federal Regulations, 2011 CFR

2011-07-01

... 30 Mineral Resources 2 2011-07-01 2011-07-01 false What are the CVA's primary duties during the design phase? 250.916 Section 250.916 Mineral Resources BUREAU OF OCEAN ENERGY MANAGEMENT, REGULATION... data; (iv) Load determinations; (v) Stress analyses; (vi) Material designations; (vii) Soil and...

Screened selection design for randomised phase II oncology trials: an example in chronic lymphocytic leukaemia

PubMed Central

2013-01-01

Background As there are limited patients for chronic lymphocytic leukaemia trials, it is important that statistical methodologies in Phase II efficiently select regimens for subsequent evaluation in larger-scale Phase III trials. Methods We propose the screened selection design (SSD), which is a practical multi-stage, randomised Phase II design for two experimental arms. Activity is first evaluated by applying Simon’s two-stage design (1989) on each arm. If both are active, the play-the-winner selection strategy proposed by Simon, Wittes and Ellenberg (SWE) (1985) is applied to select the superior arm. A variant of the design, Modified SSD, also allows the arm with the higher response rates to be recommended only if its activity rate is greater by a clinically-relevant value. The operating characteristics are explored via a simulation study and compared to a Bayesian Selection approach. Results Simulations showed that with the proposed SSD, it is possible to retain the sample size as required in SWE and obtain similar probabilities of selecting the correct superior arm of at least 90%; with the additional attractive benefit of reducing the probability of selecting ineffective arms. This approach is comparable to a Bayesian Selection Strategy. The Modified SSD performs substantially better than the other designs in selecting neither arm if the underlying rates for both arms are desirable but equivalent, allowing for other factors to be considered in the decision making process. Though its probability of correctly selecting a superior arm might be reduced, it still performs reasonably well. It also reduces the probability of selecting an inferior arm. Conclusions SSD provides an easy to implement randomised Phase II design that selects the most promising treatment that has shown sufficient evidence of activity, with available R codes to evaluate its operating characteristics. PMID:23819695

Screened selection design for randomised phase II oncology trials: an example in chronic lymphocytic leukaemia.

PubMed

Yap, Christina; Pettitt, Andrew; Billingham, Lucinda

2013-07-03

As there are limited patients for chronic lymphocytic leukaemia trials, it is important that statistical methodologies in Phase II efficiently select regimens for subsequent evaluation in larger-scale Phase III trials. We propose the screened selection design (SSD), which is a practical multi-stage, randomised Phase II design for two experimental arms. Activity is first evaluated by applying Simon's two-stage design (1989) on each arm. If both are active, the play-the-winner selection strategy proposed by Simon, Wittes and Ellenberg (SWE) (1985) is applied to select the superior arm. A variant of the design, Modified SSD, also allows the arm with the higher response rates to be recommended only if its activity rate is greater by a clinically-relevant value. The operating characteristics are explored via a simulation study and compared to a Bayesian Selection approach. Simulations showed that with the proposed SSD, it is possible to retain the sample size as required in SWE and obtain similar probabilities of selecting the correct superior arm of at least 90%; with the additional attractive benefit of reducing the probability of selecting ineffective arms. This approach is comparable to a Bayesian Selection Strategy. The Modified SSD performs substantially better than the other designs in selecting neither arm if the underlying rates for both arms are desirable but equivalent, allowing for other factors to be considered in the decision making process. Though its probability of correctly selecting a superior arm might be reduced, it still performs reasonably well. It also reduces the probability of selecting an inferior arm. SSD provides an easy to implement randomised Phase II design that selects the most promising treatment that has shown sufficient evidence of activity, with available R codes to evaluate its operating characteristics.

The Implications of Encoder/Modulator/ Phased Array Designs for Future Broadband LEO Communications

NASA Technical Reports Server (NTRS)

Vanderaar, Mark; Jensen, Chris A.; Terry, John D.

1997-01-01

In this paper we summarize the effects of modulation and channel coding on the design of wide angle scan, broadband, phased army antennas. In the paper we perform several trade studies. First, we investigate the amplifier back-off requirement as a function of variability of modulation envelope. Specifically, we contrast constant and non-constant envelope modulations, as well as single and multiple carrier schemes. Additionally, we address the issues an(f concerns of using pulse shaping filters with the above modulation types. Second, we quantify the effects of beam steering on the quality of data, recovery using selected modulation techniques. In particular, we show that the frequency response of the array introduces intersymbol interference for broadband signals and that the mode of operation for the beam steering controller may introduce additional burst or random errors. Finally, we show that the encoder/modulator design must be performed in conjunction with the phased array antenna design.

Early College Designs: An Increasingly Popular College-Readiness Strategy for School Districts to Reach More Traditionally Underserved Students

ERIC Educational Resources Information Center

Vargas, Joel H.; Miller, Marc S.

2011-01-01

Once a radical concept, early college high schools are flying soundly today. The challenge today--and the excitement of those involved--centers on learning from this successful innovation and bringing the early college design to many more young people. Expansion is taking place through the creation of early college districts covering all students…

Design of a digital multiradian phase detector and its application in fusion plasma interferometry.

PubMed

Mlynek, A; Schramm, G; Eixenberger, H; Sips, G; McCormick, K; Zilker, M; Behler, K; Eheberg, J

2010-03-01

We discuss the circuit design of a digital multiradian phase detector that measures the phase difference between two 10 kHz square wave TTL signals and provides the result as a binary number. The phase resolution of the circuit is 1/64 period and its dynamic range is 256 periods. This circuit has been developed for fusion plasma interferometry with submillimeter waves on the ASDEX Upgrade tokamak. The results from interferometric density measurement are discussed and compared to those obtained with the previously used phase detectors, especially with respect to the occurrence of phase jumps. It is illustrated that the new phase measurement provides a powerful tool for automatic real-time validation of the measured density, which is important for feedback algorithms that are sensitive to spurious density signals.

F247. INTERNALIZED STIGMA HAS A STRONGER RELATIONSHIP WITH INTRINSIC MOTIVATION COMPARED TO AMOTIVATION IN EARLY PHASE AND PROLONGED SCHIZOPHRENIA

PubMed Central

Firmin, Ruth; Luther, Lauren; Lysaker, Paul; Vohs, Jennifer

2018-01-01

Abstract Background Motivation deficits predict decreased functioning in schizophrenia. Recent work suggests deficits reflect challenges in separate domains: intrinsic motivation (one’s internal drive to engage in a behavior out of enjoyment or interest) and amotivation (one’s broader decrease in motivated behavior linked to avolition and anhedonia). Internalized stigma is another determinant of functioning for people with schizophrenia that may impact motivation. However, little is known about these relationships, including which aspects of motivation it may impact nor when these links emerge. Identifying the link between these constructs may help to identify whether internalized stigma may be a novel treatment target to facilitate improvements in motivation. Methods Forty adults with early phase schizophrenia and 66 adults with prolonged schizophrenia completed measures of internalized stigma, intrinsic motivation, and amotivation. Pearson’s correlations were examined followed by Fischer’s r-to-z transformations to compare differences in the magnitude of associations between internalized stigma and intrinsic motivation and internalized stigma and amotivation among the first episode and prolonged samples. Next, we conducted stepwise regressions to examine whether internalized stigma was associated with intrinsic motivation above and beyond associations with amotivation in each sample. Results In the early phase sample, the association between internalized stigma was greater with intrinsic motivation (r=-0.48, p=.00) compared to amotivation (r=0.27, p=0.10). Associations with internalized stigma in the prolonged sample were also greater with intrinsic motivation (r=-0.30, p=0.02) versus amotivation (r=0.19, p=0.12). The magnitude of the associations between internalized stigma and intrinsic motivation (z=1.03, p=0.15) and between internalized stigma and amotivation (z=0.41, p = 0.34) did not significantly differ when comparing phase of illness. Regression

Canadian and Siberian Boreal Fire Activity during ARCTAS Spring and Summer Phases

NASA Astrophysics Data System (ADS)

Stocks, B. J.; Fromm, M. D.; Soja, A. J.; Servranckx, R.; Lindsey, D.; Hyer, E.

2009-12-01

The summer phase of ARCTAS (Arctic Research of the Composition of the Troposphere from Aircraft and Satellites) was designed specifically around forest fire activity in the Canadian boreal forest, and located in areas of northern Canada where summer forest fires are ubiquitous. Lightning fires are most often allowed to burn naturally in these regions, and a number of large free-burning fires in northern Saskatchewan in late June/early July 2008 provided excellent targets during the summer phase of ARCTAS. Smoke generated by a large number of early spring fires in Kazakhstan and southern Siberia unexpectedly made a significant contribution to arctic haze during the Alaska-based spring phase of ARCTAS, Numerous smoke plumes were sampled during the spring phase of ARCTAS, creating interest in the origin and characteristics of the fires in the source regions of East Asia. This presentation is designed to connect aircraft and satellite smoke chemistry/transport measurements with ground-based measurements of fire activity during the spring and summer phases of ARCTAS. The Canadian Forest Fire Danger Rating System (CFFDRS) is used to determine forest fire danger conditions in regions of fire activity, and these measurements are in turn used to project fire behavior characteristics. Fuel consumption, spread rates, and frontal fire intensity are calculated using the CFFDRS. Energy release rates at ground level are related to convection/smoke column development and smoke injection heights.

Design of flood early warning system with wifi network based on smartphone

NASA Astrophysics Data System (ADS)

Supani, Ahyar; Andriani, Yuli; Taqwa, Ahmad

2017-11-01

Today, the development using internet of things enables activities surrounding us to be monitored, controlled, predicted and calculated remotely through connections to the internet network such as monitoring activities of long-distance flood warning with information technology. Applying an information technology in the field of flood early warning has been developed in the world, either connected to internet network or not. The internet network that has been done in this paper is the design of WiFi network to access data of rainfall, water level and flood status at any time with a smartphone coming from flood early warning system. The results obtained when test of data accessing with smartphone are in form of rainfall and water level graphs against time and flood status indicators consisting of 3 flood states: Standby 2, Standby 1 and Flood. It is concluded that data are from flood early warning system has been able to accessed and displayed on smartphone via WiFi network in any time and real time.

Hierarchical Thinking: A Cognitive Tool for Guiding Coherent Decision Making in Design Problem Solving

ERIC Educational Resources Information Center

Haupt, Grietjie

2018-01-01

This paper builds on two concepts, the first of which is the extended information processing model of expert design cognition. This proposes twelve internal psychological characteristics interacting with the external world of expert designers during the early phases of the design process. Here, I explore one of the characteristics, hierarchical…

Studies of high temperature ternary phases in mixed-metal-rich early transition metal sulfide and phosphide systems

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

Marking, Gregory Allen

1994-01-04

Investigations of ternary mixed early transition metal-rich sulfide and phosphide systems resulted in the discovery of new structures and new phases. A new series of Zr and Hf - group V transition metal - sulfur K-phases was synthesized and crystallographically characterized. When the group V transition metal was Nb or Ta, the unit cell volume was larger than any previously reported K-phase. The presence of adventitious oxygen was determined in two K-phases through a combination of neutron scattering and X-ray diffraction experiments. A compound Hf 10Ta 3S 3 was found to crystallize in a new-structure type similar to the knownmore » gamma brasses. This structure is unique in that it is the only reported "stuffed" gamma-brass type structure. The metal components, Hf and Ta, are larger in size and more electropositive than the metals found in normal gamma brasses (e.g. Cu and Zn) and because of the larger metallic radii, sulfur can be incorporated into the structure where it plays an integral role in stabilizing this phase relative to others. X-ray single-crystal, X-ray powder and neutron powder refinements were performed on this structure. A new structure was found in the ternary Nb-Zr-P system which has characteristics in common with many known early transition metal-rich sulfides, selenides, and phosphides. This structure has the simplest known interconnection of the basic building blocks known for this structural class. Anomalous scattering was a powerful tool for differentiating between Zr and Nb when using Mo Kα X-radiation. The compounds ZrNbP and HfNbP formed in the space group Prima with the simple Co 2Si structure which is among the most common structures found for crystalline solid materials. Solid solution compounds in the Ta-Nb-P, Ta-Zr-P, Nb-Zr-P, Hf-Nb-P, and Hf-Zr-S systems were crystallographically characterized. The structural information corroborated ideas about bonding in metal-rich compounds.« less

Novel therapies for resistant focal segmental glomerulosclerosis (FONT) phase II clinical trial: study design.

PubMed

Trachtman, Howard; Vento, Suzanne; Gipson, Debbie; Wickman, Larysa; Gassman, Jennifer; Joy, Melanie; Savin, Virginia; Somers, Michael; Pinsk, Maury; Greene, Tom

2011-02-10

The lack of adequate randomized clinical trials (RCT) has hindered identification of new therapies that are safe and effective for patients with primary focal segmental glomerulosclerosis (FSGS), especially in patients who fail to respond to corticosteroids and immunosuppressive therapies. Recent basic science advances have led to development of alternative treatments that specifically target aberrant pathways of fibrosis which are relevant to disease progression in FSGS. There is a need for a flexible Phase II study design which will test such novel antifibrotic strategies in order to identify agents suitable for phase III testing. The Novel Therapies for Resistant Focal Segmental Glomerulosclerosis (FONT) project is a multicenter Phase I/II RCT designed to investigate the potential efficacy of novel therapies for resistant FSGS. Adalimumab and galactose will be evaluated against conservative therapy consisting of the combination of lisinopril, losartan and atorvastatin. The sample size is defined to assure that if one of the treatments has a superior response rate compared to that of the other treatments, it will be selected with high probability for further evaluation. Comparison of primary and secondary endpoints in each study arm will enable a choice to be made of which treatments are worthy of further study in future Phase III RCT. This report highlights the key features of the FONT II RCT including the two-step outcome analysis that will expedite achievement of the study objectives. The proposed phase II study design will help to identify promising agents for further testing while excluding ineffective agents. This staged approach can help to prevent large expenditures on unworthy therapeutic agents in the management of serious but rare kidney diseases.

A System Analysis Approach to Robot Gripper Control Using Phase Lag Compensator Bode Designs

NASA Astrophysics Data System (ADS)

Aye, Khin Muyar; Lin, Htin; Tun, Hla Myo

2008-10-01

In this paper, we introduce the result comparisons that were developed for the phase lag compensator design using Bode Plots. The implementation of classical experiments as MATLAB m-files is described. Robot gripper control system can be designed to gain insight into a variety of concepts, including stabilization of unstable systems, compensation properties, Bode analysis and design. The analysis has resulted in a number of important conclusions for the design of a new generation of control support systems.

7T T₂*-weighted magnetic resonance imaging reveals cortical phase differences between early- and late-onset Alzheimer's disease.

PubMed

van Rooden, Sanneke; Doan, Nhat Trung; Versluis, Maarten J; Goos, Jeroen D C; Webb, Andrew G; Oleksik, Ania M; van der Flier, Wiesje M; Scheltens, Philip; Barkhof, Frederik; Weverling-Rynsburger, Annelies W E; Blauw, Gerard Jan; Reiber, Johan H C; van Buchem, Mark A; Milles, Julien; van der Grond, Jeroen

2015-01-01

The aim of this study is to explore regional iron-related differences in the cerebral cortex, indicative of Alzheimer's disease pathology, between early- and late-onset Alzheimer's disease (EOAD, LOAD, respectively) patients using 7T magnetic resonance phase images. High-resolution T2(∗)-weighted scans were acquired in 12 EOAD patients and 17 LOAD patients with mild to moderate disease and 27 healthy elderly control subjects. Lobar peak-to-peak phase shifts and regional mean phase contrasts were computed. An increased peak-to-peak phase shift was found for all lobar regions in EOAD patients compared with LOAD patients (p < 0.05). Regional mean phase contrast in EOAD patients was higher than in LOAD patients in the superior medial and middle frontal gyrus, anterior and middle cingulate gyrus, postcentral gyrus, superior and inferior parietal gyrus, and precuneus (p ≤ 0.042). These data suggest that EOAD patients have an increased iron accumulation, possibly related to an increased amyloid deposition, in specific cortical regions as compared with LOAD patients. Copyright © 2015 Elsevier Inc. All rights reserved.

On the relationship between matched filter theory as applied to gust loads and phased design loads analysis

NASA Technical Reports Server (NTRS)

Zeiler, Thomas A.; Pototzky, Anthony S.

1989-01-01

A theoretical basis and example calculations are given that demonstrate the relationship between the Matched Filter Theory approach to the calculation of time-correlated gust loads and Phased Design Load Analysis in common use in the aerospace industry. The relationship depends upon the duality between Matched Filter Theory and Random Process Theory and upon the fact that Random Process Theory is used in Phased Design Loads Analysis in determining an equiprobable loads design ellipse. Extensive background information describing the relevant points of Phased Design Loads Analysis, calculating time-correlated gust loads with Matched Filter Theory, and the duality between Matched Filter Theory and Random Process Theory is given. It is then shown that the time histories of two time-correlated gust load responses, determined using the Matched Filter Theory approach, can be plotted as parametric functions of time and that the resulting plot, when superposed upon the design ellipse corresponding to the two loads, is tangent to the ellipse. The question is raised of whether or not it is possible for a parametric load plot to extend outside the associated design ellipse. If it is possible, then the use of the equiprobable loads design ellipse will not be a conservative design practice in some circumstances.

A design procedure for the phase-controlled parallel-loaded resonant inverter

NASA Technical Reports Server (NTRS)

King, Roger J.

1989-01-01

High-frequency-link power conversion and distribution based on a resonant inverter (RI) has been recently proposed. The design of several topologies is reviewed, and a simple approximate design procedure is developed for the phase-controlled parallel-loaded RI. This design procedure seeks to ensure the benefits of resonant conversion and is verified by data from a laboratory 2.5 kVA, 20-kHz converter. A simple phasor analysis is introduced as a useful approximation for design purposes. The load is considered to be a linear impedance (or an ac current sink). The design procedure is verified using a 2.5-kVA 20-kHz RI. Also obtained are predictable worst-case ratings for each component of the resonant tank circuit and the inverter switches. For a given load VA requirement, below-resonance operation is found to result in a significantly lower tank VA requirement. Under transient conditions such as load short-circuit, a reversal of the expected commutation sequence is possible.

An Overview of the Jupiter Europa Orbiter Concept's Europa Science Phase Orbit Design

NASA Technical Reports Server (NTRS)

Lock, Robert E.; Ludwinski, Jan M.; Petropoulos, Anastassios E.; Clark, Karla B.; Pappalardo, Robert T.

2009-01-01

Jupiter Europa Orbiter (JEO), the proposed NASA element of the proposed joint NASA-ESA Europa Jupiter System Mission (EJSM), could launch in February 2020 and conceivably arrive at Jupiter in December of 2025. The concept is to perform a multi-year study of Europa and the Jupiter system, including 30 months of Jupiter system science and a comprehensive Europa orbit phase of 9 months. This paper provides an overview of the JEO concept and describes the Europa Science phase orbit design and the related science priorities, model pay-load and operations scenarios needed to conduct the Europa Science phase. This overview is for planning and discussion purposes only.

Intentionally Designed Three-Phase Time Diary (TD) as a Multi-Pronged Practice

ERIC Educational Resources Information Center

Chen, Hsin-Yu; Yarnal, Careen

2017-01-01

Adopting qualitative approaches, this study highlights the value of integrating cognitive understanding with students' daily experiences through a time diary (TD) project. Using an innovative three-phase design, the TD effectively heightened self-awareness, promoted self-reflection, inspired the desire to change, and facilitated knowledge…

BOP2: Bayesian optimal design for phase II clinical trials with simple and complex endpoints.

PubMed

Zhou, Heng; Lee, J Jack; Yuan, Ying

2017-09-20

We propose a flexible Bayesian optimal phase II (BOP2) design that is capable of handling simple (e.g., binary) and complicated (e.g., ordinal, nested, and co-primary) endpoints under a unified framework. We use a Dirichlet-multinomial model to accommodate different types of endpoints. At each interim, the go/no-go decision is made by evaluating a set of posterior probabilities of the events of interest, which is optimized to maximize power or minimize the number of patients under the null hypothesis. Unlike other existing Bayesian designs, the BOP2 design explicitly controls the type I error rate, thereby bridging the gap between Bayesian designs and frequentist designs. In addition, the stopping boundary of the BOP2 design can be enumerated prior to the onset of the trial. These features make the BOP2 design accessible to a wide range of users and regulatory agencies and particularly easy to implement in practice. Simulation studies show that the BOP2 design has favorable operating characteristics with higher power and lower risk of incorrectly terminating the trial than some existing Bayesian phase II designs. The software to implement the BOP2 design is freely available at www.trialdesign.org. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

Phase 1 Space Fission Propulsion Energy Source Design

NASA Technical Reports Server (NTRS)

Houts, Mike; VanDyke, Melissa; Godfroy, Tom; Pedersen, Kevin; Martin, James; Dickens, Ricky; Salvail, Pat; Hrbud, Ivana; Carter, Robert; Rodgers, Stephen L. (Technical Monitor)

2002-01-01

Fission technology can enable rapid, affordable access to any point in the solar system. If fission propulsion systems are to be developed to their full potential; however, near-term customers must be identified and initial fission systems successfully developed, launched, and operated. Studies conducted in fiscal year 2001 (IISTP, 2001) show that fission electric propulsion (FEP) systems with a specific mass at or below 50 kg/kWjet could enhance or enable numerous robotic outer solar system missions of interest. At the required specific mass, it is possible to develop safe, affordable systems that meet mission requirements. To help select the system design to pursue, eight evaluation criteria were identified: system integration, safety, reliability, testability, specific mass, cost, schedule, and programmatic risk. A top-level comparison of four potential concepts was performed: a Testable, Passive, Redundant Reactor (TPRR), a Testable Multi-Cell In-Core Thermionic Reactor (TMCT), a Direct Gas Cooled Reactor (DGCR), and a Pumped Liquid Metal Reactor.(PLMR). Development of any of the four systems appears feasible. However, for power levels up to at least 500 kWt (enabling electric power levels of 125-175 kWe, given 25-35% power conversion efficiency) the TPRR has advantages related to several criteria and is competitive with respect to all. Hardware-based research and development has further increased confidence in the TPRR approach. Successful development and utilization of a "Phase I" fission electric propulsion system will enable advanced Phase 2 and Phase 3 systems capable of providing rapid, affordable access to any point in the solar system.

Multimodal neuroimaging of frontal white matter microstructure in early phase schizophrenia: the impact of early adolescent cannabis use

PubMed Central

2013-01-01

Background A disturbance in connectivity between different brain regions, rather than abnormalities within the separate regions themselves, could be responsible for the clinical symptoms and cognitive dysfunctions observed in schizophrenia. White matter, which comprises axons and their myelin sheaths, provides the physical foundation for functional connectivity in the brain. Myelin sheaths are located around the axons and provide insulation through the lipid membranes of oligodendrocytes. Empirical data suggests oligodendroglial dysfunction in schizophrenia, based on findings of abnormal myelin maintenance and repair in regions of deep white matter. The aim of this in vivo neuroimaging project is to assess the impact of early adolescent onset of regular cannabis use on brain white matter tissue integrity, and to differentiate this impact from the white matter abnormalities associated with schizophrenia. The ultimate goal is to determine the liability of early adolescent use of cannabis on brain white matter, in a vulnerable brain. Methods/Design Young adults with schizophrenia at the early stage of the illness (less than 5 years since diagnosis) will be the focus of this project. Four magnetic resonance imaging measurements will be used to assess different cellular aspects of white matter: a) diffusion tensor imaging, b) localized proton magnetic resonance spectroscopy with a focus on the neurochemical N-acetylaspartate, c) the transverse relaxation time constants of regional tissue water, d) and of N-acetylaspartate. These four neuroimaging indices will be assessed within the same brain region of interest, that is, a large white matter fibre bundle located in the frontal region, the left superior longitudinal fasciculus. Discussion We will expand our knowledge regarding current theoretical models of schizophrenia with a more comprehensive multimodal neuroimaging approach to studying the underlying cellular abnormalities of white matter, while taking into

Early Detection of Sporadic Pancreatic Cancer

PubMed Central

Kenner, Barbara J.; Chari, Suresh T.; Cleeter, Deborah F.; Go, Vay Liang W.

2015-01-01

Abstract Innovation leading to significant advances in research and subsequent translation to clinical practice is urgently necessary in early detection of sporadic pancreatic cancer. Addressing this need, the Early Detection of Sporadic Pancreatic Cancer Summit Conference was conducted by Kenner Family Research Fund in conjunction with the 2014 American Pancreatic Association and Japan Pancreas Society Meeting. International interdisciplinary scientific representatives engaged in strategic facilitated conversations based on distinct areas of inquiry: Case for Early Detection: Definitions, Detection, Survival, and Challenges; Biomarkers for Early Detection; Imaging; and Collaborative Studies. Ideas generated from the summit have led to the development of a Strategic Map for Innovation built upon 3 components: formation of an international collaborative effort, design of an actionable strategic plan, and implementation of operational standards, research priorities, and first-phase initiatives. Through invested and committed efforts of leading researchers and institutions, philanthropic partners, government agencies, and supportive business entities, this endeavor will change the future of the field and consequently the survival rate of those diagnosed with pancreatic cancer. PMID:25938853

Design of Phase I Combination Trials: Recommendations of the Clinical Trial Design Task Force of the NCI Investigational Drug Steering Committee

PubMed Central

Paller, Channing J.; Bradbury, Penelope A.; Ivy, S. Percy; Seymour, Lesley; LoRusso, Patricia M.; Baker, Laurence; Rubinstein, Larry; Huang, Erich; Collyar, Deborah; Groshen, Susan; Reeves, Steven; Ellis, Lee M.; Sargent, Daniel J.; Rosner, Gary L.; LeBlanc, Michael L.; Ratain, Mark J.

2014-01-01

Anticancer drugs are combined in an effort to treat a heterogeneous tumor or to maximize the pharmacodynamic effect. The development of combination regimens, while desirable, poses unique challenges. These include the selection of agents for combination therapy that may lead to improved efficacy while maintaining acceptable toxicity, the design of clinical trials that provide informative results for individual agents and combinations, and logistical and regulatory challenges. The phase 1 trial is often the initial step in the clinical evaluation of a combination regimen. In view of the importance of combination regimens and the challenges associated with developing them, the Clinical Trial Design (CTD) Task Force of the National Cancer Institute (NCI) Investigational Drug Steering Committee developed a set of recommendations for the phase 1 development of a combination regimen. The first two recommendations focus on the scientific rationale and development plans for the combination regimen; subsequent recommendations encompass clinical design aspects. The CTD Task Force recommends that selection of the proposed regimens be based on a biological or pharmacological rationale supported by clinical and/or robust and validated preclinical evidence, and accompanied by a plan for subsequent development of the combination. The design of the phase 1 clinical trial should take into consideration the potential pharmacokinetic and pharmacodynamic interactions as well as overlapping toxicity. Depending on the specific hypothesized interaction, the primary endpoint may be dose optimization, pharmacokinetics, and/or pharmacodynamic (i.e., biomarker). PMID:25125258

Scenario for concurrent conceptual assembly line design: A case study

NASA Astrophysics Data System (ADS)

Mas, F.; Ríos, J.; Menéndez, J. L.

2012-04-01

The decision to design and build a new aircraft is preceded by years of research and study. Different disciplines work together throughout the lifecycle to ensure not only a complete functional definition of the product, but also a complete industrialization, a marketing plan, a maintenance plan, etc. This case study focuses on the conceptual design phase. During this phase, the design solutions that will meet the functional and industrial requirements are defined, i.e.: the basic requirements of industrialization. During this phase, several alternatives are studied, and the most attractive in terms of performance and cost requirements is selected. As a result of the study of these alternatives, it is possible to define an early conceptual design of the assembly line and its basic parameters. The plant needs, long cycle jigs & tools or industrial means and human resources with the necessary skills can be determined in advance.

Free-piston Stirling engine conceptual design and technologies for space power, phase 1

NASA Technical Reports Server (NTRS)

Penswick, L. Barry; Beale, William T.; Wood, J. Gary

1990-01-01

As part of the SP-100 program, a phase 1 effort to design a free-piston Stirling engine (FPSE) for a space dynamic power conversion system was completed. SP-100 is a combined DOD/DOE/NASA program to develop nuclear power for space. This work was completed in the initial phases of the SP-100 program prior to the power conversion concept selection for the Ground Engineering System (GES). Stirling engine technology development as a growth option for SP-100 is continuing after this phase 1 effort. Following a review of various engine concepts, a single-cylinder engine with a linear alternator was selected for the remainder of the study. The relationships of specific mass and efficiency versus temperature ratio were determined for a power output of 25 kWe. This parametric study was done for a temperature ratio range of 1.5 to 2.0 and for hot-end temperatures of 875 K and 1075 K. A conceptual design of a 1080 K FPSE with a linear alternator producing 25 kWe output was completed. This was a single-cylinder engine designed for a 62,000 hour life and a temperature ratio of 2.0. The heat transport systems were pumped liquid-metal loops on both the hot and cold ends. These specifications were selected to match the SP-100 power system designs that were being evaluated at that time. The hot end of the engine used both refractory and superalloy materials; the hot-end pressure vessel featured an insulated design that allowed use of the superalloy material. The design was supported by the hardware demonstration of two of the component concepts - the hydrodynamic gas bearing for the displacer and the dynamic balance system. The hydrodynamic gas bearing was demonstrated on a test rig. The dynamic balance system was tested on the 1 kW RE-1000 engine at NASA Lewis.

Rethinking the architectural design concept in the digital culture (in architecture's practice perspective)

NASA Astrophysics Data System (ADS)

Prawata, Albertus Galih

2017-11-01

The architectural design stages in architectural practices or in architectural design studio consist of many aspects. One of them is during the early phases of the design process, where the architects or designers try to interpret the project brief into the design concept. This paper is a report of the procedure of digital tools in the early design process in an architectural practice in Jakarta. It targets principally the use of BIM and digital modeling to generate information and transform them into conceptual forms, which is not very common in Indonesian architectural practices. Traditionally, the project brief is transformed into conceptual forms by using sketches, drawings, and physical model. The new method using digital tools shows that it is possible to do the same thing during the initial stage of the design process to create early architectural design forms. Architect's traditional tools and methods begin to be replaced effectively by digital tools, which would drive bigger opportunities for innovation.

Near Earth Asteroid Rendezvous (NEAR) Revised Eros Orbit Phase Trajectory Design

NASA Technical Reports Server (NTRS)

Helfrich, J; Miller, J. K.; Antreasian, P. G.; Carranza, E.; Williams, B. G.; Dunham, D. W.; Farquhar, R. W.; McAdams, J. V.

1999-01-01

Trajectory design of the orbit phase of the NEAR mission involves a new process that departs significantly from those procedures used in previous missions. In most cases, a precise spacecraft ephemeris is designed well in advance of arrival at the target body. For NEAR, the uncertainty in the dynamic environment around Eros does not allow the luxury of a precise spacecraft trajectory to be defined in advance. The principal cause of this uncertainty is the limited knowledge oi' the gravity field a,-id rotational state of Eros. As a result, the concept for the NEAR trajectory design is to define a number of rules for satisfying spacecraft, mission, and science constraints, and then apply these rules to various assumptions for the model of Eros. Nominal, high, and low Eros mass models are used for testing the trajectory design strategy and to bracket the ranges of parameter variations that are expected upon arrival at the asteroid. The final design is completed after arrival at Eros and determination of the actual gravity field and rotational state. As a result of the unplanned termination of the deep space rendezvous maneuver on December 20, 1998, the NEAR spacecraft passed within 3830 km of Eros on December 23, 1998. This flyby provided a brief glimpse of Eros, and allowed for a more accurate model of the rotational parameters and gravity field uncertainty. Furthermore, after the termination of the deep space rendezvous burn, contact with the spacecraft was lost and the NEAR spacecraft lost attitude control. During the subsequent gyrations of the spacecraft, hydrazine thruster firings were used to regain attitude control. This unplanned thruster activity used Much of the fuel margin allocated for the orbit phase. Consequently, minimizing fuel consumption is now even more important.

Design specifications for NALDA (Naval Aviation Logistics Data Analysis) CAI (computer aided instruction): Phase 2, Interim report

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

Twitty, A.F.; Handler, B.H.; Duncan, L.D.

Data Systems Engineering Organization (DSEO) personnel are developing a prototype computer aided instruction (CAI) system for the Naval Aviation Logistics Data Analysis (NALDA) system. The objective of this project is to provide a prototype for implementing CAI as an enhancement to existing NALDA training. The CAI prototype project is being performed in phases. The task undertaken in Phase I was to analyze the problem and the alternative solutions and to develop a set of recommendations on how best to proceed. In Phase II a structured design and specification document was completed that will provide the basis for development and implementationmore » of the desired CAI system. Phase III will consist of designing, developing, and testing a user interface which will extend the features of the Phase II prototype. The design of the CAI prototype has followed a rigorous structured analysis based on Yourdon/DeMarco methodology and Information Engineering tools. This document includes data flow diagrams, a data dictionary, process specifications, an entity-relationship diagram, a curriculum description, special function key definitions, and a set of standards developed for the NALDA CAI Prototype.« less