High Temperature Burst Testing of a Superalloy Disk With a Dual Grain Structure

NASA Technical Reports Server (NTRS)

Gayda, J.; Kantzos, P.

2004-01-01

Elevated temperature burst testing of a disk with a dual grain structure made from an advanced nickel-base superalloy, LSHR, was conducted. The disk had a fine grain bore and coarse grain rim, produced using NASA's low cost DMHT technology. The results of the spin testing showed the disk burst at 42 530 rpm in line with predictions based on a 2-D finite element analysis. Further, significant growth of the disk was observed before failure which was also in line with predictions.

Improved Foundry Castings Utilizing CAD/CAM (Computer Aided Design/ Computer Aided Manufacture). Volume 1. Overview

DTIC Science & Technology

1988-06-30

casting. 68 Figure 1-9: Line printer representation of roll solidification. 69 Figure I1-1: Test casting model. 76 Figure 11-2: Division of test casting...writing new casting analysis and design routines. The new routines would take advantage of advanced criteria for predicting casting soundness and cast...properties and technical advances in computer hardware and software. 11 2. CONCLUSIONS UPCAST, a comprehensive software package, has been developed for

Real-world practice patterns for patients with advanced non-small cell lung cancer: multicenter retrospective cohort study in Japan.

PubMed

Isobe, Hiroshi; Mori, Kiyoshi; Minato, Koichi; Katsura, Hideki; Taniguchi, Kazuko; Arunachalam, Ashwini; Kothari, Smita; Cao, Xiting; Kato, Terufumi

2017-01-01

Recommended therapies for advanced/metastatic non-small cell lung cancer (NSCLC) have changed with the advent of targeted therapies. The objectives of this retrospective chart review study were to describe treatment patterns, biomarker testing practices, and health care resource use for advanced NSCLC at 5 sites in Japan. We studied anonymized medical record data of patients aged ≥18 years who initiated systemic therapy for newly diagnosed stage IIIB or IV NSCLC from January 2011 through June 2013. Data were analyzed descriptively by histology and mutation status. Overall survival was estimated using the Kaplan-Meier method. We studied 175 patients, including 43 (25%), 129 (74%), and 3 (2%) with squamous, nonsquamous, and unknown NSCLC histology, respectively; 83% had stage IV NSCLC. Overall, 123 patients (70%) were male; the median age was 70 years (range, 47-86); and 33 (19%) were never-smokers. In the nonsquamous cohort, 105 (81%) and 25 (19%) of patients were tested for epidermal growth factor receptor ( EGFR ) mutation and anaplastic lymphoma kinase ( ALK ) rearrangement, respectively; 44 (42%) had EGFR -positive NSCLC and 2 (8%) had ALK -positive NSCLC, including 26/46 (57%) women and 21/46 (46%) never-smokers. In the squamous cohort, 17 (40%) and 4 (9%), respectively, were tested; 1 EGFR -positive tumor was detected. After first-line therapy, 105 (60%) patients received second-line, and 54/105 (51%; or 31% overall) received third-line therapy. EGFR tyrosine kinase inhibitors were most commonly prescribed for EGFR -positive NSCLC across all lines. In the nonsquamous EGFR / ALK -negative/unknown cohort, most received first-line platinum combinations, particularly younger patients (78% ≥75 years vs 93% <75 years old). The average hospitalization was 21 days/admission. The median (95% CI) overall survival from start of first-line therapy was 9.9 months (7.6-11.7) for all patients and 17.9 months (9.9-24.4) for patients with EGFR / ALK -positive status. Biomarker testing is common for nonsquamous NSCLC at the 5 Japanese study sites. Treatment is personalized by mutation status and age, per guideline recommendations.

ALK rearrangement testing and treatment patterns for patients with ALK-positive non-small cell lung cancer.

PubMed

Guérin, Annie; Sasane, Medha; Zhang, Jie; Macalalad, Alexander R; Galebach, Philip; Jarvis, John; Kageleiry, Andrew; Culver, Kenneth; Wu, Eric Q; Wakelee, Heather

2015-06-01

Approximately 2-8% of non-small cell lung cancer (NSCLC) patients have rearrangements in the anaplastic lymphoma kinase gene (ALK). ALK-targeted therapy is available to patients with tumors known to be ALK+. This chart review study described characteristics of patients with ALK+ NSCLC, patterns of ALK testing and subsequent treatments, and oncologists' experience with ALK testing in the US. US oncologists provided information in September and October of 2013 on patients from their practice diagnosed with ALK+ locally advanced or metastatic NSCLC, including the timing of ALK testing and treatment received after testing. Participating oncologists were also surveyed about their experience with ALK testing. 27 oncologists provided data on 273 ALK+ NSCLC patients. Patients' median age was 67 years upon NSCLC diagnosis. Smoking history varied, with 33% nonsmokers, 33% light smokers, and 33% heavy smokers. Patients were racially diverse: 59% White, 18% Black, 13% Asian, and 10% other. Upon diagnosis of advanced/metastatic NSCLC, patients who were either not tested (19%) or initially tested negative/inconclusive (1%) all received first-line chemotherapy; the other 219 patients (80%) tested positive, with 133 (61%) receiving an ALK inhibitor and 78 (29%) receiving chemotherapy as first-line treatment. Many oncologists stated being more likely to test for ALK rearrangements among Asians, nonsmokers, and light smokers. In this sample, ALK+ NSCLC patients were racially diverse with mixed smoking history. One in five patients were not tested before first-line therapy. Oncologists reported being more likely to consider ALK testing for patients with particular smoking and race characteristics. Copyright © 2015 Elsevier Ltd. All rights reserved.

Failover Switching Tests Between Two RF Communications Links

NASA Technical Reports Server (NTRS)

Brooks, David; Frantz, Brian; Hoder, Doug; Wilkins, Ryan

2003-01-01

This work presents a short report on the routing tests of the Ku band satcom and VHF line-of-sight communications systems on the Advanced Air Transportation Technologies (AATT) Aero/Mobile van. The first section is a description of the equipment used, followed by descriptions of the tests, the theoretical results, and finally, conclusions and the actual data.

Staged-Fault Testing of Distance Protection Relay Settings

NASA Astrophysics Data System (ADS)

Havelka, J.; Malarić, R.; Frlan, K.

2012-01-01

In order to analyze the operation of the protection system during induced fault testing in the Croatian power system, a simulation using the CAPE software has been performed. The CAPE software (Computer-Aided Protection Engineering) is expert software intended primarily for relay protection engineers, which calculates current and voltage values during faults in the power system, so that relay protection devices can be properly set up. Once the accuracy of the simulation model had been confirmed, a series of simulations were performed in order to obtain the optimal fault location to test the protection system. The simulation results were used to specify the test sequence definitions for the end-to-end relay testing using advanced testing equipment with GPS synchronization for secondary injection in protection schemes based on communication. The objective of the end-to-end testing was to perform field validation of the protection settings, including verification of the circuit breaker operation, telecommunication channel time and the effectiveness of the relay algorithms. Once the end-to-end secondary injection testing had been completed, the induced fault testing was performed with three-end lines loaded and in service. This paper describes and analyses the test procedure, consisting of CAPE simulations, end-to-end test with advanced secondary equipment and staged-fault test of a three-end power line in the Croatian transmission system.

33 CFR 334.260 - York River, Va.; naval restricted areas.

Code of Federal Regulations, 2014 CFR

2014-07-01

....; naval restricted areas. (a) The areas—(1) Naval mine service-testing area (prohibited). A rectangular...; and thence along the shore line to the point of beginning. (2) Naval mine service-testing area... case of emergency. Naval authorities are required to publish advance notice of mine-laying and/or...

33 CFR 334.260 - York River, Va.; naval restricted areas.

Code of Federal Regulations, 2013 CFR

2013-07-01

....; naval restricted areas. (a) The areas—(1) Naval mine service-testing area (prohibited). A rectangular...; and thence along the shore line to the point of beginning. (2) Naval mine service-testing area... case of emergency. Naval authorities are required to publish advance notice of mine-laying and/or...

Design philosophy of the Jet Propulsion Laboratory infrared detector test facility

NASA Technical Reports Server (NTRS)

Burns, R.; Blessinger, M. A.

1983-01-01

To support the development of advanced infrared remote sensing instrumentation using line and area arrays, a test facility has been developed to characterize the detectors. The necessary performance characteristics of the facility were defined by considering current and projected requirements for detector testing. The completed facility provides the desired level of detector testing capability as well as providing ease of human interaction.

Radiation-hardened microwave communications system

NASA Astrophysics Data System (ADS)

Smith, S. F.; Bible, D. W.; Crutcher, R. I.; Hannah, J. H.; Moore, J. A.; Nowlin, C. H.; Vandermolen, R. I.; Chagnot, D.; Leroy, A.

1993-03-01

To develop a wireless communication system to meet the stringent requirements for a nuclear hot cell and similar environments, including control of advanced servomanipulators, a microwave signal transmission system development program was established to produce a demonstration prototype for the Consolidated Fuel Reprocessing Program at Oak Ridge National Laboratory (ORNL). Proof-of-principle tests in a partially metal lined enclosure at ORNL successfully demonstrated the feasibility of directed microwave signal transmission techniques for remote systems applications. The potential for much more severe radio-frequency (RF) multipath propagation conditions in fully metal lined cells led to a programmatic decision to conduct additional testing in more typical hot-cell environments at other sites. Again, the test results were excellent. Based on the designs of the earlier systems, an advanced microwave signal transmission system configuration was subsequently developed that, in highly reflective environments, will support both high-performance video channels and high baud-rate digital data links at total gamma dose tolerance levels exceeding 10(exp 7) rads and at elevated ambient temperatures.

ANIMAL COGNITION. Comment on "Number-space mapping in the newborn chick resembles humans' mental number line".

PubMed

Harshaw, Christopher

2015-06-26

Rugani et al. (Reports, 30 January 2015, p. 534) presented evidence that domestic chicks employ a "mental number line." I argue that the hypothesis testing used to support this claim unjustifiably assumes that domestic chicks are unbiased when choosing between identical stimuli presented to their left and right. Copyright © 2015, American Association for the Advancement of Science.

New test techniques and analytical procedures for understanding the behavior of advanced propellers

NASA Technical Reports Server (NTRS)

Stefko, G. L.; Bober, L. J.; Neumann, H. E.

1983-01-01

Analytical procedures and experimental techniques were developed to improve the capability to design advanced high speed propellers. Some results from the propeller lifting line and lifting surface aerodynamic analysis codes are compared with propeller force data, probe data and laser velocimeter data. In general, the code comparisons with data indicate good qualitative agreement. A rotating propeller force balance demonstrated good accuracy and reduced test time by 50 percent. Results from three propeller flow visualization techniques are shown which illustrate some of the physical phenomena occurring on these propellers.

Where Should We Go With Advanced Placement?

NASA Astrophysics Data System (ADS)

Lichten, William

2001-04-01

This is a review of the Advanced Placement (AP)Program. In disagreement with claims of the College Board, there is firm evidence that the average test performance level has dropped. The College Board's scale and claims for AP qualification disagree seriously with college standards. A majority of tests taken do not qualify. It appears that "advanced placement" is coming closer to "placement." This paper recommends that the College Board's policy, which previously has concentrated on the numbers of participants, should include an emphasis on student performance and program quality. AP could accomplish its goal of reaching a wider range of students by changing along the lines followed in college introductory physics courses: multiple tracks.

Genomic Prediction of Seed Quality Traits Using Advanced Barley Breeding Lines.

PubMed

Nielsen, Nanna Hellum; Jahoor, Ahmed; Jensen, Jens Due; Orabi, Jihad; Cericola, Fabio; Edriss, Vahid; Jensen, Just

2016-01-01

Genomic selection was recently introduced in plant breeding. The objective of this study was to develop genomic prediction for important seed quality parameters in spring barley. The aim was to predict breeding values without expensive phenotyping of large sets of lines. A total number of 309 advanced spring barley lines tested at two locations each with three replicates were phenotyped and each line was genotyped by Illumina iSelect 9Kbarley chip. The population originated from two different breeding sets, which were phenotyped in two different years. Phenotypic measurements considered were: seed size, protein content, protein yield, test weight and ergosterol content. A leave-one-out cross-validation strategy revealed high prediction accuracies ranging between 0.40 and 0.83. Prediction across breeding sets resulted in reduced accuracies compared to the leave-one-out strategy. Furthermore, predicting across full and half-sib-families resulted in reduced prediction accuracies. Additionally, predictions were performed using reduced marker sets and reduced training population sets. In conclusion, using less than 200 lines in the training set can result in low prediction accuracy, and the accuracy will then be highly dependent on the family structure of the selected training set. However, the results also indicate that relatively small training sets (200 lines) are sufficient for genomic prediction in commercial barley breeding. In addition, our results indicate a minimum marker set of 1,000 to decrease the risk of low prediction accuracy for some traits or some families.

Genomic Prediction of Seed Quality Traits Using Advanced Barley Breeding Lines

PubMed Central

Nielsen, Nanna Hellum; Jahoor, Ahmed; Jensen, Jens Due; Orabi, Jihad; Cericola, Fabio; Edriss, Vahid; Jensen, Just

2016-01-01

Genomic selection was recently introduced in plant breeding. The objective of this study was to develop genomic prediction for important seed quality parameters in spring barley. The aim was to predict breeding values without expensive phenotyping of large sets of lines. A total number of 309 advanced spring barley lines tested at two locations each with three replicates were phenotyped and each line was genotyped by Illumina iSelect 9Kbarley chip. The population originated from two different breeding sets, which were phenotyped in two different years. Phenotypic measurements considered were: seed size, protein content, protein yield, test weight and ergosterol content. A leave-one-out cross-validation strategy revealed high prediction accuracies ranging between 0.40 and 0.83. Prediction across breeding sets resulted in reduced accuracies compared to the leave-one-out strategy. Furthermore, predicting across full and half-sib-families resulted in reduced prediction accuracies. Additionally, predictions were performed using reduced marker sets and reduced training population sets. In conclusion, using less than 200 lines in the training set can result in low prediction accuracy, and the accuracy will then be highly dependent on the family structure of the selected training set. However, the results also indicate that relatively small training sets (200 lines) are sufficient for genomic prediction in commercial barley breeding. In addition, our results indicate a minimum marker set of 1,000 to decrease the risk of low prediction accuracy for some traits or some families. PMID:27783639

Prioritizing molecular markers to test for in the initial workup of advanced non-small cell lung cancer: wants versus needs.

PubMed

West, Howard

2017-09-01

The current standard of care for molecular marker testing in patients with advanced non-small cell lung cancer (NSCLC) has been evolving over several years and is a product of the quality of the evidence supporting a targeted therapy for a specific molecular marker, the pre-test probability of that marker in the population, and the magnitude of benefit seen with that treatment. Among the markers that have one or more matched targeted therapies, only a few are in the subset for which they should be considered as most clearly worthy of prioritizing to detect in the first line setting in order to have them supplant other first line alternatives, and in only a subset of patients, as defined currently by NSCLC histology. Specifically, this currently includes testing for an activating epidermal growth factor receptor ( EGFR ) mutation or an anaplastic lymphoma kinase ( ALK ) or ROS1 rearrangement. This article reviews the history and data supporting the prioritization of these markers in patients with non-squamous NSCLC, a histologically selected population in whom the probability of these markers combined with the anticipated efficacy of targeted therapies against them is high enough to favor these treatments in the first line setting. In reviewing the evidence supporting this very limited core subset of most valuable molecular markers to detect in the initial workup of such patients, we can also see the criteria by which other actionable markers need to reach in order to be widely recognized as reliably valuable enough to warrant prioritization to detect in the initial workup of advanced NSCLC as well.

Quality by control: Towards model predictive control of mammalian cell culture bioprocesses.

PubMed

Sommeregger, Wolfgang; Sissolak, Bernhard; Kandra, Kulwant; von Stosch, Moritz; Mayer, Martin; Striedner, Gerald

2017-07-01

The industrial production of complex biopharmaceuticals using recombinant mammalian cell lines is still mainly built on a quality by testing approach, which is represented by fixed process conditions and extensive testing of the end-product. In 2004 the FDA launched the process analytical technology initiative, aiming to guide the industry towards advanced process monitoring and better understanding of how critical process parameters affect the critical quality attributes. Implementation of process analytical technology into the bio-production process enables moving from the quality by testing to a more flexible quality by design approach. The application of advanced sensor systems in combination with mathematical modelling techniques offers enhanced process understanding, allows on-line prediction of critical quality attributes and subsequently real-time product quality control. In this review opportunities and unsolved issues on the road to a successful quality by design and dynamic control implementation are discussed. A major focus is directed on the preconditions for the application of model predictive control for mammalian cell culture bioprocesses. Design of experiments providing information about the process dynamics upon parameter change, dynamic process models, on-line process state predictions and powerful software environments seem to be a prerequisite for quality by control realization. © 2017 The Authors. Biotechnology Journal published by WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Peanut variety tests

USDA-ARS?s Scientific Manuscript database

State-wide peanut variety trials were conducted in three Oklahoma locations. Performance of runner, Spanish, and Virginia entries were assessed. Performance of runner varieties depended on location but averages across locations indicate that advanced breeding line ARSOK R47A was the top performer....

Simulation and measurement of the electrostatic beam kicker in the low-energy undulator test line.

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

Waldschmidt, G. J.

1998-10-27

An electrostatic kicker has been constructed for use in the Low-Energy Undulator Test Line (LEUTL) at the Advanced Photon Source (APS). The function of the kicker is to limit the amount of beam current to be accelerated by the APS linac. Two electrodes within the kicker create an electric field that adjusts the trajectory of the beam. This paper will explore the static fields that are set up between the offset electrode plates and determine the reaction of the beam to this field. The kicker was numerically simulated using the electromagnetic solver package MAFIA [1].

Broadband, high-resolution investigation of advanced absorption line shapes at high temperature

NASA Astrophysics Data System (ADS)

Schroeder, Paul J.; Cich, Matthew J.; Yang, Jinyu; Swann, William C.; Coddington, Ian; Newbury, Nathan R.; Drouin, Brian J.; Rieker, Gregory B.

2017-08-01

Spectroscopic studies of planetary atmospheres and high-temperature processes (e.g., combustion) require absorption line-shape models that are accurate over extended temperature ranges. To date, advanced line shapes, like the speed-dependent Voigt and Rautian profiles, have not been tested above room temperature with broadband spectrometers. We investigate pure water vapor spectra from 296 to 1305 K acquired with a dual-frequency comb spectrometer spanning from 6800 to 7200 c m-1 at a point spacing of 0.0033 c m-1 and absolute frequency accuracy of <3.3 ×10-6c m-1 . Using a multispectral fitting analysis, we show that only the speed-dependent Voigt accurately models this temperature range with a single power-law temperature-scaling exponent for the broadening coefficients. Only the data from the analysis using this profile fall within theoretical predictions, suggesting that this mechanism captures the dominant narrowing physics for these high-temperature conditions.

Advanced CFD Methods for Hypervelocity Wind Tunnels

DTIC Science & Technology

2011-03-10

Mach 14 nozzle produces non-uniformities in the test section flow that are not desirable [1,2]. Calibration runs with Pitot pressure rakes suggest...flows is presented. The grid is based on the characteristic lines of the supersonic regions of the flow. This allows for grid alignment and clustering...novel grid generation scheme for hypersonic nozzle flows is presented. The grid is based on the characteristic lines of the supersonic regions of the

Efficacy of icotinib versus traditional chemotherapy as first-line treatment for preventing brain metastasis from advanced lung adenocarcinoma in patients with epidermal growth factor receptor-sensitive mutation.

PubMed

Zhao, Xiao; Zhu, Guangqin; Chen, Huoming; Yang, Ping; Li, Fang; Du, Nan

2016-01-01

This study aimed to investigate the potential use of icotinib as first-line treatment to prevent brain metastasis from advanced lung adenocarcinoma. This investigation was designed as a retrospective nonrandomized controlled study. Enrolled patients received either icotinib or traditional chemotherapy as their first-line treatment. The therapeutic efficacy was compared among patients with advanced. (stages IIIB and IV) lung adenocarcinoma with epidermal growth factor receptor (EGFR)-sensitive mutation. The primary endpoint was the cumulative incidence of brain metastasis, whereas, the secondary endpoint was overall survival(OS). Death without brain metastasis was considered a competitive risk to calculate the cumulative risk of brain metastasis. Survival analysis was conducted using the Kaplan-Meier method and statistical significance was determined using the log-rank test. The present study included 396 patients with 131 in the icotinib group and 265 in the chemotherapy group. Among those with EGFR-sensitive mutation, the cumulative risk of brain metastasis was lower in the icotinib group than in the chemotherapy group. However, no significant difference in OS was observed between the two groups. Icotinib can effectively reduce the incidence of brain metastasis and therefore improve prognosis in advanced lung adenocarcinoma patients with EGFR.sensitive mutation.

Efficacy of icotinib versus traditional chemotherapy as first-line treatment for preventing brain metastasis from advanced lung adenocarcinoma in patients with epidermal growth factor receptor-sensitive mutation.

PubMed

Zhao, Xiao; Zhu, Guangqin; Chen, Huoming; Yang, Ping; Li, Fang; Du, Nan

2014-11-01

This study aimed to investigate the potential use of icotinib as first-line treatment to prevent brain metastasis from advanced lung adenocarcinoma. This investigation was designed as a retrospective nonrandomized controlled study. Enrolled patients received either icotinib or traditional chemotherapy as their first-line treatment. The therapeutic efficacy was compared among patients with advanced (stages IIIB and IV) lung adenocarcinoma with epidermal growth factor receptor (EGFR)-sensitive mutation. The primary endpoint was the cumulative incidence of brain metastasis, whereas the secondary endpoint was overall survival (OS). Death without brain metastasis was considered a competitive risk to calculate the cumulative risk of brain metastasis. Survival analysis was conducted using the Kaplan-Meier method and statistical significance were determined using the log-rank test. The present study included 396 patients with 131 in the icotinib group and 265 in the chemotherapy group. Among those with EGFR-sensitive mutation, the cumulative risk of brain metastasis was lower in the icotinib group than in the chemotherapy group. However, no significant difference in OS was observed between the two groups. Icotinib can effectively reduce the incidence of brain metastasis and therefore improve prognosis in advanced lung adenocarcinoma patients with EGFR-sensitive mutation.

Disease management patterns for postmenopausal women in Europe with hormone-receptor-positive, human epidermal growth factor receptor-2 negative advanced breast cancer.

PubMed

André, Fabrice; Neven, Patrick; Marinsek, Nina; Zhang, Jie; Baladi, Jean-Francois; Degun, Ravi; Benelli, Giancarlo; Saletan, Stephen; Jerusalem, Guy

2014-06-01

International guidelines for hormone-receptor-positive (HR(+)), human epidermal growth factor receptor-2 negative (HER2(-)) advanced breast cancer (BC) recommend sequential lines of hormonal therapy (HT), and only recommend chemotherapy for patients with extensive visceral involvement or rapidly progressive disease. This study evaluated actual physician-reported treatments for advanced BC in Europe. We conducted a retrospective chart review of 355 postmenopausal women with HR(+), HER2(-) advanced BC who progressed on ≥1 line of HT (adjuvant or advanced) and completed ≥1 line of chemotherapy (advanced). Treatment choice was evaluated for each line of therapy. Of 355 patients, 111 (31%) received first-line chemotherapy, whereas 218 (61%) and 26 (7%) switched from HT to chemotherapy in second and third line, respectively. More patients receiving first-line HT had bone metastases (73% vs 27% chemotherapy). Patients treated with first-line chemotherapy had more brain (12% vs 3% HT) or extensive liver (13% vs 6% HT) metastases. Subgroup analysis of 188 patients who received first-line HT and had de novo advanced BC or relapsed/recurrent disease more than 1 year after adjuvant therapy found that the majority (89%; n = 167) of these patients switched to chemotherapy in second line. However, among these 167 patients, 27% had no significant changes in metastases between first and second line. Among the 73% of patients who had significant changes in metastases, 20% had no brain metastases or extensive visceral disease. Our study suggests that the guideline-recommended use of multiple HT lines is open to interpretation and that optimal treatment for European postmenopausal women with HR(+), HER2(-) advanced BC who responded to HT may not be achieved.

An Assessment of Early Competitive Prototyping for Major Defense Acquisition Programs

DTIC Science & Technology

2016-04-30

with 20/80 share ratio for EMD; CPFF for test execution. o Percent change in PAUC from development baseline. -2.3%. 3. FAB -T–FET. The Air Force’s...Family of Advanced Beyond Line-of-Sight Terminals ( FAB -T) provides for survivable terminals for communicating strategic nuclear execution orders via...jam-resistant, low probability of intercept waveforms through the Milstar and Advanced Extremely High Frequency (AEHF) satellite constellations. FAB

77 FR 61723 - Felgates Creek and Indian Field Creek Along the York River in Yorktown, VA; Restricted Area

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-11

.... 334.260 York River, Va.; naval restricted areas. (a) The areas--(1) Naval mine service-testing area... thence along the shore line to the point of beginning. (2) Naval mine service-testing area (restricted... delay, except in case of emergency. Naval authorities are required to publish advance notice of mine...

Advancements in Chinese Geomagnetism and Aeronomy during the Last Thirty Years,

DTIC Science & Technology

1981-02-09

movements of charged particles in geomagnetic fields and neutral line magnetic fields and they vigorously initiated simulated tests. References (120-121... telluric prospecting and related probems; (6) Magnetic prospecting and interpretation of data; (7) Some research on geomagnetic instruments; (8

Genetic heterogeneity of RPMI-8402, a T-acute lymphoblastic leukemia cell line

PubMed Central

STOCZYNSKA-FIDELUS, EWELINA; PIASKOWSKI, SYLWESTER; PAWLOWSKA, ROZA; SZYBKA, MALGORZATA; PECIAK, JOANNA; HULAS-BIGOSZEWSKA, KRYSTYNA; WINIECKA-KLIMEK, MARTA; RIESKE, PIOTR

2016-01-01

Thorough examination of genetic heterogeneity of cell lines is uncommon. In order to address this issue, the present study analyzed the genetic heterogeneity of RPMI-8402, a T-acute lymphoblastic leukemia (T-ALL) cell line. For this purpose, traditional techniques such as fluorescence in situ hybridization and immunocytochemistry were used, in addition to more advanced techniques, including cell sorting, Sanger sequencing and massive parallel sequencing. The results indicated that the RPMI-8402 cell line consists of several genetically different cell subpopulations. Furthermore, massive parallel sequencing of RPMI-8402 provided insight into the evolution of T-ALL carcinogenesis, since this cell line exhibited the genetic heterogeneity typical of T-ALL. Therefore, the use of cell lines for drug testing in future studies may aid the progress of anticancer drug research. PMID:26870252

Molecular profiling in Italian patients with advanced non-small-cell lung cancer: An observational prospective study.

PubMed

Gobbini, Elisa; Galetta, Domenico; Tiseo, Marcello; Graziano, Paolo; Rossi, Antonio; Bria, Emilio; Di Maio, Massimo; Rossi, Giulio; Gregorc, Vanesa; Riccardi, Ferdinando; Scotti, Vieri; Ceribelli, Anna; Buffoni, Lucio; Delmonte, Angelo; Franchina, Tindara; Migliorino, Maria Rita; Cortinovis, Diego; Pisconti, Salvatore; Bordi, Paola; Catino, Annamaria; Maiello, Evaristo; Arizio, Francesca; Novello, Silvia

2017-09-01

Molecular profiling of advanced non-small-cell lung cancer (NSCLC) is recommended according to European and Italian guidelines. However, molecular routine assessment remains still heterogeneous. This observational study aimed to take a picture of the real clinical practice in molecular testing and therapeutic choices in advanced Italian NSCLCs. This study prospectively enrolled newly diagnosed advanced or recurrent NSCLCs referred to 38 Italian centres, from November 2014 to November 2015. Information regarding molecular profiling and treatment choices were collected. Description of patients' outcome included overall survival (OS), progression-free survival in first (PFS1) and second-line (PFS2). Among 1787 patients enrolled, 1388 (78%) performed at least one molecular analysis during the history of disease: 76% were tested for EGFR, 53% for ALK, 27% for KRAS, 16% for ROS1, 14% for BRAF, 5% for HER2, 4% for MET and 1% for FGFR. The remaining 399 patients (22.3%) did not receive any molecular test. Among patients receiving at least one molecular analysis, 583 (42%) presented a molecular alteration. Considering EGFR mutated and/or ALK rearranged patients (402), for which target agents were routinely reimbursed at time of study in Italy, the 86% received a personalized treatment as first and/or second line: the 90% (286) of EGFR mutants received an EGFR tyrosine kinase inhibitor, mostly gefitinib (41.1%) or afatinib (36.4%) while 74% (62) of ALK translocated patients received an ALK inhibitor, mostly crizotinib (64%). Median OS was 9.34 months (95% CI 8.62-10.0), median PFS1 was 4.61 months (95%CI 4.31-4.84) and median PFS2 was 2.76 months (95%CI 2.57-3.19). In the Italian clinical practice, routine molecular assessment was largely applied in NSCLC patients, according to national guidelines, but a low level of ALK test was reached. Most of EGFR mutants an ALK rearranged patients received a personalized treatment as first and/or second line. Copyright © 2017 Elsevier B.V. All rights reserved.

[Efficacy of icotinib for advanced non-small cell lung cancer patients with EGFR status identified].

PubMed

Song, Zhengbo; Yu, Xinmin; Cai, Jufen; Shao, Lan; Lin, Baochai; He, Chunxiao; Zhang, Beibei; Zhang, Yiping

2013-03-01

As the first epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) in China, icotinib shows promising anticancer activity in vitro and vivo. The phase III clinical study (ICOGEN) showed that icotinib has a good efficacy and tolerability in Chinese patients with advanced non-small cell lung cancer (NSCLC) compared with gefitinib. This retrospective study aims to evaluate the efficacy and tolerability of icotinib monotherapy for advanced NSCLC patients with EGFR mutation and wild-type patients in our hospital. Patients with advanced NSCLC who were treated with icotinib in Zhejiang Cancer Hospital were retrospectively analyzed from August, 2011 to August, 2012. Survival was estimated using Kaplan-Meier analysis and Log-rank tests. The clinical data of 49 patients (13 with wild-type and 36 with EGFR mutation) with NSCLC were enrolled in the current study. The patients' overall objective response rate (ORR) was 58.3% and the disease control rate (DCR) in 36 EGFR mutation patients was 88.9%. The ORR was 7.7% and DCR was 53.8% in the wild-type patients. Median progression-free survival (PFS) with icotinib treatment in EGFR mutation patients was 9.5 months and 2.2 months in wild-type patients (P<0.001). Nineteen patients with EGFR mutation received icotinib as first-line and 17 in further-line treatment. The PFS was 9.5 months in the first-line and 8.5 months for second-line or further-line patients (P=0.41). Median overall survival (OS) in EGFR mutation patients was not reached, but was 12.6 months in wild-type patients. Most of the drug-related adverse events were mild (grade I or II) and reversible with no grade IV toxicity. Icotinib monotherapy showed significant antitumor activity in advanced NSCLC EGFR mutation patients. The toxicity was well tolerated and acceptable.

ANIMAL COGNITION. Comment on "Number-space mapping in the newborn chick resembles humans' mental number line".

PubMed

Mangalam, Madhur; Karve, Shraddha Madhav

2015-06-26

Rugani et al. (Reports, 30 January 3015, p. 534) tested 3-day-old domestic chicks using an innovative experimental setup and demonstrate the presence of the mental number line. We raise concerns regarding this conclusion by highlighting the possible loopholes in the experimental design and the data analysis procedures. We further suggest auxiliary experiments that can substantiate the authors' claim. Copyright © 2015, American Association for the Advancement of Science.

Health care resource use among patients with advanced non-small cell lung cancer: the PIvOTAL retrospective observational study.

PubMed

Lee, Dae Ho; Isobe, Hiroshi; Wirtz, Hubert; Aleixo, Sabina Bandeira; Parente, Phillip; de Marinis, Filippo; Huang, Min; Arunachalam, Ashwini; Kothari, Smita; Cao, Xiting; Donnini, Nello; Woodgate, Ann-Marie; de Castro, Javier

2018-03-01

Data are scarce regarding real-world health care resource use (HCRU) for non-small cell lung cancer (NSCLC). An understanding of current clinical practices and HCRU is needed to provide a benchmark for rapidly evolving NSCLC management recommendations and therapeutic options. The objective of this study was to describe real-world HCRU for patients with advanced NSCLC. This multinational, retrospective chart review study was conducted at academic and community oncology sites in Italy, Spain, Germany, Australia, Japan, South Korea, Taiwan, and Brazil. Deidentified data were drawn from medical records of 1440 adults (≥18 years old) who initiated systemic therapy (2011 to mid-2013) for a new, confirmed diagnosis of advanced or metastatic (stage IIIB or IV) NSCLC. We summarized HCRU associated with first and subsequent lines of systemic therapy for advanced/metastatic NSCLC. The proportion of patients who were hospitalized at least once varied by country from 24% in Italy to 81% in Japan during first-line therapy and from 22% in Italy to 84% in Japan during second-line therapy; overall hospitalization frequency was 2.5-11.1 per 100 patient-weeks, depending on country. Emergency visit frequency also varied among countries (overall from 0.3-5.9 per 100 patient-weeks), increasing consistently from first- through third-line therapy in each country. The outpatient setting was the most common setting of resource use. Most patients in the study had multiple outpatient visits in association with each line of therapy (overall from 21.1 to 59.0 outpatient visits per 100 patient-weeks, depending on country). The use of health care resources showed no regular pattern associated with results of tests for activating mutations of the epidermal growth factor receptor (EGFR) gene or anaplastic lymphoma kinase (ALK) gene rearrangements. HCRU varied across countries. These findings suggest differing approaches to the clinical management of advanced NSCLC among the eight countries. Comparative findings and an understanding of country-specific clinical practices can help to identify areas of need and guide future resource allocation for patients with advanced NSCLC. Further studies evaluating the costs associated with resource use are warranted.

Clinical management and outcome of patients with advanced NSCLC carrying EGFR mutations in Spain.

PubMed

Arriola, Edurne; García Gómez, Ramón; Diz, Pilar; Majem, Margarita; Martínez Aguillo, Maite; Valdivia, Javier; Paredes, Alfredo; Sánchez-Torres, José Miguel; Peralta Muñoz, Sergio; Barneto, Isidoro; Gutierrez, Vanesa; Andrade Santiago, Jesús Manuel; Aparisi, Francisco; Isla, Dolores; Ponce, Santiago; Vicente Baz, David; Artal, Angel; Amador, Mariluz; Provencio, Mariano

2018-01-30

Although the benefit of first-line epidermal growth factor receptor (EGFR) tyrosine-kinase inhibitors (TKIs) over chemotherapy has been demonstrated in several clinical trials, data from clinical practice is lacking and the optimal EGFR TKI to be used remains unclear. This study aims to assess the real-life diagnostic and clinical management and outcome of patients with advanced non-small-cell lung cancer (NSCLC) carrying EGFR mutations in Spain. All consecutive patients recently diagnosed with advanced or metastatic NSCLC from April 2010 to December 2011 in 18 Spanish hospitals and carrying EGFR mutations were retrospectively evaluated. Between March and November 2013, a total of 187 patients were enrolled (98.3% Caucasian, 61.9% female, 54.9% never-smokers, 89.0% adenocarcinoma). Mutation testing was mainly performed on biopsy tumour tissue specimens (69.0%) using a qPCR-based test (90%) (47.0% Therascreen EGFR PCR Kit). Common sensitising mutations were detected in 79.8% of patients: 57.1% had exon 19 deletions and 22.6% exon 21 L858R point mutations. The vast majority of patients received first-line therapy (n = 168; 92.8%). EGFR TKIs were the most commonly used first-line treatment (81.5%), while chemotherapy was more frequently administered as a second- and third-line option (51.9% and 56.0%, respectively). Of 141 patients who experienced disease progression, 79 (56.0%) received second-line treatment. After disease progression on first-line TKIs (n = 112), 33.9% received chemotherapy, 8.9% chemotherapy and a TKI, and 9.8% continued TKI therapy. Most patients received first-line gefitinib (83.0%), while erlotinib was more frequently used in the second-line setting (83.0%). Progression-free survival (PFS) and overall survival (OS) in patients harbouring common mutations were 11.1 months and 20.1 months respectively (exon 19 deletions: 12.4 and 21.4 months; L858R: 8.3 and 14.5 months), and 3.9 months and 11.1 months respectively for those with rare mutations. EGFR TKIs (gefitinib and erlotinib) are used as the preferred first-line treatment while chemotherapy is more frequently administered as a second- and third-line option in routine clinical practice in Spain. In addition, efficacy data obtained in the real-life setting seem to concur with data from EGFR TKI phase III pivotal studies in NSCLC.

Technologies as Rural Special Education Problem Solvers--A Status Report and Successful Strategies.

ERIC Educational Resources Information Center

Helge, Doris

Rural schools can help solve their special education problems by using advanced technology to provide instructional support (computer managed instruction, satellite television, library searches, resource networks, on-line testing), instructional applications (computer assisted instruction, reading machines, mobile vans, instructional television),…

Advanced EMI Models and Classification Algorithms: The Next Level of Sophistication to Improve Discrimination of Challenging Targets

DTIC Science & Technology

2017-01-01

Inverted effective ONVMS for an M30 Bomb in a test-stand scenario. The target is oriented 45 degrees at a depth of 150 cm depth (top) and oriented...vertically at a depth of 210 cm (bottom). The red lines are the total ONVMS for a library AN M30 Bomb , and the other lines correspond to the...Centimeter DE Differential Evolution DLL Dynamic Link Libraries DoD Department of Defense EM Electromagnetic EMA Expectation

SST Technology Follow-On Program - Phase 2. Noise Suppressor/Nozzle Development. Volume 5. Advanced Suppressor Concepts and Full Scale Tests

DTIC Science & Technology

1975-03-01

Approved for U.S. Government only. This docu- ment is exempted from public availability be- cause of restrictions imposed by the Export Con- trol Act...Transmittal of this document outside the U.S. Government must have prior approval of the Supersonic Transport Office. 20 Security Classif (of this...linings may be determined by comparing nozzle/ejector radiated noise power levels between the unlined (hardwall) ejector case and the lined ejector

Screening of Wheat Genotypes for Boron Efficiency in Bangladesh

USDA-ARS?s Scientific Manuscript database

A number of Bangladeshi wheat genotypes (varieties and advanced lines) have been tested for boron efficiency through sand culture experiments over two years (2007-08 & 2008-09) against two Thai check varieties ‘Fang 60’ (boron efficient) and ‘SW41’ (boron inefficient). Performances of the genotypes ...

Advancement and results in hostile fire indication using potassium line missile warning sensors

NASA Astrophysics Data System (ADS)

Montgomery, Joel; Montgomery, Marjorie; Hardie, Russell

2014-06-01

M&M Aviation has been developing and conducting Hostile Fire Indication (HFI) tests using potassium line emission sensors for the Air Force Visible Missile Warning System (VMWS) to advance both algorithm and sensor technologies for UAV and other airborne systems for self protection and intelligence purposes. Work began in 2008 as an outgrowth of detecting and classifying false alarm sources for the VMWS using the same K-line spectral discrimination region but soon became a focus of research due to the high interest in both machine-gun fire and sniper geo-location via airborne systems. Several initial tests were accomplished in 2009 using small and medium caliber weapons including rifles. Based on these results, the Air Force Research Laboratory (AFRL) funded the Falcon Sentinel program in 2010 to provide for additional development of both the sensor concept, algorithm suite changes and verification of basic phenomenology including variance based on ammunition type for given weapons platform. Results from testing over the past 3 years have showed that the system would be able to detect and declare a sniper rifle at upwards of 3km, medium machine gun at 5km, and explosive events like hand-grenades at greater than 5km. This paper will outline the development of the sensor systems, algorithms used for detection and classification, and test results from VMWS prototypes as well as outline algorithms used for the VMWS. The Falcon Sentinel Program will be outlined and results shown. Finally, the paper will show the future work for ATD and transition efforts after the Falcon Sentinel program completed.

Automated detection of jet contrails using the AVHRR split window

NASA Technical Reports Server (NTRS)

Engelstad, M.; Sengupta, S. K.; Lee, T.; Welch, R. M.

1992-01-01

This paper investigates the automated detection of jet contrails using data from the Advanced Very High Resolution Radiometer. A preliminary algorithm subtracts the 11.8-micron image from the 10.8-micron image, creating a difference image on which contrails are enhanced. Then a three-stage algorithm searches the difference image for the nearly-straight line segments which characterize contrails. First, the algorithm searches for elevated, linear patterns called 'ridges'. Second, it applies a Hough transform to the detected ridges to locate nearly-straight lines. Third, the algorithm determines which of the nearly-straight lines are likely to be contrails. The paper applies this technique to several test scenes.

A Summary of the Naval Postgraduate School Research Program.

DTIC Science & Technology

1982-05-01

and testing of PCM modu- lation formats, design and test of an underwater video line using a diver’s handheld camera and bi-directional interconnection...to design and develop advanced control schemes which successfully optimize the tor- pedo steering performance for Project Courageous. cummary: Work...investigating the feasibility and design of fiber optic communications in underwater torpedo ranges. Summary: An underwater fiber optic video uplink was

Non-CAR resists and advanced materials for Massively Parallel E-Beam Direct Write process integration

NASA Astrophysics Data System (ADS)

Pourteau, Marie-Line; Servin, Isabelle; Lepinay, Kévin; Essomba, Cyrille; Dal'Zotto, Bernard; Pradelles, Jonathan; Lattard, Ludovic; Brandt, Pieter; Wieland, Marco

2016-03-01

The emerging Massively Parallel-Electron Beam Direct Write (MP-EBDW) is an attractive high resolution high throughput lithography technology. As previously shown, Chemically Amplified Resists (CARs) meet process/integration specifications in terms of dose-to-size, resolution, contrast, and energy latitude. However, they are still limited by their line width roughness. To overcome this issue, we tested an alternative advanced non-CAR and showed it brings a substantial gain in sensitivity compared to CAR. We also implemented and assessed in-line post-lithographic treatments for roughness mitigation. For outgassing-reduction purpose, a top-coat layer is added to the total process stack. A new generation top-coat was tested and showed improved printing performances compared to the previous product, especially avoiding dark erosion: SEM cross-section showed a straight pattern profile. A spin-coatable charge dissipation layer based on conductive polyaniline has also been tested for conductivity and lithographic performances, and compatibility experiments revealed that the underlying resist type has to be carefully chosen when using this product. Finally, the Process Of Reference (POR) trilayer stack defined for 5 kV multi-e-beam lithography was successfully etched with well opened and straight patterns, and no lithography-etch bias.

Novel Corrosion Sensor for Vision 21 Systems

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

Heng Ban; Bharat Soni

2007-03-31

Advanced sensor technology is identified as a key component for advanced power systems for future energy plants that would have virtually no environmental impact. This project intends to develop a novel high temperature corrosion sensor and subsequent measurement system for advanced power systems. Fireside corrosion is the leading mechanism for boiler tube failures and has emerged to be a significant concern for current and future energy plants due to the introduction of technologies targeting emissions reduction, efficiency improvement, or fuel/oxidant flexibility. Corrosion damage can lead to catastrophic equipment failure, explosions, and forced outages. Proper management of corrosion requires real-time indicationmore » of corrosion rate. However, short-term, on-line corrosion monitoring systems for fireside corrosion remain a technical challenge to date due to the extremely harsh combustion environment. The overall goal of this project is to develop a technology for on-line fireside corrosion monitoring. This objective is achieved by the laboratory development of sensors and instrumentation, testing them in a laboratory muffle furnace, and eventually testing the system in a coal-fired furnace. This project successfully developed two types of sensors and measurement systems, and successful tested them in a muffle furnace in the laboratory. The capacitance sensor had a high fabrication cost and might be more appropriate in other applications. The low-cost resistance sensor was tested in a power plant burning eastern bituminous coals. The results show that the fireside corrosion measurement system can be used to determine the corrosion rate at waterwall and superheater locations. Electron microscope analysis of the corroded sensor surface provided detailed picture of the corrosion process.« less

Wrapped Multilayer Insulation

NASA Technical Reports Server (NTRS)

Dye, Scott A.

2015-01-01

New NASA vehicles, such as Earth Departure Stage (EDS), Orion, landers, and orbiting fuel depots, need improved cryogenic propellant transfer and storage for long-duration missions. Current cryogen feed line multilayer insulation (MLI) performance is 10 times worse per area than tank MLI insulation. During each launch, cryogenic piping loses approximately 150,000 gallons (equivalent to $300,000) in boil-off during transfer, chill down, and ground hold. Quest Product Development Corp., teaming with Ball Aerospace, developed an innovative advanced insulation system, Wrapped MLI (wMLI), to provide improved thermal insulation for cryogenic feed lines. wMLI is high-performance multilayer insulation designed for cryogenic piping. It uses Quest's innovative discrete-spacer technology to control layer spacing/ density and reduce heat leak. The Phase I project successfully designed, built, and tested a wMLI prototype with a measured heat leak 3.6X lower than spiral-wrapped conventional MLI widely used for piping insulation. A wMLI prototype had a heat leak of 7.3 W/sq m, or 27 percent of the heat leak of conventional MLI (26.7 W/sq m). The Phase II project is further developing wMLI technology with custom, molded polymer spacers and advancing the product toward commercialization via a rigorous testing program, including developing advanced vacuuminsulated pipe for ground support equipment.

Wrapped Multilayer Insulation

NASA Technical Reports Server (NTRS)

Dye, Scott A.

2015-01-01

New NASA vehicles, such as Earth Departure Stage (EDS), Orion, landers, and orbiting fuel depots, need improved cryogenic propellant transfer and storage for long-duration missions. Current cryogen feed line multilayer insulation (MLI) performance is 10 times worse per area than tank MLI insulation. During each launch, cryogenic piping loses approximately 150,000 gallons (equivalent to $300,000) in boil-off during transfer, chill down, and ground hold. Quest Product Development Corp., teaming with Ball Aerospace, developed an innovative advanced insulation system, Wrapped MLI (wMLI), to provide improved thermal insulation for cryogenic feed lines. wMLI is high-performance multilayer insulation designed for cryogenic piping. It uses Quest's innovative discrete-spacer technology to control layer spacing/ density and reduce heat leak. The Phase I project successfully designed, built, and tested a wMLI prototype with a measured heat leak 3.6X lower than spiral-wrapped conventional MLI widely used for piping insulation. A wMLI prototype had a heat leak of 7.3 W/m2, or 27 percent of the heat leak of conventional MLI (26.7 W/m2). The Phase II project is further developing wMLI technology with custom, molded polymer spacers and advancing the product toward commercialization via a rigorous testing program, including developing advanced vacuuminsulated pipe for ground support equipment.

Memorising Milton's Paradise lost: a study of a septuagenarian exceptional memoriser.

PubMed

Seamon, John G; Punjabi, Paawan V; Busch, Emily A

2010-07-01

At age 58, JB began memorising Milton's epic poem Paradise Lost. Nine years and thousands of study hours later, he completed this process in 2001 and recalled from memory all 12 books of this 10,565-line poem over a 3-day period. Now 74, JB continues to recite this work. We tested his memory accuracy by cueing his recall with two lines from the beginning or middle of each book and asking JB to recall the next 10 lines. JB is an exceptional memoriser of Milton, both in our laboratory tests in which he did not know the specific tests or procedures in advance, and in our analysis of a videotaped, prepared performance. Consistent with deliberate practice theory, JB achieved this remarkable ability by deeply analysing the poem's structure and meaning over lengthy repetitions. Our findings suggest that exceptional memorisers such as JB are made, not born, and that cognitive expertise can be demonstrated even in later adulthood.

Economic evaluation of first-line and maintenance treatments for advanced non-small cell lung cancer: a systematic review.

PubMed

Chouaïd, Christos; Crequit, Perinne; Borget, Isabelle; Vergnenegre, Alain

2015-01-01

During these last years, there have been an increased number of new drugs for non-small cell lung cancer (NSCLC), with a growing financial effect on patients and society. The purpose of this article was to review the economics of first-line and maintenance NSCLC treatments. We reviewed economic analyses of NSCLC therapies published between 2004 and 2014. In first-line settings, in unselected patients with advanced NSCLC, the cisplatin gemcitabine doublet appears to be cost-saving compared with other platinum doublets. In patients with nonsquamous NSCLC, the incremental cost-effectiveness ratios (ICERs) per life-year gained (LYG) were $83,537, $178,613, and more than $300,000 for cisplatin-pemetrexed compared with, respectively, cisplatin-gemcitabine, cisplatin-carboplatin-paclitaxel, and carboplatin-paclitaxel-bevacizumab. For all primary chemotherapy agents, use of carboplatin is associated with slightly higher costs than cisplatin. In all the analysis, bevacizumab had an ICER greater than $150,000 per quality-adjusted life-year (QALY). In epidermal growth factor receptor mutated advanced NSCLC, compared with carboplatin-paclitaxel doublet, targeted therapy based on testing available tissue yielded an ICER of $110,644 per QALY, and the rebiopsy strategy yielded an ICER of $122,219 per QALY. Compared with the triplet carboplatin-paclitaxel-bevacizumab, testing and rebiopsy strategies had ICERs of $25,547 and $44,036 per QALY, respectively. In an indirect comparison, ICERs per LYG and QALY of erlotinib versus gefitinib were $39,431 and $62,419, respectively. In anaplastic lymphoma kinase-positive nonsquamous advanced NSCLC, the ICER of first-line crizotinib compared with that of chemotherapy was $255,970 per QALY. For maintenance therapy, gefitinib had an ICER of $19,214 per QALY, erlotinib had an ICER of $127,343 per LYG, and pemetrexed had an ICER varying between $183,589 and $205,597 per LYG. Most recent NSCLC strategies are based on apparently no cost-effective strategies if we consider an ICER below $50,000 per QALY an acceptable threshold. We need, probably on a countrywide level, to have a debate involving public health organizations and pharmaceutical companies, as well as clinicians and patients, to challenge the rising costs of managing lung cancer.

SunLine Transit Agency Advanced Technology Fuel Cell Bus Evaluation: Fourth Results Report

DOT National Transportation Integrated Search

2013-01-01

SunLine Transit Agency provides public transit services to the Coachella Valley area of California. SunLine has demonstrated hydrogen and fuel cell bus technologies for more than 10 years. In May 2010, SunLine began demonstrating the advanced technol...

Combination Therapy with Capecitabine and Cisplatin as Second-Line Chemotherapy for Advanced Biliary Tract Cancer.

PubMed

Jung, Jang Han; Lee, Hee Seung; Jo, Jung Hyun; Cho, In Rae; Chung, Moon Jae; Bang, Seungmin; Park, Seung Woo; Song, Si Young; Park, Jeong Youp

2017-01-01

Palliative chemotherapy is the main treatment for advanced biliary tract cancer (BTC). However, there is a lack of established second-line chemotherapy to treat disease progression after first-line chemotherapy. We examined combination therapy with capecitabine and cisplatin for advanced BTC as a second-line regimen. We analyzed the medical records of 40 patients diagnosed with BTC who received palliative second-line chemotherapy with capecitabine and cisplatin. The median overall survival from the start of second-line chemotherapy was 6.3 months. The median overall survival from diagnosis was 17.9 months. The median progression-free survival during second-line chemotherapy was 2.3 months. Nine (30%) patients experienced adverse events of grade ≥3. Eastern Cooperative Oncology Group performance score was an independent predictor of adverse events. Combination therapy with capecitabine and cisplatin may be an option for second-line chemotherapy in some of patients with advanced BTC. © 2017 S. Karger AG, Basel.

Mini-Uav LIDAR for Power Line Inspection

NASA Astrophysics Data System (ADS)

Teng, G. E.; Zhou, M.; Li, C. R.; Wu, H. H.; Li, W.; Meng, F. R.; Zhou, C. C.; Ma, L.

2017-09-01

Light detection and ranging (LIDAR) system based on unmanned aerial vehicles (UAVs) recently are in rapid advancement, meanwhile portable and flexible mini-UAV-borne laser scanners have been a hot research field, especially for the complex terrain survey in the mountains and other areas. This study proposes a power line inspection system solution based on mini-UAV-borne LIDAR system-AOEagle, developed by Academy of Opto-Electronics, Chinese Academy of Sciences, which mounted on a Multi-rotor unmanned aerial vehicle for complex terrain survey according to real test. Furthermore, the point cloud data was explored to validate its applicability for power line inspection, in terms of corridor and line laser point clouds; deformation detection of power towers, etc. The feasibility and advantages of AOEagle have been demonstrated by the promising results based on the real-measured data in the field of power line inspection.

Design optimization of RF lines in vacuum environment for the MITICA experiment

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

De Muri, Michela, E-mail: michela.demuri@igi.cnr.it; Consorzio RFX, Corso Stati Uniti, 4, I-35127 Padova; Pavei, Mauro

This contribution regards the Radio Frequency (RF) transmission line of the Megavolt ITER Injector and Concept Advancement (MITICA) experiment. The original design considered copper coaxial lines of 1″ 5/8, but thermal simulations under operating conditions showed maximum temperatures of the lines at regime not compatible with the prescription of the component manufacturer. Hence, an optimization of the design was necessary. Enhancing thermal radiation and increasing the conductor size were considered for design optimization: thermal analyses were carried out to calculate the temperature of MITICA RF lines during operation, as a function of the emissivity value and of other geometrical parameters.more » Five coating products to increase the conductor surface emissivity were tested, measuring the outgassing behavior of the selected products and the obtained emissivity values.« less

Noninvasive prenatal testing in routine clinical practice--an audit of NIPT and combined first-trimester screening in an unselected Australian population.

PubMed

McLennan, Andrew; Palma-Dias, Ricardo; da Silva Costa, Fabricio; Meagher, Simon; Nisbet, Debbie L; Scott, Fergus

2016-02-01

There are limited data regarding noninvasive prenatal testing (NIPT) in low-risk populations, and the ideal aneuploidy screening model for a pregnant population has yet to be established. To assess the implementation of NIPT into clinical practice utilising both first- and second-line screening models. Three private practices specialising in obstetric ultrasound and prenatal diagnosis in Australia offered NIPT as a first-line test, ideally followed by combined first-trimester screening (cFTS), or as a second-line test following cFTS, particularly in those with a calculated risk between 1:50 and 1:1000. NIPT screening was performed in 5267 women and as a first-line screening method in 3359 (63.8%). Trisomies 21 and 13 detection was 100% and 88% for trisomy 18. Of cases with known karyotypes, the positive predictive value (PPV) of the test was highest for trisomy 21 (97.7%) and lowest for monosomy X (25%). Ultrasound detection of fetal structural abnormality resulted in the detection of five additional chromosome abnormalities, two of which had high-risk cFTS results. For all chromosomal abnormalities, NIPT alone detected 93.4%, a contingent model detected 81.8% (P = 0.097), and cFTS alone detected 65.9% (P < 0.005). NIPT achieved 100% T21 detection and had a higher DR of all aneuploidy when used as a first-line test. Given the false-positive rate for all aneuploidies, NIPT is an advanced screening test, rather than a diagnostic test. The benefit of additional cFTS was the detection of fetal structural abnormalities and some unusual chromosomal abnormalities. © 2016 The Royal Australian and New Zealand College of Obstetricians and Gynaecologists.

Conversion-Integration of MSFC Nonlinear Signal Diagnostic Analysis Algorithms for Realtime Execution of MSFC's MPP Prototype System

NASA Technical Reports Server (NTRS)

Jong, Jen-Yi

1996-01-01

NASA's advanced propulsion system Small Scale Magnetic Disturbances/Advanced Technology Development (SSME/ATD) has been undergoing extensive flight certification and developmental testing, which involves large numbers of health monitoring measurements. To enhance engine safety and reliability, detailed analysis and evaluation of the measurement signals are mandatory to assess its dynamic characteristics and operational condition. Efficient and reliable signal detection techniques will reduce the risk of catastrophic system failures and expedite the evaluation of both flight and ground test data, and thereby reduce launch turn-around time. During the development of SSME, ASRI participated in the research and development of several advanced non- linear signal diagnostic methods for health monitoring and failure prediction in turbomachinery components. However, due to the intensive computational requirement associated with such advanced analysis tasks, current SSME dynamic data analysis and diagnostic evaluation is performed off-line following flight or ground test with a typical diagnostic turnaround time of one to two days. The objective of MSFC's MPP Prototype System is to eliminate such 'diagnostic lag time' by achieving signal processing and analysis in real-time. Such an on-line diagnostic system can provide sufficient lead time to initiate corrective action and also to enable efficient scheduling of inspection, maintenance and repair activities. The major objective of this project was to convert and implement a number of advanced nonlinear diagnostic DSP algorithms in a format consistent with that required for integration into the Vanderbilt Multigraph Architecture (MGA) Model Based Programming environment. This effort will allow the real-time execution of these algorithms using the MSFC MPP Prototype System. ASRI has completed the software conversion and integration of a sequence of nonlinear signal analysis techniques specified in the SOW for real-time execution on MSFC's MPP Prototype. This report documents and summarizes the results of the contract tasks; provides the complete computer source code; including all FORTRAN/C Utilities; and all other utilities/supporting software libraries that are required for operation.

Assessing student understanding of measurement and uncertainty

NASA Astrophysics Data System (ADS)

Jirungnimitsakul, S.; Wattanakasiwich, P.

2017-09-01

The objectives of this study were to develop and assess student understanding of measurement and uncertainty. A test has been adapted and translated from the Laboratory Data Analysis Instrument (LDAI) test, consists of 25 questions focused on three topics including measures of central tendency, experimental errors and uncertainties, and fitting regression lines. The test was evaluated its content validity by three physics experts in teaching physics laboratory. In the pilot study, Thai LDAI was administered to 93 freshmen enrolled in a fundamental physics laboratory course. The final draft of the test was administered to three groups—45 freshmen taking fundamental physics laboratory, 16 sophomores taking intermediated physics laboratory and 21 juniors taking advanced physics laboratory at Chiang Mai University. As results, we found that the freshmen had difficulties in experimental errors and uncertainties. Most students had problems with fitting regression lines. These results will be used to improve teaching and learning physics laboratory for physics students in the department.

Functional toxicology: tools to advance the future of toxicity testing

PubMed Central

Gaytán, Brandon D.; Vulpe, Chris D.

2014-01-01

The increased presence of chemical contaminants in the environment is an undeniable concern to human health and ecosystems. Historically, by relying heavily upon costly and laborious animal-based toxicity assays, the field of toxicology has often neglected examinations of the cellular and molecular mechanisms of toxicity for the majority of compounds—information that, if available, would strengthen risk assessment analyses. Functional toxicology, where cells or organisms with gene deletions or depleted proteins are used to assess genetic requirements for chemical tolerance, can advance the field of toxicity testing by contributing data regarding chemical mechanisms of toxicity. Functional toxicology can be accomplished using available genetic tools in yeasts, other fungi and bacteria, and eukaryotes of increased complexity, including zebrafish, fruit flies, rodents, and human cell lines. Underscored is the value of using less complex systems such as yeasts to direct further studies in more complex systems such as human cell lines. Functional techniques can yield (1) novel insights into chemical toxicity; (2) pathways and mechanisms deserving of further study; and (3) candidate human toxicant susceptibility or resistance genes. PMID:24847352

Summary and recent results from the NASA advanced High Speed Propeller Research Program

NASA Technical Reports Server (NTRS)

Mitchell, G. A.; Mikkelson, D. C.

1982-01-01

Advanced high-speed propellers offer large performance improvements for aircraft that cruise in the Mach 0.7 to 0.8 speed regime. The current status of the NASA research program on high-speed propeller aerodynamics, acoustics, and aeroelastics is described. Recent wind tunnel results for five 8- to 10-blade advanced models are compared with analytical predictions. Test results show that blade sweep was important in achieving net efficiencies near 80 percent at Mach 0.8 and reducing near-field cruise noise by dB. Lifting line and lifting surface aerodynamic analysis codes are under development and some initial lifting line results are compared with propeller force and probe data. Some initial laser velocimeter measurements of the flow field velocities of an 8-bladed 45 deg swept propeller are shown. Experimental aeroelastic results indicate that cascade effects and blade sweep strongly affect propeller aeroelastic characteristics. Comparisons of propeller near-field noise data with linear acoustic theory indicate that the theory adequate predicts near-field noise for subsonic tip speeds but overpredicts the noise for supersonic tip speeds. Potential large gains in propeller efficiency of 7 to 11 percent at Mach 0.8 may be possible with advanced counter-rotation propellers.

Investigation of Tapered Roller Bearing Damage Detection Using Oil Debris Analysis

NASA Technical Reports Server (NTRS)

Dempsey, Paula J.; Krieder, Gary; Fichter, Thomas

2006-01-01

A diagnostic tool was developed for detecting fatigue damage to tapered roller bearings. Tapered roller bearings are used in helicopter transmissions and have potential for use in high bypass advanced gas turbine aircraft engines. This diagnostic tool was developed and evaluated experimentally by collecting oil debris data from failure progression tests performed by The Timken Company in their Tapered Roller Bearing Health Monitoring Test Rig. Failure progression tests were performed under simulated engine load conditions. Tests were performed on one healthy bearing and three predamaged bearings. During each test, data from an on-line, in-line, inductance type oil debris sensor was monitored and recorded for the occurrence of debris generated during failure of the bearing. The bearing was removed periodically for inspection throughout the failure progression tests. Results indicate the accumulated oil debris mass is a good predictor of damage on tapered roller bearings. The use of a fuzzy logic model to enable an easily interpreted diagnostic metric was proposed and demonstrated.

Integrated optomechanical analysis and testing software development at MIT Lincoln Laboratory

NASA Astrophysics Data System (ADS)

Stoeckel, Gerhard P.; Doyle, Keith B.

2013-09-01

Advanced analytical software capabilities are being developed to advance the design of prototypical hardware in the Engineering Division at MIT Lincoln Laboratory. The current effort is focused on the integration of analysis tools tailored to the work flow, organizational structure, and current technology demands. These tools are being designed to provide superior insight into the interdisciplinary behavior of optical systems and enable rapid assessment and execution of design trades to optimize the design of optomechanical systems. The custom software architecture is designed to exploit and enhance the functionality of existing industry standard commercial software, provide a framework for centralizing internally developed tools, and deliver greater efficiency, productivity, and accuracy through standardization, automation, and integration. Specific efforts have included the development of a feature-rich software package for Structural-Thermal-Optical Performance (STOP) modeling, advanced Line Of Sight (LOS) jitter simulations, and improved integration of dynamic testing and structural modeling.

Advanced microprocessor based power protection system using artificial neural network techniques

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

Chen, Z.; Kalam, A.; Zayegh, A.

This paper describes an intelligent embedded microprocessor based system for fault classification in power system protection system using advanced 32-bit microprocessor technology. The paper demonstrates the development of protective relay to provide overcurrent protection schemes for fault detection. It also describes a method for power fault classification in three-phase system based on the use of neural network technology. The proposed design is implemented and tested on a single line three phase power system in power laboratory. Both the hardware and software development are described in detail.

Efficiency of low dosage apatinib in post-first-line treatment of advanced lung adenocarcinoma.

PubMed

Zeng, Da-Xiong; Wang, Chang-Guo; Lei, Wei; Huang, Jian-An; Jiang, Jun-Hong

2017-09-12

Chemotherapy is the standard treatment of in advanced lung adenocarcinoma patients without driver mutation. However, few drugs could be selected when diseases progressed after second-line treatment. As a small molecule inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2), apatinib was suggested mainly using in advanced gastric cancer. In this study, we showed the results of apatinib as second-line to fourth-line treatment in EGFR wild-type advanced lung adenocarcinoma patients. 16 EGFR wild-type advanced lung adenocarcinoma patients were administrated apatinib (250-500 mg/d) orally. 3 patients showed partial response and 8 patients showed stable diseases response to apatinib, with a medium progression-free survival (PFS) of 4.4 month (2-10 months). The objective remission rate (ORR) was 18.75%(3/16). The total disease control rate (DCR) was 68.75% (11/16). The main toxicities were hypertension, hand-foot syndrome, proteinuria and thrombocytopenia which were tolerable and manageable. So, apatinib might be an optional choice for post-first-line treatment of EGFR wild-type advanced lung adenocarcinoma patients.

Recent Advancements in the Infrared Flow Visualization System for the NASA Ames Unitary Plan Wind Tunnels

NASA Technical Reports Server (NTRS)

Garbeff, Theodore J., II; Baerny, Jennifer K.

2017-01-01

The following details recent efforts undertaken at the NASA Ames Unitary Plan wind tunnels to design and deploy an advanced, production-level infrared (IR) flow visualization data system. Highly sensitive IR cameras, coupled with in-line image processing, have enabled the visualization of wind tunnel model surface flow features as they develop in real-time. Boundary layer transition, shock impingement, junction flow, vortex dynamics, and buffet are routinely observed in both transonic and supersonic flow regimes all without the need of dedicated ramps in test section total temperature. Successful measurements have been performed on wing-body sting mounted test articles, semi-span floor mounted aircraft models, and sting mounted launch vehicle configurations. The unique requirements of imaging in production wind tunnel testing has led to advancements in the deployment of advanced IR cameras in a harsh test environment, robust data acquisition storage and workflow, real-time image processing algorithms, and evaluation of optimal surface treatments. The addition of a multi-camera IR flow visualization data system to the Ames UPWT has demonstrated itself to be a valuable analyses tool in the study of new and old aircraft/launch vehicle aerodynamics and has provided new insight for the evaluation of computational techniques.

Roscovitine strongly enhances the effect of olaparib on radiosensitivity for HPV neg. but not for HPV pos. HNSCC cell lines.

PubMed

Ziemann, Frank; Seltzsam, Steve; Dreffke, Kristin; Preising, Stefanie; Arenz, Andrea; Subtil, Florentine S B; Rieckmann, Thorsten; Engenhart-Cabillic, Rita; Dikomey, Ekkehard; Wittig, Andrea

2017-12-01

At present, advanced stage human Papillomavirus (HPV) negative and positive head and neck squamous cell carcinoma (HNSCC) are treated by intense multimodal therapy that includes radiochemotherapy, which are associated with relevant side effects. Patients with HPV positive tumors possess a far better prognosis than those with HPV negative cancers. Therefore, new therapeutic strategies are needed to improve the outcome especially of the latter one as well as quality of life for all HNSCC patients. Here we tested whether roscovitine, an inhibitor of cyclin-dependent kinases (CDKs), which hereby also blocks homologous recombination (HR), can be used to enhance the radiation sensitivity of HNSCC cell lines. In all five HPV negative and HPV positive cell lines tested, roscovitine caused inhibition of CDK1 and 2. Surprisingly, all HPV positive cell lines were found to be defective in HR. In contrast, HPV negative strains demonstrated efficient HR, which was completely suppressed by roscovitine. In line with this, for HPV negative but not for HPV positive cell lines, treatment with roscovitine resulted in a pronounced enhancement of the radiation-induced G2 arrest as well as a significant increase in radiosensitivity. Due to a defect in HR, all HPV positive cell lines were efficiently radiosensitized by the PARP-1 inhibitor olaparib. In contrast, in HPV negative cell lines a significant radiosensitization by olaparib was only achieved when combined with roscovitine.

Should EGFR mutations be tested in advanced lung squamous cell carcinomas to guide frontline treatment?

PubMed

Chiu, Chao-Hua; Chou, Teh-Ying; Chiang, Chi-Lu; Tsai, Chun-Ming

2014-10-01

There is no argument over using epidermal growth factor receptor (EGFR) mutation status to guide the frontline treatment for advanced lung adenocarcinoma (LADC); however, the role of the testing in lung squamous cell carcinoma (LSQC) remains controversial. Currently, the guidelines/consensus statements regarding EGFR mutation testing in LSQC are not consistent among different oncology societies. American Society of Clinical Oncology recommends performing EGFR mutation testing in all patients; European Society for Medical Oncology, College of American Pathologists/International Association for the Study of Lung Cancer/Association for Molecular Pathology, and National Comprehensive Cancer Network suggest for some selected group. EGFR mutation is rarely found in LSQC; however, more importantly, it is not a valid predictive biomarker for EGFR tyrosine kinase inhibitors (EGFR-TKI) in LSQC as it has been shown in LADC. Available data showed that the response rate and progression-free survival in EGFR mutant LSQC patients treated with EGFR-TKI are not better than that observed in patients treated with platinum-doublet chemotherapy in the first-line setting. Therefore, in contrast to advanced LADC, EGFR mutation testing may not be necessarily performed upfront in advanced LSQC because not only the mutation rate is low, but also the predictive value is insufficient. For LSQC patients with known sensitizing-EGFR mutations, both conventional chemotherapy and EGFR-TKI are acceptable frontline treatment options.

[Prospect and Current Situation of Immune Checkpoint Inhibitors 
in First-line Treatment in Advanced Non-small Cell Lung Cancer Patients].

PubMed

Wang, Haiyang; Yu, Xiaoqing; Fan, Yun

2017-06-20

With the breakthroughs achieved of programmed death-1 (PD-1)/PD-L1 inhibitors monotherapy as first-line and second-line treatment in advanced non-small cell lung cancer (NSCLC), the treatment strategy is gradually evolving and optimizing. Immune combination therapy expands the benefit population and improves the curative effect. A series of randomized phase III trials are ongoing. In this review, we discuss the prospect and current situation of immune checkpoint inhibitors in first-line treatment in advanced NSCLC patients.

The Value of Experiments in Education

ERIC Educational Resources Information Center

Whitehurst, Grover J.

2012-01-01

One of the major story lines of the growth of civilization is the advance of the experiment. From the food we eat to the diseases we conquer to our understanding of how we think and behave, we have profited enormously from an approach that marries our models of the world with tests of their validity through systematic variation to determine cause…

Loudspeaker line array educational demonstration.

PubMed

Anderson, Brian E; Moser, Brad; Gee, Kent L

2012-03-01

This paper presents a physical demonstration of an audio-range line array used to teach interference of multiple sources in a classroom or laboratory exercise setting. Software has been developed that permits real-time control and steering of the array. The graphical interface permits a user to vary the frequency, the angular response by phase shading, and reduce sidelobes through amplitude shading. An inexpensive, eight-element loudspeaker array has been constructed to test the control program. Directivity measurements of this array in an anechoic chamber and in a large classroom are presented. These measurements have good agreement with theoretical directivity predictions, thereby allowing its use as a quantitative learning tool for advanced students as well as a qualitative demonstration of arrays in other settings. Portions of this paper are directed toward educators who may wish to implement a similar demonstration for their advanced undergraduate or graduate level course in acoustics. © 2012 Acoustical Society of America

F-15B in on ramp with close-up of test panels covered with advanced spray-on foam insulation materia

NASA Technical Reports Server (NTRS)

1999-01-01

Test panels covered with an advanced foam insulation material for the Space Shuttle's giant external fuel tank were test flown aboard an F-15B research aircraft at NASA's Dryden Flight Research Center, Edwards, Calif. Six panels were mounted on the left side of a heavily instrumented Flight Text Fixture mounted underneath the F-15B's fuselage. Insulation on this panel was finely machined over a horizontal rib structure to simulate in-line airflow past the tank; other panels had the ribs mounted vertically or had the insulation left in a rough as-sprayed surface. The tests were part of an effort by NASA's Marshall Space Flight Center to determine why small particles of the new insulation flaked off the tank on recent Shuttle missions. The tests with Dryden's F-15B were designed to replicate the pressure environment the Shuttle encounters during the first minute after launch. No noticeable erosion of the insulation material was noted after the flight experiment at Dryden.

Linear Power-Flow Models in Multiphase Distribution Networks: Preprint

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

Bernstein, Andrey; Dall'Anese, Emiliano

This paper considers multiphase unbalanced distribution systems and develops approximate power-flow models where bus-voltages, line-currents, and powers at the point of common coupling are linearly related to the nodal net power injections. The linearization approach is grounded on a fixed-point interpretation of the AC power-flow equations, and it is applicable to distribution systems featuring (i) wye connections; (ii) ungrounded delta connections; (iii) a combination of wye-connected and delta-connected sources/loads; and, (iv) a combination of line-to-line and line-to-grounded-neutral devices at the secondary of distribution transformers. The proposed linear models can facilitate the development of computationally-affordable optimization and control applications -- frommore » advanced distribution management systems settings to online and distributed optimization routines. Performance of the proposed models is evaluated on different test feeders.« less

A novel observational test of momentum balance in a solar flare

NASA Technical Reports Server (NTRS)

Canfield, Richard C.; Metcalf, Thomas R.; Strong, Keith T.; Zarro, Dominic M.

1987-01-01

A unique combination of SMM X-ray spectra and Sacramento Peak Observatory H-alpha imaging spectra has been used, for the first time, to measure and compare momentum values of upflowing and downflowing plasmas during the impulsive phase of a solar flare. The well-known blue asymmetry of X-ray spectral lines, indicative of upflow, was observed in the coronal Ca XIX line. The red asymmetry of H-alpha line profiles, indicative of downflow, was simultaneously observed in bright H-alpha kernels. It is found that, to within observational uncertainty, the momentum transported by the upflowing X-ray plasma was the same as that of the downflowing H-alpha material. Of the several physical mechanisms advanced to explain the observed blue asymmetry of X-ray lines, only explosive chromospheric evaporation predicts oppositely directed momenta of equal magnitude.

Detecting Gear Tooth Fatigue Cracks in Advance of Complete Fracture

NASA Technical Reports Server (NTRS)

Zakrajsek, James J.; Lewicki, David G.

1996-01-01

Results of using vibration-based methods to detect gear tooth fatigue cracks are presented. An experimental test rig was used to fail a number of spur gear specimens through bending fatigue. The gear tooth fatigue crack in each test was initiated through a small notch in the fillet area of a tooth on the gear. The primary purpose of these tests was to verify analytical predictions of fatigue crack propagation direction and rate as a function of gear rim thickness. The vibration signal from a total of three tests was monitored and recorded for gear fault detection research. The damage consisted of complete rim fracture on the two thin rim gears and single tooth fracture on the standard full rim test gear. Vibration-based fault detection methods were applied to the vibration signal both on-line and after the tests were completed. The objectives of this effort were to identify methods capable of detecting the fatigue crack and to determine how far in advance of total failure positive detection was given. Results show that the fault detection methods failed to respond to the fatigue crack prior to complete rim fracture in the thin rim gear tests. In the standard full rim gear test all of the methods responded to the fatigue crack in advance of tooth fracture; however, only three of the methods responded to the fatigue crack in the early stages of crack propagation.

Fast neutron irradiation tests of flash memories used in space environment at the ISIS spallation neutron source

NASA Astrophysics Data System (ADS)

Andreani, C.; Senesi, R.; Paccagnella, A.; Bagatin, M.; Gerardin, S.; Cazzaniga, C.; Frost, C. D.; Picozza, P.; Gorini, G.; Mancini, R.; Sarno, M.

2018-02-01

This paper presents a neutron accelerated study of soft errors in advanced electronic devices used in space missions, i.e. Flash memories performed at the ChipIr and VESUVIO beam lines at the ISIS spallation neutron source. The two neutron beam lines are set up to mimic the space environment spectra and allow neutron irradiation tests on Flash memories in the neutron energy range above 10 MeV and up to 800 MeV. The ISIS neutron energy spectrum is similar to the one occurring in the atmospheric as well as in space and planetary environments, with intensity enhancements varying in the range 108- 10 9 and 106- 10 7 respectively. Such conditions are suitable for the characterization of the atmospheric, space and planetary neutron radiation environments, and are directly applicable for accelerated tests of electronic components as demonstrated here in benchmark measurements performed on flash memories.

Tactical STOL moment balance through innovative configuration technology

NASA Technical Reports Server (NTRS)

Eckard, G. J.; Sutton, R. C.; Poth, G. E.

1981-01-01

Innovative and conventional thrust vectoring moment balance mechanisms, as applied to advanced tactical fighters, are examined. The innovative mechanisms include thrust line translation, life line translation, and auxiliary power control; the conventional mechanisms under investigation are horizontal tails, canards, and variable sweep wings. These mechanisms are tested for their ability to provide negative static margins for landing approach or relocation of the vectored thrust line nearer the aircraft's center of gravity. The net pitching moment due to wing, flaps, and vectored thrust lift would then be small, making possible beneficial trim forces from small trimming devices. These innovative mechanisms are, however, possibly heavy and must be evaluated on their complexity, reliability, maintainability, and STOL capabilities. Several candidate fighter configurations are compared and evaluated.

Antiangiogenic therapy for patients with aggressive or refractory advanced non-small cell lung cancer in the second-line setting.

PubMed

Reck, Martin; Garassino, Marina Chiara; Imbimbo, Martina; Shepherd, Frances A; Socinski, Mark A; Shih, Jin-Yuan; Tsao, Anne; Lee, Pablo; Winfree, Katherine B; Sashegyi, Andreas; Cheng, Rebecca; Varea, Rocio; Levy, Benjamin; Garon, Edward

2018-06-01

A majority of patients with advanced or metastatic non-small cell lung cancer (NSCLC) will experience disease progression after first-line therapy. Patients who have advanced NSCLC that is especially aggressive, which is defined as disease that rapidly progresses on first-line treatment or disease that is refractory to first-line treatment, have a critical unmet medical need. These patients have a poor prognosis in the second-line setting. Several studies have recently shown that treatment with an antiangiogenic therapy may benefit these patients. This review summarizes the approved antiangiogenic therapies for the treatment of patients with advanced NSCLC in the second-line setting, specifically focusing on the outcomes from subgroups of patients with rapidly progressing or refractory disease. Several antiangiogenic agents, as monotherapy or in combination with other treatments, have been or are currently being studied in patients with advanced NSCLC. Antiangiogenics that are approved for use in patients with advanced NSCLC are limited to bevacizumab in combination with chemotherapy (nonsquamous NSCLC), ramucirumab in combination with docetaxel (all histologies), and nintedanib in combination with docetaxel (adenocarcinoma histology). This review focuses on the efficacy, safety, and quality of life outcomes in the subpopulation of patients with rapidly progressing or refractory NSCLC treated with approved antiangiogenic therapies in the second-line setting. We also discuss the impact of newly approved immunotherapy agents on the outcomes of patients with aggressive or refractory disease. Studies in progress and planned future research will determine if combination treatment with antiangiogenics and immunotherapies will benefit patients with aggressive, advanced NSCLC. Copyright © 2018. Published by Elsevier B.V.

Stress Analysis and Permeability Testing of Cryogenic Composite Feed Line

NASA Technical Reports Server (NTRS)

Chu, Tsuchin Philip

1999-01-01

For the next generation Single-Stage-To-Orbit (SSTO) Reusable Launch Vehicle (RLV), the use of advanced composite materials is highly desirable and critical to the success of the mission. NASA Marshall Space Flight Center (MSFC) has been working with the aerospace industry for many years to develop and demonstrate the cryogenic composite propellant tanks and feed lines technologies. A 50.8-mm diameter composite feed line for the Clipper Graham (DCY.A) was developed and tested. The purpose of the program is to demonstrate the LH2 permeability, composite to composite and metal joints, as well as composite flange interface of the composite feed line. Stress analysis and permeability testing have been performed on this article. Recently, a larger composite feed line design is being investigated and developed at MSFC for potential use in future RLV. The diameter of the feed line is 203 mm and the overall length is approximately 2.2 meters. This one piece unlined feed line consists of three straight tubular sections joined by two 90 degree elbows. The material chosen is IM7/977-3 prepreg fabric. The lay-up pattern is [0/90, plus or minus 45]s and is built up to 18 plies to the flanges at both ends. A preliminary stress analysis has been conducted to identify potential critical stresses and to develop the finite element analysis (FEA) capability of composite feed lines. As expected, the critical stresses occurred at the rims of some flange holes and the onset of the tapered tubular sections. Further analysis is required to determine the loads, flange deflection, vibration, and combined maximum loads. Two permeability-testing apparatuses were also designed for both flat panel specimens and curved feed line sections after impact damage. A larger permeant gas exposed area is required to accurately determine the effect of impact damage on the permeability of the feed line materials. The flat panel tester was fabricated and assembled. Three test coupons were made of graphite/epoxy plain weave prepreg and unidirectional prepreg. The flow rate was calculated by measuring the change of manometer fluid height per unit time. The permeability of the coupons is then calculated according to Darcy's Law. The pressure increase due to the head rise in the manometer was not considered for the initial estimation. The result of the unidirectional composite coupon agreed with that obtained from the DC-XA feed line testing of a similar material. Further improvement on the design may be required to improve the accuracy and efficiency of permeability testing.

Progression-free survival as surrogate and as true end point: insights from the breast and colorectal cancer literature.

PubMed

Saad, E D; Katz, A; Hoff, P M; Buyse, M

2010-01-01

Significant achievements in the systemic treatment of both advanced breast cancer and advanced colorectal cancer over the past 10 years have led to a growing number of drugs, combinations, and sequences to be tested. The choice of surrogate and true end points has become a critical issue and one that is currently the subject of much debate. Many recent randomized trials in solid tumor oncology have used progression-free survival (PFS) as the primary end point. PFS is an attractive end point because it is available earlier than overall survival (OS) and is not influenced by second-line treatments. PFS is now undergoing validation as a surrogate end point in various disease settings. The question of whether PFS can be considered an acceptable surrogate end point depends not only on formal validation studies but also on a standardized definition and unbiased ascertainment of disease progression in clinical trials. In advanced breast cancer, formal validation of PFS as a surrogate for OS has so far been unsuccessful. In advanced colorectal cancer, in contrast, current evidence indicates that PFS is a valid surrogate for OS after first-line treatment with chemotherapy. The other question is whether PFS sufficiently reflects clinical benefit to be considered a true end point in and of itself.

Advanced Learners' Comprehension of Discourse Connectives: The Role of L1 Transfer across On-Line and Off-Line Tasks

ERIC Educational Resources Information Center

Zufferey, Sandrine; Mak, Willem; Degand, Liesbeth; Sanders, Ted

2015-01-01

Discourse connectives are important indicators of textual coherence, and mastering them is an essential part of acquiring a language. In this article, we compare advanced learners' sensitivity to the meaning conveyed by connectives in an off-line grammaticality judgment task and an on-line reading experiment using eye-tracking. We also assess the…

Developing Essential Understanding of Functions for Teaching Mathematics in Grades 9-12

ERIC Educational Resources Information Center

Lloyd, Gwendolyn; Beckmann, Sybilla; Zbiek, Rose Mary; Cooney, Thomas

2010-01-01

Are sequences functions? What can't the popular "vertical line test" be applied in some cases to determine if a relation is a function? How does the idea of rate of change connect with simpler ideas about proportionality as well as more advanced topics in calculus? Helping high school students develop a robust understanding of functions requires…

Erlotinib as single agent first line treatment in locally advanced or metastatic activating EGFR mutation-positive lung adenocarcinoma (CEETAC): an open-label, non-randomized, multicenter, phase IV clinical trial.

PubMed

Markóczy, Zsolt; Sárosi, Veronika; Kudaba, Iveta; Gálffy, Gabriella; Turay, Ülkü Yilmaz; Demirkazik, Ahmet; Purkalne, Gunta; Somfay, Attila; Pápai-Székely, Zsolt; Rásó, Erzsébet; Ostoros, Gyula

2018-05-25

Erlotinib is approved for the first line treatment of epidermal growth factor receptor (EGFR) mutation-positive non-small cell lung cancer. Since the number of prospective studies in Caucasian patients treated in routine clinical setting is limited we conducted a multicenter, phase IV clinical trial to determine the efficacy and safety of erlotinib and to demonstrate the feasibility of the validated standardized companion diagnostic method of EGFR mutation detection. 651 chemonaive, cytologically or histologically verified advanced stage lung adenocarcinoma patients from Hungary, Turkey and Latvia were screened for exon19 microdeletions and exon21 L858R EGFR mutations using the companion diagnostic EGFR test. EGFR mutation-positive, locally advanced or metastatic lung adenocarcinoma patients received as first line treatment erlotinib at 150 mg/day. The primary endpoint was progression-free survival (PFS). 62 EGFR mutation-positive patients (9.5% of screened) were included in the safety/intent-to-treat cohort. Median PFS was 12.8 months (95%CI, 9.9-15.8), objective response rate and one-year survival was 66.1% and 82.5%, respectively. Most frequent treatment related adverse events were diarrhoea and rash. Eastern Oncology Cooperative Group Performance Status (ECOG PS), smoking status and M1a/M1b disease stage were significant prognosticators of PFS (p = 0.017, p = 0.045 and p = 0.002, respectively). There was no significant difference in PFS between the subgroups stratified by gender, age or exon19 vs exon21 mutation. Our study confirmed the efficacy and safety of first line erlotinib monotherapy in Caucasian patients with locally advanced or metastatic lung adenocarcinoma carrying activating EGFR mutations based on the screening with the approved companion diagnostic procedure. ClinicalTrials.gov Identifier: NCT01609543.

Apatinib in gastric carcinoma: A case report of partial response for first-line treatment in advanced disease.

PubMed

Wang, Yaping; Bi, Minghong; Zhang, Haoran; Gao, Zhenyuan; Zhou, Hairong; Chang, Shu

2017-10-01

Gastric cancer (GC) is the most common gastrointestinal malignant tumor, with a gradual increasing incidence throughout the world. Mostly GC is diagnosed in its late stage. To date, there is no usable standardized treatment regimen for patients with advanced GC. Apatinib mesylate, small-molecule vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitor (TKI), has been approved as third-line treatment for patients with advanced gastric adenocarcinoma in China, October, 2014. Till now, there is no case report about apatinib as first-line treatment for patients with advanced GC in literature. We present an 83-year-old Chinese man with advanced gastric adenocarcinoma, who received apatinib as first-line option and obtained clinical benefit within 2 weeks. The lung metastases disappeared completely and the liver metastases shrank significantly. The patient's progression-free survival was 163 days and overall survival was 201 days. This paper reviews and discusses apatinib as a new targeted drug for patients with advanced GC by comparison with other effective molecular-targeted therapy. © 2016 John Wiley & Sons Australia, Ltd.

Manufacturing of Protected Lithium Electrodes for Advanced Lithium-Air, Lithium-Water & Lithium-Sulfur Batteries

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

Visco, Steven J

The global demand for rechargeable batteries is large and growing rapidly. Assuming the adoption of electric vehicles continues to increase, the need for smaller, lighter, and less expensive batteries will become even more pressing. In this vein, PolyPlus Battery Company has developed ultra-light high performance batteries based on its proprietary protected lithium electrode (PLE) technology. The Company’s Lithium-Air and Lithium-Seawater batteries have already demonstrated world record performance (verified by third party testing), and we are developing advanced lithium-sulfur batteries which have the potential deliver high performance at low cost. In this program PolyPlus Battery Company teamed with Corning Incorporated tomore » transition the PLE technology from bench top fabrication using manual tooling to a pre- commercial semi-automated pilot line. At the inception of this program PolyPlus worked with a Tier 1 battery manufacturing engineering firm to design and build the first-of-its-kind pilot line for PLE production. The pilot line was shipped and installed in Berkeley, California several months after the start of the program. PolyPlus spent the next two years working with and optimizing the pilot line and now produces all of its PLEs on this line. The optimization process successfully increased the yield, throughput, and quality of PLEs produced on the pilot line. The Corning team focused on fabrication and scale-up of the ceramic membranes that are key to the PLE technology. PolyPlus next demonstrated that it could take Corning membranes through the pilot line process to produce state-of-the-art protected lithium electrodes. In the latter part of the program the Corning team developed alternative membranes targeted for the large rechargeable battery market. PolyPlus is now in discussions with several potential customers for its advanced PLE-enabled batteries, and is building relationships and infrastructure for the transition into manufacturing. It is likely that the next step will be accomplished through a combination of joint venture partnering and licensing of the technology.« less

Composition and structure of tuber cell walls affect in vitro digestibility of potato (Solanum tuberosum L.).

PubMed

Frost, Jovyn K T; Flanagan, Bernadine M; Brummell, David A; O'Donoghue, Erin M; Mishra, Suman; Gidley, Michael J; Monro, John A

2016-10-12

The digestibility of starchy foods, such as potatoes, can be characterized by the proportion of starch that is rapidly digestible by in vitro hydrolysis (rapidly digestible starch, RDS). This study evaluated the RDS content in a potato germplasm collection consisting of 98 genotypes and identified three advanced lines, Crop39, Crop71 and Crop85, where cooked potato RDS content was significantly lower than that of their respective isolated starches (P < 0.05). In Crop39, Crop71 and Crop85, the properties of their isolated starch did not differ significantly from that of five control lines with higher RDS contents. Cell wall analyses revealed that, compared with other lines tested, Crop39, Crop71 and Crop85 had at least four times the amount of rhamnogalacturonan-I (RG-I) galactan side-chains that were very firmly attached to the wall and requiring 4 M KOH for extraction. Pectin solubilization during cooking was also remarkably low (2-4%) in these three lines compared with other lines tested (7-19%). The findings suggest that possession of higher amounts of RG-I galactan that interact strongly with cellulose may provide a sturdier wall that better resists solubilization during cooking, and effectively impedes access of digestive enzymes for starch hydrolysis in an in vitro model.

Preclinical optimization of a broad-spectrum anti-bladder cancer tri-drug regimen via the Feedback System Control (FSC) platform

NASA Astrophysics Data System (ADS)

Liu, Qi; Zhang, Cheng; Ding, Xianting; Deng, Hui; Zhang, Daming; Cui, Wei; Xu, Hongwei; Wang, Yingwei; Xu, Wanhai; Lv, Lei; Zhang, Hongyu; He, Yinghua; Wu, Qiong; Szyf, Moshe; Ho, Chih-Ming; Zhu, Jingde

2015-06-01

Therapeutic outcomes of combination chemotherapy have not significantly advanced during the past decades. This has been attributed to the formidable challenges of optimizing drug combinations. Testing a matrix of all possible combinations of doses and agents in a single cell line is unfeasible due to the virtually infinite number of possibilities. We utilized the Feedback System Control (FSC) platform, a phenotype oriented approach to test 100 options among 15,625 possible combinations in four rounds of assaying to identify an optimal tri-drug combination in eight distinct chemoresistant bladder cancer cell lines. This combination killed between 82.86% and 99.52% of BCa cells, but only 47.47% of the immortalized benign bladder epithelial cells. Preclinical in vivo verification revealed its markedly enhanced anti-tumor efficacy as compared to its bi- or mono-drug components in cell line-derived tumor xenografts. The collective response of these pathways to component drugs was both cell type- and drug type specific. However, the entire spectrum of pathways triggered by the tri-drug regimen was similar in all four cancer cell lines, explaining its broad spectrum killing of BCa lines, which did not occur with its component drugs. Our findings here suggest that the FSC platform holdspromise for optimization of anti-cancer combination chemotherapy.

Disease evaluations and agronomic traits of advanced peanut breeding lines in 2012

USDA-ARS?s Scientific Manuscript database

A total of 38 peanut cultivars and high-oleic advanced breeding lines were evaluated in small field plots in 2012 for yield, seed grade and size, and resistance to Sclerotinia minor and Sclerotium rolfsii. Among the 14 Spanish entries, the cultivar Tamnut 06 (3258 lbs/acre) and breeding line 140-1O...

The Role of Private Speech in Cognitive Regulation of Learners: The Case of English as a Foreign Language Education

ERIC Educational Resources Information Center

Sarab, Mohamad Reza Anani; Gordani, Yahya

2015-01-01

Investigations into the use of private speech by adult English foreign language (EFL) learners in regulating their mental activities have been an interesting area of research with a sociocultural framework. Following this line of research, 30 advanced adult EFL learners were selected via the administration of Oxford quick placement test and took a…

Electromagnetic Compatibility in the Defense Systems of Future Years

DTIC Science & Technology

2002-06-01

Technology activities. Its mission is to conduct and promote cooperative research and information exchange . The objective is to support the development...testing CLEARANCE PRODUCTION AND IN-SERVICE SUPPORT Modelling in support of conceptual design (structure & installation design) EMH Design guides for the... marketed by Advanced Electromagnetics [6-1]. Transmission Line Matrix Method The link between field theory and circuit theory, the major theories on

Droplet sliding on inclined superhydrophobic surfaces: the effect of anisotropic contact line

NASA Astrophysics Data System (ADS)

Jiang, Youhua; Cao, Lile; Guo, Zongqi; Choi, Chang-Hwan

2017-11-01

Although the effects of solid structures on droplet retention on superhydrophobic surfaces have been studied extensively, the investigation has been restricted to the sessile droplets on horizontal surfaces where the contact line motions are axisymmetric or isotropic (either advancing or receding). In the droplet retention on inclined surfaces, the contact line motions are asymmetric or anisotropic; the advancing and receding motions coexist. In this study, we investigate the correlation between the droplet boundary pinning and the surface morphology on inclined superhydrophobic surfaces. The evolution of the droplet contact angle and width show contrary behaviors between pillar- and pore-structured surfaces due to the distinctive microscopic contact line motions. Therefore, the visualizations of the contact line motions at different locations of the boundary on inclined superhydrophobic surfaces are performed and the averaged contact line density of the boundary is quantified. The result shows that the droplet retentive force monotonously increase with the increase in contact line density, regardless of the surface morphological types, dimensions, or the direction of contact line motion (advancing, receding, or both). The result indicates that the droplet retentive force on superhydrophobic surfaces is mainly determined by the contact line density, regardless of the isotropy of the contact line.

Randomized Phase III Placebo-Controlled Trial of Letrozole Plus Oral Temsirolimus As First-Line Endocrine Therapy in Postmenopausal Women With Locally Advanced or Metastatic Breast Cancer

PubMed Central

Wolff, Antonio C.; Lazar, Ann A.; Bondarenko, Igor; Garin, August M.; Brincat, Stephen; Chow, Louis; Sun, Yan; Neskovic-Konstantinovic, Zora; Guimaraes, Rodrigo C.; Fumoleau, Pierre; Chan, Arlene; Hachemi, Soulef; Strahs, Andrew; Cincotta, Maria; Berkenblit, Anna; Krygowski, Mizue; Kang, Lih Lisa; Moore, Laurence; Hayes, Daniel F.

2013-01-01

Purpose Recent data showed improvement in progression-free survival (PFS) when adding everolimus to exemestane in patients with advanced breast cancer experiencing recurrence/progression after nonsteroidal aromatase inhibitor (AI) therapy. Here, we report clinical outcomes of combining the mammalian target of rapamycin (mTOR) inhibitor temsirolimus with letrozole in AI-naive patients. Patients and Methods This phase III randomized placebo-controlled study tested efficacy/safety of first-line oral letrozole 2.5 mg daily/temsirolimus 30 mg daily (5 days every 2 weeks) versus letrozole/placebo in 1,112 patients with AI-naive, hormone receptor–positive advanced disease. An independent data monitoring committee recommended study termination for futility at the second preplanned interim analysis (382 PFS events). Results Patients were balanced (median age, 63 years; 10% stage III, 40% had received adjuvant endocrine therapy). Those on letrozole/temsirolimus experienced more grade 3 to 4 events (37% v 24%). There was no overall improvement in primary end point PFS (median, 9 months; hazard ratio [HR], 0.90; 95% CI, 0.76 to 1.07; P = .25) nor in the 40% patient subset with prior adjuvant endocrine therapy. An exploratory analysis showed improved PFS favoring letrozole/temsirolimus in patients ≤ age 65 years (9.0 v 5.6 months; HR, 0.75; 95% CI, 0.60 to 0.93; P = .009), which was separately examined by an exploratory analysis of 5-month PFS using subpopulation treatment effect pattern plot methodology (P = .003). Conclusion Adding temsirolimus to letrozole did not improve PFS as first-line therapy in patients with AI-naive advanced breast cancer. Exploratory analyses of benefit in younger postmenopausal patients require external confirmation. PMID:23233719

Rotorcraft flying qualities improvement using advanced control

NASA Technical Reports Server (NTRS)

Walker, D.; Postlethwaite, I.; Howitt, J.; Foster, N.

1993-01-01

We report on recent experience gained when a multivariable helicopter flight control law was tested on the Large Motion Simulator (LMS) at DRA Bedford. This was part of a study into the application of multivariable control theory to the design of full-authority flight control systems for high-performance helicopters. In this paper, we present some of the results that were obtained during the piloted simulation trial and from subsequent off-line simulation and analysis. The performance provided by the control law led to level 1 handling quality ratings for almost all of the mission task elements assessed, both during the real-time and off-line analysis.

Derivation of novel genetically diverse human embryonic stem cell lines.

PubMed

Stefanova, Valentina T; Grifo, James A; Hansis, Christoph

2012-06-10

Human embryonic stem cells (hESCs) have the potential to revolutionize many biomedical fields ranging from basic research to disease modeling, regenerative medicine, drug discovery, and toxicity testing. A multitude of hESC lines have been derived worldwide since the first 5 lines by Thomson et al. 13 years ago, but many of these are poorly characterized, unavailable, or do not represent desired traits, thus making them unsuitable for application purposes. In order to provide the scientific community with better options, we have derived 12 new hESC lines at New York University from discarded genetically normal and abnormal embryos using the latest techniques. We examined the genetic status of the NYUES lines in detail as well as their molecular and cellular features and DNA fingerprinting profile. Furthermore, we differentiated our hESCs into the tissues most affected by a specific condition or into clinically desired cell types. To our knowledge, a number of characteristics of our hESCs have not been previously reported, for example, mutation for alpha thalassemia X-linked mental retardation syndrome, linkage to conditions with a genetic component such as asthma or poor sperm morphology, and novel combinations of ethnic backgrounds. Importantly, all of our undifferentiated euploid female lines tested to date did not show X chromosome inactivation, believed to result in superior potency. We continue to derive new hESC lines and add them to the NIH registry and other registries. This should facilitate the use of our hESCs and lead to advancements for patient-benefitting applications.

Treatment algorithm in 2014 for advanced non-small cell lung cancer: therapy selection by tumour histology and molecular biology.

PubMed

Manegold, Christian

2014-09-01

The availability of antineoplastic monoclonal antibodies, small molecules and newer cytotoxics such as pemetrexed, the EGFR-tyrosine kinase inhibitors erlotinib, gefitinib, afatinib as well as the anti-angiogenic bevacizumab and the ALK-inhibitor crizotinib has recently changes the treatment algorithm of advanced non-small cell lung cancer. Decision making in 2014 is characterized by customizing therapy, by selecting a specific therapeutic regimen based on the histotype and the genotype of the tumour. This refers to first-line induction therapy and maintenance therapy as well, but also to subsequent lines of therapy since anti-neoplastic drugs and regimens used upfront clinically influence the selection of agents/regimes considered for second-/third-line treatment. Consequently, therapy customization through tumour histology and molecular markers has significantly influenced the work of pathologists around the globe and the process of obtaining an extended therapeutically relevant tumour diagnosis. Not only histological sub-typing became standard but molecular information is also considered of increasing importance for treatment selection. Routine molecular testing in certified laboratories must be established, and the diagnostic process should ideally be performed under the guidance of evidence based recommendation. The process of investigating and implementing medical targeting in lung cancer therefore, requires advanced diagnostic techniques and expertise and because of its large dimension is costly and influenced by the limitation of financial and clinical resources. Copyright © 2014. Published by Elsevier Urban & Partner Sp. z o.o.

Simulation of Assembly Line Balancing in Automotive Component Manufacturing

NASA Astrophysics Data System (ADS)

Jamil, Muthanna; Mohd Razali, Noraini

2016-02-01

This study focuses on the simulation of assembly line balancing in an automotive component in a vendor manufacturing company. A mixed-model assembly line of charcoal canister product that is used in an engine system as fuel's vapour filter was observed and found that the current production rate of the line does not achieve customer demand even though the company practices buffer stock for two days in advance. This study was carried out by performing detailed process flow and time studies along the line. To set up a model of the line by simulation, real data was taken from a factory floor and tested for distribution fit. The data gathered was then transformed into a simulation model. After verification of the model by comparing it with the actual system, it was found that the current line efficiency is not at its optimum condition due to blockage and idle time. Various what-if analysis were applied to eliminate the cause. Proposed layout shows that the line is balanced by adding buffer to avoid the blockage. Whereas, manpower is added the stations to reduce process time therefore reducing idling time. The simulation study was carried out using ProModel software.

Post-Progression Survival Associated with Overall Survival in Patients with Advanced Non-Small-Cell Lung Cancer Receiving Docetaxel Monotherapy as Second-Line Chemotherapy.

PubMed

Kotake, Mie; Miura, Yosuke; Imai, Hisao; Mori, Keita; Sakurai, Reiko; Kaira, Kyoichi; Tomizawa, Yoshio; Minato, Koichi; Saito, Ryusei; Hisada, Takeshi

2017-01-01

In patients with non-small-cell lung cancer (NSCLC), the effects of second-line chemotherapy on overall survival (OS) might be confounded by subsequent therapies. Therefore, using individual-level data, we aimed to determine the relationships between progression-free survival (PFS) and post-progression survival (PPS) with OS in patients with advanced NSCLC treated with docetaxel monotherapy as second-line chemotherapy. Between April 2002 and December 2014, data from 86 patients with advanced NSCLC who underwent second-line docetaxel monotherapy following first-line treatment with platinum combination chemotherapy were analyzed. The relationships of PFS and PPS with OS were analyzed at the individual level. Spearman rank correlation and linear regression analyses showed that PPS was strongly associated with OS (r = 0.86, p < 0.05, R2 = 0.93), whereas PFS was moderately correlated with OS (r = 0.50, p < 0.05, R2 = 0.21). Performance status at the end of second-line treatment and the number of regimens after progression beyond second-line chemotherapy were significantly associated with PPS (p < 0.05). In patients with advanced NSCLC with unknown oncogenic driver mutations undergoing docetaxel monotherapy as second-line chemotherapy, when compared with PFS, PPS had a stronger association with OS. This finding suggests that subsequent treatment after disease progression following second-line docetaxel monotherapy has a significant influence on OS. © 2017 S. Karger AG, Basel.

Environmental performance evaluation of an advanced-design solid-state television camera

NASA Technical Reports Server (NTRS)

1979-01-01

The development of an advanced-design black-and-white solid-state television camera which can survive exposure to space environmental conditions was undertaken. A 380 x 488 element buried-channel CCD is utilized as the image sensor to ensure compatibility with 525-line transmission and display equipment. Specific camera design approaches selected for study and analysis included: (1) component and circuit sensitivity to temperature; (2) circuit board thermal and mechanical design; and (3) CCD temperature control. Preferred approaches were determined and integrated into the final design for two deliverable solid-state TV cameras. One of these cameras was subjected to environmental tests to determine stress limits for exposure to vibration, shock, acceleration, and temperature-vacuum conditions. These tests indicate performance at the design goal limits can be achieved for most of the specified conditions.

Warthog: A MOOSE-Based Application for the Direct Code Coupling of BISON and PROTEUS

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

McCaskey, Alexander J.; Slattery, Stuart; Billings, Jay Jay

The Nuclear Energy Advanced Modeling and Simulation (NEAMS) program from the Department of Energy's Office of Nuclear Energy provides a robust toolkit for the modeling and simulation of current and future advanced nuclear reactor designs. This toolkit provides these technologies organized across product lines: two divisions targeted at fuels and end-to-end reactor modeling, and a third for integration, coupling, and high-level workflow management. The Fuels Product Line and the Reactor Product line provide advanced computational technologies that serve each respective field well, however, their current lack of integration presents a major impediment to future improvements of simulation solution fidelity. Theremore » is a desire for the capability to mix and match tools across Product Lines in an effort to utilize the best from both to improve NEAMS modeling and simulation technologies. This report details a new effort to provide this Product Line interoperability through the development of a new application called Warthog. This application couples the BISON Fuel Performance application from the Fuels Product Line and the PROTEUS Core Neutronics application from the Reactors Product Line in an effort to utilize the best from all parts of the NEAMS toolkit and improve overall solution fidelity of nuclear fuel simulations. To achieve this, Warthog leverages as much prior work from the NEAMS program as possible, and in doing so, enables interoperability between the disparate MOOSE and SHARP frameworks, and the libMesh and MOAB mesh data formats. This report describes this work in full. We begin with a detailed look at the individual NEAMS framework technologies used and developed in the various Product Lines, and the current status of their interoperability. We then introduce the Warthog application: its overall architecture and the ways it leverages the best existing tools from across the NEAMS toolkit to enable BISON-PROTEUS integration. Furthermore, we show how Warthog leverages a tool known as DataTransferKit to seamlessly enable the transfer for solution data between disparate frameworks and mesh formats. To end, we demonstrate tests for the direct software coupling of BISON and PROTEUS using Warthog, and discuss current impediments and solutions to the construction of physically realistic input models for this coupled BISON-PROTEUS system.« less

International Instrumentation Symposium, 32nd, Seattle, WA, May 5-8, 1986, Proceedings

NASA Astrophysics Data System (ADS)

The conference presents papers on blast, shock, and vibration instrumentation; wind tunnel instrumentation and controls; electrooptic and fiber optic instrumentation; special test facilities; reentry vehicle testing; and nondestructive test and acoustic test instrumentation. Other topic include real time systems, flight test and avionics instrumentation, data aquisition and analysis systems, thermal measurements, and advances in measurement technology. Particular attention is given to an automated fringe counting laser interferometer for low frequency vibration measurements, dynamic pressure measurements in pneumatic lines, optically interfaced sensor system for aerospace applications, the picobalance for single microparticle measurements, ellipsometric film thickness, nanometer wear measurement by ultrathin surface layer activation, a rugged electronic scanner designed for turbine test, failure mechanism characterization of platinum alloy, and the thick film strain gage.

Targeting fibroblast growth factor receptors and immune checkpoint inhibitors for the treatment of advanced bladder cancer: New direction and New Hope.

PubMed

Morales-Barrera, Rafael; Suárez, Cristina; de Castro, Ana Martínez; Racca, Fabricio; Valverde, Claudia; Maldonado, Xavier; Bastaros, Juan Maria; Morote, Juan; Carles, Joan

2016-11-01

Bladder cancer is one of the leading causes of death in Europe and the United States. About 25% of patients with bladder cancer have advanced disease (muscle-invasive or metastatic disease) at presentation and are candidates for systemic chemotherapy. In the setting of metastatic disease, use of cisplatin-based regimens improves survival. However, despite initial high response rates, the responses are typically not durable leading to recurrence and death in the vast majority of these patients with median overall survival of 15months and a 5-year survival rate of ⩽10%. Furthermore, unfit patients for cisplatin have no standard of care for first line therapy in advance disease Most second-line chemotherapeutic agents tested have been disappointing. Newer targeted drugs and immunotherapies are being studied in the metastatic setting, their usefulness in the neoadjuvant and adjuvant settings is also an intriguing area of ongoing research. Thus, new treatment strategies are clearly needed. The comprehensive evaluation of multiple molecular pathways characterized by The Cancer Genome Atlas project has shed light on potential therapeutic targets for bladder urothelial carcinomas. We have focused especially on emerging therapies in locally advanced and metastatic urothelial carcinoma with an emphasis on immune checkpoints inhibitors and FGFR targeted therapies, which have shown great promise in early clinical studies. Copyright © 2016 Elsevier Ltd. All rights reserved.

Theory-based modifications of an advanced notification letter improves screening for bowel cancer in men: A randomised controlled trial.

PubMed

Zajac, Ian T; Duncan, Amy C; Flight, Ingrid; Wittert, Gary A; Cole, Stephen R; Young, Graeme P; Wilson, Carlene J; Turnbull, Deborah A

2016-09-01

Male participation in screening for bowel cancer is sub-optimal. Theory-based interventions provide a means of improving screening uptake. To test the efficacy of modifying consumer invitation material in line with continuum and stage theories of health behaviour on screening participation. N = 9216 Australian men aged 50-74 years were randomised to one of four trial arms in a 2 × 2 factorial design randomised controlled trial. Participants received either standard invitation material (control group), or combinations of modified advance-notification and invitation letters. A subsample completed baseline and endpoint behavioural surveys. Participants who received the modified advance notification letter were 12% more likely to screen than those who received the standard version (RR = 1.12, χ(2)(1) = 10.38, p = 0.001). The modified invitation letter did not impact screening uptake (RR = 0.97, χ(2)(1) = 0.63, p = 0.424). No significant changes in psychological variables due to the intervention were observed. Modifications to advance notification letters in line with health behaviour theories significantly improves screening uptake in men. Australian New Zealand Clinical Trials Registry: ACTRN12612001122842 https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=362688. Copyright © 2016 Elsevier Ltd. All rights reserved.

Crossability of Triticum urartu and Triticum monococcum Wheats, Homoeologous Recombination, and Description of a Panel of Interspecific Introgression Lines

PubMed Central

Fricano, Agostino; Brandolini, Andrea; Rossini, Laura; Sourdille, Pierre; Wunder, Joerg; Effgen, Sigi; Hidalgo, Alyssa; Erba, Daniela; Piffanelli, Pietro; Salamini, Francesco

2014-01-01

Triticum monococcum (genome Am) and T. urartu (genome Au) are diploid wheats, with the first having been domesticated in the Neolithic Era and the second being a wild species. In a germplasm collection, rare wild T. urartu lines with the presence of T. monococcum alleles were found. This stimulated our interest to develop interspecific introgression lines of T. urartu in T. monococcum, a breeding tool currently implemented in several crop species. Moreover, the experiments reported were designed to reveal the existence in nature of Am/Au intermediate forms and to clarify whether the two species are at least marginally sexually compatible. From hand-made interspecific crosses, almost-sterile F1 plants were obtained when the seed-bearing parent was T. monococcum. A high degree of fertility was, however, evident in some advanced generations, particularly when T. urartu donors were molecularly more related to T. monococcum. Analysis of the marker populations demonstrated chromosome pairing and recombination in F1 hybrid plants. Forty-six introgression lines were developed using a line of T. monococcum with several positive agronomic traits as a recurrent parent. Microsatellite markers were tested on Au and Am genomes, ordered in a T. monococcum molecular map, and used to characterize the exotic DNA fragments present in each introgression line. In a test based on 28 interspecific introgression lines, the existence of genetic variation associated with T. urartu chromosome fragments was proven for the seed content of carotenoids, lutein, β-cryptoxanthin, and zinc. The molecular state of available introgression lines is summarized. PMID:25147190

Proposal for a new categorization of aseptic processing facilities based on risk assessment scores.

PubMed

Katayama, Hirohito; Toda, Atsushi; Tokunaga, Yuji; Katoh, Shigeo

2008-01-01

Risk assessment of aseptic processing facilities was performed using two published risk assessment tools. Calculated risk scores were compared with experimental test results, including environmental monitoring and media fill run results, in three different types of facilities. The two risk assessment tools used gave a generally similar outcome. However, depending on the tool used, variations were observed in the relative scores between the facilities. For the facility yielding the lowest risk scores, the corresponding experimental test results showed no contamination, indicating that these ordinal testing methods are insufficient to evaluate this kind of facility. A conventional facility having acceptable aseptic processing lines gave relatively high risk scores. The facility showing a rather high risk score demonstrated the usefulness of conventional microbiological test methods. Considering the significant gaps observed in calculated risk scores and in the ordinal microbiological test results between advanced and conventional facilities, we propose a facility categorization based on risk assessment. The most important risk factor in aseptic processing is human intervention. When human intervention is eliminated from the process by advanced hardware design, the aseptic processing facility can be classified into a new risk category that is better suited for assuring sterility based on a new set of criteria rather than on currently used microbiological analysis. To fully benefit from advanced technologies, we propose three risk categories for these aseptic facilities.

Flight Test Evaluation of an Unmanned Aircraft System Traffic Management (UTM) Concept for Multiple Beyond-Visual-Line-of-Sight (BVLOS) Operations

NASA Technical Reports Server (NTRS)

Johnson, Marcus; Jung, Jaewoo; Rios, Joseph; Mercer, Joey; Homola, Jeffrey; Prevot, Thomas; Mulfinger, Daniel; Kopardekar, Parimal

2017-01-01

Many applications of small Unmanned Aircraft System (UAS) have been envisioned. These include surveillance of key assets such as pipelines, rail, or electric wires, deliveries, search and rescue, traffic monitoring, videography, and precision agriculture. These operations are likely to occur in the same airspace in the presence of many static and dynamic constraints such as airports, and high wind areas. Therefore, operations of small UAS need to be managed to ensure safety and operation efficiency is maintained. NASA has advanced a concept for UAS Traffic Management (UTM) and has initiated a research effort to refine that concept and develop operational and system requirements. A UTM research platform is in development and flight test activities to evaluate core functions and key assumptions focusing exclusively on UAS operations in different environments are underway. This seminar will present lessons learned from a recent flight test focused on enabling operations of multiple UAS in lower-risk environments within and beyond visual line of sight (BVLOS).

Simulation development and evaluation of an improved longitudinal velocity vector control wheel steering mode and electronic display format

NASA Technical Reports Server (NTRS)

Steinmetz, G. G.

1980-01-01

Using simulation, an improved longitudinal velocity vector control wheel steering mode and an improved electronic display format for an advanced flight system were developed and tested. Guidelines for the development phase were provided by test pilot critique summaries of the previous system. The results include performances from computer generated step column inputs across the full airplane speed and configuration envelope, as well as piloted performance results taken from a reference line tracking task and an approach to landing task conducted under various environmental conditions. The analysis of the results for the reference line tracking and approach to landing tasks indicates clearly detectable improvement in pilot tracking accuracy with a reduction in physical workload. The original objectives of upgrading the longitudinal axis of the velocity vector control wheel steering mode were successfully met when measured against the test pilot critique summaries and the original purpose outlined for this type of augment control mode.

Successful TS-1 monotherapy as the second-line treatment for advanced extramammary Paget's disease: A report of two cases.

PubMed

Kato, Junji; Hida, Tokimasa; Yamashita, Toshiharu; Kamiya, Shiori; Horimoto, Kohei; Sato, Sayuri; Takahashi, Hitomi; Sawada, Masahide; Yamada, Mao; Uhara, Hisashi

2018-01-01

There is no standard chemotherapeutic treatment for advanced extramammary Paget's disease, though the effectiveness of some chemotherapy regimens, including docetaxel, has been reported. In this report, we report that TS-1 monotherapy was effective in two patients with advanced extramammary Paget's disease after docetaxel treatment failure. TS-1 monotherapy may be useful as the second-line treatment for patients with advanced extramammary Paget's disease. © 2017 Japanese Dermatological Association.

Re-challenge with pemetrexed in advanced mesothelioma: a multi-institutional experience

PubMed Central

2012-01-01

Background Although first-line therapy for patients affected by advanced mesothelioma is well established, there is a lack of data regarding the impact of second-line treatment. Methods We retrospectively collected data of patients affected by advanced mesothelioma, already treated with first-line therapy based on pemetrexed and platin, with a response (partial response or stable disease) lasting at least 6 months, and re-treated with a pemetrexed-based therapy at progression. The primary objective was to describe time to progression and overall survival after re-treatment. Results Overall across several Italian oncological Institutions we found 30 patients affected by advanced mesothelioma, in progression after a 6-month lasting clinical benefit following a first-line treatment with cisplatin and pemetrexed, and re-challenged with a pemetrexed-based therapy. In these patients we found a disease control rate of 66%, with reduction of pain in 43% of patients. Overall time to progression and survival were promising for a second-line setting of patients with advanced mesothelioma, being 5.1 and 13.6 months, respectively. Conclusions In our opinion, when a patient has a long-lasting benefit from previous treatment with pemetrexed combined with a platin compound, the same treatment should be offered at progression. PMID:22943698

Advanced Photon Source accelerator ultrahigh vacuum guide

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

Liu, C.; Noonan, J.

1994-03-01

In this document the authors summarize the following: (1) an overview of basic concepts of ultrahigh vacuum needed for the APS project, (2) a description of vacuum design and calculations for major parts of APS, including linac, linac waveguide, low energy undulator test line, positron accumulator ring (PAR), booster synchrotron ring, storage ring, and insertion devices, and (3) cleaning procedures of ultrahigh vacuum (UHV) components presently used at APS.

Synthetic Lethality as a Targeted Approach to Advanced Prostate Cancer

DTIC Science & Technology

2013-03-01

cell line was derived from primary human prostate epithelial cells by transformation with human papilloma virus. While not tumorigenic, they do...normal cells and tissues has no significant adverse effects. Inhibition of PKCδ in human and murine cells containing an activated Ras protein, however...initiates rapid and profound apoptosis. In this work, we are testing the hypothesis that inhibition or down-regulation of PKCδ in human and murine

Tapered Roller Bearing Damage Detection Using Decision Fusion Analysis

NASA Technical Reports Server (NTRS)

Dempsey, Paula J.; Kreider, Gary; Fichter, Thomas

2006-01-01

A diagnostic tool was developed for detecting fatigue damage of tapered roller bearings. Tapered roller bearings are used in helicopter transmissions and have potential for use in high bypass advanced gas turbine aircraft engines. A diagnostic tool was developed and evaluated experimentally by collecting oil debris data from failure progression tests conducted using health monitoring hardware. Failure progression tests were performed with tapered roller bearings under simulated engine load conditions. Tests were performed on one healthy bearing and three pre-damaged bearings. During each test, data from an on-line, in-line, inductance type oil debris sensor and three accelerometers were monitored and recorded for the occurrence of bearing failure. The bearing was removed and inspected periodically for damage progression throughout testing. Using data fusion techniques, two different monitoring technologies, oil debris analysis and vibration, were integrated into a health monitoring system for detecting bearing surface fatigue pitting damage. The data fusion diagnostic tool was evaluated during bearing failure progression tests under simulated engine load conditions. This integrated system showed improved detection of fatigue damage and health assessment of the tapered roller bearings as compared to using individual health monitoring technologies.

Simulated flight acoustic investigation of treated ejector effectiveness on advanced mechanical suppresors for high velocity jet noise reduction

NASA Technical Reports Server (NTRS)

Brausch, J. F.; Motsinger, R. E.; Hoerst, D. J.

1986-01-01

Ten scale-model nozzles were tested in an anechoic free-jet facility to evaluate the acoustic characteristics of a mechanically suppressed inverted-velocity-profile coannular nozzle with an accoustically treated ejector system. The nozzle system used was developed from aerodynamic flow lines evolved in a previous contract, defined to incorporate the restraints imposed by the aerodynamic performance requirements of an Advanced Supersonic Technology/Variable Cycle Engine system through all its mission phases. Accoustic data of 188 test points were obtained, 87 under static and 101 under simulated flight conditions. The tests investigated variables of hardwall ejector application to a coannular nozzle with 20-chute outer annular suppressor, ejector axial positioning, treatment application to ejector and plug surfaces, and treatment design. Laser velocimeter, shadowgraph photograph, aerodynamic static pressure, and temperature measurement were acquired on select models to yield diagnositc information regarding the flow field and aerodynamic performance characteristics of the nozzles.

Use of Spacecraft Command Language for Advanced Command and Control Applications

NASA Technical Reports Server (NTRS)

Mims, Tikiela L.

2008-01-01

The purpose of this work is to evaluate the use of SCL in building and monitoring command and control applications in order to determine its fitness for space operations. Approximately 24,325 lines of PCG2 code was converted to SCL yielding a 90% reduction in the number of lines of code as many of the functions and scripts utilized in SCL could be ported and reused. Automated standalone testing, simulating the actual production environment, was performed in order to generalize and gauge the relative time it takes for SCL to update and write a given display. The use of SCL rules, functions, and scripts allowed the creation of several test cases permitting the detection of the amount of time it takes update a given set of measurements given the change in a globally existing CUI or CUI. It took the SCL system an average 926.09 ticks to update the entire display of 323 measurements.

Pro-apoptotic activity of new analog of anthracyclines--WP 631 in advanced ovarian cancer cell line.

PubMed

Gajek, Arkadiusz; Denel, Marta; Bukowska, Barbara; Rogalska, Aneta; Marczak, Agnieszka

2014-03-01

In this work we investigated the mode of cell death induced by WP 631, a novel anthracycline antibiotic, in the ovarian cancer cell line (OV-90) derived from the malignant ascites of a patient diagnosed with advanced disease. The effects were compared with those of doxorubicin (DOX), a first generation anthracycline. The ability of WP 631 to induce apoptosis and necrosis was examined by double staining with Annexin V and propidium iodide, measurements of the level of intracellular calcium ions and cytochrome c, PARP cleavage. We also investigated the possible involvement of the caspases activation, DNA degradation (comet assay) and intracellular reactive oxygen species (ROS) production in the development of the apoptotic events and their significance for drug efficiency. The results obtained clearly demonstrate that antiproliferative capacity of WP 631 in tested cell line was a few times greater than that of DOX. Furthermore, ovarian cancer cells treated with WP 631 showed a higher mean level of basal DNA damage in comparison to DOX. In conclusion, WP 631 is able to induce caspase - dependent apoptosis in human ovarian cancer cells. Obtained results suggested that WP 631 may be a candidate for further evaluation as chemotherapeutic agents for human cancers. Copyright © 2013 Elsevier Ltd. All rights reserved.

Human metastatic melanoma cell lines express high levels of growth hormone receptor and respond to GH treatment

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

Sustarsic, Elahu G.; Department of Biological Sciences, Ohio University, Athens, OH; Junnila, Riia K.

2013-11-08

Highlights: •Most cancer types of the NCI60 have sub-sets of cell lines with high GHR expression. •GHR is highly expressed in melanoma cell lines. •GHR is elevated in advanced stage IV metastatic tumors vs. stage III. •GH treatment of metastatic melanoma cell lines alters growth and cell signaling. -- Abstract: Accumulating evidence implicates the growth hormone receptor (GHR) in carcinogenesis. While multiple studies show evidence for expression of growth hormone (GH) and GHR mRNA in human cancer tissue, there is a lack of quantification and only a few cancer types have been investigated. The National Cancer Institute’s NCI60 panel includesmore » 60 cancer cell lines from nine types of human cancer: breast, CNS, colon, leukemia, melanoma, non-small cell lung, ovarian, prostate and renal. We utilized this panel to quantify expression of GHR, GH, prolactin receptor (PRLR) and prolactin (PRL) mRNA with real-time RT qPCR. Both GHR and PRLR show a broad range of expression within and among most cancer types. Strikingly, GHR expression is nearly 50-fold higher in melanoma than in the panel as a whole. Analysis of human metastatic melanoma biopsies confirmed GHR gene expression in melanoma tissue. In these human biopsies, the level of GHR mRNA is elevated in advanced stage IV tumor samples compared to stage III. Due to the novel finding of high GHR in melanoma, we examined the effect of GH treatment on three NCI60 melanoma lines (MDA-MB-435, UACC-62 and SK-MEL-5). GH increased proliferation in two out of three cell lines tested. Further analysis revealed GH-induced activation of STAT5 and mTOR in a cell line dependent manner. In conclusion, we have identified cell lines and cancer types that are ideal to study the role of GH and PRL in cancer, yet have been largely overlooked. Furthermore, we found that human metastatic melanoma tumors express GHR and cell lines possess active GHRs that can modulate multiple signaling pathways and alter cell proliferation. Based on this data, GH could be a new therapeutic target in melanoma.« less

Epidermal Growth Factor Receptor Mutation (EGFR) Testing for Prediction of Response to EGFR-Targeting Tyrosine Kinase Inhibitor (TKI) Drugs in Patients with Advanced Non-Small-Cell Lung Cancer: An Evidence-Based Analysis.

PubMed

2010-01-01

In February 2010, the Medical Advisory Secretariat (MAS) began work on evidence-based reviews of the literature surrounding three pharmacogenomic tests. This project came about when Cancer Care Ontario (CCO) asked MAS to provide evidence-based analyses on the effectiveness and cost-effectiveness of three oncology pharmacogenomic tests currently in use in Ontario.Evidence-based analyses have been prepared for each of these technologies. These have been completed in conjunction with internal and external stakeholders, including a Provincial Expert Panel on Pharmacogenetics (PEPP). Within the PEPP, subgroup committees were developed for each disease area. For each technology, an economic analysis was also completed by the Toronto Health Economics and Technology Assessment Collaborative (THETA) and is summarized within the reports.THE FOLLOWING REPORTS CAN BE PUBLICLY ACCESSED AT THE MAS WEBSITE AT: http://www.health.gov.on.ca/mas or at www.health.gov.on.ca/english/providers/program/mas/mas_about.htmlGENE EXPRESSION PROFILING FOR GUIDING ADJUVANT CHEMOTHERAPY DECISIONS IN WOMEN WITH EARLY BREAST CANCER: An Evidence-Based AnalysisEpidermal Growth Factor Receptor Mutation (EGFR) Testing for Prediction of Response to EGFR-Targeting Tyrosine Kinase Inhibitor (TKI) Drugs in Patients with Advanced Non-Small-Cell Lung Cancer: an Evidence-Based AnalysisK-RAS testing in Treatment Decisions for Advanced Colorectal Cancer: an Evidence-Based Analysis The Medical Advisory Secretariat undertook a systematic review of the evidence on the clinical effectiveness and cost-effectiveness of epidermal growth factor receptor (EGFR) mutation testing compared with no EGFR mutation testing to predict response to tyrosine kinase inhibitors (TKIs), gefitinib (Iressa(®)) or erlotinib (Tarceva(®)) in patients with advanced non-small cell lung cancer (NSCLC). TARGET POPULATION AND CONDITION With an estimated 7,800 new cases and 7,000 deaths last year, lung cancer is the leading cause of cancer deaths in Ontario. Those with unresectable or advanced disease are commonly treated with concurrent chemoradiation or platinum-based combination chemotherapy. Although response rates to cytotoxic chemotherapy for advanced NSCLC are approximately 30 to 40%, all patients eventually develop resistance and have a median survival of only 8 to 10 months. Treatment for refractory or relapsed disease includes single-agent treatment with docetaxel, pemetrexed or EGFR-targeting TKIs (gefitinib, erlotinib). TKIs disrupt EGFR signaling by competing with adenosine triphosphate (ATP) for the binding sites at the tyrosine kinase (TK) domain, thus inhibiting the phosphorylation and activation of EGFRs and the downstream signaling network. Gefitinib and erlotinib have been shown to be either non-inferior or superior to chemotherapy in the first- or second-line setting (gefitinib), or superior to placebo in the second- or third-line setting (erlotinib). Certain patient characteristics (adenocarcinoma, non-smoking history, Asian ethnicity, female gender) predict for better survival benefit and response to therapy with TKIs. In addition, the current body of evidence shows that somatic mutations in the EGFR gene are the most robust biomarkers for EGFR-targeting therapy selection. Drugs used in this therapy, however, can be costly, up to C$ 2000 to C$ 3000 per month, and they have only approximately a 10% chance of benefiting unselected patients. For these reasons, the predictive value of EGFR mutation testing for TKIs in patients with advanced NSCLC needs to be determined. EGFR MUTATION TESTING The EGFR gene sequencing by polymerase chain reaction (PCR) assays is the most widely used method for EGFR mutation testing. PCR assays can be performed at pathology laboratories across Ontario. According to experts in the province, sequencing is not currently done in Ontario due to lack of adequate measurement sensitivity. A variety of new methods have been introduced to increase the measurement sensitivity of the mutation assay. Some technologies such as single-stranded conformational polymorphism, denaturing high-performance liquid chromatography, and high-resolution melting analysis have the advantage of facilitating rapid mutation screening of large numbers of samples with high measurement sensitivity but require direct sequencing to confirm the identity of the detected mutations. Other techniques have been developed for the simple, but highly sensitive detection of specific EGFR mutations, such as the amplification refractory mutations system (ARMS) and the peptide nucleic acid-locked PCR clamping. Others selectively digest wild-type DNA templates with restriction endonucleases to enrich mutant alleles by PCR. Experts in the province of Ontario have commented that currently PCR fragment analysis for deletion and point mutation conducts in Ontario, with measurement sensitivity of 1% to 5%. In patients with locally-advanced or metastatic NSCLC, what is the clinical effectiveness of EGFR mutation testing for prediction of response to treatment with TKIs (gefitinib, erlotinib) in terms of progression-free survival (PFS), objective response rates (ORR), overall survival (OS), and quality of life (QoL)?What is the impact of EGFR mutation testing on overall clinical decision-making for patients with advanced or metastatic NSCLC?What is the cost-effectiveness of EGFR mutation testing in selecting patients with advanced NSCLC for treatment with gefitinib or erlotinib in the first-line setting?What is the budget impact of EGFR mutation testing in selecting patients with advanced NSCLC for treatment with gefitinib or erlotinib in the second- or third-line setting? A literature search was performed on March 9, 2010 using OVID MEDLINE, MEDLINE In-Process and Other Non-Indexed Citations, OVID EMBASE, Wiley Cochrane, CINAHL, Centre for Reviews and Dissemination/International Agency for Health Technology Assessment for studies published from January 1, 2004 until February 28, 2010 using the following terms: Non-Small-Cell Lung CarcinomaEpidermal Growth Factor ReceptorAn automatic literature update program also extracted all papers published from February 2010 until August 2010. Abstracts were reviewed by a single reviewer and for those studies meeting the eligibility criteria full-text articles were obtained. Reference lists were also examined for any additional relevant studies not identified through the search. Articles with unknown eligibility were reviewed with a second clinical epidemiologist, and then a group of epidemiologists, until consensus was established. The quality of evidence was assessed as high, moderate, low or very low according to GRADE methodology. The inclusion criteria were as follows: patients with locally advanced or metastatic NSCLC (stage IIIB or IV)PROCEDURE: EGFR mutation testing before treatment with gefitinib or erlotinibLANGUAGE: publication in EnglishPublished health technology assessments, guidelines, and peer-reviewed literature (abstracts, full text, conference abstract) progression-free survival (PFS), Objective response rate (ORR), overall survival (OS), quality of life (QoL).The exclusion criteria were as follows: Studies lacking outcomes specific to those of interestStudies focused on erlotinib maintenance therapyStudies focused on gefitinib or erlotinib use in combination with cytotoxic agents or any other drugGrey literature, where relevant, was also reviewed. PFSORR determined by means of the Response Evaluation Criteria in Solid Tumours (RECIST)OSQoL QUALITY OF EVIDENCE: The quality of the Phase II trials and observational studies was based on the method of subject recruitment and sampling, possibility of selection bias, and generalizability to the source population. The overall quality of evidence was assessed as high, moderate, low or very low according to the GRADE Working Group criteria. Since the last published health technology assessment by Blue Cross Blue Shield Association in 2007 there have been a number of phase III trials which provide evidence of predictive value of EGFR mutation testing in patients who were treated with gefitinib compared to chemotherapy in the first- or second-line setting. The Iressa Pan Asian Study (IPASS) trial showed the superiority of gefitinib in terms of PFS in patients with EGFR mutations versus patients with wild-type EGFR (Hazard ratio [HR], 0.48, 95%CI; 0.36-0.64 versus HR, 2.85; 95%CI, 2.05-3.98). Moreover, there was a statistically significant increased ORR in patients who received gefitinib and had EGFR mutations compared to patients with wild-type EGFR (71% versus 1%). The First-SIGNAL trial in patients with similar clinical characteristics as IPASS as well as the NEJ002 and WJTOG3405 trials that included only patients with EGFR mutations, provide confirmation that gefitinib is superior to chemotherapy in terms of improved PFS or higher ORR in patients with EGFR mutations. The INTEREST trial further indicated that patients with EGFR mutations had prolonged PFS and higher ORR when treated with gefitinib compared with docetaxel. In contrast, there is still a paucity of strong evidence regarding the predictive value of EGFR mutation testing for response to erlotinib in the second- or third-line setting. The BR.21 trial randomized 731 patients with NSCLC who were refractory or intolerant to prior first- or second-line chemotherapy to receive erlotinib or placebo. While the HR of 0.61 (95%CI, 0.51-0.74) favored erlotinib in the overall population, this was not a significant in the subsequent retrospective subgroup analysis. A retrospective evaluation of 116 of the BR.21 tumor samples demonstrated that patients with EGFR mutations had significantly higher ORRs when treated with erlotinib compared with placebo (27% versus 7%; P=0.03). (ABSTRACT TRUNCATED)

Advanced Demonstration and Test Reactor Options Study

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

Petti, David Andrew; Hill, R.; Gehin, J.

Global efforts to address climate change will require large-scale decarbonization of energy production in the United States and elsewhere. Nuclear power already provides 20% of electricity production in the United States (U.S.) and is increasing in countries undergoing rapid growth around the world. Because reliable, grid-stabilizing, low emission electricity generation, energy security, and energy resource diversity will be increasingly valued, nuclear power’s share of electricity production has a potential to grow. In addition, there are non electricity applications (e.g., process heat, desalination, hydrogen production) that could be better served by advanced nuclear systems. Thus, the timely development, demonstration, and commercializationmore » of advanced nuclear reactors could diversify the nuclear technologies available and offer attractive technology options to expand the impact of nuclear energy for electricity generation and non-electricity missions. The purpose of this planning study is to provide transparent and defensible technology options for a test and/or demonstration reactor(s) to be built to support public policy, innovation and long term commercialization within the context of the Department of Energy’s (DOE’s) broader commitment to pursuing an “all of the above” clean energy strategy and associated time lines. This planning study includes identification of the key features and timing needed for advanced test or demonstration reactors to support research, development, and technology demonstration leading to the commercialization of power plants built upon these advanced reactor platforms. This planning study is consistent with the Congressional language contained within the fiscal year 2015 appropriation that directed the DOE to conduct a planning study to evaluate “advanced reactor technology options, capabilities, and requirements within the context of national needs and public policy to support innovation in nuclear energy”. Advanced reactors are defined in this study as reactors that use coolants other than water. Advanced reactor technologies have the potential to expand the energy applications, enhance the competitiveness, and improve the sustainability of nuclear energy.« less

Erlotinib or best supportive care for third-line treatment of advanced non-small-cell lung cancer: a real-world cost-effectiveness analysis.

PubMed

Cromwell, Ian; van der Hoek, Kimberly; Malfair Taylor, Suzanne C; Melosky, Barbara; Peacock, Stuart

2012-06-01

Erlotinib has been approved as a third-line treatment for advanced non-small-cell lung cancer (NSCLC) in British Columbia (BC). A cost-effectiveness analysis was conducted to compare costs and effectiveness in patients who received third-line erlotinib to those in a historical patient cohort that would have been eligible had erlotinib been available. In a population of patients who have been treated with drugs for advanced NSCLC, overall survival (OS), progression-to-death survival (PTD) and probability of survival one year after end of second-line (1YS) were determined using a Kaplan-Meier survival analysis. Costs were collected retrospectively from the perspective of the BC health care system. Incremental mean OS was 90 days (0.25 LYG), and incremental mean cost was $11,102 (CDN 2009), resulting in a mean ICER of $36,838/LYG. Univariate sensitivity analysis yielded ICERs ranging from $21,300 to $51,700/LYG. Our analysis suggests that erlotinib may be an effective and cost-effective third-line treatment for advanced NSCLC compared to best supportive care. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

STATUS OF TRISO FUEL IRRADIATIONS IN THE ADVANCED TEST REACTOR SUPPORTING HIGH-TEMPERATURE GAS-COOLED REACTOR DESIGNS

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

Davenport, Michael; Petti, D. A.; Palmer, Joe

2016-11-01

The United States Department of Energy’s Advanced Reactor Technologies (ART) Advanced Gas Reactor (AGR) Fuel Development and Qualification Program is irradiating up to seven low enriched uranium (LEU) tri-isotopic (TRISO) particle fuel (in compact form) experiments in the Advanced Test Reactor (ATR) located at the Idaho National Laboratory (INL). These irradiations and fuel development are being accomplished to support development of the next generation reactors in the United States. The experiments will be irradiated over the next several years to demonstrate and qualify new TRISO coated particle fuel for use in high temperature gas reactors. The goals of the experimentsmore » are to provide irradiation performance data to support fuel process development, to qualify fuel for normal operating conditions, to support development and validation of fuel performance and fission product transport models and codes, and to provide irradiated fuel and materials for post irradiation examination (PIE) and safety testing. The experiments, which will each consist of several independent capsules, will be irradiated in an inert sweep gas atmosphere with individual on-line temperature monitoring and control of each capsule. The sweep gas will also have on-line fission product monitoring on its effluent to track performance of the fuel in each individual capsule during irradiation. The first experiment (designated AGR-1) started irradiation in December 2006 and was completed in November 2009. The second experiment (AGR-2) started irradiation in June 2010 and completed in October 2013. The third and fourth experiments have been combined into a single experiment designated (AGR-3/4), which started its irradiation in December 2011 and completed in April 2014. Since the purpose of this experiment was to provide data on fission product migration and retention in the NGNP reactor, the design of this experiment was significantly different from the first two experiments, though the control and monitoring systems are very similar. The final experiment, AGR-5/6/7, is scheduled to begin irradiation in early summer 2017.« less

Economic Evaluation of Companion Diagnostic Testing for EGFR Mutations and First-Line Targeted Therapy in Advanced Non-Small Cell Lung Cancer Patients in South Korea.

PubMed

Lim, Eun-A; Lee, Haeyoung; Bae, Eunmi; Lim, Jaeok; Shin, Young Kee; Choi, Sang-Eun

2016-01-01

As targeted therapy becomes increasingly important, diagnostic techniques for identifying targeted biomarkers have also become an emerging issue. The study aims to evaluate the cost-effectiveness of treating patients as guided by epidermal growth factor receptor (EGFR) mutation status compared with a no-testing strategy that is the current clinical practice in South Korea. A cost-utility analysis was conducted to compare an EGFR mutation testing strategy with a no-testing strategy from the Korean healthcare payer's perspective. The study population consisted of patients with stage 3b and 4 lung adenocarcinoma. A decision tree model was employed to select the appropriate treatment regimen according to the results of EGFR mutation testing and a Markov model was constructed to simulate disease progression of advanced non-small cell lung cancer. The length of a Markov cycle was one month, and the time horizon was five years (60 cycles). In the base case analysis, the testing strategy was a dominant option. Quality-adjusted life-years gained (QALYs) were 0.556 and 0.635, and total costs were $23,952 USD and $23,334 USD in the no-testing and testing strategy respectively. The sensitivity analyses showed overall robust results. The incremental cost-effectiveness ratios (ICERs) increased when the number of patients to be treated with erlotinib increased, due to the high cost of erlotinib. Treating advanced adenocarcinoma based on EGFR mutation status has beneficial effects and saves the cost compared to no testing strategy in South Korea. However, the cost-effectiveness of EGFR mutation testing was heavily affected by the cost-effectiveness of the targeted therapy.

Effects of 60-Heartz electric and magnetic fields on implanted cardiac pacemakers. Final report. [Hazards of power transmission line frequencies

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

Bridges, J.E.; Frazier, M.J.

1979-09-01

The effects of 60-Hz electric and magnetic fields of exta-high voltage (EHV) transmission lines on the performance of implanted cardiac pacemakers were studied by: (1) in vitro bench tests of a total of thirteen cardiac pacemakers; (2) in vivo tests of six implanted cardiac pacemakers in baboons; and (3) non-hazardous skin measurement tests on four humans. Analytical methods were developed to predict the thresholds of body current and electric fields capable of affecting normal pacemaker operation in humans. The field strengths calculated to alter implanted pacemaker performance were compared with the range of maximum electric and magnetic field strengths amore » human would normally encounter under transmission lines of various voltages. Results indicate that the electric field or body current necessary to alter the normal operation of pacemakers is highly dependent on the type of pacemaker and the location of the implanted electrodes. However, cardiologists have not so far detected harmful effects of pacemaker reversion to the asynchronous mode in current types of pacemakers and with present methods of implantation. Such interferences can be eliminated by using advanced pacemakers less sensitive to 60-Hz voltages or by using implantation lead arrangements less sensitive to body current.« less

Economic Analysis of First-Line Treatment with Erlotinib in an EGFR-Mutated Population with Advanced NSCLC.

PubMed

Vergnenegre, Alain; Massuti, Bartomeu; de Marinis, Filippo; Carcereny, Enric; Felip, Enriqueta; Do, Pascal; Sanchez, Jose Miguel; Paz-Arez, Luis; Chouaid, Christos; Rosell, Rafael

2016-06-01

The cost-effectiveness of first-line tyrosine kinase inhibitor therapy in epidermal growth factor receptor gene (EGFR)-mutated advanced-stage non-small cell lung cancer (NSCLC) is poorly documented. We therefore conducted a cost-effectiveness analysis of first-line treatment with erlotinib versus standard chemotherapy in European patients with advanced-stage EGFR-mutated NSCLC who were enrolled in the European Erlotinib versus Chemotherapy trial. The European Erlotinib versus Chemotherapy study was a multicenter, open-label, randomized phase III trial performed mainly in Spain, France, and Italy. We based our economic analysis on clinical data and data on resource consumption (drugs, drug administration, adverse events, and second-line treatments) collected during this trial. Utility values were derived from the literature. Incremental cost-effectiveness ratios were calculated for the first-line treatment phase and for the overall strategy from the perspective of the three participating countries. Sensitivity analyses were performed by selecting the main cost drivers. Compared with standard first-line chemotherapy, the first-line treatment with erlotinib was cost saving (€7807, €17,311, and €19,364 for Spain, Italy and France, respectively) and yielded a gain of 0.117 quality-adjusted life-years. A probabilistic sensitivity analysis indicated that, given a willingness to pay at least €90,000 for 1 quality-adjusted life-year, the probability that a strategy of first-line erlotinib would be cost-effective was 100% in France, 100% in Italy, and 99.8% in Spain. This economic analysis shows that first-line treatment with erlotinib, versus standard chemotherapy, is a dominant strategy for EGFR-mutated advanced-stage NSCLC in three European countries. Copyright © 2016 International Association for the Study of Lung Cancer. Published by Elsevier Inc. All rights reserved.

Resources and Costs Associated with the Treatment of Advanced and Metastatic Gastric Cancer in the Mexican Public Sector: A Patient Chart Review.

PubMed

Quintana, Miguel; Toriz, José A; Novick, Diego; Jones, Kyla; Botello, Brenda S; Silva, Juan Alejandro

2018-06-01

Little evidence is available on the management and cost of treating patients with advanced or metastatic gastric cancer (GC). This study evaluates patient characteristics, treatment patterns, and resource utilization for these patients in Mexico. Data were collected from three centers of investigation (tertiary level). Patients were ≥18 years of age, diagnosed between 1 January 2009 and 1 January 2015, had advanced or metastatic GC, received first-line fluoropyrimidine/platinum, and had ≥3 months follow-up after discontinuing first-line treatment. Data were summarized using descriptive statistics. The study sample totaled 180. Patients' mean age was 57.2 years (±12.4) and 57.0% were male; 151 (83.9%) patients received second-line chemotherapy. A total of 16 and 19 regimens were identified in first- and second-line therapy. Of the sample, 51 (28.3%) received third-line therapy, and <10% received more than three lines of active chemotherapy. Supportive care received in first- and second-line chemotherapy, included pain interventions (12.2 and 7.9%), nutritional support (3.3 and 1.3%), radiotherapy (6.1 and 16.6%), and transfusions (13.3 and 10.6%), respectively. Using Mexican Institute of Social Security (IMSS) tariffs, the average total cost per patient-month in first- and second-line therapy was US$1230 [95% confidence interval (CI) 1034-1425] and US$1192 (95% CI 913-1471), respectively. Administration and acquisition of chemotherapy comprised the majority of costs. This study shows considerable variation in first- and second-line chemotherapy regimens of patients with advanced or metastatic GC. Understanding GC treatment patterns in Mexico will help address unmet needs.

Extended X-ray Absorption Fine Structure Study of Bond Constraints in Ge-Sb-Te Alloys

DTIC Science & Technology

2011-02-07

Ray Absorption Spectroscopy, or EXAFS. Using the spectroscopic capabilities provided by the MCAT line at the Advanced Photon Source at Argonne...Absorption Spectroscopy, or EXAFS. Using the spectroscopic capabilities provided by the MCAT line at the Advanced Photon Source at Argonne National

Disease evaluations and agronomic traits of advanced peanut breeding lines in 2017

USDA-ARS?s Scientific Manuscript database

Disease evaluations of advanced peanut breeding lines are conducted annually to compare the agronomic traits (crop value, yield, seed grade and characteristics) and disease resistance in cultivars that are currently available or close to being released for the Southwest. In 2017, a total of 19 comm...

[Comparison of the Efficacy and Safety of Icotinib with Standard Second-line 
Chemotherapy in Previously Treated Advanced Non-small Cell Lung Cancer].

PubMed

Yao, Shuyang; Qian, Kun; Wang, Ruotian; Li, Yuanbo; Zhang, Yi

2015-06-01

This study compared the efficacy and safety of icotinib with standard second-line chemotherapy (single-agent docetaxel or pemetrexed) in previously treated advanced non-small cell lung cancer (NSCLC). Thirty-two consecutive patients treated with icotinib and 33 consecutive patients treated with standard second-line chemotherapy in Xuanwu Hospital from January 2012 to July 2013 were enrolled in our retrospective research. The Response Evaluation Criteria in Solid Tumors were used to evaluate the tumor responses, and the progression-free survival (PFS) was evaluated by Kaplan-Meier method. Icotinib was comparable with standard second-line chemotherapy for advanced NSCLC in terms of overall response rate (ORR) (28.1% vs 18.2%, P=0.341), disease control rate (DFS)(43.8% vs 45.5%, P=0.890), and PFS (4.3 months vs 3.8 months, P=0.506). In the icotinib group, the ORR of epidermal growth factor receptor (EGFR) mutant was significantly higher than that of EGFR unknown or wild type (P=0.017). In multivariate analysis, age, gender, histology, and the optimum first-line treatment response were dependent prognostic factors based on the PFS of the icotinib group. The incidence of adverse events was significantly fewer in the icotinib group than in the chemotherapy group (P=0.001). Compared with the standard second-line chemotherapy, icotinib is active in the treatment of advanced NSCLC patients, especially with EGFR unknown in the second line, with an acceptable adverse event profile.

Vision-based mobile robot navigation through deep convolutional neural networks and end-to-end learning

NASA Astrophysics Data System (ADS)

Zhang, Yachu; Zhao, Yuejin; Liu, Ming; Dong, Liquan; Kong, Lingqin; Liu, Lingling

2017-09-01

In contrast to humans, who use only visual information for navigation, many mobile robots use laser scanners and ultrasonic sensors along with vision cameras to navigate. This work proposes a vision-based robot control algorithm based on deep convolutional neural networks. We create a large 15-layer convolutional neural network learning system and achieve the advanced recognition performance. Our system is trained from end to end to map raw input images to direction in supervised mode. The images of data sets are collected in a wide variety of weather conditions and lighting conditions. Besides, the data sets are augmented by adding Gaussian noise and Salt-and-pepper noise to avoid overfitting. The algorithm is verified by two experiments, which are line tracking and obstacle avoidance. The line tracking experiment is proceeded in order to track the desired path which is composed of straight and curved lines. The goal of obstacle avoidance experiment is to avoid the obstacles indoor. Finally, we get 3.29% error rate on the training set and 5.1% error rate on the test set in the line tracking experiment, 1.8% error rate on the training set and less than 5% error rate on the test set in the obstacle avoidance experiment. During the actual test, the robot can follow the runway centerline outdoor and avoid the obstacle in the room accurately. The result confirms the effectiveness of the algorithm and our improvement in the network structure and train parameters

Surrogate endpoints for overall survival in advanced non-small-cell lung cancer patients with mutations of the epidermal growth factor receptor gene.

PubMed

Yoshino, Reiko; Imai, Hisao; Mori, Keita; Takei, Kousuke; Tomizawa, Mai; Kaira, Kyoichi; Yoshii, Akihiro; Tomizawa, Yoshio; Saito, Ryusei; Yamada, Masanobu

2014-09-01

Subsequent therapies confound the ability to discern the effect of first-line chemotherapy on overall survival (OS). We investigated whether progression-free survival (PFS), post-progression survival (PPS) and tumor response were valid surrogate endpoints for OS following first-line chemotherapy in individual patients with advanced non-small-cell lung cancer (NSCLC) harboring sensitive epidermal growth factor receptor gene mutations. We retrospectively analyzed 35 patients with advanced NSCLC treated with first-line gefitinib. The associations of PFS, PPS and tumor response with OS were analyzed. PPS was found to be strongly correlated with OS, unlike PFS and tumor shrinkage. The factors significantly associated with PPS were performance status (PS) after first-line treatment, best response to second-line treatment and number of regimens used after disease progression. PPS may be a surrogate for OS in this patient population and further therapy after disease progression following first-line chemotherapy may significantly affect OS. However, a larger study is required to validate these results.

A retrospective analysis of efficacy and safety of adding bevacizumab to chemotherapy as first- and second-line therapy in advanced non-small-cell lung cancer (NSCLC).

PubMed

Quan, Rencui; Huang, Jiaxing; Chen, Nan; Fang, Wenfeng; Hu, Zhihuang; Zhan, Jianhua; Zhou, Ting; Zhang, Li; Zhang, Hongyu

2016-08-01

Several phase III clinical trials had authenticated that the addition of bevacizumab to paclitaxel plus carboplatin or gemcitabine plus cisplatin showed encouraging efficacy as first-line therapy for advanced NSCLC patients. However, the benefits of adding bevacizumab to other chemotherapy regimens in first- or second-line therapy have not been reported. To compare the clinical efficacy and safety of bevacizumab concomitant with chemotherapy regimens in patients with advanced NSCLC as first- or second-line therapy, we retrospectively reviewed the effects of adding bevacizumab to chemotherapy regimens in naive-chemotherapy and pre-chemotherapy patients with advanced non-squamous NSCLC. A total of 79 patients with advanced non-squamous NSCLC received at least two cycles of bevacizumab with chemotherapy between October 2010 and December 2013 were selected. Our primary end points were overall response rate (ORR) and disease control rate (DCR). The secondary objective was overall survival (OS) and safety. Seventy-nine patients were included in this study. Overall response rates at first evaluation (after 2 cycles) were 23.1 % (9/39) and 5.0 % (2/40) in first- and second-line therapy (P = 0.020), respectively. And disease control rates were 84.6 % (33/39) and 50 % (20/40), respectively (P = 0.001). The median OS were 27.2 months (95 % CI 13.3-41.1 months) and 29.6 months (95 % CI 6.7-52.5 months), respectively (P = 0.740). Grade 3-4 adverse events included leukopenia (2/39), and neutropenia (3/39) in first-line therapy versus neutropenia (1/40) and thrombocytopenia (2/40) in second-line treatment. In our experience, combination of bevacizumab and chemotherapy had encouraging anti-tumor efficacy as both first- and second-line therapy.

Multivariable Time Series Prediction for the Icing Process on Overhead Power Transmission Line

PubMed Central

Li, Peng; Zhao, Na; Zhou, Donghua; Cao, Min; Li, Jingjie; Shi, Xinling

2014-01-01

The design of monitoring and predictive alarm systems is necessary for successful overhead power transmission line icing. Given the characteristics of complexity, nonlinearity, and fitfulness in the line icing process, a model based on a multivariable time series is presented here to predict the icing load of a transmission line. In this model, the time effects of micrometeorology parameters for the icing process have been analyzed. The phase-space reconstruction theory and machine learning method were then applied to establish the prediction model, which fully utilized the history of multivariable time series data in local monitoring systems to represent the mapping relationship between icing load and micrometeorology factors. Relevant to the characteristic of fitfulness in line icing, the simulations were carried out during the same icing process or different process to test the model's prediction precision and robustness. According to the simulation results for the Tao-Luo-Xiong Transmission Line, this model demonstrates a good accuracy of prediction in different process, if the prediction length is less than two hours, and would be helpful for power grid departments when deciding to take action in advance to address potential icing disasters. PMID:25136653

Number line estimation and mental addition: examining the potential roles of language and education.

PubMed

Laski, Elida V; Yu, Qingyi

2014-01-01

This study investigated the relative importance of language and education to the development of numerical knowledge. Consistent with previous research suggesting that counting systems that transparently reflect the base-10 system facilitate an understanding of numerical concepts, Chinese and Chinese American kindergartners' and second graders' number line estimation (0-100 and 0-1000) was 1 to 2 years more advanced than that of American children tested in previous studies. However, Chinese children performed better than their Chinese American peers, who were fluent in Chinese but had been educated in America, at kindergarten on 0-100 number lines, at second grade on 0-1000 number lines, and at both time points on complex addition problems. Overall, the pattern of findings suggests that educational approach may have a greater influence on numerical development than the linguistic structure of the counting system. The findings also demonstrate that, despite generating accurate estimates of numerical magnitude on 0-100 number lines earlier, it still takes Chinese children approximately 2 years to demonstrate accurate estimates on 0-1000 number lines, which raises questions about how to promote the mapping of knowledge across numerical scales. Copyright © 2013 Elsevier Inc. All rights reserved.

Analytic validation and real-time clinical application of an amplicon-based targeted gene panel for advanced cancer

PubMed Central

Wing, Michele R.; Reeser, Julie W.; Smith, Amy M.; Reeder, Matthew; Martin, Dorrelyn; Jewell, Benjamin M.; Datta, Jharna; Miya, Jharna; Monk, J. Paul; Mortazavi, Amir; Otterson, Gregory A.; Goldberg, Richard M.; VanDeusen, Jeffrey B.; Cole, Sharon; Dittmar, Kristin; Jaiswal, Sunny; Kinzie, Matthew; Waikhom, Suraj; Freud, Aharon G.; Zhou, Xiao-Ping; Chen, Wei; Bhatt, Darshna; Roychowdhury, Sameek

2017-01-01

Multiplex somatic testing has emerged as a strategy to test patients with advanced cancer. We demonstrate our analytic validation approach for a gene hotspot panel and real-time prospective clinical application for any cancer type. The TruSight Tumor 26 assay amplifies 85 somatic hotspot regions across 26 genes. Using cell line and tumor mixes, we observed that 100% of the 14,715 targeted bases had at least 1000x raw coverage. We determined the sensitivity (100%, 95% CI: 96-100%), positive predictive value (100%, 95% CI: 96-100%), reproducibility (100% concordance), and limit of detection (3% variant allele frequency at 1000x read depth) of this assay to detect single nucleotide variants and small insertions and deletions. Next, we applied the assay prospectively in a clinical tumor sequencing study to evaluate 174 patients with metastatic or advanced cancer, including frozen tumors, formalin-fixed tumors, and enriched peripheral blood mononuclear cells in hematologic cancers. We reported one or more somatic mutations in 89 (53%) of the sequenced tumors (167 passing quality filters). Forty-three of these patients (26%) had mutations that would enable eligibility for targeted therapies. This study demonstrates the validity and feasibility of applying TruSight Tumor 26 for pan-cancer testing using multiple specimen types. PMID:29100271

Vehicle to Electric Vehicle Supply Equipment Smart Grid Communications Interface Research and Testing Report

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

Kevin Morrow; Dimitri Hochard; Jeff Wishart

2011-09-01

Plug-in electric vehicles (PEVs), including battery electric, plug-in hybrid electric, and extended range electric vehicles, are under evaluation by the U.S. Department of Energy's Advanced Vehicle Testing Activity (AVTA) and other various stakeholders to better understand their capability and potential petroleum reduction benefits. PEVs could allow users to significantly improve fuel economy over a standard hybrid electric vehicles, and in some cases, depending on daily driving requirements and vehicle design, PEVs may have the ability to eliminate petroleum consumption entirely for daily vehicle trips. The AVTA is working jointly with the Society of Automotive Engineers (SAE) to assist in themore » further development of standards necessary for the advancement of PEVs. This report analyzes different methods and available hardware for advanced communications between the electric vehicle supply equipment (EVSE) and the PEV; particularly Power Line Devices and their physical layer. Results of this study are not conclusive, but add to the collective knowledge base in this area to help define further testing that will be necessary for the development of the final recommended SAE communications standard. The Idaho National Laboratory and the Electric Transportation Applications conduct the AVTA for the United States Department of Energy's Vehicle Technologies Program.« less

Cost-effectiveness analysis of EGFR mutation testing in patients with non-small cell lung cancer (NSCLC) with gefitinib or carboplatin-paclitaxel.

PubMed

Arrieta, Oscar; Anaya, Pablo; Morales-Oyarvide, Vicente; Ramírez-Tirado, Laura Alejandra; Polanco, Ana C

2016-09-01

Assess the cost-effectiveness of an EGFR-mutation testing strategy for advanced NSCLC in first-line therapy with either gefitinib or carboplatin-paclitaxel in Mexican institutions. Cost-effectiveness analysis using a discrete event simulation (DES) model to simulate two therapeutic strategies in patients with advanced NSCLC. Strategy one included patients tested for EGFR-mutation and therapy given accordingly. Strategy two included chemotherapy for all patients without testing. All results are presented in 2014 US dollars. The analysis was made with data from the Mexican frequency of EGFR-mutation. A univariate sensitivity analysis was conducted on EGFR prevalence. Progression-free survival (PFS) transition probabilities were estimated on data from the IPASS and simulated with a Weibull distribution, run with parallel trials to calculate a probabilistic sensitivity analysis. PFS of patients in the testing strategy was 6.76 months (95 % CI 6.10-7.44) vs 5.85 months (95 % CI 5.43-6.29) in the non-testing group. The one-way sensitivity analysis showed that PFS has a direct relationship with EGFR-mutation prevalence, while the ICER and testing cost have an inverse relationship with EGFR-mutation prevalence. The probabilistic sensitivity analysis showed that all iterations had incremental costs and incremental PFS for strategy 1 in comparison with strategy 2. There is a direct relationship between the ICER and the cost of EGFR testing, with an inverse relationship with the prevalence of EGFR-mutation. When prevalence is >10 % ICER remains constant. This study could impact Mexican and Latin American health policies regarding mutation detection testing and treatment for advanced NSCLC.

Use of solar advanced oxidation processes for wastewater treatment: Follow-up on degradation products, acute toxicity, genotoxicity and estrogenicity.

PubMed

Brienza, M; Mahdi Ahmed, M; Escande, A; Plantard, G; Scrano, L; Chiron, S; Bufo, S A; Goetz, V

2016-04-01

Wastewater tertiary treatment by advanced oxidation processes is thought to produce a treated effluent with lower toxicity than the initial influent. Here we performed tertiary treatment of a secondary effluent collected from a Waste Water Treatment Plant via homogeneous (solar/HSO5(-)/Fe(2+)) and heterogeneous (solar/TiO2) solar advanced oxidation aiming at the assessment of their effectiveness in terms of contaminants' and toxicity abatement in a plain solar reactor. A total of 53 organic contaminants were qualitatively identified by liquid chromatography coupled to high-resolution mass spectrometry after solid phase extraction. Solar advanced oxidation totally or partially removed the major part of contaminants detected within 4.5 h. Standard toxicity tests were performed using Vibrio fischeri, Daphnia magna, Pseudokirchneriella subcapitata and Brachionus calyciflorus organisms to evaluate acute and chronic toxicity in the secondary or tertiary effluents, and the EC50% was calculated. Estrogenic and genotoxic tests were carried out in an attempt to obtain an even sharper evaluation of potential hazardous effects due to micropollutants or their degradation by-products in wastewater. Genotoxic effects were not detected in effluent before or after treatment. However, we observed relevant estrogenic activity due to the high sensitivity of the HELN ERα cell line. Copyright © 2016 Elsevier Ltd. All rights reserved.

The fibroblast surface markers FAP, anti-fibroblast, and FSP are expressed by cells of epithelial origin and may be altered during epithelial-to-mesenchymal transition.

PubMed

Kahounová, Zuzana; Kurfürstová, Daniela; Bouchal, Jan; Kharaishvili, Gvantsa; Navrátil, Jiří; Remšík, Ján; Šimečková, Šárka; Študent, Vladimír; Kozubík, Alois; Souček, Karel

2017-04-06

The identification of fibroblasts and cancer-associated fibroblasts from human cancer tissue using surface markers is difficult, especially because the markers used currently are usually not expressed solely by fibroblasts, and the identification of fibroblast-specific surface molecules is still under investigation. It was aimed to compare three commercially available antibodies in the detection of different surface epitopes of fibroblasts (anti-fibroblast, fibroblast activation protein α, and fibroblast surface protein). The specificity of their expression, employing fibroblast cell lines and tumor-derived fibroblasts from breast and prostate tissues was investigated. Both the established fibroblast cell line HFF-1 and ex vivo primary fibroblasts isolated from breast and prostate cancer tissues expressed the tested surface markers to different degrees. Surprisingly, those markers were expressed also by permanent cell lines of epithelial origin, both benign and cancer-derived (breast-cell lines MCF 10A, HMLE and prostate-cell lines BPH-1, DU 145, and PC-3). The expression of fibroblast activation protein α increased on the surface of previously described models of epithelial cells undergoing epithelial-to-mesenchymal transition in response to treatment with TGF-β1. To prove the co-expression of the fibroblast markers on cells of epithelial origin, we used freshly dissociated human prostate and breast cancer tissues. The results confirmed the co-expression of anti-fibroblast and fibroblast surface protein on CD31/CD45-negative/EpCAM-positive epithelial cells. In summary, our data support the findings that the tested fibroblast markers are not fibroblast specific and may be expressed also by cells of epithelial origin (e.g., cells undergoing EMT). Therefore, the expression of these markers should be interpreted with caution, and the combination of several epitopes for both positive (anti-fibroblast or fibroblast activation protein α) and negative (EpCAM) identification of fibroblasts from breast and prostate tumor tissues is advised. © 2017 International Society for Advancement of Cytometry. © 2017 International Society for Advancement of Cytometry.

Design and Development of a Miniaturized Percutaneously Deployable Wireless Left Ventricular Assist Device: Early Prototypes and Feasibility Testing.

PubMed

Letzen, Brian; Park, Jiheum; Tuzun, Zeynep; Bonde, Pramod

The current left ventricular assist devices (LVADs) are limited by a highly invasive implantation procedure in a severely unstable group of advanced heart failure patients. Additionally, the current transcutaneous power drive line acts as a nidus for infection resulting in significant morbidity and mortality. In an effort to decrease this invasiveness and eliminate drive line complications, we have conceived a wireless miniaturized percutaneous LVAD, capable of being delivered endovascularly with a tether-free operation. The system obviates the need for a transcutaneous fluid purge line required in existing temporary devices by utilizing an incorporated magnetically coupled impeller for a complete seal. The objective of this article was to demonstrate early development and proof-of-concept feasibility testing to serve as the groundwork for future formalized device development. Five early prototypes were designed and constructed to iteratively minimize the pump size and improve fluid dynamic performance. Various magnetic coupling configurations were tested. Using SolidWorks and ANSYS software for modeling and simulation, several geometric parameters were varied. HQ curves were constructed from preliminary in vitro testing to characterize the pump performance. Bench top tests showed no-slip magnetic coupling of the impeller to the driveshaft up to the current limit of the motor. The pump power requirements were tested in vitro and were within the appropriate range for powering via a wireless energy transfer system. Our results demonstrate the proof-of-concept feasibility of a novel endovascular cardiac assist device with the potential to eventually offer patients an untethered, minimally invasive support.

Unbiased roughness measurements: the key to better etch performance

NASA Astrophysics Data System (ADS)

Liang, Andrew; Mack, Chris; Sirard, Stephen; Liang, Chen-wei; Yang, Liu; Jiang, Justin; Shamma, Nader; Wise, Rich; Yu, Jengyi; Hymes, Diane

2018-03-01

Edge placement error (EPE) has become an increasingly critical metric to enable Moore's Law scaling. Stochastic variations, as characterized for lines by line width roughness (LWR) and line edge roughness (LER), are dominant factors in EPE and known to increase with the introduction of EUV lithography. However, despite recommendations from ITRS, NIST, and SEMI standards, the industry has not agreed upon a methodology to quantify these properties. Thus, differing methodologies applied to the same image often result in different roughness measurements and conclusions. To standardize LWR and LER measurements, Fractilia has developed an unbiased measurement that uses a raw unfiltered line scan to subtract out image noise and distortions. By using Fractilia's inverse linescan model (FILM) to guide development, we will highlight the key influences of roughness metrology on plasma-based resist smoothing processes. Test wafers were deposited to represent a 5 nm node EUV logic stack. The patterning stack consists of a core Si target layer with spin-on carbon (SOC) as the hardmask and spin-on glass (SOG) as the cap. Next, these wafers were exposed through an ASML NXE 3350B EUV scanner with an advanced chemically amplified resist (CAR). Afterwards, these wafers were etched through a variety of plasma-based resist smoothing techniques using a Lam Kiyo conductor etch system. Dense line and space patterns on the etched samples were imaged through advanced Hitachi CDSEMs and the LER and LWR were measured through both Fractilia and an industry standard roughness measurement software. By employing Fractilia to guide plasma-based etch development, we demonstrate that Fractilia produces accurate roughness measurements on resist in contrast to an industry standard measurement software. These results highlight the importance of subtracting out SEM image noise to obtain quicker developmental cycle times and lower target layer roughness.

Explosive vessel for coupling dynamic experiments to the X-ray beam at the Advanced Photon Source

NASA Astrophysics Data System (ADS)

Owens, Charles; Sanchez, Nathaniel; Sorensen, Christian; Jensen, Brian

2017-06-01

Recent experiments at the Advanced Photon Source have been successful in coupling gun systems to the synchrotron to take advantage of the advanced X-ray diagnostics available including X-ray diffraction and X-ray phase contrast imaging (PCI) to examine matter at extreme conditions. There are many experiments that require explosive loading capabilities, e.g. detonator and initiator dynamics, small angle X-ray scattering (SAXS), ejecta formation, and explosively driven flyer experiments. The current work highlights a new explosive vessel that was designed specifically for use at a synchrotron facility with requirements to confine up to 15 grams of explosives (TNT equivalent), couple the vessel to the X-ray beam line, and reliably position samples remotely. A description of the system and capability will be provided along with the results from qualification testing to bring the system into service (LA-UR-17-21381).

Advanced Rotorcraft Transmission (ART) program summary

NASA Technical Reports Server (NTRS)

Krantz, T. L.; Kish, J. G.

1992-01-01

The Advanced Rotorcraft Transmission (ART) Program was initiated to advance the state of the art for rotorcraft transmissions. The goal of the ART Program was to develop and demonstrate the technologies needed to reduce transmission weight by 25 pct. and reduce noise by 10 dB while obtaining a 5000 hr 'mean time between failure'. The research done under the ART Program is summarized. A split path design was selected as best able to meet the program goals. Key part technologies needed for this design were identified, studied, and developed. Two of these technologies are discussed in detail: the load sharing of split path designs including the use of a compliant elastomeric torque splitter and the application of a high ratio, low pitch line velocity gear mesh. Development of an angular contact spherical roller bearing, transmission error analysis, and fretting fatigue testing are discussed. The technologies for a light weight, quiet, and reliable rotorcraft transmission were demonstrated.

Measuring Rocket Engine Temperatures with Hydrogen Raman Spectroscopy

NASA Technical Reports Server (NTRS)

Wehrmeyer, Joseph A.; Osborne, Robin J.; Trinh, Huu P.; Turner, James (Technical Monitor)

2001-01-01

Optically accessible, high pressure, hot fire test articles are available at NASA Marshall for use in development of advanced rocket engine propellant injectors. Single laser-pulse ultraviolet (UV) Raman spectroscopy has been used in the past in these devices for analysis of high pressure H2- and CH4-fueled combustion, but relies on an independent pressure measurement in order to provide temperature information. A variation of UV Raman (High Resolution Hydrogen Raman Spectroscopy) is under development and will allow temperature measurement without the need for an independent pressure measurement, useful for flows where local pressure may not be accurately known. The technique involves the use of a spectrometer with good spectral resolution, requiring a small entrance slit for the spectrometer. The H2 Raman spectrum, when created by a narrow linewidth laser source and obtained from a good spectral resolution spectrograph, has a spectral shape related to temperature. By best-fit matching an experimental spectrum to theoretical spectra at various temperatures, a temperature measurement is obtained. The spectral model accounts for collisional narrowing, collisional broadening, Doppler broadening, and collisional line shifting of each Raman line making up the H2 Stokes vibrational Q-branch spectrum. At pressures from atmospheric up to those associated with advanced preburner components (5500 psia), collisional broadening though present does not cause significant overlap of the Raman lines, allowing high resolution H2 Raman to be used for temperature measurements in plumes and in high pressure test articles. Experimental demonstrations of the technique are performed for rich H2-air flames at atmospheric pressure and for high pressure, 300 K H2-He mixtures. Spectrometer imaging quality is identified as being critical for successful implementation of technique.

Automatic microscopy for mitotic cell location.

NASA Technical Reports Server (NTRS)

Herron, J.; Ranshaw, R.; Castle, J.; Wald, N.

1972-01-01

Advances are reported in the development of an automatic microscope with which to locate hematologic or other cells in mitosis for subsequent chromosome analysis. The system under development is designed to perform the functions of: slide scanning to locate metaphase cells; conversion of images of selected cells into binary form; and on-line computer analysis of the digitized image for significant cytogenetic data. Cell detection criteria are evaluated using a test sample of 100 mitotic cells and 100 artifacts.

Advanced Electrical Test Techniques for LSI Microcircuits.

DTIC Science & Technology

1982-03-01

high resistance polysilicon load resistors stacked in the "Z" direction for higher packing density. Featuring resistors typically in the gigaohm range...are made up of "N" diffusions, metal and/or polysilicon lines, and transistors, they are subject to leakage defects. If the leakage of the nonconducting...reference 7) show- ing a poor connection from the FF lead resistor ( Polysilicon ) to the Vcc or the transistor. The FF layout of Figure 1B shows that

Understanding the operational parameters affecting NDMA formation at Advanced Water Treatment Plants.

PubMed

Farré, Maria José; Döderer, Katrin; Hearn, Laurence; Poussade, Yvan; Keller, Jurg; Gernjak, Wolfgang

2011-01-30

N-nitrosodimethylamine (NDMA) can be formed when secondary effluents are disinfected by chloramines. By means of bench scale experiments this paper investigates operational parameters than can help Advanced Water Treatment Plants (AWTPs) to reduce the formation of NDMA during the production of high quality recycled water. The formation of NDMA was monitored during a contact time of 24h using dimethylamine as NDMA model precursor and secondary effluent from wastewater treatment plants. The three chloramine disinfection strategies tested were pre-formed and in-line formed monochloramine, and pre-formed dichloramine. Although the latter is not employed on purpose in full-scale applications, it has been suggested as the main contributing chemical generating NDMA during chloramination. After 24h, the NDMA formation decreased in both matrices tested in the order: pre-formed dichloramine>in-line formed monochloramine≫pre-formed monochloramine. The most important parameter to consider for the inhibition of NDMA formation was the length of contact time between disinfectant and wastewater. Formation of NDMA was initially inhibited for up to 6h with concentrations consistently <10 ng/L during these early stages of disinfection, regardless of the disinfection strategy. The reduction of the contact time was implemented in Bundamba AWTP (Queensland, Australia), where NDMA concentrations were reduced by a factor of 20 by optimizing the disinfection strategy. Copyright © 2010 Elsevier B.V. All rights reserved.

Atezolizumab: feasible second-line therapy for patients with non-small cell lung cancer? A review of efficacy, safety and place in therapy.

PubMed

Jean, Fanny; Tomasini, Pascale; Barlesi, Fabrice

2017-12-01

Advanced non-small cell lung cancer (NSCLC) prognosis is still poor and has recently been reformed by the development of immune checkpoint inhibitors and the approval of anti-PD-1 (programmed cell-death 1) treatments such as nivolumab and pembrolizumab in second line. More recently, atezolizumab (MDPL 3280A), a programmed cell-death-ligand 1 (PD-L1) inhibitor, was also studied in this setting. Here, we report a review of the literature assessing the efficacy, safety, and place of atezolizumab in the second-line treatment of advanced NSCLC. We performed a literature search of PubMed, American Society of Clinical Oncology, European Society of Medical Oncology and World Conference on Lung Cancer meetings. Atezolizumab showed a good tolerance profile and efficacy in comparison with docetaxel for second-line treatment of advanced NSCLC. Potential predictive biomarkers also have to be assessed.

Atezolizumab: feasible second-line therapy for patients with non-small cell lung cancer? A review of efficacy, safety and place in therapy

PubMed Central

Jean, Fanny; Tomasini, Pascale; Barlesi, Fabrice

2017-01-01

Advanced non-small cell lung cancer (NSCLC) prognosis is still poor and has recently been reformed by the development of immune checkpoint inhibitors and the approval of anti-PD-1 (programmed cell-death 1) treatments such as nivolumab and pembrolizumab in second line. More recently, atezolizumab (MDPL 3280A), a programmed cell-death-ligand 1 (PD-L1) inhibitor, was also studied in this setting. Here, we report a review of the literature assessing the efficacy, safety, and place of atezolizumab in the second-line treatment of advanced NSCLC. We performed a literature search of PubMed, American Society of Clinical Oncology, European Society of Medical Oncology and World Conference on Lung Cancer meetings. Atezolizumab showed a good tolerance profile and efficacy in comparison with docetaxel for second-line treatment of advanced NSCLC. Potential predictive biomarkers also have to be assessed. PMID:29449897

Sequential treatment of icotinib after first-line pemetrexed in advanced lung adenocarcinoma with unknown EGFR gene status.

PubMed

Zheng, Yulong; Fang, Weijia; Deng, Jing; Zhao, Peng; Xu, Nong; Zhou, Jianying

2014-07-01

In non-small cell lung cancer (NSCLC), the well-developed epidermal growth factor receptor (EGFR) is an important therapeutic target. EGFR activating gene mutations have been proved strongly predictive of response to EGFR-tyrosine kinase inhibitors (TKI) in NSCLC. However, both in daily clinical practice and clinical trials, patients with unknown EGFR gene status (UN-EGFR-GS) are very common. In this study, we assessed efficacy and tolerability of sequential treatment of first-line pemetrexed followed by icotinib in Chinese advanced lung adenocarcinoma with UN-EGFR-GS. We analyzed 38 patients with advanced lung adenocarcinoma with UN-EGFR-GS treated with first-line pemetrexed-based chemotherapy followed by icotinib as maintenance or second-line therapy. The response rates to pemetrexed and icotinib were 21.1% and 42.1%, respectively. The median overall survival was 27.0 months (95% CI, 19.7-34.2 months). The 12-month overall survival probability was 68.4%. The most common toxicities observed in icotinib phase were rashes, diarrheas, and elevated aminotransferase. Subgroup analysis indicated that the overall survival is correlated with response to icotinib. The sequence of first-line pemetrexed-based chemotherapy followed by icotinib treatment is a promising option for advanced lung adenocarcinoma with UN-EGFR-GS in China.

Zone lines

Treesearch

Kevin T. Smith

2001-01-01

Zone lines are narrow, usually dark markings formed in decaying wood. Zone lines are found most frequently in advanced white rot of hardwoods, although they occasionally are associated both with brown rot and with softwoods.

Russian Rocket Engine Test

NASA Technical Reports Server (NTRS)

1998-01-01

NASA engineers successfully tested a Russian-built rocket engine on November 4, 1998 at the Marshall Space Flight Center (MSFC) Advanced Engine Test Facility, which had been used for testing the Saturn V F-1 engines and Space Shuttle Main engines. The MSFC was under a Space Act Agreement with Lockheed Martin Astronautics of Denver to provide a series of test firings of the Atlas III propulsion system configured with the Russian-designed RD-180 engine. The tests were designed to measure the performance of the Atlas III propulsion system, which included avionics and propellant tanks and lines, and how these components interacted with the RD-180 engine. The RD-180 is powered by kerosene and liquid oxygen, the same fuel mix used in Saturn rockets. The RD-180, the most powerful rocket engine tested at the MSFC since Saturn rocket tests in the 1960s, generated 860,000 pounds of thrust.

[Clinical Analysis of Icotinib on Beneficiary of 
Advanced Non-small Cell Lung Cancer with EGFR Common Mutation].

PubMed

Jiang, Xiaowen; Wang, Wenxian; Zhang, Yiping

2016-04-20

Targeted therapy has become an indispensable therapy method in advanced non-small cell lung cancer (NSCLC) treatment. Epithelial growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) can significantly prolong the survival of patients harboring EGFR gene mutation. Icotinb is China's first EGFR-TKI with independent intellectual property rights. The aim of this study is to investigate the clinical characteristics about the beneficiary of advanced NSCLC patients with EGFR Common mutation who were treated with Icotinib. Retrospectively collect the data about beneficiary [progression-free survival (PFS)≥6 months] and analysis of the related risk factors for prognosis. From September 1, 2011 to September 30, 2015, 231 cases of advanced NSCLC beneficiary with EGFR common mutation were enrolled for treatment with icotinib in Zhejiang Cancer Hospital. The one year benefit rate was 67.9% in the group treated with Icotinib as first line, and in the groupas second line or above was 53.6%, which is statisticallysignificant. The two years benefit rate was 18.7% and 9.3%, respectively. The median PFS of first line group and the second line or above was 16.7 and 12.4 months, respectively. The presence of brain metastasis (P=0.010), Prior chemotherapy (P=0.001), Eastern Cooperative Oncology Group (ECOG) score (P=0.001) were the main factors influencing the prognosis. The most common adverse were skin rashes (51 cases, 22.1%) and diarrhea (27 cases, 11.7%). Icotinib offers long-term clinical benefit and good tolerance for advanced NSCLC harboring EGFR gene mutation. Its advantage groups in addition to the patients with brain metastases and better ECOG score, the curative effect of patients with the first-line treatment is superior to second or further line. 
.

A new critical dimension metrology for chrome-on-glass substrates based on s-parameter measurements extracted from coplanar waveguide test structures

NASA Astrophysics Data System (ADS)

Nwokoye, Chidubem A.; Zaghloul, Mona; Cresswell, Michael W.; Allen, Richard A.; Murabito, Christine E.

2006-10-01

The technical objective of the work reported here is to assess whether radio-frequency (RF) measurements made on coplanar waveguide (CPW) test structures, which are replicated in conducting material on insulating substrates, could be employed to extract the critical dimension (CD) of the signal line using its center-to-center separation from the groundlines as a reference. The specific near-term objective is to assess whether this CPW-based CD-metrology has sensitivity and repeatability competitive with the other metrology techniques that are now used for chrome-on-glass (COG) photomasks. An affirmative answer is encouraging because advancing to a non-contact and non-vacuum implementation would then seem possible for this application. Our modeling of specific cases shows that, when the pitch of the replicated lines of the CPW is maintained constant, the sensitivity of its characteristic impedance to the CDs of the signal and ground lines is approximately 60 Ω/μm. This is a potentially useful result. For the same implementation, the quantity ∂C/∂w has a value of approximately 45 (pF/m)/μm, which appears to be large enough to provide acceptable accuracy.

Reduction in Central Line-Associated Bloodstream Infection Rates After Implementations of Infection Control Measures at a Level 3 Neonatal Intensive Care Unit.

PubMed

Dumpa, Vikramaditya; Adler, Bonny; Allen, Delena; Bowman, Deborah; Gram, Amy; Ford, Pat; Sannoh, Sulaiman

2016-01-01

Advances in neonatology led to survival of micro-preemies, who need central lines. Central line-associated bloodstream infection (CLABSI) causes prolonged hospitalization, morbidities, and mortality. Health care team education decreases CLABSIs. The objective was to decrease CLABSIs using evidence-based measures. The retrospective review compared CLABSI incidence during and after changes in catheter care. In April 2011, intravenous (IV) tubing changed from Interlink to Clearlink; IV tubing changing interval increased from 24 to 72 hours. CLABSIs increased. The following measures were implemented: July 2011, reeducation of neonatal intensive care staff on Clearlink; August 2011, IV tubing changing interval returned to 24 hours; September 2011, changed from Clearlink back to Interlink; November 2011, review of entire IV process and in-service on hand hygiene; December 2011, competencies on IV access for all nurses. CLABSIs were compared during and after interventions. Means were compared using the t test and ratios using the χ(2) test; P <.05. CLABSIs decreased from 4.4/1000 to 0/1000 catheter-days; P < .05. Evidence-based interventions reduced CLABSIs. © The Author(s) 2014.

Efficacy of chemotherapy after first-line gefitinib therapy in EGFR mutation-positive advanced non-small cell lung cancer-data from a randomized Phase III study comparing gefitinib with carboplatin plus paclitaxel (NEJ002).

PubMed

Miyauchi, Eisaku; Inoue, Akira; Kobayashi, Kunihiko; Maemondo, Makoto; Sugawara, Shunichi; Oizumi, Satoshi; Isobe, Hiroshi; Gemma, Akihiko; Saijo, Yasuo; Yoshizawa, Hirohisa; Hagiwara, Koichi; Nukiwa, Toshihiro

2015-07-01

Epidermal growth factor receptor tyrosine kinase inhibitors are effective as first-line therapy for advanced non-small cell lung cancer patients harboring epidermal growth factor receptor mutations. However, it is unknown whether second-line platinum-based chemotherapy after epidermal growth factor receptor tyrosine kinase inhibitor therapy could lead to better outcomes. We evaluated the efficacy of second-line platinum-based chemotherapy after gefitinib for advanced non-small cell lung cancers harboring epidermal growth factor receptor mutations (the NEJ002 study). Seventy-one non-small cell lung cancers, treated with gefitinib as first-line therapy and then receiving platinum-based chemotherapy as second-line therapy were evaluated in NEJ002. Patients were evaluated for antitumor response to second-line chemotherapy by computed tomography according to the criteria of the Response Evaluation Criteria in Solid Tumors group (version 1.0). Of the 71 patients receiving platinum-based chemotherapy after first-line gefitinib, a partial response was documented in 25.4% (18/71), stable disease in 43.7% (31/71) and progression of disease in 21.1% (15/71). The objective response and disease control rates were 25.4% (18/71) and 69% (49/71), respectively. There was no significant difference between first- and second-line chemotherapy in objective response and disease control rates for advanced non-small cell lung cancer harboring activating epidermal growth factor receptor mutations. In the analysis of epidermal growth factor receptor mutation types, the objective responses of deletions in exon 19 and a point mutation in exon 21 (L858R) were 27.3% (9/33) and 28.1% (9/32), respectively, but these differences between objective response rates were not significant. The efficacy of second-line platinum-based chemotherapy followed at progression by gefitinib was similar to first-line platinum-based chemotherapy, and epidermal growth factor receptor mutation types did not influence the efficacy of second-line platinum-based chemotherapy. © The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Warthog: Progress on Coupling BISON and PROTEUS

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

Hart, Shane W.D.

The Nuclear Energy Advanced Modeling and Simulation (NEAMS) program from the Office of Nuclear Energy at the Department of Energy (DOE) provides a robust toolkit for modeling and simulation of current and future advanced nuclear reactor designs. This toolkit provides these technologies organized across product lines, with two divisions targeted at fuels and end-to-end reactor modeling, and a third for integration, coupling, and high-level workflow management. The Fuels Product Line (FPL) and the Reactor Product Line (RPL) provide advanced computational technologies that serve each respective field effectively. There is currently a lack of integration between the product lines, impeding futuremore » improvements of simulation solution fidelity. In order to mix and match tools across the product lines, a new application called Warthog was produced. Warthog is built on the Multi-physics Object-Oriented Simulation Environment (MOOSE) framework developed at Idaho National Laboratory (INL). This report details the continuing efforts to provide the Integration Product Line (IPL) with interoperability using the Warthog code. Currently, this application strives to couple the BISON fuel performance application from the FPL using the PROTEUS Core Neutronics application from the RPL. Warthog leverages as much prior work from the NEAMS program as possible, enabling interoperability between the independently developed MOOSE and SHARP frameworks, and the libMesh and MOAB mesh data formats. Previous work performed on Warthog allowed it to couple a pin cell between the two codes. However, as the temperature changed due to the BISON calculation, the cross sections were not recalculated, leading to errors as the temperature got further away from the initial conditions. XSProc from the SCALE code suite was used to calculate the cross sections as needed. The remainder of this report discusses the changes to Warthog to allow for the implementation of XSProc as an external code. It also discusses the changes made to Warthog to allow it to fit more cleanly into the MultiApp syntax of the MOOSE framework. The capabilities, design, and limitations of Warthog will be described, in addition to some of the test cases that were used to demonstrate the code. Future plans for Warthog will be discussed, including continuation of the modifications to the input and coupling to other SHARP codes such as Nek5000.« less

Using health communication best practices to develop a web-based provider-patient communication aid: the CONNECT study.

PubMed

Fleisher, Linda; Buzaglo, Joanne; Collins, Michael; Millard, Jennifer; Miller, Suzanne M; Egleston, Brian L; Solarino, Nicholas; Trinastic, Jonathan; Cegala, Donald J; Benson, Al B; Schulman, Kevin A; Weinfurt, Kevin P; Sulmasy, Daniel; Diefenbach, Michael A; Meropol, Neal J

2008-06-01

Although there is broad consensus that careful content vetting and user testing is important in the development of technology-based educational interventions, often these steps are overlooked. This paper highlights the development of a theory-guided, web-based communication aid (CONNECT), designed to facilitate treatment decision-making among patients with advanced cancer. The communication aid included an on-line survey, patient skills training module and an automated physician report. Development steps included: (1) evidence-based content development; (2) usability testing; (3) pilot testing; and (4) patient utilization and satisfaction. Usability testing identified some confusing directions and navigation for the on-line survey and validated the relevance of the "patient testimonials" in the skills module. Preliminary satisfaction from the implementation of the communication aid showed that 66% found the survey length reasonable and 70% found it helpful in talking with the physician. Seventy percent reported the skills module helpful and about half found it affected the consultation. Designing patient education interventions for translation into practice requires the integration of health communication best practice including user feedback along the developmental process. This developmental process can be translated to a broad array of community-based patient and provider educational interventions.

Energy Theft in the Advanced Metering Infrastructure

NASA Astrophysics Data System (ADS)

McLaughlin, Stephen; Podkuiko, Dmitry; McDaniel, Patrick

Global energy generation and delivery systems are transitioning to a new computerized "smart grid". One of the principle components of the smart grid is an advanced metering infrastructure (AMI). AMI replaces the analog meters with computerized systems that report usage over digital communication interfaces, e.g., phone lines. However, with this infrastructure comes new risk. In this paper, we consider adversary means of defrauding the electrical grid by manipulating AMI systems. We document the methods adversaries will use to attempt to manipulate energy usage data, and validate the viability of these attacks by performing penetration testing on commodity devices. Through these activities, we demonstrate that not only is theft still possible in AMI systems, but that current AMI devices introduce a myriad of new vectors for achieving it.

An Exploration of Learners' Conceptions of Language, Culture, and Learning in Advanced-Level Spanish Courses

ERIC Educational Resources Information Center

Drewelow, Isabelle; Mitchell, Claire

2015-01-01

This article reports on an exploratory study, which examines learners' rating of culture in relation to other concepts in advanced Spanish courses and their justification of the ratings attributed. Open-ended responses, elicited from a questionnaire completed by 179 respondents, were analysed line by line using an interpretive approach. Data…

Temporal Trends in Helicobacter pylori Eradication Success in a Test-and-Treat Population.

PubMed

Boltin, Doron; Schmilovitz-Weiss, Hemda; Gingold-Belfer, Rachel; Leibovitzh, Haim; Snir, Yifat; Perets, Tsachi Tsadok; Dickman, Ram; Levi, Zohar; Niv, Yaron

2018-06-05

Although the efficacy of first-line treatment for Helicobacter pylori infection should aim to be > 90%, it is unclear whether this target has been achieved in Israel. We aimed to determine the success rate of treatment for H. pylori and to describe temporal changes in our region. Methods: Adult patients who underwent a first-time -C13-urea breath test (C13-UBT) at Clalit Health Services between January 1, 2010 and December 31, 2015 were included. In order to isolate a naïve "test-and-treat" population who were unlikely to have undergone an initial endoscopy-based H. pylori test, we excluded patients ≥45 years and those with any previous C13-UBT. A total of 94,590 subjects (36.1% male, age 28.5 ± 6.0) who underwent at least one C13-UBT during the study period were included. C13-UBT was positive in 48,509 (51.3%) subjects. A confirmatory post-treatment C13-UBT was performed in 37.8, 44.1, 46.6, and 45.9% following 1st, 2nd, 3rd, and 4th-line treatment respectively. Eradication was successful in 65.4% following first-line treatment, and eradication success improved during the study period (59.2, 63.3, 65.7, 66.0, 69.0, and 73.1% in 2010, 2011, 2012, 2013, 2014, and 2015 respectively; OR 1.11; 95% CI 1.09-1.13; p < 0.0001). Eradication was successful in 44.7% following second-line treatment, although eradication success did not significantly improve during the study period (OR 1.05; 95% CI 0.99-1.10; p = 0.09). Despite the increasing success of first-line treatment for H. pylori infection over the study period, eradication rates remain suboptimal. Initiatives to implement the Toronto and Maastricht Consensus Reports should be advanced. © 2018 S. Karger AG, Basel.

Advanced EMU electrochemically regenerable CO2 and moisture absorber module breadboard

NASA Technical Reports Server (NTRS)

Lee, M. C.; Sudar, M.; Chang, B. J.

1988-01-01

The applicability of the Electrochemically Regenerable Carbon Dioxide and Moisture Absorption Technology to the advanced extravehicular mobility unit was demonstrated by designing, fabricating, and testing a breadboard Absorber Module and an Electrochemical Regenerator. Test results indicated that the absorber module meets or exceeds the carbon dioxide removal requirements specified for the design and can meet the moisture removal requirement when proper cooling is provided. CO2 concentration in the vent gas stream was reduced from 0.52 to 0.027 kPa (3.9 to 0.20 mm Hg) for the full five hour test period. Vent gas dew point was reduced from inlet values of 294 K (69 F) to 278 K (41 F) at the outlet. The regeneration of expended absorbent was achieved by the electrochemical method employed in the testing. An absorbent bed using microporous hydrophobic membrane sheets with circulating absorbent is shown to be the best approach to the design of an Absorber Module based on sizing and performance. Absorber Module safety design, comparison of various absorbents and their characteristics, moisture absorption and cooling study and subsystem design and operation time-lining study were also performed.

Advanced Power Conditioning System

NASA Technical Reports Server (NTRS)

Johnson, N. L.

1971-01-01

The second portion of the advanced power conditioning system development program is reported. Five 100-watt parallel power stages with majority-vote-logic feedback-regulator were breadboarded and tested to the design goals. The input voltage range was 22.1 to 57.4 volts at loads from zero to 500 watts. The maximum input ripple current was 200 mA pk-pk (not including spikes) at 511 watts load; the output voltage was 56V dc with a maximum change of 0.89 volts for all variations of line, load, and temperature; the maximum output ripple was 320 mV pk-pk at 512 watts load (dependent on filter capacitance value); the maximum efficiency was 93.9% at 212 watts and 50V dc input; the minimum efficiency was 87.2% at 80-watt load and 50V dc input; the efficiency was above 90% from 102 watts to 372 watts; the maximum excursion for an 80-watt load change was 2.1 volts with a recovery time of 7 milliseconds; and the unit performed within regulation limits from -20 C to +85 C. During the test sequence, margin tests and failure mode tests were run with no resulting degradation in performance.

Around Marshall

NASA Image and Video Library

1998-11-04

NASA engineers successfully tested a Russian-built rocket engine on November 4, 1998 at the Marshall Space Flight Center (MSFC) Advanced Engine Test Facility, which had been used for testing the Saturn V F-1 engines and Space Shuttle Main engines. The MSFC was under a Space Act Agreement with Lockheed Martin Astronautics of Denver to provide a series of test firings of the Atlas III propulsion system configured with the Russian-designed RD-180 engine. The tests were designed to measure the performance of the Atlas III propulsion system, which included avionics and propellant tanks and lines, and how these components interacted with the RD-180 engine. The RD-180 is powered by kerosene and liquid oxygen, the same fuel mix used in Saturn rockets. The RD-180, the most powerful rocket engine tested at the MSFC since Saturn rocket tests in the 1960s, generated 860,000 pounds of thrust.

Micromirror-based real image laser automotive head-up display

NASA Astrophysics Data System (ADS)

Fan, Chao; He, Siyuan

2017-01-01

This paper reports a micromirror-based real image laser automotive head-up display (HUD), which overcomes the limitations of the previous designs by: (1) implementing an advanced display approach which is able to display sharp corners while the previous designs can only display curved lines such as to improve the display fidelity and (2) Optimizing the optical configuration to significantly reduce the HUD module size. The optical design in the HUD is simulated to choose the off-the-shelf concave lens. The vibration test is conducted to verify that the micromirror can survive 5 g. The prototype of the HUD system is fabricated and tested.

Experimental research on femto-second laser damaging array CCD cameras

NASA Astrophysics Data System (ADS)

Shao, Junfeng; Guo, Jin; Wang, Ting-feng; Wang, Ming

2013-05-01

Charged Coupled Devices (CCD) are widely used in military and security applications, such as airborne and ship based surveillance, satellite reconnaissance and so on. Homeland security requires effective means to negate these advanced overseeing systems. Researches show that CCD based EO systems can be significantly dazzled or even damaged by high-repetition rate pulsed lasers. Here, we report femto - second laser interaction with CCD camera, which is probable of great importance in future. Femto - second laser is quite fresh new lasers, which has unique characteristics, such as extremely short pulse width (1 fs = 10-15 s), extremely high peak power (1 TW = 1012W), and especially its unique features when interacting with matters. Researches in femto second laser interaction with materials (metals, dielectrics) clearly indicate non-thermal effect dominates the process, which is of vast difference from that of long pulses interaction with matters. Firstly, the damage threshold test are performed with femto second laser acting on the CCD camera. An 800nm, 500μJ, 100fs laser pulse is used to irradiate interline CCD solid-state image sensor in the experiment. In order to focus laser energy onto tiny CCD active cells, an optical system of F/5.6 is used. A Sony production CCDs are chose as typical targets. The damage threshold is evaluated with multiple test data. Point damage, line damage and full array damage were observed when the irradiated pulse energy continuously increase during the experiment. The point damage threshold is found 151.2 mJ/cm2.The line damage threshold is found 508.2 mJ/cm2.The full-array damage threshold is found to be 5.91 J/cm2. Although the phenomenon is almost the same as that of nano laser interaction with CCD, these damage thresholds are substantially lower than that of data obtained from nano second laser interaction with CCD. Then at the same time, the electric features after different degrees of damage are tested with electronic multi meter. The resistance values between clock signal lines are measured. Contrasting the resistance values of the CCD before and after damage, it is found that the resistances decrease significantly between the vertical transfer clock signal lines values. The same results are found between the vertical transfer clock signal line and the earth electrode (ground).At last, the damage position and the damage mechanism were analyzed with above results and SEM morphological experiments. The point damage results in the laser destroying material, which shows no macro electro influence. The line damage is quite different from that of point damage, which shows deeper material corroding effect. More importantly, short circuits are found between vertical clock lines. The full array damage is even more severe than that of line damage starring with SEM, while no obvious different electrical features than that of line damage are found. Further researches are anticipated in femto second laser caused CCD damage mechanism with more advanced tools. This research is valuable in EO countermeasure and/or laser shielding applications.

Mean curvature model for a quasi-static advancing meniscus: a drop tower test

NASA Astrophysics Data System (ADS)

Chen, Yongkang; Tavan, Noel; Weislogel, Mark

A critical geometric wetting condition resulting in a significant shift of a capillary fluid from one region of a container to another was recently demonstrated during experiments performed aboard the International Space Station (the Capillary Flow Experiments, Vane Gap test units, bulk shift phenomena). Such phenomena are of interest for advanced methods of control for large quantities of liquids aboard spacecraft. The dynamics of the flows are well understood, but analytical models remain qualitative without the correct capillary pressure driving force for the shifting bulk fluid—where one large interface (meniscus) advances while another recedes. To determine this pressure an investigation of the mean curvature of the advancing meniscus is presented which is inspired by earlier studies of receding bulk menisci in non-circular cylindrical containers. The approach is permissible only in the quasi-static limit. It will be shown that the mean curvature of the advancing bulk meniscus is related to that of the receding bulk meniscus, both of which are highly sensitive to container geometry and wetting conditions. The two meniscus curvatures are identical for any control parameter at the critical value identified by the Concus-Finn analysis. However, they differ when the control parameter is below its critical value. Experiments along these lines are well suited for drop towers and comparisons with the analytical predictions implementing the mean curvature model are presented. The validation opens a pathway to the analysis of such flows in containers of great geometric complexity.

Hypofractionated Radiotherapy Is Superior to Conventional Fractionation in an Orthotopic Model of Anaplastic Thyroid Cancer.

PubMed

Oweida, Ayman; Phan, Andy; Vancourt, Benjamin; Robin, Tyler; Hararah, Mohammad K; Bhatia, Shilpa; Milner, Dallin; Lennon, Shelby; Pike, Laura; Raben, David; Haugen, Bryan; Pozdeyev, Nikita; Schweppe, Rebecca; Karam, Sana D

2018-06-01

Anaplastic thyroid cancer (ATC) is an aggressive and highly lethal disease with poor outcomes and resistance to therapy. Despite multimodality treatment, including radiation therapy and chemotherapy, response rates remain <15%, with a median time to progression of less than three months. Recent advances in radiotherapy (RT) delivery and gene-expression profiling may help guide patient selection for personalized therapy. The purpose of this study was to characterize the response to radiation in a panel of ATC cell lines and to test alternative RT fractionation schedules for overcoming radioresistance. The cellular response to radiation was characterized based on clonogenic assays. Radiation response was correlated with microarray gene-expression data. Hypofractionated and conventional RT was tested in an orthotopic ATC tumor model, and tumor growth was assayed locally and distantly with in vivo and ex vivo bioluminescence imaging. A spectrum of radiosensitivities was observed in ATC cell lines. Radioresistant cell lines had higher levels of CXCR4 compared to radiosensitive cell lines. Compared to conventionally fractionated RT, hypofractionated RT resulted in significantly improved tumor growth delay, decreased regional and distant metastases, and improved overall survival. The findings demonstrate the heterogeneity of response to radiation in ATC tumors and the superiority of hypofractionated RT in improving local control, metastatic spread, and survival in preclinical models. These data support the design of clinical trials targeting radioresistant pathways in combination with hypofractionated RT.

Frictional Performance Assessment of Cemented Carbide Surfaces Textured by Laser

NASA Astrophysics Data System (ADS)

Fang, S.; Llanes, L.; Klein, S.; Gachot, C.; Rosenkranz, A.; Bähre, D.; Mücklich, F.

2017-10-01

Cemented carbides are advanced engineering materials often used in industry for manufacturing cutting tools or supporting parts in tribological system. In order to improve service life, special attention has been paid to change surface conditions by means of different methods, since surface modification can be beneficial to reduce the friction between the contact surfaces as well as to avoid unintended damage. Laser surface texturing is one of the newly developed surface modification methods. It has been successfully introduced to fabricate some basic patterns on cemented carbide surfaces. In this work, Direct Laser Interference Patterning Technique (DLIP) is implemented to produce special line-like patterns on a cobalt (Co) and nickel (Ni) based cemented tungsten carbide grade. It is proven that the laser-produced patterns have high geometrical precision and quality stability. Furthermore, tribology testing using a nano-tribometer unit shows that friction is reduced by the line-like patterns, as compared to the polished one, under both lubricated and dry testing regimes, and the reduction is more pronounced in the latter case.

Efficacy of tegafur-uracil in advanced urothelial cancer patients after the treatment failure of platinum-based chemotherapy.

PubMed

Maolake, Aerken; Izumi, Kouji; Takahashi, Rie; Itai, Shingo; Machioka, Kazuaki; Yaegashi, Hiroshi; Nohara, Takahiro; Kitagawa, Yasuhide; Kadono, Yoshifumi; Konaka, Hiroyuki; Mizokami, Atsushi; Namiki, Mikio

2015-03-01

Platinum-based chemotherapy is the first-line treatment for advanced urinary tract urothelial cancers. However, the optimal second-line treatment is unclear. Although tegafur-uracil is sometimes used for advanced urothelial cancer patients after the treatment failure of platinum-based chemotherapy, there is little evidence regarding its use as a second-line treatment. Advanced urothelial cancer patients previously treated with platinum-based chemotherapy were retrospectively analyzed. Overall survival (OS) was compared between patients with and without tegafur-uracil treatment. Thirty-one patients (27 and 4 patients with and without tegafur-uracil treatment, respectively) were analyzed. OS from the last day of the final chemotherapy course was better in patients with tegafur-uracil treatment than in those without (p<0.001, 358 and 66.5 days of the median survival time, respectively). Tegafur-uracil may be a candidate for the secondary treatment of advanced urothelial cancer patients after the treatment failure of platinum-based chemotherapy. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

Design, analysis and test verification of advanced encapsulation systems

NASA Technical Reports Server (NTRS)

Garcia, A., III

1984-01-01

Investigations into transparent conductive polymers were begun. Polypyrrole was electrochemically deposited, but the film characteristics were poor. A proprietary polymer material supplied by Polaroid was evaluated and showed promise as a readily processable material. A method was developed for calculating the magnitude and location of the maximum electric field for the family of solar-cell-like shapes. A method for calculating the lines of force for three dimensional electric fields was developed and applied to a geometry of interest to the photovoltaic program.

Fuel cell technology program

NASA Technical Reports Server (NTRS)

1972-01-01

A program to advance the technology for a cost-effective hydrogen/oxygen fuel cell system for future manned spacecraft is discussed. The evaluation of base line design concepts and the development of product improvements in the areas of life, power, specific weight and volume, versatility of operation, field maintenance and thermal control were conducted from the material and component level through the fabrication and test of an engineering model of the fuel cell system. The program was to be accomplished in a 13 month period.

Spatial optimization of operationally relevant large fire confine and point protection strategies: Model development and test cases

Treesearch

Yu Wei; Matthew P. Thompson; Jessica R. Haas; Gregory K. Dillon; Christopher D. O’Connor

2018-01-01

This study introduces a large fire containment strategy that builds upon recent advances in spatial fire planning, notably the concept of potential wildland fire operation delineations (PODs). Multiple PODs can be clustered together to form a “box” that is referred as the “response POD” (or rPOD). Fire lines would be built along the boundary of an rPOD to contain a...

Second-line treatments: moving towards an opportunity to improve survival in advanced gastric cancer?

PubMed

Salati, Massimiliano; Di Emidio, Katia; Tarantino, Vittoria; Cascinu, Stefano

2017-01-01

Gastric cancer is the third leading cause of cancer-related death globally with approximately 723 000 deaths every year. Most patients present with advanced unresectable or metastatic disease, only amenable to palliative systemic treatment and a median survival uncommonly exceeding 12 months. Over the last years, the efficacy of chemotherapy combination has plateaued and the introduction of the anti-human epidermal growth factor receptor 2 trastuzumab has resulted in a limited survival gain in the upfront setting. After this positive experience, first-line treatment with new targeted therapies failed to improve the outcome of advanced gastric cancer. On the contrary, second-line options, including monochemotherapy with taxanes or irinotecan and the anti-vascular endothelial growth factor receptor 2 ramucirumab, either alone or combined with paclitaxel, opened new therapeutic rooms for an ever-increasing number of patients who maintain an acceptable performance status across multiple lines. This article provides an updated overview on the current management of advanced gastric cancer and discusses how the different treatment options available may be best combined to favourably impact the outcome of patients following the logic of a treatment strategy.

Second-line treatments: moving towards an opportunity to improve survival in advanced gastric cancer?

PubMed Central

Salati, Massimiliano; Di Emidio, Katia; Tarantino, Vittoria; Cascinu, Stefano

2017-01-01

Gastric cancer is the third leading cause of cancer-related death globally with approximately 723 000 deaths every year. Most patients present with advanced unresectable or metastatic disease, only amenable to palliative systemic treatment and a median survival uncommonly exceeding 12 months. Over the last years, the efficacy of chemotherapy combination has plateaued and the introduction of the anti-human epidermal growth factor receptor 2 trastuzumab has resulted in a limited survival gain in the upfront setting. After this positive experience, first-line treatment with new targeted therapies failed to improve the outcome of advanced gastric cancer. On the contrary, second-line options, including monochemotherapy with taxanes or irinotecan and the anti-vascular endothelial growth factor receptor 2 ramucirumab, either alone or combined with paclitaxel, opened new therapeutic rooms for an ever-increasing number of patients who maintain an acceptable performance status across multiple lines. This article provides an updated overview on the current management of advanced gastric cancer and discusses how the different treatment options available may be best combined to favourably impact the outcome of patients following the logic of a treatment strategy. PMID:29209523

Fluoropyrimidines plus cisplatin versus gemcitabine/gemcitabine plus cisplatin in locally advanced and metastatic biliary tract carcinoma - a retrospective study.

PubMed

Croitoru, Adina; Gramaticu, Iulia; Dinu, Ioana; Gheorghe, Liana; Alexandrescu, Sorin; Buica, Florina; Luca, Ioana; Becheanu, Gabriel; Herlea, Vlad; Simionov, Iulia; Hrehoret, Doina; Lupescu, Ioana; Popescu, Irinel; Diculescu, Mircea

2012-09-01

This is a retrospective study of patients with advanced biliary tract carcinoma (BTC), who were treated with different regimens of chemotherapy. We studied patients with advanced BTC registered at the Department of Oncology at the Fundeni Clinical Institute between 2004 and 2008. The following data were analyzed: rate of response, progression free survival (PFS) to first and second line of chemotherapy, overall survival (OS) and drug toxicity. Ninety-six patients were eligible having either advanced intra or extrahepatic cholangiocarcinoma, or gallbladder cancer with no prior chemotherapy. Out of 96 patients, 57 (59.4%) received fluoropyrimidines (FP)+cisplatin and 39 (40.6%) gemcitabine (Gem)+/-cisplatin. The median PFS for FP+cisplatin was 5.9 months (95%CI 5-6.9) and for Gem+/-cisplatin 6.3 months (95%CI 5.4-7.1), p=0.661. Median OS for FP+cisplatin was 10.3 months (95%CI 7.5-13.1) and for Gem+/-cisplatin 9.1 months (95%CI 7.0-11.2), p=0.098. On disease progression, 46 patients received second line CT (Gem or FP+/-platinum compounds). Median OS for patients with FP based first line and Gem+/-cisplatin in second line was 19 months (95%CI 8.9-29) higher than for the reverse sequence: 13.2 months (95%CI 12-14.4), but not statistically significant (p=0.830). All patients were evaluated for toxicities. Most patients (75.5%) reported at least one adverse event. Our results through direct comparison of FP+cisplatin with Gem+/-cisplatin as first line treatment did not show any statistical differences in terms of rate of response, PFS and OS. However, our study showed that FP+cisplatin as first line and Gem based second line therapy gave a better OS rate.

High-throughput testing in head and neck squamous cell carcinoma identifies agents with preferential activity in human papillomavirus-positive or negative cell lines.

PubMed

Ghasemi, Farhad; Black, Morgan; Sun, Ren X; Vizeacoumar, Frederick; Pinto, Nicole; Ruicci, Kara M; Yoo, John; Fung, Kevin; MacNeil, Danielle; Palma, David A; Winquist, Eric; Mymryk, Joe S; Ailles, Laurie A; Datti, Alessandro; Barrett, John W; Boutros, Paul C; Nichols, Anthony C

2018-05-25

Head and neck squamous cell carcinoma (HNSCC) is a common cancer diagnosis worldwide. Despite advances in treatment, HNSCC has very poor survival outcomes, emphasizing an ongoing need for development of improved therapeutic options. The distinct tumor characteristics of human papillomavirus (HPV)-positive vs . HPV-negative disease necessitate development of treatment strategies tailored to tumor HPV-status. High-throughput robotic screening of 1,433 biologically and pharmacologically relevant compounds at a single dose (4 μM) was carried out against 6 HPV-positive and 20 HPV-negative HNSCC cell lines for preliminary identification of therapeutically relevant compounds. Statistical analysis was further carried out to differentiate compounds with preferential activity against cell lines stratified by the HPV-status. These analyses yielded 57 compounds with higher activity in HPV-negative cell lines, and 34 with higher-activity in HPV-positive ones. Multi-point dose-response curves were generated for six of these compounds (Ryuvidine, MK-1775, SNS-032, Flavopiridol, AZD-7762 and ARP-101), confirming Ryuvidine to have preferential potency against HPV-negative cell lines, and MK-1775 to have preferential potency against HPV-positive cell lines. These data comprise a valuable resource for further investigation of compounds with therapeutic potential in the HNSCC.

A review of proton exchange membrane water electrolysis on degradation mechanisms and mitigation strategies

NASA Astrophysics Data System (ADS)

Feng, Qi; Yuan, Xiao-Zi; Liu, Gaoyang; Wei, Bing; Zhang, Zhen; Li, Hui; Wang, Haijiang

2017-10-01

Proton exchange membrane water electrolysis (PEMWE) is an advanced and effective solution to the primary energy storage technologies. A better understanding of performance and durability of PEMWE is critical for the engineers and researchers to further advance this technology for its market penetration, and for the manufacturers of PEM water electrolyzers to implement quality control procedures for the production line or on-site process monitoring/diagnosis. This paper reviews the published works on performance degradations and mitigation strategies for PEMWE. Sources of degradation for individual components are introduced. With degradation causes discussed and degradation mechanisms examined, the review emphasizes on feasible strategies to mitigate the components degradation. To avoid lengthy real lifetime degradation tests and their high costs, the importance of accelerated stress tests and protocols is highlighted for various components. In the end, R&D directions are proposed to move the PEMWE technology forward to become a key element in future energy scenarios.

SunLine Transit Agency Advanced Technology Fuel Cell Bus Evaluation : Third Results Report

DOT National Transportation Integrated Search

2012-05-01

SunLine Transit Agency provides public transit services to the Coachella Valley area of California. SunLine has demonstrated hydrogen and fuel cell bus technologies for more than 10 years. This report describes operations at SunLine for a prototype f...

Management of advanced pancreatic cancer in daily clinical practice.

PubMed

Giuliani, Jacopo; Piacentini, Paolo; Bonetti, Andrea

2016-01-01

The aim of this outcome study was to evaluate the management of advanced pancreatic cancer in a real-world clinical practice; few such experiences have been reported in the literature. A retrospective analysis was performed of all consecutive patients with advanced pancreatic ductal adenocarcinoma followed at our medical oncology unit between January 2003 and December 2013. We evaluated 78 patients, mostly with metastatic disease (64.1%). Median follow-up was 10.77 months, by which time 74 patients (94.9%) had died. Median overall survival was 8.29 months. Median age was 67 years. In univariate analysis, pain at onset (p = 0.020), ECOG performance status (p<0.001), stage (p = 0.047), first-line chemotherapy (p<0.001), second-line chemotherapy (p<0.001) and weight loss at diagnosis (p = 0.029) were factors that had an impact on overall survival. In multivariate analysis, the presence of pain at onset (p = 0.043), stage (p = 0.003) and second-line chemotherapy (p = 0.004) were confirmed as independent prognostic factors. Our data, derived from daily clinical practice, confirmed advanced pancreatic cancer as an aggressive malignant disease with a very short expected survival. Second-line treatment seems to provide an advantage in terms of overall survival in patients who showed a partial response as their best response to first-line treatment.

Targeted therapies in non-small cell lung cancer: a focus on ALK/ROS1 tyrosine kinase inhibitors.

PubMed

Sgambato, Assunta; Casaluce, Francesca; Maione, Paolo; Gridelli, Cesare

2018-01-01

Anaplastic lymphoma kinase (ALK) and ROS1 rearrangements define important molecular subgroups of advanced non-small cell lung cancer (NSCLC). The identification of these genetic driver alterations created new potential for highly active therapeutic interventions. After discovery of ALK rearrangements in NSCLC, it was recognized that these confer sensitivity to ALK inhibition. Areas covered: Crizotinib, the first-in-class ALK/ROS1/MET inhibitor, was initially approved as second-line treatment of ALK-positive advanced NSCLC but after this, it was firmly established as the standard first-line therapy for advanced ALK-positive NSCLC. After initial response to crizotinib, tumors inevitably relapse. Next-generation ALK inhibitors, more potent and brain-penetrable than crizotinib, may be effective in re-inducing remissions when cancers are still addicted to ALK. Ceritinib and alectinib are approved for metastatic ALK positive NSCLC patients, while brigatinib received granted accelerated approval by the United States Food and Drug Administration. Regarding ROS1 rearrangement, to date crizotinib is the only ALK-tyrosine kinase inhibitor receiving indication as treatment of ROS1 positive advanced NSCLC. Expert commentary: Although novel ALK-inhibitors are under clinical investigation compared to crizotinib as front-line treatment for ALK-positive NSCLC, nowadays the current standard first-line therapy for these patients is crizotinib. Further research will clarify the best management of ALK-positive NSCLC, above all who progress on first-line crizotinib.

Advanced Gas Turbine (AGT) powertrain system development for automotive applications

NASA Technical Reports Server (NTRS)

1984-01-01

Rotor dynamic instability investigations were conducted. Forward ball bearing hydraulic mount configurations were tested with little effect. Trial assembly of S/N 002 ceramic engine was initiated. Impeller design activities were completed on the straight line element (SLE) blade definition to address near-net-shape powder metal die forging. Performance characteristics of the Baseline Test 2A impeller were closely preserved. The modified blading design has been released for tooling procurement. Developmental testing of the diffusion flame combustor (DFC) for initial use in the S/N 002 2100 F ceramic structures engine was completed. A natural gas slave preheater was designed and fabricated. Preliminary regenerator static seal rig testing showed a significant reduction in leakage and sensitivity to stack height. Ceramic screening tests were completed and two complete sets of ceramic static structures were qualified for engine testing. Efforts on rotor dynamics development to resolve subsynchronous motion were continued.

Annual banned-substance review: analytical approaches in human sports drug testing.

PubMed

Thevis, Mario; Kuuranne, Tiia; Geyer, Hans; Schänzer, Wilhelm

2017-01-01

There has been an immense amount of visibility of doping issues on the international stage over the past 12 months with the complexity of doping controls reiterated on various occasions. Hence, analytical test methods continuously being updated, expanded, and improved to provide specific, sensitive, and comprehensive test results in line with the World Anti-Doping Agency's (WADA) 2016 Prohibited List represent one of several critical cornerstones of doping controls. This enterprise necessitates expediting the (combined) exploitation of newly generated information on novel and/or superior target analytes for sports drug testing assays, drug elimination profiles, alternative test matrices, and recent advances in instrumental developments. This paper is a continuation of the series of annual banned-substance reviews appraising the literature published between October 2015 and September 2016 concerning human sports drug testing in the context of WADA's 2016 Prohibited List. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Potential role for mammalian target of rapamycin inhibitors as first-line therapy in hormone receptor–positive advanced breast cancer

PubMed Central

Beck, J Thaddeus

2015-01-01

Despite advances in cytotoxic chemotherapy and targeted therapies, 5-year survival rates remain low for patients with advanced breast cancer at diagnosis. This highlights the limited effectiveness of current treatment options. An improved understanding of cellular functions associated with the development and progression of breast cancer has resulted in the creation of a number of novel targeted molecular therapies. However, more work is needed to improve outcomes, particularly in the first-line recurrent or metastatic hormone receptor–positive breast cancer setting. The phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (mTOR) pathway is a major intracellular signaling pathway that is often upregulated in breast cancer, and overactivation of this pathway has been associated with primary or developed resistance to endocrine treatment. Clinical data from the Phase III Breast Cancer Trials of Oral Everolimus-2 (BOLERO-2) study of the mTOR inhibitor everolimus combined with exemestane in hormone receptor–positive advanced breast cancer were very promising, highlighting the potential role of mTOR inhibitors in combination with endocrine therapies as a first-line treatment option for these patients. It is hoped that the use of mTOR inhibitors combined with current standard-of-care endocrine therapies, such as aromatase inhibitors, in the first-line advanced breast cancer setting may result in greater antitumor effects and also delay or reverse treatment resistance. PMID:26675495

Efficacy and safety of icotinib as first-line therapy in patients with advanced non-small-cell lung cancer.

PubMed

Shen, Yan-Wei; Zhang, Xiao-Man; Li, Shu-Ting; Lv, Meng; Yang, Jiao; Wang, Fan; Chen, Zhe-Ling; Wang, Bi-Yuan; Li, Pan; Chen, Ling; Yang, Jin

2016-01-01

Several clinical trials have proven that icotinib hydrochloride, a novel epidermal growth factor receptor (EGFR)-tyrosine kinase inhibitor, exhibits encouraging efficacy and tolerability in patients with advanced non-small-cell lung cancer (NSCLC) who failed previous chemotherapy. This study was performed to assess the efficacy and toxicity of icotinib as first-line therapy for patients with advanced pulmonary adenocarcinoma with EGFR-sensitive mutation. Thirty-five patients with advanced NSCLC with EGFR-sensitive mutation who were sequentially admitted to the First Affiliated Hospital of Xi'an Jiaotong University from March 2012 to March 2014 were enrolled into our retrospective research. All patients were administered icotinib as first-line treatment. The tumor responses were evaluated using Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1). Among the 35 patients, the tumor objective response rate (ORR) and disease control rate were 62.9% (22/35) and 88.6% (31/35), respectively. The median progression-free survival was 11.0 months (95% confidence interval [CI]: 10.2-11.8 months), and median overall survival was 21.0 months (95% CI: 20.1-21.9 months). The most common drug-related toxicities were rashes (eleven patients) and diarrhea (nine patients), but these were generally manageable and reversible. Icotinib monotherapy is effective and tolerable as first-line treatment for patients with advanced lung adenocarcinoma with EGFR-sensitive mutation.

Influence of histology and biomarkers on first-line treatment of advanced non-small cell lung cancer in routine care setting: baseline results of an observational study (FRAME).

PubMed

Schnabel, Philipp A; Smit, Egbert; Carpeño, Javier de Castro; Leśniewski-Kmak, Krzysztof; Aerts, Joachim; Kraaij, Kees; Visseren-Grul, Carla; Dyachkova, Yulia; Taipale, Kaisa; Girvan, Allicia; Moro-Sibilot, Denis

2012-12-01

FRAME is a prospective observational study of first-line treatments for advanced non-small cell lung cancer (NSCLC). This interim analysis examines the influence of histology and biomarkers on therapeutic decisions. Baseline characteristic, treatment, and diagnostic procedure data were collected on European patients with stage IIIB/IV NSCLC who were treated with any first-line platinum-based doublet, with or without targeted agents, in routine clinical practice. A total of 1567 patients were observed in 11 countries between April 2009 and February 2011. Patients were mostly non-Asian (96.4%), male (71.5%), smokers (84.4%) with stage IV NSCLC (76.6%) and a performance status of 0-1 (82.2%). Median age was 64 years (range, 33-87). First-line treatments were platinum-based combinations with pemetrexed (36.3%), gemcitabine (23.0%), vinorelbine (19.2%), taxanes (18.9%), or other (2.6%), with concurrent targeted agents in 8.4% of patients (mainly bevacizumab, 7.3%). Diagnosis was based on histology in 70.6%, cytology in 20.3%, and both in 9.1% of patients. The final diagnosis was nonsquamous in 72.2% (including 'not otherwise specified [NOS]' in 11.0%), squamous in 24.4%, and other in 3.4% of patients, with the most common reasons for NOS diagnosis being 'subtyping not technically possible' (42.9%) and 'not important for treatment decision' (40.5%). Only 1.1% (6 patients) in the pemetrexed cohort and 0.9% (1 patient) of patients who received bevacizumab had squamous cell carcinoma. At least one immunohistochemical (IHC) marker was used in 53.5% of patients (thyroid transcription factor-1 [TTF-1]: 47.5%, cytokeratin 7 [CK7]: 38.6%, cytokeratin 5/6 [CK5/6]: 17.9%, p63: 8.8%, cluster of differentiation 56 [CD56]: 4.2%, cytokeratin 14 [CK14]: 1.9%, and other: 24.2%). Testing for additional biomarkers was less common, with the most common being for epidermal growth factor receptor (EGFR) mutation status (26.0%). Physician-reported key factors influencing treatment choice were 'histopathological/cytological diagnosis' (77.4%), 'performance status' (63.2%), and 'age' (52.8%). Similar factors were identified using logistic regression models. Frequent histological testing was observed, likely resulting in few NOS diagnoses. In addition, IHC and predictive biomarkers were routinely assessed. Histology, performance status, and age were key factors influencing first-line treatment choice in the routine care of patients with advanced NSCLC. Clinical Trials. gov registry identifier number: NCT01067794. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

[Current standards in the treatment of gastric cancer].

PubMed

Hacker, Ulrich; Lordick, Florian

2015-08-01

Endoscopic resection is established in the treatment of early gastric cancer. More advanced gastric cancer requires gastrectomy and D2 lymphadenectomy. Perioperative chemotherapy improves overall survival in locally advanced gastric cancer representing a standard of care. Locally advanced adenocarcinomas of the esophago-gastric junction can alternatively be treated with concurrent radiochemotherapy. In metastatic disease, systemic chemotherapy improves survival, quality of life and symptom control. Trastuzumab plus chemotherapy should be used together with first-line chemotherapy in HER2 positive gastric cancer patients. Second- and third-line therapy is now well established. The anti-VEGFR2 antibody Ramucirumab improves survival in second line treatment both as a monotherapy and in combination with paclitaxel and represents a novel treatment option. © Georg Thieme Verlag KG Stuttgart · New York.

11 CFR 100.83 - Brokerage loans and lines of credit to candidates.

Code of Federal Regulations, 2010 CFR

2010-01-01

..., credit card, home equity line of credit, or other line of credit available to the candidate, including an... making such loan makes loans derived from an advance on a candidate's brokerage account, credit card... card, home equity line of credit, or other line of credit available to the candidate, for which he or...

11 CFR 100.83 - Brokerage loans and lines of credit to candidates.

Code of Federal Regulations, 2011 CFR

2011-01-01

..., credit card, home equity line of credit, or other line of credit available to the candidate, including an... making such loan makes loans derived from an advance on a candidate's brokerage account, credit card... card, home equity line of credit, or other line of credit available to the candidate, for which he or...

11 CFR 100.83 - Brokerage loans and lines of credit to candidates.

Code of Federal Regulations, 2013 CFR

2013-01-01

..., credit card, home equity line of credit, or other line of credit available to the candidate, including an... making such loan makes loans derived from an advance on a candidate's brokerage account, credit card... card, home equity line of credit, or other line of credit available to the candidate, for which he or...

11 CFR 100.83 - Brokerage loans and lines of credit to candidates.

Code of Federal Regulations, 2014 CFR

2014-01-01

..., credit card, home equity line of credit, or other line of credit available to the candidate, including an... making such loan makes loans derived from an advance on a candidate's brokerage account, credit card... card, home equity line of credit, or other line of credit available to the candidate, for which he or...

11 CFR 100.83 - Brokerage loans and lines of credit to candidates.

Code of Federal Regulations, 2012 CFR

2012-01-01

..., credit card, home equity line of credit, or other line of credit available to the candidate, including an... making such loan makes loans derived from an advance on a candidate's brokerage account, credit card... card, home equity line of credit, or other line of credit available to the candidate, for which he or...

Meta-analysis of first-line therapies with maintenance regimens for advanced non-small-cell lung cancer (NSCLC) in molecularly and clinically selected populations.

PubMed

Tan, Pui San; Bilger, Marcel; de Lima Lopes, Gilberto; Acharyya, Sanchalika; Haaland, Benjamin

2017-08-01

Evidence has suggested survival benefits of maintenance for advanced NSCLC patients not progressing after first-line chemotherapy. Additionally, particular first-line targeted therapies have shown survival improvements in selected populations. Optimal first-line and maintenance therapies remain unclear. Here, currently available evidence was synthesized to elucidate optimal first-line and maintenance therapy within patient groups. Literature was searched for randomized trials evaluating first-line and maintenance regimens in advanced NSCLC patients. Bayesian network meta-analysis was performed within molecularly and clinically selected groups. The primary outcome was combined clinically meaningful OS and PFS benefits. A total of 87 records on 56 trials evaluating first-line treatments with maintenance were included. Results showed combined clinically meaningful OS and PFS benefits with particular first-line with maintenance treatments, (1) first-line intercalated chemotherapy+erlotinib, maintenance erlotinib in patients with EGFR mutations, (2) first-line afatinib, maintenance afatinib in patients with EGFR deletion 19, (3) first-line chemotherapy + bevacizumab, maintenance bevacizumab in EGFR wild-type patients, (4) chemotherapy+conatumumab, maintenance conatumumab in patients with squamous histology, (5) chemotherapy+cetuximab, maintenance cetuximab or chemotherapy + necitumumab, maintenance necitumumab in EGFR FISH-positive patients with squamous histology, and (6) first-line chemotherapy+bevacizumab, maintenance bevacizumab or first-line sequential chemotherapy+gefitinib, maintenance gefitinib in patients clinically enriched for EGFR mutations with nonsquamous histology. No treatment showed combined clinically meaningful OS and PFS benefits in patients with EGFR L858R or nonsquamous histology. Particular first-line with maintenance treatments show meaningful OS and PFS benefits in patients selected by EGFR mutation or histology. Further research is needed to achieve effective therapy for patients with EGFR mutation L858R or nonsquamous histology. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Systemic therapy for unresectable and metastatic transitional cell carcinoma of the urothelium: first-line and beyond.

PubMed

Cheng, Tina

2008-09-01

The review aims to provide an overview of recent advances and future research direction in the management of patients with advanced transitional cell carcinoma. Early data of the randomized phase III study comparing paclitaxel, cisplatin, and gemcitabine with gemcitabine plus cisplatin for advanced urothelial cancer detected no survival difference. A phase II study investigated the safety and efficacy of trastuzumab, carboplatin, gemcitabine, and paclitaxel in human epidermal growth factor receptor-2/neu-positive advanced urothelial carcinoma and reported promising results. Renal-sparing regimens are under active development. A nonrandomized comparison of the 3-week with the 4-week schedule for gemcitabine and cisplatin showed that the 3-week schedule had less hematological toxicity and better dose intensity. Potential molecular markers such as excision repair cross-complementation group 1, emmprin, and survivin for survival and/or platinum resistance in patients with transitional cell carcinoma showed promise. Recent data do not support change in the current standard of care for advanced transitional cell carcinoma. Clinical testing of emerging anticancer therapies using new agents, new combinations, and new approaches is under active investigation. Rational combination and new strategy in clinical trial design are critical for new drug development for transitional cell carcinoma.

Management of advanced pancreatic cancer with gemcitabine plus erlotinib: efficacy and safety results in clinical practice.

PubMed

Diaz Beveridge, Robert; Alcolea, Vicent; Aparicio, Jorge; Segura, Ángel; García, Jose; Corbellas, Miguel; Fonfría, María; Giménez, Alejandra; Montalar, Joaquin

2014-01-10

The combination of gemcitabine and erlotinib is a standard first-line treatment for unresectable, locally advanced or metastatic pancreatic cancer. We reviewed our single centre experience to assess its efficacy and toxicity in clinical practice. Clinical records of patients with unresectable, locally advanced or metastatic pancreatic cancer who were treated with the combination of gemcitabine and erlotinib were reviewed. Univariate survival analysis and multivariate analysis were carried out to indentify independent predictors factors of overall survival. Our series included 55 patients. Overall disease control rate was 47%: 5% of patients presented complete response, 20% partial response and 22% stable disease. Median overall survival was 8.3 months). Cox regression analysis indicated that performance status and locally advanced versus metastatic disease were independent factors of overall survival. Patients who developed acne-like rash toxicity, related to erlotinib administration, presented a higher survival than those patients who did not develop this toxicity. Gemcitabine plus erlotinib doublet is active in our series of patients with advanced pancreatic cancer. This study provides efficacy and safety results similar to those of the pivotal phase III clinical trial that tested the same combination.

First-line therapy for advanced non-small cell lung cancer with activating EGFR mutation: is combined EGFR-TKIs and chemotherapy a better choice?

PubMed

Wang, Shuyun; Gao, Aiqin; Liu, Jie; Sun, Yuping

2018-03-01

As the standard first-line treatment for advanced non-small cell lung cancer (NSCLC) with activating epidermal growth factor receptor (EGFR) mutation, EGFR-tyrosine kinase inhibitors (EGFR-TKIs) have significantly improved the median progression-free survival (PFS) up to 18.9 months. However, almost all patients eventually develop acquired resistance to EGFR-TKIs, which limits the first-line PFS. To overcome the resistance and improve overall survival, researchers have tried to identify the resistance mechanisms and develop new treatment strategies, among which a combination of EGFR-TKIs and cytotoxic chemotherapy is one of the hotspots. The data from preclinical and clinical studies on combined EGFR-TKIs and chemotherapy have shown very interesting results. Here, we reviewed the available preclinical and clinical studies on first-line EGFR-TKIs-chemotherapy combination in patients with advanced NSCLC harboring activating EGFR mutation, aiming to provide evidences for more potential choices and shed light on clinical treatment.

Base Stock Policy in a Join-Type Production Line with Advanced Demand Information

NASA Astrophysics Data System (ADS)

Hiraiwa, Mikihiko; Tsubouchi, Satoshi; Nakade, Koichi

Production control such as the base stock policy, the kanban policy and the constant work-in-process policy in a serial production line has been studied by many researchers. Production lines, however, usually have fork-type, join-type or network-type figures. In addition, in most previous studies on production control, a finished product is required at the same time as arrival of demand at the system. Demand information is, however, informed before due date in practice. In this paper a join-type (assembly) production line under base stock control with advanced demand information in discrete time is analyzed. The recursive equations for the work-in-process are derived. The heuristic algorithm for finding appropriate base stock levels of all machines at short time is proposed and the effect of advanced demand information is examined by simulation with the proposed algorithm. It is shown that the inventory cost can decreases with little backlogs by using the appropriate amount of demand information and setting appropriate base stock levels.

Treatment of NRAS-mutated advanced or metastatic melanoma: rationale, current trials and evidence to date

PubMed Central

Boespflug, Amélie; Caramel, Julie; Dalle, Stephane; Thomas, Luc

2017-01-01

The disease course of BRAF (v-raf murine sarcoma viral oncogene homolog B1)-mutant melanoma has been drastically improved by the arrival of targeted therapies. NRAS (neuroblastoma RAS viral oncogene homolog)-mutated melanoma represents 15–25% of all metastatic melanoma patients. It currently does not have an approved targeted therapy. Metastatic patients receive immune-based therapies as first-line treatments, then cytotoxic chemotherapy like carboplatin/paclitaxel (C/P), dacarbazine (DTIC) or temozolomide (TMZ) as a second-line treatment. We will review current preclinical and clinical developments in NRAS-mutated melanoma, and analyze ongoing clinical trials that are evaluating the benefit of different targeted and immune-based therapies, either tested as single agents or in combination, in NRAS-mutant melanoma. PMID:28717400

The Changing Treatment Landscape for Metastatic Urothelial Carcinoma.

PubMed

Flaig, Thomas W

2018-05-01

Urothelial carcinoma is the predominant histologic type of bladder cancer. After 30 years of minimal progress in the treatment of advanced-stage disease, recent advances in the genomic characterization of urothelial cancer and breakthroughs in bladder cancer therapeutics have rejuvenated the field. Nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab are among the exciting recent novel therapeutic advances gaining approvals by the FDA for treatment of advanced-stage urothelial carcinoma. Yet the challenge for clinicians is to determine the optimal choice of agents as first-line or second-line therapy and which offers the best chance for overall survival for the individual patient in this rapidly changing field. Copyright © 2018 by the National Comprehensive Cancer Network.

Real-world evidence analysis of palbociclib prescribing patterns for patients with advanced/metastatic breast cancer treated in community oncology practice in the USA one year post approval.

PubMed

Kish, J K; Ward, M A; Garofalo, D; Ahmed, H V; McRoy, L; Laney, J; Zanotti, G; Braverman, J; Yu, H; Feinberg, B A

2018-05-02

Rapidly evolving understanding of cancer biology has presented novel opportunities to translate that understanding into clinically relevant therapy. Palbociclib, a novel, first-in-class cyclin-dependent kinase (CDK) 4/6 inhibitor was approved in the USA in February 2015 for the treatment of advanced/metastatic breast cancer. We examined real-world evidence in the first year post approval to understand the clinical and demographic characteristics of patients treated with palbociclib in community oncology practices and the dosing, treatment, and complete blood count (CBC) monitoring patterns. This was a retrospective observational study of structured data from a US electronic medical record (EMR) database. Female patients receiving palbociclib after 31 January 2015 were followed through 31 March 2016. Our methodological rules were constructed to aggregate drugs received according to the order in which they are given, i.e., identify the line of therapy as first, second, or third line, etc., using treatment order and course description fields from the EMR. There were 763 patients initiating palbociclib who met the selection criteria. Of those, 612 (80.2%) received palbociclib concomitantly with letrozole. Mean follow up was 6.4 months and mean age at palbociclib initiation was 64 years. Of patients with a known starting dose (n = 417), 79.9% started on palbociclib 125 mg. Dose reductions were observed in 20.1% of patients. Percentages of patients according to line of therapy at initiation of palbociclib were first-line, 39.5%; second-line, 15.7%; third-line, 13.1%; and fourth-line therapy or later, 31.7%. On average, two CBC tests were conducted during the first cycle of palbociclib treatment. Overall, 74.6% of patients had a neutropenic event during follow up including 47.3% and 8.0% of patients with a grade 3 or 4 occurrence, respectively. Real-world palbociclib use one year post US approval demonstrates a more heterogeneous patient population than that studied in the clinical trials with more than half of the patients receiving palbociclib plus letrozole in later lines of therapy. CBC testing rates suggested good provider compliance with monitoring guidelines in the USA prescribing information. The occurrence of grade 3 and 4 neutropenia (based on laboratory results) was consistent with the rates of grade 3 and 4 neutropenia in two phase-III studies (PALOMA-2, 56% and 10%; PALOMA-3, 55% and 11%, respectively). Understanding palbociclib utilization in real-world patients and how drug dosing and monitoring are performed aids in the understanding of safe and effective use of the drug.

Russian Rocket Engine Test

NASA Technical Reports Server (NTRS)

1998-01-01

NASA engineers successfully tested a Russian-built rocket engine on November 4, 1998 at the Marshall Space Flight Center (MSFC) Advanced Engine Test Facility, which had been used for testing the Saturn V F-1 engines and Space Shuttle Main engines. The MSFC was under a Space Act Agreement with Lockheed Martin Astronautics of Denver to provide a series of test firings of the Atlas III propulsion system configured with the Russian-designed RD-180 engine. The tests were designed to measure the performance of the Atlas III propulsion system, which included avionics and propellant tanks and lines, and how these components interacted with the RD-180 engine. The RD-180 is powered by kerosene and liquid oxygen, the same fuel mix used in Saturn rockets. The RD-180, the most powerful rocket engine tested at the MSFC since Saturn rocket tests in the 1960s, generated 860,000 pounds of thrust. The test was the first test ever anywhere outside Russia of a Russian designed and built engine.

Pulmonary tuberculosis in outpatients in Sabah, Malaysia: advanced disease but low incidence of HIV co-infection.

PubMed

William, Timothy; Parameswaran, Uma; Lee, Wai Khew; Yeo, Tsin Wen; Anstey, Nicholas M; Ralph, Anna P

2015-01-31

Tuberculosis (TB) is generally well controlled in Malaysia, but remains an important problem in the nation's eastern states. In order to better understand factors contributing to high TB rates in the eastern state of Sabah, our aims were to describe characteristics of patients with TB at a large outpatient clinic, and determine the prevalence of HIV co-infection. Additionally, we sought to test sensitivity and specificity of the locally-available point-of-care HIV test kits. We enrolled consenting adults with smear-positive pulmonary TB for a 2-year period at Luyang Clinic, Kota Kinabalu, Malaysia. Participants were questioned about ethnicity, smoking, prior TB, disease duration, symptoms and comorbidities. Chest radiographs were scored using a previously devised tool. HIV was tested after counselling using 2 point-of-care tests for each patient: the test routinely in use at the TB clinic (either Advanced Quality™ Rapid Anti-HIV 1&2, FACTS anti-HIV 1/2 RAPID or HIV (1 + 2) Antibody Colloidal Gold), and a comparator test (Abbott Determine™ HIV-1/2, Inverness Medical). Positive tests were confirmed by enzyme immunoassay (EIA), particle agglutination and line immunoassay. 176 participants were enrolled; 59 (33.5%) were non-Malaysians and 104 (59.1%) were male. Smoking rates were high (81/104 males, 77.9%), most had cavitary disease (51/145, 64.8%), and 81/176 (46.0%) had haemoptysis. The median period of symptoms prior to treatment onset was 8 weeks. Diabetes was present in 12. People with diabetes or other comorbidities had less severe TB, suggesting different healthcare seeking behaviours in this group. All participants consented to HIV testing: three (1.7%) were positive according to Determine™ and EIA, but one of these tested negative on the point-of-care test available at the clinic (Advanced Quality™ Rapid Anti-HIV 1&2). The low number of positive tests and changes in locally-available test type meant that accurate estimates of sensitivity and specificity were not possible. Patients had advanced disease at diagnosis, long diagnostic delays, low HIV co-infection rates, high smoking rates among males, and migrants may be over-represented. These findings provide important insights to guide local TB control efforts. Caution is required in using some point-of-care HIV tests, and ongoing quality control measures are of major importance.

GOES-R Advanced Base Line Imager Installation

NASA Image and Video Library

2016-08-30

Team members prepare the Advanced Base Line Imager, the primary optical instrument, for installation on the Geostationary Operational Environmental Satellite (GOES-R) inside the Astrotech payload processing facility in Titusville, Florida near NASA’s Kennedy Space Center. GOES-R will be the first satellite in a series of next-generation NOAA GOES Satellites. The spacecraft is to launch aboard a United Launch Alliance Atlas V rocket in November.

GOES-R Advanced Base Line Imager Installation

NASA Image and Video Library

2016-08-30

Team members install the Advanced Base Line Imager, the primary optical instrument, on the Geostationary Operational Environmental Satellite (GOES-R) inside the Astrotech payload processing facility in Titusville, Florida near NASA’s Kennedy Space Center. GOES-R will be the first satellite in a series of next-generation NOAA GOES Satellites. The spacecraft is to launch aboard a United Launch Alliance Atlas V rocket in November.

GOES-R Advanced Base Line Imager Installation

NASA Image and Video Library

2016-08-30

The Advanced Base Line Imager, the primary optical instrument, has been installed on the Geostationary Operational Environmental Satellite (GOES-R) inside the Astrotech payload processing facility in Titusville, Florida near NASA’s Kennedy Space Center. GOES-R will be the first satellite in a series of next-generation NOAA GOES Satellites. The spacecraft is to launch aboard a United Launch Alliance Atlas V rocket in November.

Expression of Recombinant Antibodies

PubMed Central

Frenzel, André; Hust, Michael; Schirrmann, Thomas

2013-01-01

Recombinant antibodies are highly specific detection probes in research, diagnostics, and have emerged over the last two decades as the fastest growing class of therapeutic proteins. Antibody generation has been dramatically accelerated by in vitro selection systems, particularly phage display. An increasing variety of recombinant production systems have been developed, ranging from Gram-negative and positive bacteria, yeasts and filamentous fungi, insect cell lines, mammalian cells to transgenic plants and animals. Currently, almost all therapeutic antibodies are still produced in mammalian cell lines in order to reduce the risk of immunogenicity due to altered, non-human glycosylation patterns. However, recent developments of glycosylation-engineered yeast, insect cell lines, and transgenic plants are promising to obtain antibodies with “human-like” post-translational modifications. Furthermore, smaller antibody fragments including bispecific antibodies without any glycosylation are successfully produced in bacteria and have advanced to clinical testing. The first therapeutic antibody products from a non-mammalian source can be expected in coming next years. In this review, we focus on current antibody production systems including their usability for different applications. PMID:23908655

Assessment of an Euler-Interacting Boundary Layer Method Using High Reynolds Number Transonic Flight Data

NASA Technical Reports Server (NTRS)

Bonhaus, Daryl L.; Maddalon, Dal V.

1998-01-01

Flight-measured high Reynolds number turbulent-flow pressure distributions on a transport wing in transonic flow are compared to unstructured-grid calculations to assess the predictive ability of a three-dimensional Euler code (USM3D) coupled to an interacting boundary layer module. The two experimental pressure distributions selected for comparative analysis with the calculations are complex and turbulent but typical of an advanced technology laminar flow wing. An advancing front method (VGRID) was used to generate several tetrahedral grids for each test case. Initial calculations left considerable room for improvement in accuracy. Studies were then made of experimental errors, transition location, viscous effects, nacelle flow modeling, number and placement of spanwise boundary layer stations, and grid resolution. The most significant improvements in the accuracy of the calculations were gained by improvement of the nacelle flow model and by refinement of the computational grid. Final calculations yield results in close agreement with the experiment. Indications are that further grid refinement would produce additional improvement but would require more computer memory than is available. The appendix data compare the experimental attachment line location with calculations for different grid sizes. Good agreement is obtained between the experimental and calculated attachment line locations.

Upgrade of Irradiation Test Capability of the Experimental Fast Reactor Joyo

NASA Astrophysics Data System (ADS)

Sekine, Takashi; Aoyama, Takafumi; Suzuki, Soju; Yamashita, Yoshioki

2003-06-01

The JOYO MK-II core was operated from 1983 to 2000 as fast neutron irradiation bed. In order to meet various requirements for irradiation tests for development of FBRs, the JOYO upgrading project named MK-III program was initiated. The irradiation capability in the MK-III core will be about four times larger than that of the MK-II core. Advanced irradiation test subassemblies such as capsule type subassembly and on-line instrumentation rig are planned. As an innovative reactor safety system, the irradiation test of Self-Actuated Shutdown System (SASS) will be conducted. In order to improve the accuracy of neutron fluence, the core management code system was upgraded, and the Monte Carlo code and Helium Accumulation Fluence Monitor (HAFM) were applied. The MK-III core is planned to achieve initial criticality in July 2003.

Duct wall impedance control as an advanced concept for acoustic impression

NASA Technical Reports Server (NTRS)

Dean, P. D.; Tester, B. J.

1975-01-01

Models and tests on an acoustic duct liner system which has the property of controlled-variable acoustic impedance are described. This is achieved by a novel concept which uses the effect of steady air flow through a multi-layer, locally reacting, resonant-cavity absorber. The scope of this work was limited to a 'proof of concept.' The test of the concept was implemented by means of a small-scale, square-section flow duct facility designed specifically for acoustic measurements, with one side of the duct acoustically lined. The test liners were designed with the aid of previously established duct acoustic theory and a semi-empirical impedance model of the liner system. Over the limited range tested, the liner behaved primarily as predicted, exhibiting significant changes in resistance and reactance, thus providing the necessary concept validation.

Jet outflow and open field line measurements on the C-2U advanced beam-driven field-reversed configuration plasma experiment.

PubMed

Sheftman, D; Gupta, D; Roche, T; Thompson, M C; Giammanco, F; Conti, F; Marsili, P; Moreno, C D

2016-11-01

Knowledge and control of the axial outflow of plasma particles and energy along open-magnetic-field lines are of crucial importance to the stability and longevity of the advanced beam-driven field-reversed configuration plasma. An overview of the diagnostic methods used to perform measurements on the open field line plasma on C-2U is presented, including passive Doppler impurity spectroscopy, microwave interferometry, and triple Langmuir probe measurements. Results of these measurements provide the jet ion temperature and axial velocity, electron density, and high frequency density fluctuations.

Jet outflow and open field line measurements on the C-2U advanced beam-driven field-reversed configuration plasma experiment

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

Sheftman, D., E-mail: dsheftman@trialphaenergy.com; Gupta, D.; Roche, T.

Knowledge and control of the axial outflow of plasma particles and energy along open-magnetic-field lines are of crucial importance to the stability and longevity of the advanced beam-driven field-reversed configuration plasma. An overview of the diagnostic methods used to perform measurements on the open field line plasma on C-2U is presented, including passive Doppler impurity spectroscopy, microwave interferometry, and triple Langmuir probe measurements. Results of these measurements provide the jet ion temperature and axial velocity, electron density, and high frequency density fluctuations.

Taking charge: front-line nurse leadership development.

PubMed

Schwarzkopf, Ruth; Sherman, Rose O; Kiger, Anna J

2012-04-01

The recent Institute of Medicine (2010) report, The Future of Nursing: Leading Change, Advancing Health, included a recommendation that nurses at all levels should be prepared and enabled to lead change to advance health care in the United States. Historically, in most organizations, nursing leadership development programs have focused on nurses in management or executive roles rather than those working in front-line leadership roles. This article describes a front-line leadership development initiative developed by Tenet Healthcare Corporation and attended by 400 charge nurses. Program development, evaluation, and lessons learned that can be applied in other organizations are discussed. Copyright 2012, SLACK Incorporated.

Tests of a low-pressure switch protected by a saturating inductor

NASA Astrophysics Data System (ADS)

Lauer, E. J.; Birx, D. L.

Low pressure switches and magnetic switches were tested as possible replacements for the high pressure switches currently used on Experimental Test Accelerator and Advanced Test Accelerator. When the low pressure switch is used with a low impedance transmission line, runaway electrons form a pinched electron beam which damages the anode. The use of the low pressure switch as the first switch in the pulsed power chain was tested; i.e., the switch would be used to connect a charged capacitor across the primary winding of a step up transformer. An inductor with a saturating core is connected in series so that, initially, there is a large inductive voltage drop. As a result, there is small voltage across the switch. By the time the inductor core saturates, the switch has developed sufficient ionization so that the switch voltage remains small, even with peak current, and an electron beam is not produced.

The Effects of Ultra Thin Films on Dynamic Wetting

NASA Astrophysics Data System (ADS)

Chen, Xia; Garoff, Stephen; Rame, Enrique

2002-11-01

Dynamic wetting, the displacement of one fluid by another immiscible fluid on a surface, controls many natural and technological phenomena, such as coating, printing, spray painting and lubricating. Particularly in coating and spraying applications, contact lines advance across pre-existing fluid films. Most previous work has focused on contact lines advancing across films sufficiently thick that they behave as simple Newtonian fluids. Ultrathin films, where the film thickness may impinge on fundamental length scales in the fluid, have received less attention. In this talk, we will discuss the effects of ultrathin polymer films on dynamic wetting. We measure the interface shape within microns of moving contact lines advancing across preexisting films and compare the measurements to existing models of viscous bending for interfaces advancing across dry surfaces and 'thick' (in the sense that they behave as liquids) films. In the experiments, we advance a contact line of 10-poise and 1-poise polydimethylsiloxane (silicone oil) across pre-coated films of the same fluid with thickness from a single chain thickness (approx. 10 A) through a couple of radii of gyration (100-200 A) to films so thick they are likely bulk in behavior (103 A). All films are physisorbed, i.e. they readily rinse from the surface. Thus, molecules in the film are not anchored to the surface and can move within the film if the hydrodynamics dictate such motion. For films of the thickness of a single chain (approx. 10 A), our experiments indicate that the advancing fluid behaves just as it would if it advanced over a dry surface. For the thicker films (103 A), we find behavior indicating that the molecules in the film are acting as a fluid with the bulk properties. In this regime, results for the two different fluids are identical when the experiments are performed at the same pre-existing film thickness and advancing capillary number, Ca. For film of thickness of a few radii of gyration (approx. 100-200 A), the behavior depends on Ca of the advancing meniscus. At low Ca, the viscous bending of the interface near the contact line does not behave as it would on a dry surface. It has a lower curvature than expected. However, at higher Ca, the viscous bending is described by the model for spreading over a dry surface. These results show that the fluid flow in the film does behave differently than bulk as the film thickness becomes comparable to molecular length scale. But even more intriguing is the unusual velocity dependence of that behavior where the film behaves more solid-like at higher contact line speeds. We will discuss these results in terms of the properties of confined polymer melts.

The Effects of Ultra Thin Films on Dynamic Wetting

NASA Technical Reports Server (NTRS)

Chen, Xia; Garoff, Stephen; Rame, Enrique

2002-01-01

Dynamic wetting, the displacement of one fluid by another immiscible fluid on a surface, controls many natural and technological phenomena, such as coating, printing, spray painting and lubricating. Particularly in coating and spraying applications, contact lines advance across pre-existing fluid films. Most previous work has focused on contact lines advancing across films sufficiently thick that they behave as simple Newtonian fluids. Ultrathin films, where the film thickness may impinge on fundamental length scales in the fluid, have received less attention. In this talk, we will discuss the effects of ultrathin polymer films on dynamic wetting. We measure the interface shape within microns of moving contact lines advancing across preexisting films and compare the measurements to existing models of viscous bending for interfaces advancing across dry surfaces and 'thick' (in the sense that they behave as liquids) films. In the experiments, we advance a contact line of 10-poise and 1-poise polydimethylsiloxane (silicone oil) across pre-coated films of the same fluid with thickness from a single chain thickness (approx. 10 A) through a couple of radii of gyration (100-200 A) to films so thick they are likely bulk in behavior (10(exp 3) A). All films are physisorbed, i.e. they readily rinse from the surface. Thus, molecules in the film are not anchored to the surface and can move within the film if the hydrodynamics dictate such motion. For films of the thickness of a single chain (approx. 10 A), our experiments indicate that the advancing fluid behaves just as it would if it advanced over a dry surface. For the thicker films (10(exp 3) A), we find behavior indicating that the molecules in the film are acting as a fluid with the bulk properties. In this regime, results for the two different fluids are identical when the experiments are performed at the same pre-existing film thickness and advancing capillary number, Ca. For film of thickness of a few radii of gyration (approx. 100-200 A), the behavior depends on Ca of the advancing meniscus. At low Ca, the viscous bending of the interface near the contact line does not behave as it would on a dry surface. It has a lower curvature than expected. However, at higher Ca, the viscous bending is described by the model for spreading over a dry surface. These results show that the fluid flow in the film does behave differently than bulk as the film thickness becomes comparable to molecular length scale. But even more intriguing is the unusual velocity dependence of that behavior where the film behaves more solid-like at higher contact line speeds. We will discuss these results in terms of the properties of confined polymer melts.

Basic and Advanced Numerical Performances Relate to Mathematical Expertise but Are Fully Mediated by Visuospatial Skills

PubMed Central

2016-01-01

Recent studies have highlighted the potential role of basic numerical processing in the acquisition of numerical and mathematical competences. However, it is debated whether high-level numerical skills and mathematics depends specifically on basic numerical representations. In this study mathematicians and nonmathematicians performed a basic number line task, which required mapping positive and negative numbers on a physical horizontal line, and has been shown to correlate with more advanced numerical abilities and mathematical achievement. We found that mathematicians were more accurate compared with nonmathematicians when mapping positive, but not negative numbers, which are considered numerical primitives and cultural artifacts, respectively. Moreover, performance on positive number mapping could predict whether one is a mathematician or not, and was mediated by more advanced mathematical skills. This finding might suggest a link between basic and advanced mathematical skills. However, when we included visuospatial skills, as measured by block design subtest, the mediation analysis revealed that the relation between the performance in the number line task and the group membership was explained by non-numerical visuospatial skills. These results demonstrate that relation between basic, even specific, numerical skills and advanced mathematical achievement can be artifactual and explained by visuospatial processing. PMID:26913930

Osimertinib: First Global Approval.

PubMed

Greig, Sarah L

2016-02-01

Osimertinib (Tagrisso(™), AZD9291) is an oral, third-generation epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) that is being developed by AstraZeneca for the treatment of advanced non-small cell lung cancer (NSCLC). Osimertinib has been designed to target the EGFR T790M mutation that is often present in NSCLC patients with acquired EGFR TKI resistance, while sparing wild-type EGFR. In November 2015, the tablet formulation of osimertinib was granted accelerated approval in the USA for the treatment of patients with metastatic EGFR T790M mutation-positive NSCLC (as detected by an FDA-approved test) who have progressed on or after EGFR TKI therapy. Osimertinib has also been granted accelerated assessment status for this indication in the EU, and is in phase III development for first- and second-line and adjuvant treatment of advanced EGFR mutation-positive NSCLC in several countries. Phase I trials in patients with advanced solid tumours are also being conducted. This article summarizes the milestones in the development of osimertinib leading to this first approval for NSCLC.

Advanced Automotive Diesel Assessment Program, executive summary

NASA Technical Reports Server (NTRS)

1983-01-01

The objectives of this analytical study were: to select one advanced automotive diesel engine (AAD) concept which would increase the tank mileage of a 3,000 pound passenger car from the present 35 mpg to at least 52 mpg; to identify long term component research and development work required to bring the selected concept to fruition; and to prepare a development strategy that will bring the selected concept to a prototype testing phase. Cummins Engine Company has completed this study. The selected concept is a 4 stroke cycle, direct injection, spark assisted, advanced adiabatic diesel engine with positive displacement compounding plus expander and part load air preheating. The engine does not use a liquid coolant nor liquid lubricants. It is a 4 cylinder, in-line, 77 mm bore x 77 mm stroke, 1.434 liters displacement engine weighing 300 lb, and rated at 70 BHP at 3000 rpm. Installation dimensions are 621 mm length x 589 mm width x 479 mm height (24.4 inch x 22 inch x 18.9 inch).

In Vitro Microfluidic Models for Neurodegenerative Disorders.

PubMed

Osaki, Tatsuya; Shin, Yoojin; Sivathanu, Vivek; Campisi, Marco; Kamm, Roger D

2018-01-01

Microfluidic devices enable novel means of emulating neurodegenerative disease pathophysiology in vitro. These organ-on-a-chip systems can potentially reduce animal testing and substitute (or augment) simple 2D culture systems. Reconstituting critical features of neurodegenerative diseases in a biomimetic system using microfluidics can thereby accelerate drug discovery and improve our understanding of the mechanisms of several currently incurable diseases. This review describes latest advances in modeling neurodegenerative diseases in the central nervous system and the peripheral nervous system. First, this study summarizes fundamental advantages of microfluidic devices in the creation of compartmentalized cell culture microenvironments for the co-culture of neurons, glial cells, endothelial cells, and skeletal muscle cells and in their recapitulation of spatiotemporal chemical gradients and mechanical microenvironments. Then, this reviews neurodegenerative-disease-on-a-chip models focusing on Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Finally, this study discusses about current drawbacks of these models and strategies that may overcome them. These organ-on-chip technologies can be useful to be the first line of testing line in drug development and toxicology studies, which can contribute significantly to minimize the phase of animal testing steps. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Use of whole genome sequencing in surveillance of drug resistant tuberculosis.

PubMed

McNerney, Ruth; Zignol, Matteo; Clark, Taane G

2018-05-01

The threat of resistance to anti-tuberculosis drugs is of global concern. Current efforts to monitor resistance rely on phenotypic testing where cultured bacteria are exposed to critical concentrations of the drugs. Capacity for such testing is low in TB endemic countries. Drug resistance is caused by mutations in the Mycobacterium tuberculosis genome and whole genome sequencing to detect these mutations offers an alternative means of assessing resistance. Areas covered: The challenges of assessing TB drug resistance are discussed. Progress in elucidating the M. tuberculosis resistome and evidence of the accuracy of next generation sequencing for detecting resistance is reviewed. Expert Commentary: There are considerable advantages to using next generation sequencing for TB drug resistance surveillance. Accuracy is high for detecting resistance to the major first-line drugs but is currently lower for the second-line drugs due to our incomplete knowledge regarding resistance causing mutations. With the advances in sequencing technology and the opportunity to replace phenotypic drug susceptibility testing with safer and more cost effective methods it would appear that the question is when to implement. Current bottlenecks are sample extraction to allow whole genome sequencing directly from sputum and the lack of bioinformatics expertise in some TB endemic countries.

Improved plutonium identification and characterization results with NaI(Tl) detector using ASEDRA

NASA Astrophysics Data System (ADS)

Detwiler, R.; Sjoden, G.; Baciak, J.; LaVigne, E.

2008-04-01

The ASEDRA algorithm (Advanced Synthetically Enhanced Detector Resolution Algorithm) is a tool developed at the University of Florida to synthetically enhance the resolved photopeaks derived from a characteristically poor resolution spectra collected at room temperature from scintillator crystal-photomultiplier detector, such as a NaI(Tl) system. This work reports on analysis of a side-by-side test comparing the identification capabilities of ASEDRA applied to a NaI(Tl) detector with HPGe results for a Plutonium Beryllium (PuBe) source containing approximately 47 year old weapons-grade plutonium (WGPu), a test case of real-world interest with a complex spectra including plutonium isotopes and 241Am decay products. The analysis included a comparison of photopeaks identified and photopeak energies between the ASEDRA and HPGe detector systems, and the known energies of the plutonium isotopes. ASEDRA's performance in peak area accuracy, also important in isotope identification as well as plutonium quality and age determination, was evaluated for key energy lines by comparing the observed relative ratios of peak areas, adjusted for efficiency and attenuation due to source shielding, to the predicted ratios from known energy line branching and source isotopics. The results show that ASEDRA has identified over 20 lines also found by the HPGe and directly correlated to WGPu energies.

GOES-R Advanced Base Line Imager Installation

NASA Image and Video Library

2016-08-30

Team members assist as a crane lifts the Advanced Base Line Imager, the primary optical instrument, for installation on the Geostationary Operational Environmental Satellite (GOES-R) inside the Astrotech payload processing facility in Titusville, Florida near NASA’s Kennedy Space Center. GOES-R will be the first satellite in a series of next-generation NOAA GOES Satellites. The spacecraft is to launch aboard a United Launch Alliance Atlas V rocket in November.

GOES-R Advanced Base Line Imager Installation

NASA Image and Video Library

2016-08-30

Team members assist as a crane moves the Advanced Base Line Imager, the primary optical instruments, for installation on the Geostationary Operational Environmental Satellite (GOES-R) inside the Astrotech payload processing facility in Titusville, Florida near NASA’s Kennedy Space Center. GOES-R will be the first satellite in a series of next-generation NOAA GOES Satellites. The spacecraft is to launch aboard a United Launch Alliance Atlas V rocket in November.

Supply and Financial Systems Training for the Line Officer Afloat.

DTIC Science & Technology

1977-09-01

Structural training is a most efficient and recognized method to obtain basic knowledge of shipboard life . The line officer’s first contact with...resources in order to support the ship’s mission. For example, when he signs requests for leave, early liberty, advancement , or any other request...Naval War College, Naval Postgraduate School, and Department Head School (formerly Destroyer School). These provide advanced training in a great

A scoring system to guide the decision for a new systemic treatment after at least two lines of palliative chemotherapy for metastatic cancers: a prospective study.

PubMed

Chanez, Brice; Bertucci, François; Gilabert, Marine; Madroszyk, Anne; Rousseau, Frédérique; Perrot, Delphine; Viens, Patrice; Raoul, Jean-Luc

2017-09-01

A four-parameter score has been identified as associated with overall survival (OS) in patients with advanced cancer with an estimated survival inferior to 6 months. Here, we tested its prognostic value for OS in patients who had received more than two lines of systemic therapy. We prospectively enrolled patients with advanced cancer who were going to receive a third or more therapeutic line outside classical clinical guidelines. The four parameters (Eastern Cooperative Oncology Group performance status, number of metastatic sites, serum LDH, and serum albumin) were collected at baseline, allowing to calculate the score, which sorted the patients in three groups, A, B, and C (low, intermediate, and high score, respectively). We then searched for correlations between this grouping and clinicopathological features particularly OS. From August 2013 to March 2014, 65 patients were enrolled and corresponded after determining their score to 26 patients in group A, 30 in B, and 9 in C. The median OS of the cohort was 4.4 months, and the 6-month OS was 42%. Overall survival was different between the three groups, with respective 6-month OS equal to 80% in group A, 17% in group B, and 0% in group C and respective median OS of 9, 2.3, and 1.6 months. Such prognostic value persisted in multivariate analysis. Similar OS differences were observed in patients with PS ≤2. This simple scoring should help oncologists identify which patients, after at least two lines of systemic therapy, might benefit from best supportive care alone.

Efficacy and safety of icotinib as first-line therapy in patients with advanced non-small-cell lung cancer

PubMed Central

Shen, Yan-Wei; Zhang, Xiao-Man; Li, Shu-Ting; Lv, Meng; Yang, Jiao; Wang, Fan; Chen, Zhe-Ling; Wang, Bi-Yuan; Li, Pan; Chen, Ling; Yang, Jin

2016-01-01

Background and objective Several clinical trials have proven that icotinib hydrochloride, a novel epidermal growth factor receptor (EGFR)–tyrosine kinase inhibitor, exhibits encouraging efficacy and tolerability in patients with advanced non-small-cell lung cancer (NSCLC) who failed previous chemotherapy. This study was performed to assess the efficacy and toxicity of icotinib as first-line therapy for patients with advanced pulmonary adenocarcinoma with EGFR-sensitive mutation. Patients and methods Thirty-five patients with advanced NSCLC with EGFR-sensitive mutation who were sequentially admitted to the First Affiliated Hospital of Xi’an Jiaotong University from March 2012 to March 2014 were enrolled into our retrospective research. All patients were administered icotinib as first-line treatment. The tumor responses were evaluated using Response Evaluation Criteria in Solid Tumors (RECIST, version 1.1). Results Among the 35 patients, the tumor objective response rate (ORR) and disease control rate were 62.9% (22/35) and 88.6% (31/35), respectively. The median progression-free survival was 11.0 months (95% confidence interval [CI]: 10.2–11.8 months), and median overall survival was 21.0 months (95% CI: 20.1–21.9 months). The most common drug-related toxicities were rashes (eleven patients) and diarrhea (nine patients), but these were generally manageable and reversible. Conclusion Icotinib monotherapy is effective and tolerable as first-line treatment for patients with advanced lung adenocarcinoma with EGFR-sensitive mutation. PMID:26966381

A New Test of Copper and Zinc Abundances in Late-Type Stars Using Cu II and Zn II lines in the Near-Ultraviolet

NASA Astrophysics Data System (ADS)

Roederer, Ian

2017-08-01

The copper (Cu, Z = 29) and zinc (Zn, Z = 30) abundances found in late-type stars provide critical constraints on models that predict the yields of massive star supernovae, hypernovae, Type Ia supernovae, and AGB stars, which are essential ingredients in Galactic chemical evolution models. Furthermore, Zn is commonly used to compare the abundance of iron-group elements in the gas phase in high-redshift DLA systems with metallicities in Local Group stars. It is thus important that the observational Cu and Zn abundances in stars are correct. My proposed archive study will address this issue by using archive STIS spectra of 14 stars to provide the first systematic observational tests of non-LTE calculations of Cu and Zn line formation in late-type stars. The non-LTE calculations predict that all LTE [Cu/Fe] abundance ratios presently found in the literature are systematically lower than the true ratios found in stars. The non-LTE calculations for Zn predict that the LTE values in the literature may be systematically overestimated in low-metallicity stars. The LTE abundances of Cu and Zn are derived from Cu I and Zn I lines. The key advance enabled by the use of NUV spectra is the detection of several lines of Cu II and Zn II, which cannot be detected in the optical or infrared. Cu II and Zn II are largely immune to non-LTE effects in the atmospheres of late-type stars. The metallicities of the 14 stars with NUV spectra span -2.6 < [Fe/H] < -0.1, which covers the range of most Cu and Zn abundances reported in the literature. The proposed study will allow me to test the non-LTE calculations and calibrate the stellar abundances.

Aerometrics' laser-based lane-tracker sensor: engineering and on-the-road evaluation of advanced prototypes

NASA Astrophysics Data System (ADS)

Schuler, Carlos A.; Tapos, Francis M.; Alayleh, Mehyeddine M.; Bachalo, William D.

1997-02-01

Aerometrics initiated and continues on the development an innovative laser-diode based device that provides a warning signal when a motor-vehicle deviates from the center of the lane. The device is based on a sensor that scans the roadway on either side of the vehicle and determines the lateral position relative to the existing painted lines marking the lane. The principles of operation of the sensor, and the results of Aerometrics' early testing were presented last year in this forum. This paper presents Aerometrics' continuing efforts in bringing the technology to market. New prototypes have been developed and tested. Aerometrics' engineering efforts and the use of latest technologies have resulted in a 24-fold reduction in sensor volume when compared to their predecessors and similar reductions in weight. The current prototype measures less than 9 cm X 8 cm X 7 cm, and can be easily fit within the cavity of rear-view mirror holders used in most present-day vehicles. Also, advances in signal conditioning and processing have improved the reliability of the sensor. Results of continuing testing of the sensor will be presented.

A phase I study of imexon plus gemcitabine as first-line therapy for advanced pancreatic cancer.

PubMed

Cohen, Steven J; Zalupski, Mark M; Modiano, Manuel R; Conkling, Paul; Patt, Yehuda Z; Davis, Peg; Dorr, Robert T; Boytim, Michelle L; Hersh, Evan M

2010-07-01

Imexon is an aziridine-derived iminopyrrolidone which has synergy with gemcitabine in pancreatic cancer cell lines. Gemcitabine is a standard therapy for pancreatic cancer. We performed a phase I trial of imexon and gemcitabine to evaluate safety, dose-limiting toxicity (DLT), and maximum tolerated dose (MTD) in patients with advanced pancreatic cancer. Patients with untreated locally advanced or metastatic pancreatic adenocarcinoma received therapy in sequential cohorts on regimen A (n = 19; imexon 200 or 280 mg/m(2) intravenously (IV) over 30 min days 1-5, 15-19 and gemcitabine 800 or 1,000 mg/m(2) IV over 30 min on days 1,8,15 every 28 days) or regimen B (n = 86; imexon 280-1,300 mg/m(2) IV over 30-60 min days 1, 8, and 15 and gemcitabine 1,000 mg/m(2) IV over 30 min on days 1, 8, and 15 every 28 days). One hundred five patients received 340 treatment cycles (median 2, range 1-16). median age 63, 61% male, ECOG PS 0/1 50%/50%, 93% metastatic. DLT was abdominal cramping and pain, often with transient, acute diarrhea. Best response was confirmed partial response (PR) in 11.4%, 8.9% unconfirmed PR, and 48.1% with stable disease. There was a dose proportional increase in imexon AUC across the doses tested with terminal half life 69 min at the MTD and no alteration of gemcitabine pharmacokinetics. The recommended phase II dose of imexon is 875 mg/m(2) with gemcitabine 1,000 mg/m(2). DLT was acute abdominal pain and cramping. Encouraging antitumor responses support further evaluation of this combination in advanced pancreatic cancer.

Cost-Effectiveness Analysis of Second-Line Chemotherapy Agents for Advanced Gastric Cancer.

PubMed

Lam, Simon W; Wai, Maya; Lau, Jessica E; McNamara, Michael; Earl, Marc; Udeh, Belinda

2017-01-01

Gastric cancer is the fifth most common malignancy and second leading cause of cancer-related mortality. Chemotherapy options for patients who fail first-line treatment are limited. Thus the objective of this study was to assess the cost-effectiveness of second-line treatment options for patients with advanced or metastatic gastric cancer. Cost-effectiveness analysis using a Markov model to compare the cost-effectiveness of six possible second-line treatment options for patients with advanced gastric cancer who have failed previous chemotherapy: irinotecan, docetaxel, paclitaxel, ramucirumab, paclitaxel plus ramucirumab, and palliative care. The model was performed from a third-party payer's perspective to compare lifetime costs and health benefits associated with studied second-line therapies. Costs included only relevant direct medical costs. The model assumed chemotherapy cycle lengths of 30 days and a maximum number of 24 cycles. Systematic review of literature was performed to identify clinical data sources and utility and cost data. Quality-adjusted life years (QALYs) and incremental cost-effectiveness ratios (ICERs) were calculated. The primary outcome measure for this analysis was the ICER between different therapies, where the incremental cost was divided by the number of QALYs saved. The ICER was compared with a willingness-to-pay (WTP) threshold that was set at $50,000/QALY gained, and an exploratory analysis using $160,000/QALY gained was also used. The model's robustness was tested by using 1-way sensitivity analyses and a 10,000 Monte Carlo simulation probabilistic sensitivity analysis (PSA). Irinotecan had the lowest lifetime cost and was associated with a QALY gain of 0.35 year. Docetaxel, ramucirumab alone, and palliative care were dominated strategies. Paclitaxel and the combination of paclitaxel plus ramucirumab led to higher QALYs gained, at an incremental cost of $86,815 and $1,056,125 per QALY gained, respectively. Based on our prespecified WTP threshold, our base case analysis demonstrated that irinotecan alone is the most cost-effective regimen, and both paclitaxel alone and the combination of paclitaxel and ramucirumab were not cost-effective (ICER more than $50,000). Both 1-way sensitivity analyses and PSA demonstrated the model's robustness. PSA illustrated that paclitaxel plus ramucirumab was extremely unlikely to be cost-effective at a WTP threshold less than $400,000/QALY gained. Irinotecan alone appears to be the most cost-effective second-line regimen for patients with gastric cancer. Paclitaxel may be cost-effective if the WTP threshold was set at $160,000/QALY gained. © 2016 Pharmacotherapy Publications, Inc.

Method development for thermal analyses testing on Reillex HPQ resin using the advanced reactive system screening tool (ARSST)

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

Best, D.

Reillex™ HPQ resin was developed by Los Alamos Laboratory and Reilly Industries Inc. in an effort to increase safety and process efficiency during the recovery and purification of plutonium. Ionac™ A-641, another strong base macroporous anion exchange resin used in the nuclear industry, was known to undergo a runaway reaction in hot nitric acid solutions. Because of this, an extensive amount of thermal analyses testing on the Reillex™ HPQ resin in SRNL was performed in 1999-2001 prior to use. A report on the thermal stability qualification of the Reillex™ HPQ resin in 8M (35%) and 12M (53%) HNO 3 wasmore » reported in 2000. In 2001, the reactivity of Reillex™ HPQ resin in 14.4M (64%) HNO 3 was evaluated. In January of 2001, thermal stability scoping tests were performed on irradiated Reillex™ HPQ resin in 14.4M (64%) HNO 3 (as a worst case scenario) and the results sent to Fauske and Associates to calculate a rupture disk size for the HB-Line resin column. A technical report by Fauske and Associates was issued in February 2001 recommending a 2.0” vent line with a rupture disk set pressure of 60 psig. This calculation was based on ARSST thermal analyses scoping tests at SRNL in which 4 grams of dried resin and 6.0 grams of 64% nitric acid in a 10 gram test cell, produced a maximum pressure rate (dP/dt) of 720 psi/min (12 psi/sec) and a maximum temperature of 250 °C. In 2015, a new batch of Reillex™ HPQ resin was manufactured by Vertellus Industries. A test sample of the resin was sent to SRNL to perform acceptance and qualification thermal stability testing using the ARSST. During these tests, method development was performed to ensure that a representative resin to acid ratios were used while running the tests in the ARSST. Fauske and Associates recommended to either use a full test cell representative of the HB-Line column or a 10 gram sample in the test cell that was representative of the ratios of resin to nitric acid in the actual HB-Line column. An observation was made during method development testing that the 4 grams of resin to 6 grams of 64% acid ratio used in 2001 to determine the rupture disk size did not entirely wet the resin and was not representative of the actual HB-Line column. The results of this study raised questions as to whether the ratio of 4 grams of resin to 6 grams of 64% nitric acid recommended by Fauske and Associates in 2001 was the correct ratio.« less

Patterns of resource utilization and cost for postmenopausal women with hormone-receptor-positive, human epidermal growth factor receptor-2-negative advanced breast cancer in Europe.

PubMed

Jerusalem, Guy; Neven, Patrick; Marinsek, Nina; Zhang, Jie; Degun, Ravi; Benelli, Giancarlo; Saletan, Stephen; Ricci, Jean-François; Andre, Fabrice

2015-10-24

Healthcare resource utilization in breast cancer varies by disease characteristics and treatment choices. However, lack of clarity in guidelines can result in varied interpretation and heterogeneous treatment management and costs. In Europe, the extent of this variability is unclear. Therefore, evaluation of chemotherapy use and costs versus hormone therapy across Europe is needed. This retrospective chart review (N = 355) examined primarily direct costs for chemotherapy versus hormone therapy in postmenopausal women with hormone-receptor-positive (HR+), human epidermal growth factor receptor-2-negative (HER2-) advanced breast cancer across 5 European countries (France, Germany, The Netherlands, Belgium, and Sweden). Total direct costs across the first 3 treatment lines were approximately €10,000 to €14,000 lower for an additional line of hormone therapy-based treatment versus switching to chemotherapy-based treatment. Direct cost difference between chemotherapy-based and hormone therapy-based regimens was approximately €1900 to €2500 per month. Chemotherapy-based regimens were associated with increased resource utilization (managing side effects; concomitant targeted therapy use; and increased frequencies of hospitalizations, provider visits, and monitoring tests). The proportion of patients taking sick leave doubled after switching from hormone therapy to chemotherapy. These results suggest chemotherapy is associated with increased direct costs and potentially with increased indirect costs (lower productivity of working patients) versus hormone therapy in HR+, HER2- advanced breast cancer.

Implementation status and explanatory analysis of early advance care planning for Stage IV non-small cell lung cancer patients.

PubMed

Tokito, Takaaki; Murakami, Haruyasu; Mori, Keita; Osaka, Iwao; Takahashi, Toshiaki

2015-03-01

The American Society of Clinical Oncology published the goals of individualized care including advance care planning for advanced cancer patients in 2011. However, no data are available on the implementation status of advance care planning. We retrospectively reviewed the electronic medical records and informed consent forms of consecutive Stage IV non-small cell lung cancer patients treated with chemotherapy between January 2010 and December 2012 at our institution. Two outcomes were defined to investigate the advance care planning implementation status: C-D, the duration from the last day of chemotherapy to death and D-D, that from the day of confirmed do-not-attempt-resuscitation order to death. The study included 136 eligible patients. The advance care planning implementation status in participating patients was as follows: 96 (70%) patients received information on 'incurable disease before first-line chemotherapy', 69 (50%) were informed about 'supportive care before first-line chemotherapy', whereas 43 (32%) learned about their prognosis. The do-not-attempt-resuscitation decision was reflected in 29 patients' will (21%). The median C-D was 64 days. Receipt of ≤2 chemotherapy regimens and provision of prognosis information to patients were significantly associated with long C-D in multivariate analysis. The median D-D was 25 days. Provision of information on supportive care before first-line chemotherapy and provision of prognosis information to patients were significantly associated with long D-D in multivariate analysis. Our results suggest that there is possible benefit from providing information on supportive care before first-line chemotherapy and informing patients about their prognosis in prolonging the duration of supportive care. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Selecting Cells for Bioartificial Liver Devices and the Importance of a 3D Culture Environment: A Functional Comparison between the HepaRG and C3A Cell Lines.

PubMed

van Wenum, Martien; Adam, Aziza A A; Hakvoort, Theodorus B M; Hendriks, Erik J; Shevchenko, Valery; van Gulik, Thomas M; Chamuleau, Robert A F M; Hoekstra, Ruurdtje

2016-01-01

Recently, the first clinical trials on Bioartificial Livers (BALs) loaded with a proliferative human hepatocyte cell source have started. There are two cell lines that are currently in an advanced state of BAL development; HepaRG and HepG2/C3A. In this study we aimed to compare both cell lines on applicability in BALs and to identify possible strategies for further improvement. We tested both cell lines in monolayer- and BAL cultures on growth characteristics, hepatic differentiation, nitrogen-, carbohydrate-, amino acid- and xenobiotic metabolism. Interestingly, both cell lines adapted the hepatocyte phenotype more closely when cultured in BALs; e.g. monolayer cultures produced lactate, while BAL cultures showed diminished lactate production (C3A) or conversion to elimination (HepaRG), and urea cycle activity increased upon BAL culturing in both cell lines. HepaRG-BALs outperformed C3A-BALs on xenobiotic metabolism, ammonia elimination and lactate elimination, while protein synthesis was comparable. In BAL cultures of both cell lines ammonia elimination correlated positively with glutamine production and glutamate consumption, suggesting ammonia elimination was mainly driven by the balance between glutaminase and glutamine synthetase activity. Both cell lines lacked significant urea cycle activity and both required multiple culture weeks before reaching optimal differentiation in BALs. In conclusion, culturing in BALs enhanced hepatic functionality of both cell lines and from these, the HepaRG cells are the most promising proliferative cell source for BAL application.

Regolith and Environment Science and Oxygen and Lunar Volatile Extraction (RESOLVE): Lunar Advanced Volatile Analysis (LAVA) Capillary Fluid Dynamic Restriction Effects on Gas Chromatography

NASA Technical Reports Server (NTRS)

Gonzalez, Marianne; Quinn, Jacqueline; Captain, Janine; Santiago-Bond, Josephine; Starr, Stanley

2015-01-01

The Resource Prospector (RP) mission with the Regolith and Environment Science and Oxygen Lunar Volatile Extraction (RESOLVE) payload aims to show the presence of water in lunar regolith, and establish a proving ground for NASAs mission to Mars. One of the analysis is performed by the Lunar Advanced Volatiles Analysis (LAVA) subsystem, which consists of a fluid network that facilitates the transport of volatile samples to a gas chromatograph and mass spectrometer (GC-MS) instrument. The understanding of fluid dynamics directed from the GC to the MS is important due to the influence of flow rates and pressures that affect the accuracy of and prevent the damage to the overall GC-MS instrument. The micro-scale capillary fluid network within the GC alone has various lengths and inner-diameters; therefore, determination of pressure differentials and flow rates are difficult to model computationally, with additional complexity from the vacuum conditions in space and lack of a lunar atmosphere. A series of tests were performed on an experimental set-up of the system where the inner diameters of the GC transfer line connecting to the MS were varied. The effect on chromatography readings were also studied by applying these lines onto a GC instrument. It was found that a smaller inner diameter transfer line resulted in a lower flow rate, as well as a lower pressure differential across the thermal conductivity detector (TCD) unit of the GC and a negligible pressure drop across the mock-up capillary column. The chromatography was affected with longer retention times and broader peak integrations. It was concluded that a 0.050 mm inner diameter line still proved most suitable for the systems flow rate preferences. In addition, it was evident that this small transfer line portrayed some expense to GC signal characteristics and the wait time for steady-state operation.

The Number Line Is a Critical Spatial-Numerical Representation: Evidence from a Fraction Intervention

ERIC Educational Resources Information Center

Hamdan, Noora; Gunderson, Elizabeth A.

2017-01-01

Children's ability to place fractions on a number line strongly correlates with math achievement. But does the number line play a causal role in fraction learning or does it simply index more advanced fraction knowledge? The number line may be a particularly effective representation for fraction learning because its properties align with the…

Assessment of Labor Behavior Factors and Selecting Line Managers' Lines of Development at Russian Industrial Enterprises

ERIC Educational Resources Information Center

Zavyalova, Elena K.; Kosheleva, Sofia V.

2009-01-01

Purpose: The paper investigates personal and environmental factors providing for the efficiency of line managers' activity and contributing to their professional and career advancement. The paper studies the prognostic value of the assessment of personal and environmental factors providing for the efficiency of line managers' activity according to…

Measurement of pattern roughness and local size variation using CD-SEM: current status

NASA Astrophysics Data System (ADS)

Fukuda, Hiroshi; Kawasaki, Takahiro; Kawada, Hiroki; Sakai, Kei; Kato, Takashi; Yamaguchi, Satoru; Ikota, Masami; Momonoi, Yoshinori

2018-03-01

Measurement of line edge roughness (LER) is discussed from four aspects: edge detection, PSD prediction, sampling strategy, and noise mitigation, and general guidelines and practical solutions for LER measurement today are introduced. Advanced edge detection algorithms such as wave-matching method are shown effective for robustly detecting edges from low SNR images, while conventional algorithm with weak filtering is still effective in suppressing SEM noise and aliasing. Advanced PSD prediction method such as multi-taper method is effective in suppressing sampling noise within a line edge to analyze, while number of lines is still required for suppressing line to line variation. Two types of SEM noise mitigation methods, "apparent noise floor" subtraction method and LER-noise decomposition using regression analysis are verified to successfully mitigate SEM noise from PSD curves. These results are extended to LCDU measurement to clarify the impact of SEM noise and sampling noise on LCDU.

Advances in the application of holography for NDE

NASA Astrophysics Data System (ADS)

Sciammarella, C. A.

1985-01-01

The basic methodology of holographic interferometry in nondestructive testing (NDT) applications are described. Applications to crack detection in ceramic materials, including a crack 50 microns deep in a turbine blade, are discussed in detail. The theoretical principles of holographic interferometry are explained, and a general description of a holographic interferometric recording system is given. A nondestructive interferometric technique for measuring the gradual erosion of calcareous stones exposed to acid rain is also presented. Detailed line drawings illustrating the hologram recording and interferometric fringe pattern analysis elements in an interferometric holographic NDT device are provided.

Acoustic charge transport technology investigation for advanced development transponder

NASA Technical Reports Server (NTRS)

Kayalar, S.

1993-01-01

Acoustic charge transport (ACT) technology has provided a basis for a new family of analog signal processors, including a programmable transversal filter (PTF). Through monolithic integration of ACT delay lines with GaAs metal semiconductor field effect transistor (MESFET) digital memory and controllers, these devices significantly extend the performance of PTF's. This article introduces the basic operation of these devices and summarizes their present and future specifications. The production and testing of these devices indicate that this new technology is a promising one for future space applications.

Individual patient data analysis of progression-free survival versus overall survival as a first-line end point for metastatic colorectal cancer in modern randomized trials: findings from the analysis and research in cancers of the digestive system database.

PubMed

Shi, Qian; de Gramont, Aimery; Grothey, Axel; Zalcberg, John; Chibaudel, Benoist; Schmoll, Hans-Joachim; Seymour, Matthew T; Adams, Richard; Saltz, Leonard; Goldberg, Richard M; Punt, Cornelis J A; Douillard, Jean-Yves; Hoff, Paulo M; Hecht, Joel Randolph; Hurwitz, Herbert; Díaz-Rubio, Eduardo; Porschen, Rainer; Tebbutt, Niall C; Fuchs, Charles; Souglakos, John; Falcone, Alfredo; Tournigand, Christophe; Kabbinavar, Fairooz F; Heinemann, Volker; Van Cutsem, Eric; Bokemeyer, Carsten; Buyse, Marc; Sargent, Daniel J

2015-01-01

Progression-free survival (PFS) has previously been established as a surrogate for overall survival (OS) for first-line metastatic colorectal cancer (mCRC). Because mCRC treatment has advanced in the last decade with extended OS, this surrogacy requires re-examination. Individual patient data from 16,762 patients were available from 22 first-line mCRC studies conducted from 1997 to 2006; 12 of those studies tested antiangiogenic and/or anti-epidermal growth factor receptor agents. The relationship between PFS (first event of progression or death) and OS was evaluated by using R(2) statistics (the closer the value is to 1, the stronger the correlation) from weighted least squares regression of trial-specific hazard ratios estimated by using Cox and Copula models. Forty-four percent of patients received a regimen that included biologic agents. Median first-line PFS was 8.3 months, and median OS was 18.2 months. The correlation between PFS and OS was modest (R(2), 0.45 to 0.69). Analyses limited to trials that tested treatments with biologic agents, nonstrategy trials, or superiority trials did not improve surrogacy. In modern mCRC trials, in which survival after the first progression exceeds time to first progression, a positive but modest correlation was observed between OS and PFS at both the patient and trial levels. This finding demonstrates the substantial variability in OS introduced by the number of lines of therapy and types of effective subsequent treatments and the associated challenge to the use of OS as an end point to assess the benefit attributable to a single line of therapy. PFS remains an appropriate primary end point for first-line mCRC trials to detect the direct treatment effect of new agents. © 2014 by American Society of Clinical Oncology.

Individual Patient Data Analysis of Progression-Free Survival Versus Overall Survival As a First-Line End Point for Metastatic Colorectal Cancer in Modern Randomized Trials: Findings From the Analysis and Research in Cancers of the Digestive System Database

PubMed Central

Shi, Qian; de Gramont, Aimery; Grothey, Axel; Zalcberg, John; Chibaudel, Benoist; Schmoll, Hans-Joachim; Seymour, Matthew T.; Adams, Richard; Saltz, Leonard; Goldberg, Richard M.; Punt, Cornelis J.A.; Douillard, Jean-Yves; Hoff, Paulo M.; Hecht, Joel Randolph; Hurwitz, Herbert; Díaz-Rubio, Eduardo; Porschen, Rainer; Tebbutt, Niall C.; Fuchs, Charles; Souglakos, John; Falcone, Alfredo; Tournigand, Christophe; Kabbinavar, Fairooz F.; Heinemann, Volker; Van Cutsem, Eric; Bokemeyer, Carsten; Buyse, Marc; Sargent, Daniel J.

2015-01-01

Purpose Progression-free survival (PFS) has previously been established as a surrogate for overall survival (OS) for first-line metastatic colorectal cancer (mCRC). Because mCRC treatment has advanced in the last decade with extended OS, this surrogacy requires re-examination. Methods Individual patient data from 16,762 patients were available from 22 first-line mCRC studies conducted from 1997 to 2006; 12 of those studies tested antiangiogenic and/or anti–epidermal growth factor receptor agents. The relationship between PFS (first event of progression or death) and OS was evaluated by using R2 statistics (the closer the value is to 1, the stronger the correlation) from weighted least squares regression of trial-specific hazard ratios estimated by using Cox and Copula models. Results Forty-four percent of patients received a regimen that included biologic agents. Median first-line PFS was 8.3 months, and median OS was 18.2 months. The correlation between PFS and OS was modest (R2, 0.45 to 0.69). Analyses limited to trials that tested treatments with biologic agents, nonstrategy trials, or superiority trials did not improve surrogacy. Conclusion In modern mCRC trials, in which survival after the first progression exceeds time to first progression, a positive but modest correlation was observed between OS and PFS at both the patient and trial levels. This finding demonstrates the substantial variability in OS introduced by the number of lines of therapy and types of effective subsequent treatments and the associated challenge to the use of OS as an end point to assess the benefit attributable to a single line of therapy. PFS remains an appropriate primary end point for first-line mCRC trials to detect the direct treatment effect of new agents. PMID:25385741

Advanced scatter search approach and its application in a sequencing problem of mixed-model assembly lines in a case company

NASA Astrophysics Data System (ADS)

Liu, Qiong; Wang, Wen-xi; Zhu, Ke-ren; Zhang, Chao-yong; Rao, Yun-qing

2014-11-01

Mixed-model assembly line sequencing is significant in reducing the production time and overall cost of production. To improve production efficiency, a mathematical model aiming simultaneously to minimize overtime, idle time and total set-up costs is developed. To obtain high-quality and stable solutions, an advanced scatter search approach is proposed. In the proposed algorithm, a new diversification generation method based on a genetic algorithm is presented to generate a set of potentially diverse and high-quality initial solutions. Many methods, including reference set update, subset generation, solution combination and improvement methods, are designed to maintain the diversification of populations and to obtain high-quality ideal solutions. The proposed model and algorithm are applied and validated in a case company. The results indicate that the proposed advanced scatter search approach is significant for mixed-model assembly line sequencing in this company.

Call for papers for special issue of Journal of Molecular Spectroscopy focusing on "Frequency-comb spectroscopy"

NASA Astrophysics Data System (ADS)

Foltynowicz, Aleksandra; Picqué, Nathalie; Ye, Jun

2018-05-01

Frequency combs are becoming enabling tools for many applications in science and technology, beyond the original purpose of frequency metrology of simple atoms. The precisely evenly spaced narrow lines of a laser frequency comb inspire intriguing approaches to molecular spectroscopy, designed and implemented by a growing community of scientists. Frequency-comb spectroscopy advances the frontiers of molecular physics across the entire electro-magnetic spectrum. Used as frequency rulers, frequency combs enable absolute frequency measurements and precise line shape studies of molecular transitions, for e.g. tests of fundamental physics and improved determination of fundamental constants. As light sources interrogating the molecular samples, they dramatically improve the resolution, precision, sensitivity and acquisition time of broad spectral-bandwidth spectroscopy and open up new opportunities and applications at the leading edge of molecular spectroscopy and sensing.

A universal mammalian vaccine cell line substrate.

PubMed

Murray, Jackelyn; Todd, Kyle V; Bakre, Abhijeet; Orr-Burks, Nichole; Jones, Les; Wu, Weilin; Tripp, Ralph A

2017-01-01

Using genome-wide small interfering RNA (siRNA) screens for poliovirus, influenza A virus and rotavirus, we validated the top 6 gene hits PV, RV or IAV to search for host genes that when knocked-down (KD) enhanced virus permissiveness and replication over wild type Vero cells or HEp-2 cells. The enhanced virus replication was tested for 12 viruses and ranged from 2-fold to >1000-fold. There were variations in virus-specific replication (strain differences) across the cell lines examined. Some host genes (CNTD2, COQ9, GCGR, NDUFA9, NEU2, PYCR1, SEC16G, SVOPL, ZFYVE9, and ZNF205) showed that KD resulted in enhanced virus replication. These findings advance platform-enabling vaccine technology, the creation of diagnostic cells substrates, and are informative about the host mechanisms that affect virus replication in mammalian cells.

Immune Checkpoint Inhibitors for Patients With Advanced Non-Small-Cell Lung Cancer: A Systematic Review.

PubMed

Ellis, Peter M; Vella, Emily T; Ung, Yee C

2017-09-01

Second-line treatment options are limited for patients with advanced non-small-cell lung cancer (NSCLC). Standard therapy includes the cytotoxic agents docetaxel and pemetrexed, and the epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors erlotinib and gefitinib. Immune checkpoint inhibitors are a new class of treatment that have shown durable overall radiologic response rates and have been well tolerated. The objective of this systematic review was to investigate the efficacy of immune checkpoint inhibitors compared with other chemotherapies in patients with advanced NSCLC. Medline, Embase, and PubMed were searched for randomized controlled trials comparing treatment with immune checkpoint inhibitors against treatment with chemotherapy in patients with stage IIIB or IV NSCLC. Nine randomized controlled trials with 15 publications were included. A significant overall survival benefit of second-line nivolumab (nonsquamous: hazard ratio [HR] = 0.72, 95% confidence interval [CI], 0.60-0.77; P < .001; squamous: HR = 0.59, 95% CI, 0.44-0.79; P < .001) or second-line atezolizumab (HR = 0.73, 95% CI, 0.62-0.87; P = .0003) or second-line pembrolizumab (in patients with programmed cell death ligand 1 [PD-L1]-positive tumors) (pembrolizumab 2 mg/kg HR = 0.71, 95% CI, 0.58-0.88; P = .0008; pembrolizumab 10 mg/kg HR = 0.61, 95% CI, 0.49-0.75; P < .0001) or first-line pembrolizumab (HR = 0.60, 95% CI, 0.41-0.89; P = .005) compared with chemotherapy was found. The adverse effects were mainly higher in the chemotherapy arms. For patients with advanced stage IIIB/IV NSCLC, the improvement in overall survival outweighed the harms and supported the use of first-line pembrolizumab (in patients with ≥ 50% PD-L1-positive tumors) or second-line nivolumab, atezolizumab, or pembrolizumab (in patients with PD-L1-positive tumors). Copyright © 2017 Elsevier Inc. All rights reserved.

Cost-benefit analysis of introducing next-generation sequencing (metagenomic) pathogen testing in the setting of pyrexia of unknown origin.

PubMed

Chai, Jia Hui; Lee, Chun Kiat; Lee, Hong Kai; Wong, Nicholas; Teo, Kahwee; Tan, Chuen Seng; Thokala, Praveen; Tang, Julian Wei-Tze; Tambyah, Paul Anantharajah; Oh, Vernon Min Sen; Loh, Tze Ping; Yoong, Joanne

2018-01-01

Pyrexia of unknown origin (PUO) is defined as a temperature of >38.3°C that lasts for >3 weeks, where no cause can be found despite appropriate investigation. Existing protocols for the work-up of PUO can be extensive and costly, motivating the application of recent advances in molecular diagnostics to pathogen testing. There have been many reports describing various analytical methods and performance of metagenomic pathogen testing in clinical samples but the economics of it has been less well studied. This study pragmatically evaluates the feasibility of introducing metagenomic testing in this setting by assessing the relative cost of clinically-relevant strategies employing this investigative tool under various cost and performance scenarios using Singapore as a demonstration case, and assessing the price and performance benchmarks, which would need to be achieved for metagenomic testing to be potentially considered financially viable relative to the current diagnostic standard. This study has some important limitations: we examined only impact of introducing the metagenomic test to the overall diagnostic cost and excluded costs associated with hospitalization and makes assumptions about the performance of the routine diagnostic tests, limiting the cost of metagenomic test, and the lack of further work-up after positive pathogen detection by the metagenomic test. However, these assumptions were necessary to keep the model within reasonable limits. In spite of these, the simplified presentation lends itself to the illustration of the key insights of our paper. In general, we find the use of metagenomic testing as second-line investigation is effectively dominated, and that use of metagenomic testing at first-line would typically require higher rates of detection or lower cost than currently available in order to be justifiable purely as a cost-saving measure. We conclude that current conditions do not warrant a widespread rush to deploy metagenomic testing to resolve any and all uncertainty, but rather as a front-line technology that should be used in specific contexts, as a supplement to rather than a replacement for careful clinical judgement.

Gemcitabine and capecitabine as third- or later-line therapy for refractory advanced colorectal cancer: a retrospective study.

PubMed

Salgado, Mercedes; Reboredo, Margarita; Mendez, Juan Carlos; Quintero, Guillermo; Pellón, María Luz; Romero, Carlos; Jorge, Mónica; Montes, Ana Fernández; Valladares-Ayerbes, Manuel; Ramos, Manuel; Varela, Silvia; Alonso, Miguel Ángel

2013-09-01

To evaluate gemcitabine plus capecitabine as third-line or later-line therapy in patients with refractory advanced colorectal cancer (CRC) who maintain a good performance status (PS). We retrospectively evaluated patients who had failed at least two lines of therapy or had contraindication to standard therapy and received gemcitabine (1,000 mg/m(2), d1 biweekly) plus capecitabine (1,700 mg/m(2)/day, d1-7 every two weeks) in a compassionate use program. Thirty-nine patients were enrolled. The majority (85%) had ECOG PS 1. Gemcitabine plus capecitabine was administered as third- and fourth-line in 49% and 23% of patients, respectively; and as fifth-line or later-line in 28%. A clinical benefit of 21% was found. The median progression-free survival and overall survival were 3.0 and 7.3 months, respectively. Toxicity was mild to moderate, with no reported grade 4 toxicities. Gemcitabine plus capecitabine was safe and well-tolerated. While the efficacy of this regimen was modest in terms of response, the survival data were acceptable and consistent with previous publications on this setting.

Combining high performance simulation, data acquisition, and graphics display computers

NASA Technical Reports Server (NTRS)

Hickman, Robert J.

1989-01-01

Issues involved in the continuing development of an advanced simulation complex are discussed. This approach provides the capability to perform the majority of tests on advanced systems, non-destructively. The controlled test environments can be replicated to examine the response of the systems under test to alternative treatments of the system control design, or test the function and qualification of specific hardware. Field tests verify that the elements simulated in the laboratories are sufficient. The digital computer is hosted by a Digital Equipment Corp. MicroVAX computer with an Aptec Computer Systems Model 24 I/O computer performing the communication function. An Applied Dynamics International AD100 performs the high speed simulation computing and an Evans and Sutherland PS350 performs on-line graphics display. A Scientific Computer Systems SCS40 acts as a high performance FORTRAN program processor to support the complex, by generating numerous large files from programs coded in FORTRAN that are required for the real time processing. Four programming languages are involved in the process, FORTRAN, ADSIM, ADRIO, and STAPLE. FORTRAN is employed on the MicroVAX host to initialize and terminate the simulation runs on the system. The generation of the data files on the SCS40 also is performed with FORTRAN programs. ADSIM and ADIRO are used to program the processing elements of the AD100 and its IOCP processor. STAPLE is used to program the Aptec DIP and DIA processors.

Video on phone lines: technology and applications

NASA Astrophysics Data System (ADS)

Hsing, T. Russell

1996-03-01

Recent advances in communications signal processing and VLSI technology are fostering tremendous interest in transmitting high-speed digital data over ordinary telephone lines at bit rates substantially above the ISDN Basic Access rate (144 Kbit/s). Two new technologies, high-bit-rate digital subscriber lines and asymmetric digital subscriber lines promise transmission over most of the embedded loop plant at 1.544 Mbit/s and beyond. Stimulated by these research promises and rapid advances on video coding techniques and the standards activity, information networks around the globe are now exploring possible business opportunities of offering quality video services (such as distant learning, telemedicine, and telecommuting etc.) through this high-speed digital transport capability in the copper loop plant. Visual communications for residential customers have become more feasible than ever both technically and economically.

Update on Advanced LIGO: the second observing run

NASA Astrophysics Data System (ADS)

Barsotti, Lisa; LIGO Scientific Collaboration Collaboration

2017-01-01

After several months of detector improvements, the two Advanced LIGO gravitational wave detectors are coming back on-line by the end of 2016 for their second Observing run, O2. In this talk I will discuss the status of Advanced LIGO and its observing plan.

Advanced Diesel Oil Fuel Processor Development

DTIC Science & Technology

1986-06-01

water exit 29 sample quencher: gas sample line inlet 30 sample quencher: gas sample line exit 31 sample quencher: cooling water inlet 32 desulfuriser ...exit line 33, 34 desulfurimer 35 heat exchanger: process gas exit (to desulfuriser ) 38 shift reactor inlet (top) 37 shift reactor: cooling air exit

FieldTrip: Open source software for advanced analysis of MEG, EEG, and invasive electrophysiological data.

PubMed

Oostenveld, Robert; Fries, Pascal; Maris, Eric; Schoffelen, Jan-Mathijs

2011-01-01

This paper describes FieldTrip, an open source software package that we developed for the analysis of MEG, EEG, and other electrophysiological data. The software is implemented as a MATLAB toolbox and includes a complete set of consistent and user-friendly high-level functions that allow experimental neuroscientists to analyze experimental data. It includes algorithms for simple and advanced analysis, such as time-frequency analysis using multitapers, source reconstruction using dipoles, distributed sources and beamformers, connectivity analysis, and nonparametric statistical permutation tests at the channel and source level. The implementation as toolbox allows the user to perform elaborate and structured analyses of large data sets using the MATLAB command line and batch scripting. Furthermore, users and developers can easily extend the functionality and implement new algorithms. The modular design facilitates the reuse in other software packages.

Upgrade of a GEP50 robot control system

NASA Astrophysics Data System (ADS)

Alounai, Ali T.; Gharsalli, Imed

2000-03-01

Recently the ASL at Tennessee Technological University was donated a GEP50 welder. The welding is done via off line point-to-point teaching. A state of the art robot was needed for research but because money was not available to purchase such an expensive item. It was therefore decided to upgrade the GEP50 control system to make the welder a multitasking robot. The robot has five degrees of freedom can be sufficient to pursue some research in robotics control. The problem was that the control system of the welder is limited to point-to-point control, using off-line teaching. To make the GEP50 a multitasking robot that can be controlled using different control strategies, the existing control system of the welder had to be replaced. The upgrade turned to be a low cost operation. This robot is currently in sue to test different advanced control strategies in the ASL. This work discusses all the steps and tasks undertaken during the upgrade operation. The hardware and software required or the upgrade are provided in this paper. The newly developed control system has been implemented and tested successfully.

A Robust Test of the Unified Model for Seyfert Galaxies with Implications for the Starburst Phenomenon

NASA Technical Reports Server (NTRS)

Weaver, Kimberly A.

1997-01-01

My research involves detailed analysis of X-ray emission from Active Galactic Nuclei (AGN). For over a decade, the paradigm for AGN has rested soundly on the unified model hypothesis, which posits that the only difference between broad-line objects (e.g., Type 1 Seyfert galaxies) and narrow-line objects (e.g., Type 2 Seyferts) is that in the former case our line of sight evades toroidal obscuration surrounding the nucleus, while in the latter, our line of sight is blocked by the optically thick torus. It is well established that some Seyfert 2s contain Seyfert I nuclei (i.e., a hidden broad line region), but whether or not all Seyfert 2s contain obscured Seyfert 1 nuclei or whether some Seyfert 2s are intrinsically Seyfert 2s is not known. Optical, IR, and UV surveys are not appropriate to examine this hypothesis because such emissions are either anisotropic or subject to the effects of obscuration, and thus depend strongly on viewing angle. Hard X-rays, on the other hand, can penetrate gas with column densities as high as 10( exp 24.5) cm(-2) and thus provide reliable, direct probes of the cores of heavily obscured AGN. Combining NASA archival data from the Advanced Satellite of Cosmology and Astrophysics (ASCA), the Rossi X-ray Timing Explorer (RXTE), and Rosat, I am accumulating X-ray data between 0.1 and 60 keV to produce a catalog of the broad-band X-ray spectral properties of Seyfert galaxies. These data will be used to perform concrete tests of the unified model, and (compared with similar data on Starbursts) to examine a possible evolutionary connection between Seyfert and Starburst galaxies.

Circulating tumour cells from patients with colorectal cancer have cancer stem cell hallmarks in ex vivo culture.

PubMed

Grillet, Fanny; Bayet, Elsa; Villeronce, Olivia; Zappia, Luke; Lagerqvist, Ebba Louise; Lunke, Sebastian; Charafe-Jauffret, Emmanuelle; Pham, Kym; Molck, Christina; Rolland, Nathalie; Bourgaux, Jean François; Prudhomme, Michel; Philippe, Claire; Bravo, Sophie; Boyer, Jean Christophe; Canterel-Thouennon, Lucile; Taylor, Graham Roy; Hsu, Arthur; Pascussi, Jean Marc; Hollande, Frédéric; Pannequin, Julie

2017-10-01

Although counting of circulating tumour cells (CTC) has attracted a broad interest as potential markers of tumour progression and treatment response, the lack of functional characterisation of these cells had become a bottleneck in taking these observations to the clinic. Our objective was to culture these cells in order to understand them and exploit their therapeutic potential to the full. Here, hypothesising that some CTC potentially have cancer stem cell (CSC) phenotype, we generated several CTC lines from the blood of patients with advanced metastatic colorectal cancer (CRC) based on their self-renewal abilities. Multiple standard tests were then employed to characterise these cells. Our CTC lines self-renew, express CSC markers and have multilineage differentiation ability, both in vitro and in vivo . Patient-derived CTC lines are tumorigenic in subcutaneous xenografts and are also able to colonise the liver after intrasplenic injection. RNA sequencing analyses strikingly demonstrate that drug metabolising pathways represent the most upregulated feature among CTC lines in comparison with primary CRC cells grown under similar conditions. This result is corroborated by the high resistance of the CTC lines to conventional cytotoxic compounds. Taken together, our results directly demonstrate the existence of patient-derived colorectal CTCs that bear all the functional attributes of CSCs. The CTC culture model described here is simple and takes <1 month from blood collection to drug testing, therefore, routine clinical application could facilitate access to personalised medicine. ClinicalTrial.gov NCT01577511. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

Pest Resistance and agronomic performance of advanced BARBREN lines compared to commercial cultivars and the germplasm line BARBREN 713

USDA-ARS?s Scientific Manuscript database

The germplasm line BARBREN 713, which has resistance to both root-knot and reniform nematodes was released in 2012. Its major resistance to reniform nematodes is due to the Ren2 gene derived from Gossypium barbadense GB 713 and located near the DNA marker BNL 3279_105 on chromosome 21. Other lines...

Mental Number Line, Number Line Estimation, and Mathematical Achievement: Their Interrelations in Grades 5 and 6

ERIC Educational Resources Information Center

Schneider, Michael; Grabner, Roland H.; Paetsch, Jennifer

2009-01-01

As indicated by the distance effect and the spatial-numerical association of response codes (SNARC) effect, natural numbers are mentally represented on a number line. Purportedly, this number line underlies children's number sense, which supports the acquisition of more advanced mathematical competencies. In 3 studies with a total of 429 fifth and…

Basic and advanced numerical performances relate to mathematical expertise but are fully mediated by visuospatial skills.

PubMed

Sella, Francesco; Sader, Elie; Lolliot, Simon; Cohen Kadosh, Roi

2016-09-01

Recent studies have highlighted the potential role of basic numerical processing in the acquisition of numerical and mathematical competences. However, it is debated whether high-level numerical skills and mathematics depends specifically on basic numerical representations. In this study mathematicians and nonmathematicians performed a basic number line task, which required mapping positive and negative numbers on a physical horizontal line, and has been shown to correlate with more advanced numerical abilities and mathematical achievement. We found that mathematicians were more accurate compared with nonmathematicians when mapping positive, but not negative numbers, which are considered numerical primitives and cultural artifacts, respectively. Moreover, performance on positive number mapping could predict whether one is a mathematician or not, and was mediated by more advanced mathematical skills. This finding might suggest a link between basic and advanced mathematical skills. However, when we included visuospatial skills, as measured by block design subtest, the mediation analysis revealed that the relation between the performance in the number line task and the group membership was explained by non-numerical visuospatial skills. These results demonstrate that relation between basic, even specific, numerical skills and advanced mathematical achievement can be artifactual and explained by visuospatial processing. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Anomalous contact angle hysteresis of a captive bubble: advancing contact line pinning.

PubMed

Hong, Siang-Jie; Chang, Feng-Ming; Chou, Tung-He; Chan, Seong Heng; Sheng, Yu-Jane; Tsao, Heng-Kwong

2011-06-07

Contact angle hysteresis of a sessile drop on a substrate consists of continuous invasion of liquid phase with the advancing angle (θ(a)) and contact line pinning of liquid phase retreat until the receding angle (θ(r)) is reached. Receding pinning is generally attributed to localized defects that are more wettable than the rest of the surface. However, the defect model cannot explain advancing pinning of liquid phase invasion driven by a deflating bubble and continuous retreat of liquid phase driven by the inflating bubble. A simple thermodynamic model based on adhesion hysteresis is proposed to explain anomalous contact angle hysteresis of a captive bubble quantitatively. The adhesion model involves two solid–liquid interfacial tensions (γ(sl) > γ(sl)′). Young’s equation with γ(sl) gives the advancing angle θ(a) while that with γ(sl)′ due to surface rearrangement yields the receding angle θ(r). Our analytical analysis indicates that contact line pinning represents frustration in surface free energy, and the equilibrium shape corresponds to a nondifferential minimum instead of a local minimum. On the basis of our thermodynamic model, Surface Evolver simulations are performed to reproduce both advancing and receding behavior associated with a captive bubble on the acrylic glass.

RESOLVE Project

NASA Technical Reports Server (NTRS)

Parker, Ray; Coan, Mary; Cryderman, Kate; Captain, Janine

2013-01-01

The RESOLVE project is a lunar prospecting mission whose primary goal is to characterize water and other volatiles in lunar regolith. The Lunar Advanced Volatiles Analysis (LAVA) subsystem is comprised of a fluid subsystem that transports flow to the gas chromatograph - mass spectrometer (GC-MS) instruments that characterize volatiles and the Water Droplet Demonstration (WDD) that will capture and display water condensation in the gas stream. The LAVA Engineering Test Unit (ETU) is undergoing risk reduction testing this summer and fall within a vacuum chamber to understand and characterize component and integrated system performance. Testing of line heaters, printed circuit heaters, pressure transducers, temperature sensors, regulators, and valves in atmospheric and vacuum environments was done. Test procedures were developed to guide experimental tests and test reports to analyze and draw conclusions from the data. In addition, knowledge and experience was gained with preparing a vacuum chamber with fluid and electrical connections. Further testing will include integrated testing of the fluid subsystem with the gas supply system, near-infrared spectrometer, WDD, Sample Delivery System, and GC-MS in the vacuum chamber. This testing will provide hands-on exposure to a flight forward spaceflight subsystem, the processes associated with testing equipment in a vacuum chamber, and experience working in a laboratory setting. Examples of specific analysis conducted include: pneumatic analysis to calculate the WDD's efficiency at extracting water vapor from the gas stream to form condensation; thermal analysis of the conduction and radiation along a line connecting two thermal masses; and proportional-integral-derivative (PID) heater control analysis. Since LAVA is a scientific subsystem, the near-infrared spectrometer and GC-MS instruments will be tested during the ETU testing phase.

Bevacizumab plus chemotherapy for patients with advanced pulmonary adenocarcinoma harboring EGFR mutations.

PubMed

Chen, R-L; Chen, H-J; Jiang, B-Y; Zhang, X-C; Zhou, Q; Tu, H-Y; Zhong, W-Z; Wu, Y-L; Yang, J-J

2018-02-01

Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) and bevacizumab plus chemotherapy were effective for EGFR-mutant patients. However, the appropriated treatment orders remained controvertible. We investigated the efficacy of treatment orders between bevacizumab plus chemotherapy and EGFR-TKIs for EGFR-mutant patients with advanced pulmonary adenocarcinoma. This study involved 40 EGFR-mutant patients with advanced pulmonary adenocarcinoma who were treated with bevacizumab plus carboplatin and paclitaxel (Bev + CP) and EGFR-TKIs in different treatment orders or gemcitabine plus cisplatin (GP) in first-line setting. Seventeen patients were treated with Bev + CP and 10 cases with GP in first-line treatment. Thirteen patients received EGFR-TKIs after first-line Bev + CP regimen, while 13 patients were treated with first-line EGFR-TKIs. Progression-free survival (PFS), the response rate (ORR) and overall survival (OS) were evaluated. Median PFS of Bev + CP treatment was significantly longer in first-line than non-first-line settings (11.7 vs. 5.6 months, P = 0.003). Median OS was 37.8 months for EGFR-mutant patients with first-line Bev + CP followed by second-line EGFR-TKIs and 31.0 months for those with first-line EGFR-TKIs and non-first-line Bev + CP, respectively (P = 0.509). Median PFS was 11.7 (95% CI 10.6-12.8) months for Bev + CP group and 4.7 (95% CI 4.4-5.0) months for GP group with the hazard ratio of 0.17 (P = 0.001). ORR was 70.6 and 50.0% in the two groups, respectively (P = 0.415). However, there was no significant difference in median OS (33.7 vs 27.8 months, P = 0.293). First-line Bev + CP followed by EGFR-TKIs might possibly provide favorable prognosis for EGFR-mutant patients. Bev + CP regimen significantly prolonged PFS in first-line than non-first-line settings. These findings warrant further investigations.

Prospective study of the evolution of blood lymphoid immune parameters during dacarbazine chemotherapy in metastatic and locally advanced melanoma patients.

PubMed

Mignot, Grégoire; Hervieu, Alice; Vabres, Pierre; Dalac, Sophie; Jeudy, Geraldine; Bel, Blandine; Apetoh, Lionel; Ghiringhelli, François

2014-01-01

The importance of immune responses in the control of melanoma growth is well known. However, the implication of these antitumor immune responses in the efficacy of dacarbazine, a cytotoxic drug classically used in the treatment of melanoma, remains poorly understood in humans. In this prospective observational study, we performed an immunomonitoring of eleven metastatic or locally advanced patients treated with dacarbazine as a first line of treatment. We assessed by flow cytometry lymphoid populations and their activation state; we also isolated NK cells to perform in vitro cytotoxicity tests. We found that chemotherapy induces lymphopenia and that a significantly higher numbers of naïve CD4+ T cells and lower proportion of Treg before chemotherapy are associated with disease control after dacarbazine treatment. Interestingly, NK cell cytotoxicity against dacarbazine-pretreated melanoma cells is only observed in NK cells from patients who achieved disease control. Together, our data pinpoint that some immune factors could help to predict the response of melanoma patients to dacarbazine. Future larger scale studies are warranted to test their validity as prediction markers.

Identification of the Ki-1 antigen (CD30) as a novel therapeutic target in systemic mastocytosis

PubMed Central

Blatt, Katharina; Cerny-Reiterer, Sabine; Schwaab, Juliana; Sotlar, Karl; Eisenwort, Gregor; Stefanzl, Gabriele; Hoermann, Gregor; Mayerhofer, Matthias; Schneeweiss, Mathias; Knapp, Sylvia; Rülicke, Thomas; Hadzijusufovic, Emir; Bauer, Karin; Smiljkovic, Dubravka; Willmann, Michael; Reiter, Andreas; Horny, Hans-Peter

2015-01-01

The Ki-1 antigen (CD30) is an established therapeutic target in patients with Hodgkin lymphoma and anaplastic large-cell lymphoma. We have recently shown that CD30 is expressed abundantly in the cytoplasm of neoplastic mast cells (MCs) in patients with advanced systemic mastocytosis (SM). In the current study, we asked whether CD30 is expressed on the surface of neoplastic MCs in advanced SM, and whether this surface structure may serve as therapeutic target in SM. As assessed by flow cytometry, CD30 was found to be expressed on the surface of neoplastic MCs in 3 of 25 patients (12%) with indolent SM, 4 of 7 patients (57%) with aggressive SM, and 4 of 7 patients (57%) with MC leukemia. The immature RAS-transformed human MC line MCPV-1.1 also expressed cell surface CD30, whereas the KIT-transformed MC line HMC-1.2 expressed no detectable CD30. The CD30-targeting antibody-conjugate brentuximab-vedotin inhibited proliferation in neoplastic MCs, with lower IC50 values obtained in CD30+ MCPV-1.1 cells (10 µg/mL) compared with CD30− HMC-1.2 cells (>50 µg/mL). In addition, brentuximab-vedotin suppressed the engraftment of MCPV-1.1 cells in NSG mice. Moreover, brentuximab-vedotin produced apoptosis in all CD30+ MC lines tested as well as in primary neoplastic MCs in patients with CD30+ SM, but did not induce apoptosis in neoplastic MCs in patients with CD30− SM. Furthermore, brentuximab-vedotin was found to downregulate anti-IgE–induced histamine release in CD30+ MCs. Finally, brentuximab-vedotin and the KIT D816V-targeting drug PKC412 produced synergistic growth-inhibitory effects in MCPV-1.1 cells. Together, CD30 is a promising new drug target for patients with CD30+ advanced SM. PMID:26486787

Characterization of thyroid cancer cell lines in murine orthotopic and intracardiac metastasis models.

PubMed

Morrison, Jennifer A; Pike, Laura A; Lund, Greg; Zhou, Qiong; Kessler, Brittelle E; Bauerle, Kevin T; Sams, Sharon B; Haugen, Bryan R; Schweppe, Rebecca E

2015-06-01

Thyroid cancer incidence has been increasing over time, and it is estimated that ∼1950 advanced thyroid cancer patients will die of their disease in 2015. To combat this disease, an enhanced understanding of thyroid cancer development and progression as well as the development of efficacious, targeted therapies are needed. In vitro and in vivo studies utilizing thyroid cancer cell lines and animal models are critically important to these research efforts. In this report, we detail our studies with a panel of authenticated human anaplastic and papillary thyroid cancer (ATC and PTC) cell lines engineered to express firefly luciferase in two in vivo murine cancer models-an orthotopic thyroid cancer model as well as an intracardiac injection metastasis model. In these models, primary tumor growth in the orthotopic model and the establishment and growth of metastases in the intracardiac injection model are followed in vivo using an IVIS imaging system. In the orthotopic model, the ATC cell lines 8505C and T238 and the PTC cell lines K1/GLAG-66 and BCPAP had take rates >90 % with final tumor volumes ranging 84-214 mm(3) over 4-5 weeks. In the intracardiac model, metastasis establishment was successful in the ATC cell lines HTh74, HTh7, 8505C, THJ-16T, and Cal62 with take rates ≥70 %. Only one of the PTC cell lines tested (BCPAP) was successful in the intracardiac model with a take rate of 30 %. These data will be beneficial to inform the choice of cell line and model system for the design of future thyroid cancer studies.

Status Report on NEAMS System Analysis Module Development

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

Hu, R.; Fanning, T. H.; Sumner, T.

2015-12-01

Under the Reactor Product Line (RPL) of DOE-NE’s Nuclear Energy Advanced Modeling and Simulation (NEAMS) program, an advanced SFR System Analysis Module (SAM) is being developed at Argonne National Laboratory. The goal of the SAM development is to provide fast-running, improved-fidelity, whole-plant transient analyses capabilities. SAM utilizes an object-oriented application framework MOOSE), and its underlying meshing and finite-element library libMesh, as well as linear and non-linear solvers PETSc, to leverage modern advanced software environments and numerical methods. It also incorporates advances in physical and empirical models and seeks closure models based on information from high-fidelity simulations and experiments. This reportmore » provides an update on the SAM development, and summarizes the activities performed in FY15 and the first quarter of FY16. The tasks include: (1) implement the support of 2nd-order finite elements in SAM components for improved accuracy and computational efficiency; (2) improve the conjugate heat transfer modeling and develop pseudo 3-D full-core reactor heat transfer capabilities; (3) perform verification and validation tests as well as demonstration simulations; (4) develop the coupling requirements for SAS4A/SASSYS-1 and SAM integration.« less

Using career ladders to motivate and retain employees: an implementation success story.

PubMed

Garletts, Joseph A

2002-01-01

In October 2000, Phoenix-based Sonora Quest Laboratories, LLC (SQL), commissioned The Gelfond Group to survey SQL employees. Responding to negative survey scores, SQL developed and implemented an entry-level career ladder for line staff of the specimen management/referral testing department. The program was piloted in February 2001, and was implemented fully shortly thereafter. The ladder was designed to provide job enrichment opportunities through company-conducted training and advancement provisions. It contained requirements for productivity and quality of work performed in addition to increasingly rigorous training and competency documentation. Employees were accountable for their own advancement and for ensuring that all documentation was complete. Advancement was automatic once requirements were completed. Pay increases accompanied each advancement on a predetermined scale. At the end of 12 months, employee turnover dropped from 39% to less than 20% annually. Both productivity and morale improved, and results on a second employee survey indicated dramatic improvement in five key areas. The career ladder concept has been replicated successfully in several other departments, including phlebotomy, and a six-tiered ladder is under development for the clinical laboratory. It will encompass CLA, MLT, and MT positions from entry level to technical coordinator.

AGR-1 Irradiation Test Final As-Run Report, Rev. 3

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

Collin, Blaise P.

2015-01-01

This document presents the as-run analysis of the AGR-1 irradiation experiment. AGR-1 is the first of eight planned irradiations for the Advanced Gas Reactor (AGR) Fuel Development and Qualification Program. Funding for this program is provided by the US Department of Energy (DOE) as part of the Next-Generation Nuclear Plant (NGNP) project. The objectives of the AGR-1 experiment are: 1. To gain experience with multi-capsule test train design, fabrication, and operation with the intent to reduce the probability of capsule or test train failure in subsequent irradiation tests. 2. To irradiate fuel produced in conjunction with the AGR fuel processmore » development effort. 3. To provide data that will support the development of an understanding of the relationship between fuel fabrication processes, fuel product properties, and irradiation performance. In order to achieve the test objectives, the AGR-1 experiment was irradiated in the B-10 position of the Advanced Test Reactor (ATR) at the Idaho National Laboratory (INL) for a total duration of 620 effective full power days of irradiation. Irradiation began on December 24, 2006 and ended on November 6, 2009 spanning 13 ATR cycles and approximately three calendar years. The test contained six independently controlled and monitored capsules. Each capsule contained 12 compacts of a single type, or variant, of the AGR coated fuel. No fuel particles failed during the AGR-1 irradiation. Final burnup values on a per compact basis ranged from 11.5 to 19.6 %FIMA, while fast fluence values ranged from 2.21 to 4.39 x 10 25 n/m 2 (E >0.18 MeV). We’ll say something here about temperatures once thermal recalc is done. Thermocouples performed well, failing at a lower rate than expected. At the end of the irradiation, nine of the originally-planned 19 TCs were considered functional. Fission product release-to-birth (R/B) ratios were quite low. In most capsules, R/B values at the end of the irradiation were at or below 10 -7 with only one capsule significantly exceeding this value. A maximum R/B of around 2 x 10 -7 was reached at the end of the irradiation in Capsule 5. Several shakedown issues were encountered and resolved during the first three cycles. These include the repair of minor gas line leaks; repair of faulty gas line valves; the need to position moisture monitors in regions of low radiation fields for proper functioning; the enforcement of proper on-line data storage and backup, the need to monitor thermocouple performance, correcting for detector spectral gain shift, and a change in the mass flow rate range of the neon flow controllers.« less

Development of advanced magnetic resonance sensor for industrial applications. Final report

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

De Los Santos, A.

1997-06-01

Southwest Research Institute (SwRI) and various subcontractors, in a cooperative agreement with the DOE, have developed and tested an advanced magnetic resonance (MR) sensor for several industrial applications and made various market surveys. The original goal of the program was to develop an advanced moisture sensor to allow more precise and rapid control of drying processes so that energy and/or product would not be wasted. Over the course of the program, it was shown that energy savings were achievable but in many processes the return in investment did not justify the cost of a magnetic resonance sensor. However, in manymore » processes, particularly chemical, petrochemical, paper and others, the return in investment can be very high as to easily justify the cost of a magnetic resonance sensor. In these industries, substantial improvements in product yield, quality, and efficiency in production can cause substantial energy savings and reductions in product wastage with substantial environmental effects. The initial applications selected for this program included measurement of corn gluten at three different points and corn germ at one point in an American Maize corn processing plant. During the initial phases (I and II) of this program, SwRI developed a prototype advanced moisture sensor utilizing NMR technology capable of accurately and reliably measuring moisture in industrial applications and tested the sensor in the laboratory under conditions simulating on-line products in the corn wet milling industry. The objective of Phase III was to test the prototype sensor in the plant environment to determine robustness, reliability and long term stability. Meeting these objectives would permit extended field testing to improve the statistical database used to calibrate the sensor and subject the sensor to true variations in operating conditions encountered in the process rather than those which could only be simulated in the laboratory.« less

Changing low income smokers' beliefs about tobacco dependence treatment.

PubMed

Christiansen, Bruce; Reeder, Kevin; Fiore, Michael C; Baker, Timothy B

2014-06-01

This field study tested an intervention that challenged beliefs about the effectiveness of various quit methods held by Salvation Army client smokers from two urban locations (N = 245). Data (surveys administered immediately after and one month post-intervention) were collected 2009-2010 and analyzed using primarily χ(2) and t-tests. The intervention changed client perceptions about the effectiveness of quitting methods. Compared to no-intervention controls, intervention participants reported significantly greater smoking reduction and greater likelihood of contacting the Wisconsin Tobacco Quit Line. Study implications/limitations are discussed and future research directions noted. This research was supported by grant UL1TR000427 from the Clinical and Translational Science Award (CTSA) program of the National Center for Advancing Translational Sciences, NIH.

77 FR 40586 - Draft NIST Interagency Report (NISTIR) 7823, Advanced Metering Infrastructure Smart Meter...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-07-10

...-01] Draft NIST Interagency Report (NISTIR) 7823, Advanced Metering Infrastructure Smart Meter... Technology (NIST) seeks comments on Draft NISTIR 7823, Advanced Metering Infrastructure Smart Meter.... Electronic comments should be sent to: Michaela Iorga at [email protected]nist.gov , with a Subject line...

Pembrolizumab Utilization and Outcomes for Advanced Melanoma in US Community Oncology Practices

PubMed Central

Liu, Frank Xiaoqing; Black-Shinn, Jenny; Stevinson, Kendall; Boyd, Marley; Frytak, Jennifer R.; Ebbinghaus, Scot W.

2018-01-01

The programmed death-1 inhibitor pembrolizumab has demonstrated efficacy and safety in clinical trials for treating advanced (unresectable/metastatic) melanoma. We investigated the real-world utilization of pembrolizumab and associated patient outcomes for advanced melanoma in US community oncology practices. This retrospective, observational study used deidentified data from electronic health records for adult patients with advanced melanoma who received pembrolizumab at The US Oncology Network sites from September 2014 through December 2015, with follow-up through September 2016. Patients enrolled in clinical trials were excluded. Overall survival (OS) and physician-stated progression-free survival (PFS) were analyzed from pembrolizumab initiation using Kaplan-Meier, and associations between pembrolizumab therapy and OS/PFS, using multivariable Cox regression. Of 168 patients studied, 110 (65%) were male; the median age was 66 years (range, 26–over 90). Pembrolizumab was prescribed as first-line, second-line, and third-line/later for 39 (23%), 87 (52%), and 42 (25%) patients, respectively. In total, 41 patients (24%) had brain metastases. At pembrolizumab initiation, 21/129 (16%) had Eastern Cooperative Oncology Group performance status (ECOG PS) >1; 51/116 (44%) had elevated lactate dehydrogenase. Median follow-up was 10.5 months (range, 0–25.1); median OS was 19.4 months (95% confidence interval, 14.0–not reached); median PFS was 4.2 months (95% confidence interval, 2.9–5.3). Brain metastases, ECOG PS>1, elevated lactate dehydrogenase, and third-line/later (vs. first-line) pembrolizumab were significant predictors (P<0.01) of decreased survival. Treatment-related toxicity was a discontinuation reason for 25% (29/117) of patients, and for 10 of these 29 patients (6% of the full-study cohort) treatment-related toxicity was the only reported reason. The real-world effectiveness and safety of pembrolizumab for advanced melanoma are consistent with clinical trial findings. PMID:29252916

What's the Bottom Line

EPA Science Inventory

Advances in analytical instrumentation have not only increased the number and types of chemicals measured, but reduced the quantitation limits, allowing these chemicals to be detected at progressively lower concentrations in various environmental matrices. Such analytical advanc...

Apatinib in the treatment of advanced lung adenocarcinoma with KRAS mutation.

PubMed

Zeng, Da-Xiong; Wang, Chang-Guo; Huang, Jian-An; Jiang, Jun-Hong

2017-01-01

Activating KRAS mutations in lung adenocarcinoma are characterized with treatment resistance and poor prognosis. As a small molecule inhibitor of vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase, apatinib has been proven successful in advanced gastric cancer and breast cancer. In this study, we show the result of apatinib as salvage treatment in lung adenocarcinoma patients with KRAS mutation. Four advanced lung adenocarcinoma patients with KRAS mutation were orally administered apatinib (250 mg/d) after second-line treatment. One patient showed progressive disease, while 3 patients showed stable disease response to apatinib, with a median progression-free survival (PFS) of 3.8 months (1.5-5.5 months). The main toxicities were hoarseness and hemoptysis, which were manageable. Therefore, apatinib might be an optional choice for advanced lung adenocarcinoma patients with KRAS mutation in post second-line treatment.

Main steam line break accident simulation of APR1400 using the model of ATLAS facility

NASA Astrophysics Data System (ADS)

Ekariansyah, A. S.; Deswandri; Sunaryo, Geni R.

2018-02-01

A main steam line break simulation for APR1400 as an advanced design of PWR has been performed using the RELAP5 code. The simulation was conducted in a model of thermal-hydraulic test facility called as ATLAS, which represents a scaled down facility of the APR1400 design. The main steam line break event is described in a open-access safety report document, in which initial conditions and assumptionsfor the analysis were utilized in performing the simulation and analysis of the selected parameter. The objective of this work was to conduct a benchmark activities by comparing the simulation results of the CESEC-III code as a conservative approach code with the results of RELAP5 as a best-estimate code. Based on the simulation results, a general similarity in the behavior of selected parameters was observed between the two codes. However the degree of accuracy still needs further research an analysis by comparing with the other best-estimate code. Uncertainties arising from the ATLAS model should be minimized by taking into account much more specific data in developing the APR1400 model.

Exploring the Action Landscape via Trial World-Lines

ERIC Educational Resources Information Center

Joglekar, Yogesh N.; Tham, Weng Kian

2011-01-01

The Hamilton action principle, also known as the principle of least action, and Lagrange equations are an integral part of intermediate and advanced undergraduate mechanics. Although the Hamilton principle is oft stated as "the action for any nearby trial world-line is greater than the action for the classical world-line," the landscape of action…

Design, fabrication, and operation of capsules for the irradiation testing of candidate advanced space reactor fuel pins

NASA Technical Reports Server (NTRS)

Thoms, K. R.

1975-01-01

Fuel irradiation experiments were designed, built, and operated to test uranium mononitride (UN) fuel clad in tungsten-lined T-111 and uranium dioxide fuel clad in both tungsten-lined T-111 and tungsten-lined Nb-1% Zr. A total of nine fuel pins was irradiated at average cladding temperatures ranging from 931 to 1015 C. The UN experiments, capsules UN-4 and -5, operated for 10,480 and 10,037 hr, respectively, at an average linear heat generation rate of 10 kW/ft. The UO2 experiment, capsule UN-6, operated for 8333 hr at an average linear heat generation rate of approximately 5 kW/ft. Following irradiation, the nine fuel pins were removed from their capsules, externally examined, and sent to the NASA Plum Brook Facility for more detailed postirradiation examination. During visual examination, it was discovered that the cladding of the fuel pin containing dense UN in each of capsules UN-4 and -5 had failed, exposing the UN fuel to the NaK in which the pins were submerged and permitting the release of fission gas from the failed pins. A rough analysis of the fission gas seen in samples of the gas in the fuel pin region indicated fission gas release-to-birth rates from these fuel pins in the range of .00001.

Effect of Berry Extracts and Bioactive Compounds on Fulvestrant (ICI 182,780) Sensitive and Resistant Cell Lines.

PubMed

Woode, Denzel R; Aiyer, Harini S; Sie, Nicole; Zwart, Alan L; Li, Liya; Seeram, Navindra P; Clarke, Robert

2012-01-01

Fulvestrant (ICI 182,780; ICI) is approved for the treatment of advanced metastatic breast cancer that is unresponsive to other endocrine therapies. Berries are frequently consumed for their antioxidant, anti-inflammatory, and anticancer potential. In this study, we tested the efficacy of two berry extracts (Jamun-EJAE and red raspberry-RRE) and their bioactive compounds (Delphinidin-Del and Ellagic acid-EA) to inhibit cell proliferation with or without a sublethal dose of ICI in various breast cancer cell lines. ICI-sensitive (LCC1, ZR75-1, and BT474) and -resistant (LCC9, ZR75-1R) cells were subjected to treatment with berry extracts alone (0.1-100 μg/mL) or with a sub-lethal dose of ICI ( 1). EA, in doses tested, did not have any significant effects on any of the cell lines. Finally, we found that the extracts were more effective at lower, physiologically relevant concentrations than at higher experimental doses.

Effect of Berry Extracts and Bioactive Compounds on Fulvestrant (ICI 182,780) Sensitive and Resistant Cell Lines

PubMed Central

Woode, Denzel R.; Aiyer, Harini S.; Sie, Nicole; Zwart, Alan L.; Li, Liya; Seeram, Navindra P.; Clarke, Robert

2012-01-01

Fulvestrant (ICI 182,780; ICI) is approved for the treatment of advanced metastatic breast cancer that is unresponsive to other endocrine therapies. Berries are frequently consumed for their antioxidant, anti-inflammatory, and anticancer potential. In this study, we tested the efficacy of two berry extracts (Jamun-EJAE and red raspberry-RRE) and their bioactive compounds (Delphinidin-Del and Ellagic acid-EA) to inhibit cell proliferation with or without a sublethal dose of ICI in various breast cancer cell lines. ICI-sensitive (LCC1, ZR75-1, and BT474) and -resistant (LCC9, ZR75-1R) cells were subjected to treatment with berry extracts alone (0.1–100 μg/mL) or with a sub-lethal dose of ICI ( 1). EA, in doses tested, did not have any significant effects on any of the cell lines. Finally, we found that the extracts were more effective at lower, physiologically relevant concentrations than at higher experimental doses. PMID:23346406

A discussion of current issues and concepts in the practice of skull-photo/craniofacial superimposition.

PubMed

Gordon, G M; Steyn, M

2016-05-01

A recent review paper on cranio-facial superimposition (CFS) stated that "there have been specific conceptual variances" from the original methods used in the practice of skull-photo superimposition, leading to poor results as far as accuracy is concerned. It was argued that the deviations in the practice of the technique have resulted in the reduced accuracies (for both failure to include and failure to exclude) that are noted in several recent studies. This paper aims to present the results from recent research to highlight the advancement of skull-photo/cranio-facial superimposition, and to discuss some of the issues raised regarding deviations from original techniques. The evolving methodology of CFS is clarified in context with the advancement of technology, forensic science and specifically within the field of forensic anthropology. Developments in the skull-photo/cranio-facial superimposition techniques have largely focused on testing reliability and accuracy objectively. Techniques now being employed by forensic anthropologists must conform to rigorous scientific testing and methodologies. Skull-photo/cranio-facial superimposition is constantly undergoing accuracy and repeatability testing which is in line with the principles of the scientific method and additionally allows for advancement in the field. Much of the research has indicated that CFS is useful in exclusion which is consistent with the concept of Popperian falsifiability - a hypothesis and experimental design which is falsifiable. As the hypothesis is disproved or falsified, another evolves to replace it and explain the new observations. Current and future studies employing different methods to test the accuracy and reliability of skull-photo/cranio-facial superimposition will enable researchers to establish the contribution the technique can have for identification purposes. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

ALFVÉN WAVES IN SIMULATIONS OF SOLAR PHOTOSPHERIC VORTICES

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

Shelyag, S.; Cally, P. S.; Reid, A.

Using advanced numerical magneto-hydrodynamic simulations of the magnetized solar photosphere, including non-gray radiative transport and a non-ideal equation of state, we analyze plasma motions in photospheric magnetic vortices. We demonstrate that apparent vortex-like motions in photospheric magnetic field concentrations do not exhibit 'tornado'-like behavior or a 'bath-tub' effect. While at each time instance the velocity field lines in the upper layers of the solar photosphere show swirls, the test particles moving with the time-dependent velocity field do not demonstrate such structures. Instead, they move in a wave-like fashion with rapidly changing and oscillating velocity field, determined mainly by magnetic tensionmore » in the magnetized intergranular downflows. Using time-distance diagrams, we identify horizontal motions in the magnetic flux tubes as torsional Alfvén perturbations propagating along the nearly vertical magnetic field lines with local Alfvén speed.« less

Composition and antiproliferative effect of essential oil of Origanum vulgare against tumor cell lines.

PubMed

Begnini, Karine Rech; Nedel, Fernanda; Lund, Rafael Guerra; Carvalho, Pedro Henrique de Azambuja; Rodrigues, Maria Regina Alves; Beira, Fátima Tereza Alves; Del-Pino, Francisco Augusto Burkert

2014-10-01

Cancer is a leading cause of death and is responsible for one in eight deaths worldwide. The use of herbs as complementary medicine for cancer, especially advanced cancer, has recently increased. The aim of this study was to evaluate in vitro, the antiproliferative effect of Origanum vulgare against human breast adenocarcinoma (MCF-7), and human colon adenocarcinoma (HT-29). The essential oil (EO) was extracted from a bought amount of O. vulgare dried leaves and analyzed in a gas chromatograph interfaced with a mass selective detector. The cytotoxicity test was performed by sulforhodamine B assay. The results show that the EO is composed mostly of 4-terpineol and induces a high cytotoxicity effect in HT-29. In the MCF-7 cell line the EO was less effective. In conclusion, this study showed that O. vulgare main component is 4-terpineol and was effective in inducing cancer cell growth inhibition.

A new FPGA architecture suitable for DSP applications

NASA Astrophysics Data System (ADS)

Liyun, Wang; Jinmei, Lai; Jiarong, Tong; Pushan, Tang; Xing, Chen; Xueyan, Duan; Liguang, Chen; Jian, Wang; Yuan, Wang

2011-05-01

A new FPGA architecture suitable for digital signal processing applications is presented. DSP modules can be inserted into FPGA conveniently with the proposed architecture, which is much faster when used in the field of digital signal processing compared with traditional FPGAs. An advanced 2-level MUX (multiplexer) is also proposed. With the added SLEEP MODE PASS to traditional 2-level MUX, static leakage is reduced. Furthermore, buffers are inserted at early returns of long lines. With this kind of buffer, the delay of the long line is improved by 9.8% while the area increases by 4.37%. The layout of this architecture has been taped out in standard 0.13 μm CMOS technology successfully. The die size is 6.3 × 4.5 mm2 with the QFP208 package. Test results show that performances of presented classical DSP cases are improved by 28.6%-302% compared with traditional FPGAs.

SunLine Transit Agency Advanced Technology Fuel Cell Bus Evaluation: Fourth Results Report

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

Eudy, L.; Chandler, K.

2013-01-01

SunLine Transit Agency, which provides public transit services to the Coachella Valley area of California, has demonstrated hydrogen and fuel cell bus technologies for more than 10 years. In May 2010, SunLine began demonstrating the advanced technology (AT) fuel cell bus with a hybrid electric propulsion system, fuel cell power system, and lithium-based hybrid batteries. This report describes operations at SunLine for the AT fuel cell bus and five compressed natural gas buses. The U.S. Department of Energy's National Renewable Energy Laboratory (NREL) is working with SunLine to evaluate the bus in real-world service to document the results and helpmore » determine the progress toward technology readiness. NREL has previously published three reports documenting the operation of the fuel cell bus in service. This report provides a summary of the results with a focus on the bus operation from February 2012 through November 2012.« less

CellLineNavigator: a workbench for cancer cell line analysis

PubMed Central

Krupp, Markus; Itzel, Timo; Maass, Thorsten; Hildebrandt, Andreas; Galle, Peter R.; Teufel, Andreas

2013-01-01

The CellLineNavigator database, freely available at http://www.medicalgenomics.org/celllinenavigator, is a web-based workbench for large scale comparisons of a large collection of diverse cell lines. It aims to support experimental design in the fields of genomics, systems biology and translational biomedical research. Currently, this compendium holds genome wide expression profiles of 317 different cancer cell lines, categorized into 57 different pathological states and 28 individual tissues. To enlarge the scope of CellLineNavigator, the database was furthermore closely linked to commonly used bioinformatics databases and knowledge repositories. To ensure easy data access and search ability, a simple data and an intuitive querying interface were implemented. It allows the user to explore and filter gene expression, focusing on pathological or physiological conditions. For a more complex search, the advanced query interface may be used to query for (i) differentially expressed genes; (ii) pathological or physiological conditions; or (iii) gene names or functional attributes, such as Kyoto Encyclopaedia of Genes and Genomes pathway maps. These queries may also be combined. Finally, CellLineNavigator allows additional advanced analysis of differentially regulated genes by a direct link to the Database for Annotation, Visualization and Integrated Discovery (DAVID) Bioinformatics Resources. PMID:23118487

Performance of advanced resuscitation skills by pediatric housestaff.

PubMed

White, J R; Shugerman, R; Brownlee, C; Quan, L

1998-12-01

To describe pediatric housestaff resuscitation experience and their ability to perform key resuscitation skills. Cohort study of 63 pediatric residents in a university-based training program. Investigators observed, scored, and timed resident performance on 4 key resuscitation skills. Cognitive ability was tested with 4 written scenarios. Housestaff provided self-reports of the number of months since their last American Heart Association Pediatric Advanced Life Support course, number of mock and actual codes attended, number of times skills were performed, and self-confidence with respect to resuscitation. A total of 45 pediatric residents (71%) participated. Median cognitive score was 5 (range, 1-5). Of all residents, 44 (97%) successfully bag mask-ventilated the mannequin; 24 (53%) and 36 (80%) used the correct bag and mask size, respectively. Thirty-nine residents (87%) placed a tube in the mannequin trachea, 12 (27%) checked that suction was working prior to intubation, and 30 (67%) chose the correct endotracheal tube size. Forty residents (89%) discharged the defibrillator, and 25 (56%) and 32 (71%) correctly chose asynchronous mode and infant paddles, respectively. Thirty-eight residents (84%) inserted an intraosseous line; 35 (78%) had correct placement. Median times for successful skill completion were 83 seconds for bag mask ventilation, 136 seconds for intubation, 149 seconds for defibrillation, and 68 seconds for intraosseous line placement. Pediatric housestaff previously trained in pediatric advanced life support were generally able to reach the end point of 4 key resuscitation skills but less frequently performed the specific subcomponents of each skill. This poor performance and the prolonged time to skill completion suggest the need for greater attention to detail during training.

Development of the automatic test pattern generation for NPP digital electronic circuits using the degree of freedom concept

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

Kim, D.S.; Seong, P.H.

1995-08-01

In this paper, an improved algorithm for automatic test pattern generation (ATG) for nuclear power plant digital electronic circuits--the combinational type of logic circuits is presented. For accelerating and improving the ATG process for combinational circuits the presented ATG algorithm has the new concept--the degree of freedom (DF). The DF, directly computed from the system descriptions such as types of gates and their interconnections, is the criterion to decide which among several alternate lines` logic values required along each path promises to be the most effective in order to accelerate and improve the ATG process. Based on the DF themore » proposed ATG algorithm is implemented in the automatic fault diagnosis system (AFDS) which incorporates the advanced fault diagnosis method of artificial intelligence technique, it is shown that the AFDS using the ATG algorithm makes Universal Card (UV Card) testing much faster than the present testing practice or by using exhaustive testing sets.« less

Phase III randomized trial comparing 5-fluorouracil and oxaliplatin with or without docetaxel in first-line advanced gastric cancer chemotherapy (GASTFOX study).

PubMed

Zaanan, Aziz; Samalin, Emmanuelle; Aparicio, Thomas; Bouche, Olivier; Laurent-Puig, Pierre; Manfredi, Sylvain; Michel, Pierre; Monterymard, Carole; Moreau, Marie; Rougier, Philippe; Tougeron, David; Taieb, Julien; Louvet, Christophe

2018-04-01

In advanced gastric cancer, doublet regimen including platinum salts and fluoropyrimidine is considered as a standard first-line treatment. The addition of docetaxel (75 mg/m 2  q3w) to cisplatin (75 mg/m 2  q3w) and 5-fluorouracil has been shown to improve efficacy. However, this regimen (DCF) was associated with frequent severe toxicities (including more complicated neutropenia), limiting its use in clinical practice. Interesting alternative docetaxel-based regimens have been developed that need to be validated. GASTFOX study is a randomized phase III trial comparing FOLFOX alone or with docetaxel at 50 mg/m 2 (TFOX regimen) in first-line treatment for advanced gastric cancer. In both arms, cycle is repeated every 2 weeks until disease progression or unacceptable toxicity. Main eligibility criteria: histologically proven locally advanced or metastatic gastric or esogastric junction adenocarcinoma, HER negative status, measurable disease, ECOG performance status 0 or 1, and adequate renal, hepatic and bone marrow functions. The primary endpoint is radiological/clinical progression-free survival (PFS). A difference of 2 months for the median PFS in favor of TFOX is expected (HR = 0.73) Based on a two-sided α risk of 5% and a power of 90%, 454 events are required to show this difference. Secondary endpoints included overall survival, overall response rate, safety, quality of life and the therapeutic index. This study is planned to include 506 patients to demonstrate the superiority of TFOX over FOLFOX in first-line advanced gastric cancer treatment (NCT03006432). Copyright © 2018 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

Randomized, Double-Blind, Placebo-Controlled Phase III Trial of Apatinib in Patients With Chemotherapy-Refractory Advanced or Metastatic Adenocarcinoma of the Stomach or Gastroesophageal Junction.

PubMed

Li, Jin; Qin, Shukui; Xu, Jianming; Xiong, Jianping; Wu, Changping; Bai, Yuxian; Liu, Wei; Tong, Jiandong; Liu, Yunpeng; Xu, Ruihua; Wang, Zhehai; Wang, Qiong; Ouyang, Xuenong; Yang, Yan; Ba, Yi; Liang, Jun; Lin, Xiaoyan; Luo, Deyun; Zheng, Rongsheng; Wang, Xin; Sun, Guoping; Wang, Liwei; Zheng, Leizhen; Guo, Hong; Wu, Jingbo; Xu, Nong; Yang, Jianwei; Zhang, Honggang; Cheng, Ying; Wang, Ningju; Chen, Lei; Fan, Zhining; Sun, Piaoyang; Yu, Hao

2016-05-01

There is currently no standard treatment strategy for patients with advanced metastatic gastric cancer experiencing progression after two or more lines of chemotherapy. We assessed the efficacy and safety of apatinib, a novel vascular endothelial growth factor receptor 2 tyrosine kinase inhibitor, in patients with advanced gastric or gastroesophageal junction adenocarcinoma for whom at least two lines of prior chemotherapy had failed. This was a randomized, double-blind, placebo-controlled phase III trial. Patients from 32 centers in China with advanced gastric or gastroesophageal junction adenocarcinoma, for whom two or more prior lines of chemotherapy had failed, were enrolled. Patients were randomly assigned to oral apatinib 850 mg or placebo once daily. The primary end points were overall (OS) and progression-free survival (PFS). Between January 2011 and November 2012, 267 patients were enrolled. Median OS was significantly improved in the apatinib group compared with the placebo group (6.5 months; 95% CI, 4.8 to 7.6 v 4.7 months; 95% CI, 3.6 to 5.4; P = .0149; hazard ratio, 0.709; 95% CI, 0.537 to 0.937; P = .0156). Similarly, apatinib significantly prolonged median PFS compared with placebo (2.6 months; 95% CI, 2.0 to 2.9 v 1.8 months; 95% CI, 1.4 to 1.9; P < .001; hazard ratio, 0.444; 95% CI, 0.331 to 0.595; P < .001). The most common grade 3 to 4 nonhematologic adverse events were hand-foot syndrome, proteinuria, and hypertension. These data show that apatinib treatment significantly improved OS and PFS with an acceptable safety profile in patients with advanced gastric cancer refractory to two or more lines of prior chemotherapy. © 2016 by American Society of Clinical Oncology.

Clinical features and response to systemic therapy in a historical cohort of advanced or unresectable mucosal melanoma.

PubMed

Shoushtari, Alexander N; Bluth, Mark J; Goldman, Debra A; Bitas, Christiana; Lefkowitz, Robert A; Postow, Michael A; Munhoz, Rodrigo R; Buchar, Gauri; Hester, Robert H; Romero, Jacqueline A; Fitzpatrick, Laura J; Weiser, Martin R; Panageas, Katherine S; Wolchok, Jedd D; Chapman, Paul B; Carvajal, Richard D

2017-02-01

There are very few data available regarding the pattern of first metastases in resected mucosal melanomas (MMs) as well as the response of advanced MM to cytotoxic therapy. A retrospective, single-institution cohort was assembled of all patients with advanced/unresectable MM between 1995 and 2012 who had received systemic therapy with available imaging (N=81). Responses to first-line and second-line systemic therapy were assessed using Response Evaluation Criteria in Solid Tumors (RECIST) 1.1. The relationship between response, overall survival, and clinical covariates was investigated using Cox proportional hazards regression. Primary sites included anorectal (N=31, 38%), vulvovaginal (N=28, 35%), head and neck (N=21, 26%), and gallbladder (N=1, 1%) mucosa. Seven percent of patients had their first relapse in the brain. Cytotoxic therapy represented 82 and 51% of first-line and second-line regimens. The best response achieved in the first-line setting was similar for single-agent [10%; 95% confidence interval (CI): 1-32%] and combination alkylator therapy (8%; 95% CI: 2-21%). Median overall survival from first-line treatment was 10.3 months (95% CI: 8.7-13.9 months). Patients with elevated lactic dehydrogenase [hazard ratio (HR): 1.87, 95% CI: 1.10-3.19, P=0.020] and Eastern Cooperative Oncology Group performance status 1-2 (HR: 1.69, 95% CI: 1.05-2.72, P=0.030) had a higher risk of death, whereas patients with 12-week objective responses had a lower risk of death (HR: 0.12, 95% CI: 0.04-0.41, P<0.001). Cytotoxic systemic therapy has modest activity in advanced/unresectable MM, belying its adjuvant benefit. Patients whose tumors have an objective response to therapy have a lower probability of death. Brain imaging should be considered in routine surveillance.

Apparatus for Hot Impact Testing of Material Specimens

NASA Technical Reports Server (NTRS)

Pawlik, Ralph J.; Choi, Sung R.

2006-01-01

An apparatus for positioning and holding material specimens is a major subsystem of a system for impact testing of the specimens at temperatures up to 1,500 C. This apparatus and the rest of the system are designed especially for hot impact testing of advanced ceramics, composites, and coating materials. The apparatus includes a retaining fixture on a rotating stage on a vertically movable cross support driven by a linear actuator. These components are located below a furnace wherein the hot impact tests are performed (see Figure 1). In preparation for a test, a specimen is mounted on the retaining fixture, then the cross support is moved upward to raise the specimen, through an opening in the bottom of the furnace, to the test position inside the furnace. On one side of the furnace there is another, relatively small opening on a direct line to the specimen. Once the specimen has become heated to the test temperature, the test is performed by using an instrumented external pressurized-gas-driven gun to shoot a projectile through the side opening at the specimen.

Design of a Parachute Canopy Instrumentation Platform

NASA Technical Reports Server (NTRS)

Alshahin, Wahab M.; Daum, Jared S.; Holley, James J.; Litteken, Douglas A.; Vandewalle, Michael T.

2015-01-01

This paper discusses the current technology available to design and develop a reliable and compact instrumentation platform for parachute system data collection and command actuation. Wireless communication with a parachute canopy will be an advancement to the state of the art of parachute design, development, and testing. Embedded instrumentation of the parachute canopy will provide reefing line tension, skirt position data, parachute health monitoring, and other telemetry, further validating computer models and giving engineering insight into parachute dynamics for both Earth and Mars entry that is currently unavailable. This will allow for more robust designs which are more optimally designed in terms of structural loading, less susceptible to adverse dynamics, and may eventually pave the way to currently unattainable advanced concepts of operations. The development of this technology has dual use potential for a variety of other applications including inflatable habitats, aerodynamic decelerators, heat shields, and other high stress environments.

FieldTrip: Open Source Software for Advanced Analysis of MEG, EEG, and Invasive Electrophysiological Data

PubMed Central

Oostenveld, Robert; Fries, Pascal; Maris, Eric; Schoffelen, Jan-Mathijs

2011-01-01

This paper describes FieldTrip, an open source software package that we developed for the analysis of MEG, EEG, and other electrophysiological data. The software is implemented as a MATLAB toolbox and includes a complete set of consistent and user-friendly high-level functions that allow experimental neuroscientists to analyze experimental data. It includes algorithms for simple and advanced analysis, such as time-frequency analysis using multitapers, source reconstruction using dipoles, distributed sources and beamformers, connectivity analysis, and nonparametric statistical permutation tests at the channel and source level. The implementation as toolbox allows the user to perform elaborate and structured analyses of large data sets using the MATLAB command line and batch scripting. Furthermore, users and developers can easily extend the functionality and implement new algorithms. The modular design facilitates the reuse in other software packages. PMID:21253357

X-ray rocking curve measurements of bent crystals. [used in High Resolution Spectrometer in Advanced X-ray Astrophysics Facility

NASA Technical Reports Server (NTRS)

Hakim, M. B.; Muney, W. S.; Fowler, W. B.; Woodgate, B. E.

1988-01-01

A three-crystal laboratory X-ray spectrometer is used to measure the Bragg reflection from concave cylindrically curved crystals to be used in the high-resolution X-ray spectrometer of the NASA Advanced X-ray Astrophysics Facility (AXAF). The first two crystals, in the dispersive (1.1) arrangement, select a narrow collimated monochromatic beam in the Cu K-alpha(1) line at 1.5 A (8.1 keV), which illuminates the test crystal. The angular centroids of rocking curves measured along the surface provide a measure of the conformity of the crystal to the desired radius of curvature. Individual and combined rocking-curve widths and areas provide a measure of the resolution and efficiency at 1.54 A. The crystals analyzed included LiF(200), PET, and acid phthalates such as TAP.

Summary of recent NASA propeller research

NASA Technical Reports Server (NTRS)

Mikkelson, D. C.; Mitchell, G. A.; Bober, L. J.

1984-01-01

Advanced high-speed propellers offer large performance improvements for aircraft that cruise in the Mach 0.7 to 0.8 speed regime. At these speeds, studies indicate that there is a 15 to near 40 percent block fuel savings and associated operating cost benefits for advanced turboprops compared to equivalent technology turbofan powered aircraft. Recent wind tunnel results for five eight to ten blade advanced models are compared with analytical predictions. Test results show that blade sweep was important in achieving net efficiencies near 80 percent at Mach 0.8 and reducing nearfield cruise noise by about 6 dB. Lifting line and lifting surface aerodynamic analysis codes are under development and some results are compared with propeller force and probe data. Also, analytical predictions are compared with some initial laser velocimeter measurements of the flow field velocities of an eightbladed 45 swept propeller. Experimental aeroelastic results indicate that cascade effects and blade sweep strongly affect propeller aeroelastic characteristics. Comparisons of propeller near-field noise data with linear acoustic theory indicate that the theory adequately predicts near-field noise for subsonic tip speeds but overpredicts the noise for supersonic tip speeds.

Summary of recent NASA propeller research

NASA Technical Reports Server (NTRS)

Mikkelson, D. C.; Mitchell, G. A.; Bober, L. J.

1985-01-01

Advanced high speed propellers offer large performance improvements for aircraft that cruise in the Mach 0.7 to 0.8 speed regime. At these speeds, studies indicate that there is a 15 to near 40 percent block fuel savings and associated operating cost benefits for advanced turboprops compared to equivalent technology turbofan powered aircraft. Recent wind tunnel results for five eight to ten blade advanced models are compared with analytical predictions. Test results show that blade sweep was important in achieving net efficiencies near 80 percent at Mach 0.8 and reducing nearfield cruise noise about 6 dB. Lifting line and lifting surface aerodynamic analysis codes are under development and some results are compared with propeller force and probe data. Also, analytical predictions are compared with some initial laser velocimeter measurements of the flow field velocities of an eight bladed 45 swept propeller. Experimental aeroelastic results indicate that cascade effects and blade sweep strongly affect propeller aeroelastic characteristics. Comparisons of propeller nearfield noise data with linear acoustic theory indicate that the theory adequately predicts nearfield noise for subsonic tip speeds, but overpredicts the noise for supersonic tip speeds.

Innovation and new trends in critical trauma disease.

PubMed

Chico-Fernández, M; Terceros-Almanza, L L; Mudarra-Reche, C C

2015-04-01

The management of critical trauma disease (CTD) has always trends the trends in military war experiences. These conflicts have historically revolutionized clinical concepts, clinical practice guidelines and medical devices, and have marked future lines of research and aspects of training and learning in severe trauma care. Moreover, in the civil setting, the development of intensive care, technological advances and the testing of our healthcare systems in the management of multiple victims, hasve also led to a need for innovation in our trauma care systems. Copyright © 2014 Elsevier España, S.L.U. and SEMICYUC. All rights reserved.

Cryogenic Thermal Management Advances during the CRYOTOOL Program

NASA Astrophysics Data System (ADS)

Bugby, D.; Stouffer, C.; Garzon, J.; Beres, M.; Gilchrist, A.; Roberts, T.; Davis, T.

2006-04-01

This paper describes the cryogenic thermal management advances made during the AFRL-sponsored CRYOTOOL program. Advances occurred as a result of conducting four technology development tasks: (1) development of a differential thermal expansion cryogenic thermal switch (DTE-CTSW) made with high purity Al end-pieces and an Ultem support rod; (2) carrying out of a dual DTE-CTSW/dual cryocooler performance test to quantify CTSW benefits in a redundant cryocooler system; (3) development of a miniaturized cryogenic loop heat pipe (mini-CLHP) that combines flex link, conduction bar, and CTSW functionalities; and (4) development of an across-gimbal cryogenic thermal transport system (GCTTS) with large diameter transport line coils for optics cooling. The results are as follows. The DTE-CTSW achieved an ON conductance of 2-3.6 W/K (from 35-90 K) and an OFF resistance of 1100-2300 K/W (300-230 K warm end). The redundant cryocooler test showed modest parasitic heat leak savings when dual DTE-CTSWs were used versus when they were not used. The mini-CLHP, using neon as the working fluid, transported 2.5 W at 35 K, achieved an OFF resistance of 1555 K/W, and had cross/axial flexibilities of 100-450 N/m. Lastly, GCTTS, using nitrogen as the working fluid, transported 20 W at 100 K in a flat configuration. Additional work is needed to verify GCTTS operation in an elevated orientation.

Palliative systemic therapy and overall survival of 1,395 patients with advanced breast cancer - Results from the prospective German TMK cohort study.

PubMed

Fietz, Thomas; Tesch, Hans; Rauh, Jacqueline; Boller, Emil; Kruggel, Lisa; Jänicke, Martina; Marschner, Norbert

2017-08-01

Data on treatment and outcome of advanced breast cancer in routine practice are rare, especially concerning recurrent disease, but important to complement the results from clinical trials and to improve the standard of care. We present data on choice of systemic first-line treatment, number of treatment lines, and survival of patients treated by medical oncologists in Germany. 1395 patients recruited by 124 sites at start of first-line therapy into the ongoing, prospective German clinical cohort study TMK (Tumour Registry Breast Cancer) between February 2007 and October 2015 were analysed. The median OS was 33.8 months (95% CI 30.2-40.2) for HR-positive/HER2-negative, 38.2 months (95% CI 31.3-43.0) for HER2-positive and 16.8 months (95% CI 11.5-22.0) for triple negative breast cancer. Patients with triple negative tumours more often died before start of a third-line therapy than patients with HR-positive or HER2-positive tumours (44% vs. 25%). Use of taxane-based chemotherapies has increased since 2007, with 65% of all first-line chemotherapy-treatments containing taxanes in 2013-15 (60% HR-positive/HER2-negative, 75% HER2-positive, 56% triple negative). 52% of the patients with HR-positive/HER2-negative tumours received first-line endocrine therapy in 2013-15; when restricted to patients with only non-visceral metastases this percentage increased to 63%. To our knowledge, this is the first cohort study showing systemic first-line therapy for all subtypes of advanced breast cancer. Overall survival in the TMK is comparable to that reported by clinical trials despite the inclusion of older and comorbid patients. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

Daratumumab resistance is frequent in advanced-stage multiple myeloma patients irrespective of CD38 expression and is related to dismal prognosis.

PubMed

Pick, Marjorie; Vainstein, Vladimir; Goldschmidt, Neta; Lavie, David; Libster, Diana; Gural, Alexander; Grisariu, Sigal; Avni, Batia; Ben Yehuda, Dina; Gatt, Moshe E

2018-05-01

Daratumumab is a promising new antimyeloma agent. We report a single center "real-world" series of multiple myeloma (MM) and amyloidosis (AL) patients treated with daratumumab. Forty-one patients were included: 7 second-line MM, 30 heavily pretreated (median number of therapies of 5) advanced MM, and 4 with AL. Second-line patients and advanced AL showed high rate of durable overall responses. However, advanced MM patients had a dismal prognosis with an overall response rate (ORR) of 36%, and a short median progression-free and overall survival of 2.3 and 6.6 months, respectively. Responses were particularly poor in patients with extramedullary plasmacytomas. Neither the addition of another agent to daratumumab nor changing to the next line of therapy produced significant durable responses in this patient population. Flow cytometry analysis demonstrated that CD38 expression level was not predictive of response. We show that CD38 expression dynamics by a commercially available anti-CD38 antibody after daratumumab administration was hindered by competitive binding of daratumumab. Responses to daratumumab and combinations in patients with advanced MM, particularly with extramedullary disease, are low and short-lived, stressing the administration of this agent should be early in the course of the disease. © 2018 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Docetaxel/S-1 Versus Docetaxel/Capecitabine as First-Line Treatment for Advanced Breast Cancer

PubMed Central

Li, Jinyu; You, Junhao; Si, Wen; Zhu, Yanyun; Chen, Yi; Yang, Bo; Han, Chun; Linghu, Ruixia; Zhang, Xingyang; Jiao, Shunchang; Yang, Junlan

2015-01-01

Abstract The treatment efficacy of advanced breast cancer is still not promising. This study aimed to compare the efficacy and safety of docetaxel/S-1 (DS1) versus docetaxel/capecitabine (DX) as the first-line treatment for advanced breast cancer. From June 2008 to June 2013, 22 patients with advanced breast cancer were treated with the DS1 regimen. Another 26 age- and disease status-matched patients treated with the DX regimen served as controls. The 2 groups were compared in terms of time to progression (TTP), objective response rate, disease control rate, clinical benefit rate, and safety profiles. Median TTP did not differ significantly between the DS1 group and the DX group (9.04 vs 10.94 months, P = 0.473). There were no significant differences in objective response rate, disease control rate, and clinical benefit rate between the 2 groups. Both the DS1 and the DX regimens showed good tolerability. The 2 regimens showed no significant difference in adverse events except degree III hand-foot syndrome (DS1 0 vs DX 23.1%, P = 0.025). For the first-line treatment of advanced breast cancer, the DS1 and the DX regimens showed similar efficacy and safety. The DS1 regimen had less severe hand-foot syndrome than the DX regimen. PMID:26469889

Docetaxel/S-1 Versus Docetaxel/Capecitabine as First-Line Treatment for Advanced Breast Cancer: A Retrospective Study.

PubMed

Li, Jinyu; You, Junhao; Si, Wen; Zhu, Yanyun; Chen, Yi; Yang, Bo; Han, Chun; Linghu, Ruixia; Zhang, Xingyang; Jiao, Shunchang; Yang, Junlan

2015-10-01

The treatment efficacy of advanced breast cancer is still not promising. This study aimed to compare the efficacy and safety of docetaxel/S-1 (DS1) versus docetaxel/capecitabine (DX) as the first-line treatment for advanced breast cancer.From June 2008 to June 2013, 22 patients with advanced breast cancer were treated with the DS1 regimen. Another 26 age- and disease status-matched patients treated with the DX regimen served as controls. The 2 groups were compared in terms of time to progression (TTP), objective response rate, disease control rate, clinical benefit rate, and safety profiles.Median TTP did not differ significantly between the DS1 group and the DX group (9.04 vs 10.94 months, P = 0.473). There were no significant differences in objective response rate, disease control rate, and clinical benefit rate between the 2 groups. Both the DS1 and the DX regimens showed good tolerability. The 2 regimens showed no significant difference in adverse events except degree III hand-foot syndrome (DS1 0 vs DX 23.1%, P = 0.025).For the first-line treatment of advanced breast cancer, the DS1 and the DX regimens showed similar efficacy and safety. The DS1 regimen had less severe hand-foot syndrome than the DX regimen.

Factors associated with prolonged time to treatment failure with fulvestrant 500 mg in patients with post-menopausal estrogen receptor-positive advanced breast cancer: a sub-group analysis of the JBCRG-C06 Safari study.

PubMed

Kawaguchi, Hidetoshi; Masuda, Norikazu; Nakayama, Takahiro; Aogi, Kenjiro; Anan, Keisei; Ito, Yoshinori; Ohtani, Shoichiro; Sato, Nobuaki; Saji, Shigehira; Takano, Toshimi; Tokunaga, Eriko; Nakamura, Seigo; Hasegawa, Yoshie; Hattori, Masaya; Fujisawa, Tomomi; Morita, Satoshi; Yamaguchi, Miki; Yamashita, Hiroko; Yamashita, Toshinari; Yamamoto, Yutaka; Yotsumoto, Daisuke; Toi, Masakazu; Ohno, Shinji

2018-01-01

The JBCRG-C06 Safari study showed that earlier fulvestrant 500 mg (F500) use, a longer time from diagnosis to F500 use, and no prior palliative chemotherapy were associated with significantly longer time to treatment failure (TTF) among Japanese patients with estrogen receptor-positive (ER+) advanced breast cancer (ABC). The objective of this sub-group analysis was to further examine data from the Safari study, focusing on ER + and human epidermal growth factor receptor-negative (HER2-) cases. The Safari study (UMIN000015168) was a retrospective, multi-center cohort study, conducted in 1,072 patients in Japan taking F500 for ER + ABC. The sub-analysis included only patients administered F500 as second-line or later therapy (n = 960). Of these, 828 patients were HER2-. Results Multivariate analysis showed that advanced age (≥65 years; p = .035), longer time (≥3 years) from ABC diagnosis to F500 use (p < .001), no prior chemotherapy (p < .001), and F500 treatment line (p < .001) were correlated with prolonged TTF (median = 5.39 months). In ER+/HER2- patients receiving F500 as a second-line or later therapy, treatment line, advanced age, no prior palliative chemotherapy use, and a longer period from ABC diagnosis to F500 use were associated with longer TTF.

VICTOR: Vinflunine in advanced metastatic transitional cell carcinoma of the urothelium: A retrospective analysis of the use of vinflunine in multi-centre real life setting as second line chemotherapy through Free of Charge Programme for patients in the UK and Ireland.

PubMed

Hussain, Syed A; Ansari, Jawaher; Huddart, Robert; Power, Derek G; Lyons, Jeanette; Wylie, James; Vilarino-Varlela, Maria; Elander, Nils O; McMenemin, Rhona; Pickering, Lisa M; Faust, Guy; Chauhan, Seema; Jackson, Richard J

2017-03-01

There is no standard of care in the UK or Ireland for second-line chemotherapy for patients with advanced transitional cell carcinoma (TCCU). Vinflunine is approved for TCCU patients who have failed a platinum-based regimen, and is standard of care in Europe but is not routinely available in the UK. Data were collected retrospectively on patients who received vinfluine as a second-line treatment. The aims were to document the toxicity and efficacy in a real life setting. Data were collected on 49 patients from 9 sites across the UK and Ireland [median age, 64 (IQR, 57-70) years, 33 males]. All patients had advanced metastatic TCCU. Thirteen patients had bone or liver metastases, 4 patients had PS 2 and 11 patients had HB <10. Median vinflunine administration was 3.5 cycles (range 1-18). Most common grade 3-4 toxicities were constipation (4 patients) and fatigue (3 patients). Partial response rate was 29% (14 PR, 11 SD, 19 PD, 4 NE, 1 not available). Median OS was 9.1 (6.0, 12.7) months. Results are consistent with real life data from Europe. Toxicity is further reduced with prophylactic laxative and oral antibiotics. Vinflunine is an efficient and tolerable second line treatment in advanced TCCU.

Second-line chemotherapy in advanced biliary cancer progressed to first-line platinum-gemcitabine combination: a multicenter survey and pooled analysis with published data.

PubMed

Fornaro, Lorenzo; Vivaldi, Caterina; Cereda, Stefano; Leone, Francesco; Aprile, Giuseppe; Lonardi, Sara; Silvestris, Nicola; Santini, Daniele; Milella, Michele; Caparello, Chiara; Musettini, Gianna; Pasquini, Giulia; Falcone, Alfredo; Brandi, Giovanni; Sperduti, Isabella; Vasile, Enrico

2015-12-23

After progression to a standard first-line platinum and gemcitabine combination (GP), there is no established second-line therapy for patients with advanced biliary tract cancers (aBTC). Indeed, literature data suggest limited activity of most second-line agents evaluated so far. We collected a large retrospective series of aBTC patients treated with second-line chemotherapy after progression to a first-line GP regimen at different Italian institutions. We then pooled the data with those reported in previous studies, which were identified with a Medline search and the on-line abstract datasets of major international oncology meetings. A total of 174 patients were included in the multicenter survey: response rate (RR) with second-line chemotherapy was low (3.4 %), with median PFS and OS of 3.0 months and 6.6 months, respectively. At multivariate analysis, preserved performance status, low CA19.9 levels and absence of distant metastases were favorable prognostic factors. Data from other five presented or published series were identified, for a total of 499 patients included in the pooled analysis. The results confirmed marginal activity of second-line chemotherapy (RR: 10.2 %), with limited efficacy in unselected patient populations (median PFS: 3.1 months; median OS: 6.3 months). The current analysis highlights the limited value of second-line chemotherapy after a first-line GP combination in aBTC. While waiting for effective biologic agents in this setting, ongoing randomized trials will identify the optimal second-line chemotherapy regimen and validate prognostic factors for individual patient management.

Control and acquisition systems for new scanning transmission x-ray microscopes at Advanced Light Source (abstract)

NASA Astrophysics Data System (ADS)

Tyliszczak, T.; Hitchcock, P.; Kilcoyne, A. L. D.; Ade, H.; Hitchcock, A. P.; Fakra, S.; Steele, W. F.; Warwick, T.

2002-03-01

Two new scanning x-ray transmission microscopes are being built at beamline 5.3.2 and beamline 7.0 of the Advanced Light Source that have novel aspects in their control and acquisition systems. Both microscopes use multiaxis laser interferometry to improve the precision of pixel location during imaging and energy scans as well as to remove image distortions. Beam line 5.3.2 is a new beam line where the new microscope will be dedicated to studies of polymers in the 250-600 eV energy range. Since this is a bending magnet beam line with lower x-ray brightness than undulator beam lines, special attention is given to the design not only to minimize distortions and vibrations but also to optimize the controls and acquisition to improve data collection efficiency. 5.3.2 microscope control and acquisition is based on a PC computer running WINDOWS 2000. All mechanical stages are moved by stepper motors with rack mounted controllers. A dedicated counter board is used for counting and timing and a multi-input/output board is used for analog acquisition and control of the focusing mirror. A three axis differential laser interferometer is being used to improve stability and precision by careful tracking of the relative positions of the sample and zone plate. Each axis measures the relative distance between a mirror placed on the sample stage and a mirror attached to the zone plate holder. Agilent Technologies HP 10889A servo-axis interferometer boards are used. While they were designed to control servo motors, our tests show that they can be used to directly control the piezo stage. The use of the interferometer servo-axis boards provides excellent point stability for spectral measurements. The interferometric feedback also provides active vibration isolation which reduces deleterious impact of mechanical vibrations up to 20-30 Hz. It also can improve the speed and precision of image scans. Custom C++ software has been written to provide user friendly control of the microscope and integration with visual light microscopy indexing of the samples. The beam line 7.0 microscope upgrade is a new design which will replace the existing microscope. The design is similar to that of beam line 5.3.2, including interferometric position encoding. However the acquisition and control is based on VXI systems, a Sun computer, and LABVIEW™ software. The main objective of the BL 7.0 microscope upgrade is to achieve precise image scans at very high speed (pixel dwells as short as 10 μs) to take full advantage of the high brightness of the 7.0 undulator beamline. Results of tests and a discussion of the benefits of our scanning microscope designs will be presented.

26 CFR 1.36B-4 - Reconciling the premium tax credit with advance credit payments.

Code of Federal Regulations, 2014 CFR

2014-04-01

... taxpayer whose household income is less than 400 percent of the Federal poverty line is limited to the... tax limitation table. Household income percentage of Federal poverty line Limitation amount for... projects A's 2014 household income to be $27,925 (250 percent of the Federal poverty line for a family of...

26 CFR 1.36B-4 - Reconciling the premium tax credit with advance credit payments.

Code of Federal Regulations, 2013 CFR

2013-04-01

... taxpayer whose household income is less than 400 percent of the Federal poverty line is limited to the... tax limitation table. Household income percentage of Federal poverty line Limitation amount for... projects A's 2014 household income to be $27,925 (250 percent of the Federal poverty line for a family of...

Recent advances of in vitro culture systems for spermatogonial stem cells in mammals.

PubMed

Sahare, Mahesh G; Suyatno; Imai, Hiroshi

2018-04-01

Spermatogonial stem cells (SSCs) in the mammalian testis are unipotent stem cells for spermatozoa. They show unique cell characteristics as stem cells and germ cells after being isolated from the testis and cultured in vitro. This review introduces recent progress in the development of culture systems for the establishment of SSC lines in mammalian species, including humans. Based on the published reports, the isolation and purification of SSCs, identification and characteristics of SSCs, and culture system for mice, humans, and domestic animals have been summarized. In mice, cell lines from SSCs are established and can be reprogrammed to show pluripotent stem cell potency that is similar to embryonic stem cells. However, it is difficult to establish cell lines for animals other than mice because of the dearth of understanding about species-specific requirements for growth factors and mechanisms supporting the self-renewal of cultured SSCs. Among the factors that are associated with the development of culture systems, the enrichment of SSCs that are isolated from the testis and the combination of growth factors are essential. Providing an example of SSC culture in cattle, a rational consideration was made about how it can be possible to establish cell lines from neonatal and immature testes.

Current and future perspectives on the development ...

EPA Pesticide Factsheets

Safety-related problems continue to be one of the major reasons of attrition in drug development. Non-testing approaches to predict toxicity could form part of the solution. This review provides a perspective of current status of non-testing approaches available for the prediction of different toxicity endpoints. A framework for the development, evaluation and assessment of (Q)SARs is presented together with several examples. A workflow for performing read-across predictions within category and analogue approaches is presented and the shortcomings discussed. In light of the advances in high throughput (HT) approaches and constructs such as adverse outcome pathways (AOPs) coming on-line to help in interpreting such HT data, the ways in which non-testing approaches are developed are also evolving. We discuss what the future of these approaches might look like and outline how their integration could be useful in screening toxicity for drug development. Invited review article for CRT for a special issue.

Extraction and Analysis of Display Data

NASA Technical Reports Server (NTRS)

Land, Chris; Moye, Kathryn

2008-01-01

The Display Audit Suite is an integrated package of software tools that partly automates the detection of Portable Computer System (PCS) Display errors. [PCS is a lap top computer used onboard the International Space Station (ISS).] The need for automation stems from the large quantity of PCS displays (6,000+, with 1,000,000+ lines of command and telemetry data). The Display Audit Suite includes data-extraction tools, automatic error detection tools, and database tools for generating analysis spread sheets. These spread sheets allow engineers to more easily identify many different kinds of possible errors. The Suite supports over 40 independent analyses, 16 NASA Tech Briefs, November 2008 and complements formal testing by being comprehensive (all displays can be checked) and by revealing errors that are difficult to detect via test. In addition, the Suite can be run early in the development cycle to find and correct errors in advance of testing.

Brake Lining for Transit Buses - Bonded vs. Bolted

DOT National Transportation Integrated Search

1985-06-01

This report points out an often cited complaint from urban transit agencies concerning the Advanced Design Bus: the relatively short brake lining life. Despite design improvements made by the equipment supply industry since the introduction of the AD...

Challenges of advanced hepatocellular carcinoma

PubMed Central

Colagrande, Stefano; Inghilesi, Andrea L; Aburas, Sami; Taliani, Gian G; Nardi, Cosimo; Marra, Fabio

2016-01-01

Hepatocellular carcinoma (HCC) is an aggressive malignancy, resulting as the third cause of death by cancer each year. The management of patients with HCC is complex, as both the tumour stage and any underlying liver disease must be considered conjointly. Although surveillance by imaging, clinical and biochemical parameters is routinely performed, a lot of patients suffering from cirrhosis have an advanced stage HCC at the first diagnosis. Advanced stage HCC includes heterogeneous groups of patients with different clinical condition and radiological features and sorafenib is the only approved treatment according to Barcelona Clinic Liver Cancer. Since the introduction of sorafenib in clinical practice, several phase III clinical trials have failed to demonstrate any superiority over sorafenib in the frontline setting. Loco-regional therapies have also been tested as first line treatment, but their role in advanced HCC is still matter of debate. No single agent or combination therapies have been shown to impact outcomes after sorafenib failure. Therefore this review will focus on the range of experimental therapeutics for patients with advanced HCC and highlights the successes and failures of these treatments as well as areas for future development. Specifics such as dose limiting toxicity and safety profile in patients with liver dysfunction related to the underlying chronic liver disease should be considered when developing therapies in HCC. Finally, robust validated and reproducible surrogate end-points as well as predictive biomarkers should be defined in future randomized trials. PMID:27678348

Updates in the genetic evaluation of the child with global developmental delay or intellectual disability.

PubMed

Flore, Leigh Anne; Milunsky, Jeff M

2012-12-01

Global developmental delay (GDD) and intellectual disability (ID) occur in up to 3% of the general population and are even more commonly encountered in the setting of the pediatric neurology clinic. New advances in technology and in the understanding of genetic disorders have led to changes in the diagnostic approach to a child with unexplained GDD or ID. Chromosomal microarray has become a first-line test for evaluation of patients in this population and has both significantly increased diagnostic yield and introduced new challenges in the interpretation of copy number variants of uncertain significance. The G-banded karyotype is now frequently utilized as an adjunct to the microarray rather than as a first-line test in individuals with GDD or ID. Fragile X DNA testing continues to be recommended in the initial evaluation of the child with GDD or ID. The presence or absence of certain cardinal features (such as microcephaly or macrocephaly, seizures, autism, abnormal neurologic examination, and facial dysmorphism) can be utilized to direct single-gene molecular testing. The availability of next-generation and massively parallel sequencing technologies has enabled the use of genetic testing panels, in which dozens of genes associated with GDD or ID may be rapidly analyzed. Most recently, the clinical availability of whole-genome and whole-exome sequencing has opened new possibilities for the evaluation of individuals with GDD or ID who have previously eluded a genetic diagnosis. Consultation with a medical geneticist is recommended when progressing beyond first-tier analyses to most efficiently prioritize testing. Copyright © 2012 Elsevier Inc. All rights reserved.

The ECLSS Advanced Automation Project Evolution and Technology Assessment

NASA Technical Reports Server (NTRS)

Dewberry, Brandon S.; Carnes, James R.; Lukefahr, Brenda D.; Rogers, John S.; Rochowiak, Daniel M.; Mckee, James W.; Benson, Brian L.

1990-01-01

Viewgraphs on Environmental Control and Life Support System (ECLSS) advanced automation project evolution and technology assessment are presented. Topics covered include: the ECLSS advanced automation project; automatic fault diagnosis of ECLSS subsystems descriptions; in-line, real-time chemical and microbial fluid analysis; and object-oriented, distributed chemical and microbial modeling of regenerative environmental control systems description.

Hydrogen, CNG, and HCNG Dispenser System – Prototype Report

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

James Francfort

2005-02-01

The U.S. Department of Energy’s Advanced Vehicle Testing Activity is currently testing a prototype gaseous fuel dispenser developed by the Electric Transportation Engineering Corporation (ETEC). The dispenser (Figure 1) delivers three types of fuels: 100% hydrogen, 100% compressed natural gas (CNG), and blends of hydrogen and CNG (HCNG) using two independent single nozzles (Figure 2). The nozzle for the 100% hydrogen dispensing is rated at 5,000 psig and used solely for 100% hydrogen fuel. The second nozzle is rated at 3,600 psig and is used for both CNG and HCNG fuels. This nozzle connects to both a CNG supply linemore » and a hydrogen supply line and blends the hydrogen and CNG to supply HCNG levels of 15, 20, 30, and 50% (by volume).« less

Orthotopic mouse models for the preclinical and translational study of targeted therapies against metastatic human thyroid carcinoma with BRAFV600E or wild-type BRAF

PubMed Central

Antonello, ZA; Nucera, C

2015-01-01

Molecular signature of advanced and metastatic thyroid carcinoma involves deregulation of multiple fundamental pathways activated in the tumor microenvironment. They include BRAFV600E and AKT that affect tumor initiation, progression and metastasis. Human thyroid cancer orthotopic mouse models are based on human cell lines that generally harbor genetic alterations found in human thyroid cancers. They can reproduce in vivo and in situ (into the thyroid) many features of aggressive and refractory human advanced thyroid carcinomas, including local invasion and metastasis. Humanized orthotopic mouse models seem to be ideal and commonly used for preclinical and translational studies of compounds and therapies not only because they may mimic key aspects of human diseases (e.g. metastasis), but also for their reproducibility. In addition, they might provide the possibility to evaluate systemic effects of treatments. So far, human thyroid cancer in vivo models were mainly used to test single compounds, non selective and selective. Despite the greater antitumor activity and lower toxicity obtained with different selective drugs in respect to non-selective ones, most of them are only able to delay disease progression, which ultimately could restart with similar aggressive behavior. Aggressive thyroid tumors (for example, anaplastic or poorly differentiated thyroid carcinoma) carry several complex genetic alterations that are likely cooperating to promote disease progression and might confer resistance to single-compound approaches. Orthotopic models of human thyroid cancer also hold the potential to be good models for testing novel combinatorial therapies. In this article, we will summarize results on preclinical testing of selective and nonselective single compounds in orthotopic mouse models based on validated human thyroid cancer cell lines harboring the BRAFV600E mutation or with wild-type BRAF. Furthermore, we will discuss the potential use of this model also for combinatorial approaches, which are expected to take place in the upcoming human thyroid cancer basic and clinical research. PMID:24362526

Methamphetamine-induced conditioned place preference in LG/J and SM/J mouse strains and an F45/F46 advanced intercross line.

PubMed

Bryant, Camron D; Kole, Loren A; Guido, Michael A; Cheng, Riyan; Palmer, Abraham A

2012-01-01

The conditioned place preference (CPP) test is frequently used to evaluate the rewarding properties of drugs of abuse in mice. Despite its widespread use in transgenic and knockout experiments, there are few forward genetic studies using CPP to identify novel genes contributing to drug reward. In this study, we tested LG/J and SM/J inbred strains and the parents/offspring of 10 families of an F(45)/F(46) advanced intercross line (AIL) for methamphetamine-induced CPP (MA-CPP) once per week over 2 weeks. Both LG/J and SM/J mice exhibited significant MA-CPP that was not significantly different between the two strains. Furthermore, LG/J mice showed significantly less acute MA-induced locomotor activity as well as locomotor sensitization following subsequent MA injections. AIL mice (N = 105) segregating LG/J and SM/J alleles also demonstrated significant MA-CPP that was equal in magnitude between the first and second week of training. Importantly, MA-CPP in AIL mice did not correlate with drug-free or MA-induced locomotor activity, indicating that MA-CPP was not confounded by test session activity and implying that MA-CPP is genetically distinct from acute psychomotor sensitivity. We estimated the heritability of MA-CPP and locomotor phenotypes using midparent-offspring regression and maximum likelihood estimates derived from the kinship coefficients of the AIL pedigree. Heritability estimates of MA-CPP were low (0-0.21) and variable (SE = 0-0.33) which reflected our poor power to estimate heritability using only 10 midparent-offspring observations. In sum, we established a short-term protocol for MA-CPP in AIL mice that could reveal LG/J and SM/J alleles important for MA reward. The use of highly recombinant genetic populations like AIL should facilitate the identification of these genes and may have implications for understanding psychostimulant abuse in humans.

Evaluation of bike boxes at signalized intersections.

DOT National Transportation Integrated Search

2011-01-01

This report presents a before-after study of bike boxes at 10 signalized intersections in Portland, Oregon. The bike boxes, also known as advanced stop lines or advanced stop boxes, were installed to increase visibility of cyclists and reduce conflic...

Cost-Effectiveness of Immune Checkpoint Inhibition in BRAF Wild-Type Advanced Melanoma

PubMed Central

Zeichner, Simon B.; Chen, Qiushi; Montero, Alberto J.; Goldstein, Daniel A.; Flowers, Christopher R.

2017-01-01

Purpose Patients who are diagnosed with stage IV metastatic melanoma have an estimated 5-year relative survival rate of only 17%. Randomized controlled trials of recent US Food and Drug Administration–approved immune checkpoint inhibitors—pembrolizumab (PEM), nivolumab (NIVO), and ipilumumab (IPI)—demonstrate improved patient outcomes, but the optimal treatment sequence in patients with BRAF wild-type metastatic melanoma remains unclear. To inform policy makers about the value of these treatments, we developed a Markov model to compare the cost-effectiveness of different strategies for sequencing novel agents for the treatment of advanced melanoma. Materials and Methods We developed Markov models by using a US-payer perspective and lifetime horizon to estimate costs (2016 US$) and quality-adjusted life years (QALYs) for treatment sequences with first-line NIVO, IPI, NIVO + IPI, PEM every 2 weeks, and PEM every 3 weeks. Health states were defined for initial treatment, first and second progression, and death. Rates for drug discontinuation, frequency of adverse events, disease progression, and death obtained from randomized phase III trials were used to determine the likelihood of transition between states. Deterministic and probabilistic sensitivity analyses were conducted to evaluate model uncertainty. Results PEM every 3 weeks followed by second-line IPI was both more effective and less costly than dacarbazine followed by IPI then NIVO, or IPI followed by NIVO. Compared with the first-line dacarbazine treatment strategy, NIVO followed by IPI produced an incremental cost effectiveness ratio of $90,871/QALY, and first-line NIVO + IPI followed by carboplatin plus paclitaxel chemotherapy produced an incremental cost effectiveness ratio of $198,867/QALY. Conclusion For patients with treatment-naive BRAF wild-type advanced melanoma, first-line PEM every 3 weeks followed by second-line IPI or first-line NIVO followed by second-line IPI are the most cost-effective, immune-based treatment strategies for metastatic melanoma. PMID:28221865

A new instrument to assess physician skill at thoracic ultrasound, including pleural effusion markup.

PubMed

Salamonsen, Matthew; McGrath, David; Steiler, Geoff; Ware, Robert; Colt, Henri; Fielding, David

2013-09-01

To reduce complications and increase success, thoracic ultrasound is recommended to guide all chest drainage procedures. Despite this, no tools currently exist to assess proceduralist training or competence. This study aims to validate an instrument to assess physician skill at performing thoracic ultrasound, including effusion markup, and examine its validity. We developed an 11-domain, 100-point assessment sheet in line with British Thoracic Society guidelines: the Ultrasound-Guided Thoracentesis Skills and Tasks Assessment Test (UGSTAT). The test was used to assess 22 participants (eight novices, seven intermediates, seven advanced) on two occasions while performing thoracic ultrasound on a pleural effusion phantom. Each test was scored by two blinded expert examiners. Validity was examined by assessing the ability of the test to stratify participants according to expected skill level (analysis of variance) and demonstrating test-retest and intertester reproducibility by comparison of repeated scores (mean difference [95% CI] and paired t test) and the intraclass correlation coefficient. Mean scores for the novice, intermediate, and advanced groups were 49.3, 73.0, and 91.5 respectively, which were all significantly different (P < .0001). There were no significant differences between repeated scores. Procedural training on mannequins prior to unsupervised performance on patients is rapidly becoming the standard in medical education. This study has validated the UGSTAT, which can now be used to determine the adequacy of thoracic ultrasound training prior to clinical practice. It is likely that its role could be extended to live patients, providing a way to document ongoing procedural competence.

DRACO Flowpath Performance and Environments

NASA Technical Reports Server (NTRS)

Komar, D. R.; McDonald, Jon

1999-01-01

The Advanced Space Transportation (AST) project office has challenged NASA to design, manufacture, ground-test and flight-test an axisymmetric, hydrocarbon-fueled, flight-weight, ejector-ramjet engine system testbed no later than 2005. To accomplish this, a multi-center NASA team has been assembled. The goal of this team, led by NASA-Marshall Space Flight Center (MSFC), is to develop propulsion technologies that demonstrate rocket and airbreathing combined-cycle operation (DRACO). Current technical activities include flowpath conceptual design, engine systems conceptual design, and feasibility studies investigating the integration and operation of the DRACO engine with a Lockheed D-21B drone. This paper focuses on the activities of the Flowpath Systems Product Development Team (PDT), led by NASA-Glenn Research Center (GRC) and supported by NASA-MSFC and TechLand Research, Inc. The objective of the Flowpath PDT at the start of the DRACO program was to establish a conceptual design of the flowpath aerodynamic lines, determine the preliminary performance, define the internal environments, and support the DRACO testbed concept feasibility studies. To accomplish these tasks, the PDT convened to establish a baseline flowpath concept. With the conceptual lines defined, cycle analysis tasks were planned and the flowpath performance and internal environments were defined. Additionally, sensitivity studies investigating the effects of inlet reference area, combustion performance, and combustor/nozzle materials selection were performed to support the Flowpath PDT design process. Results of these tasks are the emphasis of this paper and are intended to verify the feasibility of the DRACO flowpath and engine system as well as identify the primary technical challenges inherent in the flight-weight design of an advanced propulsion technology demonstration engine. Preliminary cycle performance decks were developed to support the testbed concept feasibility studies but are not discussed further in this paper.

Opportunities and challenges of real-time release testing in biopharmaceutical manufacturing.

PubMed

Jiang, Mo; Severson, Kristen A; Love, John Christopher; Madden, Helena; Swann, Patrick; Zang, Li; Braatz, Richard D

2017-11-01

Real-time release testing (RTRT) is defined as "the ability to evaluate and ensure the quality of in-process and/or final drug product based on process data, which typically includes a valid combination of measured material attributes and process controls" (ICH Q8[R2]). This article discusses sensors (process analytical technology, PAT) and control strategies that enable RTRT for the spectrum of critical quality attributes (CQAs) in biopharmaceutical manufacturing. Case studies from the small-molecule and biologic pharmaceutical industry are described to demonstrate how RTRT can be facilitated by integrated manufacturing and multivariable control strategies to ensure the quality of products. RTRT can enable increased assurance of product safety, efficacy, and quality-with improved productivity including faster release and potentially decreased costs-all of which improve the value to patients. To implement a complete RTRT solution, biologic drug manufacturers need to consider the special attributes of their industry, particularly sterility and the measurement of viral and microbial contamination. Continued advances in on-line and in-line sensor technologies are key for the biopharmaceutical manufacturing industry to achieve the potential of RTRT. Related article: http://onlinelibrary.wiley.com/doi/10.1002/bit.26378/full. © 2017 Wiley Periodicals, Inc.

OCGen Module Mooring Project

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

McEntee, Jarlath

Ocean Renewable Power Company's OCGen Module Mooring Project provided an extensive research, design, development, testing and data collection effort and analysis conducted with respect to a positively buoyant, submerged MHK device secured to the seabed using a tensioned mooring system. Different analytic tools were evaluated for their utility in the design of submerged systems and their moorings. Deployment and testing of a prototype OCGen® system provided significant data related to mooring line loads and system attitude and station keeping. Mooring line loads were measured in situ and reported against flow speeds. The Project made a significant step in the developmentmore » of designs, methodologies and practices related to floating and mooring of marine hydrokinetic (MHK) devices. Importantly for Ocean Renewable Power Company, the Project provided a sound basis for advancing a technically and commercially viable OCGen® Power System. The OCGen® Power System is unique in the MHK industry and, in itself, offers distinct advantages of MHK devices that are secured to the seabed using fixed structural frames. Foremost among these advantages are capital and operating cost reductions and increased power extraction by allowing the device to be placed at the most energetic level of the water column.« less

Immunotherapy revolutionises non-small-cell lung cancer therapy: Results, perspectives and new challenges.

PubMed

Giroux Leprieur, Etienne; Dumenil, Coraline; Julie, Catherine; Giraud, Violaine; Dumoulin, Jennifer; Labrune, Sylvie; Chinet, Thierry

2017-06-01

Immune checkpoint inhibitors (ICIs) are antibodies that target key signalling pathways such as programmed death 1 (PD1)/programmed death-ligands 1 and 2 (PDL1 and PDL2) to improve anti-tumour immune responses. Until recently, nivolumab was the only ICI validated for advanced non-small-cell lung cancer (NSCLC) in a second-line treatment setting. Results from recent phase II and phase III randomised trials testing other ICIs have been presented. In Keynote-024, pembrolizumab, an anti-PD1 antibody, was reported to have great efficacy in the first-line treatment of PDL1 ≥ 50% tumours (30% of screened tumours), with a progression-free survival (PFS, median) of 10.4 months versus 6.0 months with chemotherapy (CT; hazard ratio [HR] = 0.50; 95% confidence interval [95% CI] 0.37-0.68, P < 0.001), overall response rate (ORR) of 45% versus 28% with CT (P = 0.0011), and a 1-year overall survival (OS) of around 70%. In contrast, Checkmate-026 reported that nivolumab failed to show any benefit compared with standard platinum-based CT, with a PFS (median) in the PDL1 ≥ 5% NSCLC group of 4.2 months (nivolumab) versus 5.9 months (CT; HR = 1.15: 95% CI 0.91-1.45, P = 0.25). No benefit was observed in the PDL1 ≥ 50% subgroup. An encouraging report of the efficacy of pembrolizumab in addition to CT in first-line treatment in unselected NSCLC was also presented (Keynote-021) with an ORR of 55% versus 29% with CT alone (P = 0.0016). Atezolizumab, an anti-PDL1 antibody, showed efficacy for second-line treatment compared with docetaxel (OAK phase III study) with an OS (median) of 13.8 months versus 9.6 months with docetaxel. These results suggest a new paradigm for the treatment of advanced NSCLC using pembrolizumab for the first-line treatment of PDL1 ≥ 50% tumours. Copyright © 2017. Published by Elsevier Ltd.

Pacific Pediatric Advanced Care Initiative

DTIC Science & Technology

2009-10-01

Prepare IV ports:  Identify IV ports (UVC, Femoral venous line, other central venous lines, or PIV) for easy access to push meds or administer volume...Supply Department CVL central venous line CXR chest xray DC discontinue DI Diagnostic Imaging DIC disseminated intravascular coagulation diff...programs at KMCWC. These include the blood bank, blood utilization committee, clinical laboratories, operating room, central supply, pharmacy

Reliable in vitro studies require appropriate ovarian cancer cell lines

PubMed Central

2014-01-01

Ovarian cancer is the fifth most common cause of cancer death in women and the leading cause of death from gynaecological malignancies. Of the 75% women diagnosed with locally advanced or disseminated disease, only 30% will survive five years following treatment. This poor prognosis is due to the following reasons: limited understanding of the tumor origin, unclear initiating events and early developmental stages of ovarian cancer, lack of reliable ovarian cancer-specific biomarkers, and drug resistance in advanced cases. In the past, in vitro studies using cell line models have been an invaluable tool for basic, discovery-driven cancer research. However, numerous issues including misidentification and cross-contamination of cell lines have hindered research efforts. In this study we examined all ovarian cancer cell lines available from cell banks. Hereby, we identified inconsistencies in the reporting, difficulties in the identification of cell origin or clinical data of the donor patients, restricted ethnic and histological type representation, and a lack of tubal and peritoneal cancer cell lines. We recommend that all cell lines should be distributed via official cell banks only with strict guidelines regarding the minimal available information required to improve the quality of ovarian cancer research in future. PMID:24936210

Role of regorafenib as second-line therapy and landscape of investigational treatment options in advanced hepatocellular carcinoma

PubMed Central

Trojan, Jörg; Waidmann, Oliver

2016-01-01

Sorafenib is still the only systemic drug approved for the treatment of advanced hepatocellular carcinoma (HCC). In recent years, several investigational agents mainly targeting angiogenesis failed in late-phase clinical development due to either toxicity or lack of benefit. Recently, data of the RESORCE trial, a placebo-controlled Phase III study that evaluated the efficacy and safety of regorafenib in patients with HCC and documented disease progression after systemic first-line treatment with sorafenib, were presented at the ESMO World Congress on Gastrointestinal Cancer, 2016. Regorafenib treatment resulted in a 2.8-month survival benefit compared to placebo (10.6 months vs 7.8 months). Side effects were consistent with the known profile of regorafenib. The approval of regorafenib for this indication is expected in 2017. Further candidate agents in Phase III evaluation for second-line treatment of patients with HCC are the MET inhibitors tivantinib and cabozantinib, the vascular endothelial growth factor receptor-2 antibody ramucirumab, and the programmed death receptor-1 (PD-1) blocking antibody pembrolizumab. Furthermore, results from two first-line trials with either the tyrosine kinase inhibitor lenvatinib or the PD-1 antibody nivolumabin in comparison to sorafenib are awaited in the near future and might further change the treatment sequence of advanced HCC. PMID:27703962

Role of regorafenib as second-line therapy and landscape of investigational treatment options in advanced hepatocellular carcinoma.

PubMed

Trojan, Jörg; Waidmann, Oliver

2016-01-01

Sorafenib is still the only systemic drug approved for the treatment of advanced hepatocellular carcinoma (HCC). In recent years, several investigational agents mainly targeting angiogenesis failed in late-phase clinical development due to either toxicity or lack of benefit. Recently, data of the RESORCE trial, a placebo-controlled Phase III study that evaluated the efficacy and safety of regorafenib in patients with HCC and documented disease progression after systemic first-line treatment with sorafenib, were presented at the ESMO World Congress on Gastrointestinal Cancer, 2016. Regorafenib treatment resulted in a 2.8-month survival benefit compared to placebo (10.6 months vs 7.8 months). Side effects were consistent with the known profile of regorafenib. The approval of regorafenib for this indication is expected in 2017. Further candidate agents in Phase III evaluation for second-line treatment of patients with HCC are the MET inhibitors tivantinib and cabozantinib, the vascular endothelial growth factor receptor-2 antibody ramucirumab, and the programmed death receptor-1 (PD-1) blocking antibody pembrolizumab. Furthermore, results from two first-line trials with either the tyrosine kinase inhibitor lenvatinib or the PD-1 antibody nivolumabin in comparison to sorafenib are awaited in the near future and might further change the treatment sequence of advanced HCC.

Results from a new 193nm die-to-database reticle inspection platform

NASA Astrophysics Data System (ADS)

Broadbent, William H.; Alles, David S.; Giusti, Michael T.; Kvamme, Damon F.; Shi, Rui-fang; Sousa, Weston L.; Walsh, Robert; Xiong, Yalin

2010-05-01

A new 193nm wavelength high resolution reticle defect inspection platform has been developed for both die-to-database and die-to-die inspection modes. In its initial configuration, this innovative platform has been designed to meet the reticle qualification requirements of the IC industry for the 22nm logic and 3xhp memory generations (and shrinks) with planned extensions to the next generation. The 22nm/3xhp IC generation includes advanced 193nm optical lithography using conventional RET, advanced computational lithography, and double patterning. Further, EUV pilot line lithography is beginning. This advanced 193nm inspection platform has world-class performance and the capability to meet these diverse needs in optical and EUV lithography. The architecture of the new 193nm inspection platform is described. Die-to-database inspection results are shown on a variety of reticles from industry sources; these reticles include standard programmed defect test reticles, as well as advanced optical and EUV product and product-like reticles. Results show high sensitivity and low false and nuisance detections on complex optical reticle designs and small feature size EUV reticles. A direct comparison with the existing industry standard 257nm wavelength inspection system shows measurable sensitivity improvement for small feature sizes

Completion summary for borehole USGS 136 near the Advanced Test Reactor Complex, Idaho National Laboratory, Idaho

USGS Publications Warehouse

Twining, Brian V.; Bartholomay, Roy C.; Hodges, Mary K.V.

2012-01-01

In 2011, the U.S. Geological Survey, in cooperation with the U.S. Department of Energy, cored and completed borehole USGS 136 for stratigraphic framework analyses and long-term groundwater monitoring of the eastern Snake River Plain aquifer at the Idaho National Laboratory. The borehole was initially cored to a depth of 1,048 feet (ft) below land surface (BLS) to collect core, open-borehole water samples, and geophysical data. After these data were collected, borehole USGS 136 was cemented and backfilled between 560 and 1,048 ft BLS. The final construction of borehole USGS 136 required that the borehole be reamed to allow for installation of 6-inch (in.) diameter carbon-steel casing and 5-in. diameter stainless-steel screen; the screened monitoring interval was completed between 500 and 551 ft BLS. A dedicated pump and water-level access line were placed to allow for aquifer testing, for collecting periodic water samples, and for measuring water levels.Geophysical and borehole video logs were collected after coring and after the completion of the monitor well. Geophysical logs were examined in conjunction with the borehole core to describe borehole lithology and to identify primary flow paths for groundwater, which occur in intervals of fractured and vesicular basalt.A single-well aquifer test was used to define hydraulic characteristics for borehole USGS 136 in the eastern Snake River Plain aquifer. Specific-capacity, transmissivity, and hydraulic conductivity from the aquifer test were at least 975 gallons per minute per foot, 1.4 × 105 feet squared per day (ft2/d), and 254 feet per day, respectively. The amount of measureable drawdown during the aquifer test was about 0.02 ft. The transmissivity for borehole USGS 136 was in the range of values determined from previous aquifer tests conducted in other wells near the Advanced Test Reactor Complex: 9.5 × 103 to 1.9 × 105 ft2/d.Water samples were analyzed for cations, anions, metals, nutrients, total organic carbon, volatile organic compounds, stable isotopes, and radionuclides. Water samples from borehole USGS 136 indicated that concentrations of tritium, sulfate, and chromium were affected by wastewater disposal practices at the Advanced Test Reactor Complex. Depth-discrete groundwater samples were collected in the open borehole USGS 136 near 965, 710, and 573 ft BLS using a thief sampler; on the basis of selected constituents, deeper groundwater samples showed no influence from wastewater disposal at the Advanced Test Reactor Complex.

Patient Comprehension and Attitudes toward Maintenance Chemotherapy for Lung Cancer

PubMed Central

Gerber, David E.; Hamann, Heidi A.; Rasco, Drew W.; Woodruff, Sharon; Craddock Lee, Simon J.

2012-01-01

Objective Maintenance chemotherapy is a recently approved approach to the treatment of advanced non-small cell lung cancer (NSCLC). We sought to gain insight into patients’ perceptions of maintenance chemotherapy using qualitative methods. Methods We conducted thematic content analysis of focus groups at a freestanding cancer center and at an associated safety-net county hospital. Patients with advanced NSCLC who had started but not yet completed first-line platinum doublet chemotherapy were provided visual and written explanations of maintenance chemotherapy before being guided in group discussion. Results Key themes to emerge for consideration of maintenance chemotherapy included (1) survival benefits, disease control, and “buying time”; (2) the importance of “doing something”; (3) quality of life concerns; (4) the role of provider opinion/preference; and (5) the importance of logistics. Conclusions Patients undergoing first-line chemotherapy for advanced NSCLC were able to understand the concept of maintenance chemotherapy, distinguish it from traditional treatment paradigms, identify pros and cons of this approach, and convey reasons for considering it. Practice Implications Advances in oncology care that alter therapy modalities and delivery may significantly impact patient perceptions and treatment experiences. Clinical team members may wish to elicit treatment preferences of first-line patients through clinical discussions that anticipate these considerations. PMID:22632736

Clinical cancer advances 2006: major research advances in cancer treatment, prevention, and screening--a report from the American Society of Clinical Oncology.

PubMed

Ozols, Robert F; Herbst, Roy S; Colson, Yolonda L; Gralow, Julie; Bonner, James; Curran, Walter J; Eisenberg, Burton L; Ganz, Patricia A; Kramer, Barnett S; Kris, Mark G; Markman, Maurie; Mayer, Robert J; Raghavan, Derek; Reaman, Gregory H; Sawaya, Raymond; Schilsky, Richard L; Schuchter, Lynn M; Sweetenham, John W; Vahdat, Linda T; Winn, Rodger J

2007-01-01

A MESSAGE FROM ASCO's PRESIDENT For the second consecutive year, the American Society of Clinical Oncology (ASCO) is publishing Clinical Cancer Advances: Major Research Advances in Cancer Treatment, Prevention, and Screening, an annual review of the most significant cancer research presented or published over the past year. ASCO developed this report to demonstrate the enormous progress being made on the front lines of cancer research today. The report is intended to give all those with an interest in cancer care-the general public, cancer patients and physicians, policymakers, oncologists, and other medical professionals-an accessible summary of the year's most important cancer research advances. These pages report on new targeted therapies that are improving survival and response rates in hard-to-treat cancers such as kidney cancer, HER-2-positive breast cancer, head and neck cancer, and chronic myelogenous leukemia; the FDA's approval of the world's first preventive vaccine for human papillomavirus (HPV), which has the potential to dramatically reduce the global burden of cervical cancer; and advances in the fast-growing field of personalized medicine, including a new lung cancer test that could help physicians better target treatments and predict prognosis. These advances are only part of the landscape. Survival rates are on the rise, the number of cancer deaths in the United States began declining for the first time since 1930, and new research is showing that the rates of certain common cancers, such as those of the breast and colon, have stabilized, and may have even begun to decline. However, cancer research still faces a number of major obstacles. At a time of extraordinary scientific potential, declining federal funding of cancer research threatens to stall or even reverse recent progress. Such funding cuts have already led to fewer clinical trials, fewer talented young physicians entering the field, and a growing bottleneck of basic science discoveries waiting to be "translated" into useful therapies and diagnostics. In addition to highlighting the major research advances over the past year, this report also identifies key barriers to accelerating the pace of cancer research and outlines ASCO's recommendations for overcoming them. Despite these and other challenges, there is much good news on the front lines of cancer research. This report demonstrates the essential role of clinical cancer research in finding new and better ways to treat, diagnose, and prevent a group of diseases that strike half of men and one-third of women in the United States.

AEOLUS mission: the latest preparations before launch

NASA Astrophysics Data System (ADS)

Culoma, A.; Elfving, A.; Meynart, R.; Straume, A.; Wernham, D.

2017-09-01

The European Space Agency is developing a direct detection Doppler Wind Lidar for measuring wind profiles from space. The main objective of Aeolus is to provide tropospheric and lower stratospheric wind profiles globally for the improvement of weather forecast on short and medium term. Aeolus data are expected to greatly contribute to weather and air quality monitoring and to scientific advances in atmospheric dynamics. The UV Lidar instrument, ALADIN, will deliver horizontally-projected single line-of-sight wind profiles from the Doppler shift of molecular and particle backscatter. The development of the AEOLUS mission passed a major milestone with the integration of the full instrument and its functional and performance tests in 2016 and a 6-month life test of the spare UV laser transmitter. The satellite has been assembled and has successfully been subjected to a programme of functional and environmental (vibration, acoustic, shock, EMC) tests. The preparation of thermal vacuum testing, including instrument performance in vacuum, is close to completion.

In-line height profiling metrology sensor for zero defect production control

NASA Astrophysics Data System (ADS)

Snel, Rob; Winters, Jasper; Liebig, Thomas; Jonker, Wouter

2017-06-01

Contemporary production systems of mechanical precision parts show challenges as increased complexity, tolerances shrinking to sub-microns and yield losses that must be mastered to the extreme. More advanced automation and process control is required to accomplish this task. Often a solution based on feedforward/feedback control is chosen requiring innovative and more advanced in line metrology. This article concentrates first on the context of in line metrology for process control and then on the development of a specific in line height profiling sensor. The novel sensor technology is based on full field time domain white light interferometry which is well know from the quality lab. The novel metrology system is to be mounted close to the production equipment, as required to minimize time delay in the control loop, and is thereby fully exposed to vibrations. This sensor is innovated to perform in line with an orders of magnitude faster throughput than laboratory instruments; it's robust to withstand the rigors of workshops and has a height resolution that is in the nanometer range.

Advanced propeller aerodynamic analysis

NASA Technical Reports Server (NTRS)

Bober, L. J.

1980-01-01

The analytical approaches as well as the capabilities of three advanced analyses for predicting propeller aerodynamic performance are presented. It is shown that two of these analyses use a lifting line representation for the propeller blades, and the third uses a lifting surface representation.

Marketing potential of advanced breeding clones

USDA-ARS?s Scientific Manuscript database

The accumulation of reducing sugars during cold storage of potato tubers is a serious and costly problem for producers and processors. The degree to which cultivars accumulate reducing sugars during storage determines their processing and market potential. Cultivars or advanced breeding lines with...

Prospective Study of the Evolution of Blood Lymphoid Immune Parameters during Dacarbazine Chemotherapy in Metastatic and Locally Advanced Melanoma Patients

PubMed Central

Vabres, Pierre; Dalac, Sophie; Jeudy, Geraldine; Bel, Blandine; Apetoh, Lionel; Ghiringhelli, François

2014-01-01

Background The importance of immune responses in the control of melanoma growth is well known. However, the implication of these antitumor immune responses in the efficacy of dacarbazine, a cytotoxic drug classically used in the treatment of melanoma, remains poorly understood in humans. Methods In this prospective observational study, we performed an immunomonitoring of eleven metastatic or locally advanced patients treated with dacarbazine as a first line of treatment. We assessed by flow cytometry lymphoid populations and their activation state; we also isolated NK cells to perform in vitro cytotoxicity tests. Results We found that chemotherapy induces lymphopenia and that a significantly higher numbers of naïve CD4+ T cells and lower proportion of Treg before chemotherapy are associated with disease control after dacarbazine treatment. Interestingly, NK cell cytotoxicity against dacarbazine-pretreated melanoma cells is only observed in NK cells from patients who achieved disease control. Conclusion Together, our data pinpoint that some immune factors could help to predict the response of melanoma patients to dacarbazine. Future larger scale studies are warranted to test their validity as prediction markers. PMID:25170840

Comparative cognitive effects of bilateral subthalamic stimulation and subcutaneous continuous infusion of apomorphine in Parkinson's disease.

PubMed

Alegret, Montse; Valldeoriola, Francesc; Martí, MaJosé; Pilleri, Manuela; Junqué, Carme; Rumià, Jordi; Tolosa, Eduardo

2004-12-01

Bilateral subthalamic deep brain stimulation (STN-DBS) and continuous subcutaneous infusion of apomorphine (APM-csi) can provide a comparable improvement on motor function in patients with advanced Parkinson's disease (PD), but the mechanisms by which both therapies exert their effects are different. We analyzed the cognitive effects of APM-csi. We also compared neuropsychological effects induced by STN-DBS and APM-csi in advanced PD to ascertain the neuropsychological aspects relevant in determining the therapeutic procedure that is the most appropriate in a particular patient. We studied 9 patients treated with STN-DBS and 7 patients with APM-csi. Neuropsychological measures included Rey's Auditory-Verbal Learning, Stroop, Trail Making, phonetic verbal fluency, and Judgment of Line Orientation tests. In the APM-csi group, significant changes were not observed in the neuropsychological tests performance. By contrast, in the STN-DBS group, moderate worsening was found in phonetic verbal fluency and Stroop Naming scores that was partially reversible at long-term follow-up and did not have consequences on regular activities. Consequently, these findings could be interpreted as being not relevant in deciding the most suitable treatment in a given patient. 2004 Movement Disorder Society.

A Universal and Robust Integrated Platform for the Scalable Production of Human Cardiomyocytes From Pluripotent Stem Cells.

PubMed

Fonoudi, Hananeh; Ansari, Hassan; Abbasalizadeh, Saeed; Larijani, Mehran Rezaei; Kiani, Sahar; Hashemizadeh, Shiva; Zarchi, Ali Sharifi; Bosman, Alexis; Blue, Gillian M; Pahlavan, Sara; Perry, Matthew; Orr, Yishay; Mayorchak, Yaroslav; Vandenberg, Jamie; Talkhabi, Mahmood; Winlaw, David S; Harvey, Richard P; Aghdami, Nasser; Baharvand, Hossein

2015-12-01

Recent advances in the generation of cardiomyocytes (CMs) from human pluripotent stem cells (hPSCs), in conjunction with the promising outcomes from preclinical and clinical studies, have raised new hopes for cardiac cell therapy. We report the development of a scalable, robust, and integrated differentiation platform for large-scale production of hPSC-CM aggregates in a stirred suspension bioreactor as a single-unit operation. Precise modulation of the differentiation process by small molecule activation of WNT signaling, followed by inactivation of transforming growth factor-β and WNT signaling and activation of sonic hedgehog signaling in hPSCs as size-controlled aggregates led to the generation of approximately 100% beating CM spheroids containing virtually pure (∼90%) CMs in 10 days. Moreover, the developed differentiation strategy was universal, as demonstrated by testing multiple hPSC lines (5 human embryonic stem cell and 4 human inducible PSC lines) without cell sorting or selection. The produced hPSC-CMs successfully expressed canonical lineage-specific markers and showed high functionality, as demonstrated by microelectrode array and electrophysiology tests. This robust and universal platform could become a valuable tool for the mass production of functional hPSC-CMs as a prerequisite for realizing their promising potential for therapeutic and industrial applications, including drug discovery and toxicity assays. Recent advances in the generation of cardiomyocytes (CMs) from human pluripotent stem cells (hPSCs) and the development of novel cell therapy strategies using hPSC-CMs (e.g., cardiac patches) in conjunction with promising preclinical and clinical studies, have raised new hopes for patients with end-stage cardiovascular disease, which remains the leading cause of morbidity and mortality globally. In this study, a simplified, scalable, robust, and integrated differentiation platform was developed to generate clinical grade hPSC-CMs as cell aggregates under chemically defined culture conditions. This approach resulted in approximately 100% beating CM spheroids with virtually pure (∼90%) functional cardiomyocytes in 10 days from multiple hPSC lines. This universal and robust bioprocessing platform can provide sufficient numbers of hPSC-CMs for companies developing regenerative medicine technologies to rescue, replace, and help repair damaged heart tissues and for pharmaceutical companies developing advanced biologics and drugs for regeneration of lost heart tissue using high-throughput technologies. It is believed that this technology can expedite clinical progress in these areas to achieve a meaningful impact on improving clinical outcomes, cost of care, and quality of life for those patients disabled and experiencing heart disease. ©AlphaMed Press.

A Universal and Robust Integrated Platform for the Scalable Production of Human Cardiomyocytes From Pluripotent Stem Cells

PubMed Central

Fonoudi, Hananeh; Ansari, Hassan; Abbasalizadeh, Saeed; Larijani, Mehran Rezaei; Kiani, Sahar; Hashemizadeh, Shiva; Zarchi, Ali Sharifi; Bosman, Alexis; Blue, Gillian M.; Pahlavan, Sara; Perry, Matthew; Orr, Yishay; Mayorchak, Yaroslav; Vandenberg, Jamie; Talkhabi, Mahmood; Winlaw, David S.; Harvey, Richard P.; Aghdami, Nasser

2015-01-01

Recent advances in the generation of cardiomyocytes (CMs) from human pluripotent stem cells (hPSCs), in conjunction with the promising outcomes from preclinical and clinical studies, have raised new hopes for cardiac cell therapy. We report the development of a scalable, robust, and integrated differentiation platform for large-scale production of hPSC-CM aggregates in a stirred suspension bioreactor as a single-unit operation. Precise modulation of the differentiation process by small molecule activation of WNT signaling, followed by inactivation of transforming growth factor-β and WNT signaling and activation of sonic hedgehog signaling in hPSCs as size-controlled aggregates led to the generation of approximately 100% beating CM spheroids containing virtually pure (∼90%) CMs in 10 days. Moreover, the developed differentiation strategy was universal, as demonstrated by testing multiple hPSC lines (5 human embryonic stem cell and 4 human inducible PSC lines) without cell sorting or selection. The produced hPSC-CMs successfully expressed canonical lineage-specific markers and showed high functionality, as demonstrated by microelectrode array and electrophysiology tests. This robust and universal platform could become a valuable tool for the mass production of functional hPSC-CMs as a prerequisite for realizing their promising potential for therapeutic and industrial applications, including drug discovery and toxicity assays. Significance Recent advances in the generation of cardiomyocytes (CMs) from human pluripotent stem cells (hPSCs) and the development of novel cell therapy strategies using hPSC-CMs (e.g., cardiac patches) in conjunction with promising preclinical and clinical studies, have raised new hopes for patients with end-stage cardiovascular disease, which remains the leading cause of morbidity and mortality globally. In this study, a simplified, scalable, robust, and integrated differentiation platform was developed to generate clinical grade hPSC-CMs as cell aggregates under chemically defined culture conditions. This approach resulted in approximately 100% beating CM spheroids with virtually pure (∼90%) functional cardiomyocytes in 10 days from multiple hPSC lines. This universal and robust bioprocessing platform can provide sufficient numbers of hPSC-CMs for companies developing regenerative medicine technologies to rescue, replace, and help repair damaged heart tissues and for pharmaceutical companies developing advanced biologics and drugs for regeneration of lost heart tissue using high-throughput technologies. It is believed that this technology can expedite clinical progress in these areas to achieve a meaningful impact on improving clinical outcomes, cost of care, and quality of life for those patients disabled and experiencing heart disease. PMID:26511653

Design Considerations for Human Rating of Liquid Rocket Engines

NASA Technical Reports Server (NTRS)

Parkinson, Douglas

2010-01-01

I.Human-rating is specific to each engine; a. Context of program/project must be understood. b. Engine cannot be discussed independently from vehicle and mission. II. Utilize a logical combination of design, manufacturing, and test approaches a. Design 1) It is crucial to know the potential ways a system can fail, and how a failure can propagate; 2) Fault avoidance, fault tolerance, DFMR, caution and warning all have roles to play. b. Manufacturing and Assembly; 1) As-built vs. as-designed; 2) Review procedures for assembly and maintenance periodically; and 3) Keep personnel trained and certified. c. There is no substitute for test: 1) Analytical tools are constantly advancing, but still need test data for anchoring assumptions; 2) Demonstrate robustness and explore sensitivities; 3) Ideally, flight will be encompassed by ground test experience. III. Consistency and repeatability is key in production a. Maintain robust processes and procedures for inspection and quality control based upon development and qualification experience; b. Establish methods to "spot check" quality and consistency in parts: 1) Dedicated ground test engines; 2) Random components pulled from the line/lot to go through "enhanced" testing.

Marshall Team Complete Testing for Lunar Atmosphere and Dust Environment Explorer

NASA Technical Reports Server (NTRS)

Swofford, Philip

2013-01-01

Dr. Huu Trinh and his team with the Propulsion Systems and Test Departments at Marshall Space Flight Center in Huntsville, Ala. successfully complete a simulated cold-flow test series on the propulsion system used for the Lunar Atmosphere and Dust Environment Explorer (LADEE) spacecraft. NASA Ames Research Center, Moffett Field, Calif., is leading NASA s work on the development of the LADEE spacecraft, and the Marshall center is the program office for the project. The spacecraft, scheduled for launch this fall, will orbit the Moon and gather information about the lunar atmosphere, conditions near the surface of the Moon, and collect samples of lunar dust. A thorough understanding of these characteristics will address long-standing unknowns, and help scientists understand other planetary bodies as well. The test team at the Marshall center conducted the cold flow test to identify how the fluid flows through the propulsion system feed lines, especially during critical operation modes. The test data will be used to assist the LADEE team in identifying any potential flow issues in the propulsion system, and allow them to address and correct them in advance of the launch.

Cyclophosphamide-hydroxycamptothecin as second-line chemotherapy for advanced Ewing's sarcoma: experience of a single institution.

PubMed

Han, Kun; Sun, Yuanjue; Zhang, Jianjun; He, Aina; Zheng, Shui'er; Shen, Zan; Yao, Yang

2014-06-01

To investigate the feasibility and efficacy of cyclophosphamide (CTX)-hydroxycamptothecin (HCPT) as second-line chemotherapy on advanced Ewing's sarcoma. From April 2009 to November 2010, 27 patients with advanced Ewing's sarcoma who had progressive disease after the first-line chemotherapy regimen of vincristine, dactinomycin and cyclophosphamide and ifosfamide and etoposide were retrospectively reviewed in this analysis. CTX was given (0.6 g/m(2), i.v. push day 1) and HCPT (6 mg/m(2), i.v. drip days 1-5) as second-line chemotherapy every 3 weeks. The primary end-point was overall response rate, the secondary end-point included progression-free, overall survival, disease control rate and toxicities. A total of 134 cycles were given, median four cycles per patient (range 2-6). Overall response rate was 30% and disease control rate was 82%, with two complete response (8%), six partial remission (22%) and 14 stable disease (52%). The median time to progression and overall survival time were 7 months (95% CI 3-10) and 11 months (95% CI 5-18), respectively. Major severe toxicities (grade 3 and 4) were: nausea/vomiting (17%), alopecia (17%); leukopenia (27%) in total cycles. Mild toxicities (grade 1 or 2) were leukopenia (73%), nausea/vomiting (83%), hepatic lesion (14%) and anemia (44%). A CTX-HCPT regimen can control disease progression effectively and the side effects can be tolerable for Chinese advanced Ewing's sarcoma patients. Further assessment is necessary to confirm the safety and efficacy of this treatment. © 2012 Wiley Publishing Asia Pty Ltd.

Three-gradient regular solution model for simple liquids wetting complex surface topologies

PubMed Central

Akerboom, Sabine; Kamperman, Marleen

2016-01-01

Summary We use regular solution theory and implement a three-gradient model for a liquid/vapour system in contact with a complex surface topology to study the shape of a liquid drop in advancing and receding wetting scenarios. More specifically, we study droplets on an inverse opal: spherical cavities in a hexagonal pattern. In line with experimental data, we find that the surface may switch from hydrophilic (contact angle on a smooth surface θY < 90°) to hydrophobic (effective advancing contact angle θ > 90°). Both the Wenzel wetting state, that is cavities under the liquid are filled, as well as the Cassie–Baxter wetting state, that is air entrapment in the cavities under the liquid, were observed using our approach, without a discontinuity in the water front shape or in the water advancing contact angle θ. Therefore, air entrapment cannot be the main reason why the contact angle θ for an advancing water front varies. Rather, the contact line is pinned and curved due to the surface structures, inducing curvature perpendicular to the plane in which the contact angle θ is observed, and the contact line does not move in a continuous way, but via depinning transitions. The pinning is not limited to kinks in the surface with angles θkink smaller than the angle θY. Even for θkink > θY, contact line pinning is found. Therefore, the full 3D-structure of the inverse opal, rather than a simple parameter such as the wetting state or θkink, determines the final observed contact angle. PMID:27826512

Advanced training of specialists in area of fiber-optic communication lines maintenance

NASA Astrophysics Data System (ADS)

Andreev, Vladimir A.; Voronkov, Andrey A.; Bukashkin, Sergey A.; Buzova, Maria A.

2017-04-01

The paper considers the concept of fiber-optic communication lines (FOCL) maintenance. Performance criterion of FOCL technical maintenance was proposed. For the first time the algorithm for evaluation of the FOCL maintenance efficiency at telecommunication specialists training was applied.

Hedgehog Pathway Inhibition Radiosensitizes Non-Small Cell Lung Cancers

PubMed Central

Zeng, Jing; Aziz, Khaled; Chettiar, Sivarajan T.; Aftab, Blake T.; Armour, Michael; Gajula, Rajendra; Gandhi, Nishant; Salih, Tarek; Herman, Joseph M.; Wong, John; Rudin, Charles M.; Tran, Phuoc T.; Hales, Russell K.

2012-01-01

Purpose Despite improvements in chemoradiation, local control remains a major clinical problem in locally advanced non-small cell lung cancer. The Hedgehog pathway has been implicated in tumor recurrence by promoting survival of tumorigenic precursors and through effects on tumor-associated stroma. Whether Hedgehog inhibition can affect radiation efficacy in vivo has not been reported. Methods and Materials We evaluated the effects of a targeted Hedgehog inhibitor (HhAntag) and radiation on clonogenic survival of human non-small cell lung cancer lines in vitro. Using an A549 cell line xenograft model, we examined tumor growth, proliferation, apoptosis, and gene expression changes after concomitant HhAntag and radiation. In a transgenic mouse model of KrasG12D-induced and Twist1-induced lung adenocarcinoma, we assessed tumor response to radiation and HhAntag by serial micro-computed tomography (CT) scanning. Results In 4 human lung cancer lines in vitro, HhAntag showed little or no effect on radio-sensitivity. By contrast, in both the human tumor xenograft and murine inducible transgenic models, HhAntag enhanced radiation efficacy and delayed tumor growth. By use of the human xenograft model to differentiate tumor and stromal effects, mouse stromal cells, but not human tumor cells, showed significant and consistent downregulation of Hedgehog pathway gene expression. This was associated with increased tumor cell apoptosis. Conclusions Targeted Hedgehog pathway inhibition can increase in vivo radiation efficacy in lung cancer preclinical models. This effect is associated with pathway suppression in tumor-associated stroma. These data support clinical testing of Hedgehog inhibitors as a component of multimodality therapy for locally advanced non-small cell lung cancer. PMID:23182391

Hedgehog pathway inhibition radiosensitizes non-small cell lung cancers.

PubMed

Zeng, Jing; Aziz, Khaled; Chettiar, Sivarajan T; Aftab, Blake T; Armour, Michael; Gajula, Rajendra; Gandhi, Nishant; Salih, Tarek; Herman, Joseph M; Wong, John; Rudin, Charles M; Tran, Phuoc T; Hales, Russell K

2013-05-01

Despite improvements in chemoradiation, local control remains a major clinical problem in locally advanced non-small cell lung cancer. The Hedgehog pathway has been implicated in tumor recurrence by promoting survival of tumorigenic precursors and through effects on tumor-associated stroma. Whether Hedgehog inhibition can affect radiation efficacy in vivo has not been reported. We evaluated the effects of a targeted Hedgehog inhibitor (HhAntag) and radiation on clonogenic survival of human non-small cell lung cancer lines in vitro. Using an A549 cell line xenograft model, we examined tumor growth, proliferation, apoptosis, and gene expression changes after concomitant HhAntag and radiation. In a transgenic mouse model of Kras(G12D)-induced and Twist1-induced lung adenocarcinoma, we assessed tumor response to radiation and HhAntag by serial micro-computed tomography (CT) scanning. In 4 human lung cancer lines in vitro, HhAntag showed little or no effect on radiosensitivity. By contrast, in both the human tumor xenograft and murine inducible transgenic models, HhAntag enhanced radiation efficacy and delayed tumor growth. By use of the human xenograft model to differentiate tumor and stromal effects, mouse stromal cells, but not human tumor cells, showed significant and consistent downregulation of Hedgehog pathway gene expression. This was associated with increased tumor cell apoptosis. Targeted Hedgehog pathway inhibition can increase in vivo radiation efficacy in lung cancer preclinical models. This effect is associated with pathway suppression in tumor-associated stroma. These data support clinical testing of Hedgehog inhibitors as a component of multimodality therapy for locally advanced non-small cell lung cancer. Copyright © 2013 Elsevier Inc. All rights reserved.

Hedgehog Pathway Inhibition Radiosensitizes Non-Small Cell Lung Cancers

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

Zeng, Jing; Aziz, Khaled; Chettiar, Sivarajan T.

2013-05-01

Purpose: Despite improvements in chemoradiation, local control remains a major clinical problem in locally advanced non-small cell lung cancer. The Hedgehog pathway has been implicated in tumor recurrence by promoting survival of tumorigenic precursors and through effects on tumor-associated stroma. Whether Hedgehog inhibition can affect radiation efficacy in vivo has not been reported. Methods and Materials: We evaluated the effects of a targeted Hedgehog inhibitor (HhAntag) and radiation on clonogenic survival of human non-small cell lung cancer lines in vitro. Using an A549 cell line xenograft model, we examined tumor growth, proliferation, apoptosis, and gene expression changes after concomitant HhAntagmore » and radiation. In a transgenic mouse model of Kras{sup G12D}-induced and Twist1-induced lung adenocarcinoma, we assessed tumor response to radiation and HhAntag by serial micro-computed tomography (CT) scanning. Results: In 4 human lung cancer lines in vitro, HhAntag showed little or no effect on radiosensitivity. By contrast, in both the human tumor xenograft and murine inducible transgenic models, HhAntag enhanced radiation efficacy and delayed tumor growth. By use of the human xenograft model to differentiate tumor and stromal effects, mouse stromal cells, but not human tumor cells, showed significant and consistent downregulation of Hedgehog pathway gene expression. This was associated with increased tumor cell apoptosis. Conclusions: Targeted Hedgehog pathway inhibition can increase in vivo radiation efficacy in lung cancer preclinical models. This effect is associated with pathway suppression in tumor-associated stroma. These data support clinical testing of Hedgehog inhibitors as a component of multimodality therapy for locally advanced non-small cell lung cancer.« less

Resistance to Soybean Aphid Among Soybean Lines, Growth-chamber Tests, 2006 Through 2008

USDA-ARS?s Scientific Manuscript database

We tested for resistance to the soybean aphid (SBA, Aphis glycines) among several soybean lines, and rated lines as resistant or susceptible in seven tests. The ratings of plants with respect to SBA infestation differed among lines in all tests. Kosamame (PI 171451, test II), Bhart (PI 165989, tes...

49 CFR 192.719 - Transmission lines: Testing of repairs.

Code of Federal Regulations, 2010 CFR

2010-10-01

... pipe before it is installed. (b) Testing of repairs made by welding. Each repair made by welding in... 49 Transportation 3 2010-10-01 2010-10-01 false Transmission lines: Testing of repairs. 192.719... Transmission lines: Testing of repairs. (a) Testing of replacement pipe. If a segment of transmission line is...

Safety behavior of in-line skaters

PubMed Central

Osberg, J; Stiles, S.

2000-01-01

Objectives and setting—Injuries from in-line skating have risen sharply in many cities around the world. To understand risk taking behavior and safety practices associated with urban in-line skating, 2210 outdoor skaters were observed in Boston, Massachusetts. Methods—Estimated age, gender, use of helmets, wrist guards, elbow and kneepads were recorded. Skaters were coded as beginner, average, or advanced, and skating locations were classified as street, sidewalk, or bicycle path. Results—About 60% of skaters wore wrist guards, but only 5.7% wore helmets. Males wore less protective equipment than females, and were more likely to skate on streets. Beginners and advanced skaters wore more protective gear than average skaters. Surprisingly, street skaters wore less protective gear than skaters on sidewalks or paths. Conclusions—Renewed focus on the importance of wearing helmets is needed. Given the higher injury risks for males, clinicians and public health experts need to target male skaters in prevention efforts. In addition, average and advanced skaters need to be convinced that even though they have improved, it is still important to wear protective gear. PMID:11003191

Compact advanced extreme-ultraviolet imaging spectrometer for spatiotemporally varying tungsten spectra from fusion plasmas.

PubMed

Song, Inwoo; Seon, C R; Hong, Joohwan; An, Y H; Barnsley, R; Guirlet, R; Choe, Wonho

2017-09-01

A compact advanced extreme-ultraviolet (EUV) spectrometer operating in the EUV wavelength range of a few nanometers to measure spatially resolved line emissions from tungsten (W) was developed for studying W transport in fusion plasmas. This system consists of two perpendicularly crossed slits-an entrance aperture and a space-resolved slit-inside a chamber operating as a pinhole, which enables the system to obtain a spatial distribution of line emissions. Moreover, a so-called v-shaped slit was devised to manage the aperture size for measuring the spatial resolution of the system caused by the finite width of the pinhole. A back-illuminated charge-coupled device was used as a detector with 2048 × 512 active pixels, each with dimensions of 13.5 × 13.5 μm 2 . After the alignment and installation on Korea superconducting tokamak advanced research, the preliminary results were obtained during the 2016 campaign. Several well-known carbon atomic lines in the 2-7 nm range originating from intrinsic carbon impurities were observed and used for wavelength calibration. Further, the time behavior of their spatial distributions is presented.

Aeroelastic Response of the Adaptive Compliant Trailing Edge Transtition Section

NASA Technical Reports Server (NTRS)

Herrera, Claudia Y.; Spivey, Natalie D.; Lung, Shun-fat

2016-01-01

The Adaptive Compliant Trailing Edge demonstrator was a joint task under the Environmentally Responsible Aviation Project in partnership with the Air Force Research Laboratory and FlexSys, Inc. (Ann Arbor, Michigan), chartered by the National Aeronautics and Space Administration to develop advanced technologies that enable environmentally friendly aircraft, such as continuous mold-line technologies. The Adaptive Compliant Trailing Edge demonstrator encompassed replacing the Fowler flaps on the SubsoniC Aircraft Testbed, a Gulfstream III (Gulfstream Aerospace, Savannah, Georgia) aircraft, with control surfaces developed by FlexSys, Inc., a pair of uniquely-designed, unconventional flaps to be used as lifting surfaces during flight-testing to substantiate their structural effectiveness. The unconventional flaps consisted of a main flap section and two transition sections, inboard and outboard, which demonstrated the continuous mold-line technology. Unique characteristics of the transition sections provided a challenge to the airworthiness assessment for this part of the structure. A series of build-up tests and analyses were conducted to ensure the data required to support the airworthiness assessment were acquired and applied accurately. The transition sections were analyzed both as individual components and as part of the flight-test article assembly. Instrumentation was installed in the transition sections based on the analysis to best capture the in-flight aeroelastic response. Flight-testing was conducted and flight data were acquired to validate the analyses. This paper documents the details of the aeroelastic assessment and in-flight response of the transition sections of the unconventional Adaptive Compliant Trailing Edge flaps.

Combined MEK and PI3K inhibition in a mouse model of pancreatic cancer.

PubMed

Alagesan, Brinda; Contino, Gianmarco; Guimaraes, Alex R; Corcoran, Ryan B; Deshpande, Vikram; Wojtkiewicz, Gregory R; Hezel, Aram F; Wong, Kwok-Kin; Loda, Massimo; Weissleder, Ralph; Benes, Cyril H; Engelman, Jeffrey; Bardeesy, Nabeel

2015-01-15

Improved therapeutic approaches are needed for the treatment of pancreatic ductal adenocarcinoma (PDAC). As dual MEK and PI3K inhibition is presently being used in clinical trials for patients with PDAC, we sought to test the efficacy of combined targeting of these pathways in PDAC using both in vitro drug screens and genetically engineered mouse models (GEMM). We performed high-throughput screening of >500 human cancer cell lines (including 46 PDAC lines), for sensitivity to 50 clinically relevant compounds, including MEK and PI3K inhibitors. We tested the top hit in the screen, the MEK1/2 inhibitor, AZD6244, for efficacy alone or in combination with the PI3K inhibitors, BKM120 or GDC-0941, in a Kras(G12D)-driven GEMM that recapitulates the histopathogenesis of human PDAC. In vitro screens revealed that PDAC cell lines are relatively resistant to single-agent therapies. The response profile to the MEK1/2 inhibitor, AZD6244, was an outlier, showing the highest selective efficacy in PDAC. Although MEK inhibition alone was mainly cytostatic, apoptosis was induced when combined with PI3K inhibitors (BKM120 or GDC-0941). When tested in a PDAC GEMM and compared with the single agents or vehicle controls, the combination delayed tumor formation in the setting of prevention and extended survival when used to treat advanced tumors, although no durable responses were observed. Our studies point to important contributions of MEK and PI3K signaling to PDAC pathogenesis and suggest that dual targeting of these pathways may provide benefit in some patients with PDAC. Clin Cancer Res; 21(2); 396-404. ©2014 AACR. ©2014 American Association for Cancer Research.

EFFECT OF MICROWAVE POWER ON SHAPE OF EPR SPECTRA--APPLICATION TO EXAMINATION OF COMPLEX FREE RADICAL SYSTEM IN THERMALLY STERILIZED ACIDUM BORICUM.

PubMed

Ramos, Paweł; Pieprzyca, Małgorzata; Pilawa, Barbara

2016-01-01

Complex free radical system in thermally sterilized acidum boricum (AB) was studied. Acidum boricum was sterilized at temperatures and times given by pharmaceutical norms: 160 degrees C and 120 min, 170 degrees C and 60 min and 180 degrees C and 30 min. The advanced spectroscopic tests were performed. The EPR spectra of free radicals were measured as the first derivatives with microwaves of 9.3 GHz frequency and magnetic modulation of 100 kHz. The Polish X-band electron paramagnetic resonance spectrometer of Radiopan (Poznań) was used. EPR lines were not observed for the nonheated AB. The broad EPR asymmetric lines were obtained for all the heated AB samples. The influence of microwave power in the range of 2.2-70 mW on the shape of EPR spectra of the heated drug samples was tested. The following asymmetry parameters: A1/A2, A1-A2, B1/B2, and B1-B2, were analyzed. The changes of these parameters with microwave power were observed. The strong dependence of shape and its parameters on microwave power proved the complex character of free radical system in thermally sterilized AB. Changes of microwave power during the detection of EPR spectra indicated complex character of free radicals in AB sterilized in hot air under all the tested conditions. Thermolysis, interactions between free radicals and interactions of free radicals with oxygen may be responsible for the complex free radicals system in thermally treated AB. Usefulness of continuous microwave saturation of EPR lines and shape analysis to examine free radicals in thermally sterilized drugs was confirmed.

Combined MEK and PI3K inhibition in a mouse model of pancreatic cancer

PubMed Central

Guimaraes, Alex R.; Corcoran, Ryan B.; Deshpande, Vikram; Wojtkiewicz, Gregory R.; Hezel, Aram F.; Wong, Kwok-Kin; Loda, Massimo; Weissleder, Ralph; Benes, Cyril H.; Engelman, Jeffrey; Bardeesy, Nabeel

2015-01-01

Purpose Improved therapeutic approaches are needed for the treatment of pancreatic ductal adenocarcinoma (PDAC). As dual MEK and PI3K inhibition is presently being employed in clinical trials for PDAC patients, we sought to test the efficacy of combined targeting of these pathways in PDAC using both in vitro drug screens and genetically engineered mouse models (GEMMs). Experimental Design We performed high-throughput screening of >500 human cancer cell lines (including 46 PDAC lines), for sensitivity to 50 clinically-relevant compounds, including MEK and PI3K inhibitors. We tested the top hit in the screen, the MEK1/2 inhibitor, AZD-6244, for efficacy alone or in combination with the PI3K inhibitors, BKM-120 or GDC-0941, in a KRASG12D-driven GEMM that recapitulates the histopathogenesis of human PDAC. Results In vitro screens revealed that PDAC cell lines are relatively resistant to single-agent therapies. The response profile to the MEK1/2 inhibitor, AZD-6244, was an outlier, showing the highest selective efficacy in PDAC. While MEK inhibition alone was mainly cytostatic, apoptosis was induced when combined with PI3K inhibitors (BKM-120 or GDC-0941). When tested in a PDAC GEMM and compared to the single agents or vehicle controls, the combination delayed tumor formation in the setting of prevention and extended survival when used to treat advanced tumors, although no durable responses were observed. Conclusions Our studies point to important contributions of MEK and PI3K signaling to PDAC pathogenesis and suggest that dual targeting of these pathways may provide benefit in some PDAC patients. PMID:25348516

[Research on diagnosis of gas-liquid detonation exhaust based on double optical path absortion spectroscopy technique].

PubMed

Lü, Xiao-Jing; Li, Ning; Weng, Chun-Sheng

2014-03-01

The effect detection of detonation exhaust can provide measurement data for exploring the formation mechanism of detonation, the promotion of detonation efficiency and the reduction of fuel waste. Based on tunable diode laser absorption spectroscopy technique combined with double optical path cross-correlation algorithm, the article raises the diagnosis method to realize the on-line testing of detonation exhaust velocity, temperature and H2O gas concentration. The double optical path testing system is designed and set up for the valveless pulse detonation engine with the diameter of 80 mm. By scanning H2O absorption lines of 1343nm with a high frequency of 50 kHz, the on-line detection of gas-liquid pulse detonation exhaust is realized. The results show that the optical testing system based on tunable diode laser absorption spectroscopy technique can capture the detailed characteristics of pulse detonation exhaust in the transient process of detonation. The duration of single detonation is 85 ms under laboratory conditions, among which supersonic injection time is 5.7 ms and subsonic injection time is 19.3 ms. The valveless pulse detonation engine used can work under frequency of 11 Hz. The velocity of detonation overflowing the detonation tube is 1,172 m x s(-1), the maximum temperature of detonation exhaust near the nozzle is 2 412 K. There is a transitory platform in the velocity curve as well as the temperature curve. H2O gas concentration changes between 0-7% during detonation under experimental conditions. The research can provide measurement data for the detonation process diagnosis and analysis, which is of significance to advance the detonation mechanism research and promote the research of pulse detonation engine control technology.

Cork boiling wastewater treatment and reuse through combination of advanced oxidation technologies.

PubMed

Ponce-Robles, L; Miralles-Cuevas, S; Oller, I; Agüera, A; Trinidad-Lozano, M J; Yuste, F J; Malato, S

2017-03-01

Industrial preparation of cork consists of its immersion for approximately 1 hour in boiling water. The use of herbicides and pesticides in oak tree forests leads to absorption of these compounds by cork; thus, after boiling process, they are present in wastewater. Cork boiling wastewater shows low biodegradability and high acute toxicity involving partial inhibition of their biodegradation when conventional biological treatment is applied. In this work, a treatment line strategy based on the combination of advanced physicochemical technologies is proposed. The final objective is the reuse of wastewater in the cork boiling process; thus, reducing consumption of fresh water in the industrial process itself. Coagulation pre-treatment with 0.5 g/L of FeCl 3 attained the highest turbidity elimination (86 %) and 29 % of DOC elimination. Similar DOC removal was attained when using 1 g/L of ECOTAN BIO (selected for ozonation tests), accompanied of 64 % of turbidity removal. Ozonation treatments showed less efficiency in the complete oxidation of cork boiling wastewater, compared to solar photo-Fenton process, under the studied conditions. Nanofiltration system was successfully employed as a final purification step with the aim of obtaining a high-quality reusable permeate stream. Monitoring of unknown compounds by LC-QTOF-MS allowed the qualitative evaluation of the whole process. Acute and chronic toxicity as well as biodegradability assays were performed throughout the whole proposed treatment line.

Automatic cell cloning assay for determining the clonogenic capacity of cancer and cancer stem-like cells.

PubMed

Fedr, Radek; Pernicová, Zuzana; Slabáková, Eva; Straková, Nicol; Bouchal, Jan; Grepl, Michal; Kozubík, Alois; Souček, Karel

2013-05-01

The clonogenic assay is a well-established in vitro method for testing the survival and proliferative capability of cells. It can be used to determine the cytotoxic effects of various treatments including chemotherapeutics and ionizing radiation. However, this approach can also characterize cells with different phenotypes and biological properties, such as stem cells or cancer stem cells. In this study, we implemented a faster and more precise method for assessing the cloning efficiency of cancer stem-like cells that were characterized and separated using a high-speed cell sorter. Cell plating onto a microplate using an automatic cell deposition unit was performed in a single-cell or dilution rank mode by the fluorescence-activated cell sorting method. We tested the new automatic cell-cloning assay (ACCA) on selected cancer cell lines and compared it with the manual approach. The obtained results were also compared with the results of the limiting dilution assay for different cell lines. We applied the ACCA to analyze the cloning capacity of different subpopulations of prostate and colon cancer cells based on the expression of the characteristic markers of stem (CD44 and CD133) and cancer stem cells (TROP-2, CD49f, and CD44). Our results revealed that the novel ACCA is a straightforward approach for determining the clonogenic capacity of cancer stem-like cells identified in both cell lines and patient samples. Copyright © 2013 International Society for Advancement of Cytometry.

The reverse transcriptase encoded by LINE-1 retrotransposons in the genesis, progression and therapy of cancer

NASA Astrophysics Data System (ADS)

Sciamanna, Ilaria; De Luca, Chiara; Spadafora, Corrado

2016-02-01

In higher eukaryotic genomes, Long Interspersed Nuclear Element 1 (LINE-1) retrotransposons represent a large family of repeated genomic elements. They transpose using a reverse transcriptase (RT), which they encode as part of the ORF2p product. RT inhibition in cancer cells, either via RNA interference-dependent silencing of active LINE-1 elements, or using RT inhibitory drugs, reduces cancer cell proliferation, promotes their differentiation and antagonizes tumor progression in animal models. Indeed, the nonnucleoside RT inhibitor efavirenz has recently been tested in a phase II clinical trial with metastatic prostate cancer patients. An in-depth analysis of ORF2p in a mouse model of breast cancer showed ORF2p to be precociously expressed in precancerous lesions and highly abundant in advanced cancer stages, while being barely detectable in normal breast tissue, providing a rationale for the finding that RT-expressing tumours are therapeutically sensitive to RT inhibitors. We summarise mechanistic and gene profiling studies indicating that highly abundant LINE-1-derived RT can “sequester” RNA substrates for reverse transcription in tumor cells, entailing the formation of RNA:DNA hybrid molecules and impairing the overall production of regulatory miRNAs, with a global impact on the cell transcriptome. Based on these data, LINE-1-ORF2 encoded RT has a tumor-promoting potential that is exerted at an epigenetic level. We propose a model whereby LINE1-RT drives a previously unrecognized global regulatory process, the deregulation of which drives cell transformation and tumorigenesis and possibly implicated in cancer cell heterogeneity.

[Retrospective Study of Efficacy in BIM Gene Polymorphism on First-line EGFR-TKIs Treatment for Advanced Lung Adenocarcinoma].

PubMed

Qian, Kun; Zhang, Yi; Zhi, Xiuyi

2017-08-20

The aim of this study is to detect the BIM polymorphism in 85 formalin-fixed and parrffin-embedded (FFPE) and some blood samples of advanced lung adenocarcinoma patients and study the relativity betweenthe BIM polymorphism and tyrosine kinase inhibitor (TKI). The correlation between BIM detection of different types of specimens was discussed. There were 85 patients who were diagnosed as advanced lung adenocarcinoma with epidermal growth factor receptor (EGFR) 19 or 21 exon mutation in thoracic surgery of Xuanwu Hospital from February 2013 to November 2014, all of who were received EGFR-TKI as first-line treatment in the study. FFPE and some blood were used to detect the BIM polymorphism. The objective response rate (ORR) and progression-free survival (PFS) of two groups were compared. According to smoking, sex, EGFR mutation and other factors, the single factor analysis was performed, and the correlation between paraffin samples and blood test BIM was compared. The ORR in BIM polymorphism and non-polymorphism groups was no significant differences (P>0.05). The median PFS in BIM polymorphism and non-polymorphism group was 7.1 months and 12.8 months, respectively (P=0.013). Univariate analysis the median PFS, women were longer than men (12.1 months vs 10.7 months, P=0.835); Non-smokers were longer than smokers (12.1 months vs 9.7 months, P=0.974). Group in EGFR exon 21 is longer than group in EGFR exon 19 (12.2 months vs 8.7 months, P=0.303). Detection of BIM gene polymorphism in lung cancer patients with EGFR-TKIs treatment might be helpful for predicting prognosis. But a large sample study is needed.

Characterization of the Murine Myeloid Precursor Cell Line MuMac-E8

PubMed Central

Fricke, Stephan; Riemschneider, Sina; Kohlschmidt, Janine; Hilger, Nadja; Fueldner, Christiane; Knauer, Jens; Sack, Ulrich; Emmrich, Frank; Lehmann, Jörg

2014-01-01

Starting point for the present work was the assumption that the cell line MuMac-E8 represents a murine cell population with stem cell properties. Preliminary studies already pointed to the expression of stem-cell associated markers and a self-regenerative potential of the cells. The cell line MuMac-E8 should be examined for their differential stage within stem cell hierarchy. MuMac-E8 cells were derived from a chimeric mouse model of arthritis. It could be shown that MuMac-E8 cells express mRNA of some genes associated with pluripotent stem cells (Nanog, Nucleostemin), of genes for hematopoietic markers (EPCR, Sca-1, CD11b, CD45), for the mesenchymal marker CD105 and of genes for the neural markers Pax-6 and Ezrin. In methylcellulose and May-Grünwald-Giemsa staining, hematopoietic colonies were obtained but the hematopoietic system of lethally irradiated mice could not be rescued. Osteogenic differentiation was not detectable. Thus, it became evident that MuMac-E8 represents not a stem cell line. However, MuMac-E8 cells expressed several myeloid surface markers (i.e. CD11b, F4/80, CD14, CD64), showed phagocytosis and is capable of producing nitric oxide. Thus, this cell line seems to be arrested an advanced stage of myeloid differentiation. Adherence data measured by impedance-based real-time cell analysis together with cell morphology data suggested that MuMac-E8 represents a new macrophage precursor cell line exhibiting weak adherence. This cell line is suitable as an in-vitro model for testing of macrophage functions. Moreover, it might be also useful for differentiation or reprogramming studies. PMID:25546418

Comprehensive Evaluation of the Role of EZH2 in the Growth, Invasion, and Aggression of a Panel of Prostate Cancer Cell Lines

PubMed Central

Karanikolas, Breanne D.W.; Figueiredo, Marxa L.; Wu, Lily

2010-01-01

Background Although most prostate cancers respond well to initial treatments, a fraction of prostate cancers are more aggressive and will recur and metastasize. At that point, there are few treatment options available. Significant efforts have been made to identify biomarkers that will identify these more aggressive cancers to tailor a more vigorous treatment in order to improve outcome. Polycomb Group protein Enhancer of Zeste 2 (EZH2) was found to be overexpressed in metastatic prostate tumors, and is considered an excellent candidate for such a biomarker. Scattered studies have found that EZH2 overexpression causes neoplastic transformation, invasion, and growth of prostate cells. However, these studies utilized different systems and cell lines, and so are difficult to correlate with one another. Methods In this study, a comprehensive evaluation of the phenotypic effects of EZH2 in a panel of five prostate cancer cell lines was performed. By using multiple cell lines, and examining overexpression and knockdown of EZH2 concurrently, a broad view of EZH2's role in prostate cancer was achieved. Results Overexpression of EZH2 led to more aggressive behaviors in all prostate cell lines tested. In contrast, downregulation of EZH2 reduced invasion and tumorigenicity of androgen-independent cell lines CWR22Rv1, PC3, and DU145, but not of androgen-dependent cell lines LAPC4 and LNCaP. Conclusions Findings from this study suggest androgen-independent prostate tumors are more dependent on EZH2 expression than androgen-dependent tumors. Our observations provide an explanation for the strong correlation between EZH2 overexpression and advanced stage, aggressive prostate cancers. PMID:20087897

Appearance on face reading (cheek line) after orthognathic surgery.

PubMed

Tseng, Y-C; Chen, H-J; Cheng, J-H; Chen, P-H; Pan, C-Y; Chou, S-T; Chen, C-M

2018-04-12

The cheek line (face reading) is an aesthetic element of the facial profile. The purpose of our study was to investigate the changes in the cheek line after mandibular setback surgery. Forty patients (20 female and 20 male, mean (SD) age 22 (5) years) were diagnosed with mandibular prognathism and treated by intraoral vertical ramus osteotomy alone. Cephalograms were obtained before operation (T1), at least a year postoperatively (T2), and final surgical changes over a year (T2-T1). The cheek line and landmarks (soft and hard tissues) were compared using the paired t test. The hypothesis was that the cheek line did not change significantly after mandibular setback. At the time of the final follow-up (T2-T1), the mean (SD) horizontal setback of pogonion (Pog) was 12.3 (3.5) mm for women and 11.7 (4.3) mm for men. The ratios of soft:hard tissue, labrale inferius:incisor inferius, labiomental sulcus:point B, soft tissue Pog:Pog, and cheek point:Pog in women were 0.96, 0.98, 0.98, and 0.08, and in men 0.91, 1.01, 0.94, and 0.13, respectively. The nasolabial and cervicomental angles in women were significantly increased by 11.1° and 11.4°, respectively, and in men the nasolabial angle was significantly increased by 11.1° and the mentolabial angle reduced by 9.9°. The cheek line (T2-T1) was moved significantly forwards. The hypothesis was therefore rejected. In conclusion, the cheek line was advanced significantly after isolated mandibular setback. Copyright © 2018 The British Association of Oral and Maxillofacial Surgeons. Published by Elsevier Ltd. All rights reserved.

Benefit in lung function improvement and side-effect profile of long-term responders: an analysis of 14 NSCLC patients treated for at least 9 months with gefitinib.

PubMed

Reck, Martin; Gatzemeier, Ulrich

2005-10-01

Gefitinib is the first approved EGFR tyrosine-kinase inhibitor indicated for the treatment of patients with locally advanced (IIIB) or metastatic NSCLC after failure of platinum-based first-line therapy and docetaxel chemotherapy. Following rapid approval in Japan and accelerated approval based on phase-II results in the US, a large compassionate-use program has been set up in parallel to extended phase-III testing. Offering therefore access to state-of-the-art therapy to patients who are not candidates for clinical studies; Iressatrade mark EAP allows physicians to test the new EGFR inhibitor across a heterogeneous patient population characteristic for advanced NSCLC. After having treated 240 patients at the Grosshansdorf hospital, we have retrospectively analysed the efficacy and tolerability of 250 mg/day gefitinib in patients showing a long-term tumor control. We reviewed the patient records of 14 patients with advanced NSCLC that received daily gefitinib for at least 9 months. Long-term tumor control, defined as confirmed objective tumor response for at least 6 months or disease stabilisation for above 9 months, was observed in chemo-naive patients as well as in fourth-line therapy patients for the latter ones independently of the composition of prior chemotherapy. Most patients (9/14) with such a lasting benefit were female; patients' histology was in most cases uniform: adenocarcinomas were dominant in women and bronchioloalveolar carcinoma in men. Patients with moderate to severe dyspnoea benefited from a measurable improvement of their respiratory capacity. No cumulative toxicity was observed; characteristic side-effects for gefitinib as grades 1-2 diarrhoea or mild to moderate skin toxicity were well manageable. For 14 (6%) out of 240 patients with patterns of diffuse disseminated metastatic disease, gefitinib offered a lasting tumor control with a disease progression-free survival interval between 9 and 25 months. In parallel to therapy, patients' performance status (PS) could be conserved or even improved in many cases. Patients with lung function impairment, as well as patients with other disease-related symptoms obtained additional therapy benefits.

Man-made flows from a fish's perspective: autonomous classification of turbulent fishway flows with field data collected using an artificial lateral line.

PubMed

Tuhtan, Jeffrey A; Fuentes-Perez, Juan Francisco; Toming, Gert; Schneider, Matthias; Schwarzenberger, Richard; Schletterer, Martin; Kruusmaa, Maarja

2018-05-25

The lateral line system provides fish with advanced mechanoreception over a wide range of flow conditions. Inspired by the abilities of their biological counterparts, artificial lateral lines have been developed and tested exclusively under laboratory settings. Motivated by the lack of flow measurements taken in the field which consider fluid-body interactions, we built a fish-shaped lateral line probe. The device is outfitted with 11 high-speed (2.5 kHz) time-synchronized pressure transducers, and designed to capture and classify flows in fish passage structures. A total of 252 field measurements, each with a sample size of 132 000 discrete sensor readings were recorded in the slots and across the pools of vertical slot fishways. These data were used to estimate the time-averaged flow velocity (R 2   =  0.952), which represents the most common metric to assess fishway flows. The significant contribution of this work is the creation and application of hydrodynamic signatures generated by the spatial distribution of pressure fluctuations on the fish-shaped body. The signatures are based on the collection of the pressure fluctuations' probability distributions, and it is shown that they can be used to automatically classify distinct flow regions within the pools of three different vertical slot fishways. For the first time, field data from operational fishway measurements are sampled and classified using an artificial lateral line, providing a completely new source of bioinspired flow information.

2014 European guideline on the management of syphilis.

PubMed

Janier, M; Hegyi, V; Dupin, N; Unemo, M; Tiplica, G S; Potočnik, M; French, P; Patel, R

2014-12-01

Syphilis remains a major public health problem in Europe (both in Eastern Europe since the 1990's and in Western Europe since the re-emergence of the disease in the late 1990's-early 2000's). This guideline is an update of the IUSTI: 2008 European guideline on the management of syphilis and is produced by the European Guideline Editorial Board (http://www.iusti.org/regions/Europe/pdf/2013/Editorial_Board.pdf) and EDF Guideline Committee. It provides recommendations concerning the diagnosis and management of syphilis in Europe. Major advances include (1) broader use of PCR, immunohistochemistry, subtyping of the etiological agent Treponema pallidum subspecies pallidum, new treponemal tests, and rapid-point-of-care (POC) tests detecting both treponemal and non-treponemal antibodies, (2) more flexible options for screening (TT-treponemal test- first or NTT -non treponemal test- first or both TT and NTT), and (3) procaine penicillin is no longer the first line therapy option in any phase of the disease, i.e. long acting penicillin G (i.e. benzathine penicillin G-BPG) is the only first line therapy regimen in early syphilis and in late latent syphilis. Syphilis is a disease that is relatively easy to detect by appropriate serological tests, however, all laboratory results should be considered together with clinical data and sexual risk anamnesis. Syphilis is also easy to treat with BPG. A major concern about the supply of BPG in many European countries could threaten the efficacy of the policies of eradication of the disease in Europe. © 2014 European Academy of Dermatology and Venereology.

Calculation of stresses in a rock mass and lining in stagewise face drivage

NASA Astrophysics Data System (ADS)

Seryakov, VM; Zhamalova, BR

2018-03-01

Using the method of calculating mechanical state of a rock mass for the conditions of stagewise drivage of a production face in large cross-section excavations, the specific features of stress redistribution in lining of excavations are found. The zones of tensile stresses in the lining are detected. The authors discuss the influence of the initial stress state of rocks on the tension stress zones induced in the lining in course of the heading advance

Manufacturing an advanced process characterization reticle incorporating halftone biasing

NASA Astrophysics Data System (ADS)

Nakagawa, Kent H.; Van Den Broeke, Douglas J.; Chen, J. Fung; Laidig, Thomas L.; Wampler, Kurt E.; Caldwell, Roger F.

1999-04-01

As the semiconductor roadmap continues to require imaging of smaller feature son wafers, we continue to explore new approaches in OPC strategies to extend the lifespan of existing technology. In this paper, we study a new OPC technology, called halftone biasing, and its application on an OPC characterization reticle, designed by MicroUnity Systems Engineering, Inc. The RTP9 test reticle is the latest in a series of 'LineSweeper' characterization reticles. Each reticle contains a wide range of line width sand pitches, each with several alternative OPC treatments, including references cases, scattering bars, and fine biasing. One of RTP9's design requirements was to support very fine, incremental biases for densely-pitched lines. Ordinarily, this would dictate a reduced address unit and with it the costly penalty of a square-law increase in e- beam write time. RTP9 incorporates a new OPC strategy, called halftone biasing, which has been proposed to address this problem. Taking advantage of optical reduction printing, this technique applies a sub-resolution halftone screen to the edges of figures to accomplish fine biasing equivalent to using an address unit one-fourth of the size of the actual e-beam writing grid. The resulting edge structure has some of the characteristics of aggressive OPC structures, but can be used in areas where traditional scattering bars cannot be placed. The trade-off between the faster write times achieved and the inflation of pattern file size is examined. The manufacturability and inspectability of halftone-biased lines on the RTP9 test reticle are explored. Pattern fidelity is examined using both optical and SEM tools. Printed 0.18 micrometers DUV resist line edge profiles are compared for both halftone and non- halftone feature edges. The CD uniformity of the OPC features, and result of die-to-database inspection are reported. The application of halftone biasing to real circuits, including the impact of data volume and saved write time, is also discussed.

ON-LINE TOXICITY MONITORS AND WATERSHED EARLY WARNING SYSTEMS

EPA Science Inventory

A Water Quality Early Warning System using On-line Toxicity Monitors (OTMs) has been deployed in the East Fork of the Little Miami River, Clermont County, OH. Living organisms have long been used to determine the toxicity of environmental samples. With advancements in electronic ...

Power transmission cable development for the Space Station Freedom electrical power system

NASA Technical Reports Server (NTRS)

Schmitz, Gregory V.; Biess, John J.

1989-01-01

Power transmission cable is presently being evaluated under a NASA Lewis Research Center advanced development contract for application in the Space Station Freedom (SSF) electrical power system (EPS). Evaluation testing has been performed by TRW and NASA Lewis Research Center. The results of this development contract are presented. The primary cable design goals are to provide (1) a low characteristic inductance to minimize line voltage drop at 20 kHz, (2) electromagnetic compatibility control of the 20-kHz ac power current, (3) a physical configuration that minimizes ac resistance and (4) release of trapped air for corona-free operation.

Camp Blanding Lightning Mapping Array

NASA Technical Reports Server (NTRS)

Blakeslee,Richard; Christian, Hugh; Bailey, Jeffrey; Hall, John; Uman, Martin; Jordan, Doug; Krehbiel, Paul; Rison, William; Edens, Harald

2011-01-01

A seven station, short base-line Lightning Mapping Array was installed at the Camp Blanding International Center for Lightning Research and Testing (ICLRT) during April 2011. This network will support science investigations of Terrestrial Gamma-Ray Flashes (TGFs) and lightning initiation using rocket triggered lightning at the ICLRT. The network operations and data processing will be carried out through a close collaboration between several organizations, including the NASA Marshall Space Flight Center, University of Alabama in Huntsville, University of Florida, and New Mexico Tech. The deployment was sponsored by the Defense Advanced Research Projects Agency (DARPA). The network does not have real-time data dissemination. Description, status and plans will be discussed.

Signal Acquisition Using AXIe

NASA Astrophysics Data System (ADS)

Narciso, Steven J.

2011-08-01

An emerging test and measurement standard called AXIe, AdvancedTCA extensions for Instrumentation, is expected to find wide acceptance within the Physics community as it offers many benefits to applications including shock, plasma, particle and nuclear physics. It is expected that many COTS (commercial off-the-shelf) signal conditioning, acquisition and processing modules will become available from a range of different suppliers. AXIe uses AdvancedTCA® as its basis, but then levers test and measurement industry standards such as PXI, IVI, and LXI to facilitate cooperation and plug-and-play interoperability between COTS instrument suppliers. AXIe's large board footprint and power allows high density in a 19" rack, enabling the development of high-performance signal conditioning, analog-to-digital conversion, and data processing, while offering channel count scalability inherent in modular systems. Synchronization between modules is flexible and provided by two triggering structures: a parallel trigger bus, and radially-distributed, time-matched point-to-point trigger lines. Inter-module communication is also provided with an adjacent module local bus allowing data transfer to 600 Gbits/s in each direction, for example between a front-end digitizer and DSP. AXIe allows embedding high performance computing and a range of COTS AdvancedTCA® computer blades are currently available that provide low cost alternatives to the development of custom signal processing modules. The availability of both LAN and PCI Express allow interconnection between modules, as well as industry-standard high-performance data paths to external host computer systems. AXIe delivers a powerful environment for custom module devel opment. As in the case of VXIbus and PXI before it, commercial development kits are expected to be available. This paper will give an overview of the architectural elements of AXIe 1.0, the compatibility model with AdvancedTCA, and signal acquisition performance of many of the AXIe structures.

Quality of life, symptom status and physical performance in patients with advanced non-small cell lung cancer undergoing chemotherapy: an exploratory analysis of secondary data.

PubMed

Shallwani, Shirin M; Simmonds, Maureen J; Kasymjanova, Goulnar; Spahija, Jadranka

2016-09-01

Our objectives were: (a) to identify predictors of change in health-related quality of life (HRQOL) in patients with advanced non-small cell lung cancer (NSCLC) undergoing chemotherapy; and (b) to characterize symptom status, nutritional status, physical performance and HRQOL in this population and to estimate the extent to which these variables change following two cycles of chemotherapy. A secondary analysis of a longitudinal observational study of 47 patients (24 men and 23 women) with newly diagnosed advanced NSCLC receiving two cycles of first-line chemotherapy was performed. Primary outcomes were changes in HRQOL (physical and mental component summaries (PCS and MCS) of the 36-item Short-Form Health Survey (SF-36)). Predictors in the models included pre-chemotherapy patient-reported symptoms (Schwartz Cancer Fatigue Scale (SCFS) and Lung Cancer Subscale), nutritional screening (Patient-Generated Subjective Global Assessment) and physical performance measures (6-min Walk Test (6MWT), one-minute chair rise test and grip strength). Mean SF-36 PCS score, 6MWT distance and grip strength declined following two cycles of chemotherapy (p<0.05). Multiple linear regression modelling revealed pre-chemotherapy SCFS score and 6MWT distance as the strongest predictors of change in the mental component of HRQOL accounting for 13% and 9% of the variance, respectively. No significant predictors were found for change in the physical component of HRQOL. Pre-chemotherapy 6MWT distance and fatigue severity predicted change in the mental component of HRQOL in patients with advanced NSCLC undergoing chemotherapy, while physical performance declined during treatment. Clinical management of these factors may be useful for HRQOL optimization in this population. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

40 CFR 94.510 - Compliance with criteria for production line testing.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 20 2011-07-01 2011-07-01 false Compliance with criteria for production line testing. 94.510 Section 94.510 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Manufacturer Production Line Testing Programs § 94.510 Compliance with criteria for production line testing. (a...

40 CFR 91.510 - Compliance with criteria for production line testing.

Code of Federal Regulations, 2011 CFR

2011-07-01

... 40 Protection of Environment 20 2011-07-01 2011-07-01 false Compliance with criteria for production line testing. 91.510 Section 91.510 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY... Production Line Testing Program § 91.510 Compliance with criteria for production line testing. (a) A failed...

Cost-effectiveness of Paclitaxel + Ramucirumab Combination Therapy for Advanced Gastric Cancer Progressing After First-line Chemotherapy in Japan.

PubMed

Saito, Shota; Muneoka, Yusuke; Ishikawa, Takashi; Akazawa, Kouhei

2017-12-01

The combination of paclitaxel + ramucirumab is a standard second-line treatment in patients with advanced gastric cancer. This therapy has been associated with increased median overall survival and progression-free survival compared with those with paclitaxel monotherapy. We evaluated the cost-effectiveness of paclitaxel + ramucirumab combination therapy in patients with advanced gastric cancer, from the perspective of health care payers in Japan. We constructed a Markov model to compare, over a time horizon of 3 years, the costs and effectiveness of the combination of paclitaxel + ramucirumab and paclitaxel alone as second-line therapies for advanced gastric cancer in Japan. Health outcomes were measured in life-years (LYs) and quality-adjusted (QA) LYs gained. Costs were calculated using year-2016 Japanese yen (¥1 = US $17.79) according to the social insurance reimbursement schedule and drug tariff of the fee-for-service system in Japan. Model robustness was addressed through 1-way and probabilistic sensitivity analyses. The costs and QALYs were discounted at a rate of 2% per year. The willingness-to-pay threshold was set at the World Health Organization's criterion of ¥12 million, because no consensus exists regarding the threshold for acceptable cost per QALY ratios in Japan's health policy. Paclitaxel + ramucirumab combination therapy was estimated to provide an additional 0.09 QALYs (0.10 LYs) at a cost of ¥3,870,077, resulting in an incremental cost-effectiveness ratio of ¥43,010,248/QALY. The incremental cost-effectiveness ratio for the combination therapy was >¥12 million/QALY in all of the 1-way and probabilistic sensitivity analyses. Adding ramucirumab to a regimen of paclitaxel in the second-line treatment of advanced gastric cancer is expected to provide a minimal incremental benefit at a high incremental cost per QALY. Based on our findings, adjustments in the price of ramucirumab, as well as improves in other clinical parameters such as survival time and adverse event in advanced gastric cancer therapy, are needed. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.

Advanced uncooled sensor product development

NASA Astrophysics Data System (ADS)

Kennedy, A.; Masini, P.; Lamb, M.; Hamers, J.; Kocian, T.; Gordon, E.; Parrish, W.; Williams, R.; LeBeau, T.

2015-06-01

The partnership between RVS, Seek Thermal and Freescale Semiconductor continues on the path to bring the latest technology and innovation to both military and commercial customers. The partnership has matured the 17μm pixel for volume production on the Thermal Weapon Sight (TWS) program in efforts to bring advanced production capability to produce a low cost, high performance product. The partnership has developed the 12μm pixel and has demonstrated performance across a family of detector sizes ranging from formats as small as 206 x 156 to full high definition formats. Detector pixel sensitivities have been achieved using the RVS double level advanced pixel structure. Transition of the packaging of microbolometers from a traditional die level package to a wafer level package (WLP) in a high volume commercial environment is complete. Innovations in wafer fabrication techniques have been incorporated into this product line to assist in the high yield required for volume production. The WLP seal yield is currently > 95%. Simulated package vacuum lives >> 20 years have been demonstrated through accelerated life testing where the package has been shown to have no degradation after 2,500 hours at 150°C. Additionally the rugged assembly has shown no degradation after mechanical shock and vibration and thermal shock testing. The transition to production effort was successfully completed in 2014 and the WLP design has been integrated into multiple new production products including the TWS and the innovative Seek Thermal commercial product that interfaces directly to an iPhone or android device.

In vitro testing of drug combinations employing nilotinib and alkylating agents with regard to pretransplant conditioning treatment of advanced-phase chronic myeloid leukemia.

PubMed

Radujkovic, Aleksandar; Luft, Thomas; Dreger, Peter; Ho, Anthony D; Jens Zeller, W; Fruehauf, Stefan; Topaly, Julian

2014-08-01

The prognosis of patients with advanced-phase chronic myeloid leukemia (CML) remains dismal despite the availability of targeted therapies and allogeneic stem cell transplantation (allo-SCT). Increasing the antileukemic efficacy of the pretransplant conditioning regimen may be a strategy to increase remission rates and duration. We therefore investigated the antiproliferative effects of nilotinib in combination with drugs that are usually used for conditioning: the alkylating agents mafosfamide, treosulfan, and busulfan. Drug combinations were tested in vitro in different imatinib-sensitive and imatinib-resistant BCR-ABL-positive cell lines. A tetrazolium-based MTT assay was used for the assessment and quantification of growth inhibition after exposure to alkylating agents alone or to combinations with nilotinib. Drug interaction was analyzed using the median-effect method of Chou and Talalay, and combination index (CI) values were calculated according to the classic isobologram equation. Treatment of imatinib-sensitive, BCR-ABL-positive K562 and LAMA84 cells with nilotinib in combination with mafosfamide, treosulfan, or busulfan resulted in synergistic (CI < 1), additive (CI ~ 1), and predominantly antagonistic (CI > 1) effects, respectively. In imatinib-resistant K562-R and LAMA84-R cells, all applied drug combinations were synergistic (CI < 1) at higher growth inhibition levels. Our in vitro data warrant further investigation and may provide the basis for nilotinib-supplemented conditioning regimens for allo-SCT in advanced-phase CML.

A Study to Assess the Efficacy of IMAB362 Plus mFOLFOX6 Compared With Placebo Plus mFOLFOX6 as First-line Treatment of Subjects With Claudin (CLDN) 18.2 Positive, HER2-Negative, Locally Advanced Unresectable or Metastatic Gastric or Gastroesophageal Junction (GEJ) Adenocarcinoma

ClinicalTrials.gov

2018-05-30

Locally Advanced Unresectable Gastroesophageal Junction (GEJ) Adenocarcinoma or Cancer; Locally Advanced Unresectable Gastric Adenocarcinoma or Cancer; Metastatic Gastric Adenocarcinoma or Cancer; Metastatic Gastroesophageal Junction (GEJ) Adenocarcinoma

Advanced X-ray Imaging Crystal Spectrometer for Magnetic Fusion Tokamak Devices

NASA Astrophysics Data System (ADS)

Lee, S. G.; Bak, J. G.; Bog, M. G.; Nam, U. W.; Moon, M. K.; Cheon, J. K.

2008-03-01

An advanced X-ray imaging crystal spectrometer is currently under development using a segmented position sensitive detector and time-to-digital converter (TDC) based delay-line readout electronics for burning plasma diagnostics. The proposed advanced XICS utilizes an eight-segmented position sensitive multi-wire proportional counter and supporting electronics to increase the spectrometer performance includes the photon count-rate capability and spatial resolution.

A new computerized adaptive test advancing the measurement of health-related quality of life (HRQoL) in children: the Kids-CAT.

PubMed

Devine, J; Otto, C; Rose, M; Barthel, D; Fischer, F; Mühlan, H; Mülhan, H; Nolte, S; Schmidt, S; Ottova-Jordan, V; Ravens-Sieberer, U

2015-04-01

Assessing health-related quality of life (HRQoL) via Computerized Adaptive Tests (CAT) provides greater measurement precision coupled with a lower test burden compared to conventional tests. Currently, there are no European pediatric HRQoL CATs available. This manuscript aims at describing the development of a HRQoL CAT for children and adolescents: the Kids-CAT, which was developed based on the established KIDSCREEN-27 HRQoL domain structure. The Kids-CAT was developed combining classical test theory and item response theory methods and using large archival data of European KIDSCREEN norm studies (n = 10,577-19,580). Methods were applied in line with the US PROMIS project. Item bank development included the investigation of unidimensionality, local independence, exploration of Differential Item Functioning (DIF), evaluation of Item Response Curves (IRCs), estimation and norming of item parameters as well as first CAT simulations. The Kids-CAT was successfully built covering five item banks (with 26-46 items each) to measure physical well-being, psychological well-being, parent relations, social support and peers, and school well-being. The Kids-CAT item banks proved excellent psychometric properties: high content validity, unidimensionality, local independence, low DIF, and model conform IRCs. In CAT simulations, seven items were needed to achieve a measurement precision between .8 and .9 (reliability). It has a child-friendly design, is easy accessible online and gives immediate feedback reports of scores. The Kids-CAT has the potential to advance pediatric HRQoL measurement by making it less burdensome and enhancing the patient-doctor communication.

Hypervelocity impact testing of the Space Station utility distribution system carrier

NASA Technical Reports Server (NTRS)

Lazaroff, Scott

1993-01-01

A two-phase, joint JSC and McDonnell Douglas Aerospace-Huntington Beach hypervelocity impact (HVI) test program was initiated to develop an improved understanding of how meteoroid and orbital debris (M/OD) impacts affect the Space Station Freedom (SSF) avionic and fluid lines routed in the Utility Distribution System (UDS) carrier. This report documents the first phase of the test program which covers nonpowered avionic line segment and pressurized fluid line segment HVI testing. From these tests, a better estimation of avionic line failures is approximately 15 failures per year and could very well drop to around 1 or 2 avionic line failures per year (depending upon the results of the second phase testing of the powered avionic line at White Sands). For the fluid lines, the initial McDonnell Douglas analysis calculated 1 to 2 line failures over a 30 year period. The data obtained from these tests indicate the number of predicted fluid line failures increased slightly to as many as 3 in the first 10 years and up to 15 for the entire 30 year life of SSF.

Design and test of a double-nuclear RF coil for 1H MRI and 13C MRSI at 7 T

NASA Astrophysics Data System (ADS)

Rutledge, Omar; Kwak, Tiffany; Cao, Peng; Zhang, Xiaoliang

2016-06-01

RF coil operation at the ultrahigh field of 7 T is fraught with technical challenges that limit the advancement of novel human in vivo applications at 7 T. In this work, a hybrid technique combining a microstrip transmission line and a lumped-element L-C loop coil to form a double-nuclear RF coil for proton magnetic resonance imaging and carbon magnetic resonance spectroscopy at 7 T was proposed and investigated. Network analysis revealed a high Q-factor and excellent decoupling between the coils. Proton images and localized carbon spectra were acquired with high sensitivity. The successful testing of this novel double-nuclear coil demonstrates the feasibility of this hybrid design for double-nuclear MR imaging and spectroscopy studies at the ultrahigh field of 7 T.

Manufacture and quality control of interconnecting wire hardnesses, Volume 1

NASA Technical Reports Server (NTRS)

1972-01-01

A standard is presented for manufacture, installation, and quality control of eight types of interconnecting wire harnesses. The processes, process controls, and inspection and test requirements reflected are based on acknowledgment of harness design requirements, acknowledgment of harness installation requirements, identification of the various parts, materials, etc., utilized in harness manufacture, and formulation of a typical manufacturing flow diagram for identification of each manufacturing and quality control process, operation, inspection, and test. The document covers interconnecting wire harnesses defined in the design standard, including type 1, enclosed in fluorocarbon elastomer convolute, tubing; type 2, enclosed in TFE convolute tubing lines with fiberglass braid; type 3, enclosed in TFE convolute tubing; and type 5, combination of types 3 and 4. Knowledge gained through experience on the Saturn 5 program coupled with recent advances in techniques, materials, and processes was incorporated.

9 CFR 147.9 - Standard test procedures for avian influenza.

Code of Federal Regulations, 2012 CFR

2012-01-01

..., Sigma Chemical Co. Cat.# A-6877 or equivalent). (iii) Avian influenza AGID antigen and positive control... test serum well. The control lines will pass through the non-specific line and continue on into the test serum well. The non-specific line does not form a continuous line with positive control lines...

9 CFR 147.9 - Standard test procedures for avian influenza.

Code of Federal Regulations, 2011 CFR

2011-01-01

..., Sigma Chemical Co. Cat.# A-6877 or equivalent). (iii) Avian influenza AGID antigen and positive control... test serum well. The control lines will pass through the non-specific line and continue on into the test serum well. The non-specific line does not form a continuous line with positive control lines...

9 CFR 147.9 - Standard test procedures for avian influenza.

Code of Federal Regulations, 2014 CFR

2014-01-01

..., Sigma Chemical Co. Cat.# A-6877 or equivalent). (iii) Avian influenza AGID antigen and positive control... test serum well. The control lines will pass through the non-specific line and continue on into the test serum well. The non-specific line does not form a continuous line with positive control lines...

9 CFR 147.9 - Standard test procedures for avian influenza.

Code of Federal Regulations, 2013 CFR

2013-01-01

..., Sigma Chemical Co. Cat.# A-6877 or equivalent). (iii) Avian influenza AGID antigen and positive control... test serum well. The control lines will pass through the non-specific line and continue on into the test serum well. The non-specific line does not form a continuous line with positive control lines...

9 CFR 147.9 - Standard test procedures for avian influenza.

Code of Federal Regulations, 2010 CFR

2010-01-01

..., Sigma Chemical Co. Cat.# A-6877 or equivalent). (iii) Avian influenza AGID antigen and positive control... test serum well. The control lines will pass through the non-specific line and continue on into the test serum well. The non-specific line does not form a continuous line with positive control lines...

Experimental equipment for an advanced ISOL facility[Isotope Separation On-Line Facility

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

Baktash, C.; Lee, I.Y.; Rehm, K.E.

This report summarizes the proceedings and recommendations of the Workshop on the Experimental Equipment for an Advanced ISOL Facility which was held at Lawrence Berkeley National Laboratory on July 22--25, 1998. The purpose of this workshop was to discuss the performance requirements, manpower and cost estimates, as well as a schedule of the experimental equipment needed to fully exploit the new physics which can be studied at an advanced ISOL facility. An overview of the new physics opportunities that would be provided by such a facility has been presented in the White Paper that was issued following the Columbus Meeting.more » The reactions and experimental techniques discussed in the Columbus White Paper served as a guideline for the formulation of the detector needs at the Berkeley Workshop. As outlined a new ISOL facility with intense, high-quality beams of radioactive nuclei would provide exciting new research opportunities in the areas of: the nature of nucleonic matter; the origin of the elements; and tests of the Standard Model. After an introductory section, the following equipment is discussed: gamma-ray detectors; recoil separators; magnetic spectrographs; particle detectors; targets; and apparatus using non-accelerated beams.« less

Advanced unresectable hepatocellular carcinoma: new biologics as fresh ammunition or clues to disease understanding?

PubMed

Dekervel, Jeroen; van Pelt, Jos; Verslype, Chris

2013-07-01

Hepatocellular carcinoma (HCC) is a prevalent malignancy associated with a guarded prognosis. At present, sorafenib is the only approved systemic therapy for patients with advanced disease. The effect of sorafenib on overall survival is modest and limited in time by the occurrence of drug resistance. Together with the increasing knowledge of molecular pathways involved in HCC, targeted molecules have been developed and tested in first and second line following sorafenib. These include antiangiogenic drugs, as well as biologicals inhibiting cell proliferation and survival. Recent phase III trials investigated sunitinib, linifanib, brivanib and erlotinib, but none of them were found superior to sorafenib. New findings in mechanisms of drug resistance create opportunities in the treatment of sorafenib-refractory disease, with cMET inhibition as the most promising approach. This article reviews the pathways involved in HCC and their targets as well as potential strategies for drug development in the future. Advanced HCC has been the subject of intensive clinical research following the success of sorafenib. Despite many failures, some agents show promising results in phase II trials. Targeting new pathways, using multidrug regimens and tailoring treatment guided by predictive markers should allow new successes.

Cost-effectiveness of precision medicine in the fourth-line treatment of metastatic lung adenocarcinoma: An early decision analytic model of multiplex targeted sequencing.

PubMed

Doble, Brett; John, Thomas; Thomas, David; Fellowes, Andrew; Fox, Stephen; Lorgelly, Paula

2017-05-01

To identify parameters that drive the cost-effectiveness of precision medicine by comparing the use of multiplex targeted sequencing (MTS) to select targeted therapy based on tumour genomic profiles to either no further testing with chemotherapy or no further testing with best supportive care in the fourth-line treatment of metastatic lung adenocarcinoma. A combined decision tree and Markov model to compare costs, life-years, and quality-adjusted life-years over a ten-year time horizon from an Australian healthcare payer perspective. Data sources included the published literature and a population-based molecular cohort study (Cancer 2015). Uncertainty was assessed using deterministic sensitivity analyses and quantified by estimating expected value of perfect/partial perfect information. Uncertainty due to technological/scientific advancement was assessed through a number of plausible future scenario analyses. Point estimate incremental cost-effective ratios indicate that MTS is not cost-effective for selecting fourth-line treatment of metastatic lung adenocarcinoma. Lower mortality rates during testing and for true positive patients, lower health state utility values for progressive disease, and targeted therapy resulting in reductions in inpatient visits, however, all resulted in more favourable cost-effectiveness estimates for MTS. The expected value to decision makers of removing all current decision uncertainty was estimated to be between AUD 5,962,843 and AUD 13,196,451, indicating that additional research to reduce uncertainty may be a worthwhile investment. Plausible future scenarios analyses revealed limited improvements in cost-effectiveness under scenarios of improved test performance, decreased costs of testing/interpretation, and no biopsy costs/adverse events. Reductions in off-label targeted therapy costs, when considered together with the other scenarios did, however, indicate more favourable cost-effectiveness of MTS. As more clinical evidence is generated for MTS, the model developed should be revisited and cost-effectiveness re-estimated under different testing scenarios to further understand the value of precision medicine and its potential impact on the overall health budget. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

40 CFR 1048.315 - How do I know when my engine family fails the production-line testing requirements?

Code of Federal Regulations, 2012 CFR

2012-07-01

... fails the production-line testing requirements? 1048.315 Section 1048.315 Protection of Environment... fails the production-line testing requirements? This section describes the pass/fail criteria for the... the requirements that apply to individual engines that fail a production-line test. (a) Calculate your...

40 CFR 1048.315 - How do I know when my engine family fails the production-line testing requirements?

Code of Federal Regulations, 2010 CFR

2010-07-01

... fails the production-line testing requirements? 1048.315 Section 1048.315 Protection of Environment... fails the production-line testing requirements? This section describes the pass/fail criteria for the... the requirements that apply to individual engines that fail a production-line test. (a) Calculate your...

40 CFR 1048.315 - How do I know when my engine family fails the production-line testing requirements?

Code of Federal Regulations, 2011 CFR

2011-07-01

... fails the production-line testing requirements? 1048.315 Section 1048.315 Protection of Environment... fails the production-line testing requirements? This section describes the pass/fail criteria for the... the requirements that apply to individual engines that fail a production-line test. (a) Calculate your...

A systematic approach to advanced cockpit warning systems for air transport operations: Line pilot preferences

NASA Technical Reports Server (NTRS)

Williams, D. H.; Simpson, C. A.

1976-01-01

Line pilots (fifty captains, first officers, and flight engineers) from 8 different airlines were administered a structured questionnaire relating to future warning system design and solutions to current warning system problems. This was followed by a semantic differential to obtain a factor analysis of 18 different cockpit warning signals on scales such as informative/distracting, annoying/soothing. Half the pilots received a demonstration of the experimental text and voice synthesizer warning systems before answering the questionnaire and the semantic differential. A control group answered the questionnaire and the semantic differential first, thus providing a check for the stability of pilot preferences with and without actual exposure to experimental systems. Generally, the preference data obtained revealed much consistency and strong agreement among line pilots concerning advance cockpit warning system design.

Apatinib: A Review in Advanced Gastric Cancer and Other Advanced Cancers.

PubMed

Scott, Lesley J

2018-05-01

Apatinib [Aitan ® (brand name in China)], also known as rivoceranib, is a novel, small molecule, selective vascular endothelial growth factor receptor-2 (VEGFR-2) tyrosine kinase inhibitor and is the second anti-angiogenic drug to be approved in China for the treatment of advanced or metastatic gastric cancer. This article summarizes the pharmacological properties of apatinib and reviews its clinical use in chemotherapy-experienced patients with advanced gastric adenocarcinoma, including gastroesophageal adenocarcinoma (GEA), or with other advanced cancers such as non-small cell lung cancer (NSCLC), breast cancer, gynaecological cancers, hepatocellular carcinoma (HCC), thyroid cancer and sarcomas. As third- or subsequent-line therapy, oral apatinib significantly prolonged median progression-free survival (PFS) and overall survival (OS) compared with placebo and had a manageable safety profile in Chinese patients with advanced or metastatic gastric cancer or GEA participating in randomized, double-blind, multicentre, phase 2 and 3 trials. More limited evidence also supports it use as subsequent-line treatment in Chinese patients with other advanced or metastatic solid tumours, including NSCLC, breast cancer and HCC. Further clinical experience and long-term pharmacovigilance data are required to more definitively establish the efficacy and safety profile of apatinib, including its use in combination with other chemotherapy agents and its role in the management of other types of advanced or metastatic solid tumours. In the meantime, given its convenient administration regimen and the limited treatment options and poor prognosis for patients with advanced or metastatic solid tumours, apatinib is an important, emerging treatment option for adult patients with advanced gastric adenocarcinoma or GEA who have progressed or relapsed after chemotherapy.

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

Stovall, J.P.; RIzy, D.T.; Kisner, R.A.

The 3M Company has developed a high-temperature low-sag conductor referred to as Aluminum- Conductor Composite-Reinforced or ACCR. The conductor uses an aluminum metal matrix material to replace the steel in conventional conductors so the core has a lower density and higher conductivity. The objective of this work is to accelerate the commercial acceptance by electric utilities of these new conductor designs by testing four representative conductor classes in controlled conditions. Overhead transmission lines use bare aluminum conductor strands wrapped around a steel core strands to transmit electricity. The typical cable is referred to as aluminum-conductor steel-reinforced (ACSR). The outer strandsmore » are aluminum, chosen for its conductivity, low weight, and low cost. The center strand is of steel for the strength required to support the weight without stretching the aluminum due to its ductility. The power density of a transmission corridor has been directly increased by increasing the voltage level. Transmission voltages have increased from 115-kV to 765- kV over the past 80 years. In the United States, further increasing the voltage level is not feasible at this point in time, so in order to further increase the power density of a transmission corridor, conductor designs that increase the current carrying capability have been examined. One of the key limiting factors in the design of a transmission line is the conductor sag which determines the clearance of the conductor above ground or underlying structures needed for electrical safety. Increasing the current carrying capability of a conductor increases the joule heating in the conductor which increases the conductor sag. A conductor designed for high-temperature and lowsag operation requires an engineered modification of the conductor materials. To make an advanced cable, the 3M Company solution has been the development of a composite conductor consisting of Nextel ceramic fibers to replace the steel core and an aluminum-zirconium alloy to improve the outer strands. The result is a cable that can carry more current than steelaluminum lines without sagging as much at higher temperatures. A unique facility called the Powerline Conductor Accelerated Testing (PCAT) Facility was built at ORNL for testing overhead conductors. The PCAT has been uniquely designed for testing overhead bare transmission line conductors at high currents and temperatures after they have been installed and tensioned to the manufacturer's specifications. The ability to operate a transmission line conductor in this manner does not exist elsewhere in the United States. Four classes of ACCR cable designed by 3M have been successfully test at ORNL – small, medium, large and small/compact. Based on these and other manufacturer tests, the 3M Company has successfully introduced the ACCR into the commercial market and has completed over twenty installations for utility companies.« less

Inducible expression of photoacoustic reporter gene tyrosinase in cells using a single plasmid

NASA Astrophysics Data System (ADS)

Paproski, Robert J.; Zemp, Roger J.

2012-02-01

We have previously demonstrated that tyrosinase is a reporter gene for photoacoustic imaging since tyrosinase is the rate-limiting step in the synthesis of melanin, a pigment capable of producing strong photoacoustic signals. We previously created a cell line capable of inducible tyrosinase expression (important due to toxicity of melanin) by stably transfecting tyrosinase in MCF-7 Tet-OnR cell line (Clontech) which expresses a doxycycline-controlled transactivator. Unfortunately, Clontech provides few Tet-On Advanced cell lines making it difficult to have inducible tyrosinase expression in cell lines not provided by Clontech. In order to simplify the creation of cell lines with inducible expression of tyrosinase, we created a single plasmid that encodes both the transactivator as well as tyrosinase. PCR was used to amplify both the transactivator and tyrosinase from the Tet-OnR Advanced and pTRE-Tight-TYR plasmids, respectively. Both PCR products were cloned into the pEGFP-N1 plasmid and the newly created plasmid was transfected into ZR-75-1, MCF-7, and MIA PaCa-1 cells using lipofectamine. After several days, brown melanin was only observed in cells incubated with doxycycline, suggesting that the newly created single plasmid allowed inducible tyrosinase expression in many different cells lines.

Technological advances in the surgical treatment of movement disorders.

PubMed

Gross, Robert E; McDougal, Margaret E

2013-08-01

Technological innovations have driven the advancement of the surgical treatment of movement disorders, from the invention of the stereotactic frame to the adaptation of deep brain stimulation (DBS). Along these lines, this review will describe recent advances in inserting neuromodulation modalities, including DBS, to the target, and in the delivery of therapy at the target. Recent radiological advances are altering the way that DBS leads are targeted and inserted, by refining the ability to visualize the subcortical targets using high-field strength magnetic resonance imaging and other innovations, such as diffusion tensor imaging, and the development of novel targeting devices enabling purely anatomical implantations without the need for neurophysiological monitoring. New portable computed tomography scanners also are facilitating lead implantation without monitoring, as well as improving radiological verification of DBS lead location. Advances in neurophysiological mapping include efforts to develop automatic target verification algorithms, and probabilistic maps to guide target selection. The delivery of therapy at the target is being improved by the development of the next generation of internal pulse generators (IPGs). These include constant current devices that mitigate the variability introduced by impedance changes of the stimulated tissue and, in the near future, devices that deliver novel stimulation patterns with improved efficiency. Closed-loop adaptive IPGs are being tested, which may tailor stimulation to ongoing changes in the nervous system, reflected in biomarkers continuously recorded by the devices. Finer-grained DBS leads, in conjunction with new IPGs and advanced programming tools, may offer improved outcomes via current steering algorithms. Finally, even thermocoagulation-essentially replaced by DBS-is being advanced by new minimally-invasive approaches that may improve this therapy for selected patients in whom it may be preferred. Functional neurosurgery has a history of being driven by technological innovation, a tradition that continues into its future.

Prognostic Factors for Survival in Patients with Advanced Intrahepatic Cholangiocarcinoma Treated with Gemcitabine plus Cisplatin as First-Line Treatment.

PubMed

Ishimoto, Utako; Kondo, Shunsuke; Ohba, Akihiro; Sasaki, Mitsuhito; Sakamoto, Yasunari; Morizane, Chigusa; Ueno, Hideki; Okusaka, Takuji

2018-01-01

Intrahepatic cholangiocarcinoma (ICC) is a rare type of liver cancer. No clinically useful prognostic factors have been reported for patients with advanced ICC. In the present study, we aimed to evaluate the clinical prognostic factors of patients with advanced ICC receiving gemcitabine plus cisplatin combination therapy (GC) as standard first-line chemotherapy. A retrospective analysis was performed of the data of patients with ICC treated at our institution from March 2011 to January 2016. We used the Cox regression model and estimated the hazard ratios of potential prognostic factors for survival. Of 216 patients with biliary tract cancer receiving GC as first-line chemotherapy, we extracted data for 77 patients who were diagnosed with ICC and received GC as first-line chemotherapy. The median overall survival was 13.8 months (95% CI, 8.9-18.6). In multivariate analysis, pretreatment serum lactate dehydrogenase (hazard ratio [HR]: 2.53, p = 0.005), C-reactive protein (HR: 3.06, p = 0.001), and carcinoembryonic antigen (HR: 2.39, p = 0.03) levels were significantly associated with overall survival. Readily available clinical laboratory values reliably predicted the prognosis of ICC patients receiving GC therapy. If validated in other studies, these results may provide a useful tool for individual patient-risk evaluation and the design and interpretation of future trials. © 2017 S. Karger AG, Basel.

Mapping osmotic adjustment in an advanced back-cross inbred population of rice.

PubMed

Robin, S; Pathan, M S; Courtois, B; Lafitte, R; Carandang, S; Lanceras, S; Amante, M; Nguyen, H T; Li, Z

2003-11-01

Osmotic adjustment is one of several characters putatively associated with drought tolerance in rice. Indica cultivars are known to have a greater capacity for osmotic adjustment than japonica cultivars. We developed an advanced back-cross population using an indica donor, IR62266-42-6-2, to introgress osmotic adjustment into an elite japonica cultivar, IR60080-46A. One hundred and fifty BC(3)F(3) families were genotyped using microsatellites and RFLP markers, and a few candidate genes. We evaluated osmotic adjustment in these lines under greenhouse conditions using the re-hydration technique. Using the composite interval mapping technique, we detected 14 QTLs located on chromosomes 1, 2, 3, 4, 5, 7, 8 and 10 that together explained 58% of the phenotypic variability. Most, but not all, of the alleles with positive effects came from the donor parent. On chromosome 8, two QTLs were associated in repulsion. The QTL locations were in good agreement with previous studies on this trait on rice and in other cereals. Some BC(3)F(3) lines carried the favorable alleles at the two markers flanking up to four QTLs. Intercrossing these lines followed by marker-aided selection in their progenies will be necessary to recover lines with levels of osmotic adjustment equal to the donor parent. The advanced back-cross strategy appeared to be an appropriate method to accelerate the process of introgressing interesting traits into elite material.

First-line treatment of advanced ALK-positive non-small-cell lung cancer

PubMed Central

Gandhi, Shipra; Chen, Hongbin; Zhao, Yujie; Dy, Grace K

2015-01-01

Non-small-cell lung cancer (NSCLC) is one of the leading causes of cancer deaths, both within the US and worldwide. There have been major treatment advances in NSCLC over the past decade with the discovery of molecular drivers of NSCLC, which has ushered in an era of personalized medicine. There are several actionable genetic aberrations in NSCLC, such as epidermal growth factor receptor and anaplastic lymphoma kinase (ALK). In 3%–7% of NSCLC, a chromosomal inversion event in chromosome 2 leads to fusion of a portion of the ALK gene with the echinoderm microtubule–associated protein-like 4 (EML4) gene. The constitutive activation of the ALK fusion oncogene renders it vulnerable to therapeutic intervention. This review focuses on the first-line treatment of advanced ALK-positive NSCLC using ALK inhibitors. Crizotinib was the first agent proven to be efficacious as first-line treatment for ALK-positive NSCLC. However, acquired resistance inevitably develops. The central nervous system is a sanctuary site that represents a common site for disease progression as well. Hence, more potent, selective next-generation ALK inhibitors that are able to cross the blood–brain barrier have been developed for treatment against crizotinib-resistant ALK-positive NSCLC and are also currently being evaluated for first-line therapy as well. In this review, we provide summary of the clinical experience with these drugs in the treatment of ALK-positive NSCLC. PMID:28210152

A comparison of individualized treatment guided by VeriStrat with standard of care treatment strategies in patients receiving second-line treatment for advanced non-small cell lung cancer: A cost-utility analysis.

PubMed

Nelson, Richard E; Stenehjem, David; Akerley, Wallace

2013-12-01

Two therapies are appropriate as 2nd-line treatment of non-small cell lung cancer (NSCLC) patients: chemotherapy and epidermal growth factor receptor (EGFR) inhibitor therapy. VeriStrat, a serum proteomic test, can be used to guide treatment decisions for NSCLC patients. The test classifies patients as likely to benefit from either of these two treatment options. The objective of this research was to model the anticipated survival and cost-effectiveness of four different treatment strategies: chemotherapy for all patients (C-all), EGFR inhibitor for all (E-all), a performance status guided selection strategy (PS-guided), and a strategy guided by VeriStrat test results (V-guided). We developed a Markov model with the perspective of the U.S. health care system. Model inputs were taken from published literature for the base-case analysis. One-way and probabilistic sensitivity analyses were performed. The C-all treatment strategy showed the best overall survival outcome (10.1 months), followed by V-guided (9.6 months), PS-guided (9.2 months), and E-all (8.2 months) strategies. The incremental cost-effectiveness ratio (ICER) of a V-guided treatment strategy was $91,111 (vs. E-all) and $8462 (vs. PS-guided) per quality-adjusted life year (QALY). The ICER for C-all compared to V-guided was $105,616. This cost-utility analysis indicates that a treatment strategy guided by the VeriStrat test in patients receiving second-line therapy for NSCLC may experience an overall survival benefit at an incremental cost-effectiveness ratio that is reasonable when compared with other practices, including cancer treatments, generally covered in the U.S. health care system. However, treating all patients with chemotherapy yielded the greatest expected survival. Copyright © 2013. Published by Elsevier Ireland Ltd.

Multimodal imaging of central retinal disease progression in a 2 year mean follow up of Retinitis Pigmentosa

PubMed Central

Sujirakul, Tharikarn; Lin, Michael K.; Duong, Jimmy; Wei, Ying; Lopez-Pintado, Sara; Tsang, Stephen H.

2015-01-01

Purpose To determine the rate of progression and optimal follow up time in patients with advanced stage retinitis pigmentosa (RP) comparing the use of fundus autofluorescence imaging and spectral domain optical coherence tomography. Design Retrospective analysis of progression rate. Methods Longitudinal imaging follow up in 71 patients with retinitis pigmentosa was studied using the main outcome measurements of hyperautofluoresent ring horizontal diameter and vertical diameter along with ellipsoid zone line width from spectral domain optical coherence tomography. Test-retest reliability and the rate of progression were calculated. The interaction between the progression rates was tested for sex, age, mode of inheritance, and baseline measurement size. Symmetry of left and right eye progression rate was also tested. Results Significant progression was observed in >75% of patients during the 2 year mean follow up. The mean annual progression rates of ellipsoid zone line, and hyperautofluorescent ring horizontal diameter and vertical diameter were 0.45° (4.9%), 0.51° (4.1%), and 0.42° (4.0%), respectively. The e llipsoid zone line width, and hyperautofluorescent ring horizontal diameter and vertical diameter had low test-retest variabilities of 8.9%, 9.5% and 9.6%, respectively. This study is the first to demonstrate asymmetrical structural progression rate between right and left eye, which was found in 19% of patients. The rate of progression was significantly slower as the disease approached the fovea, supporting the theory that RP progresses in an exponential fashion. No significant interaction between progression rate and patient age, sex, or mode of inheritance was observed. Conclusions Fundus autofluorescence and optical coherence tomography detect progression in patients with RP reliably and with strong correlation. These parameters may be useful alongside functional assessments as the outcome measurements for future therapeutic trials. Follow-up at 1 year intervals should be adequate to efficiently detect progression. PMID:26164827

Demonstrating the feasibility of large-scale development of standardized assays to quantify human proteins

PubMed Central

Kennedy, Jacob J.; Abbatiello, Susan E.; Kim, Kyunggon; Yan, Ping; Whiteaker, Jeffrey R.; Lin, Chenwei; Kim, Jun Seok; Zhang, Yuzheng; Wang, Xianlong; Ivey, Richard G.; Zhao, Lei; Min, Hophil; Lee, Youngju; Yu, Myeong-Hee; Yang, Eun Gyeong; Lee, Cheolju; Wang, Pei; Rodriguez, Henry; Kim, Youngsoo; Carr, Steven A.; Paulovich, Amanda G.

2014-01-01

The successful application of MRM in biological specimens raises the exciting possibility that assays can be configured to measure all human proteins, resulting in an assay resource that would promote advances in biomedical research. We report the results of a pilot study designed to test the feasibility of a large-scale, international effort in MRM assay generation. We have configured, validated across three laboratories, and made publicly available as a resource to the community 645 novel MRM assays representing 319 proteins expressed in human breast cancer. Assays were multiplexed in groups of >150 peptides and deployed to quantify endogenous analyte in a panel of breast cancer-related cell lines. Median assay precision was 5.4%, with high inter-laboratory correlation (R2 >0.96). Peptide measurements in breast cancer cell lines were able to discriminate amongst molecular subtypes and identify genome-driven changes in the cancer proteome. These results establish the feasibility of a scaled, international effort. PMID:24317253

Long Corridor Survey for High Voltage Power Lines Design Using Uav

NASA Astrophysics Data System (ADS)

Skarlatos, D.; Vamvakousis, V.

2017-11-01

The term Unmanned Aerial Vehicle (UAV) is often directly associated with the armed forces due to their widely-criticized use of such vehicles on the modern battlefield. However, with the advancement of UAV technology, the acquisition and operational cost of small civilian UAV have reduced while their functionalities have increased. Therefore, a wide variety of new civilian applications have emerged. Mapping industry has been benefited as affordable UAV can partially replace traditional platforms, such as helicopters and small aircrafts, for low altitude photography acquisition. Although relatively new to the industry, the use of UAV is rapidly commercialized and they are expected to have a sizeable impact on the mapping industry in the coming years. The aim of this work was to test the use of a low-cost UAV for orthophoto production and Digital Surface Model (DSM) creation, to be used for the design of a new 23km high voltage line of Electricity Authority of Cyprus.

Improving mobile robot localization: grid-based approach

NASA Astrophysics Data System (ADS)

Yan, Junchi

2012-02-01

Autonomous mobile robots have been widely studied not only as advanced facilities for industrial and daily life automation, but also as a testbed in robotics competitions for extending the frontier of current artificial intelligence. In many of such contests, the robot is supposed to navigate on the ground with a grid layout. Based on this observation, we present a localization error correction method by exploring the geometric feature of the tile patterns. On top of the classical inertia-based positioning, our approach employs three fiber-optic sensors that are assembled under the bottom of the robot, presenting an equilateral triangle layout. The sensor apparatus, together with the proposed supporting algorithm, are designed to detect a line's direction (vertical or horizontal) by monitoring the grid crossing events. As a result, the line coordinate information can be fused to rectify the cumulative localization deviation from inertia positioning. The proposed method is analyzed theoretically in terms of its error bound and also has been implemented and tested on a customary developed two-wheel autonomous mobile robot.

Renal cell carcinoma in one year: Going inside the news of 2017 - A report of the main advances in RCC cancer research.

PubMed

Mosillo, Claudia; Ciccarese, Chiara; Bimbatti, Davide; Fantinel, Emanuela; Volta, Alberto Dalla; Bisogno, Iolanda; Zampiva, Ilaria; Santoni, Matteo; Massar, Francesco; Brunelli, Matteo; Montironi, Rodolfo; Tortora, Giampaolo; Iacovelli, Roberto

2018-06-01

Very interesting issues regarding RCC treatment have been raised during 2017. We analysed the main news that may potentially modified clinical practice. Conflicting data came from trials testing targeted therapies in the adjuvant setting, supporting the necessity of further investigations. One of the key goals of RCC research is focused on the first-line therapy, with particular interest focus on immunotherapy combinations. Redefine the standard of care with the aim of improving patients' survival represents an imperative need. Enhancing immunotherapy antitumor activity by combining immune checkpoint inhibitors with anti-angiogenetic therapies is a noteworthy research field, with promising results. In addiction, we analysed in the metastatic setting data about the role of cytoreductive nephrectomy and the possibility of delay the start of first-line therapy after an active surveillance period. Based on recent developments, the paper outlines future prospective of RCC research. Copyright © 2018 Elsevier Ltd. All rights reserved.

Advanced Prop-fan Engine Technology (APET) single- and counter-rotation gearbox/pitch change mechanism

NASA Technical Reports Server (NTRS)

Reynolds, C. N.

1985-01-01

The preliminary design of advanced technology (1992) turboprop engines for single-rotation prop-fans and conceptual designs of pitch change mechanisms for single- and counter-rotation prop-fan application are discussed. The single-rotation gearbox is a split path, in-line configuration. The counter-rotation gearbox is an in-line, differential planetary design. The pitch change mechanisms for both the single- and counter-rotation arrangements are rotary/hydraulic. The advanced technology single-rotation gearbox yields a 2.4 percent improvement in aircraft fuel burn and a one percent improvement in operating cost relative to a current technology gearbox. The 1992 counter-rotation gearbox is 15 percent lighter, 15 percent more reliable, 5 percent lower in cost, and 45 percent lower in maintenance cost than the 1992 single-rotation gearbox. The pitch controls are modular, accessible, and external.

Airborne differential absorption lidar system for measurements of atmospheric water vapor and aerosols

NASA Technical Reports Server (NTRS)

Carter, Arlen F.; Allen, Robert J.; Mayo, M. Neale; Butler, Carolyn F.; Grossman, Benoist E.; Ismail, Syed; Grant, William B.; Browell, Edward V.; Higdon, Noah S.; Mayor, Shane D.;

The emerging role of histology in the choice of first-line treatment of advanced non-small cell lung cancer: implication in the clinical decision-making.

PubMed

Rossi, Antonio; Maione, Paolo; Bareschino, Maria Anna; Schettino, Clorinda; Sacco, Paola Claudia; Ferrara, Marianna Luciana; Castaldo, Vincenzo; Gridelli, Cesare

2010-01-01

Lung cancer is the leading cause of cancer mortality worldwide. Non-small cell lung cancer (NSCLC), accounting for about 85% of all lung cancers, includes squamous carcinoma, adenocarcinoma and undifferentiated large cell carcinoma. The majority of patients have advanced disease at diagnosis, and medical treatment is the cornerstone of management. Several randomized trials comparing third-generation platinum-based doublets concluded that all such combinations are comparable in their clinical efficacy, failing to document a difference based on histology. However, recent evidences, arising from the availability of pemetrexed, have shown that histology represents an important variable in the decision making. The major progresses in the understanding cancer biology and mechanism of oncogenesis have allowed the development of several potential molecular targets for cancer treatment such as vascular growth factor and its receptors and epidermal growth factor receptor. Targeted drugs seem to be safer or more effective in a specific histology subtype. All of these data have led to choose the optimal first-line treatment of advanced NSCLC based on histologic diagnosis. However, this scenario raises a diagnostic issue: a specific diagnosis of NSCLC histologic subtype is mandatory. This review will discuss these new evidences in the first-line treatment of advanced NSCLC and their implication in the current clinical decision-making.

Bevacizumab, Carboplatin and Paclitaxel Combination Treatment in Advanced Stage Ovarian Cancer: The First Experience in Thammasat University Hospital, Thailand: A Case Report.

PubMed

Suwannarurk, Komsun; Thaweekul, Yudthadej; Mairaing, Karicha; Poomtavorn, Yenrudee; Tangtiang, Kaan; Piyawang, Wichet; Bhamarapravatana, Kornkarn

2015-04-01

Bevacizumab, a humanized monoclonal antibody targeting vascular endothelial growthfactor (VEGF), has been approvedfor concurrent treatment with first line chemotherapy in advanced epithelial ovarian cancer. A case of an advanced stage epithelial ovarian cancer (EOC) receiving a combination of bevacizumab, carboplatin andpaclitaxel chemotherapy was reported. A 44-year-old woman was presented with abdominal discomfort and distention for 4 months. Bilateral 12 cm diameter ovarian tumors were diagnosed as FIGO stage IIIc after surgical staging operation. Histopathology report showed the mixed type of serous and endometriod adenocarcinoma. The patient was then started on carboplatin/paclitaxel combination chemotherapy for 6 cycles after surgery every 3 weeks. Bevacizumab (7.5 mg/ m2) was concurrently administered with chemotherapy every 3 weeks startingfrom the 2nd cycle. A complete remission was achieved after the end of the chemotherapy treatment. Bevacizumab was continued for one year after the completion of the standard chemotherapy. Bone marrow suppression, hypertension and proteinuria were not found during Bevacizumab treatment. At bevacizumab treatment completion, a platinum-sensitive recurrent ovarian cancer was diagnosed at the two weeks postprogram routine check-up. The patient was counseled to start second line chemotherapy treatment and has yet to come back with her decision. Combination of bevacizumab, carboplatin and paclitaxelfor first line chemotherapy in advanced EOC in this case had no serious side effects and need further study.

Extensive retreat and re-advance of the West Antarctic Ice Sheet during the Holocene.

PubMed

Kingslake, J; Scherer, R P; Albrecht, T; Coenen, J; Powell, R D; Reese, R; Stansell, N D; Tulaczyk, S; Wearing, M G; Whitehouse, P L

2018-06-01

To predict the future contributions of the Antarctic ice sheets to sea-level rise, numerical models use reconstructions of past ice-sheet retreat after the Last Glacial Maximum to tune model parameters 1 . Reconstructions of the West Antarctic Ice Sheet have assumed that it retreated progressively throughout the Holocene epoch (the past 11,500 years or so) 2-4 . Here we show, however, that over this period the grounding line of the West Antarctic Ice Sheet (which marks the point at which it is no longer in contact with the ground and becomes a floating ice shelf) retreated several hundred kilometres inland of today's grounding line, before isostatic rebound caused it to re-advance to its present position. Our evidence includes, first, radiocarbon dating of sediment cores recovered from beneath the ice streams of the Ross Sea sector, indicating widespread Holocene marine exposure; and second, ice-penetrating radar observations of englacial structure in the Weddell Sea sector, indicating ice-shelf grounding. We explore the implications of these findings with an ice-sheet model. Modelled re-advance of the grounding line in the Holocene requires ice-shelf grounding caused by isostatic rebound. Our findings overturn the assumption of progressive retreat of the grounding line during the Holocene in West Antarctica, and corroborate previous suggestions of ice-sheet re-advance 5 . Rebound-driven stabilizing processes were apparently able to halt and reverse climate-initiated ice loss. Whether these processes can reverse present-day ice loss 6 on millennial timescales will depend on bedrock topography and mantle viscosity-parameters that are difficult to measure and to incorporate into ice-sheet models.

Advanced Turbofan Duct Liner Concepts

NASA Technical Reports Server (NTRS)

Bielak, Gerald W.; Premo, John W.; Hersh, Alan S.

1999-01-01

The Advanced Subsonic Technology Noise Reduction Program goal is to reduce aircraft noise by 10 EPNdB by the year 2000 relative, to 1992 technology. The improvement goal for nacelle attenuation is 25% relative to 1992 technology by 1997 and 50% by 2000. The Advanced Turbofan Duct Liner Concepts Task work by Boeing presented in this document was in support of these goals. The basis for the technical approach was a Boeing study conducted in 1993-94 under NASA/FAA contract NAS1-19349, Task 6, investigating broadband acoustic liner concepts. As a result of this work, it was recommended that linear double layer, linear and perforate triple layer, parallel element, and bulk absorber liners be further investigated to improve nacelle attenuations. NASA LaRC also suggested that "adaptive" liner concepts that would allow "in-situ" acoustic impedance control also be considered. As a result, bias flow and high-temperature liner concepts were also added to the investigation. The major conclusion from the above studies is that improvements in nacelle liner average acoustic impedance characteristics alone will not result in 25% increased nacelle noise reduction relative to 1992 technology. Nacelle design advancements currently being developed by Boeing are expected to add 20-40% more acoustic lining to hardwall regions in current inlets, which is predicted to result in and additional 40-80% attenuation improvement. Similar advancements are expected to allow 10-30% more acoustic lining in current fan ducts with 10-30% more attenuation expected. In addition, Boeing is currently developing a scarf inlet concept which is expected to give an additional 40-80% attenuation improvement for equivalent lining areas.

Molecular diagnostics of lung cancer in the clinic.

PubMed

Sholl, Lynette

2017-10-01

According to current practice guidelines, all patients with advanced non-small cell lung cancer (NSCLC) should undergo predictive biomarker testing. For squamous cell carcinoma patients, PD-L1 immunohistochemistry is indicated to select patients for immunotherapy in the first line. For lung adenocarcinoma, all patients with advanced disease should undergo testing for epidermal growth factor receptor ( EGFR ) mutations, ALK and ROS1 rearrangements, and PD-L1 expression to predict response to EGFR, ALK, or ROS1 targeted inhibitors or immunotherapy, respectively. Besides these, a number of other biomarkers are under clinical investigation as predictors of response to targeted therapies, including BRAF , ERBB2 , MET splice mutations and amplification, and RET rearrangements. Successful testing for this complex array of molecular targets demands careful coordination between proceduralists, pathologists and molecular laboratories to ensure proper tumor tissue handling following biopsy as well as judicious use of diagnostic immunohistochemistry. Even so, sample failure rates due to inadequate tumor tissue are high in practice, particularly when using sequential testing methods. Use of next generation sequencing (NGS) in clinical practice can enable detection of multiple targets and multiple alteration types (mutation, gene copy change, and rearrangement) simultaneously even with small amounts of input nucleic acids, thus increasing molecular testing success rates. In patients with an established lung cancer diagnosis but with prohibitively limited amounts of tumor tissue or who are experiencing relapse, analyses of circulating tumor DNA (ctDNA) from the plasma can serve as an alternate testing substrate, however the more limited clinical sensitivity of this approach must be taken into account. This review will explore the indications for and pitfalls of routine NGS and plasma genotyping in the clinic, including the intersection of these technologies.

Molecular diagnostics of lung cancer in the clinic

PubMed Central

2017-01-01

According to current practice guidelines, all patients with advanced non-small cell lung cancer (NSCLC) should undergo predictive biomarker testing. For squamous cell carcinoma patients, PD-L1 immunohistochemistry is indicated to select patients for immunotherapy in the first line. For lung adenocarcinoma, all patients with advanced disease should undergo testing for epidermal growth factor receptor (EGFR) mutations, ALK and ROS1 rearrangements, and PD-L1 expression to predict response to EGFR, ALK, or ROS1 targeted inhibitors or immunotherapy, respectively. Besides these, a number of other biomarkers are under clinical investigation as predictors of response to targeted therapies, including BRAF, ERBB2, MET splice mutations and amplification, and RET rearrangements. Successful testing for this complex array of molecular targets demands careful coordination between proceduralists, pathologists and molecular laboratories to ensure proper tumor tissue handling following biopsy as well as judicious use of diagnostic immunohistochemistry. Even so, sample failure rates due to inadequate tumor tissue are high in practice, particularly when using sequential testing methods. Use of next generation sequencing (NGS) in clinical practice can enable detection of multiple targets and multiple alteration types (mutation, gene copy change, and rearrangement) simultaneously even with small amounts of input nucleic acids, thus increasing molecular testing success rates. In patients with an established lung cancer diagnosis but with prohibitively limited amounts of tumor tissue or who are experiencing relapse, analyses of circulating tumor DNA (ctDNA) from the plasma can serve as an alternate testing substrate, however the more limited clinical sensitivity of this approach must be taken into account. This review will explore the indications for and pitfalls of routine NGS and plasma genotyping in the clinic, including the intersection of these technologies. PMID:29114472

Exploring the power of rice (O. sativa x O. rufipogon) chromosome segment substitution line libraries

USDA-ARS?s Scientific Manuscript database

Transgressive variation was reported as an increase in grain yield for several rice (Oryza sativa x O. rufipogon) advanced backcross mapping populations. The objective of this study was to develop chromosome segment substitution line (CSSL) libraries to further dissect the reported transgressive var...

Line-scan hyperspectral imaging platform for agro-food safety and quality evaluation: System enhancement and characterization

USDA-ARS?s Scientific Manuscript database

Line-scan-based hyperspectral imaging techniques have often served as a research tool to develop rapid multispectral methods based on only a few spectral bands for rapid online applications. With continuing technological advances and greater accessibility to and availability of optoelectronic imagin...

Humanities On (the) line: Classrooms, Space, and the Supplement.

ERIC Educational Resources Information Center

Nunes, Mark

New technological advances, in particular the Internet, can alter the architectural limits that restrict education by providing "lines of flight" outside of traditional structures. For example, students can access a library catalogue using computers in class, rather than actually having to go as a class to the library. In a…

Coaching and Counseling: Where To Draw the Line.

ERIC Educational Resources Information Center

Colvert, Audra L.

Examining the role of the forensics coach as counselor, this paper attempts to define the role more clearly and offers guidelines and suggestions concerning where to draw the line between coaching and counseling "forensicators." The paper advances the premise that coaches have many responsibilities which include significant dimensions of…

Two Dimensional Positioning and Heading Solution for Flying Vehicles using a Line-Scanning Laser Radar (LADAR)

DTIC Science & Technology

2011-03-24

6 2.4.1 Reference Frames . . . . . . . . . . . . . . . . . 6 2.4.2 Line and Feature Extraction . . . . . . . . . . . 7 2.4.3 SLAM ...Positioning System . . . . . . . . . . . . . . . . . . 1 LADAR Laser Radar . . . . . . . . . . . . . . . . . . . . . . . . . . 1 LiDAR Light Detection and...Ranging . . . . . . . . . . . . . . . . 2 SLAM Simultaneous Localization and Mapping . . . . . . . . . . 2 ANT Advanced Navigation Technology

Response to oxalic acid as a resistance assay for Sclerotinia minor in peanut

USDA-ARS?s Scientific Manuscript database

Response to oxalic acid was evaluated as a potential assay for screening peanut breeding lines for resistance to Sclerotinia blight caused by Sclerotinia minor. Detached stems of seven Spanish- and six runner-type peanut cultivars and advanced breeding lines, varying in resistance to Sclerotinia bl...

40 CFR 1051.315 - How do I know when my engine family fails the production-line testing requirements?

Code of Federal Regulations, 2012 CFR

2012-07-01

... fails the production-line testing requirements? 1051.315 Section 1051.315 Protection of Environment... family fails the production-line testing requirements? This section describes the pass-fail criteria for....320 for the requirements that apply to individual vehicles or engines that fail a production-line test...

40 CFR 1045.315 - How do I know when my engine family fails the production-line testing requirements?

Code of Federal Regulations, 2011 CFR

2011-07-01

... fails the production-line testing requirements? 1045.315 Section 1045.315 Protection of Environment... family fails the production-line testing requirements? This section describes the pass-fail criteria for... § 1045.320 for the requirements that apply to individual engines that fail a production-line test. (a...

40 CFR 1054.315 - How do I know when my engine family fails the production-line testing requirements?

Code of Federal Regulations, 2011 CFR

2011-07-01

... fails the production-line testing requirements? 1054.315 Section 1054.315 Protection of Environment... family fails the production-line testing requirements? This section describes the pass-fail criteria for... § 1054.320 for the requirements that apply to individual engines that fail a production-line test. (a...

40 CFR 1045.315 - How do I know when my engine family fails the production-line testing requirements?

Code of Federal Regulations, 2010 CFR

2010-07-01

... fails the production-line testing requirements? 1045.315 Section 1045.315 Protection of Environment... family fails the production-line testing requirements? This section describes the pass-fail criteria for... § 1045.320 for the requirements that apply to individual engines that fail a production-line test. (a...

40 CFR 1045.315 - How do I know when my engine family fails the production-line testing requirements?

Code of Federal Regulations, 2012 CFR

2012-07-01

... fails the production-line testing requirements? 1045.315 Section 1045.315 Protection of Environment... family fails the production-line testing requirements? This section describes the pass-fail criteria for... § 1045.320 for the requirements that apply to individual engines that fail a production-line test. (a...

40 CFR 1054.315 - How do I know when my engine family fails the production-line testing requirements?

Code of Federal Regulations, 2012 CFR

2012-07-01

... fails the production-line testing requirements? 1054.315 Section 1054.315 Protection of Environment... family fails the production-line testing requirements? This section describes the pass-fail criteria for... § 1054.320 for the requirements that apply to individual engines that fail a production-line test. (a...

40 CFR 1051.315 - How do I know when my engine family fails the production-line testing requirements?

Code of Federal Regulations, 2011 CFR

2011-07-01

... fails the production-line testing requirements? 1051.315 Section 1051.315 Protection of Environment... family fails the production-line testing requirements? This section describes the pass-fail criteria for....320 for the requirements that apply to individual vehicles or engines that fail a production-line test...

Advances in laser technology for the atmospheric sciences; Proceedings of the Seminar, San Diego, Calif., August 25, 26, 1977

NASA Technical Reports Server (NTRS)

Trolinger, J. D. (Editor); Moore, W. W.

1977-01-01

These papers deal with recent research, developments, and applications in laser and electrooptics technology, particularly with regard to atmospheric effects in imaging and propagation, laser instrumentation and measurements, and particle measurement. Specific topics include advanced imaging techniques, image resolution through atmospheric turbulence over the ocean, an efficient method for calculating transmittance profiles, a comparison of a corner-cube reflector and a plane mirror in folded-path and direct transmission through atmospheric turbulence, line-spread instrumentation for propagation measurements, scaling laws for thermal fluctuations in the layer adjacent to ocean waves, particle sizing by laser photography, and an optical Fourier transform analysis of satellite cloud imagery. Other papers discuss a subnanosecond photomultiplier tube for laser application, holography of solid propellant combustion, diagnostics of turbulence by holography, a camera for in situ photography of cloud particles from a hail research aircraft, and field testing of a long-path laser transmissometer designed for atmospheric visibility measurements.

Ares First Stage "Systemology" - Combining Advanced Systems Engineering and Planning Tools to Assure Mission Success

NASA Technical Reports Server (NTRS)

Seiler, James; Brasfield, Fred; Cannon, Scott

2008-01-01

Ares is an integral part of NASA s Constellation architecture that will provide crew and cargo access to the International Space Station as well as low earth orbit support for lunar missions. Ares replaces the Space Shuttle in the post 2010 time frame. Ares I is an in-line, two-stage rocket topped by the Orion Crew Exploration Vehicle, its service module, and a launch abort system. The Ares I first stage is a single, five-segment reusable solid rocket booster derived from the Space Shuttle Program's reusable solid rocket motor. The Ares second or upper stage is propelled by a J-2X main engine fueled with liquid oxygen and liquid hydrogen. This paper describes the advanced systems engineering and planning tools being utilized for the design, test, and qualification of the Ares I first stage element. Included are descriptions of the current first stage design, the milestone schedule requirements, and the marriage of systems engineering, detailed planning efforts, and roadmapping employed to achieve these goals.

SmallSat Innovations for Planetary Science

NASA Astrophysics Data System (ADS)

Weinberg, Jonathan; Petroy, Shelley; Roark, Shane; Schindhelm, Eric

2017-10-01

As NASA continues to look for ways to fly smaller planetary missions such as SIMPLEX, MoO, and Venus Bridge, it is important that spacecraft and instrument capabilities keep pace to allow these missions to move forward. As spacecraft become smaller, it is necessary to balance size with capability, reliability and payload capacity. Ball Aerospace offers extensive SmallSat capabilities matured over the past decade, utilizing our broad experience developing mission architecture, assembling spacecraft and instruments, and testing advanced enabling technologies. Ball SmallSats inherit their software capabilities from the flight proven Ball Configurable Platform (BCP) line of spacecraft, and may be tailored to meet the unique requirements of Planetary Science missions. We present here recent efforts in pioneering both instrument miniaturization and SmallSat/sensorcraft development through mission design and implementation. Ball has flown several missions with small, but capable spacecraft. We also have demonstrated a variety of enhanced spacecraft/instrument capabilities in the laboratory and in flight to advance autonomy in spaceflight hardware that can enable some small planetary missions.

Dental Pulp and Dentin Tissue Engineering and Regeneration – Advancement and Challenge

PubMed Central

Huang, George T.-J.

2012-01-01

Hard tissue is difficult to repair especially dental structures. Tooth enamel is incapable of self-repairing whereas dentin and cememtum can regenerate with limited capacity. Enamel and dentin are commonly under the attack by caries. Extensive forms of caries destroy enamel and dentin and can lead to dental pulp infection. Entire pulp amputation followed by the pulp space disinfection and filled with an artificial rubber-like material is employed to treat the infection --commonly known as root canal or endodontic therapy. Regeneration of dentin relies on having vital pulps; however, regeneration of pulp tissue has been difficult as the tissue is encased in dentin without collateral blood supply except from the root apical end. With the advent of modern tissue engineering concept and the discovery of dental stem cells, regeneration of pulp and dentin has been tested. This article will review the recent endeavor on pulp and dentin tissue engineering and regeneration. The prospective outcome of the current advancement and challenge in this line of research will be discussed. PMID:21196351

Oxaliplatin-Related Ocular Toxicity

PubMed Central

Mesquida, Marina; Sanchez-Dalmau, Bernardo; Ortiz-Perez, Santiago; Pelegrín, Laura; Molina-Fernandez, Juan José; Figueras-Roca, Marc; Casaroli-Marano, Ricardo; Adán, Alfredo

2010-01-01

We report the case of a 52-year-old woman with advanced colorectal cancer who was treated with oxaliplatin on a FOLFOX schedule. After 3 cycles of chemotherapy, she started to complain of visual loss, altered color vision and neurological symptoms. Due to the suspicion of ocular and neurological toxicity, antineoplastic treatment was stopped. Her visual field showed a concentric bilateral scotoma and the electrooculogram test revealed severe impairment of the retinal pigment epithelium. Visual acuity, color vision and visual field recovered completely 8 months later, although electrooculogram remained abnormal. Ocular toxicity has been reported as an infrequent adverse event of oxaliplatin. Findings in this case indicate toxicity of this chemotherapeutic agent on the retinal pigment epithelium, which has not been reported before. This damage could be permanent, and it thus differs from previously described oxaliplatin-induced ocular toxicities, which are usually transient and reversible. With increasing use of oxaliplatin as first-line treatment in advanced colorectal cancer, we have to be aware of this possible toxicity. PMID:21151636

Development of advanced, continuous mild gasification process for the production of co-products

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

Ness, R.O. Jr.; Aulich, T.R.

1991-05-01

The current objective of the University of North Dakota Energy and Environmental Research Center (EERC) mild gasification project is to optimize reaction char and marketable liquids production on a 100-lb/hr scale using Wyodak subbituminous and Indiana No. 3 bituminous coals. Tests performed using the EERC 100-lb/hr process development unit (PDU) include a refractory-cure (Test P001), a test using petroleum coke (Test P002), and tests using Wyodak and Indiana coals. The reactor system used for the 11 PDU tests conducted to date consists of a spouted, fluid-bed carbonizer equipped with an on-line condensation train that yields three boiling point fractions ofmore » coal liquids ranging in volatility from about (77{degrees}--750{degrees}F) (25{degrees}--400{degrees}C). The September--December 1990 quarterly report described reaction conditions and the bulk of the analytical results for Tests P010 and P011. This report describes further P010 and P011 analytical work, including the generation of simulated distillation curves for liquid samples on the basis of sulfur content, using gas chromatography coupled with atomic emission detection (GC/AED) analysis. 13 figs., 3 tabs.« less

Current Molecular Targeted Therapy in Advanced Gastric Cancer: A Comprehensive Review of Therapeutic Mechanism, Clinical Trials, and Practical Application

PubMed Central

Li, Kaichun; Li, Jin

2016-01-01

Despite the great progress in the treatment of gastric cancer, it is still the third leading cause of cancer death worldwide. Patients often miss the opportunity for a surgical cure, because the cancer has already developed into advanced cancer when identified. Compared to best supportive care, chemotherapy can improve quality of life and prolong survival time, but the overall survival is often short. Due to the molecular study of gastric cancer, new molecular targeted drugs have entered the clinical use. Trastuzumab, an antibody targeting human epidermal growth factor receptor 2 (HER2), can significantly improve survival in advanced gastric cancer patients with HER2 overexpression. Second-line treatment of advanced gastric cancer with ramucirumab, an antibody targeting VEGFR-2, alone or in combination with paclitaxel, has been proved to provide a beneficial effect. The VEGFR-2 tyrosine kinase inhibitor, apatinib, can improve the survival of advanced gastric cancer patients after second-line chemotherapy failure. Unfortunately, none of the EGFR targeting antibodies (cetuximab or panitumumab), VEGF targeting monoclonal antibodies (bevacizumab), mTOR inhibitor (everolimus), or HGF/MET pathway targeting drugs has a significant survival benefit. Many other clinical trials based on molecular markers are underway. This review will summarize targeted therapies for advanced gastric cancer. PMID:26880889

Advanced eddy current test signal analysis for steam generator tube defect classification and characterization

NASA Astrophysics Data System (ADS)

McClanahan, James Patrick

Eddy Current Testing (ECT) is a Non-Destructive Examination (NDE) technique that is widely used in power generating plants (both nuclear and fossil) to test the integrity of heat exchanger (HX) and steam generator (SG) tubing. Specifically for this research, laboratory-generated, flawed tubing data were examined. The purpose of this dissertation is to develop and implement an automated method for the classification and an advanced characterization of defects in HX and SG tubing. These two improvements enhanced the robustness of characterization as compared to traditional bobbin-coil ECT data analysis methods. A more robust classification and characterization of the tube flaw in-situ (while the SG is on-line but not when the plant is operating), should provide valuable information to the power industry. The following are the conclusions reached from this research. A feature extraction program acquiring relevant information from both the mixed, absolute and differential data was successfully implemented. The CWT was utilized to extract more information from the mixed, complex differential data. Image Processing techniques used to extract the information contained in the generated CWT, classified the data with a high success rate. The data were accurately classified, utilizing the compressed feature vector and using a Bayes classification system. An estimation of the upper bound for the probability of error, using the Bhattacharyya distance, was successfully applied to the Bayesian classification. The classified data were separated according to flaw-type (classification) to enhance characterization. The characterization routine used dedicated, flaw-type specific ANNs that made the characterization of the tube flaw more robust. The inclusion of outliers may help complete the feature space so that classification accuracy is increased. Given that the eddy current test signals appear very similar, there may not be sufficient information to make an extremely accurate (>95%) classification or an advanced characterization using this system. It is necessary to have a larger database fore more accurate system learning.

Multiple-Line Inference of Selection on Quantitative Traits

PubMed Central

Riedel, Nico; Khatri, Bhavin S.; Lässig, Michael; Berg, Johannes

2015-01-01

Trait differences between species may be attributable to natural selection. However, quantifying the strength of evidence for selection acting on a particular trait is a difficult task. Here we develop a population genetics test for selection acting on a quantitative trait that is based on multiple-line crosses. We show that using multiple lines increases both the power and the scope of selection inferences. First, a test based on three or more lines detects selection with strongly increased statistical significance, and we show explicitly how the sensitivity of the test depends on the number of lines. Second, a multiple-line test can distinguish between different lineage-specific selection scenarios. Our analytical results are complemented by extensive numerical simulations. We then apply the multiple-line test to QTL data on floral character traits in plant species of the Mimulus genus and on photoperiodic traits in different maize strains, where we find a signature of lineage-specific selection not seen in two-line tests. PMID:26139839

Equity, Status and Freedom: A Note on Higher Education

ERIC Educational Resources Information Center

Marginson, Simon

2011-01-01

Strategies to enhance socio-economic equity in higher education embody one or both of two objectives. The first strategy is to advance "fairness" by changing the composition of participation, bringing higher education into line with the ideal model of a socially representative system. The second strategy advances "inclusion" by…

The evaluation of advanced traveler information services (ATIS) impacts on truck travel time reliability : using the simulated yoked study concept

DOT National Transportation Integrated Search

2004-03-01

The ability of Advanced Traveler Information Systems (ATIS) to improve the on-time reliability of urban truck movements is evaluated through the application of the Heuristic On-Line Web- : Linked Arrival Time Estimation (HOWLATE) methodology. In HOWL...

Development of cost effective fenceline monitoring approaches to support advanced leak detection and repair strategies

EPA Science Inventory

Cost-effective fence line and process monitoring systems to support advanced leak detection and repair (LDAR) strategies can enhance protection of public health, facilitate worker safety, and help companies realize cost savings by reducing lost product. The U.S. EPA Office of Re...

School Integration Matters: Research-Based Strategies to Advance Equity

ERIC Educational Resources Information Center

Frankenberg, Erica, Ed.; Garces, Liliana M., Ed.; Hopkins, Megan, Ed.

2016-01-01

More than 60 years after the "Brown v. Board of Education" decision declared segregated schooling inherently unequal, this timely book sheds light on how and why U.S. schools are experiencing increasing segregation along racial, socioeconomic, and linguistic lines. It offers policy and programmatic alternatives for advancing equity and…

Computer aided statistical process control for on-line instrumentation

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

Meils, D.E.

1995-01-01

On-line chemical process instrumentation historically has been used for trending. Recent technological advances in on-line instrumentation have improved the accuracy and reliability of on-line instrumentation. However, little attention has been given to validating and verifying on-line instrumentation. This paper presents two practical approaches for validating instrument performance by comparison of on-line instrument response to either another portable instrument or another bench instrument. Because the comparison of two instruments` performance to each other requires somewhat complex statistical calculations, a computer code (Lab Stats Pack{reg_sign}) is used to simplify the calculations. Lab Stats Pack{reg_sign} also develops control charts that may be usedmore » for continuous verification of on-line instrument performance.« less

Paclitaxel: a pharmacoeconomic review of its use in the treatment of ovarian cancer.

PubMed

Young, M; Plosker, G L

2001-01-01

Paclitaxel belongs to the group of antitumour agents called the taxanes. Its efficacy in advanced ovarian cancer has been established in large, randomised phase III clinical trials. When used in combination with cisplatin for first-line treatment of advanced ovarian cancer, it is superior to cyclophosphamide/cisplatin, with gains in median survival of around 1 year. Paclitaxel plus carboplatin has similar efficacy to paclitaxel plus cisplatin. There is now consensus that paclitaxel plus either carboplatin or cisplatin is the recommended first-line therapy for patients with advanced ovarian cancer. The particular combination employed may vary between institutions and geographical regions, although paclitaxel plus carboplatin is generally better tolerated (i.e. lower incidence of non-haematological adverse events) than paclitaxel plus cisplatin and is widely used in many countries. Paclitaxel is also used as monotherapy in second-line (salvage) treatment of ovarian cancer. Pharmacoeconomic analyses performed to date have primarily focused on first-line therapy comparing the combination of paclitaxel/cisplatin with cyclophosphamide/cisplatin. All studies incorporated clinical outcomes data, most commonly from the Gynecologic Oncology Group (GOG) 111 trial, showing a survival advantage for paclitaxel/cisplatin. These studies report incremental cost-effectiveness ratios (ICERs) ranging from $US 6395 per additional life-year gained (LYG) in Spain (1995/96 values) to $US 44,690 per additional progression-free LYG in France (year of costs not reported). Five studies were based in the US and Canada and these reported very similar ICERs of $US 13,135 (year of costs not reported) to $US 25,131 (1993 costs) per additional LYG. In all of these studies the incremental costs of paclitaxel/cisplatin therapy fall well within the commonly cited threshold limit of $US 50,000 for new therapies and compare well with incremental costs reported for other oncological and life-saving therapies. Patient preferences and quality of life are important issues due to the short survival of patients with advanced ovarian cancer. Two cost-utility studies reported similar incremental cost-utility ratios (ICURs). In the study based on US costs, the ICUR of paclitaxel/cisplatin treatment was US $18,200 per additional quality-adjusted life-year (QALY) [1995 drug costs]. In a Canadian study the ICUR ranged from 11,600 Canadian dollars ($Can) to $Can 24,200 (1996 costs) per additional progression-free QALY depending on the choice of second-line treatment. Paclitaxel used in combination with cisplatin offers survival and utility gains versus cyclophosphamide plus cisplatin, when used as first-line treatment in patients with stage III or IV ovarian cancer. The incremental cost for these gains is within the accepted range for healthcare interventions. However, pharmacoeconomic analyses of paclitaxel plus carboplatin--a combination widely accepted for use in women with advanced ovarian cancer and with clinical advantages over paclitaxel plus cisplatin in terms of ease of administration and tolerability profile--are currently lacking. Nevertheless, results of available pharmacoeconomic data support the clinical use of paclitaxel/platinum combinations, particularly paclitaxel plus cisplatin, as a first-line chemotherapy treatment option in patients with advanced ovarian cancer.

Efficacy and safety of cytotoxic drug chemotherapy after first-line EGFR-TKI treatment in elderly patients with non-small-cell lung cancer harboring sensitive EGFR mutations.

PubMed

Imai, Hisao; Minemura, Hiroyuki; Sugiyama, Tomohide; Yamada, Yutaka; Kaira, Kyoichi; Kanazawa, Kenya; Kasai, Takashi; Kaburagi, Takayuki; Minato, Koichi

2018-05-08

Epidermal growth factor receptor-tyrosine kinase inhibitor (EGFR-TKI) is effective as first-line chemotherapy for patients with advanced non-small-cell lung cancer (NSCLC) harboring sensitive EGFR mutations. However, whether the efficacy of second-line cytotoxic drug chemotherapy after first-line EGFR-TKI treatment is similar to that of first-line cytotoxic drug chemotherapy in elderly patients aged ≥ 75 years harboring sensitive EGFR mutations is unclear. Therefore, we aimed to investigate the efficacy and safety of cytotoxic drug chemotherapy after first-line EGFR-TKI treatment in elderly patients with NSCLC harboring sensitive EGFR mutations. We retrospectively evaluated the clinical effects and safety profiles of second-line cytotoxic drug chemotherapy after first-line EGFR-TKI treatment in elderly patients with NSCLC harboring sensitive EGFR mutations (exon 19 deletion/exon 21 L858R mutation). Between April 2008 and December 2015, 78 elderly patients with advanced NSCLC harboring sensitive EGFR mutations received first-line EGFR-TKI at four Japanese institutions. Baseline characteristics, regimens, responses to first- and second-line treatments, whether or not patients received subsequent treatment, and if not, the reasons for non-administration were recorded. Overall, 20 patients with a median age of 79.5 years (range 75-85 years) were included in our analysis. The overall response, disease control, median progression-free survival, and overall survival rates were 15.0, 60.0%, 2.4, and 13.2 months, respectively. Common adverse events included leukopenia, neutropenia, anemia, thrombocytopenia, malaise, and anorexia. Major grade 3 or 4 toxicities included leukopenia (25.0%) and neutropenia (45.0%). No treatment-related deaths were noted. Second-line cytotoxic drug chemotherapy after first-line EGFR-TKI treatment among elderly patients with NSCLC harboring sensitive EGFR mutations was effective and safe and showed equivalent outcomes to first-line cytotoxic drug chemotherapy.

Improvement of the mechanical reliability of monolithic refractory linings for coal gasification process vessels. Final report

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

Potter, R.A.

1981-09-01

Eighteen heat-up tests were run on nine standard and experimental dual component monolithic refractory concrete linings. These tests were run with a five foot diameter by 14-ft high Pressure Vessel/Test Furnace designed to accommodate a 12-inch thick by 5-ft high refractory lining, heat the hot face to 2000/sup 0/F and expose the lining to air or steam pressures up to 150 psig. Results obtained from standard type linings in the test facility indicated that lining degradation duplicated that observed in field installations. The lining performance was significantly improved due to information gained from a systematic study of the cracking thatmore » occurred in the linings; the analysis of the lining strains, shell stresses and acoustic emission results; and the stress analyses performed on the standard and experimental lining designs with the finite element analysis computer programs, REFSAM and RESGAP.« less

Laparoscopic resection of locally advanced gastrointestinal stromal tumour (GIST) of the stomach following neoadjuvant imatinib chemoreduction.

PubMed

Berney, Christophe R

2015-01-01

Laparoscopic resection of locally advanced gastrointestinal stromal tumours (GISTs) is rarely offered to patients as a first line of treatment. We present two cases of locally advanced gastric GISTs successfully treated with neoadjuvant imatinib and followed up by complete laparoscopic excision of the residual tumour mass. There was no evidence of local recurrence or distant metastases after a mean follow up of more than 40 months. Over the last decade, the development of imatinib has totally revolutionized management of metastatic GISTs and it is now possible to achieve primary tumour downstaging of more than 80%. Unfortunately, current literature on laparoscopic excision of locally advanced gastric GISTs following neoadjuvant treatment of imatinib remains scarce. The present cases strongly suggest that this new therapeutic approach might become the preferred medical option in such clinical situation. Patients with locally advanced non-metastatic gastric GISTs should be offered first-line neoadjuvant. Imatinib-based cytoreductive chemotherapy as an alternative to radical debulking surgery, as a substantial proportion of them will experience significant tumour shrinkage and therefore benefit from a much less invasive laparoscopic approach. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Advanced optical imaging platform for CD metrology and defect review on 130-nm to 100-nm node reticles: an overview of preliminary results

NASA Astrophysics Data System (ADS)

Hourd, Andrew C.; Grimshaw, Anthony; Scheuring, Gerd; Gittinger, Christian; Brueck, Hans-Juergen; Chen, Shiuh-Bin; Chen, Parkson W.; Hartmann, Hans; Ordynskyy, Volodymyr; Jonckheere, Rik M.; Philipsen, Vicky; Schaetz, Thomas; Sommer, Karl

2002-08-01

Critical Dimension fidelity continues to be one of the key driving parameters defining photomask quality and printing performance. The present advanced optical CD metrology systems, operating at i-line, will very soon be challenged as viable tools owing to their restricted resolution and measurement linearity impact on the ability to produce repeatable measurements. Alternative measurement technologies such as CD-SEM and -AFM have started to appear, but are also not without tier concerns in the field of reticle CD metrology. This paper introduces a new optical metrology system (MueTec /) operating at DUV wavelength (248nm), which has been specifically designed to meet the resolution and measurement repeatability requirements of reticle manufacture at the 130nm and 100nm nodes. The system is based upon a specially designed mechanical-optical platform for maximum stability and very advanced optical, illumination, alignment and software systems. The at wavelength operation of this system also makes it an ideal platform for defect printability analysis and review. The system is currently part of a European Commission funded assessment project (IST-2000-28086: McD'OR) to develop a testing strategy to verify the system performance, agree on equipment specifications and demonstrate its capability on advanced production reticles - including long-term reliability. It is the preliminary results from this evaluation that are presented here.

Advanced RF Sources Based on Novel Nonlinear Transmission Lines

DTIC Science & Technology

2015-01-26

microwave (HPM) sources. It is also critical to thin film devices and integrated circuits, carbon nanotube based cathodes and interconnects, field emitters ... line model (TLM) in Fig. 6b. Our model is compared with TLM, shown in Fig. 7a. When the interface resistance rc is small, TLM becomes inaccurate...due to current crowding. Fig. 6. (a) Electrical contact including specific interfacial resistivity ρc, and (b) its transmission line model

A Solar-Pumped Fluorescence Model for Line-By-Line Emission Intensities in the B-X, A-X, and X-X Band Systems of 12C14N

NASA Technical Reports Server (NTRS)

Paganini, L.; Mumma, M. J.

2016-01-01

We present a new quantitative model for detailed solar-pumped fluorescent emission of the main isotopologue of CN. The derived fluorescence efficiencies permit estimation and interpretation of ro-vibrational infrared line intensities of CN in exospheres exposed to solar (or stellar) radiation. Our g-factors are applicable to astronomical observations of CN extending from infrared to optical wavelengths, and we compare them with previous calculations in the literature. The new model enables extraction of rotational temperature, column abundance, and production rate from astronomical observations of CN in the inner coma of comets. Our model accounts for excitation and de-excitation of rotational levels in the ground vibrational state by collisions, solar excitation to the A(sup 2)Pi(sub I) and B(sup 2)Sum(sup +) electronically excited states followed by cascade to ro-vibrational levels of X(sup 2)Sum(sup +), and direct solar infrared pumping of ro-vibrational levels in the X(sup 2)Sum(sup +) state. The model uses advanced solar spectra acquired at high spectral resolution at the relevant infrared and optical wavelengths and considers the heliocentric radial velocity of the comet (the Swings effect) when assessing the exciting solar flux for a given transition. We present model predictions for the variation of fluorescence rates with rotational temperature and heliocentric radial velocity. Furthermore, we test our fluorescence model by comparing predicted and measured line-by-line intensities for X(sup 2)Sum(sup +) (1-0) in comet C/2014 Q2 (Lovejoy), thereby identifying multiple emission lines observed at IR wavelengths.

DKK1 and Kremen Expression Predicts the Osteoblastic Response to Bone Metastasis.

PubMed

Clines, Katrina L; Clines, Gregory A

2018-05-14

Bone metastasis is a complication of advanced breast and prostate cancer. Tumor-secreted Dickkopf homolog 1 (DKK1), an inhibitor of canonical Wnt signaling and osteoblast differentiation, was proposed to regulate the osteoblastic response to metastatic cancer in bone. The objectives of this study were to compare DKK1 expression with the in vivo osteoblastic response in a panel of breast and prostate cancer cell lines, and to discover mechanisms that regulate cancer DKK1 expression. DKK1 expression was highest in MDA-MB-231 and PC3 cells that produce osteolytic lesions, and hence a suppressed osteoblastic response, in animal models of bone metastasis. LnCaP, C4-2B, LuCaP23.1, T47D, ZR-75-1, MCF-7, ARCaP and ARCaP M cancer cells that generate osteoblastic, mixed or no bone lesions had the lowest DKK1 expression. The cell lines with negligible expression, LnCaP, C4-2B and T47D, exhibited methylation of the DKK1 promoter. Canonical Wnt signaling activity was then determined and found in all cell lines tested, even in the MDA-MB-231 and PC3 cell lines despite sizeable amounts of DKK1 protein expression expected to block canonical Wnt signaling. A mechanism of DKK1 resistance in the osteolytic cell lines was investigated and determined to be at least partially due to down-regulation of the DKK1 receptors Kremen1 and Kremen2 in the MDA-MB-231 and PC3 cell lines. Combined DKK1 and Kremen expression in cancer cells may serve as predictive markers of the osteoblastic response of breast and prostate cancer bone metastasis. Published by Elsevier Inc.

RESOLVE (Regolith & Environmental Science Oxygen & Lunar Volatile Extraction) Project

NASA Technical Reports Server (NTRS)

Parker, Ray; Coan, Mary; Captain, Janine; Cryderman, Kate; Quinn, Jacqueline

2015-01-01

The RESOLVE Project is a lunar prospecting mission whose primary goal is to characterize water and other volatiles in lunar regolith. The Lunar Advanced Volatiles Analysis (LAVA) subsystem is comprised of a fluid subsystem that transports flow to the gas chromatograph - mass spectrometer (GC-MS) instruments that characterize volatiles and the Water Droplet Demonstration (WDD) that will capture and display water condensation in the gas stream. The LAVA Engineering Test Unit (ETU) is undergoing risk reduction testing this summer and fall within a vacuum chamber to understand and characterize component and integrated system performance. Testing of line heaters, printed circuit heaters, pressure transducers, temperature sensors, regulators, and valves in atmospheric and vacuum environments was done. Test procedures were developed to guide experimental tests and test reports to analyze and draw conclusions from the data. In addition, knowledge and experience was gained with preparing a vacuum chamber with fluid and electrical connections. Further testing will include integrated testing of the fluid subsystem with the gas supply system, near-infrared spectrometer for the Surge Tank (NIRST), WDD, Sample Delivery System, and GC-MS in the vacuum chamber. Since LAVA is a scientific subsystem, the near infrared spectrometer and GC-MS instruments will be tested during the ETU testing phase.

Lightning protection guidelines and test data for adhesively bonded aircraft structures

NASA Technical Reports Server (NTRS)

Pryzby, J. E.; Plumer, J. A.

1984-01-01

The highly competitive marketplace and increasing cost of energy has motivated manufacturers of general aviation aircraft to utilize composite materials and metal-to-metal bonding in place of conventional fasteners and rivets to reduce weight, obtain smoother outside surfaces and reduce drag. The purpose of this program is protection of these new structures from hazardous lightning effects. The program began with a survey of advance-technology materials and fabrication methods under consideration for future designs. Sub-element specimens were subjected to simulated lightning voltages and currents. Measurements of bond line voltages, electrical sparking, and mechanical strength degradation were made to comprise a data base of electrical properties for new technology materials and basic structural configurations. The second hase of the program involved tests on full scale wing structures which contained integral fuel tanks and which were representative of examples of new technology structures and fuel systems. The purpose of these tests was to provide a comparison between full scale structural measurements and those obtained from the sub-element specimens.

Initial Navigation Alignment of Optical Instruments on GOES-R

NASA Technical Reports Server (NTRS)

Isaacson, Peter J.; DeLuccia, Frank J.; Reth, Alan D.; Igli, David A.; Carter, Delano R.

2016-01-01

Post-launch alignment errors for the Advanced Baseline Imager (ABI) and Geospatial Lightning Mapper (GLM) on GOES-R may be too large for the image navigation and registration (INR) processing algorithms to function without an initial adjustment to calibration parameters. We present an approach that leverages a combination of user-selected image-to-image tie points and image correlation algorithms to estimate this initial launch-induced offset and calculate adjustments to the Line of Sight Motion Compensation (LMC) parameters. We also present an approach to generate synthetic test images, to which shifts and rotations of known magnitude are applied. Results of applying the initial alignment tools to a subset of these synthetic test images are presented. The results for both ABI and GLM are within the specifications established for these tools, and indicate that application of these tools during the post-launch test (PLT) phase of GOES-R operations will enable the automated INR algorithms for both instruments to function as intended.

Illustrating idiographic methods for translation research: moderation effects, natural clinical experiments, and complex treatment-by-subgroup interactions.

PubMed

Ridenour, Ty A; Wittenborn, Andrea K; Raiff, Bethany R; Benedict, Neal; Kane-Gill, Sandra

2016-03-01

A critical juncture in translation research involves the preliminary studies of intervention tools, provider training programs, policies, and other mechanisms used to leverage knowledge garnered at one translation stage into another stage. Potentially useful for such studies are rigorous techniques for conducting within-subject clinical trials, which have advanced incrementally over the last decade. However, these methods have largely not been utilized within prevention or translation contexts. The purpose of this manuscript is to demonstrate the flexibility, wide applicability, and rigor of idiographic clinical trials for preliminary testing of intervention mechanisms. Specifically demonstrated are novel uses of state-space modeling for testing intervention mechanisms of short-term outcomes, identifying heterogeneity in and moderation of within-person treatment mechanisms, a horizontal line plot to refine sampling design during the course of a clinic-based experimental study, and the need to test a treatment's efficacy as treatment is administered along with (e.g., traditional 12-month outcomes).

Systemic Treatment Patterns With Advanced or Recurrent Non-small Cell Lung Cancer in Japan: A Retrospective Hospital Administrative Database Study.

PubMed

Wang, Feng; Mishina, Sari; Takai, Shinji; Le, T Kim; Ochi, Kenya; Funato, Kotaro; Matsuoka, Shozo; Ohe, Yuichiro

2017-06-01

Data on the treatment of non-small cell lung cancer (NSCLC) in real-world clinical practice in Japan are limited. This large-scale, retrospective cohort study examined data on patients' characteristics and systemic therapies for advanced or recurrent NSCLC in routine practice in Japan. This study used an electronic health records-based database of health claims and Diagnosis Procedure Combination data from 215 consenting hospitals in Japan. Records from April 2008 to September 2015 were analyzed. Regimens were examined by histology, age, sex, and therapeutic line. Logistic regression analysis was performed to predict which clinical and demographic factors affected patients' probability of receiving first- or second-line therapy or completing first-line platinum-based chemotherapy. Among 16,413 patients, 67.9%, 39.2%, and 22.3% received first-, second-, and third-line systemic treatment, respectively. Treatment was more common in patients aged <75 versus ≥75 years (76.0% vs 51.6%), in female versus male patients (71.6% vs 65.4%), and in patients with nonsquamous versus squamous disease (75.6% vs 61.9%). More than 30 systemic regimens were administered. The most common first-line therapy was platinum-based chemotherapy (nonsquamous, 53.6%; squamous, 73.7%). Non-platinum-based chemotherapy use increased in the second-line setting, but platinum-based chemotherapy use remained high (nonsquamous, 33.9%; squamous, 38.6%). Tyrosine kinase inhibitors were used in 32.0% and 29.4% of patients with nonsquamous NSCLC in the first- and second-line settings, respectively. Switches from first- to second-line platinum-based chemotherapy and from first- to second-line tyrosine kinase inhibitors occurred. Forty-two percent of the patients died during hospitalization. In the logistic regression analysis, factors associated with a decreased likelihood of receiving first-line therapy were male sex, squamous histology, age >75 years, treatment at a general (vs cancer-specific) hospital, worse scores on certain activities of daily living, presence of chronic pulmonary disease, worse Hugh-Jones classification, and positive smoking status. The likelihood of completing first-line platinum-based chemotherapy was increased with greater body mass index, better activities of daily living scores, absence of chronic pulmonary disease, and better Hugh-Jones classification. The likelihood of continuing with second-line therapy was decreased with older age and recurrence of NSCLC. Systemic treatment patterns for advanced or recurrent NSCLC in Japan were varied. Nearly 30% of all patients and approximately half of elderly patients did not receive systemic treatment. Treatment rates declined with subsequent therapeutic lines. Generally, guidelines were followed with first-line treatment administration, but not with second-line administration. These results underscore the need for better guideline adherence and more optimal treatment in and elderly patients and in those receiving later-line treatment in Japan. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Recent advances at NASA in calculating the electronic spectra of diatomic molecules

NASA Technical Reports Server (NTRS)

Whiting, Ellis E.; Paterson, John A.

1988-01-01

Advanced entry vehicles, such as the proposed Aero-assisted Orbital Transfer Vehicle, provide new and challenging problems for spectroscopy. Large portions of the flow field about such vehicles will be characterized by chemical and thermal nonequilibrium. Only by considering the actual overlap of the atomic and rotational lines emitted by the species present can the impact of radiative transport within the flow field be assessed correctly. To help make such an assessment, a new computer program is described that can generate high-resolution, line-by-line spectra for any spin-allowed transitions in diatomic molecules. The program includes the matrix elements for the rotational energy and distortion to the fourth order; the spin-orbit, spin-spin, and spin-rotation interactions to first order; and the lambda splitting by a perturbation calculation. An overview of the Computational Chemistry Branch at Ames Research Center is also presented.

Evaluating the effect of four extracts of avocado fruit on esophageal squamous carcinoma and colon adenocarcinoma cell lines in comparison with peripheral blood mononuclear cells.

PubMed

Vahedi Larijani, Laleh; Ghasemi, Maryam; AbedianKenari, Saeid; Naghshvar, Farshad

2014-01-01

Most patients with gastrointestinal cancers refer to the health centers at advanced stages of the disease and conventional treatments are not significantly effective for these patients. Therefore, using modern therapeutic approaches with lower toxicity bring higher chance for successful treatment and reduced adverse effects in such patients. The aim of this study is to evaluate the effect of avocado fruit extracts on inhibition of the growth of cancer cells in comparison with normal cells. In an experimental study, ethanol, chloroform, ethyl acetate, and petroleum extracts of avocado (Persea americana) fruit were prepared. Then, the effects if the extracts on the growth of esophageal squamous cell carcinoma and colon adenocarcinoma cell lines were evaluated in comparison with the control group using the MTT test in the cell culture medium. Effects of the four extracts of avocado fruit on three cells lines of peripheral blood mononuclear cells, esophageal squamous cell carcinoma, and colon adenocarcinoma were tested. The results showed that avocado fruit extract is effective in inhibition of cancer cell growth in comparison with normal cells (P<0.05). Avocado fruit is rich in phytochemicals, which play an important role in inhibition of growth of cancer cells. The current study for the first time demonstrates the anti-cancer effect of avocado fruit extracts on two cancers common in Iran. Therefore, it is suggested that the fruit extracts can be considered as appropriate complementary treatments in treatment of esophageal and colon cancers.

Sleep, Off-Line Processing, and Vocal Learning

ERIC Educational Resources Information Center

Margoliash, Daniel; Schmidt, Marc F.

2010-01-01

The study of song learning and the neural song system has provided an important comparative model system for the study of speech and language acquisition. We describe some recent advances in the bird song system, focusing on the role of off-line processing including sleep in processing sensory information and in guiding developmental song…

Equity and Excellence in Education Reform: An Unfinished Agenda.

ERIC Educational Resources Information Center

Sadker, Myra; Sadker, David

This paper argues that the recent wave of school reform literature has neglected females, thereby threatening to close already narrowing windows of opportunity for their advanced education beyond high school. A line-by-line content analysis of 138 articles on educational reform published in nine influential professional journals between 1983 and…

78 FR 13100 - Models for Plant-Specific Adoption of Technical Specifications Task Force Traveler TSTF-535...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-02-26

... Definition To Address Advanced Fuel Designs,'' Using the Consolidated Line Item Improvement Process AGENCY...-specific adoption using the Consolidated Line Item Improvement Process (CLIIP). Additionally, the NRC staff..., which may be more reactive at shutdown temperatures above 68[emsp14][deg]F. This STS improvement is part...

Interarea Oscillation Damping Control Using High Voltage DC Transmission: a Survey

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

Elizondo, Marcelo Anibal; Fan, Rui; Kirkham, Harold

High-voltage, direct current (HVDC) transmission lines are increasingly being installed in power systems around the world, and this trend is expected to continue with advancements in power electronics technology. These advancements are also bringing multi-terminal direct current (MTDC) systems closer to practical application. In addition, the continued deployment of phasor measurement units (PMUs) makes dynamic information about a large power system readily available for highly controllable components, such as HVDC lines. All these trends have increased the appeal of modulating HVDC lines and MTDC systems to provide grid services in addition to bulk power transfers. This paper provides a literaturemore » survey of HVDC and MTDC damping controllers for interarea oscillations in large interconnected power systems. The literature shows a progression from theoretical research to practical applications. Finally, there are already practical implementations of HVDC modulation for lines in point-to-point configuration, although the modulation of MTDC systems is still in the research stage. As a conclusion, this paper identifies and summarizes open questions that remain to be tackled by researchers and engineers.« less

Interarea Oscillation Damping Control Using High Voltage DC Transmission: a Survey

DOE PAGES

Elizondo, Marcelo Anibal; Fan, Rui; Kirkham, Harold; ...

2018-05-02

High-voltage, direct current (HVDC) transmission lines are increasingly being installed in power systems around the world, and this trend is expected to continue with advancements in power electronics technology. These advancements are also bringing multi-terminal direct current (MTDC) systems closer to practical application. In addition, the continued deployment of phasor measurement units (PMUs) makes dynamic information about a large power system readily available for highly controllable components, such as HVDC lines. All these trends have increased the appeal of modulating HVDC lines and MTDC systems to provide grid services in addition to bulk power transfers. This paper provides a literaturemore » survey of HVDC and MTDC damping controllers for interarea oscillations in large interconnected power systems. The literature shows a progression from theoretical research to practical applications. Finally, there are already practical implementations of HVDC modulation for lines in point-to-point configuration, although the modulation of MTDC systems is still in the research stage. As a conclusion, this paper identifies and summarizes open questions that remain to be tackled by researchers and engineers.« less

EMISSION SIGNATURES FROM SUB-PARSEC BINARY SUPERMASSIVE BLACK HOLES. I. DIAGNOSTIC POWER OF BROAD EMISSION LINES

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

Nguyen, Khai; Bogdanović, Tamara

Motivated by advances in observational searches for sub-parsec supermassive black hole binaries (SBHBs) made in the past few years, we develop a semi-analytic model to describe spectral emission-line signatures of these systems. The goal of this study is to aid the interpretation of spectroscopic searches for binaries and to help test one of the leading models of binary accretion flows in the literature: SBHB in a circumbinary disk. In this work, we present the methodology and a comparison of the preliminary model with the data. We model SBHB accretion flows as a set of three accretion disks: two mini-disks thatmore » are gravitationally bound to the individual black holes and a circumbinary disk. Given a physically motivated parameter space occupied by sub-parsec SBHBs, we calculate a synthetic database of nearly 15 million broad optical emission-line profiles and explore the dependence of the profile shapes on characteristic properties of SBHBs. We find that the modeled profiles show distinct statistical properties as a function of the semimajor axis, mass ratio, eccentricity of the binary, and the degree of alignment of the triple disk system. This suggests that the broad emission-line profiles from SBHB systems can in principle be used to infer the distribution of these parameters and as such merit further investigation. Calculated profiles are more morphologically heterogeneous than the broad emission lines in observed SBHB candidates and we discuss improved treatment of radiative transfer effects, which will allow a direct statistical comparison of the two groups.« less

Cytotoxicity of gemcitabine enhanced by polyphenolics from Aronia melanocarpa in pancreatic cancer cell line AsPC-1.

PubMed

Thani, Noor Azela Abdullah; Keshavarz, Sholeh; Lwaleed, Bashir A; Cooper, Alan J; Rooprai, Harcharan K

2014-11-01

Extending work with brain tumours, the hypothesis that micronutrients may usefully augment anticancer regimens, chokeberry (Aronia melanocarpa) extract was tested to establish whether it has pro-apoptotic effects in AsPC-1, an established human pancreatic cell line, and whether it potentiates cytotoxicity in combination with gemcitabine. Pancreatic cancer was chosen as a target, as its prognosis remains dismal despite advances in therapy. An MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay was used to assess the growth of the single pancreatic cancer cell line AsPC-1, alone and in comparison or combination with gemcitabine. This was backed up by flow cytometric DRAQ7 cell viability analysis. TUNEL assays were also carried out to investigate pro-apoptotic properties as responsible for the effects of chokeberry extract. Chokeberry extract alone and its IC75 value (1 µg/mL) in combination with gemcitabine were used to assess the growth of the AsPC-1 cell line. Gemcitabine in combination with chokeberry extract was more effective than gemcitabine alone. TUNEL assays showed apoptosis to be a mechanism occurring at 1 µg/mL concentration of chokeberry, with apoptotic bodies detected by both colourimetric and fluorometric methods. The implication of this study, using single cancer cell line, is that chemotherapy (at least with gemcitabine) might be usefully augmented with the use of micronutrients such as chokeberry extract. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Control of Propellant Lead/Lag to the LAE in the AXAF Propulsion System

NASA Technical Reports Server (NTRS)

Casillas, A. R.; Eninger, J.; Joseph, G.; Kenney, J.; Trinidad, M.

1998-01-01

Control of the rate at which hypergolic propellants are supplied to a rocket engine prior to ignition is critically important. Potentially damaging explosions may result from excessive lead of either propellant into the combustion chamber. Because the injector fill process is governed by the engine as well as the propellant feed system design, proper management of this issue must take both into consideration. This was recognized early in the development of TRW's Advanced Columbium-Liquid Apogee Engine (LAE), which was flight-qualified in 1996 to maneuver the Advanced X-Ray Astrophysics Facility (AXAF) spacecraft into orbit. The LAE runs on hydrazine and nitrogen tetroxide (MON-3) at a nominal mixture ratio of 1.0. This paper describes the comprehensive test program conducted to ensure reliable startup operation of the LAE in the AYAF propulsion system. The most significant factors affecting chamber fuel lead were found to be: (1) engine location, (2) propellant saturation level, (3) amount of undissolved gas in the lines, and (4) off- nominal tank pressures. Hot-fire tests at a chamber fuel lead range over and above that expected for the LAEs in AXAF demonstrated extremely tolerant behavior of the engine. AY-AF is scheduled for launch on NASA's STS-93 in December 1998.

Advanced life support control/monitor instrumentation concepts for flight application

NASA Technical Reports Server (NTRS)

Heppner, D. B.; Dahlhausen, M. J.; Fell, R. B.

1986-01-01

Development of regenerative Environmental Control/Life Support Systems requires instrumentation characteristics which evolve with successive development phases. As the development phase moves toward flight hardware, the system availability becomes an important design aspect which requires high reliability and maintainability. This program was directed toward instrumentation designs which incorporate features compatible with anticipated flight requirements. The first task consisted of the design, fabrication and test of a Performance Diagnostic Unit. In interfacing with a subsystem's instrumentation, the Performance Diagnostic Unit is capable of determining faulty operation and components within a subsystem, perform on-line diagnostics of what maintenance is needed and accept historical status on subsystem performance as such information is retained in the memory of a subsystem's computerized controller. The second focus was development and demonstration of analog signal conditioning concepts which reduce the weight, power, volume, cost and maintenance and improve the reliability of this key assembly of advanced life support instrumentation. The approach was to develop a generic set of signal conditioning elements or cards which can be configured to fit various subsystems. Four generic sensor signal conditioning cards were identified as being required to handle more than 90 percent of the sensors encountered in life support systems. Under company funding, these were detail designed, built and successfully tested.

SCOUT: a small vacuum chamber for nano-wire grid polarizer tests in the ultraviolet band

NASA Astrophysics Data System (ADS)

Landini, F.; Pancrazzi, M.; Totaro, M.; Pennelli, G.; Romoli, M.

2012-01-01

Within the Section of Astronomy of the Department of Physics and Astronomy of the University of Firenze, Italy), the XUVLab laboratory is active since 1998 dedicated to technological development, mainly UV oriented. The technological research is focused both on electronics and optics. Our last approach is dedicated to the development of innovative wiregrid polarizers optimized to work in transmission at 121.6 nm. The manufacturing of such optical devices requires advanced technological expertise and suitable experimental structures. First, nanotechnology capability is necessary, in order to build several tiny parallel conductive lines separated by tens of nanometers on wide areas to be macroscopically exploitable in an optical laboratory. Moreover, the characterization of such an advanced optical device has to be performed in vacuum, being air absorptive at 121.6 nm. A dedicated small vacuum chamber, SCOUT (Small Chamber for Optical UV Tests) was developed within our laboratory in order to perform practical and fast measurements. SCOUT hosts an optical bench and is equipped with several opening flanges, in order to be as flexible as possible. The flexibility that has been reached with SCOUT allows us to use the chamber beyond the goals it was thought for. It is exploitable by whatever compact (within 1 m) optical experiment that investigates the UV band of the spectrum.

A comparison of paper-and-pencil and computerized forms of Line Orientation and Enhanced Cued Recall Tests.

PubMed

Aşkar, Petek; Altun, Arif; Cangöz, Banu; Cevik, Vildan; Kaya, Galip; Türksoy, Hasan

2012-04-01

The purpose of this study was to assess whether a computerized battery of neuropsychological tests could produce similar results as the conventional forms. Comparisons on 77 volunteer undergraduates were carried out with two neuropsychological tests: Line Orientation Test and Enhanced Cued Recall Test. Firstly, students were assigned randomly across the test medium (paper-and-pencil versus computerized). Secondly, the groups were given the same test in the other medium after a 30-day interval between tests. Results showed that the Enhanced Cued Recall Test-Computer-based did not correlate with the Enhanced Cued Recall Test-Paper-and-pencil results. Line Orientation Test-Computer-based scores, on the other hand, did correlate significantly with the Line Orientation Test-Paper-and-pencil version. In both tests, scores were higher on paper-and-pencil tests compared to computer-based tests. Total score difference between modalities was statistically significant for both Enhanced Cued Recall Tests and for the Line Orientation Test. In both computer-based tests, it took less time for participants to complete the tests.

Targeted therapies in gastric cancer and future perspectives.

PubMed

Yazici, Ozan; Sendur, M Ali Nahit; Ozdemir, Nuriye; Aksoy, Sercan

2016-01-14

Advanced gastric cancer (AGC) is associated with a high mortality rate and, despite multiple new chemotherapy options, the survival rates of patients with AGC remains poor. After the discovery of targeted therapies, research has focused on the new treatment options for AGC. In the last two decades, many targeted molecules were developed against AGC. Currently, two targeted therapy molecules have been approved for patients with AGC. In 2010, trastuzumab was the first molecule shown to improve survival in patients with HER2-positive AGC as part of a first-line combination regimen. In 2014, ramucirumab was the second targeted molecule to improve survival rates and was suggested as treatment for patients with AGC who had progressed after first-line platinum plus fluoropyrimidine with or without anthracycline chemotherapy. Ramucirumab was the first targeted therapy acting as a single agent in patients with advanced gastroesophageal cancers. Although these two molecules were introduced into clinical use, many other promising molecules have been tested in phase I-II trials. It is obvious that in the near future many different targeted therapies will be in use for treatment of AGC. In this review, the current status of targeted therapies in the treatment of AGC and gastroesophageal junction tumors, including HER (2-3) inhibitors, epidermal growth factor receptor inhibitors, tyrosine kinase inhibitors, antiangiogenic agents, c-MET inhibitors, mammalian target of rapamycin inhibitors, agents against other molecular pathways fibroblast growth factor, Claudins, insulin-like growth factor, heat shock proteins, and immunotherapy, will be discussed.

Circulating programmed death ligand-1 (cPD-L1) in non-small-cell lung cancer (NSCLC)

PubMed Central

Vecchiarelli, Silvia; Passiglia, Francesco; D’Incecco, Armida; Gallo, Marianna; De Luca, Antonella; Rossi, Elisa; D’Incà, Federica; Minuti, Gabriele; Landi, Lorenza; Bennati, Chiara; Spreafico, Michela; D’Arcangelo, Manolo; Mazza, Valentina; Normanno, Nicola; Cappuzzo, Federico

2018-01-01

Background This study aimed at investigating feasibility of programmed death ligand-1 (PD-L1) testing in plasma samples of advanced NSCLC patients receiving first-line treatment, assessing whether circulating (c)PD-L1 levels were modified by the therapy and whether baseline cPD-L1 levels were associated with patients’ clinical responses and survival outcome. Methods Peripheral blood samples were collected from 16 healthy volunteers and 56 newly diagnosed NSCLC patients before and at 12th week during the course of first-line therapy. The level of PD-L1 was measured in plasma samples using the human (PD-L1/CD274) ELISA kit (CUSABIO, MD, USA). The Mann Whitney test or Fisher’s test were used for comparisons. Survival analysis was performed using Kaplan Meyer method, providing median and p-value. Results Baseline median cPD-L1 was 42.21 pg/ml (range 12.00-143.49) in NSCLC patients and 37.81 pg/ml (range 9.73-90.21) in healthy control cohort (p = 0.78). Median cPD-L1 increased in patients treated with first-line chemotherapy (63.20 pg/ml vs 39.34 pg/ml; p = 0.002), with no changes in patients exposed to non-chemotherapy drugs (42.39 pg/ml vs 50.67 pg/ml; p = 0.398). Time to progression and overall survival were 4.4 vs 6.9 months (p = 0.062) and 8.8 vs 9.3 months (p = 0.216) in cPD-L1 positive vs cPD-L1 negative patients. Baseline cPD-L1 levels increased with the ascending number of metastatic sites, even if the association was not statistically significant (p = 0.063). Conclusions This study showed that cPD-L1 testing is feasible, with chemotherapy influencing PD-L1 plasma levels. The possibility of using such test for predicting or monitoring the effect of immunotherapy or combination of chemotherapy and immunotherapy warrant further investigations. PMID:29707129

40 CFR 1060.515 - How do I test EPA Nonroad Fuel Lines and EPA Cold-Weather Fuel Lines for permeation emissions?

Code of Federal Regulations, 2011 CFR

2011-07-01

... and EPA Cold-Weather Fuel Lines for permeation emissions? 1060.515 Section 1060.515 Protection of... Nonroad Fuel Lines and EPA Cold-Weather Fuel Lines for permeation emissions? Measure emission as follows for EPA Nonroad Fuel Lines and EPA Cold-Weather Fuel Lines: (a) Prior to permeation testing, use good...

40 CFR 1060.515 - How do I test EPA Nonroad Fuel Lines and EPA Cold-Weather Fuel Lines for permeation emissions?

Code of Federal Regulations, 2013 CFR

2013-07-01

... and EPA Cold-Weather Fuel Lines for permeation emissions? 1060.515 Section 1060.515 Protection of... Nonroad Fuel Lines and EPA Cold-Weather Fuel Lines for permeation emissions? Measure emission as follows for EPA Nonroad Fuel Lines and EPA Cold-Weather Fuel Lines: (a) Prior to permeation testing, use good...

40 CFR 1060.515 - How do I test EPA Nonroad Fuel Lines and EPA Cold-Weather Fuel Lines for permeation emissions?

Code of Federal Regulations, 2012 CFR

2012-07-01

... and EPA Cold-Weather Fuel Lines for permeation emissions? 1060.515 Section 1060.515 Protection of... Nonroad Fuel Lines and EPA Cold-Weather Fuel Lines for permeation emissions? Measure emission as follows for EPA Nonroad Fuel Lines and EPA Cold-Weather Fuel Lines: (a) Prior to permeation testing, use good...

40 CFR 1060.515 - How do I test EPA Nonroad Fuel Lines and EPA Cold-Weather Fuel Lines for permeation emissions?

Code of Federal Regulations, 2010 CFR

2010-07-01

... and EPA Cold-Weather Fuel Lines for permeation emissions? 1060.515 Section 1060.515 Protection of... Nonroad Fuel Lines and EPA Cold-Weather Fuel Lines for permeation emissions? Measure emission as follows for EPA Nonroad Fuel Lines and EPA Cold-Weather Fuel Lines: (a) Prior to permeation testing, use good...

40 CFR 1060.515 - How do I test EPA Nonroad Fuel Lines and EPA Cold-Weather Fuel Lines for permeation emissions?

Code of Federal Regulations, 2014 CFR

2014-07-01

... and EPA Cold-Weather Fuel Lines for permeation emissions? 1060.515 Section 1060.515 Protection of... Nonroad Fuel Lines and EPA Cold-Weather Fuel Lines for permeation emissions? Measure emission as follows for EPA Nonroad Fuel Lines and EPA Cold-Weather Fuel Lines: (a) Prior to permeation testing, use good...

Nanofluid based on self-nanoencapsulated metal/metal alloys phase change materials with tuneable crystallisation temperature.

PubMed

Navarrete, Nuria; Gimeno-Furio, Alexandra; Mondragon, Rosa; Hernandez, Leonor; Cabedo, Luis; Cordoncillo, Eloisa; Julia, J Enrique

2017-12-14

Nanofluids using nanoencapsulated Phase Change Materials (nePCM) allow increments in both the thermal conductivity and heat capacity of the base fluid. Incremented heat capacity is produced by the melting enthalpy of the nanoparticles core. In this work two important advances in this nanofluid type are proposed and experimentally tested. It is firstly shown that metal and metal alloy nanoparticles can be used as self-encapsulated nePCM using the metal oxide layer that forms naturally in most commercial synthesis processes as encapsulation. In line with this, Sn/SnOx nanoparticles morphology, size and thermal properties were studied by testing the suitability and performance of encapsulation at high temperatures and thermal cycling using a commercial thermal oil (Therminol 66) as the base fluid. Secondly, a mechanism to control the supercooling effect of this nePCM type based on non-eutectic alloys was developed.

Understanding gene functions and disease mechanisms: Phenotyping pipelines in the German Mouse Clinic.

PubMed

Fuchs, Helmut; Aguilar-Pimentel, Juan Antonio; Amarie, Oana V; Becker, Lore; Calzada-Wack, Julia; Cho, Yi-Li; Garrett, Lillian; Hölter, Sabine M; Irmler, Martin; Kistler, Martin; Kraiger, Markus; Mayer-Kuckuk, Philipp; Moreth, Kristin; Rathkolb, Birgit; Rozman, Jan; da Silva Buttkus, Patricia; Treise, Irina; Zimprich, Annemarie; Gampe, Kristine; Hutterer, Christine; Stöger, Claudia; Leuchtenberger, Stefanie; Maier, Holger; Miller, Manuel; Scheideler, Angelika; Wu, Moya; Beckers, Johannes; Bekeredjian, Raffi; Brielmeier, Markus; Busch, Dirk H; Klingenspor, Martin; Klopstock, Thomas; Ollert, Markus; Schmidt-Weber, Carsten; Stöger, Tobias; Wolf, Eckhard; Wurst, Wolfgang; Yildirim, Ali Önder; Zimmer, Andreas; Gailus-Durner, Valérie; Hrabě de Angelis, Martin

2017-09-29

Since decades, model organisms have provided an important approach for understanding the mechanistic basis of human diseases. The German Mouse Clinic (GMC) was the first phenotyping facility that established a collaboration-based platform for phenotype characterization of mouse lines. In order to address individual projects by a tailor-made phenotyping strategy, the GMC advanced in developing a series of pipelines with tests for the analysis of specific disease areas. For a general broad analysis, there is a screening pipeline that covers the key parameters for the most relevant disease areas. For hypothesis-driven phenotypic analyses, there are thirteen additional pipelines with focus on neurological and behavioral disorders, metabolic dysfunction, respiratory system malfunctions, immune-system disorders and imaging techniques. In this article, we give an overview of the pipelines and describe the scientific rationale behind the different test combinations. Copyright © 2017 Elsevier B.V. All rights reserved.

Genes, embryos, and future people.

PubMed

Glannon, Walter

1998-07-01

Testing embryonic cells for genetic abnormalities gives us the capacity to predict whether and to what extent people will exist with disease and disability. Moreover, the freezing of embryos for long periods of time enables us to alter the length of a normal human lifespan. After highlighting the shortcomings of somatic-cell gene therapy and germ-line genetic alteration, I argue that the testing and selective termination of genetically defective embryos is the only medically and morally defensible way to prevent the existence of people with severe disability, pain and suffering that make their lives not worth living for them on the whole. In addition, I consider the possible harmful effects on children born from frozen embryos after the deaths of their biological parents, or when their parents are at an advanced age. I also explore whether embryos have moral status and whether the prospects for disease-preventing genetic alteration can justify long-term cryopreservation of embryos.

Low-speed investigation of effects of wing leading- and trailing-edge flap deflections and canard incidence on a fighter configuration equipped with a forward-swept wing

NASA Technical Reports Server (NTRS)

Gainer, T. G.; Mann, M. J.; Huffman, J. K.

1984-01-01

An advanced fighter configuration with a forward-swept wing of aspect ratio 3.28 is tested in the Langley 7 by 10 Foot High Speed Tunnel at a Mach number of 0.3. The wing has 29.5 degrees of forward sweep of the quarter chord line and is equipped with 15 percent chord leading edge and 30 percent chord trailing edge flaps. The canard is sweptback 45 degrees. Tests were made through a range of angle of attack from about -2 degrees to 22 degrees. Deflecting the flaps significantly improves the lift drag characteristics at the higher angles of attack. The canard is able to trim the configurations with different flap deflections over most of the range of angle of attack. The penalty in maximum lift coefficient due to trimming is about 0.10.

Reducing unscheduled plant maintenance delays -- Field test of a new method to predict electric motor failure

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

Homce, G.T.; Thalimer, J.R.

1996-05-01

Most electric motor predictive maintenance methods have drawbacks that limit their effectiveness in the mining environment. The US Bureau of Miens (USBM) is developing an alternative approach to detect winding insulation breakdown in advance of complete motor failure. In order to evaluate the analysis algorithms necessary for this approach, the USBM has designed and installed a system to monitor 120 electric motors in a coal preparation plant. The computer-based experimental system continuously gathers, stores, and analyzes electrical parameters for each motor. The results are then correlated to data from conventional motor-maintenance methods and in-service failures to determine if the analysismore » algorithms can detect signs of insulation deterioration and impending failure. This paper explains the on-line testing approach used in this research, and describes monitoring system design and implementation. At this writing data analysis is underway, but conclusive results are not yet available.« less

Methods and methodology for FTIR spectral correction of channel spectra and uncertainty, applied to ferrocene.

PubMed

Islam, M T; Trevorah, R M; Appadoo, D R T; Best, S P; Chantler, C T

2017-04-15

We present methodology for the first FTIR measurements of ferrocene using dilute wax solutions for dispersion and to preserve non-crystallinity; a new method for removal of channel spectra interference for high quality data; and a consistent approach for the robust estimation of a defined uncertainty for advanced structural χ r 2 analysis and mathematical hypothesis testing. While some of these issues have been investigated previously, the combination of novel approaches gives markedly improved results. Methods for addressing these in the presence of a modest signal and how to quantify the quality of the data irrespective of preprocessing for subsequent hypothesis testing are applied to the FTIR spectra of Ferrocene (Fc) and deuterated ferrocene (dFc, Fc-d 10 ) collected at the THz/Far-IR beam-line of the Australian Synchrotron at operating temperatures of 7K through 353K. Copyright © 2017 Elsevier B.V. All rights reserved.

Methods and methodology for FTIR spectral correction of channel spectra and uncertainty, applied to ferrocene

NASA Astrophysics Data System (ADS)

Islam, M. T.; Trevorah, R. M.; Appadoo, D. R. T.; Best, S. P.; Chantler, C. T.

2017-04-01

We present methodology for the first FTIR measurements of ferrocene using dilute wax solutions for dispersion and to preserve non-crystallinity; a new method for removal of channel spectra interference for high quality data; and a consistent approach for the robust estimation of a defined uncertainty for advanced structural χr2 analysis and mathematical hypothesis testing. While some of these issues have been investigated previously, the combination of novel approaches gives markedly improved results. Methods for addressing these in the presence of a modest signal and how to quantify the quality of the data irrespective of preprocessing for subsequent hypothesis testing are applied to the FTIR spectra of Ferrocene (Fc) and deuterated ferrocene (dFc, Fc-d10) collected at the THz/Far-IR beam-line of the Australian Synchrotron at operating temperatures of 7 K through 353 K.

A naturally occurring nanomaterial from the Sundew (Drosera) for tissue engineering.

PubMed

Lenaghan, S C; Serpersu, K; Xia, L; He, W; Zhang, M

2011-12-01

In recent years advances have been made in the design of novel materials for tissue engineering through the use of polysaccharides. This study evaluated the ability of a naturally secreted polysaccharide adhesive from the Sundew (Drosera capensis) as a support for cell growth. The Sundew adhesive has several advantages including its high elasticity and antibiotic nature. By coating glass cover slips with the Sundew adhesive, a network of nanofibers was generated that was capable of promoting attachment and differentiation of a model neuronal cell line, PC-12. We also demonstrated the potential of this material for repairing bone and soft tissue injuries, by testing attachment of osteoblasts and endothelial cells. Finally, it was determined that the Sundew biomaterial was stable through testing by atomic force microscopy and prolonged cell growth. This work has proven the capabilities of using a nanomaterial derived from the Sundew adhesive for the purpose of tissue engineering.

Systemic treatment in advanced biliary cancers: A multicenter Australian analysis and review.

PubMed

Brungs, Daniel; Aghmesheh, Morteza; Sjoquist, Katrin; Goldstein, David

2017-10-01

While first-line palliative chemotherapy (CT1) improves survival and quality of life in advanced biliary cancer (ABC), there is no randomized evidence to support second-line chemotherapy (CT2) in ABC. We aim to explore to role of CT2 in ABC. We performed a retrospective review of all patients who received one or more lines of chemotherapy for ABC at four Australian cancer centers between 2008 and 2011. A Cox proportional hazard model was developed to determine the impact of clinicopathologic variables on overall survival (OS) from time of progression on CT1. We identified 73 patients who received palliative chemotherapy for ABC. Twenty-five patients (34%) received two or more lines of chemotherapy. Patients with a preserved performance status on progression on first-line chemotherapy (CT1) were more likely to receive second-line chemotherapy (CT2) (P < 0.001). Disease control rate with CT2 was 36%, and mean progression-free survival was 3.2 months (95% confidence interval 1.5-4.9 months). The following variables were significant in the univariate analysis of OS from time of progression on CT1: lines of chemotherapy (P = 0.0001), Eastern Cooperative Oncology Group performance status at progression on CT1 (P < 0.0001) and disease control with CT1 (P = 0.027). Lines of chemotherapy received and performance status remained significant in the multivariate analysis for OS from progression on CT1. Second-line chemotherapy is feasible in a subset of patients with ABC. Even after accounting for confounding variables, CT2 appears to increase OS in ABC, although we are unable to exclude other unmeasured factors such as tumor biology. These findings warrant further evaluation with prospective trials. © 2016 John Wiley & Sons Australia, Ltd.

Blurring the Lines: Leveraging Internet Technology for Successful Blending of Secondary/Post-Secondary Technical Education

ERIC Educational Resources Information Center

Ryan, Kenneth; Kopischke, Kevin

2008-01-01

The Remote Automation Management Platform (RAMP) is a real-time, interactive teaching tool which leverages common off-the-shelf internet technologies to provide high school learners extraordinary access to advanced technical education opportunities. This outreach paradigm is applicable to a broad range of advanced technical skills from automation…