Derivatization of inhibitor of apoptosis protein (IAP) ligands yields improved inducers of estrogen receptor α degradation.

PubMed

Ohoka, Nobumichi; Morita, Yoko; Nagai, Katsunori; Shimokawa, Kenichiro; Ujikawa, Osamu; Fujimori, Ikuo; Ito, Masahiro; Hayase, Youji; Okuhira, Keiichiro; Shibata, Norihito; Hattori, Takayuki; Sameshima, Tomoya; Sano, Osamu; Koyama, Ryokichi; Imaeda, Yasuhiro; Nara, Hiroshi; Cho, Nobuo; Naito, Mikihiko

2018-05-04

Aberrant expression of proteins often underlies many diseases, including cancer. A recently developed approach in drug development is small molecule-mediated, selective degradation of dysregulated proteins. We have devised a protein-knockdown system that utilizes chimeric molecules termed specific and nongenetic IAP-dependent protein erasers (SNIPERs) to induce ubiquitylation and proteasomal degradation of various target proteins. SNIPER(ER)-87 consists of an inhibitor of apoptosis protein (IAP) ligand LCL161 derivative that is conjugated to the estrogen receptor α (ERα) ligand 4-hydroxytamoxifen by a PEG linker, and we have previously reported that this SNIPER efficiently degrades the ERα protein. Here, we report that derivatization of the IAP ligand module yields SNIPER(ER)s with superior protein-knockdown activity. These improved SNIPER(ER)s exhibited higher binding affinities to IAPs and induced more potent degradation of ERα than does SNIPER(ER)-87. Further, they induced simultaneous degradation of cellular inhibitor of apoptosis protein 1 (cIAP1) and delayed degradation of X-linked IAP (XIAP). Notably, these reengineered SNIPER(ER)s efficiently induced apoptosis in MCF-7 human breast cancer cells that require IAPs for continued cellular survival. We found that one of these molecules, SNIPER(ER)-110, inhibits the growth of MCF-7 tumor xenografts in mice more potently than the previously characterized SNIPER(ER)-87. Mechanistic analysis revealed that our novel SNIPER(ER)s preferentially recruit XIAP, rather than cIAP1, to degrade ERα. Our results suggest that derivatized IAP ligands could facilitate further development of SNIPERs with potent protein-knockdown and cytocidal activities against cancer cells requiring IAPs for survival. © 2018 by The American Society for Biochemistry and Molecular Biology, Inc.

Description and Evaluation of IAP-AACM: A Global-regional Aerosol Chemistry Model for the Earth System Model CAS-ESM

NASA Astrophysics Data System (ADS)

Wei, Y.; Chen, X.

2017-12-01

We present a first description and evaluation of the IAP Atmospheric Aerosol Chemistry Model (IAP-AACM) which has been integrated into the earth system model CAS-ESM. In this way it is possible to research into interaction of clouds and aerosol by its two-way coupling with the IAP Atmospheric General Circulation Model (IAP-AGCM). The model has a nested global-regional grid based on the Global Environmental Atmospheric Transport Model (GEATM) and the Nested Air Quality Prediction Modeling System (NAQPMS). The AACM provides two optional gas chemistry schemes, the CBM-Z gas chemistry as well as a sulfur oxidize box designed specifically for the CAS-ESM. Now the model driven by AGCM has been applied to a 1-year simulation of tropospheric chemistry both on global and regional scales for 2014, and been evaluated against various observation datasets, including aerosol precursor gas concentration, aerosol mass and number concentrations. Furthermore, global budgets in AACM are compared with other global aerosol models. Generally, the AACM simulations are within the range of other global aerosol model predictions, and the model has a reasonable agreement with observations of gases and particles concentration both on global and regional scales.

A cluster-based approach to selecting representative stimuli from the International Affective Picture System (IAPS) database.

PubMed

Constantinescu, Alexandra C; Wolters, Maria; Moore, Adam; MacPherson, Sarah E

2017-06-01

The International Affective Picture System (IAPS; Lang, Bradley, & Cuthbert, 2008) is a stimulus database that is frequently used to investigate various aspects of emotional processing. Despite its extensive use, selecting IAPS stimuli for a research project is not usually done according to an established strategy, but rather is tailored to individual studies. Here we propose a standard, replicable method for stimulus selection based on cluster analysis, which re-creates the group structure that is most likely to have produced the valence arousal, and dominance norms associated with the IAPS images. Our method includes screening the database for outliers, identifying a suitable clustering solution, and then extracting the desired number of stimuli on the basis of their level of certainty of belonging to the cluster they were assigned to. Our method preserves statistical power in studies by maximizing the likelihood that the stimuli belong to the cluster structure fitted to them, and by filtering stimuli according to their certainty of cluster membership. In addition, although our cluster-based method is illustrated using the IAPS, it can be extended to other stimulus databases.

Informal Allopathic Provider Knowledge and Practice Regarding Hypertension in Urban and Rural Bangladesh

PubMed Central

Parr, John; Lindeboom, Wietze; Khanam, Masuma; Sanders, James; Koehlmoos, Tracey Pérez

2012-01-01

Objectives Describe informal allopathic practitioner (IAP) knowledge and practice about management of hypertension and identify gaps in IAP knowledge and practice amenable to interventions. Methods A cross sectional descriptive survey of 642 IAPs in Kamalapur (urban) and Mirsarai (rural) Bangladesh was conducted from March to April, 2011. Using a structured, pre-tested questionnaire sociodemographic, training, knowledge and practice data about management of hypertension was collected. Comparative statistics were preformed to show differences between urban and rural practitioners using SAS 8.0. Findings 99.4% of IAPs were male, mean age was 37.5 (12.5 SD) years. Greater than 65% correctly identified the upper limit of normal blood pressure. 50.2% underestimated lower limit of systolic hypertension. 79.8% allowed age to affect their treatment approach. As blood pressure increased, willingness to treat with medication decreased and tendency to refer increased. Sedative/sleeping pills, antidepressants, and beta blockers were the most commonly prescribed medications for prehypertension (58.7%, 50.3% and 53.7% respectively), stage I hypertension (55.0%, 38.6%, 49.8% respectively) and stage II hypertension (42.4%, 23.7%, and 28.8% respectively). Rural IAPs were more likely than urban IAPs to treat (84.7% vs 77.7%), order tests (27.1% vs 6.0%) and write prescriptions (60.4% vs 18.7%). Conclusion While IAPs are crucial to Bangladesh’s pluralistic healthcare system, gaps in knowledge and practice could cause unnecessary harm. To include IAPs in the public sector’s fight against the chronic disease epidemic, interventions aimed at standardizing IAPs knowledge and practice will be essential. Successfully utilizing IAPs will have beneficial implications not only for Bangladesh, but for all developing countries. PMID:23133546

Wireless system for monitoring Intra-abdominal pressure in patient with severe abdominal pathology

NASA Astrophysics Data System (ADS)

Sokolovskiy, S. S.; Shtotskiy, Y. V.; Leljanov, A. D.

2017-01-01

The paper discusses an experimental design of the wireless system for monitoring intra-abdominal pressure (IAP) using Bluetooth Low Energy technology. The possibility of measuring IAP via the bladder using a wireless pressure sensor with a hydrophobic bacteria filter between the liquid transmitting medium and the sensor element is grounded.

Intestinal alkaline phosphatase: a summary of its role in clinical disease.

PubMed

Fawley, Jason; Gourlay, David M

2016-05-01

Over the past few years, there is increasing evidence implicating a novel role for Intestinal Alkaline Phosphatase (IAP) in mitigating inflammatory mediated disorders. IAP is an endogenous protein expressed by the intestinal epithelium that is believed to play a vital role in maintaining gut homeostasis. Loss of IAP expression or function is associated with increased intestinal inflammation, dysbiosis, bacterial translocation and subsequently systemic inflammation. As these events are a cornerstone of the pathophysiology of many diseases relevant to surgeons, we sought to review recent research in both animal and humans on IAP's physiologic function, mechanisms of action and current research in specific surgical diseases. Copyright © 2016 Elsevier Inc. All rights reserved.

Liquid oxygen/liquid hydrogen auxiliary power system thruster investigation

NASA Technical Reports Server (NTRS)

Eberle, E. E.; Kusak, L.

1979-01-01

The design, fabrication, and demonstration of a 111 newton (25 lb) thrust, integrated auxiliary propulsion system (IAPS) thruster for use with LH2/LO2 propellants is described. Hydrogen was supplied at a temperature range of 22 to 33 K (40 to 60 R), and oxygen from 89 to 122 K (160 to 220 R). The thruster was designed to operate in both pulse mode and steady-state modes for vehicle attitude control, space maneuvering, and as an abort backup in the event of failure of the main propulsion system. A dual-sleeve, tri-axial injection system was designed that utilizes a primary injector/combustor where 100 percent of the oxygen and 8 percent of the hydrogen is introduced; a secondary injector/combustor where 45 percent of the hydrogen is introduced to mix with the primary combustor gases; and a boundary layer injector that uses the remaining 45 percent of the hydrogen to cool the thrust throat/nozzle design. Hot-fire evaluation of this thruster with a BLC injection distance of 2.79 cm (1.10 in.) indicated that a specific impulse value of 390 sec can be attained using a coated molybdenum thrust chamber. Pulse mode tests indicated that a chamber pressure buildup to 90 percent thrust can be achieved in a time on the order of 48 msec. Some problems were encountered in achieving ignition of each pulse during pulse trains. This was interpreted to indicate that a higher delivered spark energy level ( 100 mJ) would be required to maintain ignition reliability of the plasma torch ignition system under the extra 'cold' conditions resulting during pulsing.

Testing of Mortar Systems

DTIC Science & Technology

2010-03-11

IEP /TDP) or Independent Assessment Plan (IAP), and the test item and the procedures as outlined in this TOP. The following must also be considered...Command DTIC = Defense Technical Information Center DTP = Detailed Test Plan IAP = Independent Assessment Plan IEP = Independent Evaluation Plan IPT

Hyaluronic acid-fabricated nanogold delivery of the inhibitor of apoptosis protein-2 siRNAs inhibits benzo[a]pyrene-induced oncogenic properties of lung cancer A549 cells

NASA Astrophysics Data System (ADS)

Lin, Chung-Ming; Kao, Wei-Chien; Yeh, Chun-An; Chen, Hui-Jye; Lin, Shinn-Zong; Hsieh, Hsien-Hsu; Sun, Wei-Shen; Chang, Chih-Hsuan; Hung, Huey-Shan

2015-03-01

Benzo[a]pyrene (BaP), a component of cooking oil fumes (COF), promotes lung cancer cell proliferation and survival via the induction of inhibitor of apoptosis protein-2 (IAP-2) proteins. Thus knockdown of IAP-2 would be a promising way to battle against lung cancer caused by COF. Functionalized gold nanoparticle (AuNP) is an effective delivery system for bio-active materials. Here, biocompatible hyaluronic acid (HA) was fabricated into nanoparticles to increase the target specificity by binding to CD44-over-expressed cancer cells. IAP-2-specific small-interfering RNA (siRNAs) or fluorescein isothiocyanate (FITC) were then incorporated into AuNP-HA. Conjugation of IAP-2 siRNA into AuNPs-HA was verified by the UV-vis spectrometer and Fourier transform infrared spectrometer. Further studies showed that AuNP-HA/FITC were effectively taken up by A549 cells through CD44-mediated endocytosis. Incubation of BaP-challenged cells with AuNP-HA-IAP-2 siRNAs silenced the expression of IAP-2, decreased cell proliferation and triggered pronounced cell apoptosis by the decrease in Bcl-2 protein and the increase in Bax protein as well as the active form of caspases-3. The BaP-elicited cell migration and enzymatic activity of the secreted matrix metalloproteinase-2 were also substantially suppressed by treatment with AuNP-HA-IAP-2 siRNAs. These results indicated that IAP-2 siRNAs can be efficiently delivered into A549 cells by functionalized AuNP-HA to repress the IAP-2 expression and BaP-induced oncogenic events, suggesting the potential therapeutic application of IAP-2 siRNA or other siRNA-conjugated AuNP-HA composites to COF-induced lung cancer and other gene-caused diseases in the future.

Indoor air pollution and respiratory health of children in the developing world.

PubMed

Nandasena, Sumal; Wickremasinghe, Ananda Rajitha; Sathiakumar, Nalini

2013-05-08

Indoor air pollution (IAP) is a key contributor to the global burden of disease mainly in developing countries. The use of solid fuel for cooking and heating is the main source of IAP in developing countries, accounting for an estimated 3.5 million deaths and 4.5% of Disability-Adjusted Life Years in 2010. Other sources of IAP include indoor smoking, infiltration of pollutants from outdoor sources and substances emitted from an array of human utilities and biological materials. Children are among the most vulnerable groups for adverse effects of IAP. The respiratory system is a primary target of air pollutants resulting in a wide range of acute and chronic effects. The spectrum of respiratory adverse effects ranges from mild subclinical changes and mild symptoms to life threatening conditions and even death. However, IAP is a modifiable risk factor having potential mitigating interventions. Possible interventions range from simple behavior change to structural changes and from shifting of unclean cooking fuel to clean cooking fuel. Shifting from use of solid fuel to clean fuel invariably reduces household air pollution in developing countries, but such a change is challenging. This review aims to summarize the available information on IAP exposure during childhood and its effects on respiratory health in developing countries. It specifically discusses the common sources of IAP, susceptibility of children to air pollution, mechanisms of action, common respiratory conditions, preventive and mitigating strategies.

Evaluation of the New Dynamic Global Vegetation Model in CAS-ESM

NASA Astrophysics Data System (ADS)

Zhu, Jiawen; Zeng, Xiaodong; Zhang, Minghua; Dai, Yongjiu; Ji, Duoying; Li, Fang; Zhang, Qian; Zhang, He; Song, Xiang

2018-06-01

In the past several decades, dynamic global vegetation models (DGVMs) have been the most widely used and appropriate tool at the global scale to investigate vegetation-climate interactions. At the Institute of Atmospheric Physics, a new version of DGVM (IAP-DGVM) has been developed and coupled to the Common Land Model (CoLM) within the framework of the Chinese Academy of Sciences' Earth System Model (CAS-ESM). This work reports the performance of IAP-DGVM through comparisons with that of the default DGVM of CoLM (CoLM-DGVM) and observations. With respect to CoLMDGVM, IAP-DGVM simulated fewer tropical trees, more "needleleaf evergreen boreal tree" and "broadleaf deciduous boreal shrub", and a better representation of grasses. These contributed to a more realistic vegetation distribution in IAP-DGVM, including spatial patterns, total areas, and compositions. Moreover, IAP-DGVM also produced more accurate carbon fluxes than CoLM-DGVM when compared with observational estimates. Gross primary productivity and net primary production in IAP-DGVM were in better agreement with observations than those of CoLM-DGVM, and the tropical pattern of fire carbon emissions in IAP-DGVM was much more consistent with the observation than that in CoLM-DGVM. The leaf area index simulated by IAP-DGVM was closer to the observation than that of CoLM-DGVM; however, both simulated values about twice as large as in the observation. This evaluation provides valuable information for the application of CAS-ESM, as well as for other model communities in terms of a comparative benchmark.

IAP/APA evidence-based guidelines for the management of acute pancreatitis.

PubMed

2013-01-01

There have been substantial improvements in the management of acute pancreatitis since the publication of the International Association of Pancreatology (IAP) treatment guidelines in 2002. A collaboration of the IAP and the American Pancreatic Association (APA) was undertaken to revise these guidelines using an evidence-based approach. Twelve multidisciplinary review groups performed systematic literature reviews to answer 38 predefined clinical questions. Recommendations were graded using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) system. The review groups presented their recommendations during the 2012 joint IAP/APA meeting. At this one-day, interactive conference, relevant remarks were voiced and overall agreement on each recommendation was quantified using plenary voting. The 38 recommendations covered 12 topics related to the clinical management of acute pancreatitis: A) diagnosis of acute pancreatitis and etiology, B) prognostication/predicting severity, C) imaging, D) fluid therapy, E) intensive care management, F) preventing infectious complications, G) nutritional support, H) biliary tract management, I) indications for intervention in necrotizing pancreatitis, J) timing of intervention in necrotizing pancreatitis, K) intervention strategies in necrotizing pancreatitis, and L) timing of cholecystectomy. Using the GRADE system, 21 of the 38 (55%) recommendations, were rated as 'strong' and plenary voting revealed 'strong agreement' for 34 (89%) recommendations. The 2012 IAP/APA guidelines provide recommendations concerning key aspects of medical and surgical management of acute pancreatitis based on the currently available evidence. These recommendations should serve as a reference standard for current management and guide future clinical research on acute pancreatitis. Copyright © 2013 IAP and EPC. Published by Elsevier B.V. All rights reserved.

Rapid Assessment of Stakeholder Concerns about Public Health. An Introduction to a Fast and Inexpensive Approach Applied on Health Concerns about Intensive Animal Production Systems

PubMed Central

van der Ree, Joost; Lebret, Erik

2017-01-01

To effectively manage environmental health risks, stakeholders often need to act collectively. Stakeholders vary in their desire to act due to many factors, such as knowledge, risk perception, interests, and worldviews. Understanding their perceptions of the issues at stake is crucial to support the risk governance process. Even though concern assessment is a pivotal element of risk governance, few tools for rapid assessment are reported in the literature. We tested a rapid and relatively cheap approach, taking the Dutch debate on Intensive Animal Production Systems (IAPS) and health as an example. Dutch policy-oriented publications on IAPS and health and ten semi-structured in-depth interviews with a variety of stakeholders were analyzed to identify stakeholders and concerns involved in the Dutch debate about IAPS and health. Concerns were mapped and a stakeholder network was derived. Three classes of concerns were recognized in the discussions about IAPS and health: concerns related to health risks, concerns regarding the activity causing the risks (IAPS), and concerns about the process to control the risks. The notions of ‘trust’ and ‘scientific uncertainty’ appeared as important themes in the discussions. Argumentation based on concerns directly related to health risks, the activity causing the risk (IAPS), and its risk management can easily become muddled up in a societal debate, limiting the development of effective action perspectives. Acknowledging these multiple stakeholder concerns can clarify the positions taken by stakeholders and allow for more and other action perspectives to develop. PMID:29232902

Rapid Assessment of Stakeholder Concerns about Public Health. An Introduction to a Fast and Inexpensive Approach Applied on Health Concerns about Intensive Animal Production Systems.

PubMed

Kraaij-Dirkzwager, Marleen; van der Ree, Joost; Lebret, Erik

2017-12-11

To effectively manage environmental health risks, stakeholders often need to act collectively. Stakeholders vary in their desire to act due to many factors, such as knowledge, risk perception, interests, and worldviews. Understanding their perceptions of the issues at stake is crucial to support the risk governance process. Even though concern assessment is a pivotal element of risk governance, few tools for rapid assessment are reported in the literature. We tested a rapid and relatively cheap approach, taking the Dutch debate on Intensive Animal Production Systems (IAPS) and health as an example. Dutch policy-oriented publications on IAPS and health and ten semi-structured in-depth interviews with a variety of stakeholders were analyzed to identify stakeholders and concerns involved in the Dutch debate about IAPS and health. Concerns were mapped and a stakeholder network was derived. Three classes of concerns were recognized in the discussions about IAPS and health: concerns related to health risks, concerns regarding the activity causing the risks (IAPS), and concerns about the process to control the risks. The notions of 'trust' and 'scientific uncertainty' appeared as important themes in the discussions. Argumentation based on concerns directly related to health risks, the activity causing the risk (IAPS), and its risk management can easily become muddled up in a societal debate, limiting the development of effective action perspectives. Acknowledging these multiple stakeholder concerns can clarify the positions taken by stakeholders and allow for more and other action perspectives to develop.

Microbiota-host interplay at the gut epithelial level, health and nutrition.

PubMed

Lallès, Jean-Paul

2016-01-01

Growing evidence suggests the implication of the gut microbiota in various facets of health and disease. In this review, the focus is put on microbiota-host molecular cross-talk at the gut epithelial level with special emphasis on two defense systems: intestinal alkaline phosphatase (IAP) and inducible heat shock proteins (iHSPs). Both IAP and iHSPs are induced by various microbial structural components (e.g. lipopolysaccharide, flagellin, CpG DNA motifs), metabolites (e.g. n-butyrate) or secreted signal molecules (e.g., toxins, various peptides, polyphosphate). IAP is produced in the small intestine and secreted into the lumen and in the interior milieu. It detoxifies microbial components by dephosphorylation and, therefore, down-regulates microbe-induced inflammation mainly by inhibiting NF-κB pro-inflammatory pathway in enterocytes. IAP gene expression and enzyme activity are influenced by the gut microbiota. Conversely, IAP controls gut microbiota composition both directly, and indirectly though the detoxification of pro-inflammatory free luminal adenosine triphosphate and inflammation inhibition. Inducible HSPs are expressed by gut epithelial cells in proportion to the microbial load along the gastro-intestinal tract. They are also induced by various microbial components, metabolites and secreted molecules. Whether iHSPs contribute to shape the gut microbiota is presently unknown. Both systems display strong anti-inflammatory and anti-oxidant properties that are protective to the gut and the host. Importantly, epithelial gene expressions and protein concentrations of IAP and iHSPs can be stimulated by probiotics, prebiotics and a large variety of dietary components, including macronutrients (protein and amino acids, especially L-glutamine, fat, fiber), and specific minerals (e.g. calcium) and vitamins (e.g. vitamins K1 and K2). Some food components (e.g. lectins, soybean proteins, various polyphenols) may inhibit or disturb these systems. The general cellular and molecular mechanisms involved in the microbiota-host epithelial crosstalk and subsequent gut protection through IAP and iHSPs are reviewed along with their nutritional modulation. Special emphasis is also given to the pig, an economically important species and valuable biomedical model.

Relationship between intra-abdominal pressure and trunk EMG.

PubMed

McGill, S M; Sharratt, M T

1990-05-01

Intra-abdominal pressure (IAP) has been proposed as an important mechanism in manual lifting and breathing mechanics. Direct (invasive) measures of IAP have required the swallowing of a radio transducer or insertion of a pressure sensor into the rectum or down the oesophagus to the stomach. The purpose of this study was to investigate the relationship between a non-invasive method (EMG) and IAP. Several tasks involving abdominal muscle activation were performed to assess whether or not IAP played a common role in these tasks. IAP and EMG from rectus abdominis, the abdominal obliques, intercostals and erector spinae were measured. Peak IAP reached 340 mmHg (valsalva) for one subject but most values were less than 100 mmHg for tasks other than valsalva. The IAP and EMG data provide some insight into the role of IAP during the performance of specific tasks. Peak IAP within 60 ms of the onset of vigorous abdominal activation indicated the importance of a very rapid pressure response to abdominal muscle activation. The correlations between various muscle EMG time histories and IAP exceeded 0·80 for only two activities (i.e. r(2) = 0·82 between the intercostals and IAP during valsalva manoeuvres). These data suggest that no unifying hypothesis exists to explain the role of IAP for a wide variety of movement tasks; rather, the role of IAP is task specific. Copyright © 1990. Published by Elsevier Ltd.

Active Depletion of Host Cell Inhibitor-of-Apoptosis Proteins Triggers Apoptosis upon Baculovirus DNA Replication▿

PubMed Central

Vandergaast, Rianna; Schultz, Kimberly L. W.; Cerio, Rebecca J.; Friesen, Paul D.

2011-01-01

Apoptosis is an important antivirus defense by virtue of its impact on virus multiplication and pathogenesis. To define molecular mechanisms by which viruses are detected and the apoptotic response is initiated, we examined the antiviral role of host inhibitor-of-apoptosis (IAP) proteins in insect cells. We report here that the principal IAPs, DIAP1 and SfIAP, of the model insects Drosophila melanogaster and Spodoptera frugiperda, respectively, are rapidly depleted and thereby inactivated upon infection with the apoptosis-inducing baculovirus Autographa californica multicapsid nucleopolyhedrovirus (AcMNPV). Virus-induced loss of these host IAPs triggered caspase activation and apoptotic death. Elevation of IAP levels by ectopic expression repressed caspase activation. Loss of host IAP in both species was triggered by AcMNPV DNA replication. By using selected inhibitors, we found that virus-induced IAP depletion was mediated in part by the proteasome but not by caspase cleavage. Consistent with this conclusion, mutagenic disruption of the SfIAP RING motif, which acts as an E3 ubiquitin ligase, stabilized SfIAP during infection. Importantly, SfIAP was also stabilized upon the removal of its 99-residue N-terminal leader, which serves as a critical determinant of IAP turnover. These data indicated that a host pathway initiated by virus DNA replication and acting through instability motifs embedded within IAP triggers IAP depletion and thereby causes apoptosis. Taken together, the results of our study suggest that host modulation of cellular IAP levels is a conserved mechanism by which insects mount an apoptotic antiviral response. Thus, host IAPs may function as critical sentinels of virus invasion in insects. PMID:21653668

Intestinal alkaline phosphatase inhibits the proinflammatory nucleotide uridine diphosphate.

PubMed

Moss, Angela K; Hamarneh, Sulaiman R; Mohamed, Mussa M Rafat; Ramasamy, Sundaram; Yammine, Halim; Patel, Palak; Kaliannan, Kanakaraju; Alam, Sayeda N; Muhammad, Nur; Moaven, Omeed; Teshager, Abeba; Malo, Nondita S; Narisawa, Sonoko; Millán, José Luis; Warren, H Shaw; Hohmann, Elizabeth; Malo, Madhu S; Hodin, Richard A

2013-03-15

Uridine diphosphate (UDP) is a proinflammatory nucleotide implicated in inflammatory bowel disease. Intestinal alkaline phosphatase (IAP) is a gut mucosal defense factor capable of inhibiting intestinal inflammation. We used the malachite green assay to show that IAP dephosphorylates UDP. To study the anti-inflammatory effect of IAP, UDP or other proinflammatory ligands (LPS, flagellin, Pam3Cys, or TNF-α) in the presence or absence of IAP were applied to cell cultures, and IL-8 was measured. UDP caused dose-dependent increase in IL-8 release by immune cells and two gut epithelial cell lines, and IAP treatment abrogated IL-8 release. Costimulation with UDP and other inflammatory ligands resulted in a synergistic increase in IL-8 release, which was prevented by IAP treatment. In vivo, UDP in the presence or absence of IAP was instilled into a small intestinal loop model in wild-type and IAP-knockout mice. Luminal contents were applied to cell culture, and cytokine levels were measured in culture supernatant and intestinal tissue. UDP-treated luminal contents induced more inflammation on target cells, with a greater inflammatory response to contents from IAP-KO mice treated with UDP than from WT mice. Additionally, UDP treatment increased TNF-α levels in intestinal tissue of IAP-KO mice, and cotreatment with IAP reduced inflammation to control levels. Taken together, these studies show that IAP prevents inflammation caused by UDP alone and in combination with other ligands, and the anti-inflammatory effect of IAP against UDP persists in mouse small intestine. The benefits of IAP in intestinal disease may be partly due to inhibition of the proinflammatory activity of UDP.

Intestinal alkaline phosphatase regulates protective surface microclimate pH in rat duodenum.

PubMed

Mizumori, Misa; Ham, Maggie; Guth, Paul H; Engel, Eli; Kaunitz, Jonathan D; Akiba, Yasutada

2009-07-15

Regulation of localized extracellular pH (pH(o)) maintains normal organ function. An alkaline microclimate overlying the duodenal enterocyte brush border protects the mucosa from luminal acid. We hypothesized that intestinal alkaline phosphatase (IAP) regulates pH(o) due to pH-sensitive ATP hydrolysis as part of an ecto-purinergic pH regulatory system, comprised of cell-surface P2Y receptors and ATP-stimulated duodenal bicarbonate secretion (DBS). To test this hypothesis, we measured DBS in a perfused rat duodenal loop, examining the effect of the competitive alkaline phosphatase inhibitor glycerol phosphate (GP), the ecto-nucleoside triphosphate diphosphohydrolase inhibitor ARL67156, and exogenous nucleotides or P2 receptor agonists on DBS. Furthermore, we measured perfusate ATP concentration with a luciferin-luciferase bioassay. IAP inhibition increased DBS and luminal ATP output. Increased luminal ATP output was partially CFTR dependent, but was not due to cellular injury. Immunofluorescence localized the P2Y(1) receptor to the brush border membrane of duodenal villi. The P2Y(1) agonist 2-methylthio-ADP increased DBS, whereas the P2Y(1) antagonist MRS2179 reduced ATP- or GP-induced DBS. Acid perfusion augmented DBS and ATP release, further enhanced by the IAP inhibitor l-cysteine, and reduced by the exogenous ATPase apyrase. Furthermore, MRS2179 or the highly selective P2Y(1) antagonist MRS2500 co-perfused with acid induced epithelial injury, suggesting that IAP/ATP/P2Y signalling protects the mucosa from acid injury. Increased DBS augments IAP activity presumably by raising pH(o), increasing the rate of ATP degradation, decreasing ATP-mediated DBS, forming a negative feedback loop. The duodenal epithelial brush border IAP-P2Y-HCO(3-) surface microclimate pH regulatory system effectively protects the mucosa from acid injury.

cIAPs promote the proteasomal degradation of mutant SOD1 linked to familial amyotrophic lateral sclerosis.

PubMed

Choi, Jin Sun; Kim, Kidae; Lee, Do Hee; Cho, Sayeon; Ha, Jae Du; Park, Byoung Chul; Kim, Sunhong; Park, Sung Goo; Kim, Jeong-Hoon

2016-11-18

Although the ubiquitin-proteasome system is believed to play an important role in the pathogenesis of familial amyotrophic lateral sclerosis (FALS), caused by mutations in Cu/Zn-superoxide dismutase 1 (SOD1), the mechanism of how mutant SOD1 protein is regulated in cells is still poorly understood. Here we have demonstrated that cellular inhibitor of apoptosis proteins (cIAPs) are specifically associated with FALS-linked mutant SOD1 (mSOD1) and that this interaction promotes the ubiquitin-dependent proteasomal degradation of mutant SOD1. By utilizing cumate inducible SOD1 cells, we also showed that knock-down or pharmacologic depletion of cIAPs leads to H 2 O 2 induced cytotoxicity in mSOD1 expressing cells. Altogether, our results reveal a novel role of cIAPs in FALS-associated mutant SOD1 regulation. Copyright © 2016 Elsevier Inc. All rights reserved.

Intestinal alkaline phosphatase inhibits the proinflammatory nucleotide uridine diphosphate

PubMed Central

Hamarneh, Sulaiman R.; Mohamed, Mussa M. Rafat; Ramasamy, Sundaram; Yammine, Halim; Patel, Palak; Kaliannan, Kanakaraju; Alam, Sayeda N.; Muhammad, Nur; Moaven, Omeed; Teshager, Abeba; Malo, Nondita S.; Narisawa, Sonoko; Millán, José Luis; Warren, H. Shaw; Hohmann, Elizabeth; Malo, Madhu S.; Hodin, Richard A.

2013-01-01

Uridine diphosphate (UDP) is a proinflammatory nucleotide implicated in inflammatory bowel disease. Intestinal alkaline phosphatase (IAP) is a gut mucosal defense factor capable of inhibiting intestinal inflammation. We used the malachite green assay to show that IAP dephosphorylates UDP. To study the anti-inflammatory effect of IAP, UDP or other proinflammatory ligands (LPS, flagellin, Pam3Cys, or TNF-α) in the presence or absence of IAP were applied to cell cultures, and IL-8 was measured. UDP caused dose-dependent increase in IL-8 release by immune cells and two gut epithelial cell lines, and IAP treatment abrogated IL-8 release. Costimulation with UDP and other inflammatory ligands resulted in a synergistic increase in IL-8 release, which was prevented by IAP treatment. In vivo, UDP in the presence or absence of IAP was instilled into a small intestinal loop model in wild-type and IAP-knockout mice. Luminal contents were applied to cell culture, and cytokine levels were measured in culture supernatant and intestinal tissue. UDP-treated luminal contents induced more inflammation on target cells, with a greater inflammatory response to contents from IAP-KO mice treated with UDP than from WT mice. Additionally, UDP treatment increased TNF-α levels in intestinal tissue of IAP-KO mice, and cotreatment with IAP reduced inflammation to control levels. Taken together, these studies show that IAP prevents inflammation caused by UDP alone and in combination with other ligands, and the anti-inflammatory effect of IAP against UDP persists in mouse small intestine. The benefits of IAP in intestinal disease may be partly due to inhibition of the proinflammatory activity of UDP. PMID:23306083

INTESTINAL ALKALINE PHOSPHATASE: A SUMMARY OF ITS ROLE IN CLINICAL DISEASE

PubMed Central

Fawley, Jason; Gourlay, David

2016-01-01

Over the past few years, there is increasing evidence implicating a novel role for Intestinal Alkaline Phosphatase (IAP) in mitigating inflammatory mediated disorders. IAP is an endogenous protein expressed by the intestinal epithelium that is believed to play a vital role in maintaining gut homeostasis. Loss of IAP expression or function is associated with increased intestinal inflammation, dysbiosis, bacterial translocation and subsequently systemic inflammation. As these events are a cornerstone of the pathophysiology of many diseases relevant to surgeons, we sought to review recent research in both animal and humans on IAP’s physiologic function, mechanisms of action and current research in specific surgical diseases. PMID:27083970

A Discrete Ubiquitin-Mediated Network Regulates the Strength of NOD2 Signaling

PubMed Central

Tigno-Aranjuez, Justine T.; Bai, Xiaodong

2013-01-01

Dysregulation of NOD2 signaling is implicated in the pathology of various inflammatory diseases, including Crohn's disease, asthma, and sarcoidosis, making signaling proteins downstream of NOD2 potential therapeutic targets. Inhibitor-of-apoptosis (IAP) proteins, particularly cIAP1, are essential mediators of NOD2 signaling, and in this work, we describe a molecular mechanism for cIAP1's regulation in the NOD2 signaling pathway. While cIAP1 promotes RIP2's tyrosine phosphorylation and subsequent NOD2 signaling, this positive regulation is countered by another E3 ubiquitin ligase, ITCH, through direct ubiquitination of cIAP1. This ITCH-mediated ubiquitination leads to cIAP1's lysosomal degradation. Pharmacologic inhibition of cIAP1 expression in ITCH−/− macrophages attenuates heightened ITCH−/− macrophage muramyl dipeptide-induced responses. Transcriptome analysis, combined with pharmacologic inhibition of cIAP1, further defines specific pathways within the NOD2 signaling pathway that are targeted by cIAP1. This information provides genetic signatures that may be useful in repurposing cIAP1-targeted therapies to correct NOD2-hyperactive states and identifies a ubiquitin-regulated signaling network centered on ITCH and cIAP1 that controls the strength of NOD2 signaling. PMID:23109427

Optimizing working space in laparoscopy: CT measurement of the effect of pre-stretching of the abdominal wall in a porcine model.

PubMed

Vlot, John; Wijnen, René; Stolker, Robert Jan; Bax, Klaas N

2014-03-01

Determinants of working space in minimal access surgery have not been well studied. Using computed tomography (CT) to measure volumes and linear dimensions, we are studying the effect of a number of determinants of CO2 working space in a porcine laparoscopy model. Here we report the effects of pre-stretching of the abdominal wall. Earlier we had noted an increase in CO2 pneumoperitoneum volume at repeat insufflation with an intra-abdominal pressure (IAP) of 5 mmHg after previous stepwise insufflation up to an IAP of 15 mmHg. We reviewed the data of this serendipity group; data of 16 pigs were available. In a new group of eight pigs, we also explored this effect at repeat IAPs of 10 and 15 mmHg. Volumes and linear dimensions of the CO2 pneumoperitoneum were measured on reconstructed CT images and compared between the initial and repeat insufflation runs. Previous stepwise insufflation of the abdomen with CO2 up to 15 mmHg significantly (p < 0.01) increased subsequent working-space volume at a repeat IAP of 5 mmHg by 21 %, 7 % at a repeat IAP of 10 mmHg and 3 % at a repeat IAP of 15 mmHg. The external anteroposterior diameter significantly (p < 0.01) increased by 0.5 cm (14 %) at repeat 5 mmHg. Other linear dimensions showed a much smaller change. There was no statistically significant correlation between the duration of the insufflation run and the volume increase after pre-stretching at all IAP levels. Pre-stretching of the abdominal wall allows for the same surgical-field exposure at lower IAPs, reducing the negative effects of prolonged high-pressure CO2 pneumoperitoneum on the cardiorespiratory system and microcirculation. Pre-stretching has important scientific consequences in studies addressing ways of increasing working space in that its effect may confound the possible effects of other interventions aimed at increasing working space.

Targeted Degradation of Proteins Localized in Subcellular Compartments by Hybrid Small Molecules.

PubMed

Okuhira, Keiichiro; Shoda, Takuji; Omura, Risa; Ohoka, Nobumichi; Hattori, Takayuki; Shibata, Norihito; Demizu, Yosuke; Sugihara, Ryo; Ichino, Asato; Kawahara, Haruka; Itoh, Yukihiro; Ishikawa, Minoru; Hashimoto, Yuichi; Kurihara, Masaaki; Itoh, Susumu; Saito, Hiroyuki; Naito, Mikihiko

2017-03-01

Development of novel small molecules that selectively degrade pathogenic proteins would provide an important advance in targeted therapy. Recently, we have devised a series of hybrid small molecules named SNIPER (specific and nongenetic IAP-dependent protein ERaser) that induces the degradation of target proteins via the ubiquitin-proteasome system. To understand the localization of proteins that can be targeted by this protein knockdown technology, we examined whether SNIPER molecules are able to induce degradation of cellular retinoic acid binding protein II (CRABP-II) proteins localized in subcellular compartments of cells. CRABP-II is genetically fused with subcellular localization signals, and they are expressed in the cells. SNIPER(CRABP) with different IAP-ligands, SNIPER(CRABP)-4 with bestatin and SNIPER(CRABP)-11 with MV1 compound, induce the proteasomal degradation of wild-type (WT), cytosolic, nuclear, and membrane-localized CRABP-II proteins, whereas only SNIPER(CRABP)-11 displayed degradation activity toward the mitochondrial CRABP-II protein. The small interfering RNA-mediated silencing of cIAP1 expression attenuated the knockdown activity of SNIPER(CRABP) against WT and cytosolic CRABP-II proteins, indicating that cIAP1 is the E3 ligase responsible for degradation of these proteins. Against membrane-localized CRABP-II protein, cIAP1 is also a primary E3 ligase in the cells, but another E3 ligase distinct from cIAP2 and X-linked inhibitor of apoptosis protein (XIAP) could also be involved in the SNIPER(CRABP)-11-induced degradation. However, for the degradation of nuclear and mitochondrial CRABP-II proteins, E3 ligases other than cIAP1, cIAP2, and XIAP play a role in the SNIPER-mediated protein knockdown. These results indicate that SNIPER can target cytosolic, nuclear, membrane-localized, and mitochondrial proteins for degradation, but the responsible E3 ligase is different, depending on the localization of the target protein. Copyright © 2017 by The American Society for Pharmacology and Experimental Therapeutics.

Biliary tract instillation of a SMAC mimetic induces TRAIL-dependent acute sclerosing cholangitis-like injury in mice

PubMed Central

Guicciardi, Maria Eugenia; Krishnan, Anuradha; Bronk, Steven F; Hirsova, Petra; Griffith, Thomas S; Gores, Gregory J

2017-01-01

Primary sclerosing cholangitis (PSC) is a cholestatic liver disease of unknown etiopathogenesis characterized by fibrous cholangiopathy of large and small bile ducts. Systemic administration of a murine TNF-related apoptosis-inducing ligand (TRAIL) receptor agonist induces a sclerosing cholangitis injury in C57BL/6 mice, suggesting endogenous TRAIL may contribute to sclerosing cholangitis syndromes. Cellular inhibitor of apoptosis proteins (cIAP-1 and cIAP-2) are negative regulators of inflammation and TRAIL receptor signaling. We hypothesized that if endogenous TRAIL promotes sclerosing cholangitis, then cIAP depletion should also induce this biliary tract injury. Herein, we show that cIAP protein levels are reduced in the interlobular bile ducts of human PSC livers. Downregulation of cIAPs in normal human cholangiocytes in vitro by use of a SMAC mimetic (SM) induces moderate, ripoptosome-mediated apoptosis and RIP1-independent upregulation of proinflammatory cytokines and chemokines. Cytokine and chemokine expression was mediated by the non-canonical activation of NF-κB. To investigate whether downregulation of cIAPs is linked to generation of a PSC-like phenotype, an SM was directly instilled into the mouse biliary tree. Twelve hours after biliary instillation, TUNEL-positive cholangiocytes were identified; 5 days later, PSC-like changes were observed in the SM-treated mice, including a fibrous cholangiopathy of the interlobular bile ducts, portal inflammation, significant elevation of serum markers of cholestasis and cholangiographic evidence of intrahepatic biliary tract injury. In contrast, TRAIL and TRAIL-receptor deficient mice showed no sign of cholangiopathy following SM intrabiliary injection. We conclude that in vivo antagonism of cIAPs in mouse biliary epithelial cells is sufficient to trigger cholangiocytes apoptosis and a proinflammatory response resulting in a fibrous cholangiopathy resembling human sclerosing cholangitis. Therefore, downregulation of cIAPs in PSC cholangiocytes may contribute to the development of the disease. Our results also indicate that inhibition of TRAIL signaling pathways may be beneficial in the treatment of PSC. PMID:28055006

[Control of intubator associated pneumonia in intensive care unit: results of the GISIO-SItI SPIN-UTI Project].

PubMed

Agodi, Antonella; Auxilia, Francesco; Barchitta, Martina; D'Errico, Marcello Mario; Montagna, Maria Teresa; Pasquarella, Cesira; Tardivo, Stefano; Mura, Ida

2014-01-01

To document reported Intubator Associated Pneumonia (IAP) prevention practices in Intensive Care Units (ICUs) and attitudes towards the implementation of a measurement system. In the framework of the SPIN-UTI project the «Italian Nosocomial Infections Surveillance in ICUs network», two questionnaires were made available online. The first was filled out by physicians working in ICUs in order to collect data on characteristics of physicians and ICUs, on clinical and measurement practices for IAP prevention, and attitudes towards the implementation of a measurement system. The second questionnaire was filled out for each intubated patient in order to collect data on prevention practices during ICU stay. ICUs participating to the fourth edition (2012-2013) of the SPIN-UTI project. Compliance to the component of the European bundle. The components of the bundle for the prevention of IAP are implemented, although to a different level, in the 26 participating ICUs. Overall compliance to all five practices of the European bundle has been reported in 21.1% of the 768 included patients. The present survey has documented a large potential for improvement in clinical and non-clinical practices aimed at preventing IAP in ICUs.

Intestinal alkaline phosphatase deficiency leads to dysbiosis and bacterial translocation in the newborn intestine.

PubMed

Fawley, Jason; Koehler, Shannon; Cabrera, Susan; Lam, Vy; Fredrich, Katherine; Hessner, Martin; Salzman, Nita; Gourlay, David

2017-10-01

Intestinal alkaline phosphatase (IAP) has been shown to help maintain intestinal homeostasis. Decreased expression of IAP has been linked with pediatric intestinal diseases associated with bacterial overgrowth and subsequent inflammation. We hypothesize that the absence of IAP leads to dysbiosis, with increased inflammation and permeability of the newborn intestine. Sprague-Dawley heterozygote IAP cross-matches were bred. Pups were dam fed ad lib and euthanized at weaning. The microbiotas of terminal ileum (TI) and colon was determined by quantitative real-time polymerase chain reaction (qRT-PCR) of subphylum-specific bacterial 16S ribosomal RNA. RT-PCR was performed on TI for inflammatory cytokines. Intestinal permeability was quantified by fluorescein isothiocyanate-dextran permeability and bacterial translocation by qRT-PCR for bacterial 16S ribosomal RNA in mesenteric lymph nodes. Statistical analysis was done by chi-square analysis. All three genotypes had similar concentrations of bacteria in the TI and colon. However, IAP knockout (IAP-KO) had significantly decreased diversity of bacterial species in their colonic stool compared with heterozygous and wild-type (WT). IAP-KO pups had a nonstatistically significant 3.9-fold increased inducible nitric oxide synthase messenger RNA expression compared with WT (IAP-KO, 3.92 ± 1.36; WT, 1.0 ± 0.27; P = 0.03). IAP-KO also had significantly increased bacterial translocation to mesenteric lymph nodes occurred in IAP-KO (IAP-KO, 7625 RFU/g ± 3469; WT, 4957 RFU/g ± 1552; P = 0.04). Furthermore, IAP-KO had increased permeability (IAP-KO, 0.297 mg/mL ± 0.2; WT, 0.189 mg/mL ± 0.15 P = 0.07), but was not statistically significant. Deficiency of IAP in the newborn intestine is associated with dysbiosis and increased inflammation, permeability, and bacterial translocation. Copyright © 2017 Elsevier Inc. All rights reserved.

Perinatal lead (Pb) exposure results in sex and tissue-dependent adult DNA methylation alterations in murine IAP transposons.

PubMed

Montrose, L; Faulk, C; Francis, J; Dolinoy, D C

2017-10-01

Epidemiological and animal data suggest that adult chronic disease is influenced by early-life exposure-induced changes to the epigenome. Previously, we observed that perinatal lead (Pb) exposure results in persistent murine metabolic- and activity-related effects. Using phylogenetic and DNA methylation analysis, we have also identified novel intracisternal A particle (IAP) retrotransposons exhibiting regions of variable methylation as candidate loci for environmental effects on the epigenome. Here, we now evaluate brain and kidney DNA methylation profiles of four representative IAPs in adult mice exposed to human physiologically relevant levels of Pb two weeks prior to mating through lactation. When IAPs across the genome were evaluated globally, average (sd) methylation levels were 92.84% (3.74) differing by tissue (P < 0.001), but not sex or dose. By contrast, the four individual IAPs displayed tissue-specific Pb and sex effects. Medium Pb-exposed mice had 3.86% less brain methylation at IAP 110 (P < 0.01), while high Pb-exposed mice had 2.83% less brain methylation at IAP 236 (P = 0.01) and 1.77% less at IAP 506 (P = 0.05). Individual IAP DNA methylation differed by sex for IAP 110 in the brain and kidney, IAP 236 in the kidney, and IAP 1259 in the kidney. Using Tomtom, we identified three binding motifs that matched to each of our novel IAPs impacted by Pb, one of which (HMGA2) has been linked to metabolic-related conditions in both mice and humans. Thus, these recently identified IAPs display tissue-specific environmental lability as well as sex-specific differences supporting an epigenetic link between early exposure to Pb and later-in-life health outcomes. Environ. Mol. Mutagen. 58:540-550, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

A High Level of Intestinal Alkaline Phosphatase Is Protective Against Type 2 Diabetes Mellitus Irrespective of Obesity.

PubMed

Malo, Madhu S

2015-12-01

Mice deficient in intestinal alkaline phosphatase (IAP) develop type 2 diabetes mellitus (T2DM). We hypothesized that a high level of IAP might be protective against T2DM in humans. We determined IAP levels in the stools of 202 diabetic patients and 445 healthy non-diabetic control people. We found that compared to controls, T2DM patients have approx. 50% less IAP (mean +/- SEM: 67.4 +/- 3.2 vs 35.3 +/- 2.5 U/g stool, respectively; p < 0.000001) indicating a protective role of IAP against T2DM. Multiple logistic regression analyses showed an independent association between the IAP level and diabetes status. With each 25 U/g decrease in stool IAP, there is a 35% increased risk of diabetes. The study revealed that obese people with high IAP (approx. 65 U/g stool) do not develop T2DM. Approx. 65% of the healthy population have < 65.0 U/g stool IAP, and predictably, these people might have 'the incipient metabolic syndrome', including 'incipient diabetes', and might develop T2DM and other metabolic disorders in the near future. In conclusion, high IAP levels appear to be protective against diabetes irrespective of obesity, and a 'temporal IAP profile' might be a valuable tool for predicting 'the incipient metabolic syndrome', including 'incipient diabetes'.

Interplay between intestinal alkaline phosphatase, diet, gut microbes and immunity.

PubMed

Estaki, Mehrbod; DeCoffe, Daniella; Gibson, Deanna L

2014-11-14

Intestinal alkaline phosphatase (IAP) plays an essential role in intestinal homeostasis and health through interactions with the resident microbiota, diet and the gut. IAP's role in the intestine is to dephosphorylate toxic microbial ligands such as lipopolysaccharides, unmethylated cytosine-guanosine dinucleotides and flagellin as well as extracellular nucleotides such as uridine diphosphate. IAP's ability to detoxify these ligands is essential in protecting the host from sepsis during acute inflammation and chronic inflammatory conditions such as inflammatory bowel disease. Also important in these complications is IAP's ability to regulate the microbial ecosystem by forming a complex relationship between microbiota, diet and the intestinal mucosal surface. Evidence reveals that diet alters IAP expression and activity and this in turn can influence the gut microbiota and homeostasis. IAP's ability to maintain a healthy gastrointestinal tract has accelerated research on its potential use as a therapeutic agent against a multitude of diseases. Exogenous IAP has been shown to have beneficial effects when administered during ulcerative colitis, coronary bypass surgery and sepsis. There are currently a handful of human clinical trials underway investigating the effects of exogenous IAP during sepsis, rheumatoid arthritis and heart surgery. In light of these findings IAP has been marked as a novel agent to help treat a variety of other inflammatory and infectious diseases. The purpose of this review is to highlight the essential characteristics of IAP in protection and maintenance of intestinal homeostasis while addressing the intricate interplay between IAP, diet, microbiota and the intestinal epithelium.

A High Level of Intestinal Alkaline Phosphatase Is Protective Against Type 2 Diabetes Mellitus Irrespective of Obesity☆

PubMed Central

Malo, Madhu S.

2015-01-01

Mice deficient in intestinal alkaline phosphatase (IAP) develop type 2 diabetes mellitus (T2DM). We hypothesized that a high level of IAP might be protective against T2DM in humans. We determined IAP levels in the stools of 202 diabetic patients and 445 healthy non-diabetic control people. We found that compared to controls, T2DM patients have approx. 50% less IAP (mean +/− SEM: 67.4 +/− 3.2 vs 35.3 +/− 2.5 U/g stool, respectively; p < 0.000001) indicating a protective role of IAP against T2DM. Multiple logistic regression analyses showed an independent association between the IAP level and diabetes status. With each 25 U/g decrease in stool IAP, there is a 35% increased risk of diabetes. The study revealed that obese people with high IAP (approx. 65 U/g stool) do not develop T2DM. Approx. 65% of the healthy population have < 65.0 U/g stool IAP, and predictably, these people might have ‘the incipient metabolic syndrome’, including ‘incipient diabetes’, and might develop T2DM and other metabolic disorders in the near future. In conclusion, high IAP levels appear to be protective against diabetes irrespective of obesity, and a ‘temporal IAP profile’ might be a valuable tool for predicting ‘the incipient metabolic syndrome’, including ‘incipient diabetes’. PMID:26844282

Intestinal alkaline phosphatase in the colonic mucosa of children with inflammatory bowel disease

PubMed Central

Molnár, Kriszta; Vannay, Ádám; Szebeni, Beáta; Bánki, Nóra Fanni; Sziksz, Erna; Cseh, Áron; Győrffy, Hajnalka; Lakatos, Péter László; Papp, Mária; Arató, András; Veres, Gábor

2012-01-01

AIM: To investigate intestinal alkaline phosphatase (iAP) in the intestinal mucosa of children with inflammatory bowel disease (IBD). METHODS: Colonic biopsy samples were taken from 15 newly diagnosed IBD patients and from 10 healthy controls. In IBD patients, specimens were obtained both from inflamed and non-inflamed areas. The iAP mRNA and protein expression was determined by reverse transcription-polymerase chain reaction and Western blotting analysis, respectively. Tissue localization of iAP and Toll-like receptor (TLR) 4 was investigated by immunofluorescent staining. RESULTS: The iAP protein level in the inflamed mucosa of children with Crohn’s disease (CD) and ulcerative colitis (UC) was significantly decreased when compared with controls (both P < 0.05). Similarly, we found a significantly decreased level of iAP protein in the inflamed mucosa in CD compared with non-inflamed mucosa in CD (P < 0.05). In addition, the iAP protein level in inflamed colonic mucosa in patients with UC was decreased compared with non-inflamed mucosa in patients with CD (P < 0.05). iAP protein levels in the non-inflamed mucosa of patients with CD were similar to controls. iAP mRNA expression in inflamed colonic mucosa of children with CD and UC was not significantly different from that in non-inflamed colonic mucosa with CD. Expression of iAP mRNA in patients with non-inflamed mucosa and in controls were similar. Co-localization of iAP with TLR4 showed intense staining with a dotted-like pattern. iAP was present in the inflamed and non-inflamed mucosa of patients with CD, UC, and in control biopsy specimens, irrespective of whether it was present in the terminal ileum or in the colon. However, the fluorescent signal of TLR4 was more pronounced in the colon compared with the terminal ileum in all groups studied. CONCLUSION: Lower than normal iAP protein levels in inflamed mucosa of IBD patients may indicate a role for iAP in inflammatory lesions in IBD. Based on our results, administration of exogenous iAP enzyme to patients with the active form of IBD may be a therapeutic option. PMID:22783049

EnOI-IAU Initialization Scheme Designed for Decadal Climate Prediction System IAP-DecPreS

NASA Astrophysics Data System (ADS)

Wu, Bo; Zhou, Tianjun; Zheng, Fei

2018-02-01

A decadal climate prediction system named as IAP-DecPreS was constructed in the Institute of Atmospheric Physics (IAP), Chinese Academy of Sciences, based on a fully coupled model FGOALS-s2 and a newly developed initialization scheme, referred to as EnOI-IAU. In this paper, we introduce the design of the EnOI-IAU scheme, assess the accuracies of initialization integrations using the EnOI-IAU and preliminarily evaluate hindcast skill of the IAP-DecPreS. The EnOI-IAU scheme integrates two conventional assimilation approaches, ensemble optimal interpolation (EnOI) and incremental analysis update (IAU). The EnOI and IAU were applied to calculate analysis increments and incorporate them into the model, respectively. Three continuous initialization (INIT) runs were conducted for the period of 1950-2015, in which observational sea surface temperature (SST) from the HadISST1.1 and subsurface ocean temperature profiles from the EN4.1.1 data set were assimilated. Then nine-member 10 year long hindcast runs initiated from the INIT runs were conducted for each year in the period of 1960-2005. The accuracies of the INIT runs are evaluated from the following three aspects: upper 700 m ocean temperature, temporal evolution of SST anomalies, and dominant interdecadal variability modes, Pacific Decadal Oscillation (PDO) and Atlantic Multidecadal Oscillation (AMO). Finally, preliminary evaluation of the ensemble mean of the hindcast runs suggests that the IAP-DecPreS has skill in the prediction of the PDO-related SST anomalies in the midlatitude North Pacific and AMO-related SST anomalies in the tropical North Atlantic.

Inhibitors of apoptosis (IAPs) regulate intestinal immunity and inflammatory bowel disease (IBD) inflammation.

PubMed

Pedersen, Jannie; LaCasse, Eric C; Seidelin, Jakob B; Coskun, Mehmet; Nielsen, Ole H

2014-11-01

The inhibitor of apoptosis (IAP) family members, notably cIAP1, cIAP2, and XIAP, are critical and universal regulators of tumor necrosis factor (TNF) mediated survival, inflammatory, and death signaling pathways. Furthermore, IAPs mediate the signaling of nucleotide-binding oligomerization domain (NOD)1/NOD2 and other intracellular NOD-like receptors in response to bacterial pathogens. These pathways are important to the pathogenesis and treatment of inflammatory bowel disease (IBD). Inactivating mutations in the X-chromosome-linked IAP (XIAP) gene causes an immunodeficiency syndrome, X-linked lymphoproliferative disease type 2 (XLP2), in which 20% of patients develop severe intestinal inflammation. In addition, 4% of males with early-onset IBD also have inactivating mutations in XIAP. Therefore, the IAPs play a greater role in gut homeostasis, immunity and IBD development than previously suspected, and may have therapeutic potential. Copyright © 2014 Elsevier Ltd. All rights reserved.

[Expression and significance of immunosuppressive acidic protein (IAP) in human esophageal squamous cell carcinoma].

PubMed

Guo, S Z; Shen, Q; Zhang, H B

1994-03-01

The expression of IAP in the esophageal tissues of 74 patients with esophageal squamous cell carcinoma and 12 normal controls were determined by using MI2, and anti-IAP monoclonal antibody, and ABC immunohistochemical staining. The results showed that there was no expression of IAP in normal esophageal epithelium of all control subjects, and the positive rate in specimens of the esophageal carcinomas was 90.3% (P < 0.001). The staining intensity of IAP was increasing with the decrease in degrees of cell differentiation of the tumors (P < 0.05). The expression of IAP in long survivors without lymph node metastasis were lower than that in cases with metastasis (P < 0.005) and short survivors (P < 0.001). The results suggest that IAP may play an important role in tumor cell differentiation, clinical course and prognosis of esophageal carcinoma, and may be used as a tumor marker for the diagnosis of this malignancy.

The respiratory pressure-abdominal volume curve in a porcine model.

PubMed

Regli, Adrian; De Keulenaer, Bart Leon; Singh, Bhajan; Hockings, Lisen Emma; Noffsinger, Bill; van Heerden, Peter Vernon

2017-12-01

Increasing intra-abdominal volume (IAV) can lead to intra-abdominal hypertension (IAH) or abdominal compartment syndrome. Both are associated with raised morbidity and mortality. IAH can increase airway pressures and impair ventilation. The relationship between increasing IAV and airway pressures is not known. We therefore assessed the effect of increasing IAV on airway and intra-abdominal pressures (IAP). Seven pigs (41.4 +/-8.5 kg) received standardized anesthesia and mechanical ventilation. A latex balloon inserted in the peritoneal cavity was inflated in 1-L increments until IAP exceeded 40 cmH 2 O. Peak airway pressure (pP AW ), respiratory compliance, and IAP (bladder pressure) were measured. Abdominal compliance was calculated. Different equations were tested that best described the measured pressure-volume curves. An exponential equation best described the measured pressure-volume curves. Raising IAV increased pP AW and IAP in an exponential manner. Increases in IAP were associated with parallel increases in pP AW with an approximate 40% transmission of IAP to pP AW . The higher the IAP, the greater IAV effected pP AW and IAP. The exponential nature of the effect of IAV on pP AW and IAP implies that, in the presence of high grades of IAH, small reductions in IAV can lead to significant reductions in airway and abdominal pressures. Conversely, in the presence of normal IAP levels, large increases in IAV may not affect airway and abdominal pressures.

Effect of abdominal negative-pressure wound therapy on the measurement of intra-abdominal pressure.

PubMed

García, Alberto Federico; Sánchez, Álvaro Ignacio; Gutiérrez, Álvaro José; Bayona, Juan Gabriel; Naranjo, María Paula; Lago, Sebastián; Puyana, Juan Carlos

2018-07-01

In critically ill surgical patients undergoing abdominal negative-pressure wound therapy (NPWT), it remains uncertain whether or not intra-abdominal pressure (IAP) measurements should be obtained when NPWT is activated. We aimed to determine agreement between IAP measured with and without NPWT. In this analytic cross-sectional study, critically ill surgical adults (≥18 y) requiring abdominal NPWT for temporary abdominal closure after a damage control laparotomy were selected. Patients with urinary tract injuries or with pelvic packing were excluded. Paired IAP measures were performed in the same patient, with and without NPWT; two different operators performed the measures unaware of the other's result. Bland-Altman methods assessed the agreement between the two measures. Subgroup analyses (trauma and nontrauma) were performed. There were 198 IAP measures (99 pairs) in 38 patients. Mean IAP with and without NPWT were 8.33 (standard deviation 4.01) and 8.65 (standard deviation 4.04), respectively. Mean IAP difference was -0.323 (95% confidence interval -0.748 to 0.101), and reference range for difference was -4.579 to 3.932 (P = 0.864). From 112 IAP measures (56 pairs) in 21 trauma patients, mean IAP difference was -0.268 (95% confidence interval -0.867 to 0.331), and reference range for the difference was -4.740 to 4.204 (P = 0.427). There was no statistically significant disagreement in IAP measures. IAP could be measured with or without NPWT. In critically ill surgical patients with abdominal NPWT for temporary abdominal closure, monitoring and management of IAP either with or without NPWT is recommended. Copyright © 2018 Elsevier Inc. All rights reserved.

TRAF2-binding BIR1 domain of c-IAP2/MALT1 fusion protein is essential for activation of NF-kappaB.

PubMed

Garrison, J B; Samuel, T; Reed, J C

2009-04-02

Marginal zone mucosa-associated lymphoid tissue (MALT) B-cell lymphoma is the most common extranodal non-Hodgkin lymphoma. The t(11;18)(q21;q21) translocation occurs frequently in MALT lymphomas and creates a chimeric NF-kappaB-activating protein containing the baculoviral IAP repeat (BIR) domains of c-IAP2 (inhibitor of apoptosis protein 2) fused with portions of the MALT1 protein. The BIR1 domain of c-IAP2 interacts directly with TRAF2 (TNFalpha-receptor-associated factor-2), but its role in NF-kappaB activation is still unclear. Here, we investigated the role of TRAF2 in c-IAP2/MALT1-induced NF-kappaB activation. We show the BIR1 domain of c-IAP2 is essential for NF-kappaB activation, whereas BIR2 and BIR3 domains are not. Studies of c-IAP2/MALT1 BIR1 mutant (E47A/R48A) that fails to activate NF-kappaB showed loss of TRAF2 binding, but retention of TRAF6 binding, suggesting that interaction of c-IAP2/MALT1 with TRAF6 is insufficient for NF-kappaB induction. In addition, a dominant-negative TRAF2 mutant or downregulation of TRAF2 achieved by small interfering RNA inhibited NF-kappaB activation by c-IAP2/MALT1 showing that TRAF2 is indispensable. Comparisons of the bioactivity of intact c-IAP2/MALT1 oncoprotein and BIR1 E47A/R48A c-IAP2/MALT1 mutant that cannot bind TRAF2 in a lymphoid cell line provided evidence that TRAF2 interaction is critical for c-IAP2/MALT1-mediated increases in the NF-kappaB activity, increased expression of endogenous NF-kappaB target genes (c-FLIP, TRAF1), and resistance to apoptosis.

Oral antibodies to human intestinal alkaline phosphatase reduce dietary phytate phosphate bioavailability in the presence of dietary 1α-hydroxycholecalciferol.

PubMed

Bobeck, Elizabeth A; Hellestad, Erica M; Helvig, Christian F; Petkovich, P Martin; Cook, Mark E

2016-03-01

While it is well established that active vitamin D treatment increases dietary phytate phosphate utilization, the mechanism by which intestinal alkaline phosphatase (IAP) participates in phytate phosphate use is less clear. The ability of human IAP (hIAP) oral antibodies to prevent dietary phytate phosphate utilization in the presence of 1α-hydroxycholecalciferol (1α-(OH) D3) in a chick model was investigated. hIAP specific chicken immunoglobulin Y (IgY) antibodies were generated by inoculating laying hens with 17 synthetic peptides derived from the human IAP amino acid sequence and harvesting egg yolk. Western blot analysis showed all antibodies recognized hIAP and 6 of the 8 antibodies selected showed modest inhibition of hIAP activity in vitro (6 to 33% inhibition). In chicks where dietary phosphate was primarily in the form of phytate, 4 selected hIAP antibodies inhibited 1α-(OH) D3-induced increases in blood phosphate, one of which, generated against selected peptide (MFPMGTPD), was as effective as sevelamer hydrochloride in preventing the 1α-(OH) D3-induced increase in blood phosphate, but ineffective in preventing an increase in body weight gain and bone ash induced by 1α-(OH) D3. These studies demonstrated that orally-delivered antibodies to IAP limit dietary phytate-phosphate utilization in chicks treated with 1α-(OH) D3, and implicate IAP as an important host enzyme in increasing phytate phosphate bioavailability in 1α-(OH) D3 fed chicks. © 2015 Poultry Science Association Inc.

Areas of high conservation value at risk by plant invaders in Georgia under climate change.

PubMed

Slodowicz, Daniel; Descombes, Patrice; Kikodze, David; Broennimann, Olivier; Müller-Schärer, Heinz

2018-05-01

Invasive alien plants (IAP) are a threat to biodiversity worldwide. Understanding and anticipating invasions allow for more efficient management. In this regard, predicting potential invasion risks by IAPs is essential to support conservation planning into areas of high conservation value (AHCV) such as sites exhibiting exceptional botanical richness, assemblage of rare, and threatened and/or endemic plant species. Here, we identified AHCV in Georgia, a country showing high plant richness, and assessed the susceptibility of these areas to colonization by IAPs under present and future climatic conditions. We used actual protected areas and areas of high plant endemism (identified using occurrences of 114 Georgian endemic plant species) as proxies for AHCV. Then, we assessed present and future potential distribution of 27 IAPs using species distribution models under four climate change scenarios and stacked single-species potential distribution into a consensus map representing IAPs richness. We evaluated present and future invasion risks in AHCV using IAPs richness as a metric of susceptibility. We show that the actual protected areas cover only 9.4% of the areas of high plant endemism in Georgia. IAPs are presently located at lower elevations around the large urban centers and in western Georgia. We predict a shift of IAPs toward eastern Georgia and higher altitudes and an increased susceptibility of AHCV to IAPs under future climate change. Our study provides a good baseline for decision makers and stakeholders on where and how resources should be invested in the most efficient way to protect Georgia's high plant richness from IAPs.

Intestinal Alkaline Phosphatase: Potential Roles in Promoting Gut Health in Weanling Piglets and Its Modulation by Feed Additives - A Review.

PubMed

Melo, A D B; Silveira, H; Luciano, F B; Andrade, C; Costa, L B; Rostagno, M H

2016-01-01

The intestinal environment plays a critical role in maintaining swine health. Many factors such as diet, microbiota, and host intestinal immune response influence the intestinal environment. Intestinal alkaline phosphatase (IAP) is an important apical brush border enzyme that is influenced by these factors. IAP dephosphorylates bacterial lipopolysaccharides (LPS), unmethylated cytosine-guanosine dinucleotides, and flagellin, reducing bacterial toxicity and consequently regulating toll-like receptors (TLRs) activation and inflammation. It also desphosphorylates extracellular nucleotides such as uridine diphosphate and adenosine triphosphate, consequently reducing inflammation, modulating, and preserving the homeostasis of the intestinal microbiota. The apical localization of IAP on the epithelial surface reveals its role on LPS (from luminal bacteria) detoxification. As the expression of IAP is reported to be downregulated in piglets at weaning, LPS from commensal and pathogenic gram-negative bacteria could increase inflammatory processes by TLR-4 activation, increasing diarrhea events during this phase. Although some studies had reported potential IAP roles to promote gut health, investigations about exogenous IAP effects or feed additives modulating IAP expression and activity yet are necessary. However, we discussed in this paper that the critical assessment reported can suggest that exogenous IAP or feed additives that could increase its expression could show beneficial effects to reduce diarrhea events during the post weaning phase. Therefore, the main goals of this review are to discuss IAP's role in intestinal inflammatory processes and present feed additives used as growth promoters that may modulate IAP expression and activity to promote gut health in piglets.

Estimating the duration of intracellular action potentials in muscle fibres from single-fibre extracellular potentials.

PubMed

Rodríguez, Javier; Navallas, Javier; Gila, Luis; Dimitrova, Nonna Alexandrovna; Malanda, Armando

2011-04-30

In situ recording of the intracellular action potential (IAP) of human muscle fibres is not yet possible, and consequently, knowledge concerning certain IAP characteristics is still limited. According to the core-conductor theory, close to a fibre, a single fibre action potential (SFAP) can be assumed to be proportional to the IAP second derivative. Thus, we might expect to be able to derive some characteristics of the IAP, such as the duration of its spike, from the SFAP waveform. However, SFAP properties not only depend on the IAP shape but also on the fibre-to-electrode (radial) distance and other physiological properties of the fibre. In this paper we, first, propose an SFAP parameter (the negative phase duration, NPD) appropriate for estimating the IAP spike duration and, second, show that this parameter is largely independent of changes in radial distance and muscle fibre propagation velocity. Estimation of the IAP spike duration from a direct measurement taken from the SFAP waveform provides a possible way to enhance the accuracy of SFAP models. Because IAP spike duration is known to be sensitive to the effects of fatigue and calcium accumulation, the proposed SFAP parameter, the NPD, has potential value in electrodiagnosis and as an indicator of IAP profile changes due to peripheral fatigue. Copyright © 2011 Elsevier B.V. All rights reserved.

In Vivo Knockdown of Pathogenic Proteins via Specific and Nongenetic Inhibitor of Apoptosis Protein (IAP)-dependent Protein Erasers (SNIPERs).

PubMed

Ohoka, Nobumichi; Okuhira, Keiichiro; Ito, Masahiro; Nagai, Katsunori; Shibata, Norihito; Hattori, Takayuki; Ujikawa, Osamu; Shimokawa, Kenichiro; Sano, Osamu; Koyama, Ryokichi; Fujita, Hisashi; Teratani, Mika; Matsumoto, Hirokazu; Imaeda, Yasuhiro; Nara, Hiroshi; Cho, Nobuo; Naito, Mikihiko

2017-03-17

Many diseases, especially cancers, result from aberrant or overexpression of pathogenic proteins. Specific inhibitors against these proteins have shown remarkable therapeutic effects, but these are limited mainly to enzymes. An alternative approach that may have utility in drug development relies on selective degradation of pathogenic proteins via small chimeric molecules linking an E3 ubiquitin ligase to the targeted protein for proteasomal degradation. To this end, we recently developed a protein knockdown system based on hybrid small molecule SNIPERs ( S pecific and N ongenetic I AP-dependent P rotein Er asers) that recruit inhibitor of the apoptosis protein (IAP) ubiquitin ligases to specifically degrade targeted proteins. Here, we extend our previous study to show a proof of concept of the SNIPER technology in vivo By incorporating a high affinity IAP ligand, we developed a novel SNIPER against estrogen receptor α (ERα), SNIPER(ER)-87, that has a potent protein knockdown activity. The SNIPER(ER) reduced ERα levels in tumor xenografts and suppressed the growth of ERα-positive breast tumors in mice. Mechanistically, it preferentially recruits X-linked IAP (XIAP) rather than cellular IAP1, to degrade ERα via the ubiquitin-proteasome pathway. With this IAP ligand, potent SNIPERs against other pathogenic proteins, BCR-ABL, bromodomain-containing protein 4 (BRD4), and phosphodiesterase-4 (PDE4) could also be developed. These results indicate that forced ubiquitylation by SNIPERs is a useful method to achieve efficient protein knockdown with potential therapeutic activities and could also be applied to study the role of ubiquitylation in many cellular processes. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Intestinal alkaline phosphatase: multiple biological roles in maintenance of intestinal homeostasis and modulation by diet.

PubMed

Lallès, Jean-Paul

2010-06-01

The diverse nature of intestinal alkaline phosphatase (IAP) functions has remained elusive, and it is only recently that four additional major functions of IAP have been revealed. The present review analyzes the earlier literature on the dietary factors modulating IAP activity in light of these new findings. IAP regulates lipid absorption across the apical membrane of enterocytes, participates in the regulation of bicarbonate secretion and of duodenal surface pH, limits bacterial transepithelial passage, and finally controls bacterial endotoxin-induced inflammation by dephosphorylation, thus detoxifying intestinal lipopolysaccharide. Many dietary components, including fat, protein, and carbohydrate, modulate IAP expression or activity and may be combined to sustain a high level of IAP activity. In conclusion, IAP has a pivotal role in intestinal homeostasis and its activity could be increased through the diet. This is especially true in pathological situations (e.g., inflammatory bowel diseases) in which the involvement of commensal bacteria is suspected and when intestinal AP is too low to detoxify a sufficient amount of bacterial lipopolysaccharide.

Intestinal alkaline phosphatase to treat necrotizing enterocolitis.

PubMed

Biesterveld, Ben E; Koehler, Shannon M; Heinzerling, Nathan P; Rentea, Rebecca M; Fredrich, Katherine; Welak, Scott R; Gourlay, David M

2015-06-15

Intestinal alkaline phosphatase (IAP) activity is decreased in necrotizing enterocolitis (NEC), and IAP supplementation prevents NEC development. It is not known if IAP given after NEC onset can reverse the course of the disease. We hypothesized that enteral IAP given after NEC induction would not reverse intestinal injury. NEC was induced in Sprague-Dawley pups by delivery preterm followed by formula feedings with lipopolysaccharide (LPS) and hypoxia exposure and continued up to 4 d. IAP was added to feeds on day 2 until being sacrificed on day 4. NEC severity was scored based on hematoxylin and eosin-stained terminal ileum sections, and AP activity was measured using a colorimetric assay. IAP and interleukin-6 expression were measured using real time polymerase chain reaction. NEC pups' alkaline phosphatase (AP) activity was decreased to 0.18 U/mg compared with controls of 0.57 U/mg (P < 0.01). Discontinuation of LPS and hypoxia after 2 d increased AP activity to 0.36 U/mg (P < 0.01). IAP supplementation in matched groups did not impact total AP activity or expression. Discontinuing LPS and hypoxia after NEC onset improved intestinal injury scores to 1.14 compared with continued stressors, score 2.25 (P < 0.01). IAP supplementation decreased interleukin-6 expression two-fold (P < 0.05), though did not reverse NEC intestinal damage (P = 0.5). This is the first work to demonstrate that removing the source of NEC improves intestinal damage and increases AP activity. When used as a rescue treatment, IAP decreased intestinal inflammation though did not impact injury making it likely that IAP is best used preventatively to those neonates at risk. Copyright © 2015 Elsevier Inc. All rights reserved.

Cost-effectiveness of a potential group B streptococcal vaccine for pregnant women in the United States.

PubMed

Kim, Sun-Young; Nguyen, Chi; Russell, Louise B; Tomczyk, Sara; Abdul-Hakeem, Fatimah; Schrag, Stephanie J; Verani, Jennifer R; Sinha, Anushua

2017-10-27

In the U.S., intrapartum antibiotic prophylaxis (IAP) for pregnant women colonized with group B streptococcus (GBS) has reduced GBS disease in the first week of life (early-onset/EOGBS). Nonetheless, GBS remains a leading cause of neonatal sepsis, including 1000 late-onset (LOGBS) cases annually. A maternal vaccine under development could prevent EOGBS and LOGBS. Using a decision-analytic model, we compared the public health impact, costs, and cost-effectiveness of five strategies to prevent GBS disease in infants: (1) no prevention; (2) currently recommended screening/IAP; (3) maternal GBS immunization; (4) maternal immunization with IAP when indicated for unimmunized women; (5) maternal immunization plus screening/IAP for all women. We modeled a pentavalent vaccine covering serotypes 1a, 1b, II, III, and V, which cause almost all GBS disease. In the base case, screening/IAP alone prevents 46% of EOGBS compared to no prevention, at a cost of $70,275 per quality-adjusted life-year (QALY) from a healthcare and $51,249/QALY from a societal perspective (2013 US$). At coverage rates typical of maternal vaccines in the U.S., a pentavalent vaccine alone would not prevent as much disease as screening/IAP until its efficacy approached 90%, but would cost less per QALY. At vaccine efficacy of ≥70%, maternal immunization together with IAP for unimmunized women would prevent more disease than screening/IAP, at a similar cost/QALY. GBS maternal immunization, with IAP as indicated for unvaccinated women, could be an attractive alternative to screening/IAP if a pentavalent vaccine is sufficiently effective. Coverage, typically low for maternal vaccines, is key to the vaccine's public health impact. Copyright © 2017 Elsevier Ltd. All rights reserved.

Chlamydia trachomatis can protect host cells against apoptosis in the absence of cellular Inhibitor of Apoptosis Proteins and Mcl-1.

PubMed

Ying, Songmin; Christian, Jan G; Paschen, Stefan A; Häcker, Georg

2008-01-01

Infection with Chlamydia protects mammalian host cells against apoptosis. Hypotheses have been proposed to explain this molecularly, including the up-regulation of host anti-apoptotic proteins such as cellular Inhibitor of Apoptosis Protein (IAP) 2 and the Bcl-2 protein Mcl-1. To test for the importance of these proteins, we used mouse embryonic fibroblasts from gene-targeted mice that were deficient in cIAP1, cIAP2, cIAP1/cIAP2, XIAP, or Mcl-1. Infection with Chlamydia trachomatis protected all cells equally well against apoptosis, which was induced either with tumour necrosis factor/cycloheximide (IAP-knock-out cells) or staurosporine (Mcl-1-knock-out). Therefore, these cellular anti-apoptotic proteins are not essential for apoptosis-protection by C. trachomatis.

Intestinal alkaline phosphatase preserves the normal homeostasis of gut microbiota.

PubMed

Malo, M S; Alam, S Nasrin; Mostafa, G; Zeller, S J; Johnson, P V; Mohammad, N; Chen, K T; Moss, A K; Ramasamy, S; Faruqui, A; Hodin, S; Malo, P S; Ebrahimi, F; Biswas, B; Narisawa, S; Millán, J L; Warren, H S; Kaplan, J B; Kitts, C L; Hohmann, E L; Hodin, R A

2010-11-01

The intestinal microbiota plays a critical role in maintaining human health; however, the mechanisms governing the normal homeostatic number and composition of these microbes are largely unknown. Previously it was shown that intestinal alkaline phosphatase (IAP), a small intestinal brush border enzyme, functions as a gut mucosal defence factor limiting the translocation of gut bacteria to mesenteric lymph nodes. In this study the role of IAP in the preservation of the normal homeostasis of the gut microbiota was investigated. Bacterial culture was performed in aerobic and anaerobic conditions to quantify the number of bacteria in the stools of wild-type (WT) and IAP knockout (IAP-KO) C57BL/6 mice. Terminal restriction fragment length polymorphism, phylogenetic analyses and quantitative real-time PCR of subphylum-specific bacterial 16S rRNA genes were used to determine the compositional profiles of microbiotas. Oral supplementation of calf IAP (cIAP) was used to determine its effects on the recovery of commensal gut microbiota after antibiotic treatment and also on the colonisation of pathogenic bacteria. IAP-KO mice had dramatically fewer and also different types of aerobic and anaerobic microbes in their stools compared with WT mice. Oral supplementation of IAP favoured the growth of commensal bacteria, enhanced restoration of gut microbiota lost due to antibiotic treatment and inhibited the growth of a pathogenic bacterium (Salmonella typhimurium). IAP is involved in the maintenance of normal gut microbial homeostasis and may have therapeutic potential against dysbiosis and pathogenic infections.

Perceptions of impact: Invasive alien plants in the urban environment.

PubMed

Potgieter, Luke J; Gaertner, Mirijam; O'Farrell, Patrick J; Richardson, David M

2018-06-08

Many alien plant species are introduced to urban areas to create, augment or restore ecosystem services (ES). However, many of these species spread beyond original plantings, sometimes causing negative effects on existing ES or creating novel ecosystem disservices (EDS). An understanding of the perceptions of urban residents regarding invasive alien plants (IAPs) and the ES and EDS they provide is needed for the effective prioritisation of IAP management efforts in cities. Using the city of Cape Town, South Africa as a case study, we conducted questionnaire-based surveys (online and face-to-face) to determine the perceptions of urban residents regarding IAPs and their capacity to provide ES and EDS. Most urban residents perceive IAPs negatively (i.e. agreeing that they create EDS), but many recognise their importance in providing ES. Although most residents are not opposed to the management of IAPs, such actions are not perceived as a high priority relative to other environmental problems. Socio-demographic variables such as age, education, environmental awareness, and ethnicity shape urban residents' perceptions of IAPs. Older, more educated respondents were more likely to perceive IAPs negatively, while respondents with greater environmental awareness were aware of the benefits provided by IAPs. This study highlights the need to integrate public perceptions into the planning and management of IAPs and emphasises the importance of including ES assessments into the decision-making process, particularly in urban areas. Copyright © 2018 Elsevier Ltd. All rights reserved.

Overcoming chemotherapy drug resistance by targeting inhibitors of apoptosis proteins (IAPs).

PubMed

Rathore, Rama; McCallum, Jennifer E; Varghese, Elizabeth; Florea, Ana-Maria; Büsselberg, Dietrich

2017-07-01

Inhibitors of apoptosis (IAPs) are a family of proteins that play a significant role in the control of programmed cell death (PCD). PCD is essential to maintain healthy cell turnover within tissue but also to fight disease or infection. Uninhibited, IAPs can suppress apoptosis and promote cell cycle progression. Therefore, it is unsurprising that cancer cells demonstrate significantly elevated expression levels of IAPs, resulting in improved cell survival, enhanced tumor growth and subsequent metastasis. Therapies to target IAPs in cancer has garnered substantial scientific interest and as resistance to anti-cancer agents becomes more prevalent, targeting IAPs has become an increasingly attractive strategy to re-sensitize cancer cells to chemotherapies, antibody based-therapies and TRAIL therapy. Antagonism strategies to modulate the actions of XIAP, cIAP1/2 and survivin are the central focus of current research and this review highlights advances within this field with particular emphasis upon the development and specificity of second mitochondria-derived activator of caspase (SMAC) mimetics (synthetic analogs of endogenously expressed inhibitors of IAPs SMAC/DIABLO). While we highlight the potential of SMAC mimetics as effective single agent or combinatory therapies to treat cancer we also discuss the likely clinical implications of resistance to SMAC mimetic therapy, occasionally observed in cancer cell lines.

The evaluation of the effect of body positioning on intra-abdominal pressure measurement and the effect of intra-abdominal pressure at different body positioning on organ function and prognosis in critically ill patients.

PubMed

Yi, Min; Leng, Yuxin; Bai, Yu; Yao, Gaiqi; Zhu, Xi

2012-04-01

Current literatures confirmed the widespread and frequent development of both intra-abdominal hypertension (IAH) and abdominal compartment syndrome (ACS) among the critically ill with a significant associated risk of organ failure and increased mortality. The 2004 International ACS Consensus Conference committee proposed that intra-abdominal pressure (IAP) be measured in complete supine position; however, the supine position of intensive care unit (ICU) patients (<30° of bed increase) presented a significant risk for ventilator-associated pneumonia. Therefore, the potential contribution of head of bed (HOB) position in elevating IAP should be considered. The purpose of this study was to evaluate the effect of body positioning on IAP measurement and the effect of IAP at different body positions on organ function and prognosis in critically ill patients. A prospective cohort study to investigate the effect of different patient positioning on IAP, organ function, and prognosis was conducted on 88 patients admitted to a medical-surgical ICU. On admission, patients' epidemiological data and risk factors for IAH were studied; daily mean IAPs, abdominal perfusion pressure, filtration gradient, Acute Physiology and Chronic Health Evaluation II score, sequential organ failure assessment score, and multiple organ dysfunction scores were registered; next, conventional hemodynamic variables, intrathoracic blood volume index, global end-diastolic volume index and extravascular lung water using the pulse contour cardiac output system were recorded. Intra-abdominal pressures were recorded through a bladder catheter every 4 hours on the first day. Intra-abdominal pressure was measured with the patient HOB increases from 0° to 45°. Mean arterial pressure was recorded simultaneously, whereas abdominal perfusion pressure and filtration gradient (FG) were also calculated simultaneously. The main results of this study were the incidence of IAH (28.4%) and ACS (2.3%) in ICU patients; the significant and independent relationship between IAP and HOB increases. Considering the absolute numbers of IAP, the HOB of 10° and 20° showed slight differences, whereas that of 30° and 45° showed clinically significant differences; HOB elevation was associated with clinically significant decreases in abdominal perfusion pressure and FG; patients with IAH were prone to the development of shock and multiple organ dysfunction syndrome and exhibited significantly lower intrathoracic blood volume index and global end-diastolic volume index and higher extravascular lung water. There is a significant and independent relationship between IAP and HOB positioning in critically ill patients, with the HOB of 30° and 45° showing significant difference. Abdominal perfusion pressure and FG are significantly decreased when the patient's HOB is elevated. The potential contribution of body position in elevating IAP should be considered in critically ill patients with the risk of IAH and ACS. Copyright © 2012 Elsevier Inc. All rights reserved.

The Ubiquitin-associated Domain of Cellular Inhibitor of Apoptosis Proteins Facilitates Ubiquitylation*

PubMed Central

Budhidarmo, Rhesa; Day, Catherine L.

2014-01-01

The cellular inhibitor of apoptosis (cIAP) proteins are essential RING E3 ubiquitin ligases that regulate apoptosis and inflammatory responses. cIAPs contain a ubiquitin-associated (UBA) domain that binds ubiquitin and is implicated in the regulation of cell survival and proteasomal degradation. Here we show that mutation of the MGF and LL motifs in the UBA domain of cIAP1 caused unfolding and increased cIAP1 multimonoubiquitylation. By developing a UBA mutant that disrupted ubiquitin binding but not the structure of the UBA domain, we found that the UBA domain enhances cIAP1 and cIAP2 ubiquitylation. We demonstrate that the UBA domain binds to the UbcH5b∼Ub conjugate, and this promotes RING domain-dependent monoubiquitylation. This study establishes ubiquitin-binding modules, such as the UBA domain, as important regulatory modules that can fine tune the activity of E3 ligases. PMID:25065467

Solution Structure of an Intramembrane Aspartyl Protease via Small Angle Neutron Scattering

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

Naing, Swe-Htet; Oliver, Ryan C.; Weiss, Kevin L.

Intramembrane aspartyl proteases (IAPs) comprise one of four families of integral membrane proteases that hydrolyze substrates within the hydrophobic lipid bilayer. IAPs include signal peptide peptidase, which processes remnant signal peptides from nascent polypeptides in the endoplasmic reticulum, and presenilin, the catalytic component of the γ-secretase complex that processes Notch and amyloid precursor protein. Despite their broad biomedical reach, basic structure-function relationships of IAPs remain active areas of research. Characterization of membrane-bound proteins is notoriously challenging due to their inherently hydrophobic character. For IAPs, oligomerization state in solution is one outstanding question, with previous proposals for monomer, dimer, tetramer, andmore » octamer. Here we used small angle neutron scattering (SANS) to characterize n-dodecyl-β-D-maltopyranoside (DDM) detergent solutions containing and absent a microbial IAP ortholog. A unique feature of SANS is the ability to modulate the solvent composition to mask all but the enzyme of interest. The signal from the IAP was enhanced by deuteration and, uniquely, scattering from DDM and buffers were matched by the use of both tail-deuterated DDM and D 2O. The radius of gyration calculated for IAP and the corresponding ab initio consensus model are consistent with a monomer. The model is slightly smaller than the crystallographic IAP monomer, suggesting a more compact protein in solution compared with the crystal lattice. In conclusion, our study provides direct insight into the oligomeric state of purified IAP in surfactant solution, and demonstrates the utility of fully contrast-matching the detergent in SANS to characterize other intramembrane proteases and their membrane-bound substrates.« less

More complicated than it looks: The vagaries of calculating intra-abdominal pressure

PubMed Central

Hamad, Nadia M.; Shaw, Janet M.; Nygaard, Ingrid E.; Coleman, Tanner J.; Hsu, Yvonne; Egger, Marlene; Hitchcock, Robert W.

2013-01-01

Activities thought to induce high intra-abdominal pressure (IAP), such as lifting weights, are restricted in women with pelvic floor disorders. Standardized procedures to assess IAP during activity are lacking and typically only focus on maximal IAP, variably defined. Our intent in this methods paper is to establish the best strategies for calculating maximal IAP and to add area under the curve and first moment of the area as potentially useful measures in understanding biologic effects of IAP. Thirteen women completed a range of activities while wearing an intra-vaginal pressure transducer. We first analyzed various strategies heuristically using data from 3 women. The measure that appeared to best represent maximal IAP was an average of the three, five or ten highest values, depending on activity, determined using a top down approach, with peaks at least 1 second apart using algorithms written for Matlab computer software, we then compared this strategy with others commonly reported in the literature quantitatively using data from 10 additional volunteers. Maximal IAP calculated using the top down approach differed for some, but not all, activities compared to the single highest peak or to averaging all peaks. We also calculated area under the curve, which allows for a time component, and first moment of the area, which maintains the time component while weighting pressure amplitude. We validated methods of assessing IAP using computer-generated sine waves. We offer standardized methods for assessing maximal, area under the curve and first moment of the area for IAP to improve future reporting and application of this clinically relevant measure in exercise science. PMID:23439349

Pellino-1 confers chemoresistance in lung cancer cells by upregulating cIAP2 through Lys63-mediated polyubiquitination

PubMed Central

Koh, Jaemoon; Chung, Doo Hyun

2016-01-01

Pellino-1 is an E3 ubiquitin ligase that mediates immune receptor signaling pathways. The role of Pellino-1 in oncogenesis of lung cancer was investigated in this study. Pellino-1 expression was increased in human lung cancer cell lines compared with non-neoplastic lung cell lines. Pellino-1 overexpression in human lung cancer cells, A549 and H1299 cells, increased the survival and colony forming ability. Pellino-1 overexpression in these cells also conferred resistance to cisplatin- or paclitaxel-induced apoptosis. In contrast, depletion of Pellino-1 decreased the survival of A549 and H1299 cells and sensitized these cells to cisplatin- and paclitaxel-induced apoptosis. Pellino-1 overexpression in A549 and H1299 cells upregulated the expression of inhibitor of apoptosis (IAP) proteins, including cIAP1 and cIAP2, while Pellino-1 depletion downregulated these molecules. Notably, Pellino-1 directly interacted with cIAP2 and stabilized cIAP2 through lysine63-mediated polyubiquitination via its E3 ligase activity. Pellino-1-mediated chemoresistance in lung cancer cells was dependent on the induction of cIAP2. Moreover, a strong positive correlation between Pellino-1 and the cIAP2 expression was observed in human lung adenocarcinoma tissues. Taken together, these results demonstrate that Pellino-1 contributes to lung oncogenesis through the overexpression of cIAP2 and promotion of cell survival and chemoresistance. Pellino-1 might be a novel oncogene and potential therapeutic target in lung cancer. PMID:27248820

Solution Structure of an Intramembrane Aspartyl Protease via Small Angle Neutron Scattering

DOE PAGES

Naing, Swe-Htet; Oliver, Ryan C.; Weiss, Kevin L.; ...

2018-02-06

Intramembrane aspartyl proteases (IAPs) comprise one of four families of integral membrane proteases that hydrolyze substrates within the hydrophobic lipid bilayer. IAPs include signal peptide peptidase, which processes remnant signal peptides from nascent polypeptides in the endoplasmic reticulum, and presenilin, the catalytic component of the γ-secretase complex that processes Notch and amyloid precursor protein. Despite their broad biomedical reach, basic structure-function relationships of IAPs remain active areas of research. Characterization of membrane-bound proteins is notoriously challenging due to their inherently hydrophobic character. For IAPs, oligomerization state in solution is one outstanding question, with previous proposals for monomer, dimer, tetramer, andmore » octamer. Here we used small angle neutron scattering (SANS) to characterize n-dodecyl-β-D-maltopyranoside (DDM) detergent solutions containing and absent a microbial IAP ortholog. A unique feature of SANS is the ability to modulate the solvent composition to mask all but the enzyme of interest. The signal from the IAP was enhanced by deuteration and, uniquely, scattering from DDM and buffers were matched by the use of both tail-deuterated DDM and D 2O. The radius of gyration calculated for IAP and the corresponding ab initio consensus model are consistent with a monomer. The model is slightly smaller than the crystallographic IAP monomer, suggesting a more compact protein in solution compared with the crystal lattice. In conclusion, our study provides direct insight into the oligomeric state of purified IAP in surfactant solution, and demonstrates the utility of fully contrast-matching the detergent in SANS to characterize other intramembrane proteases and their membrane-bound substrates.« less

Design Considerations for IAP Charts Approach Course Track and Communication Frequencies

DOT National Transportation Integrated Search

1991-08-01

This report describes two experiments evaluating format changes on instrument approach : plates (IAPs). The study used a simple chart reading task to assess information : transfer in IAPs. : The first experiment addressed different methods of display...

Optimizing working space in porcine laparoscopy: CT measurement of the effects of intra-abdominal pressure.

PubMed

Vlot, John; Wijnen, Rene; Stolker, Robert Jan; Bax, Klaas

2013-05-01

Several factors may affect volume and dimensions of the working space in laparoscopic surgery. The precise impact of these factors has not been well studied. In a porcine model, we used computed tomographic (CT) scanning for measuring working space volume and distances. In a first series of experiments, we studied the relationship between intra-abdominal pressure (IAP) and working space. Eleven 20 kg pigs were studied under standardized anesthesia and volume-controlled ventilation. Cardiorespiratory parameters were monitored continuously, and blood gas samples were taken at different IAP levels. Respiratory rate was increased when ETCO₂ exceeded 7 kPa. Breath-hold CT scans were made at IAP levels of 0, 5, 10, and 15 mmHg. Insufflator volumes were compared to CT-measured volumes. Maximum dimensions of pneumoperitoneum were measured on reconstructed CT images. Respiratory rate had to be increased in three animals. Mild hypercapnia and acidosis occurred at 15 mmHg IAP. Peak inspiratory pressure rose significantly at 10 and 15 mmHg. CT-measured volume increased relatively by 93 % from 5 to 10 mmHg IAP and by 19 % from 10 to 15 mmHg IAP. Comparing CT volumes to insufflator volumes gave a bias of 76 mL. The limits of agreement were -0.31 to +0.47, a range of 790 mL. The internal anteroposterior diameter increased by 18 % by increasing IAP from 5 to 10 mmHg and by 5 % by increasing IAP from 10 to 15 mmHg. At 15 mmHg, the total relative increase of the pubis-diaphragm distance was only 6 %. Abdominal width did not increase. CT allows for precise calculation of the actual CO₂ pneumoperitoneum volume, whereas the volume of CO₂ released by the insufflator does not. Increasing IAP up to 10 mmHg achieved most gain in volume and in internal anteroposterior diameter. At an IAP of 10 mmHg, higher peak inspiratory pressure was significantly elevated.

Structural and kinetic properties of a novel purple acid phosphatase from phosphate-starved tomato (Lycopersicon esculentum) cell cultures.

PubMed Central

Bozzo, Gale G; Raghothama, Kashchandra G; Plaxton, William C

2004-01-01

An intracellular acid phosphatase (IAP) from P(i)-starved (-P(i)) tomato ( Lycopersicon esculentum ) suspension cells has been purified to homogeneity. IAP is a purple acid phosphatase (PAP), as the purified protein was violet in colour (lambda(max)=546 nm) and was insensitive to L-tartrate. PAGE, periodic acid-Schiff staining and peptide mapping demonstrated that the enzyme exists as a 142 kDa heterodimer composed of an equivalent ratio of glycosylated and structurally dissimilar 63 (alpha-subunit) and 57 kDa (beta-subunit) polypeptides. However, the nine N-terminal amino acids of the alpha- and beta-subunits were identical, exhibiting similarity to the deduced N-terminal portions of several putative plant PAPs. Quantification of immunoblots probed with rabbit anti-(tomato acid phosphatase) immune serum revealed that the 4-fold increase in IAP activity due to P(i)-deprivation was correlated with similar increases in the amount of antigenic IAP alpha- and beta-subunits. IAP displayed optimal activity at pH 5.1, was activated 150% by 10 mM Mg(2+), but was potently inhibited by Zn(2+), Cu(2+), Fe(3+), molybdate, vanadate, fluoride and P(i). Although IAP demonstrated broad substrate selectivity, its specificity constant ( V (max)/ K (m)) with phosphoenolpyruvate was >250% greater than that obtained with any other substrate. IAP exhibited significant peroxidase activity, which was optimal at pH 9.0 and insensitive to Mg(2+) or molybdate. This IAP is proposed to scavenge P(i) from intracellular phosphate esters in -P(i) tomato. A possible secondary IAP role in the metabolism of reactive oxygen species is discussed. IAP properties are compared with those of two extracellular PAP isoenzymes that are secreted into the medium of -P(i) tomato cells [Bozzo, Raghothama and Plaxton (2002) Eur. J. Biochem. 269, 6278-6286]. PMID:14521509

Structural Insight into Inhibitor of Apoptosis Proteins Recognition by a Potent Divalent Smac-Mimetic

PubMed Central

Vachette, Patrice; Malvezzi, Francesca; Grassi, Serena; Lecis, Daniele; Delia, Domenico; Drago, Carmelo; Seneci, Pierfausto; Bolognesi, Martino; Mastrangelo, Eloise

2012-01-01

Genetic alterations enhancing cell survival and suppressing apoptosis are hallmarks of cancer that significantly reduce the efficacy of chemotherapy or radiotherapy. The Inhibitor of Apoptosis Protein (IAP) family hosts conserved proteins in the apoptotic pathway whose over-expression, frequently found in tumours, potentiates survival and resistance to anticancer agents. In humans, IAPs comprise eight members hosting one or more structural Baculoviral IAP Repeat (BIR) domains. Cellular IAPs (cIAP1 and 2) indirectly inhibit caspase-8 activation, and regulate both the canonical and the non-canonical NF-κB signaling pathways. In contrast to cIAPs, XIAP (X chromosome-linked Inhibitor of Apoptosis Protein) inhibits directly the effector caspases-3 and -7 through its BIR2 domain, and initiator caspase-9 through its BIR3 domain; molecular docking studies suggested that Smac/DIABLO antagonizes XIAP by simultaneously targeting both BIR2 and BIR3 domains. Here we report analytical gel filtration, crystallographic and SAXS experiments on cIAP1-BIR3, XIAP-BIR3 and XIAP-BIR2BIR3 domains, alone and in the presence of compound 9a, a divalent homodimeric Smac mimetic. 9a is shown to bind two BIR domains inter- (in the case of two BIR3) and intra-molecularly (in the case of XIAP-BIR2BIR3), with higher affinity for cIAP1-BIR3, relative to XIAP-BIR3. Despite the different crystal lattice packing, 9a maintains a right handed helical conformation in both cIAP1-BIR3 and XIAP-BIR3 crystals, that is likely conserved in solution as shown by SAXS data. Our structural results demonstrate that the 9a linker length, its conformational degrees of freedom and its hydrophobicity, warrant an overall compact structure with optimal solvent exposure of its two active moieties for IAPs binding. Our results show that 9a is a good candidate for pre-clinical and clinical studies, worth of further investigations in the field of cancer therapy. PMID:23166698

African swine fever virus IAP-like protein induces the activation of nuclear factor kappa B.

PubMed

Rodríguez, Clara I; Nogal, María L; Carrascosa, Angel L; Salas, María L; Fresno, Manuel; Revilla, Yolanda

2002-04-01

African swine fever virus (ASFV) encodes a homologue of the inhibitor of apoptosis (IAP) that promotes cell survival by controlling the activity of caspase-3. Here we show that ASFV IAP is also able to activate the transcription factor NF-kappaB. Thus, transient transfection of the viral IAP increases the activity of an NF-kappaB reporter gene in a dose-responsive manner in Jurkat cells. Similarly, stably transfected cells expressing ASFV IAP have elevated basal levels of c-rel, an NF-kappaB-dependent gene. NF-kappaB complexes in the nucleus were increased in A224L-expressing cells compared with control cells upon stimulation with phorbol myristate acetate (PMA) plus ionomycin. This resulted in greater NF-kappaB-dependent promoter activity in ASFV IAP-expressing than in control cells, both in basal conditions and after PMA plus ionophore stimulation. The elevated NF-kappaB activity seems to be the consequence of higher IkappaB kinase (IKK) basal activity in these cells. The NF-kappaB-inducing activity of ASFV IAP was abrogated by an IKK-2 dominant negative mutant and enhanced by expression of tumor necrosis factor receptor-associated factor 2.

African Swine Fever Virus IAP-Like Protein Induces the Activation of Nuclear Factor Kappa B

PubMed Central

Rodríguez, Clara I.; Nogal, María L.; Carrascosa, Angel L.; Salas, María L.; Fresno, Manuel; Revilla, Yolanda

2002-01-01

African swine fever virus (ASFV) encodes a homologue of the inhibitor of apoptosis (IAP) that promotes cell survival by controlling the activity of caspase-3. Here we show that ASFV IAP is also able to activate the transcription factor NF-κB. Thus, transient transfection of the viral IAP increases the activity of an NF-κB reporter gene in a dose-responsive manner in Jurkat cells. Similarly, stably transfected cells expressing ASFV IAP have elevated basal levels of c-rel, an NF-κB-dependent gene. NF-κB complexes in the nucleus were increased in A224L-expressing cells compared with control cells upon stimulation with phorbol myristate acetate (PMA) plus ionomycin. This resulted in greater NF-κB-dependent promoter activity in ASFV IAP-expressing than in control cells, both in basal conditions and after PMA plus ionophore stimulation. The elevated NF-κB activity seems to be the consequence of higher IκB kinase (IKK) basal activity in these cells. The NF-κB-inducing activity of ASFV IAP was abrogated by an IKK-2 dominant negative mutant and enhanced by expression of tumor necrosis factor receptor-associated factor 2. PMID:11907233

Intestinal alkaline phosphatase and sodium butyrate may be beneficial in attenuating LPS-induced intestinal inflammation.

PubMed

Melo, A D B; Silveira, H; Bortoluzzi, C; Lara, L J; Garbossa, C A P; Preis, G; Costa, L B; Rostagno, M H

2016-10-17

In this study, we evaluated the effect of intestinal alkaline phosphatase (IAP) and sodium butyrate (NaBu) on lipopolysaccharide (LPS)-induced intestinal inflammation. Intestinal alkaline phosphatase and RelA/p65 (NF-κB) gene expressions in porcine jejunum explants were evaluated following exposure to sodium butyrate (NaBu) and essential oil from Brazilian red pepper (EO), alone or in combination with NaBu, as well as exogenous IAP with or without LPS challenge. Five piglets weighing approximately 20 kg each were sacrificed, and their jejunum were extracted. The tissues were segmented into 10 parts, which were exposed to 10 treatments. Gene expressions of IAP and RelA/p65 (NF-κB) in jejunal explants were evaluated via RT-PCR. We found that EO, NaBu, and exogenous IAP were able to up-regulate endogenous IAP and enhance RelA/p65 (NF-κB) gene expression. However, only NaBu and exogenous IAP down-regulated LPS-induced inflammatory response via RelA/p65 (NF-κB). In conclusion, we demonstrated that exogenous IAP and NaBu may be beneficial in attenuating LPS-induced intestinal inflammation.

RIPK3 promotes cell death and NLRP3 inflammasome activation in the absence of MLKL.

PubMed

Lawlor, Kate E; Khan, Nufail; Mildenhall, Alison; Gerlic, Motti; Croker, Ben A; D'Cruz, Akshay A; Hall, Cathrine; Kaur Spall, Sukhdeep; Anderton, Holly; Masters, Seth L; Rashidi, Maryam; Wicks, Ian P; Alexander, Warren S; Mitsuuchi, Yasuhiro; Benetatos, Christopher A; Condon, Stephen M; Wong, W Wei-Lynn; Silke, John; Vaux, David L; Vince, James E

2015-02-18

RIPK3 and its substrate MLKL are essential for necroptosis, a lytic cell death proposed to cause inflammation via the release of intracellular molecules. Whether and how RIPK3 might drive inflammation in a manner independent of MLKL and cell lysis remains unclear. Here we show that following LPS treatment, or LPS-induced necroptosis, the TLR adaptor protein TRIF and inhibitor of apoptosis proteins (IAPs: X-linked IAP, cellular IAP1 and IAP2) regulate RIPK3 and MLKL ubiquitylation. Hence, when IAPs are absent, LPS triggers RIPK3 to activate caspase-8, promoting apoptosis and NLRP3-caspase-1 activation, independent of RIPK3 kinase activity and MLKL. In contrast, in the absence of both IAPs and caspase-8, RIPK3 kinase activity and MLKL are essential for TLR-induced NLRP3 activation. Consistent with in vitro experiments, interleukin-1 (IL-1)-dependent autoantibody-mediated arthritis is exacerbated in mice lacking IAPs, and is reduced by deletion of RIPK3, but not MLKL. Therefore RIPK3 can promote NLRP3 inflammasome and IL-1β inflammatory responses independent of MLKL and necroptotic cell death.

Optimization of infrared two-color multicycle field synthesis for intense-isolated-attosecond-pulse generation

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

Lan Pengfei; Takahashi, Eiji J.; Midorikawa, Katsumi

2010-11-15

We present the optimization of the two-color synthesis method for generating an intense isolated attosecond pulse (IAP) in the multicycle regime. By mixing an infrared assistant pulse with a Ti:sapphire main pulse, we show that an IAP can be produced using a multicycle two-color pulse with a duration longer than 30 fs. We also discuss the influence of the carrier-envelope phase (CEP) and the relative intensity on the generation of IAPs. By optimizing the wavelength of the assistant field, IAP generation becomes insensitive to the CEP slip. Therefore, the optimized two-color method enables us to relax the requirements of pulsemore » duration and easily produce the IAP with a conventional multicycle laser pulse. In addition, it enables us to markedly suppress the ionization of the harmonic medium. This is a major advantage for efficiently generating intense IAPs from a neutral medium by applying the appropriate phase-matching and energy-scaling techniques.« less

Intestinal alkaline phosphatase detoxifies lipopolysaccharide and prevents inflammation in zebrafish in response to the gut microbiota.

PubMed

Bates, Jennifer M; Akerlund, Janie; Mittge, Erika; Guillemin, Karen

2007-12-13

Vertebrates harbor abundant lipopolysaccharide (LPS) in their gut microbiota. Alkaline phosphatases can dephosphorylate and detoxify the endotoxin component of LPS. Here, we show that expression of the zebrafish intestinal alkaline phosphatase (Iap), localized to the intestinal lumen brush border, is induced during establishment of the gut microbiota. Iap-deficient zebrafish are hypersensitive to LPS toxicity and exhibit the excessive intestinal neutrophil influx characteristic of wild-type zebrafish exposed to LPS. Both of these Iap mutant phenotypes are dependent on Myd88 and Tumor Necrosis Factor Receptor (Tnfr), proteins also involved in LPS sensitivity in mammals. When reared germ-free, the intestines of Iap-deficient zebrafish are devoid of neutrophils. Together, these findings demonstrate that the endogenous microbiota establish the normal homeostatic level of neutrophils in the zebrafish intestine through a process involving Iap, Myd88, and Tnfr. Thus, by preventing inflammatory responses, Iap plays a crucial role in promoting mucosal tolerance to resident gut bacteria.

Development of protein degradation inducers of oncogenic BCR-ABL protein by conjugation of ABL kinase inhibitors and IAP ligands.

PubMed

Shibata, Norihito; Miyamoto, Naoki; Nagai, Katsunori; Shimokawa, Kenichiro; Sameshima, Tomoya; Ohoka, Nobumichi; Hattori, Takayuki; Imaeda, Yasuhiro; Nara, Hiroshi; Cho, Nobuo; Naito, Mikihiko

2017-08-01

Chromosomal translocation occurs in some cancer cells, which results in the expression of aberrant oncogenic fusion proteins that include BCR-ABL in chronic myelogenous leukemia (CML). Inhibitors of ABL tyrosine kinase, such as imatinib and dasatinib, exhibit remarkable therapeutic effects, although emergence of drug resistance hampers the therapy during long-term treatment. An alternative approach to treat CML is to downregulate the BCR-ABL protein. We have devised a protein knockdown system by hybrid molecules named Specific and Non-genetic inhibitor of apoptosis protein [IAP]-dependent Protein Erasers (SNIPER), which is designed to induce IAP-mediated ubiquitylation and proteasomal degradation of target proteins, and a couple of SNIPER(ABL) against BCR-ABL protein have been developed recently. In this study, we tested various combinations of ABL inhibitors and IAP ligands, and the linker was optimized for protein knockdown activity of SNIPER(ABL). The resulting SNIPER(ABL)-39, in which dasatinib is conjugated to an IAP ligand LCL161 derivative by polyethylene glycol (PEG) × 3 linker, shows a potent activity to degrade the BCR-ABL protein. Mechanistic analysis suggested that both cellular inhibitor of apoptosis protein 1 (cIAP1) and X-linked inhibitor of apoptosis protein (XIAP) play a role in the degradation of BCR-ABL protein. Consistent with the degradation of BCR-ABL protein, the SNIPER(ABL)-39 inhibited the phosphorylation of signal transducer and activator of transcription 5 (STAT5) and Crk like proto-oncogene (CrkL), and suppressed the growth of BCR-ABL-positive CML cells. These results suggest that SNIPER(ABL)-39 could be a candidate for a degradation-based novel anti-cancer drug against BCR-ABL-positive CML. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

Integrated Analysis Platform: An Open-Source Information System for High-Throughput Plant Phenotyping1[C][W][OPEN

PubMed Central

Klukas, Christian; Chen, Dijun; Pape, Jean-Michel

2014-01-01

High-throughput phenotyping is emerging as an important technology to dissect phenotypic components in plants. Efficient image processing and feature extraction are prerequisites to quantify plant growth and performance based on phenotypic traits. Issues include data management, image analysis, and result visualization of large-scale phenotypic data sets. Here, we present Integrated Analysis Platform (IAP), an open-source framework for high-throughput plant phenotyping. IAP provides user-friendly interfaces, and its core functions are highly adaptable. Our system supports image data transfer from different acquisition environments and large-scale image analysis for different plant species based on real-time imaging data obtained from different spectra. Due to the huge amount of data to manage, we utilized a common data structure for efficient storage and organization of data for both input data and result data. We implemented a block-based method for automated image processing to extract a representative list of plant phenotypic traits. We also provide tools for build-in data plotting and result export. For validation of IAP, we performed an example experiment that contains 33 maize (Zea mays ‘Fernandez’) plants, which were grown for 9 weeks in an automated greenhouse with nondestructive imaging. Subsequently, the image data were subjected to automated analysis with the maize pipeline implemented in our system. We found that the computed digital volume and number of leaves correlate with our manually measured data in high accuracy up to 0.98 and 0.95, respectively. In summary, IAP provides a multiple set of functionalities for import/export, management, and automated analysis of high-throughput plant phenotyping data, and its analysis results are highly reliable. PMID:24760818

Intestinal alkaline phosphatase is protective to the preterm rat pup intestine.

PubMed

Heinzerling, Nathan P; Liedel, Jennifer L; Welak, Scott R; Fredrich, Katherine; Biesterveld, Ben E; Pritchard, Kirkwood A; Gourlay, David M

2014-06-01

Necrotizing enterocolitis (NEC) is the most common surgical emergency in neonates, with a mortality rate between 10 and 50%. The onset of necrotizing enterocolitis is highly variable and associated with numerous risk factors. Prior research has shown that enteral supplementation with intestinal alkaline phosphatase (IAP) decreases the severity of NEC. The aim of this study is to investigate whether IAP is protective to the preterm intestine in the presence of formula feeding and in the absence of NEC. Preterm rat pups were fed formula with or without supplementation with IAP, and intestine was obtained on day of life 3 for analysis of IAP activity, mRNA expression of TNFα, IL-6 and iNOS and permeability and cytokine expression after LPS exposure. There was no difference in the absolute and intestine specific alkaline phosphatase activity in both groups. Rat pups fed IAP had decreased mRNA expression of the inflammatory cytokines TNFα, IL-6 and iNOS. Pups supplemented with IAP had decreased permeability and inflammatory cytokine expression after exposure to LPS ex vivo when compared to formula fed controls. Our results support that IAP is beneficial to preterm intestine and decreases intestinal injury and inflammation caused by LPS. Copyright © 2014 Elsevier Inc. All rights reserved.

Intestinal Alkaline Phosphatase Is Protective to the Preterm Rat Pup Intestine

PubMed Central

Heinzerling, Nathan P.; Liedel, Jennifer L.; Welak, Scott R.; Fredrich, Katherine; Biesterveld, Ben E.; Pritchard, Kirkwood A.; Gourlay, David M.

2014-01-01

Background Necrotizing enterocolitis (NEC) is the most common surgical emergency in neonates, with a mortality rate between 10 and 50%. The onset of necrotizing enterocolitis is highly variable and associated with numerous risk factors. Prior research has shown enteral supplementation with intestinal alkaline phosphatase (IAP) decreases the severity of NEC. The aim of this study is to investigate whether IAP is protective to the preterm intestine in the presence of formula feeding and in the absence of NEC. Methods Preterm rat pups were fed formula with or without supplementation with IAP, and intestine was obtained on day of life 3 for analysis of IAP activity, mRNA expression of TNF-a, IL-6 and iNOS and permeability and cytokine expression after LPS. exposure. Results There was no difference in the absolute and intestine specific alkaline phosphatase activity in both groups. Rat pups fed IAP had decreased mRNA expression of the inflammatory cytokines TNFα, IL-6 and iNOS. Pups supplemented with IAP had decreased permeability and inflammatory cytokine expression after exposure to LPS ex vivo when compared to formula fed controls. Conclusions Our results support that IAP is beneficial to preterm intestine and decreases intestinal injury and inflammation caused by LPS. PMID:24888842

Drosophila BRUCE inhibits apoptosis through non-lysine ubiquitination of the IAP-antagonist REAPER

PubMed Central

Domingues, C; Ryoo, H D

2012-01-01

Active caspases execute apoptosis to eliminate superfluous or harmful cells in animals. In Drosophila, living cells prevent uncontrolled caspase activation through an inhibitor of apoptosis protein (IAP) family member, dIAP1, and apoptosis is preceded by the expression of IAP-antagonists, such as Reaper, Hid and Grim. Strong genetic modifiers of this pathway include another IAP family gene encoding an E2 ubiquitin conjugating enzyme domain, dBruce. Although the genetic effects of dBruce mutants are well documented, molecular targets of its encoded protein have remained elusive. Here, we report that dBruce targets Reaper for ubiquitination through an unconventional mechanism. Specifically, we show that dBruce physically interacts with Reaper, dependent upon Reaper's IAP-binding (IBM) and GH3 motifs. Consistently, Reaper levels were elevated in a dBruce −/− background. Unexpectedly, we found that dBruce also affects the levels of a mutant form of Reaper without any internal lysine residues, which normally serve as conventional ubiquitin acceptor sites. Furthermore, we were able to biochemically detect ubiquitin conjugation on lysine-deficient Reaper proteins, and knockdown of dBruce significantly reduced the extent of this ubiquitination. Our results indicate that dBruce inhibits apoptosis by promoting IAP-antagonist ubiquitination on unconventional acceptor sites. PMID:21886178

Impact of intrapartum antimicrobial prophylaxis upon the intestinal microbiota and the prevalence of antibiotic resistance genes in vaginally delivered full-term neonates.

PubMed

Nogacka, Alicja; Salazar, Nuria; Suárez, Marta; Milani, Christian; Arboleya, Silvia; Solís, Gonzalo; Fernández, Nuria; Alaez, Lidia; Hernández-Barranco, Ana M; de Los Reyes-Gavilán, Clara G; Ventura, Marco; Gueimonde, Miguel

2017-08-08

Disturbances in the early establishment of the intestinal microbiota may produce important implications for the infant's health and for the risk of disease later on. Different perinatal conditions may be affecting the development of the gut microbiota. Some of them, such as delivery mode or feeding habits, have been extensively assessed whereas others remain to be studied, being critical to identify their impact on the microbiota and, if any, to minimize it. Antibiotics are among the drugs most frequently used in early life, the use of intrapartum antimicrobial prophylaxis (IAP), present in over 30% of deliveries, being the most frequent source of exposure. However, our knowledge on the effects of IAP on the microbiota establishment is still limited. The aim of the present work was to evaluate the impact of IAP investigating a cohort of 40 full-term vaginally delivered infants born after an uncomplicated pregnancy, 18 of which were born from mothers receiving IAP. Fecal samples were collected at 2, 10, 30, and 90 days of age. We analyzed the composition of the fecal microbiota during the first 3 months of life by 16S rRNA gene sequencing and quantified fecal short chain fatty acids by gas chromatography. The presence of genes for resistance to antibiotics was determined by PCR in the samples from 1-month-old infants. Our results showed an altered pattern of intestinal microbiota establishment in IAP infants during the first weeks of life, with lower relative proportions of Actinobacteria and Bacteroidetes and increased of Preoteobacteria and Firmicutes. A delay in the increase on the levels of acetate was observed in IAP infants. The analyses of specific antibiotic resistance genes showed a higher occurrence of some β-lactamase coding genes in infants whose mothers received IAP. Our results indicate an effect of IAP on the establishing early microbiota during the first months of life, which represent a key moment for the development of the microbiota-induced host homeostasis. Understanding the impact of IAP in the gut microbiota development is essential for developing treatments to minimize it, favoring a proper gut microbiota development in IAP-exposed neonates.

Loss of inhibitor of apoptosis proteins as a determinant of polyamine analog-induced apoptosis in human melanoma cells.

PubMed

Chen, Ying; Kramer, Debora L; Li, Fengzhi; Porter, Carl W

2003-08-07

We have previously shown that the clinically relevant polyamine analog N1,N11-diethylnorspermine (DENSPM) causes rapid apoptosis in human melanoma SK-MEL-28 cells via a series of events that include mitochondrial release of cytochrome c and activation of the caspase cascade. Upstream to these events, DENSPM downregulates polyamine biosynthesis and potently upregulates polyamine catabolism at the level of spermidine/spermine N1-acetyltransferase (SSAT). In searching for downstream effectors that either contribute to or abrogate the apoptotic response, we observed that DENSPM treatment of SK-MEL-28 cells for 30 h led to cytosolic release of Smac/Diablo, a mitochondrial protein known to bind and inhibit the function of inhibitor of apoptosis proteins (IAPs). Subsequently, we found that DENSPM markedly lowered survivin and ML-IAP protein (but not XIAP) levels by 18 h via an apparently Smac/Diablo-independent pathway. Proteasome inhibitors fully prevented survivin and ML-IAP protein loss as well as apoptosis, suggesting that the proteasome-mediated degradation of survivin and ML-IAP is causally linked to the cellular outcome. We also observed that structural analogs of DENSPM which differentially induced SSAT and apoptosis lowered survivin and ML-IAP levels in a manner that correlated with enzyme activity. The linkage between IAPs and SSAT was more directly established by the finding that selective prevention of SSAT induction by small interfering RNA prevented survivin and ML-IAP loss as well as apoptosis during DENSPM treatment. Among the melanoma cell lines (SK-MEL-28, MALME-3M, A375 and LOX), survivin degradation correlated temporally with the onset of DENSPM induced apoptosis or growth inhibition. By contrast, ML-IAP degradation occurred only during rapid apoptosis seen in SK-MEL-28 cells. These data suggest a sequence of events whereby DENSPM induction of SSAT leads to loss of IAP proteins and a more fulminate apoptotic response. The findings implicate survivin and ML-IAP as important determinants of polyamine analog drug action in melanoma cells.

Functional evaluation of the role of inhibitor of apoptosis proteins in chronic lymphocytic leukemia.

PubMed

Schliep, Stefan; Decker, Thomas; Schneller, Folker; Wagner, Hermann; Häcker, Georg

2004-06-01

The slow accumulation of malignant cells in chronic lymphocytic leukemia (CLL) suggests a defect in the induction of apoptosis in these cells. Previous studies have found sporadic alterations in the apoptotic apparatus in CLL cells, but a widespread defect has not been detected until now. A crucial checkpoint in the progression of apoptosis is the activity of inhibitor of apoptosis proteins (IAP) that control the activity of caspases upon the release of cytochrome c from mitochondria. The aim of this study was to evaluate the role of IAP in the regulation of apoptosis in CLL cells. Lysates from CLL cells were prepared, and the regular function of components of the cytochrome c-dependent caspase-activating machinery (the apoptosome) was investigated. The effect of IAP in caspase-inhibition was tested using a peptide derived from the mitochondrial IAP antagonist Smac/DIABLO. Regulation of expression as well as inhibitory function of the X-linked IAP (XIAP) by cytokines was analyzed. The apoptosome was found to be structurally and functionally competent in CLL. XIAP expression was enhanced by culture in the presence of cytokines. Smac/DIABLO was easily detectable in CLL cells and was released into the cytosol during apoptosis. No inhibitory effect of IAP was detected in CLL, irrespective of XIAP levels and culture conditions. Although XIAP is present in CLL cells and is up-regulated in conditions where apoptosis is prevented, no caspase-inhibiting anti-apoptotic effect of IAP is detectable. This is likely due to the high expression of Smac/DIABLO in CLL cells that is sufficient to overcome the caspase-inhibiting effect of IAP.

Associations of maximal voluntary isometric hip extension torque with muscle size of hamstring and gluteus maximus and intra-abdominal pressure.

PubMed

Tayashiki, Kota; Hirata, Kosuke; Ishida, Kiraku; Kanehisa, Hiroaki; Miyamoto, Naokazu

2017-06-01

Muscle size of the hamstring and gluteus maximus (GM) as well as intra-abdominal pressure (IAP) are considered as factors affecting the torque development during hip extension. This study examined the associations of torque development during maximal voluntary isometric hip extension with IAP and muscle size of the hamstring and GM. Anatomical cross-sectional area (ACSA) of the hamstring and thickness of GM were determined in 20 healthy young males using an ultrasonography apparatus (Experiment 1). Torque and IAP were simultaneously measured while subjects performed maximal voluntary isometric hip extension. The IAP was measured using a pressure transducer placed in the rectum and determined at the time at which the developed torque reached to the maximal. In Experiment 2, torque and IAP were measured during maximal voluntary isometric hip flexion in 18 healthy young males. The maximal hip extension torque was significantly correlated with the IAP (r = 0.504, P = 0.024), not with the ACSA of the hamstring (r = 0.307, P = 0.188) or the thickness of GM (r = 0.405, P = 0.076). The relationship was still significant even when the ACSA of the hamstring and the thickness of GM were adjusted statistically (r = 0.486, P = 0.041). The maximal hip flexion torque was not significantly correlated with the IAP (r = -0.118, P = 0.642). The current results suggest that IAP can contribute independently of the muscle size of the agonists to maximal voluntary hip extension torque.

African Swine Fever Virus IAP Homologue Inhibits Caspase Activation and Promotes Cell Survival in Mammalian Cells

PubMed Central

Nogal, María L.; González de Buitrago, Gonzalo; Rodríguez, Clara; Cubelos, Beatriz; Carrascosa, Angel L.; Salas, María L.; Revilla, Yolanda

2001-01-01

African swine fever virus (ASFV) A224L is a member of the inhibitor of apoptosis protein (IAP) family. We have investigated the antiapoptotic function of the viral IAP both in stably transfected cells and in ASFV-infected cells. A224L was able to substantially inhibit caspase activity and cell death induced by treatment with tumor necrosis factor alpha and cycloheximide or staurosporine when overexpressed in Vero cells by gene transfection. We have also observed that ASFV infection induces caspase activation and apoptosis in Vero cells. Furthermore, using a deletion mutant of ASFV lacking the A224L gene, we have shown that the viral IAP modulates the proteolytic processing of the effector cell death protease caspase-3 and the apoptosis which are induced in the infected cells. Our findings indicate that A224L interacts with the proteolytic fragment of caspase-3 and inhibits the activity of this protease during ASFV infection. These observations could indicate a conserved mechanism of action for ASFV IAP and other IAP family members to suppress apoptosis. PMID:11222676

African swine fever virus IAP homologue inhibits caspase activation and promotes cell survival in mammalian cells.

PubMed

Nogal, M L; González de Buitrago, G; Rodríguez, C; Cubelos, B; Carrascosa, A L; Salas, M L; Revilla, Y

2001-03-01

African swine fever virus (ASFV) A224L is a member of the inhibitor of apoptosis protein (IAP) family. We have investigated the antiapoptotic function of the viral IAP both in stably transfected cells and in ASFV-infected cells. A224L was able to substantially inhibit caspase activity and cell death induced by treatment with tumor necrosis factor alpha and cycloheximide or staurosporine when overexpressed in Vero cells by gene transfection. We have also observed that ASFV infection induces caspase activation and apoptosis in Vero cells. Furthermore, using a deletion mutant of ASFV lacking the A224L gene, we have shown that the viral IAP modulates the proteolytic processing of the effector cell death protease caspase-3 and the apoptosis which are induced in the infected cells. Our findings indicate that A224L interacts with the proteolytic fragment of caspase-3 and inhibits the activity of this protease during ASFV infection. These observations could indicate a conserved mechanism of action for ASFV IAP and other IAP family members to suppress apoptosis.

Design, synthesis, and biological activities of novel hexahydropyrazino[1,2-a]indole derivatives as potent inhibitors of apoptosis (IAP) proteins antagonists with improved membrane permeability across MDR1 expressing cells.

PubMed

Shiokawa, Zenyu; Hashimoto, Kentaro; Saito, Bunnai; Oguro, Yuya; Sumi, Hiroyuki; Yabuki, Masato; Yoshimatsu, Mie; Kosugi, Yohei; Debori, Yasuyuki; Morishita, Nao; Dougan, Douglas R; Snell, Gyorgy P; Yoshida, Sei; Ishikawa, Tomoyasu

2013-12-15

We previously reported octahydropyrrolo[1,2-a]pyrazine derivative 2 (T-3256336) as a potent antagonist for inhibitors of apoptosis (IAP) proteins. Because compound 2 was susceptible to MDR1 mediated efflux, we developed another scaffold, hexahydropyrazino[1,2-a]indole, using structure-based drug design. The fused benzene ring of this scaffold was aimed at increasing the lipophilicity and decreasing the basicity of the scaffold to improve the membrane permeability across MDR1 expressing cells. We established a chiral pool synthetic route to yield the desired tricyclic chiral isomers. Chemical modification of the core scaffold led to a representative compound 50, which showed strong inhibition of IAP binding (X chromosome-linked IAP [XIAP]: IC50 23 nM and cellular IAP [cIAP]: IC50 1.1 nM) and cell growth inhibition (MDA-MB-231 cells: GI50 2.8 nM) with high permeability and low potential of MDR1 substrate. Copyright © 2013 Elsevier Ltd. All rights reserved.

IAP-Based Cell Sorting Results in Homogeneous Transplantable Dopaminergic Precursor Cells Derived from Human Pluripotent Stem Cells.

PubMed

Lehnen, Daniela; Barral, Serena; Cardoso, Tiago; Grealish, Shane; Heuer, Andreas; Smiyakin, Andrej; Kirkeby, Agnete; Kollet, Jutta; Cremer, Harold; Parmar, Malin; Bosio, Andreas; Knöbel, Sebastian

2017-10-10

Human pluripotent stem cell (hPSC)-derived mesencephalic dopaminergic (mesDA) neurons can relieve motor deficits in animal models of Parkinson's disease (PD). Clinical translation of differentiation protocols requires standardization of production procedures, and surface-marker-based cell sorting is considered instrumental for reproducible generation of defined cell products. Here, we demonstrate that integrin-associated protein (IAP) is a cell surface marker suitable for enrichment of hPSC-derived mesDA progenitor cells. Immunomagnetically sorted IAP + mesDA progenitors showed increased expression of ventral midbrain floor plate markers, lacked expression of pluripotency markers, and differentiated into mature dopaminergic (DA) neurons in vitro. Intrastriatal transplantation of IAP + cells sorted at day 16 of differentiation in a rat model of PD resulted in functional recovery. Grafts from sorted IAP + mesDA progenitors were more homogeneous in size and DA neuron density. Thus, we suggest IAP-based sorting for reproducible prospective enrichment of mesDA progenitor cells in clinical cell replacement strategies. Copyright © 2017 Miltenyi Biotec GmbH. Published by Elsevier Inc. All rights reserved.

Molecular Dynamics simulations of Inhibitor of Apoptosis Proteins and identification of potential small molecule inhibitors.

PubMed

Jayakumar, Jayanthi; Anishetty, Sharmila

2014-05-01

Chemotherapeutic resistance due to over expression of Inhibitor of Apoptosis Proteins (IAPs) XIAP, survivin and livin has been observed in various cancers. In the current study, Molecular Dynamics (MD) simulations were carried out for all three IAPs and a common ligand binding scaffold was identified. Further, a novel sequence based motif specific to these IAPs was designed. SMAC is an endogenous inhibitor of IAPs. Screening of ChemBank for compounds similar to lead SMAC-non-peptidomimetics yielded a cemadotin related compound NCIMech_000654. Cemadotin is a derivative of natural anti-tumor peptide dolastatin-15; hence these compounds were docked against all three IAPs. Based on our analysis, we propose that NCIMech_000654/dolastatin-15/cemadotin derivatives may be investigated for their potential in inhibiting XIAP, survivin and livin. Copyright © 2014 Elsevier Ltd. All rights reserved.

Revised IAP growth charts for height, weight and body mass index for 5- to 18-year-old Indian children.

PubMed

Khadilkar, Vaman; Yadav, Sangeeta; Agrawal, K K; Tamboli, Suchit; Banerjee, Monidipa; Cherian, Alice; Goyal, Jagdish P; Khadilkar, Anuradha; Kumaravel, V; Mohan, V; Narayanappa, D; Ray, I; Yewale, Vijay

2015-01-01

The need to revise Indian Academy of Pediatrics (IAP) growth charts for 5- to 18-year-old Indian children and adolescents was felt as India is in nutrition transition and previous IAP charts are based on data which are over two decades old. The Growth Chart Committee was formed by IAP in January 2014 to design revised growth charts. Consultative meeting was held in November 2014 in Mumbai. Studies performed on Indian children's growth, nutritional assessment and anthropometry from upper and middle socioeconomic classes in last decade were identified. Committee contacted 13 study groups; total number of children in the age group of 5 to 18 years were 87022 (54086 boys). Data from fourteen cities (Agartala, Ahmadabad, Chandigarh, Chennai, Delhi, Hyderabad, Kochi, Kolkata, Madurai, Mumbai, Mysore, Pune, Raipur and Surat) in India were collated. Data of children with weight for height Z scores >2 SD were removed from analyses. Data on 33148 children (18170 males, 14978 females) were used to construct growth charts using Cole's LMS method. To construct revised IAP growth charts for 5-18 year old Indian children based on collated national data from published studies performed on apparently healthy children and adolescents in the last 10 years. The IAP growth chart committee recommends these revised growth charts for height, weight and body mass index (BMI) for assessment of growth of 5-18 year old Indian children to replace the previous IAP charts; rest of the recommendations for monitoring height and weight remain as per the IAP guidelines published in 2007. To define overweight and obesity in children from 5-18 years of age, adult equivalent of 23 and 27 cut-offs presented in BMI charts may be used. IAP recommends use of WHO standards for growth assessment of children below 5 years of age.

Anti-apoptotic signaling as a cytoprotective mechanism in mammalian hibernation.

PubMed

Rouble, Andrew N; Hefler, Joshua; Mamady, Hapsatou; Storey, Kenneth B; Tessier, Shannon N

2013-01-01

In the context of normal cell turnover, apoptosis is a natural phenomenon involved in making essential life and death decisions. Apoptotic pathways balance signals which promote cell death (pro-apoptotic pathways) or counteract these signals (anti-apoptotic pathways). We proposed that changes in anti-apoptotic proteins would occur during mammalian hibernation to aid cell preservation during prolonged torpor under cellular conditions that are highly injurious to most mammals (e.g. low body temperatures, ischemia). Immunoblotting was used to analyze the expression of proteins associated with pro-survival in six tissues of thirteen-lined ground squirrels, Ictidomys tridecemlineatus. The brain showed a concerted response to torpor with significant increases in the levels of all anti-apoptotic targets analyzed (Bcl-2, Bcl-xL, BI-1, Mcl-1, cIAP1/2, xIAP) as well as enhanced phosphorylation of Bcl-2 at S70 and T56. Heart responded similarly with most anti-apoptotic proteins elevated significantly during torpor except for Bcl-xL and xIAP that decreased and Mcl-1 that was unaltered. In liver, BI-1 increased whereas cIAP1/2 decreased. In kidney, there was an increase in BI-1, cIAP and xIAP but decreases in Bcl-xL and p-Bcl-2(T56) content. In brown adipose tissue, protein levels of BI-1, cIAP1/2, and xIAP decreased significantly during torpor (compared with euthermia) whereas Bcl-2, Bcl-xL, Mcl-1 were unaltered; however, Bcl-2 showed enhanced phosphorylation at Thr56 but not at Ser70. In skeletal muscle, only xIAP levels changed significantly during torpor (an increase). The data show that anti-apoptotic pathways have organ-specific responses in hibernators with a prominent potential role in heart and brain where coordinated enhancement of anti-apoptotic proteins occurred in response to torpor.

Anti-apoptotic signaling as a cytoprotective mechanism in mammalian hibernation

PubMed Central

Mamady, Hapsatou; Tessier, Shannon N.

2013-01-01

In the context of normal cell turnover, apoptosis is a natural phenomenon involved in making essential life and death decisions. Apoptotic pathways balance signals which promote cell death (pro-apoptotic pathways) or counteract these signals (anti-apoptotic pathways). We proposed that changes in anti-apoptotic proteins would occur during mammalian hibernation to aid cell preservation during prolonged torpor under cellular conditions that are highly injurious to most mammals (e.g. low body temperatures, ischemia). Immunoblotting was used to analyze the expression of proteins associated with pro-survival in six tissues of thirteen-lined ground squirrels, Ictidomys tridecemlineatus. The brain showed a concerted response to torpor with significant increases in the levels of all anti-apoptotic targets analyzed (Bcl-2, Bcl-xL, BI-1, Mcl-1, cIAP1/2, xIAP) as well as enhanced phosphorylation of Bcl-2 at S70 and T56. Heart responded similarly with most anti-apoptotic proteins elevated significantly during torpor except for Bcl-xL and xIAP that decreased and Mcl-1 that was unaltered. In liver, BI-1 increased whereas cIAP1/2 decreased. In kidney, there was an increase in BI-1, cIAP and xIAP but decreases in Bcl-xL and p-Bcl-2(T56) content. In brown adipose tissue, protein levels of BI-1, cIAP1/2, and xIAP decreased significantly during torpor (compared with euthermia) whereas Bcl-2, Bcl-xL, Mcl-1 were unaltered; however, Bcl-2 showed enhanced phosphorylation at Thr56 but not at Ser70. In skeletal muscle, only xIAP levels changed significantly during torpor (an increase). The data show that anti-apoptotic pathways have organ-specific responses in hibernators with a prominent potential role in heart and brain where coordinated enhancement of anti-apoptotic proteins occurred in response to torpor. PMID:23638364

Structures of BIR domains from human NAIP and cIAP2.

PubMed

Herman, Maria Dolores; Moche, Martin; Flodin, Susanne; Welin, Martin; Trésaugues, Lionel; Johansson, Ida; Nilsson, Martina; Nordlund, Pär; Nyman, Tomas

2009-11-01

The inhibitor of apoptosis (IAP) family of proteins contains key modulators of apoptosis and inflammation that interact with caspases through baculovirus IAP-repeat (BIR) domains. Overexpression of IAP proteins frequently occurs in cancer cells, thus counteracting the activated apoptotic program. The IAP proteins have therefore emerged as promising targets for cancer therapy. In this work, X-ray crystallography was used to determine the first structures of BIR domains from human NAIP and cIAP2. Both structures harbour an N-terminal tetrapeptide in the conserved peptide-binding groove. The structures reveal that these two proteins bind the tetrapeptides in a similar mode as do other BIR domains. Detailed interactions are described for the P1'-P4' side chains of the peptide, providing a structural basis for peptide-specific recognition. An arginine side chain in the P3' position reveals favourable interactions with its hydrophobic moiety in the binding pocket, while hydrophobic residues in the P2' and P4' pockets make similar interactions to those seen in other BIR domain-peptide complexes. The structures also reveal how a serine in the P1' position is accommodated in the binding pockets of NAIP and cIAP2. In addition to shedding light on the specificity determinants of these two proteins, the structures should now also provide a framework for future structure-based work targeting these proteins.

Structures of BIR domains from human NAIP and cIAP2

PubMed Central

Herman, Maria Dolores; Moche, Martin; Flodin, Susanne; Welin, Martin; Trésaugues, Lionel; Johansson, Ida; Nilsson, Martina; Nordlund, Pär; Nyman, Tomas

2009-01-01

The inhibitor of apoptosis (IAP) family of proteins contains key modulators of apoptosis and inflammation that interact with caspases through baculovirus IAP-repeat (BIR) domains. Overexpression of IAP proteins frequently occurs in cancer cells, thus counteracting the activated apoptotic program. The IAP proteins have therefore emerged as promising targets for cancer therapy. In this work, X-ray crystallography was used to determine the first structures of BIR domains from human NAIP and cIAP2. Both structures harbour an N-terminal tetrapeptide in the conserved peptide-binding groove. The structures reveal that these two proteins bind the tetrapeptides in a similar mode as do other BIR domains. Detailed interactions are described for the P1′–P4′ side chains of the peptide, providing a structural basis for peptide-specific recognition. An arginine side chain in the P3′ position reveals favourable interactions with its hydrophobic moiety in the binding pocket, while hydrophobic residues in the P2′ and P4′ pockets make similar interactions to those seen in other BIR domain–peptide complexes. The structures also reveal how a serine in the P1′ position is accommodated in the binding pockets of NAIP and cIAP2. In addition to shedding light on the specificity determinants of these two proteins, the structures should now also provide a framework for future structure-based work targeting these proteins. PMID:19923725

Intra-abdominal pressure during Pilates: unlikely to cause pelvic floor harm.

PubMed

Coleman, Tanner J; Nygaard, Ingrid E; Holder, Dannielle N; Egger, Marlene J; Hitchcock, Robert

2015-08-01

The objective was to describe the intra-abdominal pressures (IAP) generated during Pilates Mat and Reformer activities, and determine whether these activities generate IAP above a sit-to-stand threshold. Twenty healthy women with no symptomatic vaginal bulge, median age 43 (range 22-59 years), completed Pilates Mat and Reformer exercise routines each consisting of 11 exercises. IAP was collected by an intra-vaginal pressure transducer, transmitted wirelessly to a base station, and analyzed for maximal and area under the curve (AUC) IAP. There were no statistically significant differences in the mean maximal IAP between sit-to-stand and any of the Mat or Reformer exercises in the study population. Six to twenty-five percent of participants exceeded their individual mean maximal IAP sit-to-stand thresholds for 10 of the 22 exercises. When measuring AUC from 0 cm H2O, half the exercises exceeded the mean AUC of sit-to-stand, but only Pilates Reformer and Mat roll-ups exceeded the mean AUC of sit-to-stand when calculated from a threshold of 40 cm H2O (consistent with, for example, walking). Our results support recommending this series of introductory Pilates exercises, including five Mat exercises and six Reformer exercises to women desiring a low IAP exercise routine. More research is needed to determine the long-term effects of Pilates exercise on post-surgical exercise rehabilitation and pelvic floor health.

Situational analysis of household energy and biomass use and associated health burden of indoor air pollution and mitigation efforts in Pakistan.

PubMed

Fatmi, Zafar; Rahman, Asma; Kazi, Ambreen; Kadir, M Masood; Sathiakumar, Nalini

2010-07-01

Biomass fuel burning leads to high levels of suspended particulate matter and hazardous chemicals in the indoor environment in countries where it is in common use, contributing significantly to indoor air pollution (IAP). A situational analysis of household energy and biomass use and associated health effects of IAP was conducted by reviewing published and un-published literature about the situation in Pakistan. In addition to attempt to quantify the burden of ill health due to IAP, this paper also appraises the mitigation measures undertaken to avert the problem in Pakistan. Unfortunately, IAP is still not a recognized environmental hazard in Pakistan and there are no policies and standards to control it at the household level. Only a few original studies related to health effects of IAP have been conducted, mainly on women's health and birth outcome, and only a few governmental, non-governmental and academic institutions are working to improve the IAP situation by introducing improved stoves and renewable energy technology at a small scale. Control of IAP health hazards in Pakistan requires an initial meeting of the stakeholders to define a policy and an action agenda. Simultaneously, studies gathering evidence of impact of intervention through available technologies such as improved stoves would have favorable impact on the health, especially of women and children in Pakistan.

Intracarotid amobarbital procedure: I. Prediction of decreased modality-specific memory scores after temporal lobectomy.

PubMed

Wyllie, E; Naugle, R; Awad, I; Chelune, G; Lüders, H; Dinner, D; Skibinski, C; Ahl, J

1991-01-01

To assess predictive value of the intracarotid amobarbital procedure (IAP) for decreased postoperative modality-specific memory, we studied 37 temporal lobectomy patients with intractable partial epilepsy who were selected for operation independent of preoperative IAP findings. When ipsilateral IAP failure was defined by an absolute method as a retention score less than 67%, the results were not associated with decreased modality-specific memory after operation. When ipsilateral IAP failure was defined by a comparative method as a retention score at least 20% lower after ipsilateral than contralateral injection, the results showed greater differences between groups, but differences still did not achieve statistical significance. Four left-resection patients who failed the ipsilateral IAP had a median postoperative change in the Wechsler Memory Scale-Revised (WMS-R) Verbal Memory Index score of -14%, whereas 16 left-resection patients who passed the ipsilateral IAP had a mean postoperative change in the WMS-R Verbal Memory Index score of -7.5% (p = 0.12). These results suggested that the IAP interpreted comparatively may be a helpful adjunctive test in assessment of relative risk for modality-specific memory dysfunction after temporal lobectomy, but larger series of operated patients are needed to confirm this possibility. In this series, complete amnesia was not noted after ipsilateral injection, even in patients with postoperative modality-specific memory decline.

Intra-abdominal Pressure during Pilates: Unlikely to Cause Pelvic Floor Harm

PubMed Central

Coleman, Tanner J.; Holder, Dannielle N.; Egger, Marlene J.; Hitchcock, Robert

2015-01-01

Aims To describe intra-abdominal pressures (IAP) generated during Pilates Mat and Reformer activities, and determine whether these activities generate IAP above a sit-to-stand threshold. Methods Twenty healthy women with no symptomatic vaginal bulge, median age 43 (range 22 – 59 years), completed Pilates Mat and Reformer exercise routines each consisting of 11 exercises. IAP was collected by an intra-vaginal pressure transducer, transmitted wirelessly to a base station, and analyzed for maximal and area under the curve (AUC) IAP. Results There were no statistically significant differences in mean max IAP between sit-to-stand and any of the Mat or Reformer exercises in the study population. Six to twenty-five percent of participants exceeded their individual mean max IAP sit-to-stand thresholds for 10 of the 22 exercises. When measuring AUC from 0 cm H2O, half the exercises exceeded the mean AUC of sit-to-stand but only Pilates Reformer and Mat roll-ups exceeded the mean AUC of sit-to-stand when calculated from a threshold of 40 cm H2O (consistent with, for example, walking). Conclusion Our results support recommending this series of introductory Pilates exercises including five Mat exercises and six Reformer exercises to women desiring a low IAP exercise routine. More research is needed to determine the long term effects of Pilates exercise on post-surgical exercise rehabilitation and pelvic floor health. PMID:25672647

Prevention of antibiotic-associated metabolic syndrome in mice by intestinal alkaline phosphatase

PubMed Central

Economopoulos, K. P.; Ward, N. L.; Phillips, C. D.; Teshager, A.; Patel, P.; Mohamed, M. M.; Hakimian, S.; Cox, S. B.; Ahmed, R.; Moaven, O.; Kaliannan, K.; Alam, S. N.; Haller, J. F.; Goldstein, A. M.; Bhan, A. K.; Malo, M. S.; Hodin, R. A.

2016-01-01

Aims Early childhood exposure to antibiotics has been implicated in the pathogenesis of metabolic syndrome (MetS) later on in adulthood. Intestinal alkaline phosphatase (IAP) preserves the normal homeostasis of intestinal microbiota and restores the normal microbiota upon cessation of antibiotic treatment. We aim to examine whether co-administration of IAP with antibiotics early in life may have a preventive role against MetS in mice. Materials and Methods Fifty mice were allocated to four treatment groups after weaning. Mice were treated with azithromycin±IAP, or with no azithromycin±IAP, for three intermittent 7-day cycles. After the last treatment course, the mice were administered regular chow diet for five weeks and subsequently high-fat diet for five weeks. Animal body weight, food intake, water intake, serum lipids, glucose levels and liver lipids were compared. 16S rRNA gene pyrosequencing was used to determine differences in microbiome composition. Results Azithromycin exposure early in life rendered mice susceptible to MetS in adulthood. Co-administration of IAP with azithromycin completely prevented this susceptibility by decreasing total body weight, serum lipids, glucose levels and liver lipids to the levels of control mice. These effects of IAP likely occur due to changes in the composition of specific bacterial taxa at the genus and species levels (e.g. members of Anaeroplasma and Parabacteroides). Conclusions Co-administration of IAP with azithromycin early in life prevents mice from susceptibility to the later development of MetS. This effect is associated with alterations in the composition of the gut microbiota. IAP may represent a novel treatment against MetS in humans. PMID:26876427

Cellular inhibitor of apoptosis proteins prevent clearance of hepatitis B virus.

PubMed

Ebert, Gregor; Preston, Simon; Allison, Cody; Cooney, James; Toe, Jesse G; Stutz, Michael D; Ojaimi, Samar; Scott, Hamish W; Baschuk, Nikola; Nachbur, Ueli; Torresi, Joseph; Chin, Ruth; Colledge, Danielle; Li, Xin; Warner, Nadia; Revill, Peter; Bowden, Scott; Silke, John; Begley, C Glenn; Pellegrini, Marc

2015-05-05

Hepatitis B virus (HBV) infection can result in a spectrum of outcomes from immune-mediated control to disease progression, cirrhosis, and liver cancer. The host molecular pathways that influence and contribute to these outcomes need to be defined. Using an immunocompetent mouse model of chronic HBV infection, we identified some of the host cellular and molecular factors that impact on infection outcomes. Here, we show that cellular inhibitor of apoptosis proteins (cIAPs) attenuate TNF signaling during hepatitis B infection, and they restrict the death of infected hepatocytes, thus allowing viral persistence. Animals with a liver-specific cIAP1 and total cIAP2 deficiency efficiently control HBV infection compared with WT mice. This phenotype was partly recapitulated in mice that were deficient in cIAP2 alone. These results indicate that antagonizing the function of cIAPs may promote the clearance of HBV infection.

Intestinal Alkaline Phosphatase Detoxifies Lipopolysaccharide and Prevents Inflammation in Response to the Gut Microbiota

PubMed Central

Bates, Jennifer M.; Akerlund, Janie; Mittge, Erika; Guillemin, Karen

2009-01-01

SUMMARY Vertebrates harbor abundant lipopolysaccharide (LPS) or endotoxin in their gut microbiota. Here we demonstrate that the brush border enzyme intestinal alkaline phosphatase (Iap), which dephosphorylates LPS, is induced during establishment of the microbiota and plays a crucial role in promoting mucosal tolerance to gut bacteria in zebrafish. We demonstrate that Iap deficient animals are hypersensitive to LPS toxicity through a mechanism mediated by Myd88 and Tumor Necrosis Factor Receptor (Tnfr). We further show that the endogenous microbiota establish the normal homeostatic level of neutrophils in the intestine through a process involving Myd88 and Tnfr. Iap deficient animals exhibit excessive intestinal neutrophil influx, similar to wild type animals exposed to LPS. When reared germ-free, however, the intestines of Iap deficient animals are devoid of neutrophils, demonstrating that Iap functions to prevent inflammatory responses to resident gut bacteria. PMID:18078689

Cell death in response to antimetabolites directed at ribonucleotide reductase and thymidylate synthase

PubMed Central

Asuncion Valenzuela, Malyn M; Castro, Imilce; Gonda, Amber; Diaz Osterman, Carlos J; Jutzy, Jessica M; Aspe, Jonathan R; Khan, Salma; Neidigh, Jonathan W; Wall, Nathan R

2015-01-01

New agent development, mechanistic understanding, and combinatorial partnerships with known and novel modalities continue to be important in the study of pancreatic cancer and its improved treatment. In this study, known antimetabolite drugs such as gemcitabine (ribonucleotide reductase inhibitor) and 5-fluorouracil (thymidylate synthase inhibitor) were compared with novel members of these two drug families in the treatment of a chemoresistant pancreatic cancer cell line PANC-1. Cellular survival data, along with protein and messenger ribonucleic acid expression for survivin, XIAP, cIAP1, and cIAP2, were compared from both the cell cytoplasm and from exosomes after single modality treatment. While all antimetabolite drugs killed PANC-1 cells in a time- and dose-dependent manner, neither family significantly altered the cytosolic protein level of the four inhibitors of apoptosis (IAPs) investigated. Survivin, XIAP, cIAP1, and cIAP2 were found localized to exosomes where no significant difference in expression was recorded. This inability for significant and long-lasting expression may be a reason why pancreatic cancer lacks responsiveness to these and other cancer-killing agents. Continued investigation is required to determine the responsibilities of these IAPs in their role in chemoresistance in pancreatic adenocarcinoma. PMID:25767396

IAP Antagonists Enhance Apoptotic Response to Enzalutamide in Castration-Resistant Prostate Cancer Cells via Autocrine TNF-α Signaling.

PubMed

Pilling, Amanda B; Hwang, Ok; Boudreault, Alain; Laurent, Alain; Hwang, Clara

2017-06-01

Castration-resistant prostate cancer (CRPC) remains incurable and identifying effective treatments continues to present a clinical challenge. Although treatment with enzalutamide, a second generation androgen receptor (AR) antagonist, prolongs survival in prostate cancer patients, responses can be limited by intrinsic resistance or acquired resistance. A potential mechanism of resistance to androgen axis inhibition is evasion of apoptosis. Inhibitor of apoptosis proteins (IAPs) are found to be overexpressed in prostate cancer and function to block apoptosis and promote survival signaling. Novel, small-molecule IAP antagonists, such as AEG40995, are emerging as a strategy to induce apoptosis and increase therapeutic response in cancer. Human prostate cancer cell lines LNCaP and C4-2 were treated with enzalutamide with or without addition of IAP antagonist AEG40995 and proliferation and survival were determined by MTS and clonogenic assay. Western blot was used to evaluate IAP protein expression changes and PARP-1 cleavage was assessed as indication of apoptosis. Flow cytometry was performed to analyze apoptosis in treated cells. Caspase activity was determined by luminescence assay. Quantitative real-time PCR and immunometric ELISA was used to assess TNF-α (transcript and protein levels, respectively) in response to treatment. In this study, we demonstrate that IAP antagonist AEG40995 exhibits minimal effects on prostate cancer cell proliferation or survival, but rapidly degrades cIAP1 protein. Combination treatment with enzalutamide demonstrates that AEG40995 increases apoptosis and reduces proliferation and clonogenic survival in cell line models of prostate cancer. Mechanistically, we demonstrate that apoptosis in response to enzalutamide and IAP antagonist requires activation of caspase-8, suggesting extrinsic/death receptor apoptosis signaling. Assessment of TNF-α in response to combination treatment with enzalutamide and AEG40995 reveals increased mRNA expression and autocrine protein secretion. Blocking TNF-α signaling abrogates the apoptotic response demonstrating that TNF-α plays a critical role in executing cell death in response to this drug combination. These findings suggest that IAP antagonists can increase sensitivity and amplify the caspase-mediated apoptotic response to enzalutamide through TNF-α signaling mechanisms. Combination with an IAP antagonist increases enzalutamide sensitivity, lowers the apoptotic threshold and may combat drug resistance in patients with prostate cancer. Prostate 77:866-877, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Prevention of antibiotic-associated metabolic syndrome in mice by intestinal alkaline phosphatase.

PubMed

Economopoulos, K P; Ward, N L; Phillips, C D; Teshager, A; Patel, P; Mohamed, M M; Hakimian, S; Cox, S B; Ahmed, R; Moaven, O; Kaliannan, K; Alam, S N; Haller, J F; Goldstein, A M; Bhan, A K; Malo, M S; Hodin, R A

2016-05-01

To examine whether co-administration of intestinal alkaline phosphatase (IAP) with antibiotics early in life may have a preventive role against metabolic syndrome (MetS) in mice. A total of 50 mice were allocated to four treatment groups after weaning. Mice were treated with azithromycin (AZT) ± IAP, or with no AZT ± IAP, for three intermittent 7-day cycles. After the last treatment course, the mice were administered a regular chow diet for 5 weeks and subsequently a high-fat diet for 5 weeks. Body weight, food intake, water intake, serum lipids, glucose levels and liver lipids were compared. 16S rRNA gene pyrosequencing was used to determine the differences in microbiome composition. Exposure to AZT early in life rendered mice susceptible to MetS in adulthood. Co-administration of IAP with AZT completely prevented this susceptibility by decreasing total body weight, serum lipids, glucose levels and liver lipids to the levels of control mice. These effects of IAP probably occur as a result of changes in the composition of specific bacterial taxa at the genus and species levels (e.g. members of Anaeroplasma and Parabacteroides). Co-administration of IAP with AZT early in life prevents mice from susceptibility to the later development of MetS. This effect is associated with alterations in the composition of the gut microbiota. IAP may represent a novel treatment against MetS in humans. © 2016 John Wiley & Sons Ltd.

Interplay between intestinal alkaline phosphatase, diet, gut microbes and immunity

PubMed Central

Estaki, Mehrbod; DeCoffe, Daniella; Gibson, Deanna L

2014-01-01

Intestinal alkaline phosphatase (IAP) plays an essential role in intestinal homeostasis and health through interactions with the resident microbiota, diet and the gut. IAP’s role in the intestine is to dephosphorylate toxic microbial ligands such as lipopolysaccharides, unmethylated cytosine-guanosine dinucleotides and flagellin as well as extracellular nucleotides such as uridine diphosphate. IAP’s ability to detoxify these ligands is essential in protecting the host from sepsis during acute inflammation and chronic inflammatory conditions such as inflammatory bowel disease. Also important in these complications is IAP’s ability to regulate the microbial ecosystem by forming a complex relationship between microbiota, diet and the intestinal mucosal surface. Evidence reveals that diet alters IAP expression and activity and this in turn can influence the gut microbiota and homeostasis. IAP’s ability to maintain a healthy gastrointestinal tract has accelerated research on its potential use as a therapeutic agent against a multitude of diseases. Exogenous IAP has been shown to have beneficial effects when administered during ulcerative colitis, coronary bypass surgery and sepsis. There are currently a handful of human clinical trials underway investigating the effects of exogenous IAP during sepsis, rheumatoid arthritis and heart surgery. In light of these findings IAP has been marked as a novel agent to help treat a variety of other inflammatory and infectious diseases. The purpose of this review is to highlight the essential characteristics of IAP in protection and maintenance of intestinal homeostasis while addressing the intricate interplay between IAP, diet, microbiota and the intestinal epithelium. PMID:25400448

Is heart rate variability (HRV) an adequate tool for evaluating human emotions? - A focus on the use of the International Affective Picture System (IAPS).

PubMed

Choi, Kwang-Ho; Kim, Junbeom; Kwon, O Sang; Kim, Min Ji; Ryu, Yeon Hee; Park, Ji-Eun

2017-05-01

Because human emotion varies greatly among individuals and is a qualitative factor, measuring it with any degree of accuracy is very difficult. Heart rate variability (HRV), which is used in evaluations of the autonomic nervous system (ANS), is used to evaluate human emotions. This study examines the validity of HRV as a tool to evaluate emotions using the International Affective Picture System (IAPS). For experimentation, five photos were selected for each of the categories of "happy," "unhappy", and "neutral" from among the images provided by the IAPS. The subjects were required to complete the Self-Assessment Manikin (SAM) after being shown each picture. We extracted the R-R interval (RRI) value of each photo from the PPG, as well as the valence, arousal, and dominance value of each photo from the SAM to analyze their correlation. As results, there was significant positive correlation with valence and significant negative correlation with dominance in the photo simulation associated with the "unhappy" emotion, only when the arousal value exceeded a critical value. Therefore, the findings of this study suggest that it is possible to use an HRV-based evaluation only when a high level of emotion is induced by visual stimulation. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Michelob_x is the missing inhibitor of apoptosis protein antagonist in mosquito genomes

PubMed Central

Zhou, Lei; Jiang, Guohua; Chan, Gina; Santos, Carl P; Severson, David W; Xiao, Lei

2005-01-01

Apoptosis is implicated in the life cycle of the malaria parasite in mosquitoes. The genome project for the primary malaria vector Anopheles gambiae showed a significant expansion of the inhibitor of apoptosis protein (IAP) and caspase gene families in comparison with Drosophila. However, because of extensive sequence divergence, no orthologue was identified for the reaper/grim-like IAP antagonist genes that have a pivotal role in cell death regulation in Drosophila. Using a customized searching strategy, we identified michelob_x(mx), a gene not predicted by the genome project, as the missing IAP antagonist in the An. gambiae and other mosquito genomes. Mx has a highly conserved amino-terminal IAP-binding motif. Expression of Mx induces rapid cell death in insect cell lines and is a potent tissue ablator in vivo. Its proapoptotic activity is totally dependent on the IAP-binding motif. Like reaper in Drosophila, mx is transcriptionally induced by ultraviolet irradiation to mediate cell death. PMID:16041319

The effects of nursing activities on the intra-abdominal pressure of patients at risk for intra-abdominal hypertension.

PubMed

Lee, Rosemary K

2017-01-01

Intra-abdominal hypertension (IAH) occurs frequently in critically ill patients, and adds to their morbidity and mortality. There is no published evidence on the effects of nursing activities on the intra-abdominal pressure (IAP) for patients at risk of IAH. The purpose of this study was to identify the effects of hygiene care on the IAP of patients at risk for IAH. Hygiene care was provided to 34 at-risk patients. IAP was measured prior to initiating the hygiene care, immediately after and 10 minutes later. This was a quasi-experimental, pre-test/ post-test design. The 10 minute post-hygiene care measurement of the IAP was significantly lower than the pre or immediate post-measurement of the IAP. There were no significant changes in the mean arterial pressure (MAP) or the abdominal perfusion pressure (APP). It is safe and possibly therapeutic to provide hygiene care to patients at risk for IAH.

Evaluation of (/sup 18/F)-4-fluoroantipyrine as a new blood flow tracer for multiradionuclide autoradiography

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

Sako, K.; Diksic, M.; Kato, A.

This article reports the evaluation of (/sup 18/F)-4-fluoroantipyrine (FAP) as a quantitative blood flow tracer by comparing blood flow measured with (/sup 18/F)FAP to that determined simultaneously with (/sup 14/C)-4-iodoantipyrine (IAP), a standard blood flow tracer, by means of double-tracer autoradiography. The single-pass extraction value (m), which indicates diffusibility of a tracer, was determined according to the procedure described by Crone. The diffusibility of FAP was essentially the same as that of IAP. The brain-blood partition coefficient for FAP was found to be similar to that for IAP, 0.89 +/- 0.01. Values of local cerebral blood flow obtained with FAPmore » agree with those determined with IAP. From these results, we concluded that FAP is indeed as good a blood flow tracer as IAP. Since /sup 18/F is a positron-emitting radionuclide, it might be a useful tracer for blood flow measurement by positron emission tomography.« less

Identification of mTOR as a primary resistance factor of the IAP antagonist AT406 in hepatocellular carcinoma cells

PubMed Central

Wu, Shao-Feng; Zhao, Yi-Lin; Liu, Ping-Guo; Yin, Zhen-Yu

2017-01-01

Dysregulation of inhibitor of apoptosis (IAP) proteins (IAPs) in hepatocellular carcinoma (HCC) is often associated with poor prognosis. Here we showed that AT406, an IAP antagonist, was cytotoxic and pro-apoptotic to both established (HepG2, SMMC-7721 lines) and primary HCC cells. Activation of mTOR could be a key resistance factor of AT406 in HCC cells. mTOR inhibition (by OSI-027), kinase-dead mutation or knockdown remarkably enhanced AT406-induced lethality in HCC cells. Reversely, forced-activation of mTOR by adding SC79 or exogenous expressing a constitutively active S6K1 (T389E) attenuated AT406-induced cytotoxicity against HCC cells. We showed that AT406 induced degradation of IAPs (cIAP-1 and XIAP), but didn't affect another anti-apoptosis protein Mcl-1. Co-treatment of OSI-027 caused simultaneous Mcl-1 downregulation to overcome AT406's resistance. Significantly, shRNA knockdown of Mcl-1 remarkably facilitated AT406-induced apoptosis in HCC cells. In vivo, AT406 oral administration suppressed HepG2 tumor growth in nude mice. Its activity was potentiated with co-administration of OSI-027. We conclude that mTOR could be a key resistance factor of AT406 in HCC cells. PMID:28036295

Identification of mTOR as a primary resistance factor of the IAP antagonist AT406 in hepatocellular carcinoma cells.

PubMed

Zhen, Mao-Chuan; Wang, Fu-Qiang; Wu, Shao-Feng; Zhao, Yi-Lin; Liu, Ping-Guo; Yin, Zhen-Yu

2017-02-07

Dysregulation of inhibitor of apoptosis (IAP) proteins (IAPs) in hepatocellular carcinoma (HCC) is often associated with poor prognosis. Here we showed that AT406, an IAP antagonist, was cytotoxic and pro-apoptotic to both established (HepG2, SMMC-7721 lines) and primary HCC cells. Activation of mTOR could be a key resistance factor of AT406 in HCC cells. mTOR inhibition (by OSI-027), kinase-dead mutation or knockdown remarkably enhanced AT406-induced lethality in HCC cells. Reversely, forced-activation of mTOR by adding SC79 or exogenous expressing a constitutively active S6K1 (T389E) attenuated AT406-induced cytotoxicity against HCC cells. We showed that AT406 induced degradation of IAPs (cIAP-1 and XIAP), but didn't affect another anti-apoptosis protein Mcl-1. Co-treatment of OSI-027 caused simultaneous Mcl-1 downregulation to overcome AT406's resistance. Significantly, shRNA knockdown of Mcl-1 remarkably facilitated AT406-induced apoptosis in HCC cells. In vivo, AT406 oral administration suppressed HepG2 tumor growth in nude mice. Its activity was potentiated with co-administration of OSI-027. We conclude that mTOR could be a key resistance factor of AT406 in HCC cells.

Inhibition by islet-activating protein, pertussis toxin, of P2-purinergic receptor-mediated iodide efflux and phosphoinositide turnover in FRTL-5 cells

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

Okajima, F.; Sho, K.; Kondo, Y.

1988-08-01

Exposure of FRTL-5 thyroid cells to ATP (1 microM to 1 mM) resulted in the stimulation of I- efflux in association with the induction of inositol trisphosphate production and intracellular Ca2+ mobilization. Nonhydrolyzable ATP derivatives, ADP and GTP, were also as effective in magnitude as ATP, whereas neither AMP nor adenosine exerted significant effect on I- efflux, suggesting a P2-purinergic receptor-mediated activation of I- efflux. Treatment of the cells with the islet-activating protein (IAP) pertussis toxin, which ADP-ribosylated a 41,000 mol wt membrane protein, effectively suppressed the phosphoinositide response to ATP in addition to ATP-dependent I- efflux at agonist concentrationsmore » below 10 microM. In contrast, the I- efflux stimulated by TSH, A23187, or phorbol myristate acetate was insusceptible to IAP. The IAP substrate, probably GTP-binding protein, is hence proposed to mediate the activation of P2-purinergic receptor-linked phospholipase-C in FRTL-5 cells. However, the responses to ATP, its nonhydrolyzable derivatives, or ADP at the higher agonist concentrations, especially above 100 microM, were only partially inhibited by IAP, even though the IAP substrate was totally ADP ribosylated by the toxin. The responses to GTP in the whole concentration range tested were not influenced by IAP treatment. Thus, signals arising from the P2-receptor might be transduced to phospholipase-C by two different pathways, i.e. IAP-sensitive and insensitive ones, and result in the stimulation of I- efflux.« less

Both positional and chemical variables control in vitro proteolytic cleavage of a presenilin ortholog

PubMed Central

Naing, Swe-Htet; Kalyoncu, Sibel; Smalley, David M.; Kim, Hyojung; Tao, Xingjian; George, Josh B.; Jonke, Alex P.; Oliver, Ryan C.; Urban, Volker S.; Torres, Matthew P.; Lieberman, Raquel L.

2018-01-01

Mechanistic details of intramembrane aspartyl protease (IAP) chemistry, which is central to many biological and pathogenic processes, remain largely obscure. Here, we investigated the in vitro kinetics of a microbial intramembrane aspartyl protease (mIAP) fortuitously acting on the renin substrate angiotensinogen and the C-terminal transmembrane segment of amyloid precursor protein (C100), which is cleaved by the presenilin subunit of γ-secretase, an Alzheimer disease (AD)-associated IAP. mIAP variants with substitutions in active-site and putative substrate-gating residues generally exhibit impaired, but not abolished, activity toward angiotensinogen and retain the predominant cleavage site (His–Thr). The aromatic ring, but not the hydroxyl substituent, within Tyr of the catalytic Tyr–Asp (YD) motif plays a catalytic role, and the hydrolysis reaction incorporates bulk water as in soluble aspartyl proteases. mIAP hydrolyzes the transmembrane region of C100 at two major presenilin cleavage sites, one corresponding to the AD-associated Aβ42 peptide (Ala–Thr) and the other to the non-pathogenic Aβ48 (Thr–Leu). For the former site, we observed more favorable kinetics in lipid bilayer–mimicking bicelles than in detergent solution, indicating that substrate–lipid and substrate–enzyme interactions both contribute to catalytic rates. High-resolution MS analyses across four substrates support a preference for threonine at the scissile bond. However, results from threonine-scanning mutagenesis of angiotensinogen demonstrate a competing positional preference for cleavage. Our results indicate that IAP cleavage is controlled by both positional and chemical factors, opening up new avenues for selective IAP inhibition for therapeutic interventions. PMID:29382721

Critical role of endogenous Akt/IAPs and MEK1/ERK pathways in counteracting endoplasmic reticulum stress-induced cell death.

PubMed

Hu, Ping; Han, Zhang; Couvillon, Anthony D; Exton, John H

2004-11-19

Endoplasmic reticulum (ER) stress has been implicated in the pathogenesis of many diseases and in cancer therapy. Although the unfolded protein response is known to alleviate ER stress by reducing the accumulation of misfolded proteins, the exact survival elements and their downstream signaling pathways that directly counteract ER stress-stimulated apoptotic signaling remain elusive. Here, we have shown that endogenous Akt and ERK are rapidly activated and act as downstream effectors of phosphatidylinositol 3-kinase in thapsigargin- or tunicamycin-induced ER stress. Introduction of either dominant-negative Akt or MEK1 or the inhibitors LY294002 and U0126 sensitized cells to ER stress-induced cell death in different cell types. Reverse transcription-PCR analysis of gene expression during ER stress revealed that cIAP-2 and XIAP, members of the IAP family of potent caspase suppressors, were strongly induced. Transcription of cIAP-2 and XIAP was up-regulated by the phosphatidylinositol 3-kinase/Akt pathway as shown by its reversal by dominant-negative Akt or LY294002. Ablation of these IAPs by RNA interference sensitized cells to ER stress-induced death, which was reversed by the caspase inhibitor benzyloxycarbonyl-VAD-fluoromethyl ketone. The protective role of IAPs in ER stress coincided with Smac release from mitochondria to the cytosol. Furthermore, it was shown that mTOR was not required for Akt-mediated survival. These results represent the first demonstration that activation of endogenous Akt/IAPs and MEK/ERK plays a critical role in controlling cell survival by resisting ER stress-induced cell death signaling.

What Is the Most Representative Parameter for Describing the Size of the Atlas? CT Morphometric Analysis of the Atlas with Special Reference to Atlas Hypoplasia.

PubMed

Yamahata, Hitoshi; Hirano, Hirofumi; Yamaguchi, Satoshi; Mori, Masanao; Niiro, Tadaaki; Tokimura, Hiroshi; Arita, Kazunori

2017-09-15

The spinal canal diameter (SCD) is one of the most studied factors for the assessment of cervical spinal canal stenosis. The inner anteroposterior diameter (IAP), the SCD, and the cross-sectional area (CSA) of the atlas have been used for the evaluation of the size of the atlas in patients with atlas hypoplasia, a rare form of developmental spinal canal stenosis, however, there is little information on their relationship. The aim of this study was to identify the most useful parameter for depicting the size of the atlas. The CSA, the IAP, and the SCD were measured on computed tomography (CT) images at the C1 level of 213 patients and compared in this retrospective study. These three parameters increased with increasing patient height and weight. There was a strong correlation between IAP and SCD (r = 0.853) or CSA (r = 0.822), while correlation between SCD and CSA (r = 0.695) was weaker than between IAP and CSA. Partial correlation analysis showed that IAP was positively correlated with SCD (r = 0.687) and CSA (r = 0.612) when CSA or SCD were controlled. SCD was negatively correlated with CSA when IAP was controlled (r = -0.21). The IAP can serve as the CSA for the evaluation of the size of the atlas ring, while the SCD does not correlate with the CSA. As the patient height and weight affect the size of the atlas, analysis of the spinal canal at the C1 level should take into account physiologic patient data.

Racial differences in the expression of inhibitors of apoptosis (IAP) proteins in extracellular vesicles (EV) from prostate cancer patients.

PubMed

Khan, Salma; Simpson, Jennifer; Lynch, James C; Turay, David; Mirshahidi, Saied; Gonda, Amber; Sanchez, Tino W; Casiano, Carlos A; Wall, Nathan R

2017-01-01

African-American men with prostate cancer typically develop more aggressive tumors than men from other racial/ethnic groups, resulting in a disproportionately high mortality from this malignancy. This study evaluated differences in the expression of inhibitors of apoptosis proteins (IAPs), a known family of oncoproteins, in blood-derived exosomal vesicles (EV) between African-American and European-American men with prostate cancer. The ExoQuick™ method was used to isolate EV from both plasma and sera of African-American (n = 41) and European-American (n = 31) men with prostate cancer, as well as from controls with no cancer diagnosis (n = 10). EV preparations were quantified by acetylcholinesterase activity assays, and assessed for their IAP content by Western blotting and densitometric analysis. Circulating levels of the IAP Survivin were evaluated by ELISA. We detected a significant increase in the levels of circulating Survivin in prostate cancer patients compared to controls (P<0.01), with the highest levels in African-American patients (P<0.01). African-American patients with prostate cancer also contained significantly higher amounts of EVs in their plasma (P<0.01) and sera (P<0.05) than European-American patients. In addition, EVs from African-American patients with prostate cancer contained significantly higher amounts of the IAPs Survivin (P<0.05), XIAP (P<0.001), and cIAP-2 (P<0.01) than EVs from European-American patients. There was no significant correlation between expression of IAPs and clinicopathological parameters in the two patient groups. Increased expression of IAPs in EVs from African-American patients with prostate cancer may influence tumor aggressiveness and contribute to the mortality disparity observed in this patient population. EVs could serve as reservoirs of novel biomarkers and therapeutic targets that may have clinical utility in reducing prostate cancer health disparities.

Home environment and indoor air pollution exposure in an African birth cohort study.

PubMed

Vanker, Aneesa; Barnett, Whitney; Nduru, Polite M; Gie, Robert P; Sly, Peter D; Zar, Heather J

2015-12-01

Household indoor air pollution (IAP) is a global health problem and a risk factor for childhood respiratory disease; the leading cause of mortality in African children. This study aimed to describe the home environment and measure IAP in the Drakenstein Child Health Study (DCHS), an African birth cohort. An antenatal home visit to assess the home environment and measure IAP (particulate matter, sulphur dioxide, nitrogen dioxide, carbon monoxide and volatile organic compounds (VOCs)) was done on pregnant women enrolled to the DCHS, in a low-socioeconomic, peri-urban South African community. Urine cotinine measured maternal tobacco smoking and exposure. Dwellings were categorised according to 6 household dimensions. Univariate and multivariate analysis explored associations between home environment, seasons and IAP levels measured. 633 home visits were completed, with IAP measured in 90% of homes. Almost a third of participants were of the lowest socio-economic status and the majority of homes (65%) lacked 2 or more of the dwelling category dimensions. Most households had electricity (92%), however, fossil fuels were still used for cooking (19%) and heating (15%) in homes. Antenatal maternal smoking prevalence was 31%; 44% had passive smoke exposure. Of IAP measured, benzene (VOC) was significantly above ambient standards with median 5.6 μg/m3 (IQR 2.6-17.1). There were significant associations between the use of fossil fuels for cooking and increased benzene [OR 3.4 (95% CI 2.1-5.4)], carbon monoxide [OR 2.9 (95% CI 1.7-5.0)] and nitrogen dioxide [OR 18.6 (95% CI 3.9-88.9)] levels. A significant seasonal association was found with higher IAP levels in winter. In this low-socioeconomic African community, multiple environmental factors and pollutants, with the potential to affect child health, were identified. Measurement of IAP in a resource-limited setting is feasible. Recognising and quantifying these risk factors is important in effecting public health policy changes. Copyright © 2015 Elsevier B.V. All rights reserved.

Intrapartum Antibiotic Chemoprophylaxis Policies for the Prevention of Group B Streptococcal Disease Worldwide: Systematic Review.

PubMed

Le Doare, Kirsty; O'Driscoll, Megan; Turner, Kim; Seedat, Farah; Russell, Neal J; Seale, Anna C; Heath, Paul T; Lawn, Joy E; Baker, Carol J; Bartlett, Linda; Cutland, Clare; Gravett, Michael G; Ip, Margaret; Madhi, Shabir A; Rubens, Craig E; Saha, Samir K; Schrag, Stephanie; Sobanjo-Ter Meulen, Ajoke; Vekemans, Johan; Kampmann, Beate

2017-11-06

Intrapartum antibiotic chemoprophylaxis (IAP) prevents most early-onset group B streptococcal (GBS) disease. However, there is no description of how IAP is used around the world. This article is the sixth in a series estimating the burden of GBS disease. Here we aimed to review GBS screening policies and IAP implementation worldwide. We identified data through (1) systematic literature reviews (PubMed/Medline, Embase, Literature in the Health Sciences in Latin America and the Caribbean [LILACS], World Health Organization library database [WHOLIS], and Scopus) and unpublished data from professional societies and (2) an online survey and searches of policies from medical societies and professionals. We included data on whether an IAP policy was in use, and if so whether it was based on microbiological or clinical risk factors and how these were applied, as well as the estimated coverage (percentage of women receiving IAP where indicated). We received policy information from 95 of 195 (49%) countries. Of these, 60 of 95 (63%) had an IAP policy; 35 of 60 (58%) used microbiological screening, 25 of 60 (42%) used clinical risk factors. Two of 15 (13%) low-income, 4 of 16 (25%) lower-middle-income, 14 of 20 (70%) upper-middle-income, and 40 of 44 (91%) high-income countries had any IAP policy. The remaining 35 of 95 (37%) had no national policy (25/33 from low-income and lower-middle-income countries). Coverage varied considerably; for microbiological screening, median coverage was 80% (range, 20%-95%); for clinical risk factor-based screening, coverage was 29% (range, 10%-50%). Although there were differences in the microbiological screening methods employed, the individual clinical risk factors used were similar. There is considerable heterogeneity in IAP screening policies and coverage worldwide. Alternative global strategies, such as maternal vaccination, are needed to enhance the scope of global prevention of GBS disease. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America.

A Herpes Simplex Virus Type 1 Mutant Expressing a Baculovirus Inhibitor of Apoptosis Gene in Place of Latency-Associated Transcript Has a Wild-Type Reactivation Phenotype in the Mouse

PubMed Central

Jin, Ling; Perng, Guey-Chuen; Mott, Kevin R.; Osorio, Nelson; Naito, Julia; Brick, David J.; Carpenter, Dale; Jones, Clinton; Wechsler, Steven L.

2005-01-01

The latency-associated transcript (LAT) is essential for the wild-type herpes simplex virus type 1 (HSV-1) high-reactivation phenotype since LAT− mutants have a low-reactivation phenotype. We previously reported that LAT can decrease apoptosis and proposed that this activity is involved in LAT's ability to enhance the HSV-1 reactivation phenotype. The first 20% of the primary 8.3-kb LAT transcript is sufficient for enhancing the reactivation phenotype and for decreasing apoptosis, supporting this proposal. For this study, we constructed an HSV-1 LAT− mutant that expresses the baculovirus antiapoptosis gene product cpIAP under control of the LAT promoter and in place of the LAT region mentioned above. Mice were ocularly infected with this mutant, designated dLAT-cpIAP, and the reactivation phenotype was determined using the trigeminal ganglion explant model. dLAT-cpIAP had a reactivation phenotype similar to that of wild-type virus and significantly higher than that of (i) the LAT− mutant dLAT2903; (ii) dLAT1.5, a control virus containing the same LAT deletion as dLAT-cpIAP, but with no insertion of foreign DNA, thereby controlling for potential readthrough transcription past the cpIAP insert; and (iii) dLAT-EGFP, a control virus identical to dLAT-cpIAP except that it contained the enhanced green fluorescent protein open reading frame (ORF) in place of the cpIAP ORF, thereby controlling for expression of a random foreign gene instead of the cpIAP gene. These results show that an antiapoptosis gene with no sequence similarity to LAT can efficiently substitute for the LAT function involved in enhancing the in vitro-induced HSV-1 reactivation phenotype in the mouse. PMID:16160155

Indoor air pollution affects hypertension risk in rural women in Northern China by interfering with the uptake of metal elements: A preliminary cross-sectional study.

PubMed

Wang, Bin; Zhu, Yibing; Pang, Yiming; Xie, Jing; Hao, Yongxiu; Yan, Huina; Li, Zhiwen; Ye, Rongwei

2018-05-07

Coal combustion and passive smoking are two important contributors to indoor air pollution (IAP) in rural areas of northern China. Although the association between outdoor air pollutants and hypertension risk had been widely reported, fewer studies have examined the relationship between IAP and hypertension risk. This study evaluated the association between IAP and hypertension risk in housewives in rural areas of northern China and the potential mediation pathway of metal elements. Our cross-sectional study, conducted in Shanxi Province, China, enrolled 367 subjects without taking anti-hypertensive drugs, including 142 subjects with hypertension (case group) and 225 subjects without hypertension (control group). We collected information on energy use characteristics and lifestyle using questionnaires. An IAP exposure index was developed to indicate the population exposure to coal combustion and passive smoking. Scalp hair samples were collected from the housewives and various trace and major metal elements were measured. Our results revealed that the IAP index was positively correlated with systolic and diastolic blood pressure. A significant association between the IAP index and hypertension risk was found both without [odds ratio (95% confidence interval, CI) = 2.08 (1.30-3.31)] and with [OR (95% CI) = 2.52 (1.46-4.36)] adjustment for confounders. We also observed that the IAP index was positively correlated with the arsenic, lead, and rare earth element levels in hair samples, and negatively correlated with the levels of some other trace elements (i.e., chromium, cobalt, nickel, and tin) and alkaline earth elements (i.e., calcium, magnesium, and barium) with an overall p value of <0.01. We concluded that IAP may contribute to the development of hypertension in rural housewives in northern China, possibly by interfering with the uptake of metal elements. Copyright © 2018 Elsevier Ltd. All rights reserved.

Computational design and biophysical characterization of aggregation-resistant point mutations for γD crystallin illustrate a balance of conformational stability and intrinsic aggregation propensity.

PubMed

Sahin, Erinc; Jordan, Jacob L; Spatara, Michelle L; Naranjo, Andrea; Costanzo, Joseph A; Weiss, William F; Robinson, Anne Skaja; Fernandez, Erik J; Roberts, Christopher J

2011-02-08

γD crystallin is a natively monomeric eye-lens protein that is associated with hereditary juvenile cataract formation. It is an attractive model system as a multidomain Greek-key protein that aggregates through partially folded intermediates. Point mutations M69Q and S130P were used to test (1) whether the protein-design algorithm RosettaDesign would successfully predict mutants that are resistant to aggregation when combined with informatic sequence-based predictors of peptide aggregation propensity and (2) how the mutations affected relative unfolding free energies (ΔΔG(un)) and intrinsic aggregation propensity (IAP). M69Q was predicted to have ΔΔG(un) ≫ 0, without significantly affecting IAP. S130P was predicted to have ΔΔG(un) ∼ 0 but with reduced IAP. The stability, conformation, and aggregation kinetics in acidic solution were experimentally characterized and compared for the variants and wild-type (WT) protein using circular dichroism and intrinsic fluorescence spectroscopy, calorimetric and chemical unfolding, thioflavin-T binding, chromatography, static laser light scattering, and kinetic modeling. Monomer secondary and tertiary structures of both variants were indistinguishable from WT, while ΔΔG(un) > 0 for M69Q and ΔΔG(un) < 0 for S130P. Surprisingly, despite being the least conformationally stable, S130P was the most resistant to aggregation, indicating a significant decrease of its IAP compared to WT and M69Q.

Quantitative assessment of the rheumatoid synovial microvascular bed by gadolinium-DTPA enhanced magnetic resonance imaging

PubMed Central

Gaffney, K.; Cookson, J.; Blades, S.; Coumbe, A.; Blake, D.

1998-01-01

OBJECTIVE—To examine the relation between rate of synovial membrane enhancement, intra-articular pressure (IAP), and histologically determined synovial vascularity in rheumatoid arthritis, using gadolinium-DTPA enhanced magnetic resonance imaging (MRI).
METHODS—Dynamic gadolinium-DTPA enhanced MRI was performed in 31 patients with knee synovitis (10 patients IAP study, 21 patients vascular morphometry study). Rate of synovial membrane enhancement was quantified by line profile analysis using the image processing package ANALYZE. IAP was measured using an intra-compartmental pressure monitor system. Multiple synovial biopsy specimens were obtained by a blind biopsy technique. Blood vessels were identified immunohistochemically using the endothelial cell marker QBend30 and quantified (blood vessel numerical density and fractional area).
RESULTS—Median blood vessel numerical density and fractional area were 77.5/mm2 (IQR; 69.3-110.7) and 5.6% (IQR; 3.4-8.5) respectively. The rate of synovial membrane enhancement (median 2.74 signal intensity units/s, IQR 2.0-3.8) correlated with both blood vessel numerical density (r = 0.46, p < 0.05) and blood vessel fractional area (r = 0.55, p < 0.02). IAP did not influence the rate of enhancement.
CONCLUSIONS—Gadolinium-DTPA enhanced MRI may prove to be a valuable technique for evaluating drugs that influence angiogenesis.

 Keywords: magnetic resonance imaging; rheumatoid arthritis; synovitis; vascularity PMID:9640130

Correlation of Noninvasive Blood Pressure and Invasive Intra-arterial Blood Pressure in Patients Treated with Vasoactive Medications in a Neurocritical Care Unit.

PubMed

Saherwala, Ali A; Stutzman, Sonja E; Osman, Mohamed; Kalia, Junaid; Figueroa, Stephen A; Olson, DaiWai M; Aiyagari, Venkatesh

2018-03-22

The correlation between noninvasive (oscillometric) blood pressure (NBP) and intra-arterial blood pressure (IAP) in critically ill patients receiving vasoactive medications in a Neurocritical Care Unit has not been systematically studied. The purpose of this study is to examine the relationship between simultaneously measured NBP and IAP recordings in these patients. Prospective observational study of patients (N = 70) admitted to a neurocritical care unit receiving continuous vasopressor or antihypertensive infusions. Paired NBP/IAP observations along with covariate and demographic data were abstracted via chart audit. Analysis was performed using SAS v9.4. A total of 2177 paired NBP/IAP observations from 70 subjects (49% male, 63% white, mean age 59 years) receiving vasopressors (n = 21) or antihypertensive agents (n = 49) were collected. Paired t test analysis showed significant differences between NBP versus IAP readings: ([systolic blood pressure (SBP): mean = 136 vs. 140 mmHg; p < 0.0001], [diastolic blood pressure (DBP): mean = 70 vs. 68 mmHg, p < 0.0001], [mean arterial blood pressure (MAP): mean = 86 vs. 90 mmHg, p < 0.0001]). Bland-Altman plots for MAP, SBP, and DBP demonstrate good inter-method agreement between paired measures (excluding outliers) and demonstrate NBP-IAP SBP differences at extremes of blood pressures. Pearson correlation coefficients show strong positive correlations for paired MAP (r = 0.82), SBP (r = 0.84), and DBP (r = 0.73) recordings. An absolute NBP-IAP SBP difference of > 20 mmHg was seen in ~ 20% of observations of nicardipine, ~ 25% of observations of norepinephrine, and ~ 35% of observations of phenylephrine. For MAP, the corresponding numbers were ~ 10, 15, and 25% for nicardipine, norepinephrine, and phenylephrine, respectively. Despite overall strong positive correlations between paired NBP and IAP readings of MAP and SBP, clinically relevant differences in blood pressure are frequent. When treating with vasoactive infusions targeted to a specific BP goal, it is important to keep in mind that NBP and IAP values are not interchangeable.

The small-molecule IAP antagonist AT406 inhibits pancreatic cancer cells in vitro and in vivo

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

Jiang, Yongsheng; Meng, Qinghua; Chen, Bo

In the present study, we tested the anti-pancreatic cancer activity by AT406, a small-molecule antagonist of IAP (inhibitor of apoptosis proteins). In established (Panc-1 and Mia-PaCa-2 lines) and primary human pancreatic cancer cells, treatment of AT406 significantly inhibited cell survival and proliferation. Yet, same AT406 treatment was non-cytotoxic to pancreatic epithelial HPDE6c7 cells. AT406 increased caspase-3/-9 activity and provoked apoptosis in the pancreatic cancer cells. Reversely, AT406′ cytotoxicity in these cells was largely attenuated with pre-treatment of caspase inhibitors. AT406 treatment caused degradation of IAP family proteins (cIAP1 and XIAP) and release of cytochrome C, leaving Bcl-2 unaffected in pancreaticmore » cancer cells. Bcl-2 inhibition (by ABT-737) or shRNA knockdown dramatically sensitized Panc-1 cells to AT406. In vivo, oral administration of AT406 at well-tolerated doses downregulated IAPs (cIAP1/XIAP) and inhibited Panc-1 xenograft tumor growth in severe combined immunodeficient (SCID) nude mice. Together, our preclinical results suggest that AT406 could be further evaluated as a promising anti-pancreatic cancer agent. - Highlights: • AT406 is cytotoxic to established/primary human pancreatic cancer cells. • AT406 provokes caspase-dependent apoptosis in pancreatic cancer cells. • AT406 causes degradation of key IAPs and promotes cytochrome C release. • Bcl-2 inhibition or knockdown dramatically sensitizes Panc-1 cells to AT406. • Oral administration of AT406 inhibits Panc-1 tumor growth in SCID nude mice.« less

Impact of maternal intrapartum antibiotics, method of birth and breastfeeding on gut microbiota during the first year of life: a prospective cohort study.

PubMed

Azad, M B; Konya, T; Persaud, R R; Guttman, D S; Chari, R S; Field, C J; Sears, M R; Mandhane, P J; Turvey, S E; Subbarao, P; Becker, A B; Scott, J A; Kozyrskyj, A L

2016-05-01

Dysbiosis of the infant gut microbiota may have long-term health consequences. This study aimed to determine the impact of maternal intrapartum antibiotic prophylaxis (IAP) on infant gut microbiota, and to explore whether breastfeeding modifies these effects. Prospective pregnancy cohort of Canadian infants born in 2010-2012: the Canadian Healthy Infant Longitudinal Development (CHILD) Study. General community. Representative sub-sample of 198 healthy term infants from the CHILD Study. Maternal IAP exposures and birth method were documented from hospital records and breastfeeding was reported by mothers. Infant gut microbiota was characterised by Illumina 16S rRNA sequencing of faecal samples at 3 and 12 months. Infant gut microbiota profiles. In this cohort, 21% of mothers received IAP for Group B Streptococcus prophylaxis or pre-labour rupture of membranes; another 23% received IAP for elective or emergency caesarean section (CS). Infant gut microbiota community structures at 3 months differed significantly with all IAP exposures, and differences persisted to 12 months for infants delivered by emergency CS. Taxon-specific composition also differed, with the genera Bacteroides and Parabacteroides under-represented, and Enterococcus and Clostridium over-represented at 3 months following maternal IAP. Microbiota differences were especially evident following IAP with emergency CS, with some changes (increased Clostridiales and decreased Bacteroidaceae) persisting to 12 months, particularly among non-breastfed infants. Intrapartum antibiotics in caesarean and vaginal delivery are associated with infant gut microbiota dysbiosis, and breastfeeding modifies some of these effects. Further research is warranted to explore the health consequences of these associations. Maternal #antibiotics during childbirth alter the infant gut #microbiome. © 2015 Royal College of Obstetricians and Gynaecologists.

Intestinal alkaline phosphatase at the crossroad of intestinal health and disease - a putative role in type 1 diabetes.

PubMed

Lassenius, M I; Fogarty, C L; Blaut, M; Haimila, K; Riittinen, L; Paju, A; Kirveskari, J; Järvelä, J; Ahola, A J; Gordin, D; Härma, M-A; Kumar, A; Hamarneh, S R; Hodin, R A; Sorsa, T; Tervahartiala, T; Hörkkö, S; Pussinen, P J; Forsblom, C; Jauhiainen, M; Taskinen, M-R; Groop, P-H; Lehto, M

2017-06-01

Patients with type 1 diabetes have shown an increase in circulating cytokines, altered lipoprotein metabolism and signs of vascular dysfunction in response to high-fat meals. Intestinal alkaline phosphatase (IAP) regulates lipid transport and inflammatory responses in the gastrointestinal tract. We therefore hypothesized that changes in IAP activity could have profound effects on gut metabolic homeostasis in patients with type 1 diabetes. Faecal samples of 41 nondiabetic controls and 46 patients with type 1 diabetes were analysed for IAP activity, calprotectin, immunoglobulins and short-chain fatty acids (SCFAs). The impact of oral IAP supplementation on intestinal immunoglobulin levels was evaluated in C57BL/6 mice exposed to high-fat diet for 11 weeks. Patients with type 1 diabetes exhibited signs of intestinal inflammation. Compared to controls, patients with diabetes had higher faecal calprotectin levels, lower faecal IAP activities accompanied by lower propionate and butyrate concentrations. Moreover, the amount of faecal IgA and the level of antibodies binding to oxidized LDL were decreased in patients with type 1 diabetes. In mice, oral IAP supplementation increased intestinal IgA levels markedly. Deprivation of protective intestinal factors may increase the risk of inflammation in the gut - a phenomenon that seems to be present already in patients with uncomplicated type 1 diabetes. Low levels of intestinal IgA and antibodies to oxidized lipid epitopes may predispose such patients to inflammation-driven complications such as cardiovascular disease and diabetic nephropathy. Importantly, oral IAP supplementation could have beneficial therapeutic effects on gut metabolic homeostasis, possibly through stimulation of intestinal IgA secretion. © 2017 The Association for the Publication of the Journal of Internal Medicine.

Gaze differences in processing pictures with emotional content.

PubMed

Budimir, Sanja; Palmović, Marijan

2011-01-01

The International Affective Picture System (IAPS) is a set of standardized emotionally evocative color photographs developed by NIMH Center for Emotion and Attention at the University of Florida. It contains more than 900 emotional pictures indexed by emotional valence, arousal and dominance. However, when IAPS pictures were used in studying emotions with the event-related potentials, the results have shown a great deal of variation and inconsistency. In this research arousal and dominance of pictures were controlled while emotional valence was manipulated as 3 categories, pleasant, neutral and unpleasant pictures. Two experiments were conducted with an eye-tracker in order to determine to what the participants turn their gaze. Participants were 25 psychology students with normal vision. Every participant saw all pictures in color and same pictures in black/white version. This makes 200 analyzed units for color pictures and 200 for black and white pictures. Every picture was divided into figure and ground. Considering that perception can be influenced by color, edges, luminosity and contrast and since all those factors are collapsed on the pictures in IAPS, we compared color pictures with same black and white pictures. In first eye-tracking IAPS research we analyzed 12 emotional pictures and showed that participants have higher number of fixations for ground on neutral and unpleasant pictures and for figure on pleasant pictures. Second experiment was conducted with 4 sets of emotional complementary pictures (pleasant/unpleasant) which differ only on the content in the figure area and it was shown that participants were more focused on the figure area than on the ground area. Future ERP (event related potential) research with IAPS pictures should take into consideration these findings and to either choose pictures with blank ground or adjust pictures in the way that ground is blank. For the following experiments suggestion is to put emotional content in the figure area and to use different non complementary pictures to see if there is difference between different emotional categories.

Bonding Pictures: Affective Ratings Are Specifically Associated to Loneliness But Not to Empathy

PubMed Central

Silva, Heraldo D.; Campagnoli, Rafaela R.; Mota, Bruna Eugênia F.; Araújo, Cássia Regina V.; Álvares, Roberta Sônia R.; Mocaiber, Izabela; Rocha-Rego, Vanessa; Volchan, Eliane; Souza, Gabriela G. L.

2017-01-01

Responding to pro-social cues plays an important adaptive role in humans. Our aims were (i) to create a catalog of bonding and matched-control pictures to compare the emotional reports of valence and arousal with the International Affective Picture System (IAPS) pictures; (ii) to verify sex influence on the valence and arousal of bonding and matched-control pictures; (iii) to investigate if empathy and loneliness traits exert a specific influence on emotional reports for the bonding pictures. To provide a finer tool for social interaction studies, the present work defined two new sets of pictures consisting of “interacting dyads” (Bonding: N = 70) and matched controls “non-interacting dyads” (Controls: N = 70). The dyads could be either a child and an adult, or two children. Participants (N = 283, 182 women) were divided in 10 groups for the experimental sessions. The task was to rate the hedonic valence and emotional arousal of bonding and controls; and of pleasant, neutral, and unpleasant pictures from the IAPS. Effects of social-related traits, empathy and loneliness, on affective ratings were tested. Participants rated bonding pictures as more pleasant and arousing than control ones. Ratings did not differentiate bonding from IAPS pleasant pictures. Control pictures showed lower ratings than pleasant but higher ratings than neutral IAPS pictures. Women rated bonding and control pictures as more positive than men. There was no sex difference for arousal ratings. High empathic participants rated bonding and control pictures higher than low empathic participants. Also, they rated pleasant IAPS pictures more positive and arousing; and unpleasant pictures more negative and arousing than the less empathic ones. Loneliness trait, on the other hand, affected very specifically the ratings of bonding pictures; lonelier participants rated them less pleasant and less arousing than less lonely. Loneliness trait did not modulate ratings of other categories. In conclusion, high empathy seems related to emotional strength in general, while high loneliness seems to weaken the engagement in social interaction cues. PMID:28740473

Bonding Pictures: Affective Ratings Are Specifically Associated to Loneliness But Not to Empathy.

PubMed

Silva, Heraldo D; Campagnoli, Rafaela R; Mota, Bruna Eugênia F; Araújo, Cássia Regina V; Álvares, Roberta Sônia R; Mocaiber, Izabela; Rocha-Rego, Vanessa; Volchan, Eliane; Souza, Gabriela G L

2017-01-01

Responding to pro-social cues plays an important adaptive role in humans. Our aims were (i) to create a catalog of bonding and matched-control pictures to compare the emotional reports of valence and arousal with the International Affective Picture System (IAPS) pictures; (ii) to verify sex influence on the valence and arousal of bonding and matched-control pictures; (iii) to investigate if empathy and loneliness traits exert a specific influence on emotional reports for the bonding pictures. To provide a finer tool for social interaction studies, the present work defined two new sets of pictures consisting of "interacting dyads" (Bonding: N = 70) and matched controls "non-interacting dyads" (Controls: N = 70). The dyads could be either a child and an adult, or two children. Participants ( N = 283, 182 women) were divided in 10 groups for the experimental sessions. The task was to rate the hedonic valence and emotional arousal of bonding and controls; and of pleasant, neutral, and unpleasant pictures from the IAPS. Effects of social-related traits, empathy and loneliness, on affective ratings were tested. Participants rated bonding pictures as more pleasant and arousing than control ones. Ratings did not differentiate bonding from IAPS pleasant pictures. Control pictures showed lower ratings than pleasant but higher ratings than neutral IAPS pictures. Women rated bonding and control pictures as more positive than men. There was no sex difference for arousal ratings. High empathic participants rated bonding and control pictures higher than low empathic participants. Also, they rated pleasant IAPS pictures more positive and arousing; and unpleasant pictures more negative and arousing than the less empathic ones. Loneliness trait, on the other hand, affected very specifically the ratings of bonding pictures; lonelier participants rated them less pleasant and less arousing than less lonely. Loneliness trait did not modulate ratings of other categories. In conclusion, high empathy seems related to emotional strength in general, while high loneliness seems to weaken the engagement in social interaction cues.

Tumors acquire inhibitor of apoptosis protein (IAP)-mediated apoptosis resistance through altered specificity of cytosolic proteolysis.

PubMed

Hong, Xu; Lei, Lu; Glas, Rickard

2003-06-16

Many tumors overexpress members of the inhibitor of apoptosis protein (IAP) family. IAPs contribute to tumor cell apoptosis resistance by the inhibition of caspases, and are degraded by the proteasome to allow further progression of apoptosis. Here we show that tumor cells can alter the specificity of cytosolic proteolysis in order to acquire apoptosis resistance, which promotes formation of rapidly growing tumors. Survival of tumor cells with low proteasomal activity can occur in the presence of high expression of Tri-peptidyl-peptidase II (TPP II), a large subtilisin-like peptidase that complements proteasomal activity. We find that this state leaves tumor cells unable of effectively degrading IAPs, and that cells in this state form rapidly growing tumors in vivo. We also find, in studies of apoptosis resistant cells derived from large in vivo tumors, that these have acquired an altered peptidase activity, with up-regulation of TPP II activity and decreased proteasomal activity. Importantly, we find that growth of subcutaneous tumors is limited by maintenance of the apoptosis resistant phenotype. The apoptosis resistant phenotype was reversed by increased expression of Smac/DIABLO, an antagonist of IAP molecules. Our data suggest a reversible mechanism in regulation of apoptosis resistance that drives tumor progression in vivo. These data are relevant in relation to the multitude of therapy-resistant clinical tumors that have increased levels of IAP molecules.

Derivativation of the human erythrocyte glucose transporter using a novel forskolin photoaffinity label

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

Wadzinski, B.; Shanahan, M.; Ruoho, A.

1987-05-01

An iodinated photoaffinity label for the glucose transporter, 3-iodo-4-azidophenethylamido-7-0-succinyldeacetyl-forskolin (IAPS-Fsk), has been synthesized, purified, and characterized. The K/sub i/ for inhibition of 3-0-methylglucose transport by TAPS-Fsk in human erythrocytes was found to be 0.1 uM. The carrier-free radioiodinated label has been shown to be a highly specific photoaffinity label for the human erythrocyte glucose transporter. Photolysis of erythrocyte membranes with 1-10 nM (I-125)IAPS-Fsk and analysis by SDS-PAGE showed specific derivatization of a broad band with an apparent molecular weight of 40-70 kDa. Photoincorporation using 2 nM (I-125)IAPS-Fsk was protected with D-glucose, cytochalasin B, and forskolin. No protection was observed withmore » L-glucose. Endo-B-galactosidase digestion and trypsinization of (I-125)IAPS-Fsk labelled erythrocytes reduced the specifically radiolabelled transporter to 40 kDa and 18 kDa respectively. (I-125)-IAPS-Fsk will be used to study the structural aspects of the glucose transporter.« less

Radiation-induced changes in intestinal and tissue-nonspecific alkaline phosphatase: implications for recovery after radiation therapy.

PubMed

Rentea, Rebecca M; Lam, Vy; Biesterveld, Ben; Fredrich, Katherine M; Callison, Jennifer; Fish, Brian L; Baker, John E; Komorowski, Richard; Gourlay, David M; Otterson, Mary F

2016-10-01

Exogenous replacement of depleted enterocyte intestinal alkaline phosphatase (IAP) decreases intestinal injury in models of colitis. We determined whether radiation-induced intestinal injury could be mitigated by oral IAP supplementation and the impact on tissue-nonspecific AP. WAG/RjjCmcr rats (n = 5 per group) received lower hemibody irradiation (13 Gy) followed by daily gavage with phosphate-buffered saline or IAP (40 U/kg/d) for 4 days. Real-time polymerase chain reaction, AP activity, and microbiota analysis were performed on intestine. Lipopolysaccharide and cytokine analysis was performed on serum. Data were expressed as a mean ± SEM with P greater than .05 considered significant. Intestine of irradiated animals demonstrates lower hemibody irradiation and is associated with upregulation of tissue-nonspecific AP, downregulation of IAP, decreased AP activity, and altered composition of the intestinal microbiome. Supplemental IAP after radiation may be beneficial in mitigating intestinal radiation syndrome as evidenced by improved histologic injury, decreased acute intestinal inflammation, and normalization of intestinal microbiome. Copyright © 2016 Elsevier Inc. All rights reserved.

Alkaline Phosphatase, an Unconventional Immune Protein.

PubMed

Rader, Bethany A

2017-01-01

Recent years have seen an increase in the number of studies focusing on alkaline phosphatases (APs), revealing an expanding complexity of function of these enzymes. Of the four human AP (hAP) proteins, most is known about tissue non-specific AP (TNAP) and intestinal AP (IAP). This review highlights current understanding of TNAP and IAP in relation to human health and disease. TNAP plays a role in multiple processes, including bone mineralization, vitamin B6 metabolism, and neurogenesis, is the genetic cause of hypophosphatasia, influences inflammation through regulation of purinergic signaling, and has been implicated in Alzheimer's disease. IAP regulates fatty acid absorption and has been implicated in the regulation of diet-induced obesity and metabolic syndrome. IAP and TNAP can dephosphorylate bacterial-derived lipopolysaccharide, and IAP has been identified as a potential regulator of the composition of the intestinal microbiome, an evolutionarily conserved function. Endogenous and recombinant bovine APs and recombinant hAPs are currently being explored for their potential as pharmacological agents to treat AP-associated diseases and mitigate multiple sources of inflammation. Continued research on these versatile proteins will undoubtedly provide insight into human pathophysiology, biochemistry, and the human holobiont.

Intestinal alkaline phosphatase prevents metabolic syndrome in mice.

PubMed

Kaliannan, Kanakaraju; Hamarneh, Sulaiman R; Economopoulos, Konstantinos P; Nasrin Alam, Sayeda; Moaven, Omeed; Patel, Palak; Malo, Nondita S; Ray, Madhury; Abtahi, Seyed M; Muhammad, Nur; Raychowdhury, Atri; Teshager, Abeba; Mohamed, Mussa M Rafat; Moss, Angela K; Ahmed, Rizwan; Hakimian, Shahrad; Narisawa, Sonoko; Millán, José Luis; Hohmann, Elizabeth; Warren, H Shaw; Bhan, Atul K; Malo, Madhu S; Hodin, Richard A

2013-04-23

Metabolic syndrome comprises a cluster of related disorders that includes obesity, glucose intolerance, insulin resistance, dyslipidemia, and fatty liver. Recently, gut-derived chronic endotoxemia has been identified as a primary mediator for triggering the low-grade inflammation responsible for the development of metabolic syndrome. In the present study we examined the role of the small intestinal brush-border enzyme, intestinal alkaline phosphatase (IAP), in preventing a high-fat-diet-induced metabolic syndrome in mice. We found that both endogenous and orally supplemented IAP inhibits absorption of endotoxin (lipopolysaccharides) that occurs with dietary fat, and oral IAP supplementation prevents as well as reverses metabolic syndrome. Furthermore, IAP supplementation improves the lipid profile in mice fed a standard, low-fat chow diet. These results point to a potentially unique therapy against metabolic syndrome in at-risk humans.

Effects of zero reference position on bladder pressure measurements: an observational study.

PubMed

Soler Morejón, Caridad De Dios; Lombardo, Tomás Ariel; Tamargo Barbeito, Teddy Osmin; Sandra, Barquín García

2012-07-05

Although the World Society for Abdominal Compartment Syndrome in its guidelines recommends midaxillary line (MAL) as zero reference level in intra-abdominal pressure (IAP) measurements in aiming at standardizing the technique, evidence supporting this suggestion is scarce. The aim of this study is to study if the zero reference position influences bladder pressure measurements as estimate for IAP. The IAP of 100 surgical patients was measured during the first 24 h of admission to the surgical intensive care unit of General Calixto Garcia Hospital in Havana (Cuba) following laparotomy. The period was January 2009 to January 2010. The IAP was measured twice with a six-hour interval using the transurethral technique with a priming volume of 25 ml. IAP was first measured with the zero reference level placed at MAL (IAPMAL), followed by a second measurement at the level of the symphysis pubis (SP) after 3 minutes (IAPSP). Correlations were made between IAP and body mass index (BMI), type of surgery, gender, and age. Mean IAPMAL was 8.5 ± 2.8 mmHg vs. IAPSP 6.5 ± 2.8 mmHg (p < 0.0001). The bias between measurements was 2.0 ± 1.5, 95% confidence interval of 1.4 to 3.0, upper limit of 4.9, lower limit of -0.9, and a percentage error of 35.1%. IAPMAL was consistently higher than IAPSP regardless of the type of surgery. The BMI correlated with IAP values regardless of the zero reference level (R2 = 0.4 and 0.3 with IAPMAL and IAPSP respectively, p < 0.0001). The zero reference level has an important impact on IAP measurement in surgical patients after laparotomy and can potentially lead to over or underestimation. Further anthropometric studies are needed with regard to the relative MAL and SP zero reference position in relation to the theoretical ideal reference level at midpoint of the abdomen. Until better evidence is available, MAL remains the recommended zero reference position due to its best anatomical localization at iliac crest.

Effects of zero reference position on bladder pressure measurements: an observational study

PubMed Central

2012-01-01

Background Although the World Society for Abdominal Compartment Syndrome in its guidelines recommends midaxillary line (MAL) as zero reference level in intra-abdominal pressure (IAP) measurements in aiming at standardizing the technique, evidence supporting this suggestion is scarce. The aim of this study is to study if the zero reference position influences bladder pressure measurements as estimate for IAP. Methods The IAP of 100 surgical patients was measured during the first 24 h of admission to the surgical intensive care unit of General Calixto Garcia Hospital in Havana (Cuba) following laparotomy. The period was January 2009 to January 2010. The IAP was measured twice with a six-hour interval using the transurethral technique with a priming volume of 25 ml. IAP was first measured with the zero reference level placed at MAL (IAPMAL), followed by a second measurement at the level of the symphysis pubis (SP) after 3 minutes (IAPSP). Correlations were made between IAP and body mass index (BMI), type of surgery, gender, and age. Results Mean IAPMAL was 8.5 ± 2.8 mmHg vs. IAPSP 6.5 ± 2.8 mmHg (p < 0.0001). The bias between measurements was 2.0 ± 1.5, 95% confidence interval of 1.4 to 3.0, upper limit of 4.9, lower limit of -0.9, and a percentage error of 35.1%. IAPMAL was consistently higher than IAPSP regardless of the type of surgery. The BMI correlated with IAP values regardless of the zero reference level (R2 = 0.4 and 0.3 with IAPMAL and IAPSP respectively, p < 0.0001). Conclusions The zero reference level has an important impact on IAP measurement in surgical patients after laparotomy and can potentially lead to over or underestimation. Further anthropometric studies are needed with regard to the relative MAL and SP zero reference position in relation to the theoretical ideal reference level at midpoint of the abdomen. Until better evidence is available, MAL remains the recommended zero reference position due to its best anatomical localization at iliac crest. PMID:22873414

Inhibition of the gut enzyme intestinal alkaline phosphatase may explain how aspartame promotes glucose intolerance and obesity in mice.

PubMed

Gul, Sarah S; Hamilton, A Rebecca L; Munoz, Alexander R; Phupitakphol, Tanit; Liu, Wei; Hyoju, Sanjiv K; Economopoulos, Konstantinos P; Morrison, Sara; Hu, Dong; Zhang, Weifeng; Gharedaghi, Mohammad Hadi; Huo, Haizhong; Hamarneh, Sulaiman R; Hodin, Richard A

2017-01-01

Diet soda consumption has not been associated with tangible weight loss. Aspartame (ASP) commonly substitutes sugar and one of its breakdown products is phenylalanine (PHE), a known inhibitor of intestinal alkaline phosphatase (IAP), a gut enzyme shown to prevent metabolic syndrome in mice. We hypothesized that ASP consumption might contribute to the development of metabolic syndrome based on PHE's inhibition of endogenous IAP. The design of the study was such that for the in vitro model, IAP was added to diet and regular soda, and IAP activity was measured. For the acute model, a closed bowel loop was created in mice. ASP or water was instilled into it and IAP activity was measured. For the chronic model, mice were fed chow or high-fat diet (HFD) with/without ASP in the drinking water for 18 weeks. The results were that for the in vitro study, IAP activity was lower (p < 0.05) in solutions containing ASP compared with controls. For the acute model, endogenous IAP activity was reduced by 50% in the ASP group compared with controls (0.2 ± 0.03 vs 0.4 ± 0.24) (p = 0.02). For the chronic model, mice in the HFD + ASP group gained more weight compared with the HFD + water group (48.1 ± 1.6 vs 42.4 ± 3.1, p = 0.0001). Significant difference in glucose intolerance between the HFD ± ASP groups (53 913 ± 4000.58 (mg·min)/dL vs 42 003.75 ± 5331.61 (mg·min)/dL, respectively, p = 0.02). Fasting glucose and serum tumor necrosis factor-alpha levels were significantly higher in the HFD + ASP group (1.23- and 0.87-fold increases, respectively, p = 0.006 and p = 0.01). In conclusion, endogenous IAP's protective effects in regard to the metabolic syndrome may be inhibited by PHE, a metabolite of ASP, perhaps explaining the lack of expected weight loss and metabolic improvements associated with diet drinks.

Vitamin D-restricted high-fat diet down-regulates expression of intestinal alkaline phosphatase isozymes in ovariectomized rats.

PubMed

Nakaoka, Kanae; Yamada, Asako; Noda, Seiko; Goseki-Sone, Masae

2018-05-01

Intestinal alkaline phosphatase (IAP) is expressed at a high concentration in the brush border membrane of intestinal epithelial cells. Intestinal alkaline phosphatase controls bacterial endotoxin-induced inflammation by dephosphorylating lipopolysaccharide and is a gut mucosal defense factor. Previously, we reported that IAP activity in the duodenum was significantly decreased in male rats receiving a high-fat diet with vitamin D restriction. Here, we tested the hypothesis that IAP is also regulated by a vitamin D-restricted high-fat diet in an animal model of menopause. Twenty-four female rats were ovariectomized (OVX), and another 6 female rats were sham operated. The OVX rats were divided into 4 groups and fed experimental diets: a basic control diet, a basic control diet with vitamin D restriction, a high-fat diet, and a high-fat diet with vitamin D restriction. After 28days of the experimental diets, the vitamin D-restricted high-fat diet decreased alkaline phosphatase activity in the duodenum of the OVX groups. The vitamin D-restricted high-fat diet down-regulated mRNA expressions of IAP isozymes in the duodenum of the OVX groups. These findings support the hypothesis that the expression of IAP is suppressed by a vitamin D-restricted high-fat diet in OVX rats. An adequate vitamin D intake and prevention of low vitamin D levels may be important for IAP expression in gut homeostasis. Copyright © 2018 Elsevier Inc. All rights reserved.

Risk of low birth weight and stillbirth associated with indoor air pollution from solid fuel use in developing countries.

PubMed

Pope, Daniel P; Mishra, Vinod; Thompson, Lisa; Siddiqui, Amna Rehana; Rehfuess, Eva A; Weber, Martin; Bruce, Nigel G

2010-01-01

Exposure to indoor air pollution from solid fuel use (IAP) has been linked to approximately 1.5 million annual deaths (World Health Organization (http://www.who.int/indoorair/publications/fuelforlife/en/index.html)) due to acute lower respiratory infections in children <5 years of age and chronic obstructive lung disease and lung cancer in adults. Emerging evidence suggests that IAP increases the risk of other conditions, including adverse pregnancy outcomes. To establish the relation of IAP with birth weight and stillbirth, systematic reviews with meta-analyses were conducted. Studies reporting outcomes of mean birth weight, percentage of low birth weight (LBW; <2,500 g), and/or stillbirth and assessing IAP were identified. Five LBW studies (of 982) and 3 stillbirth studies (of 171) met inclusion criteria for the reviews. Fixed-effect meta-analyses (I(2) = 0%) found that IAP was associated with increased risk of percentage LBW (odds ratio = 1.38, 95% confidence interval: 1.25, 1.52) and stillbirth (odds ratio = 1.51, 95% confidence interval: 1.23, 1.85) and reduced mean birth weight (-95.6 g, 95% confidence interval: -68.5, -124.7). Evidence from secondhand smoke, ambient air pollution, and animal studies--and suggested plausible mechanisms--substantiate these associations. Because a majority of pregnant women in developing countries, where rates of LBW and stillbirth are high, are heavily exposed to IAP, increased relative risk translates into substantial population attributable risks of 21% (LBW) and 26% (stillbirth).

Heliothis zea nudivirus 1 gene hhi1 induces apoptosis which is blocked by the Hz-iap2 gene and a noncoding gene, pag1.

PubMed

Wu, Yueh-Lung; Wu, Carol P; Liu, Catherine Y Y; Lee, Song-Tay; Lee, Hsiao-Ping; Chao, Yu-Chan

2011-07-01

Heliothis zea nudivirus 1 (HzNV-1 or Hz-1 virus), previously regarded as a nonoccluded baculovirus, recently has been placed in the Nudivirus genus. This virus generates HzNV-1 HindIII-I 1 (hhi1) and many other transcripts during productive viral infection; during latent viral infection, however, persistency-associated gene 1 (pag1) is the only gene expressed. In this report, we used transient expression assays to show that hhi1 can trigger strong apoptosis in transfected cells, which can be blocked, at least partially, by the inhibitor of apoptosis genes Autographa californica iap2 (Ac-iap2) and H. zea iap2 (Hz-iap2). In addition to these two genes, unexpectedly, pag1, which encodes a noncoding RNA with no detectable protein product, was found to efficiently suppress hhi1-induced apoptosis. The assay of pro-Sf-caspase-1 processing by hhi1 transfection did not detect the small P12 subunit at any of the time intervals tested, suggesting that hhi1 of HzNV-1 induces apoptosis through alternative caspase pathways.

Propulsion Systems Panel deliberations

NASA Technical Reports Server (NTRS)

Bianca, Carmelo J.; Miner, Robert; Johnston, Lawrence M.; Bruce, R.; Dennies, Daniel P.; Dickenson, W.; Dreshfield, Robert; Karakulko, Walt; Mcgaw, Mike; Munafo, Paul M.

1993-01-01

The Propulsion Systems Panel was established because of the specialized nature of many of the materials and structures technology issues related to propulsion systems. This panel was co-chaired by Carmelo Bianca, MSFC, and Bob Miner, LeRC. Because of the diverse range of missions anticipated for the Space Transportation program, three distinct propulsion system types were identified in the workshop planning process: liquid propulsion systems, solid propulsion systems and nuclear electric/nuclear thermal propulsion systems.

Propulsion Systems Panel deliberations

NASA Astrophysics Data System (ADS)

Bianca, Carmelo J.; Miner, Robert; Johnston, Lawrence M.; Bruce, R.; Dennies, Daniel P.; Dickenson, W.; Dreshfield, Robert; Karakulko, Walt; McGaw, Mike; Munafo, Paul M.

1993-02-01

The Propulsion Systems Panel was established because of the specialized nature of many of the materials and structures technology issues related to propulsion systems. This panel was co-chaired by Carmelo Bianca, MSFC, and Bob Miner, LeRC. Because of the diverse range of missions anticipated for the Space Transportation program, three distinct propulsion system types were identified in the workshop planning process: liquid propulsion systems, solid propulsion systems and nuclear electric/nuclear thermal propulsion systems.

Coronary heart disease and household air pollution from use of solid fuel: a systematic review.

PubMed

Fatmi, Zafar; Coggon, David

2016-06-01

Evidence is emerging that indoor air pollution (IAP) from use of solid fuels for cooking and heating may be an important risk factor for coronary heart disease (CHD). We searched the Ovid Medline, Embase Classic, Embase and Web of Science databases from inception through to June 12, 2015, to identify reports of primary epidemiological research concerning the relationship of CHD to IAP from solid fuel, the likely magnitude of any increase in risk, and potential pathogenic mechanisms. The current balance of epidemiological evidence points to an increased risk of CHD from IAP as a consequence of using solid, and especially biomass, fuels for cooking and heating. Relative risks from long-term exposure could be 2- to 4-fold. The evidence base is still limited, and although an association of CHD with such IAP from solid fuel is consistent with the known hazards from smoking, environmental tobacco smoke and ambient air pollution, and supported by evidence of effects on inflammatory processes, atherosclerosis and blood pressure, it requires confirmation by larger and more robust studies. The completion of two relatively small case-control studies on CHD and IAP from use of biomass fuel demonstrates the feasibility of such research, and is an encouragement to further, larger studies using similar methods. The need for such research is particularly pressing because the incidence of CHD in developing countries is rising, and IAP may interact synergistically with the risk factors that are driving that increase. Furthermore, relatively cheap methods are available to reduce IAP from use of solid fuels, and there are indications from intervention studies that these may impact beneficially on CHD as well as other diseases caused by such pollution. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

The effect of intermittent intraabdominal pressure elevations and low cardiac output on the femoral to carotid arterial blood pressure difference in piglets.

PubMed

Aksakal, Devrim; Hückstädt, Thomas; Richter, Steffen; Klitscher, Daniela; Wowra, Tobias; Schier, Felix; Wessel, Lucas M; Kubiak, Rainer

2016-11-01

Our previous work in a laparoscopic setting in piglets revealed that the systolic femoral artery pressure was approximately 5 % higher than its carotid counterpart, whereas the mean and diastolic values showed no significant difference. This remained idem when the intraabdominal pressure (IAP) was gradually increased. In this study, we aimed to investigate the effect of (1) intermittent IAP elevations and (2) a low cardiac output (CO) on the blood pressure (BP) difference cranially (carotid artery) and caudally (femoral artery) of a capnoperitoneum (ΔP = P a fem -P a carot ). A total of twenty-two piglets (mean body weight 11.0 kg; range 8.9-13.3 kg) were studied. Of these, 14 underwent intermittent IAP elevations at 8 and 16 mmHg, and ΔP was measured. In another 8 piglets, a model of reduced CO was created by introducing an air embolism (2 ml/kg over 30 s) in the inferior caval vein (VCI) at 12 mmHg IAP to further assess the influence of this variable on ΔP. Systolic ΔP remained at a mean of 5.6 mmHg and was not significantly affected by insufflation or exsufflation up to an IAP of 16 mmHg. Diastolic and mean values showed no differences between P a carot and P a fem . P a fem, systol remained higher than its carotid counterpart as long as the cardiac index (CI) was above 1.5 l/min/m 2 , but fell significantly below P a carot, systol at a low CI. There was no CO-dependent effect on diastolic and mean ΔP. Repeated IAP elevations do not significantly influence ΔP. Intermittent IAP elevations do not significantly influence ΔP. Despite of a CO-dependent inversion of systolic ΔP, mean BP measurements at the leg during laparoscopy remain representative even at low CO values.

Early enteral nutrition prevents intra-abdominal hypertension and reduces the severity of severe acute pancreatitis compared with delayed enteral nutrition: a prospective pilot study.

PubMed

Sun, Jia-Kui; Li, Wei-Qin; Ke, Lu; Tong, Zhi-Hui; Ni, Hai-Bin; Li, Gang; Zhang, Lu-Yao; Nie, Yao; Wang, Xin-Ying; Ye, Xiang-Hong; Li, Ning; Li, Jie-Shou

2013-09-01

To investigate the effects of early enteral nutrition (EEN) on intra-abdominal pressure (IAP) and disease severity in patients with severe acute pancreatitis (SAP). Enteral nutrition (EN) was started within 48 h after admission in the EEN group and from the 8th day in the delayed enteral nutrition (DEN) group. The IAP and intra-abdominal hypertension (IAH) incidence were recorded for 2 weeks. The caloric intake and feeding intolerance (FI) incidence were recorded daily after EN was started. The severity markers and clinical outcome variables were also recorded. Sixty patients were enrolled to this study. No difference about IAP was found. The IAH incidence of the EEN group was significantly lower than that of the DEN group from the 9th day (8/30 versus 18/30; P = 0.009) after admission. The FI incidence of the EEN group was higher than that of the DEN group during the initial 3 days of feeding (25/30 versus 12/30; P = 0.001; 22/30 versus 9/30; P = 0.001; 15/30 versus 4/30; P = 0.002). Patients with an IAP <15 mmHg had lower FI incidence than those with an IAP ≥15 mmHg on the 1st day (20/22 versus 17/38; P < 0.001), the 3rd day (11/13 versus 8/47; P < 0.001), and the 7th day (3/5 versus 3/55; P = 0.005) of feeding. The severity markers and clinical outcome variables of the EEN group were significantly improved. Early enteral nutrition did not increase IAP. In contrast, it might prevent the development of IAH. In addition, EEN might be not appropriate during the initial 3-4 days of SAP onset. Moreover, EN might be of benefit to patients with an IAP <15 mmHg. Early enteral nutrition could improve disease severity and clinical outcome, but did not decrease mortality of SAP.

Role of Microphysical Parameterizations with Droplet Relative Dispersion in IAP AGCM 4.1

DOE PAGES

Xie, Xiaoning; Zhang, He; Liu, Xiaodong; ...

2018-01-10

In previous studies we see that accurate descriptions of the cloud droplet effective radius (Re) and the autoconversion process of cloud droplets to raindrops (Au) can effectively improve simulated clouds and surface precipitation, and reduce the uncertainty of aerosol indirect effects in global climate models (GCMs). In this paper, we implement cloud microphysical schemes including two-moment Au and R e considering relative dispersion of the cloud droplet size distribution into version 4.1 of the Institute of Atmospheric Physics atmospheric GCM (IAP AGCM 4.1), which is the atmospheric component of the Chinese Academy of Sciences-Earth System model (CAS-ESM 1.0). An analysismore » of the effects of different schemes shows that the newly implemented schemes can improve both the simulated shortwave (SWCF) and longwave cloud radiative forcings (LWCF) as compared to the standard scheme in IAP AGCM 4.1. The new schemes also effectively enhance the large-scale precipitation, especially over low latitudes, although the influences of total precipitation are insignificant for different schemes. Further studies show that similar results can be found with the Community Atmosphere Model 5.1 (CAM5.1).« less

Role of Microphysical Parameterizations with Droplet Relative Dispersion in IAP AGCM 4.1

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

Xie, Xiaoning; Zhang, He; Liu, Xiaodong

In previous studies we see that accurate descriptions of the cloud droplet effective radius (Re) and the autoconversion process of cloud droplets to raindrops (Au) can effectively improve simulated clouds and surface precipitation, and reduce the uncertainty of aerosol indirect effects in global climate models (GCMs). In this paper, we implement cloud microphysical schemes including two-moment Au and R e considering relative dispersion of the cloud droplet size distribution into version 4.1 of the Institute of Atmospheric Physics atmospheric GCM (IAP AGCM 4.1), which is the atmospheric component of the Chinese Academy of Sciences-Earth System model (CAS-ESM 1.0). An analysismore » of the effects of different schemes shows that the newly implemented schemes can improve both the simulated shortwave (SWCF) and longwave cloud radiative forcings (LWCF) as compared to the standard scheme in IAP AGCM 4.1. The new schemes also effectively enhance the large-scale precipitation, especially over low latitudes, although the influences of total precipitation are insignificant for different schemes. Further studies show that similar results can be found with the Community Atmosphere Model 5.1 (CAM5.1).« less

Finite-volume Atmospheric Model of the IAP/LASG (FAMIL)

NASA Astrophysics Data System (ADS)

Bao, Q.

2015-12-01

The Finite-volume Atmospheric Model of the IAP/LASG (FAMIL) is introduced in this work. FAMIL have the flexible horizontal and vertical resolutions up to 25km and 1Pa respectively, which currently running on the "Tianhe 1A&2" supercomputers. FAMIL is the atmospheric component of the third-generation Flexible Global Ocean-Atmosphere-Land climate System model (FGOALS3) which will participate in the Coupled Model Intercomparison Project Phase 6 (CMIP6). In addition to describing the dynamical core and physical parameterizations of FAMIL, this talk describes the simulated characteristics of energy and water balances, precipitation, Asian Summer Monsoon and stratospheric circulation, and compares them with observational/reanalysis data. Finally, the model biases as well as possible solutions are discussed.

Revised Indian Academy of Pediatrics 2015 growth charts for height, weight and body mass index for 5-18-year-old Indian children.

PubMed

Khadilkar, Vaman V; Khadilkar, Anuradha V

2015-01-01

Growth chart committee of Indian Academy of Pediatrics (IAP) has revised growth charts for 5-18-year-old Indian children in Jan 2015. The last IAP growth charts (2007) were based on data collected in 1989-92 which is now >2 decades old. India is in an economic and nutrition transition and hence growth pattern of Indian children has changed over last few years. Thus, it was necessary to produce contemporary, updated growth references for Indian children. The new IAP charts were prepared by collating data from nine groups who had published studies in indexed journals on growth from India in the last decade. Growth charts were constructed from a total of 87022 middle and upper socioeconomic class children (m 54086, f 32936) from all five zones of India. Data from middle and upper socioeconomic class children are likely to have higher prevalence of overweight and obesity and hence growth charts produced on such populations are likely to "normalize" obesity. To remove such unhealthy weights form the data, method suggested by World Health Organization was used to produce weight charts. Thus, the new IAP weight charts are much lower than the recently published studies on affluent Indian children. Since Indian's are at a higher risk of obesity-related cardiometabolic complications at lower body mass index (BMI), BMI charts adjusted for 23, and 27 adult equivalent cut-offs as per International obesity task force guidelines were constructed. IAP now recommends use of these new charts to replace the 2007 IAP charts.

Responses of intra-abdominal pressure and abdominal muscle activity during dynamic trunk loading in man.

PubMed

Cresswell, A G

1993-01-01

The purpose of this study was to determine and compare interactions between the abdominal musculature and intra-abdominal pressure (IAP) during controlled dynamic and static trunk muscle loading. Myoelectric activity was recorded in six subjects from the rectus abdominis, obliquus externus, obliquus internus, transversus abdominis and erector spinae muscles using surface and intra-muscular fine-wire electrodes. The IAP was recorded intra-gastrically. Trunk flexions and extensions were performed lying on one side on a swivel table. An adjustable brake provided different friction loading conditions, while adding weights to an unbraked swivel table afforded various levels of inertial loading. During trunk extensions at all friction loads, IAP was elevated (1.8-7.2 kPa) with concomitant activity in transversus abdominis and obliquus internus muscles--little or no activity was seen from rectus abdominis and obliquus externus muscles. For inertia loading during trunk extension, IAP levels were somewhat lower (1.8-5.6 kPa) and displayed a second peak when abdominal muscle activity occurred in the course of decelerating the movement. For single trunk flexions with friction loading, IAP was higher than that seen in extension conditions and increased with added resistance. For inertial loading during trunk flexion, IAP showed two peaks, the larger first peak matched peak forward acceleration and general abdominal muscle activation, while the second corresponded to peak deceleration and was accompanied by activity in transversus abdominis and erector spinae muscles. It was apparent that different loading strategies produced markedly different patterns of response in both trunk musculature and intra-abdominal pressure.

22 CFR Appendix A to Part 62 - Certification of Responsible Officers and Sponsors

Code of Federal Regulations, 2013 CFR

2013-04-01

... IAP-66 transferred to it. Signed in ink by (Name) (Title) Witness: This ______ day of ______, 19... of or accounting for all Forms IAP-66 transferred to it. Signed in ink by (Name) (Title) Attestation...

22 CFR Appendix A to Part 62 - Certification of Responsible Officers and Sponsors

Code of Federal Regulations, 2012 CFR

2012-04-01

... IAP-66 transferred to it. Signed in ink by (Name) (Title) Witness: This ______ day of ______, 19... of or accounting for all Forms IAP-66 transferred to it. Signed in ink by (Name) (Title) Attestation...

22 CFR Appendix A to Part 62 - Certification of Responsible Officers and Sponsors

Code of Federal Regulations, 2014 CFR

2014-04-01

... IAP-66 transferred to it. Signed in ink by (Name) (Title) Witness: This ______ day of ______, 19... of or accounting for all Forms IAP-66 transferred to it. Signed in ink by (Name) (Title) Attestation...

22 CFR Appendix A to Part 62 - Certification of Responsible Officers and Sponsors

Code of Federal Regulations, 2010 CFR

2010-04-01

... IAP-66 transferred to it. Signed in ink by (Name) (Title) Witness: This ______ day of ______, 19... of or accounting for all Forms IAP-66 transferred to it. Signed in ink by (Name) (Title) Attestation...

22 CFR Appendix A to Part 62 - Certification of Responsible Officers and Sponsors

Code of Federal Regulations, 2011 CFR

2011-04-01

... IAP-66 transferred to it. Signed in ink by (Name) (Title) Witness: This ______ day of ______, 19... of or accounting for all Forms IAP-66 transferred to it. Signed in ink by (Name) (Title) Attestation...

Expression of inhibitor of apoptosis proteins (IAPs) in rat granulosa cells during ovarian follicular development and atresia.

PubMed

Li, J; Kim, J M; Liston, P; Li, M; Miyazaki, T; Mackenzie, A E; Korneluk, R G; Tsang, B K

1998-03-01

The inhibitor of apoptosis proteins (IAPs) constitute a family of highly conserved apoptosis suppressor proteins that was originally identified in baculoviruses. Although IAP homologs have been recently identified and demonstrated to suppress apoptosis in mammalian cells, their expression and role during follicular development and atresia are unknown. The present study was conducted to address these questions. Using established in vivo models for the induction of follicular development and atresia in immature rats, it was possible to compare the immunolocalization of X-link inhibitor of apoptosis protein (Xiap) and human inhibitor of apoptosis protein-2 (Hiap-2), two members of the IAP family, at defined stages of follicular maturation and to relate the differences observed with those of follicular cell proliferation and apoptosis [as determined by proliferating cell nuclear antigen (PCNA) immunohistochemistry and in situ terminal deoxynucleotidyl transferase-mediated dUTP-biotin end labeling (TUNEL), respectively]. In addition, granulosa cell DNA and proteins were assessed for apoptotic fragmentation by 3'-end labeling/agarose gel electrophoresis (DNA ladder) and Hiap-2 and Xiap protein content by Western blot analysis, respectively. Hiap-2 and Xiap expression in both granulosa and theca cells increased with follicular maturation, reaching maximal levels at the antral stage of development. The immunoreactivity for PCNA, Xiap, and Hiap-2 decreased markedly in atretic (TUNEL-positive) follicles at the small to medium sized antral stage of development, suggesting follicular atresia may be associated with decreased granulosa cell IAP protein content and decreased proliferation. Atresia was also associated with a change in the intracellular distribution of IAPs in granulosa cells. Biochemical analysis of DNA fragmentation (DNA ladder) in granulosa cells from preantral and early antral follicles indicates extensive apoptosis that was associated with minimal IAP protein content. Gonadotropin treatment increased Hiap-2 and Xiap protein content and suppressed apoptosis in granulosa cells, resulting in the development of follicles to the antral and preovulatory stages. In addition, gonadotropin withdrawal induced apoptotic DNA fragmentation in granulosa cells in early antral and antral follicles, which is accompanied by a marked decrease in Hiap-2 and Xiap expression. These data suggest that IAPs may be involved in the suppression of granulosa cell apoptosis by gonadotropin in small to medium-sized antral follicles and play an important role in determining the fate of the cells, and thus also the eventual follicular destiny (atresia vs. ovulation).

The role of abdominal compliance, the neglected parameter in critically ill patients - a consensus review of 16. Part 1: definitions and pathophysiology.

PubMed

Malbrain, Manu L N G; Roberts, Derek J; De Laet, Inneke; De Waele, Jan J; Sugrue, Michael; Schachtrupp, Alexander; Duchesne, Juan; Van Ramshorst, Gabrielle; De Keulenaer, Bart; Kirkpatrick, Andrew W; Ahmadi-Noorbakhsh, Siavash; Mulier, Jan; Ivatury, Rao; Pracca, Francisco; Wise, Robert; Pelosi, Paolo

2014-01-01

Over the last few decades, increasing attention has been paid to understanding the pathophysiology, aetiology, prognosis, and treatment of elevated intra-abdominal pressure (IAP) in trauma, surgical, and medical patients. However, there is presently a relatively poor understanding of intra-abdominal volume (IAV) and the relationship between IAV and IAP (i.e. abdominal compliance). Consensus definitions on Cab were discussed during the 5th World Congress on Abdominal Compartment Syndrome and a writing committee was formed to develop this article. During the writing process, a systematic and structured Medline and PubMed search was conducted to identify relevant studies relating to the topic. According to the recently updated consensus definitions of the World Society on Abdominal Compartment Syndrome (WSACS), abdominal compliance (Cab) is defined as a measure of the ease of abdominal expansion, which is determined by the elasticity of the abdominal wall and diaphragm. It should be expressed as the change in IAV per change in IAP (mL [mm Hg]⁻¹). Importantly, Cab is measured differently than IAP and the abdominal wall (and its compliance) is only a part of the total abdominal pressure-volume (PV) relationship. During an increase in IAV, different phases are encountered: the reshaping, stretching, and pressurisation phases. The first part of this review article starts with a comprehensive list of the different definitions related to IAP (at baseline, during respiratory variations, at maximal IAV), IAV (at baseline, additional volume, abdominal workspace, maximal and unadapted volume), and abdominal compliance and elastance (i.e. the relationship between IAV and IAP). An historical background on the pathophysiology related to IAP, IAV and Cab follows this. Measurement of Cab is difficult at the bedside and can only be done in a case of change (removal or addition) in IAV. The Cab is one of the most neglected parameters in critically ill patients, although it plays a key role in understanding the deleterious effects of unadapted IAV on IAP and end-organ perfusion. The definitions presented herein will help to understand the key mechanisms in relation to Cab and clinical conditions and should be used for future clinical and basic science research. Specific measurement methods, guidelines and recommendations for clinical management of patients with low Cab are published in a separate review.

Affective reactions differ between Chinese and American healthy young adults: a cross-cultural study using the international affective picture system.

PubMed

Huang, Jinwen; Xu, Dongrong; Peterson, Bradley S; Hu, Jianbo; Cao, Linfeng; Wei, Ning; Zhang, Yingran; Xu, Weijuan; Xu, Yi; Hu, Shaohua

2015-03-27

Several cross-cultural studies have suggested that emotions are influenced by the cultural background. Emotional reactions to International Affective Picture System (IAPS) images were compared between Chinese and American young adults. 120 Chinese undergraduates (53 females, 67 males; aged 18-25 years) were enrolled at Zhejiang University, China, and the valence and arousal components of their emotional responses to IAPS images were rated using the Self-Assessment Manikin (SAM) system. Then, valence and arousal scores were compared to those of 100 American undergraduates (50 females, 50 males) of the same age group, enrolled at Florida University and surveyed by Prof. PJ Lang in 2001. Valence scores assigned to 259/816 (31.74%) pictures differed significantly between Chinese and American female participants, while those assigned to 165/816 (20.22%) pictures differed significantly between Chinese and American males (P < 6 × 10(-5)). Of the 816 pictures, the arousal scores assigned to 101/816 (12.38%) pictures differed significantly between Chinese and American female participants; these scores significantly differed in 130/816 (15.93%) pictures between Chinese and American males (P < 6 × 10(-5)). Valence scores for pictures in the Erotic category differed significantly between Chinese and American females (P < 6 × 10(-5)). There were no significant differences in valence scores for the remaining eight categories studied between participants from the two countries, whether female or male. The IAPS norms require a modification for their appropriate application in Asian cultures.

XIAP Limits Autophagic Degradation of Sox2 and Is A Therapeutic Target in Nasopharyngeal Carcinoma Stem Cells

PubMed Central

Ji, Jiao; Yu, Yan; Li, Zhi-Ling; Chen, Ming-Yuan; Deng, Rong; Huang, Xiang; Wang, Guang-Feng; Zhang, Meng-Xia; Yang, Qi; Ravichandran, Senthilkumar; Feng, Gong-Kan; Xu, Xue-Lian; Yang, Chen-Lu; Qiu, Miao-Zhen; Jiao, Lin; Yang, Dajun; Zhu, Xiao-Feng

2018-01-01

Rationale: Nasopharyngeal carcinoma (NPC) is the most frequent head and neck tumor in South China. The presence of cancer stem cells (CSCs) in NPC contributes to tumor maintenance and therapeutic resistance, while the ability of CSCs to escape from the apoptosis pathway may render them the resistant property to the therapies. Inhibitor of apoptosis proteins family proteins (IAPs), which are overexpressed in nasopharyngeal carcinoma stem cells, may play an important role in maintaining nasopharyngeal cancer stem cell properties. Here, we develop a novel CSC-targeting strategy to treat NPC through inhibiting IAPs. Methods: Human NPC S-18 and S-26 cell lines were used as the model system in vitro and in vivo. Fluorescence activated cell sorting (FACS) assay was used to detect nasopharyngeal SP cells and CD44+ cells. The characteristics of CSCs were defined by sphere suspension culture, colony formation assay and cell migration. The role of XIAP on the regulation of Sox2 protein stability and ERK1-mediated phosphorylation of Sox2 signaling pathway were analyzed using immunoblotting, immunoprecipitation, immunofluorescence, phosphorylation mass spectrometry, siRNA silencing and plasmid overexpression. The correlation between XIAP and Sox2 in NPC biopsies and their role in prognosis was performed by immunohistochemistry. APG-1387 or chemotherapies-induced cell death and apoptosis in S-18 and S-26 were determined by WST, immunoblotting and flow cytometry assay. Results: IAPs, especially X chromosome-linked IAP (XIAP), were elevated in CSCs of NPC, and these proteins were critically involved in the maintenance of CSCs properties by enhancing the stability of Sox2. Mechanistically, ERK1 kinase promoted autophagic degradation of Sox2 via phosphorylation of Sox2 at Ser251 and further SUMOylation of Sox2 at Lys245 in non-CSCs. However, XIAP blocked autophagic degradation of Sox2 by inhibiting ERK1 activation in CSCs. Additionally, XIAP was positively correlated with Sox2 expression in NPC tissues, which were associated with NPC progression. Finally, we discovered that a novel antagonist of IAPs, APG-1387, exerted antitumor effect on CSCs. Also, the combination of APG-1387 with CDDP /5-FU has a synergistic effect on NPC. Conclusion: Our study highlights the importance of IAPs in the maintenance of CSCs in NPC. Thus, XIAP is a promising therapeutic target in CSCs and suggests that NPC patients may benefit from a combination treatment of APG-1387 with conventional chemotherapy. PMID:29556337

Evaluation of prototype air carrier instrument approach procedure charts.

DOT National Transportation Integrated Search

1995-07-31

The objective of this study was to evaluate the design features of two prototype Instrument Approach Procedure (IAP) charts. The John A. Volpe National Transportation System's Center in cooperation with the Air Transport Association's Chart and Data ...

Electronic depiction of Instrument Approach Procedure (IAP) charts phase 1: development and evaluation

DOT National Transportation Integrated Search

1995-05-01

This report describes the research program being conducted at the Volpe National Transportation Systems Center on the development of electronic aeronautical charts. The design of electronic aeronautical navigation charts raises many interrelated huma...

Evaluation of prototype air carrier instrument approach procedure charts

DOT National Transportation Integrated Search

1995-07-01

The objective of this study was to evaluate the design features of two prototype Instrument Approach Procedure (IAP) charts. The John A. Volpe National Transportation Systems Center in cooperation with the Air Transport Association's Chart and Data D...

Robust generation of isolated attosecond pulse against the variation of carrier envelope phase of driving laser pulses

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

Zou Pu; Zeng Zhinan; Zheng Yinghui

2010-11-15

We propose a scheme for generating isolated attosecond pulse (IAP) via high-order harmonic generation in gases using a chirped two-color laser field of multicycle duration. In contrast to previous techniques where the stable carrier-envelope phase (CEP) of the driving laser pulses is a prerequisite for IAP generation, the proposed scheme is robust against the large variation of CEP. We show the generation of IAP with an intensity fluctuation less than 50% and an intensity contrast ratio higher than 5:1 when the CEP shift is as large as 1.35{pi}.

Inducing death in tumor cells: roles of the inhibitor of apoptosis proteins.

PubMed

Finlay, Darren; Teriete, Peter; Vamos, Mitchell; Cosford, Nicholas D P; Vuori, Kristiina

2017-01-01

The heterogeneous group of diseases collectively termed cancer results not just from aberrant cellular proliferation but also from a lack of accompanying homeostatic cell death. Indeed, cancer cells regularly acquire resistance to programmed cell death, or apoptosis, which not only supports cancer progression but also leads to resistance to therapeutic agents. Thus, various approaches have been undertaken in order to induce apoptosis in tumor cells for therapeutic purposes. Here, we will focus our discussion on agents that directly affect the apoptotic machinery itself rather than on drugs that induce apoptosis in tumor cells indirectly, such as by DNA damage or kinase dependency inhibition. As the roles of the Bcl-2 family have been extensively studied and reviewed recently, we will focus in this review specifically on the inhibitor of apoptosis protein (IAP) family. IAPs are a disparate group of proteins that all contain a baculovirus IAP repeat domain, which is important for the inhibition of apoptosis in some, but not all, family members. We describe each of the family members with respect to their structural and functional similarities and differences and their respective roles in cancer. Finally, we also review the current state of IAPs as targets for anti-cancer therapeutics and discuss the current clinical state of IAP antagonists.

Characterization of mammalian glucose transport proteins using photoaffinity labeling techniques

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

Wadzinski, B.E.

1989-01-01

A carrier-free radioiodinated phenylazide derivative of forskolin, 3-iodo-4-azidophenethylamido-7-O-succinyl-deacetyl-forskolin (({sup 125}I)IAPS-forskolin), has been shown to be a highly selective photoaffinity probe for the human erythrocyte glucose transported and the glucose transport proteins found in several mammalian tissues and cultured cells where the glucose transport protein is present at a low concentration. The photoincorporation of ({sup 125}I)IAPS-forskolin into these glucose transporters was blocked by D- (but not L-) glucose, cytochalasin B, and forskolin. In addition to labeling the mammalian glucose transport proteins, ({sup 125}I)IAPS-forskolin also labeled the L-arabinose transporter from E. coli. In muscle and adipose tissues, glucose transport is markedly increasedmore » in response to insulin. ({sup 125}I)IAPS-forskolin was shown to selectivity tag the glucose transporter in membranes derived from these cells. In addition, the covalent derivatization of the transport protein in subcellular fractions of the adipocyte has provided a means to study the hormonal regulation of glucose transport. ({sup 125}I)IAPS-forskolin has also been used to label the purified human erythrocyte glucose transporter. The site of insertion has therefore been localized by analysis of the radiolabeled peptides which were produced following chemical and proteolytic digestion of the labeled transport protein.« less

Latency and Persistence of 'Candidatus Liberibacter asiaticus' in Its Psyllid Vector, Diaphorina citri (Hemiptera: Liviidae).

PubMed

Canale, Maria Cristina; Tomaseto, Arthur Fernando; Haddad, Marineia de Lara; Della Coletta-Filho, Helvécio; Lopes, João Roberto Spotti

2017-03-01

Although 'Candidatus Liberibacter asiaticus' (Las) is a major pathogen associated with citrus huanglongbing (HLB), some characteristics of transmission by the psyllid vector Diaphorina citri are not fully understood. We examined the latent period and persistence of transmission of Las by D. citri in a series of experiments at 25°C, in which third-instar psyllid nymphs and 1-week-old adults were confined on infected citrus for an acquisition access period (AAP), and submitted to sequential inoculation access periods (IAPs) on healthy citrus seedlings. The median latent period (LP 50 , i.e., acquisition time after which 50% of the individuals can inoculate) of 16.8 and 17.8 days for psyllids that acquired Las as nymphs and adults, respectively, was determined by transferring single individuals in 48-h IAPs. Inoculation events were intermittent and randomly distributed over the IAPs, but were more frequent after acquisition by nymphs. A minimum latent period of 7 to 10 days was observed by transferring groups of 10 psyllids in 48-h IAPs, after a 96-h AAP by nymphs. Psyllids transmitted for up to 5 weeks, when submitted to sequential 1-week IAPs after a 14-day AAP as nymphs. The long latent period and persistence of transmission are indirect evidences of circulative propagation of Las in D. citri.

Curcumin Induces Pancreatic Adenocarcinoma Cell Death via Reduction of the Inhibitors of Apoptosis

PubMed Central

Osterman, Carlos J. Díaz; Gonda, Amber; Stiff, TessaRae; Sigaran, Ulysses; Valenzuela, Malyn May Asuncion; Bennit, Heather R. Ferguson; Moyron, Ron B.; Khan, Salma; Wall, Nathan R.

2015-01-01

Objectives The inhibitor of apoptosis (IAP) proteins are critical modulators of chemotherapeutic resistance in various cancers. To address the alarming emergence of chemotherapeutic resistance in pancreatic cancer, we investigated the efficacy of the turmeric derivative curcumin in reducing IAP protein and mRNA expression resulting in pancreatic cancer cell death. Methods The pancreatic adenocarcinoma cell line PANC-1 was used to assess curcumin’s effects in pancreatic cancer. Curcumin uptake was measured by spectral analysis and fluorescence microscopy. AlamarBlue and Trypan blue exclusion assays were used to determine PANC-1 cell viability following curcumin treatment. Visualization of PANC-1 cell death was performed using Hoffman Modulation Contrast microscopy. Western blot and PCR analyses were used to evaluate curcumin’s effects on IAP protein and mRNA expression. Results Curcumin enters PANC-1 cells and is ubiquitously present within the cell following treatment. Furthermore, curcumin reduces cell viability and induces morphological changes characteristic of cell death. Additionally, curcumin decreases IAP protein and mRNA expression in PANC-1 cells. Conclusions These data demonstrate that PANC-1 cells are sensitive to curcumin treatment. Furthermore, curcumin as a potential therapeutic tool for overcoming chemotherapeutic resistance mediated by IAPs, supports a role for curcumin as part of the therapeutic approach for pancreatic cancer. PMID:26348467

Autophagy-mediated degradation of IAPs and c-FLIP L potentiates apoptosis induced by combination of TRAIL and Chal-24

DOE PAGES

Xu, Jennings; Xu, Xiuling; Shi, Shaoqing; ...

2015-11-02

Combination chemotherapy is an effective strategy for increasing anticancer efficacy, reducing side effects and alleviating drug resistance. In this paper, we report that combination of the recently identified novel chalcone derivative, chalcone-24 (Chal-24), and TNF-related apoptosis-inducing ligand (TRAIL) significantly increases cytotoxicity in lung cancer cells. Chal-24 treatment significantly enhanced TRAIL-induced activation of caspase-8 and caspase-3, and the cytotoxicity induced by combination of these agents was effectively suppressed by the pan-caspase inhibitor z-VAD-fmk. Chal-24 and TRAIL combination suppressed expression of cellular FLICE (FADD-like IL-1β-converting enzyme)-inhibitory protein large (c-FLIPL) and cellular inhibitor of apoptosis proteins (c-IAPs), and ectopic expression of c-FLIPL andmore » c-IAPs inhibited the potentiated cytotoxicity. In addition, TRAIL and Chal-24 cooperatively activated autophagy. Suppression of autophagy effectively attenuated cytotoxicity induced by Chal-24 and TRAIL combination, which was associated with attenuation of c-FLIPL and c-IAPs degradation. In conclusion, these results suggest that Chal-24 potentiates the anticancer activity of TRAIL through autophagy-mediated degradation of c-FLIPL and c-IAPs, and that combination of Chal-24 and TRAIL could be an effective approach in improving chemotherapy efficacy.« less

Spacecraft Chemical Propulsion Systems at NASA's Marshall Space Flight Center: Heritage and Capabilities

NASA Technical Reports Server (NTRS)

McRight, Patrick S.; Sheehy, Jeffrey A.; Blevins, John A.

2005-01-01

NASA Marshall Space Flight Center (MSFC) is well known for its contributions to large ascent propulsion systems such as the Saturn V and the Space Shuttle. This paper highlights a lesser known but equally rich side of MSFC - its heritage in spacecraft chemical propulsion systems and its current capabilities for in-space propulsion system development and chemical propulsion research. The historical narrative describes the efforts associated with developing upper-stage main propulsion systems such as the Saturn S-IVB as well as orbital maneuvering and reaction control systems such as the S-IVB auxiliary propulsion system, the Skylab thruster attitude control system, and many more recent activities such as Chandra, the Demonstration of Automated Rendezvous Technology, X-37, the X-38 de-orbit propulsion system, the Interim Control Module, the US Propulsion Module, and several technology development activities. Also discussed are MSFC chemical propulsion research capabilities, along with near- and long-term technology challenges to which MSFC research and system development competencies are relevant.

Guanosine 5'-triphosphate binding protein (G/sub i/) and two additional pertussis toxin substrates associated with muscarinic receptors in rat heart myocytes: characterization and age dependency

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

Moscona-Amir, E.; Henis, Y.I.; Sokolovsky, M.

1988-07-12

The coupling of muscarinic receptors with G-proteins was investigated in cultured myocytes prepared from the hearts of newborn rats. The coupling was investigated in both young (5 days after plating) and aged (14 days after plating) cultures, in view of the completely different effects of 5'-guanylyl imidodiphosphate (Gpp(NH)p) on muscarinic agonist binding to homogenates from young vs aged cultures. Pretreatment of cultures from both ages by Bordetella pertussis toxin (IAP) was found to eliminate any Gpp(NH)p effect on carbamylcholine binding. IAP by itself induced a rightward shift in the carbamylcholine competition curve in homogenates from aged cultures, but no suchmore » effect was observed in homogenates from young cultures. IAP-catalyzed (/sup 32/P)ADP-ribosylation of membrane preparations from young and aged cultures revealed major differences between them. Young cultures exhibited a major IAP substrate at 40 kDa, which was also recognized by anti-..cap alpha../sub i/ antibodies, and two novel IAP substrates at 28 and 42 kDa, which were weakly ADP-ribosylated by the toxin and were not recognized with either anti-..cap alpha../sub i/ or anti-..cap alpha../sub 0/ antibodies. In aged cultures, only the 40-kDa band (ribosylated to a lower degree) was detected. The parallel age-dependent changes in the three IAP substrates (28, 40, and 42 kDa) and in the interactions of the G-protein(s) with the muscarinic receptors strongly suggest close association between the two phenomena. All of these age-dependent changes in the G-protein related parameters were prevented by phosphatidylcholine-liposome treatment of the aged cultures. The role of the membrane lipid composition in these phenomena is discussed.« less

Diagnosis of chronic conditions with modifiable lifestyle risk factors in selected urban and rural areas of Bangladesh and sociodemographic variability therein

PubMed Central

2011-01-01

Background Bangladesh suffers from a lack of healthcare providers. The growing chronic disease epidemic's demand for healthcare resources will further strain Bangladesh's limited healthcare workforce. Little is known about how Bangladeshis with chronic disease seek care. This study describes chronic disease patients' care seeking behavior by analyzing which providers diagnose these diseases. Methods During 2 month periods in 2009, a cross-sectional survey collected descriptive data on chronic disease diagnoses among 3 surveillance populations within the International Center for Diarrheal Disease Research, Bangladesh (ICDDR, B) network. The maximum number of respondents (over age 25) who reported having ever been diagnosed with a chronic disease determined the sample size. Using SAS software (version 8.0) multivariate regression analyses were preformed on related sociodemographic factors. Results Of the 32,665 survey respondents, 8,591 self reported having a chronic disease. Chronically ill respondents were 63.4% rural residents. Hypertension was the most prevalent disease in rural (12.4%) and urban (16.1%) areas. In rural areas chronic disease diagnoses were made by MBBS doctors (59.7%) and Informal Allopathic Providers (IAPs) (34.9%). In urban areas chronic disease diagnoses were made by MBBS doctors (88.0%) and IAP (7.9%). Our analysis identified several groups that depended heavily on IAP for coverage, particularly rural, poor and women. Conclusion IAPs play important roles in chronic disease care, particularly in rural areas. Input and cooperation from IAPs are needed to minimize rural health disparities. More research on IAP knowledge and practices regarding chronic disease is needed to properly utilize this potential healthcare resource. PMID:22078128

Preliminary Assessment of Using Gelled and Hybrid Propellant Propulsion for VTOL/SSTO Launch Systems

NASA Technical Reports Server (NTRS)

Palaszewski, Bryan; OLeary, Robert; Pelaccio, Dennis G.

1998-01-01

A novel, reusable, Vertical-Takeoff-and-Vertical-Takeoff-and-Landing, Single-Stage-to-Orbit (VTOL/SSTO) launch system concept, named AUGMENT-SSTO, is presented in this paper to help quantify the advantages of employing gelled and hybrid propellant propulsion system options for such applications. The launch vehicle system concept considered uses a highly coupled, main high performance liquid oxygen/liquid hydrogen (LO2/LH2) propulsion system, that is used only for launch, while a gelled or hybrid propellant propulsion system auxiliary propulsion system is used during final orbit insertion, major orbit maneuvering, and landing propulsive burn phases of flight. Using a gelled or hybrid propellant propulsion system for major orbit maneuver burns and landing has many advantages over conventional VTOL/SSTO concepts that use LO2/LH2 propulsion system(s) burns for all phases of flight. The applicability of three gelled propellant systems, O2/H2/Al, O2/RP-1/Al, and NTO/MMH/Al, and a state-of-the-art (SOA) hybrid propulsion system are examined in this study. Additionally, this paper addresses the applicability of a high performance gelled O2/H2 propulsion system to perform the primary, as well as the auxiliary propulsion system functions of the vehicle.

Resource Document for the Design of Electronic Instrument Approach Procedure Displays

DOT National Transportation Integrated Search

1995-03-01

Instrument approach procedure (IAP) charts play a large role in contributing to the success or failure of approaches and : landings. Paper IAP charts have been criticized for excessive clutter, for text sizes that are too small to read, and : for ina...

Targeting Non-proteolytic Protein Ubiquitination for the Treatment of Diffuse Large B Cell Lymphoma.

PubMed

Yang, Yibin; Kelly, Priscilla; Shaffer, Arthur L; Schmitz, Roland; Yoo, Hee Min; Liu, Xinyue; Huang, Da Wei; Webster, Daniel; Young, Ryan M; Nakagawa, Masao; Ceribelli, Michele; Wright, George W; Yang, Yandan; Zhao, Hong; Yu, Xin; Xu, Weihong; Chan, Wing C; Jaffe, Elaine S; Gascoyne, Randy D; Campo, Elias; Rosenwald, Andreas; Ott, German; Delabie, Jan; Rimsza, Lisa; Staudt, Louis M

2016-04-11

Chronic active B cell receptor (BCR) signaling, a hallmark of the activated B cell-like (ABC) subtype of diffuse large B cell lymphoma (DLBCL), engages the CARD11-MALT1-BCL10 (CBM) adapter complex to activate IκB kinase (IKK) and the classical NF-κB pathway. Here we show that the CBM complex includes the E3 ubiquitin ligases cIAP1 and cIAP2, which are essential mediators of BCR-dependent NF-κB activity in ABC DLBCL. cIAP1/2 attach K63-linked polyubiquitin chains on themselves and on BCL10, resulting in the recruitment of IKK and the linear ubiquitin chain ligase LUBAC, which is essential for IKK activation. SMAC mimetics target cIAP1/2 for destruction, and consequently suppress NF-κB and selectively kill BCR-dependent ABC DLBCL lines, supporting their clinical evaluation in patients with ABC DLBCL. Copyright © 2016 Elsevier Inc. All rights reserved.

Electrolysis Propulsion for Spacecraft Applications

NASA Technical Reports Server (NTRS)

deGroot, Wim A.; Arrington, Lynn A.; McElroy, James F.; Mitlitsky, Fred; Weisberg, Andrew H.; Carter, Preston H., II; Myers, Blake; Reed, Brian D.

1997-01-01

Electrolysis propulsion has been recognized over the last several decades as a viable option to meet many satellite and spacecraft propulsion requirements. This technology, however, was never used for in-space missions. In the same time frame, water based fuel cells have flown in a number of missions. These systems have many components similar to electrolysis propulsion systems. Recent advances in component technology include: lightweight tankage, water vapor feed electrolysis, fuel cell technology, and thrust chamber materials for propulsion. Taken together, these developments make propulsion and/or power using electrolysis/fuel cell technology very attractive as separate or integrated systems. A water electrolysis propulsion testbed was constructed and tested in a joint NASA/Hamilton Standard/Lawrence Livermore National Laboratories program to demonstrate these technology developments for propulsion. The results from these testbed experiments using a I-N thruster are presented. A concept to integrate a propulsion system and a fuel cell system into a unitized spacecraft propulsion and power system is outlined.

Connective tissue growth factor confers drug resistance in breast cancer through concomitant up-regulation of Bcl-xL and cIAP1.

PubMed

Wang, Ming-Yang; Chen, Pai-Sheng; Prakash, Ekambaranellore; Hsu, Hsing-Chih; Huang, Hsin-Yi; Lin, Ming-Tsan; Chang, King-Jen; Kuo, Min-Liang

2009-04-15

Connective tissue growth factor (CTGF) expression is elevated in advanced breast cancer and promotes metastasis. Chemotherapy response is only transient in most metastatic diseases. In the present study, we examined whether CTGF expression could confer drug resistance in human breast cancer. In breast cancer patients who received neoadjuvant chemotherapy, CTGF expression was inversely associated with chemotherapy response. Overexpression of CTGF in MCF7 cells (MCF7/CTGF) enhanced clonogenic ability, cell viability, and resistance to apoptosis on exposure to doxorubicin and paclitaxel. Reducing the CTGF level in MDA-MB-231 (MDA231) cells by antisense CTGF cDNA (MDA231/AS cells) mitigated this drug resistance capacity. CTGF overexpression resulted in resistance to doxorubicin- and paclitaxel-induced apoptosis by up-regulation of Bcl-xL and cellular inhibitor of apoptosis protein 1 (cIAP1). Knockdown of Bcl-xL or cIAP1 with specific small interfering RNAs abolished the CTGF-mediated resistance to apoptosis induced by the chemotherapeutic agents in MCF7/CTGF cells. Inhibition of extracellular signal-regulated kinase (ERK)-1/2 effectively reversed the resistance to apoptosis as well as the up-regulation of Bcl-xL and cIAP1 in MCF7/CTGF cells. A neutralizing antibody against integrin alpha(v)beta(3) significantly attenuated CTGF-mediated ERK1/2 activation and up-regulation of Bcl-xL and cIAP1, indicating that the integrin alpha(v)beta(3)/ERK1/2 signaling pathway is essential for CTGF functions. The Bcl-xL level also correlated with the CTGF level in breast cancer patients. We also found that a COOH-terminal domain peptide from CTGF could exert activities similar to full-length CTGF, in activation of ERK1/2, up-regulation of Bcl-xL/cIAP1, and resistance to apoptosis. We conclude that CTGF expression could confer resistance to chemotherapeutic agents through augmenting a survival pathway through ERK1/2-dependent Bcl-xL/cIAP1 up-regulation.

Inhibition of the gut enzyme intestinal alkaline phosphatase may explain how aspartame promotes glucose intolerance and obesity in mice

PubMed Central

Gul, Sarah S.; Hamilton, A. Rebecca L.; Munoz, Alexander R.; Phupitakphol, Tanit; Liu, Wei; Hyoju, Sanjiv K.; Economopoulos, Konstantinos P.; Morrison, Sara; Hu, Dong; Zhang, Weifeng; Gharedaghi, Mohammad Hadi; Huo, Haizhong; Hamarneh, Sulaiman R.; Hodin, Richard A.

2017-01-01

Diet soda consumption has not been associated with tangible weight loss. Aspartame (ASP) commonly substitutes sugar and one of its breakdown products is phenylalanine (PHE), a known inhibitor of intestinal alkaline phosphatase (IAP), a gut enzyme shown to prevent metabolic syndrome in mice. We hypothesized that ASP consumption might contribute to the development of metabolic syndrome based on PHE’s inhibition of endogenous IAP. The design of the study was such that for the in vitro model, IAP was added to diet and regular soda, and IAP activity was measured. For the acute model, a closed bowel loop was created in mice. ASP or water was instilled into it and IAP activity was measured. For the chronic model, mice were fed chow or high-fat diet (HFD) with/without ASP in the drinking water for 18 weeks. The results were that for the in vitro study, IAP activity was lower (p < 0.05) in solutions containing ASP compared with controls. For the acute model, endogenous IAP activity was reduced by 50% in the ASP group compared with controls (0.2 ± 0.03 vs 0.4 ± 0.24) (p = 0.02). For the chronic model, mice in the HFD + ASP group gained more weight compared with the HFD + water group (48.1 ± 1.6 vs 42.4 ± 3.1, p = 0.0001). Significant difference in glucose intolerance between the HFD ± ASP groups (53 913 ± 4000.58 (mg·min)/dL vs 42 003.75 ± 5331.61 (mg·min)/dL, respectively, p = 0.02). Fasting glucose and serum tumor necrosis factor-alpha levels were significantly higher in the HFD + ASP group (1.23- and 0.87-fold increases, respectively, p = 0.006 and p = 0.01). In conclusion, endogenous IAP’s protective effects in regard to the metabolic syndrome may be inhibited by PHE, a metabolite of ASP, perhaps explaining the lack of expected weight loss and metabolic improvements associated with diet drinks. PMID:27997218

Ground correlation investigation of thruster spacecraft interactions to be measured on the IAPS flight test

NASA Technical Reports Server (NTRS)

Power, J. L.

1984-01-01

Preliminary ground correlation testing has been conducted with an 8 cm mercury ion thruster and diagnostic instrumentation replicating to a large extent the IAPS flight test hardware, configuration, and electrical grounding/isolation. Thruster efflux deposition retained at 25 C was measured and characterized. Thruster ion efflux was characterized with retarding potential analyzers. Thruster-generated plasma currents, the spacecraft common (SCC) potential, and ambient plasma properties were evaluated with a spacecraft potential probe (SPP). All the measured thruster/spacecraft interactions or their IAPS measurements depend critically on the SCC potential, which can be controlled by a neutralizer ground switch and by the SPP operation.

Solar-Powered Electric Propulsion Systems: Engineering and Applications

NASA Technical Reports Server (NTRS)

Stearns, J. W.; Kerrisk, D. J.

1966-01-01

Lightweight, multikilowatt solar power arrays in conjunction with electric propulsion offer potential improvements to space exploration, extending the usefulness of existing launch vehicles to higher-energy missions. Characteristics of solar-powered electric propulsion missions are outlined, and preliminary performance estimates are shown. Spacecraft system engineering is discussed with respect to parametric trade-offs in power and propulsion system design. Relationships between mission performance and propulsion system performance are illustrated. The present state of the art of electric propulsion systems is reviewed and related to the mission requirements identified earlier. The propulsion system design and test requirements for a mission spacecraft are identified and discussed. Although only ion engine systems are currently available, certain plasma propulsion systems offer some advantages in over-all system design. These are identified, and goals are set for plasma-thrustor systems to make them competitive with ion-engine systems for mission applications.

Introduction: The challenge of optimum integration of propulsion systems and large space structures

NASA Technical Reports Server (NTRS)

Carlisle, R. F.

1980-01-01

A functional matrix of possible propulsion system characteristics for a spacecraft for deployable and assembled spacecraft structures shows that either electric propulsion or low thrust chemical propulsion systems could provide the propulsion required. The trade-off considerations of a single propulsion engine or multiengines are outlined and it is shown that a single point engine is bounded by some upper limit of thrust for assembled spacecraft. The matrix also shows several additional functions that can be provided to the spacecraft if a propulsion system is an integral part of the spacecraft. A review of all of the functions that can be provided for a spacecraft by an integral propulsion system may result in the inclusion of the propulsion for several functions even if no single function were mandatory. Propulsion interface issues for each combination of engines are identified.

46 CFR 62.35-5 - Remote propulsion-control systems.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 2 2014-10-01 2014-10-01 false Remote propulsion-control systems. 62.35-5 Section 62.35... AUTOMATION Requirements for Specific Types of Automated Vital Systems § 62.35-5 Remote propulsion-control systems. (a) Manual propulsion control. All vessels having remote propulsion control from the navigating...

46 CFR 62.35-5 - Remote propulsion-control systems.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 2 2013-10-01 2013-10-01 false Remote propulsion-control systems. 62.35-5 Section 62.35... AUTOMATION Requirements for Specific Types of Automated Vital Systems § 62.35-5 Remote propulsion-control systems. (a) Manual propulsion control. All vessels having remote propulsion control from the navigating...

46 CFR 62.35-5 - Remote propulsion-control systems.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 2 2011-10-01 2011-10-01 false Remote propulsion-control systems. 62.35-5 Section 62.35... AUTOMATION Requirements for Specific Types of Automated Vital Systems § 62.35-5 Remote propulsion-control systems. (a) Manual propulsion control. All vessels having remote propulsion control from the navigating...

46 CFR 62.35-5 - Remote propulsion-control systems.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 2 2010-10-01 2010-10-01 false Remote propulsion-control systems. 62.35-5 Section 62.35... AUTOMATION Requirements for Specific Types of Automated Vital Systems § 62.35-5 Remote propulsion-control systems. (a) Manual propulsion control. All vessels having remote propulsion control from the navigating...

46 CFR 62.35-5 - Remote propulsion-control systems.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 2 2012-10-01 2012-10-01 false Remote propulsion-control systems. 62.35-5 Section 62.35... AUTOMATION Requirements for Specific Types of Automated Vital Systems § 62.35-5 Remote propulsion-control systems. (a) Manual propulsion control. All vessels having remote propulsion control from the navigating...

Join This Cool Club!

ERIC Educational Resources Information Center

Novelli, Joan

1995-01-01

Students can study the Arctic by creating Arctic clubs, using modems to communicate with students nationwide who are following International Arctic Project (IAP) explorers. The article describes the IAP, explains how to form a club, and discusses issues that clubs can tackle, for example, pollution, Arctic animals, natural resources, and the…

Electric Propulsion Applications and Impacts

NASA Technical Reports Server (NTRS)

Curran, Frank M.; Wickenheiser, Timothy J.

1996-01-01

Most space missions require on-board propulsion systems and these systems are often dominant spacecraft mass drivers. Presently, on-board systems account for more than half the injected mass for commercial communications systems and even greater mass fractions for ambitious planetary missions. Anticipated trends toward the use of both smaller spacecraft and launch vehicles will likely increase pressure on the performance of on-board propulsion systems. The acceptance of arcjet thrusters for operational use on commercial communications satellites ushered in a new era in on-board propulsion and exponential growth of electric propulsion across a broad spectrum of missions is anticipated. NASA recognizes the benefits of advanced propulsion and NASA's Office of Space Access and Technology supports an aggressive On-Board Propulsion program, including a strong electric propulsion element, to assure the availability of high performance propulsion systems to meet the goals of the ambitious missions envisioned in the next two decades. The program scope ranges from fundamental research for future generation systems through specific insertion efforts aimed at near term technology transfer. The On-Board propulsion program is committed to carrying technologies to levels required for customer acceptance and emphasizes direct interactions with the user community and the development of commercial sources. This paper provides a discussion of anticipated missions, propulsion functions, and electric propulsion impacts followed by an overview of the electric propulsion element of the NASA On-Board Propulsion program.

High-speed flight propulsion systems. Progress in Astronautics and Aeronautics. Vol. 137

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

Murthy, S.N.B.; Curran, E.T.

1991-01-01

Various papers on high-speed flight propulsion systems are presented. The topics addressed are: propulsion systems from takeoff to high-speed flight, propulsion system performance and integration for high Mach air-breathing flight, energy analysis of high-speed flight systems, waves and thermodynamics in high Mach number propulsive ducts, turbulent free shear layer mixing and combustion, turbulent mixing in supersonic combustion systems, mixing and mixing enhancement in supersonic reacting flowfields, study of combustion and heat-exchange processes in high-enthalpy short-duration facilities, and facility requirements for hypersonic propulsion system testing.

Cost-effective technology advancement directions for electric propulsion transportation systems in earth-orbital missions

NASA Technical Reports Server (NTRS)

Regetz, J. D., Jr.; Terwilliger, C. H.

1979-01-01

The directions that electric propulsion technology should take to meet the primary propulsion requirements for earth-orbital missions in the most cost effective manner are determined. The mission set requirements, state of the art electric propulsion technology and the baseline system characterized by it, adequacy of the baseline system to meet the mission set requirements, cost optimum electric propulsion system characteristics for the mission set, and sensitivities of mission costs and design points to system level electric propulsion parameters are discussed. The impact on overall costs than specific masses or costs of propulsion and power systems is evaluated.

Status of the NASA YF-12 Propulsion Research Program

NASA Technical Reports Server (NTRS)

Albers, J. A.

1976-01-01

The YF-12 research program was initiated to establish a technology base for the design of an efficient propulsion system for supersonic cruise aircraft. The major technology areas under investigation in this program are inlet design analysis, propulsion system steady-state performance, propulsion system dynamic performance, inlet and engine control systems, and airframe/propulsion system interactions. The objectives, technical approach, and status of the YF-12 propulsion program are discussed. Also discussed are the results obtained to date by the NASA Ames, Lewis, and Dryden research centers. The expected technical results and proposed future programs are also given. Propulsion system configurations are shown.

The Emotional Experience of People with Intellectual Disability: An Analysis Using the International Affective Pictures System

ERIC Educational Resources Information Center

Bermejo, Belen G.; Mateos, Pedro M.; Sanchez-Mateos, Juan Degado

2014-01-01

The present study provides information on the emotional experience of people with intellectual disability. To evaluate this emotional experience, we have used the International Affective Pictures System (IAPS). The most important result from this study is that the emotional reaction of people with intellectual disability to affective stimuli is…

Identification of propulsion systems

NASA Technical Reports Server (NTRS)

Merrill, Walter; Guo, Ten-Huei; Duyar, Ahmet

1991-01-01

This paper presents a tutorial on the use of model identification techniques for the identification of propulsion system models. These models are important for control design, simulation, parameter estimation, and fault detection. Propulsion system identification is defined in the context of the classical description of identification as a four step process that is unique because of special considerations of data and error sources. Propulsion system models are described along with the dependence of system operation on the environment. Propulsion system simulation approaches are discussed as well as approaches to propulsion system identification with examples for both air breathing and rocket systems.

Recommendations of 2nd National Consultative Meeting of Indian Academy of Pediatrics (IAP) on polio eradication and improvement of routine immunization.

PubMed

Vashishtha, Vipin M; Kalra, Ajay; John, T Jacob; Thacker, Naveen; Agarwal, R K

2008-05-01

Persistence of intense wild poliovirus (WPV) transmission, particularly type 3 in northern India necessitated the Indian Academy of Pediatrics (IAP) to convene a National Consultative Meeting to review its earlier recommendations on polio eradication and improvement of routine immunization. More than thirty experts were invited and intense deliberations were held over two days to draw consensus statements on various issues related with polio eradication. To review the ongoing strategy, identify the existing challenges, and suggest modifications to the current strategy for eradication of poliomyelitis in India. IAP reiterates its support to ongoing efforts on polio eradication but demand some flexibility in the strategy. The immediate challenges identified include persistent WPV type 1 transmission in Uttar Pradesh (UP) and Bihar, intense type 3 transmission also in UP and Bihar, and maintaining polio-free status of all other states. Circulating vaccine derived poliovirus (cVDPV), particularly type 2, was identified as a great future threat. Neglect of routine immunization (RI), poor efficacy of oral polio vaccine (OPV), operational issues, and inadequate uptake of OPV in the 2 endemic states are the main reasons of failure to interrupt transmission of WPV 1 and 3. However, for the first time in history the intensity of WPV 1 circulation is very low in western UP. IAP suggests that high-quality, uniform and consistent performance of supplementary immunization activities (SIAs) in all districts of western UP, particularly using mOPV1(monovalent OPV1) should be maintained to avoid reestablishment of circulation of type 1 poliovirus. A judicious mix of mOPV1 and mOPV3, given sequentially or even simultaneously (after validating the efficacies) will be necessary to address the upsurge of WPV3. Re-establishing routine immunization should be the foremost priority. IAP strongly recommends to Government of India (GOI) to take urgent measures to attain coverage of a minimum of 90% against all UIP antigens in all the states by the end of 2008. In view of the need to simultaneously raise immunity levels to protect against WPVs 1, 3 and cVDPV2, IPV may be given immediate consideration as an additional tool. IPV will be essential in the postWPVeradication phase; it can play a useful role even in the current WPV eradication phase. IAP urges the GOI to urgently sort out various issues associated with implementation of the proposal to use IPV. More transparency is needed on cases of vaccine associated paralytic poliomyelitis (VAPP). Further improvement in stool collection rates is also warranted to minimize the tally of compatible cases. IAP urges the social mobilization network to address the issues of waning interest and shifting focus and negative media coverage. Alternate tactics like reduced numbers of SIAs applied in the low transmission season, along with IPVDTP combination vaccine in RI can also be considered. IAP believes it will be risky to stop vaccination against poliomyelitis in postWPV eradication phase. The best option is to gradually introduce IPV starting now, so that a switch to IPV following high-performance national immunization days (NIDs) can be made to ensure sustained high immunity against all polioviruses, wild and vaccine derived. IAP requests the global polio eradication initiative (GPEI) to continue relevant research to inform on various aspects related to polio eradication, defined as zero incidence of any poliovirus infection. IAP also urges GOI to take immediate measures for improvement of environmental sanitation.

Predicting and evaluation the severity in acute pancreatitis using a new modeling built on body mass index and intra-abdominal pressure.

PubMed

Fei, Yang; Gao, Kun; Tu, Jianfeng; Wang, Wei; Zong, Guang-Quan; Li, Wei-Qin

2017-06-03

Acute pancreatitis (AP) keeps as severe medical diagnosis and treatment problem. Early evaluation for severity and risk stratification in patients with AP is very important. Some scoring system such as acute physiology and chronic health evaluation-II (APACHE-II), the computed tomography severity index (CTSI), Ranson's score and the bedside index of severity of AP (BISAP) have been used, nevertheless, there're a few shortcomings in these methods. The aim of this study was to construct a new modeling including intra-abdominal pressure (IAP) and body mass index (BMI) to evaluate the severity in AP. The study comprised of two independent cohorts of patients with AP, one set was used to develop modeling from Jinling hospital in the period between January 2013 and October 2016, 1073 patients were included in it; another set was used to validate modeling from the 81st hospital in the period between January 2012 and December 2016, 326 patients were included in it. The association between risk factors and severity of AP were assessed by univariable analysis; multivariable modeling was explored through stepwise selection regression. The change in IAP and BMI were combined to generate a regression equation as the new modeling. Statistical indexes were used to evaluate the value of the prediction in the new modeling. Univariable analysis confirmed change in IAP and BMI to be significantly associated with severity of AP. The predict sensitivity, specificity, positive predictive value, negative predictive value and accuracy by the new modeling for severity of AP were 77.6%, 82.6%, 71.9%, 87.5% and 74.9% respectively in the developing dataset. There were significant differences between the new modeling and other scoring systems in these parameters (P < 0.05). In addition, a comparison of the area under receiver operating characteristic curves of them showed a statistically significant difference (P < 0.05). The same results could be found in the validating dataset. A new modeling based on IAP and BMI is more likely to predict the severity of AP. Copyright © 2017. Published by Elsevier Inc.

Comparison of Mars Aircraft Propulsion Systems

NASA Technical Reports Server (NTRS)

Colozza, Anthony J.

2003-01-01

The propulsion system is a critical aspect of the performance and feasibility of a Mars aircraft. Propulsion system mass and performance greatly influence the aircraft s design and mission capabilities. Various propulsion systems were analyzed to estimate the system mass necessary for producing 35N of thrust within the Mars environment. Three main categories of propulsion systems were considered: electric systems, combustion engine systems and rocket systems. Also, the system masses were compared for mission durations of 1, 2, and 4 h.

Advanced NSTS propulsion system verification study

NASA Technical Reports Server (NTRS)

Wood, Charles

1989-01-01

The merits of propulsion system development testing are discussed. The existing data base of technical reports and specialists is utilized in this investigation. The study encompassed a review of all available test reports of propulsion system development testing for the Saturn stages, the Titan stages, and the Space Shuttle main propulsion system. The knowledge on propulsion system development and system testing available from specialists and managers was also 'tapped' for inclusion.

Spatio-temporal shaping of photocathode laser pulses for linear electron accelerators

NASA Astrophysics Data System (ADS)

Mironov, S. Yu; Andrianov, A. V.; Gacheva, E. I.; Zelenogorskii, V. V.; Potemkin, A. K.; Khazanov, E. A.; Boonpornprasert, P.; Gross, M.; Good, J.; Isaev, I.; Kalantaryan, D.; Kozak, T.; Krasilnikov, M.; Qian, H.; Li, X.; Lishilin, O.; Melkumyan, D.; Oppelt, A.; Renier, Y.; Rublack, T.; Felber, M.; Huck, H.; Chen, Y.; Stephan, F.

2017-10-01

Methods for the spatio-temporal shaping of photocathode laser pulses for generating high brightness electron beams in modern linear accelerators are discussed. The possibility of forming triangular laser pulses and quasi-ellipsoidal structures is analyzed. The proposed setup for generating shaped laser pulses was realised at the Institute of Applied Physics (IAP) of the Russian Academy of Sciences (RAS). Currently, a prototype of the pulse-shaping laser system is installed at the Photo Injector Test facility at DESY, Zeuthen site (PITZ). Preliminary experiments on electron beam generation using ultraviolet laser pulses from this system were carried out at PITZ, in which electron bunches with a 0.5-nC charge and a transverse normalized emittance of 1.1 mm mrad were obtained. A new scheme for the three-dimensional shaping of laser beams using a volume Bragg profiled grating is proposed at IAP RAS and is currently being tested for further electron beam generation experiments at the PITZ photoinjector.

INSPACE CHEMICAL PROPULSION SYSTEMS AT NASA's MARSHALL SPACE FLIGHT CENTER: HERITAGE AND CAPABILITIES

NASA Technical Reports Server (NTRS)

McRight, P. S.; Sheehy, J. A.; Blevins, J. A.

2005-01-01

NASA s Marshall Space Flight Center (MSFC) is well known for its contributions to large ascent propulsion systems such as the Saturn V rocket and the Space Shuttle external tank, solid rocket boosters, and main engines. This paper highlights a lesser known but very rich side of MSFC-its heritage in the development of in-space chemical propulsion systems and its current capabilities for spacecraft propulsion system development and chemical propulsion research. The historical narrative describes the flight development activities associated with upper stage main propulsion systems such as the Saturn S-IVB as well as orbital maneuvering and reaction control systems such as the S-IVB auxiliary propulsion system, the Skylab thruster attitude control system, and many more recent activities such as Chandra, the Demonstration of Automated Rendezvous Technology (DART), X-37, the X-38 de-orbit propulsion system, the Interim Control Module, the US Propulsion Module, and multiple technology development activities. This paper also highlights MSFC s advanced chemical propulsion research capabilities, including an overview of the center s Propulsion Systems Department and ongoing activities. The authors highlight near-term and long-term technology challenges to which MSFC research and system development competencies are relevant. This paper concludes by assessing the value of the full range of aforementioned activities, strengths, and capabilities in light of NASA s exploration missions.

X-37 Storable Propulsion System Design and Operations

NASA Technical Reports Server (NTRS)

Rodriguez, Henry; Popp, Chris; Rehagen, Ronald J.

2005-01-01

In a response to NASA's X-37 TA-10 Cycle-1 contract, Boeing assessed nitrogen tetroxide (N2O4) and monomethyl hydrazine (MMH) Storable Propellant Propulsion Systems to select a low risk X-37 propulsion development approach. Space Shuttle lessons learned, planetary spacecraft, and Boeing Satellite HS-601 systems were reviewed to arrive at a low risk and reliable storable propulsion system. This paper describes the requirements, trade studies, design solutions, flight and ground operational issues which drove X-37 toward the selection of a storable propulsion system. The design of storable propulsion systems offers the leveraging of hardware experience that can accelerate progress toward critical design. It also involves the experience gained from launching systems using MMH and N2O4 propellants. Leveraging of previously flight-qualified hardware may offer economic benefits and may reduce risk in cost and schedule. This paper summarizes recommendations based on experience gained from Space Shuttle and similar propulsion systems utilizing MMH and N2O4 propellants. System design insights gained from flying storable propulsion are presented and addressed in the context of the design approach of the X-37 propulsion system.

X-37 Storable Propulsion System Design and Operations

NASA Technical Reports Server (NTRS)

Rodriguez, Henry; Popp, Chris; Rehegan, Ronald J.

2006-01-01

In a response to NASA's X-37 TA-10 Cycle-1 contract, Boeing assessed nitrogen tetroxide (N2O4) and monomethyl hydrazine (MMH) Storable Propellant Propulsion Systems to select a low risk X-37 propulsion development approach. Space Shuttle lessons learned, planetary spacecraft, and Boeing Satellite HS-601 systems were reviewed to arrive at a low risk and reliable storable propulsion system. This paper describes the requirements, trade studies, design solutions, flight and ground operational issues which drove X-37 toward the selection of a storable propulsion system. The design of storable propulsion systems offers the leveraging of hardware experience that can accelerate progress toward critical design. It also involves the experience gained from launching systems using MMH and N2O4 propellants. Leveraging of previously flight-qualified hardware may offer economic benefits and may reduce risk in cost and schedule. This paper summarizes recommendations based on experience gained from Space Shuttle and similar propulsion systems utilizing MMH and N2O4 propellants. System design insights gained from flying storable propulsion are presented and addressed in the context of the design approach of the X-37 propulsion system.

Advanced space power and propulsion based on lasers

NASA Astrophysics Data System (ADS)

Roth, M.; Logan, B. G.

2015-10-01

One of the key components for future space exploration, manned or unmanned, is the availability of propulsion systems beyond the state of the art. The rapid development in conventional propulsion systems since the middle of the 20th century has already reached the limits of chemical propulsion technology. To enhance mission radius, shorten the transit time and also extend the lifetime of a spacecraft more efficient, but still powerful propulsion system must be developed. Apart from the propulsion system a major weight contribution arises from the required energy source. Envisioning rapid development of future high average power laser systems and especially the ICAN project we review the prospect of advanced space propulsion based on laser systems.

Electro-acupuncture attenuates inflammatory responses and intraabdominal pressure in septic patients: A randomized controlled trial.

PubMed

Meng, Jian-Biao; Jiao, Yan-Na; Xu, Xiu-Juan; Lai, Zhi-Zhen; Zhang, Geng; Ji, Chun-Lian; Hu, Ma-Hong

2018-04-01

A pathological increase in intraabdominal pressure (IAP) and inflammatory responses have negative effects on splanchnic, respiratory, cardiovascular, renal, and neurological function in septic patients with intestinal dysfunction. Electro-acupuncture (EA) has been evidenced to have a bidirectional neuron-endocrine-immune system regulating effect in patients with intestinal dysfunction. The purpose of current study was to evaluate the effects of EA at "Zusanli" (ST36) and "Shangjuxu" (ST37) on inflammatory responses and IAP in septic patients with intestinal dysfunction manifested syndrome of obstruction of the bowels Qi. Eighty-two septic patients with intestinal dysfunction manifested syndrome of obstruction of the bowels Qi were randomly assigned to control group (n = 41) and EA group (n = 41). Patients in control group were given conventional therapies including fluid resuscitation, antiinfection, vasoactive agents, mechanical ventilation (MV), supply of enteral nutrition, and glutamine as soon as possible. In addition to conventional therapies, patients in EA group underwent 20-minutes of EA at ST36-ST37 twice a day for 5 days. At baseline, posttreatment 1, 3, and 7 days, serum levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) and IAP levels, were measured, respectively. And days on MV, length of stay in intensive care unit (ICU) and 28 days mortality were recorded. The serum levels of TNF-α and IL-1β and IAP levels at posttreatment 1, 3, and 7 days were lower significantly in the EA group compared with the control group (mean [SD]; 61.03 [20.39] vs 79.28 [20.69]; P < .005, mean [SD]; 35.34 [18.75] vs 66.53 [30.43]; P < .005 and mean [SD]; 20.32 [11.30] vs 32.99 [20.62]; P = .001, respectively, TNF-α. Mean [SD]; 14.11 [5.21] vs 16.72 [5.59]; P = .032, mean [SD]; 9.02 [3.62] vs 12.10 [4.13]; P = .001 and mean [SD]; 5.11 [1.79] vs 8.19 [2.99]; P < .005, respectively, IL-1β. Mean [SD]; 14.83 [5.58] vs 17.55 [3.37]; P = .009, mean [SD]; 11.20 [2.57] vs 14.85 [3.01]; P < .005 and mean [SD]; 8.62 [2.55] vs 11.25 [2.72]; P < .005, respectively, IAP). There were no significant differences in the duration of MV, length of stay in ICU, and 28d mortality between the groups. EA at ST36-ST37 attenuated inflammatory responses through reduction in serum levels of TNF-α and IL-1β and IAP in septic patients with intestinal dysfunction manifested syndrome of obstruction of the bowels Qi.

Pharmacist and physician satisfaction and rates of switching to preferred medications associated with an instant prior authorization program for proton pump inhibitors in the North Carolina Medicaid program.

PubMed

Jacobson Vann, Julie C; Christofferson, Stephanie; Humble, Charles G; Wegner, Steven E; Feaganes, John R; Trygstad, Troy K

2010-05-01

Proton pump inhibitors (PPIs) are among the highest expenditure drugs covered by health care plans. During fiscal year 2001-2002, Medicaid programs nationwide spent nearly $2 billion on PPIs. Although the costs of individual PPIs vary widely, there is little variation in therapeutic effectiveness. On June 1, 2007, the North Carolina Medicaid program implemented an "instant approval" option simultaneously with a prior authorization (PA) program for PPIs with the goal of managing costs and maintaining high-quality care. Preferred PPIs included generic omeprazole and Prilosec OTC. This instant approval process (IAP) was expected to impose less administrative burden than is typically associated with PA programs by permitting physician and nonphysician prescribers to either write the PA criteria directly on a prescription form or use "MD Easy," a preprinted form that could be faxed by the prescriber to the dispensing pharmacy. A previous study found that from the prescriber's perspective the IAP reduced practice-related administrative burden and was associated with a reduced gap in PPI therapy when compared with traditional PA. To evaluate the acceptability and effectiveness of this IAP for PPIs as assessed by the outcome measures of (a) pharmacist satisfaction with the IAP; (b) physician and pharmacist satisfaction with the MD Easy form; and (c) utilization rates for preferred PPIs, comparing medical practices that used the MD Easy form with practices that did not. A cross-sectional design was used to assess pharmacist and physician satisfaction. A stratified random sample of 240 pharmacies was selected from 1,561 North Carolina pharmacies with claims in the Medicaid claims data file during state fiscal year 2006. Additionally, a stratified random sample of 240 medical practices was selected from 1,045 primary care practices serving Medicaid beneficiaries during 2006. Surveys were administered to pharmacists using either in-person interviews or self-administered questionnaires and to physicians using a mailed questionnaire with follow-up to nonrespondents. An interrupted time series analysis was used to evaluate the effect of the MD Easy form on switching to preferred PPIs using paid Medicaid claims of surveyed practices from calendar year 2007. Practices that reported both using the IAP and receiving the MD Easy form were defined as MD Easy users. Monthly market share data were analyzed using log negative binomial regression models to account for autocorrelation in the time series data. The pharmacy survey was completed by 202 (84.2%) pharmacies selected for participation. Of 198 permanently employed pharmacists, 140 (70.7%) reported experience with the IAP for PPIs. More than two-thirds (68.6%) of the pharmacist respondents with IAP experience indicated that the IAP is better (34.3%) or much better (34.3%) than traditional PA with RESEARCH respect to overall administrative burden of phone calls, faxes, patient interactions, and doctor contacts. Surveys were completed by 171 (71.3%) of selected physician practices, of which 56 (32.7%) reported experience with the MD Easy forms. Of practices that recalled receiving the MD Easy forms, 52 of 56 (92.9%) reported that the forms "very much" or "somewhat" helped prevent gaps in PPI therapy; 54 of 55 (98.2%) reported that they helped identify patients affected by Medicaid PPI PA; and 100% reported that they helped physicians to follow PA requirements. Immediately after implementation of the IAP and MD Easy form, the observed market share of preferred PPIs increased by 4.1 times (95% CI = 3.57-4.62). From May to June 2007, the preferred PPI market share increased by 64.0 percentage points, from 19.3% to 83.3% (P < 0.001), for practices that reported using the IAP and receiving the MD Easy form (n = 56) and by 55.4 percentage points, from 21.8% to 77.2% (P < 0.001), for practices that either (a) reported not receiving the MD Easy form (n = 25) or (b) reported not using the IAP (n = 84) or (c) did not respond to the survey item asking about the MD Easy form (n = 4). The overall increase in preferred PPI market share after implementation of the IAP was 1.29 times higher for practices that used the MD Easy form than for those that did not based on negative binomial regression modeling; this difference approached statistical significance (95% CI = 1.00-1.68; P = 0.053). This study suggests that an IAP for PPIs using either handwritten prescriptions or a preprinted form is an effective alternative to traditional PA. The IAP was associated with an increase in market share for preferred PPIs and was perceived by pharmacists as less administratively burdensome than traditional PA. Additional studies are needed to determine sustainability and the applicability to other prescription drugs.

Understanding the dynamics in distribution of invasive alien plant species under predicted climate change in Western Himalaya

PubMed Central

Chitale, Vishwas; Rijal, Srijana Joshi; Bisht, Neha; Shrestha, Bharat Babu

2018-01-01

Invasive alien plant species (IAPS) can pose severe threats to biodiversity and stability of native ecosystems, therefore, predicting the distribution of the IAPS plays a crucial role in effective planning and management of ecosystems. In the present study, we use Maximum Entropy (MaxEnt) modelling approach to predict the potential of distribution of eleven IAPS under future climatic conditions under RCP 2.6 and RCP 8.5 in part of Kailash sacred landscape region in Western Himalaya. Based on the model predictions, distribution of most of these invasive plants is expected to expand under future climatic scenarios, which might pose a serious threat to the native ecosystems through competition for resources in the study area. Native scrublands and subtropical needle-leaved forests will be the most affected ecosystems by the expansion of these IAPS. The present study is first of its kind in the Kailash Sacred Landscape in the field of invasive plants and the predictions of potential distribution under future climatic conditions from our study could help decision makers in planning and managing these forest ecosystems effectively. PMID:29664961

PET imaging and quantitation of Internet-addicted patients and normal controls

NASA Astrophysics Data System (ADS)

Jeong, Ha-Kyu; Kim, Hee-Joung; Jung, Haijo; Son, Hye-Kyung; Kim, Dong-Hyeon; Yun, Mijin; Shin, Yee-Jin; Lee, Jong-Doo

2002-04-01

Internet addicted patients (IAPs) have widely been increased, as Internet games are becoming very popular in daily life. The purpose of this study was to investigate regional brain activation patterns associated with excessive use of Internet games in adolescents. Six normal controls (NCs) and eight IAPs who were classified as addiction group by adapted version of DSM-IV for pathologic gambling were participated. 18F-FDG PET studies were performed for all adolescents at their rest and activated condition after 20 minutes of each subject's favorite Internet game. To investigate quantitative metabolic differences in both groups, all possible combinations of group comparison were carried out using Statistical Parametric Mapping (SPM 99). Regional brain activation foci were identified on Talairach coordinate. SPM results showed increased metabolic activation in occipital lobes for both groups. Higher metabolisms were seen at resting condition in IAPs than that of in NCs. In comparison to both groups, IAPs showed different patterns of regional brain metabolic activation compared with that of NCs. It suggests that addictive use of Internet games may result in functional alteration of developing brain in adolescents.

Understanding the dynamics in distribution of invasive alien plant species under predicted climate change in Western Himalaya.

PubMed

Thapa, Sunil; Chitale, Vishwas; Rijal, Srijana Joshi; Bisht, Neha; Shrestha, Bharat Babu

2018-01-01

Invasive alien plant species (IAPS) can pose severe threats to biodiversity and stability of native ecosystems, therefore, predicting the distribution of the IAPS plays a crucial role in effective planning and management of ecosystems. In the present study, we use Maximum Entropy (MaxEnt) modelling approach to predict the potential of distribution of eleven IAPS under future climatic conditions under RCP 2.6 and RCP 8.5 in part of Kailash sacred landscape region in Western Himalaya. Based on the model predictions, distribution of most of these invasive plants is expected to expand under future climatic scenarios, which might pose a serious threat to the native ecosystems through competition for resources in the study area. Native scrublands and subtropical needle-leaved forests will be the most affected ecosystems by the expansion of these IAPS. The present study is first of its kind in the Kailash Sacred Landscape in the field of invasive plants and the predictions of potential distribution under future climatic conditions from our study could help decision makers in planning and managing these forest ecosystems effectively.

IKKε-mediated tumorigenesis requires K63-linked polyubiquitination by a cIAP1/cIAP2/TRAF2 E3 ubiquitin ligase complex

PubMed Central

Zhou, Alicia Y.; Shen, Rhine R.; Kim, Eejung; Lock, Ying J.; Xu, Ming; Chen, Zhijian J.; Hahn, William C.

2014-01-01

SUMMARY IκB kinase ε (IKKε, IKBKE) is a key regulator of innate immunity and a breast cancer oncogene, amplified in ~30% of breast cancers, that promotes malignant transformation through NF-κB activation. Here we show that IKKε is modified and regulated by K63-linked polyubiquitination at Lysine 30 and Lysine 401. TNFα and IL-1β stimulation induces IKKε K63-linked polyubiquitination over baseline levels in both macrophages and breast cancer cell lines, and this modification is essential for IKKε kinase activity, IKKε-mediated NF-κB activation and IKKε-induced malignant transformation. Disruption of K63-linked ubiquitination of IKKε does not affect its overall structure but impairs the recruitment of canonical NF-κB proteins. A cIAP1/cIAP2/TRAF2 E3 ligase complex binds to and ubiquitinates IKKε. Together, these observations demonstrate that K63-linked polyubiquitination regulates IKKε activity in both inflammatory and oncogenic contexts and suggests an alterative approach to target this breast cancer oncogene. PMID:23453969

Relationships between hostility, affective ratings of pictures, and state affects during task-induced stress.

PubMed

Heponiemi, Tarja; Ravaja, Niklas; Elovainio, Marko; Keltikangas-Järvinen, Liisa

2007-03-01

The authors examined the relationship of hostility with (a) affective ratings of pictures and (b) state affects evoked by task-induced stress in 95 healthy men and women 22-37 years of age. Pictures were from the International Affective Picture System (IAPS; P. J. Lang, M. M. Bradley, & B. N. Cuthbert, 1999). Stressors included a startle task, mental arithmetic task, and choice-deadline reaction time task. The circumplex model of affect was used to structure the self-reported state affects. The authors found that hostility was associated with displeasure, high arousal, and low dominance ratings of IAPS pictures. Hostility was related to unpleasant affect and unactivated unpleasant affect during the experiment, and subscale paranoia was related to activated unpleasant affect. Findings suggest that participants scoring high on hostility are prone to negative emotional reactions.

Lunar surface base propulsion system study, volume 1

NASA Technical Reports Server (NTRS)

1987-01-01

The efficiency, capability, and evolution of a lunar base will be largely dependent on the transportation system that supports it. Beyond Space Station in low Earth orbit (LEO), a Lunar-derived propellant supply could provide the most important resource for the transportation infrastructure. The key to an efficient Lunar base propulsion system is the degree of Lunar self-sufficiency (from Earth supply) and reasonable propulsion system performance. Lunar surface propellant production requirements must be accounted in the measurement of efficiency of the entire space transportation system. Of all chemical propellant/propulsion systems considered, hydrogen/oxygen (H/O) OTVs appear most desirable, while both H/O and aluminum/oxygen propulsion systems may be considered for the lander. Aluminized-hydrogen/oxygen and Silane/oxygen propulsion systems are also promising candidates. Lunar propellant availability and processing techniques, chemical propulsion/vehicle design characteristics, and the associated performance of the total transportation infrastructure are reviewed, conceptual propulsion system designs and vehicle/basing concepts, and technology requirements are assessed in context of a Lunar Base mission scenario.

Deriving the Generalized Power and Efficiency Equations for Jet Propulsion Systems

NASA Astrophysics Data System (ADS)

Lee, Hsing-Juin; Chang, Chih-Luong

The kinetic power and efficiency equations for general jet propulsion systems are classically given in a much cursory, incomplete, and ununified format. This situation prohibits the propulsion designer from seeing the panorama of interrelated propulsion parameters and effects. And in some cases, it may lead to an energy-inefficient propulsion system design, or induce significant offset in propulsion performance as demonstrated in this study. Thus, herein we attempt to clarify some related concepts and to rigorously derive the associated generalized equations with a complete spectrum of physical parameters to be manipulated in quest of better performance. By a highly efficient interweaved transport scheme, we have derived the following equations for general jet propulsion systems: i.e., generalized total kinetic power, generalized kinetic power delivered to the jet propulsion system, generalized thrust power, generalized available propulsion power, and relevant generalized propulsive, thermal, and overall efficiency equations. Further, the variants of these equations under special conditions are also considered. For taking advantage of the above propulsion theories, we also illustrate some novel propulsion strategies in the final discussion, such as the dive-before-climb launch of rocket from highland mountain on eastbound rail, with perhaps minisatellites as the payloads.

Osthole induces lung cancer cell apoptosis through inhibition of inhibitor of apoptosis family proteins

PubMed Central

Xu, Xiao-Man; Zhang, Man-Li; Zhang, Yi; Zhao, Li

2016-01-01

In the present study, we investigated the effects and mechanisms of Osthole on the apoptosis of non-small cell lung cancer (NSCLC) cells and its synergistic effect with Embelin. Our results revealed that treatment with both Osthole and Embelin inhibited cell proliferation. Notably, combination treatment of Osthole and Embelin inhibited cell proliferation more significantly compared with monotherapy. In addition, morphological analysis and Annexin V/propidium iodide analysis revealed that the combination of Osthole and Embelin enhanced their effect on cell apoptosis. We further examined the effect of Osthole on the expression of inhibitor of apoptosis protein (IAP) family proteins. That treatment of A549 lung cancer cells with various concentrations of Osthole was observed to decrease the protein expression of X-chromosome-encoded IAP, c-IAP1, c-IAP2 and Survivin, and increase Smac expression in a dose-dependent manner. Furthermore, it was noted that Osthole or Embelin alone increased the expression of BAX, caspase-3, caspase-9, cleaved caspase-3 and cleaved caspase-9, and decreased Bcl-2 levels following treatment. Osthole and Embelin combination treatment had a synergistic effect on the regulation of these proteins. In conclusion, our study demonstrated that Osthole inhibited proliferation and induced the apoptosis of lung cancer cells via IAP family proteins in a dose-dependent manner. Osthole enhances the antitumor effect of Embelin, indicating that combination of Osthole and Embelin has potential clinical significance in the treatment of NSCLC. PMID:27895730

Dynamics of hemispheric dominance for language assessed by magnetoencephalographic imaging.

PubMed

Findlay, Anne M; Ambrose, Josiah B; Cahn-Weiner, Deborah A; Houde, John F; Honma, Susanne; Hinkley, Leighton B N; Berger, Mitchel S; Nagarajan, Srikantan S; Kirsch, Heidi E

2012-05-01

The goal of the current study was to examine the dynamics of language lateralization using magnetoencephalographic (MEG) imaging, to determine the sensitivity and specificity of MEG imaging, and to determine whether MEG imaging can become a viable alternative to the intracarotid amobarbital procedure (IAP), the current gold standard for preoperative language lateralization in neurosurgical candidates. MEG was recorded during an auditory verb generation task and imaging analysis of oscillatory activity was initially performed in 21 subjects with epilepsy, brain tumor, or arteriovenous malformation who had undergone IAP and MEG. Time windows and brain regions of interest that best discriminated between IAP-determined left or right dominance for language were identified. Parameters derived in the retrospective analysis were applied to a prospective cohort of 14 patients and healthy controls. Power decreases in the beta frequency band were consistently observed following auditory stimulation in inferior frontal, superior temporal, and parietal cortices; similar power decreases were also seen in inferior frontal cortex prior to and during overt verb generation. Language lateralization was clearly observed to be a dynamic process that is bilateral for several hundred milliseconds during periods of auditory perception and overt speech production. Correlation with the IAP was seen in 13 of 14 (93%) prospective patients, with the test demonstrating a sensitivity of 100% and specificity of 92%. Our results demonstrate excellent correlation between MEG imaging findings and the IAP for language lateralization, and provide new insights into the spatiotemporal dynamics of cortical speech processing. Copyright © 2012 American Neurological Association.

A Profile of Biomass Stove Use in Sri Lanka

PubMed Central

Elledge, Myles F.; Phillips, Michael J.; Thornburg, Vanessa E.; Everett, Kibri H.; Nandasena, Sumal

2012-01-01

A large body of evidence has confirmed that the indoor air pollution (IAP) from biomass fuel use is a major cause of premature deaths, and acute and chronic diseases. Over 78% of Sri Lankans use biomass fuel for cooking, the major source of IAP in developing countries. We conducted a review of the available literature and data sources to profile biomass fuel use in Sri Lanka. We also produced two maps (population density and biomass use; and cooking fuel sources by district) to illustrate the problem in a geographical context. The biomass use in Sri Lanka is limited to wood while coal, charcoal, and cow dung are not used. Government data sources indicate poor residents in rural areas are more likely to use biomass fuel. Respiratory diseases, which may have been caused by cooking emissions, are one of the leading causes of hospitalizations and death. The World Health Organization estimated that the number of deaths attributable to IAP in Sri Lanka in 2004 was 4300. Small scale studies have been conducted in-country in an attempt to associate biomass fuel use with cataracts, low birth weight, respiratory diseases and lung cancer. However, the IAP issue has not been broadly researched and is not prominent in Sri Lankan public health policies and programs to date. Our profile of Sri Lanka calls for further analytical studies and new innovative initiatives to inform public health policy, advocacy and program interventions to address the IAP problem of Sri Lanka. PMID:22690185

Is intra-bladder pressure measurement a reliable indicator for raised intra-abdominal pressure? A prospective comparative study.

PubMed

Al-Abassi, Abdulla Ahmed; Al Saadi, Azan Saleh; Ahmed, Faisal

2018-06-19

Intra-abdominal pressure (IAP) can be measured by several indirect methods; however, the urinary bladder is largely preferred. The aim of this study was to compare intra-bladder pressure (IBP) at different levels of IAPs and assess its reliability as an indirect method for IAP measurement. We compared IBP with IAP in twenty-one patients undergoing laparoscopic cholecystectomy under general anesthesia. Measurements were recorded at increasing levels of insufflation pressures to approximately 22 mmHg. Pearson's correlation coefficient was calculated to establish the relationship between the two pressure measurements and Bland-Altman analysis was used to assess the limits of agreement between the two methods of measurements. The urinary bladder pressures reflected well the pressures in the abdominal cavity. Pearson correlation coefficient showed a good correlation between the two measurement techniques (r = 0.966, p < 0.0001) and Bland-Altman analysis indicated that the 95% limits of agreement between the two methods ranged from - 2.83 to 2.64. This range is accepted both clinically and according to the recommendations of the World Society of Abdominal Compartment Syndrome (WSACS). Our study showed that IBP measurement is a simple, minimally invasive method that may reliably estimates IAP in patients placed in supine position. Measurements for pressures higher than 12 mmHg may be less reliable. When applied clinically, this should alert the clinician to take safety measures to avoid abdominal compartment syndrome (ACS).

Restriction by APOBEC3 proteins of endogenous retroviruses with an extracellular life cycle: ex vivo effects and in vivo "traces" on the murine IAPE and human HERV-K elements

PubMed Central

Esnault, Cécile; Priet, Stéphane; Ribet, David; Heidmann, Odile; Heidmann, Thierry

2008-01-01

Background APOBEC3 cytosine deaminases have been demonstrated to restrict infectivity of a series of retroviruses, with different efficiencies depending on the retrovirus. In addition, APOBEC3 proteins can severely restrict the intracellular transposition of a series of retroelements with a strictly intracellular life cycle, including the murine IAP and MusD LTR-retrotransposons. Results Here we show that the IAPE element, which is the infectious progenitor of the strictly intracellular IAP elements, and the infectious human endogenous retrovirus HERV-K are restricted by both murine and human APOBEC3 proteins in an ex vivo assay for infectivity, with evidence in most cases of strand-specific G-to-A editing of the proviruses, with the expected signatures. In silico analysis of the naturally occurring genomic copies of the corresponding endogenous elements performed on the mouse and human genomes discloses "traces" of APOBEC3-editing, with the specific signature of the murine APOBEC3 and human APOBEC3G enzymes, respectively, and to a variable extent depending on the family member. Conclusion These results indicate that the IAPE and HERV-K elements, which can only replicate via an extracellular infection cycle, have been restricted at the time of their entry, amplification and integration into their target host genomes by definite APOBEC3 proteins, most probably acting in evolution to limit the mutagenic effect of these endogenized extracellular parasites. PMID:18702815

Space Propulsion Technology Program Overview

NASA Technical Reports Server (NTRS)

Escher, William J. D.

1991-01-01

The topics presented are covered in viewgraph form. Focused program elements are: (1) transportation systems, which include earth-to-orbit propulsion, commercial vehicle propulsion, auxiliary propulsion, advanced cryogenic engines, cryogenic fluid systems, nuclear thermal propulsion, and nuclear electric propulsion; (2) space platforms, which include spacecraft on-board propulsion, and station keeping propulsion; and (3) technology flight experiments, which include cryogenic orbital N2 experiment (CONE), SEPS flight experiment, and cryogenic orbital H2 experiment (COHE).

System Analysis and Performance Benefits of an Optimized Rotorcraft Propulsion System

NASA Technical Reports Server (NTRS)

Bruckner, Robert J.

2007-01-01

The propulsion system of rotorcraft vehicles is the most critical system to the vehicle in terms of safety and performance. The propulsion system must provide both vertical lift and forward flight propulsion during the entire mission. Whereas propulsion is a critical element for all flight vehicles, it is particularly critical for rotorcraft due to their limited safe, un-powered landing capability. This unparalleled reliability requirement has led rotorcraft power plants down a certain evolutionary path in which the system looks and performs quite similarly to those of the 1960 s. By and large the advancements in rotorcraft propulsion have come in terms of safety and reliability and not in terms of performance. The concept of the optimized propulsion system is a means by which both reliability and performance can be improved for rotorcraft vehicles. The optimized rotorcraft propulsion system which couples an oil-free turboshaft engine to a highly loaded gearbox that provides axial load support for the power turbine can be designed with current laboratory proven technology. Such a system can provide up to 60% weight reduction of the propulsion system of rotorcraft vehicles. Several technical challenges are apparent at the conceptual design level and should be addressed with current research.

Apollo Command and Service Module Propulsion Systems Overview

NASA Technical Reports Server (NTRS)

Interbartolo, Michael A.

2009-01-01

An overview of the Apollo Command and Service Module (CSM) propulsion systems is provided. The systems for CSM propulsion and control are defined, the times during the mission when each system is used are listed, and, the basic components and operation of the service propulsion system, SM reaction control system and CM reaction control system are described.

PTEN deficiency promotes macrophage infiltration and hypersensitivity of prostate cancer to IAP antagonist/radiation combination therapy

PubMed Central

Armstrong, Chris W.D.; Maxwell, Pamela J.; Ong, Chee Wee; Redmond, Kelly M.; McCann, Christopher; Neisen, Jessica; Ward, George A.; Chessari, Gianni; Johnson, Christopher; Crawford, Nyree T.; LaBonte, Melissa J.; Prise, Kevin M.; Robson, Tracy; Salto-Tellez, Manuel; Longley, Daniel B.; Waugh, David J.J.

2016-01-01

PTEN loss is prognostic for patient relapse post-radiotherapy in prostate cancer (CaP). Infiltration of tumor-associated macrophages (TAMs) is associated with reduced disease-free survival following radical prostatectomy. However, the association between PTEN loss, TAM infiltration and radiotherapy response of CaP cells remains to be evaluated. Immunohistochemical and molecular analysis of surgically-resected Gleason 7 tumors confirmed that PTEN loss correlated with increased CXCL8 expression and macrophage infiltration. However PTEN status had no discernable correlation with expression of other inflammatory markers by CaP cells, including TNF-α. In vitro, exposure to conditioned media harvested from irradiated PTEN null CaP cells induced chemotaxis of macrophage-like THP-1 cells, a response partially attenuated by CXCL8 inhibition. Co-culture with THP-1 cells resulted in a modest reduction in the radio-sensitivity of DU145 cells. Cytokine profiling revealed constitutive secretion of TNF-α from CaP cells irrespective of PTEN status and IR-induced TNF-α secretion from THP-1 cells. THP-1-derived TNF-α increased NFκB pro-survival activity and elevated expression of anti-apoptotic proteins including cellular inhibitor of apoptosis protein-1 (cIAP-1) in CaP cells, which could be attenuated by pre-treatment with a TNF-α neutralizing antibody. Treatment with a novel IAP antagonist, AT-IAP, decreased basal and TNF-α-induced cIAP-1 expression in CaP cells, switched TNF-α signaling from pro-survival to pro-apoptotic and increased radiation sensitivity of CaP cells in co-culture with THP-1 cells. We conclude that targeting cIAP-1 can overcome apoptosis resistance of CaP cells and is an ideal approach to exploit high TNF-α signals within the TAM-rich microenvironment of PTEN-deficient CaP cells to enhance response to radiotherapy. PMID:26799286

Screening for group B Streptococcus (GBS) at labour onset using PCR: accuracy and potential impact - a pilot study.

PubMed

Ramesh Babu, Sandhya; McDermott, Rachel; Farooq, Irum; Le Blanc, David; Ferguson, Wendy; McCallion, Naomi; Drew, Richard; Eogan, Maeve

2018-01-01

This pilot study assessed the diagnostic accuracy and potential impact of a rapid PCR-based screening test for the detection of group B Streptococcus (GBS) at the onset of labour for the purpose of optimising intrapartum antibiotic prophylaxis (IAP). Vaginal and rectal swabs from a convenience sample of 158 women were analysed by conventional broth-enriched culture and a rapid PCR test. Overall, GBS carriage was 18.98% by culture and 19.62% by PCR. PCR for the detection of GBS had a sensitivity of 93.1%, specificity of 96.67% and area under the curve (AUC) of 0.95. Only 19.3% GBS-positive women received IAP. Three-fourths of babies born to GBS-positive mothers did not receive surveillance for early-onset GBS disease. Of the women who received IAP, only 32.5% were GBS carriers. Seventy-four percent of the GBS-positive mothers delivered more than 5 h after recruitment, which gives adequate swab to delivery interval for appropriate antibiotic prophylaxis in labour. Impact statement What is already known about this subject: Appropriate intra-partum treatment of colonized mothers reduces the risk of GBS transmission to neonates. Universal ante partum screening of pregnant women or IAP based on risk factors in labour for GBS prevention fail to accurately identify and treat the woman who actually harbors GBS in the birth canal in labour. A PCR based rapid test, allows for real-time assessment of GBS carriage in labour. This study highlights the fact that a large number of GBS carriers in labour, who could potentially infect their babies, do not receive IAP, and most of their babies do not receive added surveillance in the neonatal period for EOGBS disease. It also confirms that PCR testing at onset of labour is a highly sensitive and reliable test that identifies the women who are GBS carriers in labour and hence need IAP. What the implications are of these findings for clinical practice and/or further research: Timely provision of IAP for the appropriate woman is possible by adopting universal GBS screening at the onset of labor using GBS-PCR. This would involve additional costs to health care facilities and added work to laboratory personnel.

A real time Pegasus propulsion system model for VSTOL piloted simulation evaluation

NASA Technical Reports Server (NTRS)

Mihaloew, J. R.; Roth, S. P.; Creekmore, R.

1981-01-01

A real time propulsion system modeling technique suitable for use in man-in-the-loop simulator studies was developd. This technique provides the system accuracy, stability, and transient response required for integrated aircraft and propulsion control system studies. A Pegasus-Harrier propulsion system was selected as a baseline for developing mathematical modeling and simulation techniques for VSTOL. Initially, static and dynamic propulsion system characteristics were modeled in detail to form a nonlinear aerothermodynamic digital computer simulation of a Pegasus engine. From this high fidelity simulation, a real time propulsion model was formulated by applying a piece-wise linear state variable methodology. A hydromechanical and water injection control system was also simulated. The real time dynamic model includes the detail and flexibility required for the evaluation of critical control parameters and propulsion component limits over a limited flight envelope. The model was programmed for interfacing with a Harrier aircraft simulation. Typical propulsion system simulation results are presented.

NASA's Evolutionary Xenon Thruster: The NEXT Ion Propulsion System for Solar System Exploration

NASA Technical Reports Server (NTRS)

Pencil, Eric J.; Benson, Scott W.

2008-01-01

This viewgraph presentation reviews NASA s Evolutionary Xenon Thruster (NEXT) Ion Propulsion system. The NEXT project is developing a solar electric ion propulsion system. The NEXT project is advancing the capability of ion propulsion to meet NASA robotic science mission needs. The NEXT system is planned to significantly improve performance over the state of the art electric propulsion systems, such as NASA Solar Electric Propulsion Technology Application Readiness (NSTAR). The status of NEXT development is reviewed, including information on the NEXT Thruster, the power processing unit, the propellant management system (PMS), the digital control interface unit, and the gimbal. Block diagrams NEXT system are presented. Also a review of the lessons learned from the Dawn and NSTAR systems is provided. In summary the NEXT project activities through 2007 have brought next-generation ion propulsion technology to a sufficient maturity level.

46 CFR 111.33-11 - Propulsion systems.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 4 2010-10-01 2010-10-01 false Propulsion systems. 111.33-11 Section 111.33-11 Shipping... REQUIREMENTS Power Semiconductor Rectifier Systems § 111.33-11 Propulsion systems. Each power semiconductor rectifier system in a propulsion system must meet sections 4-8-5/5.17.9 and 4-8-5/5.17.10 of ABS Steel...

46 CFR 111.33-11 - Propulsion systems.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 4 2013-10-01 2013-10-01 false Propulsion systems. 111.33-11 Section 111.33-11 Shipping... REQUIREMENTS Power Semiconductor Rectifier Systems § 111.33-11 Propulsion systems. Each power semiconductor rectifier system in a propulsion system must meet sections 4-8-5/5.17.9 and 4-8-5/5.17.10 of ABS Steel...

46 CFR 111.33-11 - Propulsion systems.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 4 2014-10-01 2014-10-01 false Propulsion systems. 111.33-11 Section 111.33-11 Shipping... REQUIREMENTS Power Semiconductor Rectifier Systems § 111.33-11 Propulsion systems. Each power semiconductor rectifier system in a propulsion system must meet sections 4-8-5/5.17.9 and 4-8-5/5.17.10 of ABS Steel...

46 CFR 111.33-11 - Propulsion systems.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 4 2012-10-01 2012-10-01 false Propulsion systems. 111.33-11 Section 111.33-11 Shipping... REQUIREMENTS Power Semiconductor Rectifier Systems § 111.33-11 Propulsion systems. Each power semiconductor rectifier system in a propulsion system must meet sections 4-8-5/5.17.9 and 4-8-5/5.17.10 of ABS Steel...

46 CFR 111.33-11 - Propulsion systems.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 4 2011-10-01 2011-10-01 false Propulsion systems. 111.33-11 Section 111.33-11 Shipping... REQUIREMENTS Power Semiconductor Rectifier Systems § 111.33-11 Propulsion systems. Each power semiconductor rectifier system in a propulsion system must meet sections 4-8-5/5.17.9 and 4-8-5/5.17.10 of ABS Steel...

Propulsion System and Orbit Maneuver Integration in CubeSats: Trajectory Control Strategies Using Micro Ion Propulsion

NASA Technical Reports Server (NTRS)

Hudson, Jennifer; Martinez, Andres; Petro, Andrew

2015-01-01

The Propulsion System and Orbit Maneuver Integration in CubeSats project aims to solve the challenges of integrating a micro electric propulsion system on a CubeSat in order to perform orbital maneuvers and control attitude. This represents a fundamentally new capability for CubeSats, which typically do not contain propulsion systems and cannot maneuver far beyond their initial orbits.

An overview of the NASA Advanced Propulsion Concepts program

NASA Technical Reports Server (NTRS)

Curran, Francis M.; Bennett, Gary L.; Frisbee, Robert H.; Sercel, Joel C.; Lapointe, Michael R.

1992-01-01

NASA Advanced Propulsion Concepts (APC) program for the development of long-term space propulsion system schemes is managed by both NASA-Lewis and the JPL and is tasked with the identification and conceptual development of high-risk/high-payoff configurations. Both theoretical and experimental investigations have been undertaken in technology areas deemed essential to the implementation of candidate concepts. These APC candidates encompass very high energy density chemical propulsion systems, advanced electric propulsion systems, and an antiproton-catalyzed nuclear propulsion concept. A development status evaluation is presented for these systems.

Development of Laser Propulsion and Tracking System for Laser-Driven Micro-Airplane

NASA Astrophysics Data System (ADS)

Ishikawa, Hiroyasu; Kajiwara, Itsuro; Hoshino, Kentaro; Yabe, Takashi; Uchida, Shigeaki; Shimane, Yoshichika

2004-03-01

The purposes of this paper are to improve the control performance of the developed laser tracking system and to develop an integrated laser propulsion/tracking system for realizing a continuous flight and control of the micro-airplane. The laser propulsion is significantly effective to achieve the miniaturization and lightening of the micro-airplane. The laser-driven micro-airplane has been studied with a paper-craft airplane and YAG laser, resulting in a successful glide of the airplane. In the next stage of the laser-driven micro-airplane development, the laser tracking is expected as key technologies to achieve continuous propulsion. Furthermore, the laser propulsion system should be combined with the laser tracking system to supply continuous propulsion. Experiments are carried out to evaluate the performance of the developed laser tracking system and integrated laser propulsion/tracking system.

Microwave Sintering of Ceramic Materials for Industrial Application Final Report CRADA No. TC-1116-95

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

Caplan, M.; Tandon, R.; Callis, R.

The goal of this project was to develop the commercial capability in the US to sinter alumina oxide ceramic parts for the semiconductor manufacturing equipment industry. We planned to use the millimeter microwave (30 GHz) sintering system first developed by IAP in Russia.

Putting the Pressure On

NASA Technical Reports Server (NTRS)

2000-01-01

Langley Research Center's interest in hypersonic flight led to a SBIR contract with IAP Research, Inc. to develop an electromagnetic launcher. The launcher technology was the basis for IAP's Magnepress process which manufactures high-density parts at rapid rates. The powder compaction technology can be used in the automotive industry and has also been sold to ice cream dispenser manufacturers.

Status of Propulsion Technology Development Under the NASA In-space Propulsion Technology Program

NASA Technical Reports Server (NTRS)

Anderson, David; Kamhawi, Hani; Patterson, Mike; Dankanich, John; Pencil, Eric; Pinero, Luis

2014-01-01

Since 2001, the In-Space Propulsion Technology (ISPT) program has been developing and delivering in-space propulsion technologies for NASA's Science Mission Directorate (SMD). These in-space propulsion technologies are applicable, and potentially enabling for future NASA Discovery, New Frontiers, Flagship and sample return missions currently under consideration. The ISPT program is currently developing technology in three areas that include Propulsion System Technologies, Entry Vehicle Technologies, and Systems Mission Analysis. ISPT's propulsion technologies include: 1) the 0.6-7 kW NASA's Evolutionary Xenon Thruster (NEXT) gridded ion propulsion system; 2) a 0.3-3.9kW Hall-effect electric propulsion (HEP) system for low cost and sample return missions; 3) the Xenon Flow Control Module (XFCM); 4) ultra-lightweight propellant tank technologies (ULTT); and 5) propulsion technologies for a Mars Ascent Vehicle (MAV). The HEP system is composed of the High Voltage Hall Accelerator (HiVHAc) thruster, a power processing unit (PPU), and the XFCM. NEXT and the HiVHAc are throttle-able electric propulsion systems for planetary science missions. The XFCM and ULTT are two component technologies which being developed with nearer-term flight infusion in mind. Several of the ISPT technologies are related to sample return missions needs like: MAV propulsion and electric propulsion. And finally, one focus of the SystemsMission Analysis area is developing tools that aid the application or operation of these technologies on wide variety of mission concepts. This paper provides a brief overview of the ISPT program, describing the development status and technology infusion readiness.

Atrx promotes heterochromatin formation at retrotransposons

PubMed Central

Sadic, Dennis; Schmidt, Katharina; Groh, Sophia; Kondofersky, Ivan; Ellwart, Joachim; Fuchs, Christiane; Theis, Fabian J; Schotta, Gunnar

2015-01-01

More than 50% of mammalian genomes consist of retrotransposon sequences. Silencing of retrotransposons by heterochromatin is essential to ensure genomic stability and transcriptional integrity. Here, we identified a short sequence element in intracisternal A particle (IAP) retrotransposons that is sufficient to trigger heterochromatin formation. We used this sequence in a genome-wide shRNA screen and identified the chromatin remodeler Atrx as a novel regulator of IAP silencing. Atrx binds to IAP elements and is necessary for efficient heterochromatin formation. In addition, Atrx facilitates a robust and largely inaccessible heterochromatin structure as Atrx knockout cells display increased chromatin accessibility at retrotransposons and non-repetitive heterochromatic loci. In summary, we demonstrate a direct role of Atrx in the establishment and robust maintenance of heterochromatin. PMID:26012739

A Brief Review of the Need for Robust Smart Wireless Sensor Systems for Future Propulsion Systems, Distributed Engine Controls, and Propulsion Health Management

NASA Technical Reports Server (NTRS)

Hunter, Gary W.; Behbahani, Alireza

2012-01-01

Smart Sensor Systems with wireless capability operational in high temperature, harsh environments are a significant component in enabling future propulsion systems to meet a range of increasingly demanding requirements. These propulsion systems must incorporate technology that will monitor engine component conditions, analyze the incoming data, and modify operating parameters to optimize propulsion system operations. This paper discusses the motivation towards the development of high temperature, smart wireless sensor systems that include sensors, electronics, wireless communication, and power. The challenges associated with the use of traditional wired sensor systems will be reviewed and potential advantages of Smart Sensor Systems will be discussed. A brief review of potential applications for wireless smart sensor networks and their potential impact on propulsion system operation, with emphasis on Distributed Engine Control and Propulsion Health Management, will be given. A specific example related to the development of high temperature Smart Sensor Systems based on silicon carbide electronics will be discussed. It is concluded that the development of a range of robust smart wireless sensor systems are a foundation for future development of intelligent propulsion systems with enhanced capabilities.

46 CFR 184.620 - Propulsion engine control systems.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 7 2014-10-01 2014-10-01 false Propulsion engine control systems. 184.620 Section 184... Communications Systems § 184.620 Propulsion engine control systems. (a) A vessel must have two independent means of controlling each propulsion engine. Control must be provided for the engine speed, direction of...

46 CFR 184.620 - Propulsion engine control systems.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 7 2013-10-01 2013-10-01 false Propulsion engine control systems. 184.620 Section 184... Communications Systems § 184.620 Propulsion engine control systems. (a) A vessel must have two independent means of controlling each propulsion engine. Control must be provided for the engine speed, direction of...

46 CFR 184.620 - Propulsion engine control systems.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 7 2011-10-01 2011-10-01 false Propulsion engine control systems. 184.620 Section 184... Communications Systems § 184.620 Propulsion engine control systems. (a) A vessel must have two independent means of controlling each propulsion engine. Control must be provided for the engine speed, direction of...

46 CFR 184.620 - Propulsion engine control systems.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 7 2012-10-01 2012-10-01 false Propulsion engine control systems. 184.620 Section 184... Communications Systems § 184.620 Propulsion engine control systems. (a) A vessel must have two independent means of controlling each propulsion engine. Control must be provided for the engine speed, direction of...

46 CFR 184.620 - Propulsion engine control systems.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 7 2010-10-01 2010-10-01 false Propulsion engine control systems. 184.620 Section 184... Communications Systems § 184.620 Propulsion engine control systems. (a) A vessel must have two independent means of controlling each propulsion engine. Control must be provided for the engine speed, direction of...

Rocket Based Combined Cycle (RBCC) Propulsion Technology Workshop. Volume 1: Executive summary

NASA Technical Reports Server (NTRS)

Chojnacki, Kent T.

1992-01-01

The goal of the Rocket-Based Combined Cycle (RBCC) Propulsion Technology Workshop was to assess the RBCC propulsion system's viability for Earth-to-Orbit (ETO) transportation systems. This was accomplished by creating a forum (workshop) in which past work in the field of RBCC propulsion systems was reviewed, current technology status was evaluated, and future technology programs in the field of RBCC propulsion systems were postulated, discussed, and recommended.

Electric propulsion for lunar exploration and lunar base development

NASA Technical Reports Server (NTRS)

Palaszewski, Bryan

1992-01-01

Using electric propulsion to deliver materials to lunar orbit for the development and construction of a lunar base was investigated. Because the mass of the base and its life-cycle resupply mass are large, high specific impulse propulsion systems may significantly reduce the transportation system mass and cost. Three electric propulsion technologies (arcjet, ion, and magnetoplasmadynamic (MPD) propulsion) were compared with oxygen/hydrogen propulsion for a lunar base development scenario. Detailed estimates of the orbital transfer vehicles' (OTV's) masses and their propellant masses are presented. The fleet sizes for the chemical and electric propulsion systems are estimated. Ion and MPD propulsion systems enable significant launch mass savings over O2/H2 propulsion. Because of the longer trip time required for the low-thrust OTV's, more of them are required to perform the mission model. By offloading the lunar cargo from the manned O2/H2 OTV missions onto the electric propulsion OTV's, a significant reduction of the low Earth orbit (LEO) launch mass is possible over the 19-year base development period.

Integrated propulsion/energy transfer control systems for lift-fan V/STOL aircraft. [reduction of total propulsion system and control system installation requirements

NASA Technical Reports Server (NTRS)

Deckert, W. H.; Rolls, L. S.

1974-01-01

An integrated propulsion/control system for lift-fan transport aircraft is described. System behavior from full-scale experimental and piloted simulator investigations are reported. The lift-fan transport is a promising concept for short-to-medium haul civil transportation and for other missions. The lift-fan transport concept features high cruise airspeed, favorable ride qualities, small perceived noise footprints, high utilization, transportation system flexibility, and adaptability to VTOL, V/STOL, or STOL configurations. The lift-fan transport has high direct operating costs in comparison to conventional aircraft, primarily because of propulsion system and aircraft low-speed control system installation requirements. An integrated lift-fan propulsion system/aircraft low-speed control system that reduces total propulsion system and control system installation requirements is discussed.

Mission Benefits of Gridded Ion and Hall Thruster Hybrid Propulsion Systems

NASA Technical Reports Server (NTRS)

Dankanich, John W.; Polsgrove, Tara

2006-01-01

The NASA In-Space Propulsion Technology (ISPT) Project Office has been developing the NEXT gridded ion thruster system and is planning to procure a low power Hall system. The new ion propulsion systems will join NSTAR as NASA's primary electric propulsion system options. Studies have been performed to show mission benefits of each of the stand alone systems. A hybrid ion propulsion system (IPS) can have the advantage of reduced cost, decreased flight time and greater science payload delivery over comparable homogeneous systems. This paper explores possible advantages of combining various thruster options for a single mission.

Space propulsion systems. Present performance limits and application and development trends

NASA Technical Reports Server (NTRS)

Buehler, R. D.; Lo, R. E.

1981-01-01

Typical spaceflight programs and their propulsion requirements as a comparison for possible propulsion systems are summarized. Chemical propulsion systems, solar, nuclear, or even laser propelled rockets with electrical or direct thermal fuel acceleration, nonrockets with air breathing devices and solar cells are considered. The chemical launch vehicles have similar technical characteristics and transportation costs. A possible improvement of payload by using air breathing lower stages is discussed. The electrical energy supply installations which give performance limits of electrical propulsion and the electrostatic ion propulsion systems are described. The development possibilities of thermal, magnetic, and electrostatic rocket engines and the state of development of the nuclear thermal rocket and propulsion concepts are addressed.

Application of selection techniques to electric-propulsion options on an advanced synchronous satellite

NASA Technical Reports Server (NTRS)

Holcomb, L. B.; Degrey, S. P.

1973-01-01

This paper addresses the comparison of several candidate auxiliary-propulsion systems and system combinations for an advanced synchronous satellite. Economic selection techniques, evolved at the Jet Propulsion Laboratory, are used as a basis for system option comparisons. Electric auxiliary-propulsion types considered include pulsed plasma and ion bombardment, with hydrazine systems used as a state-of-the-art reference. Current as well as projected electric-propulsion system performance data are used, as well as projected hydrazine system costs resulting from NASA standardization program projections.

Propulsion for CubeSats

NASA Astrophysics Data System (ADS)

Lemmer, Kristina

2017-05-01

At present, very few CubeSats have flown in space featuring propulsion systems. Of those that have, the literature is scattered, published in a variety of formats (conference proceedings, contractor websites, technical notes, and journal articles), and often not available for public release. This paper seeks to collect the relevant publically releasable information in one location. To date, only two missions have featured propulsion systems as part of the technology demonstration. The IMPACT mission from the Aerospace Corporation launched several electrospray thrusters from Massachusetts Institute of Technology, and BricSAT-P from the United States Naval Academy had four micro-Cathode Arc Thrusters from George Washington University. Other than these two missions, propulsion on CubeSats has been used only for attitude control and reaction wheel desaturation via cold gas propulsion systems. As the desired capability of CubeSats increases, and more complex missions are planned, propulsion is required to accomplish the science and engineering objectives. This survey includes propulsion systems that have been designed specifically for the CubeSat platform and systems that fit within CubeSat constraints but were developed for other platforms. Throughout the survey, discussion of flight heritage and results of the mission are included where publicly released information and data have been made available. Major categories of propulsion systems that are in this survey are solar sails, cold gas propulsion, electric propulsion, and chemical propulsion systems. Only systems that have been tested in a laboratory or with some flight history are included.

Evaluation of propfan propulsion applied to general aviation

NASA Technical Reports Server (NTRS)

Awker, R. W.

1986-01-01

Propfan propulsion on business aircraft was evaluated. Comparisons, in terms of cost and performance, were made between propfan propulsion systems and conventional turbofan propulsion systems on a typical business aircraft. In addition, configuration and cost sensitivity studies were conducted to further assess the potential of propfan propulsion.

Study of electrical and chemical propulsion systems for auxiliary propulsion of large space systems, volume 2

NASA Technical Reports Server (NTRS)

Smith, W. W.

1981-01-01

The five major tasks of the program are reported. Task 1 is a literature search followed by selection and definition of seven generic spacecraft classes. Task 2 covers the determination and description of important disturbance effects. Task 3 applies the disturbances to the generic spacecraft and adds maneuver and stationkeeping functions to define total auxiliary propulsion systems requirements for control. The important auxiliary propulsion system characteristics are identified and sensitivities to control functions and large space system characteristics determined. In Task 4, these sensitivities are quantified and the optimum auxiliary propulsion system characteristics determined. Task 5 compares the desired characteristics with those available for both electrical and chemical auxiliary propulsion systems to identify the directions technology advances should take.

Propulsion System Models for Rotorcraft Conceptual Design

NASA Technical Reports Server (NTRS)

Johnson, Wayne

2014-01-01

The conceptual design code NDARC (NASA Design and Analysis of Rotorcraft) was initially implemented to model conventional rotorcraft propulsion systems, consisting of turboshaft engines burning jet fuel, connected to one or more rotors through a mechanical transmission. The NDARC propulsion system representation has been extended to cover additional propulsion concepts, including electric motors and generators, rotor reaction drive, turbojet and turbofan engines, fuel cells and solar cells, batteries, and fuel (energy) used without weight change. The paper describes these propulsion system components, the architecture of their implementation in NDARC, and the form of the models for performance and weight. Requirements are defined for improved performance and weight models of the new propulsion system components. With these new propulsion models, NDARC can be used to develop environmentally-friendly rotorcraft designs.

NASA Electric Propulsion System Studies

NASA Technical Reports Server (NTRS)

Felder, James L.

2015-01-01

An overview of NASA efforts in the area of hybrid electric and turboelectric propulsion in large transport. This overview includes a list of reasons why we are looking at transmitting some or all of the propulsive power for the aircraft electrically, a list of the different types of hybrid-turbo electric propulsion systems, and the results of 4 aircraft studies that examined different types of hybrid-turbo electric propulsion systems.

System controls challenges of hypersonic combined-cycle engine powered vehicles

NASA Technical Reports Server (NTRS)

Morrison, Russell H.; Ianculescu, George D.

1992-01-01

Hypersonic aircraft with air-breathing engines have been described as the most complex and challenging air/space vehicle designs ever attempted. This is particularly true for aircraft designed to accelerate to orbital velocities. The propulsion system for the National Aerospace Plane will be an active factor in maintaining the aircraft on course. Typically addressed are the difficulties with the aerodynamic vehicle design and development, materials limitations and propulsion performance. The propulsion control system requires equal materials limitations and propulsion performance. The propulsion control system requires equal concern. Far more important than merely a subset of propulsion performance, the propulsion control system resides at the crossroads of trajectory optimization, engine static performance, and vehicle-engine configuration optimization. To date, solutions at these crossroads are multidisciplinary and generally lag behind the broader performance issues. Just how daunting these demands will be is suggested. A somewhat simplified treatment of the behavioral characteristics of hypersonic aircraft and the issues associated with their air-breathing propulsion control system design are presented.

Beamed energy propulsion

NASA Technical Reports Server (NTRS)

Shoji, James M.

1992-01-01

Beamed energy concepts offer an alternative for an advanced propulsion system. The use of a remote power source reduces the weight of the propulsion system in flight and this, combined with the high performance, provides significant payload gains. Within the context of this study's baseline scenario, two beamed energy propulsion concepts are potentially attractive: solar thermal propulsion and laser thermal propulsion. The conceived beamed energy propulsion devices generally provide low thrust (tens of pounds to hundreds of pounds); therefore, they are typically suggested for cargo transportation. For the baseline scenario, these propulsion system can provide propulsion between the following nodes: (1) low Earth orbit to geosynchronous Earth orbit; (2) low Earth orbit to low lunar orbit; (3) low lunar orbit to low Mars orbit--only solar thermal; and (4) lunar surface to low lunar orbit--only laser thermal.

Sensitivity Analysis of Hybrid Propulsion Transportation System for Human Mars Expeditions

NASA Technical Reports Server (NTRS)

Chai, Patrick R.; Joyce, Ryan T.; Kessler, Paul D.; Merrill, Raymond G.; Qu, Min

2017-01-01

The National Aeronautics and Space Administration continues to develop and refine various transportation options to successfully field a human Mars campaign. One of these transportation options is the Hybrid Transportation System which utilizes both solar electric propulsion and chemical propulsion. The Hybrid propulsion system utilizes chemical propulsion to perform high thrust maneuvers, where the delta-V is most optimal when ap- plied to save time and to leverage the Oberth effect. It then utilizes solar electric propulsion to augment the chemical burns throughout the interplanetary trajectory. This eliminates the need for the development of two separate vehicles for crew and cargo missions. Previous studies considered single point designs of the architecture, with fixed payload mass and propulsion system performance parameters. As the architecture matures, it is inevitable that the payload mass and the performance of the propulsion system will change. It is desirable to understand how these changes will impact the in-space transportation system's mass and power requirements. This study presents an in-depth sensitivity analysis of the Hybrid crew transportation system to payload mass growth and solar electric propulsion performance. This analysis is used to identify the breakpoints of the current architecture and to inform future architecture and campaign design decisions.

Space shuttle propulsion systems on-board checkout and monitoring system development study

NASA Technical Reports Server (NTRS)

1971-01-01

Investigations on the fundamental space shuttle propulsion systems program are reported, with emphasis on in-depth reviews of preliminary drafts of the guidelines. The guidelines will be used to incorporate the onboard checkout and monitoring function into the basic design of the propulsion systems and associated interfacing systems. The analysis of checkout and monitoring requirements of the Titan 3 L expandable booster propulsion systems was completed, and the techniques for accomplishing the checkout and monitoring functions were determined. Updating results of the basic study of propulsion system checkout and monitoring is continuing.

Status of Propulsion Technology Development Under the NASA In-Space Propulsion Technology Program

NASA Technical Reports Server (NTRS)

Anderson, David; Kamhawi, Hani; Patterson, Mike; Pencil, Eric; Pinero, Luis; Falck, Robert; Dankanich, John

2014-01-01

Since 2001, the In-Space Propulsion Technology (ISPT) program has been developing and delivering in-space propulsion technologies for NASA's Science Mission Directorate (SMD). These in-space propulsion technologies are applicable, and potentially enabling for future NASA Discovery, New Frontiers, Flagship and sample return missions currently under consideration. The ISPT program is currently developing technology in three areas that include Propulsion System Technologies, Entry Vehicle Technologies, and Systems/Mission Analysis. ISPT's propulsion technologies include: 1) the 0.6-7 kW NASA's Evolutionary Xenon Thruster (NEXT) gridded ion propulsion system; 2) a 0.3-3.9kW Halleffect electric propulsion (HEP) system for low cost and sample return missions; 3) the Xenon Flow Control Module (XFCM); 4) ultra-lightweight propellant tank technologies (ULTT); and 5) propulsion technologies for a Mars Ascent Vehicle (MAV). The NEXT Long Duration Test (LDT) recently exceeded 50,000 hours of operation and 900 kg throughput, corresponding to 34.8 MN-s of total impulse delivered. The HEP system is composed of the High Voltage Hall Accelerator (HIVHAC) thruster, a power processing unit (PPU), and the XFCM. NEXT and the HIVHAC are throttle-able electric propulsion systems for planetary science missions. The XFCM and ULTT are two component technologies which being developed with nearer-term flight infusion in mind. Several of the ISPT technologies are related to sample return missions needs: MAV propulsion and electric propulsion. And finally, one focus of the Systems/Mission Analysis area is developing tools that aid the application or operation of these technologies on wide variety of mission concepts. This paper provides a brief overview of the ISPT program, describing the development status and technology infusion readiness.

Development of Impregnated Agglomerate Pelletization (IAP) process for fabrication of (Th,U)O 2 mixed oxide pellets

NASA Astrophysics Data System (ADS)

Khot, P. M.; Nehete, Y. G.; Fulzele, A. K.; Baghra, Chetan; Mishra, A. K.; Afzal, Mohd.; Panakkal, J. P.; Kamath, H. S.

2012-01-01

Impregnated Agglomerate Pelletization (IAP) technique has been developed at Advanced Fuel Fabrication Facility (AFFF), BARC, Tarapur, for manufacturing (Th, 233U)O 2 mixed oxide fuel pellets, which are remotely fabricated in hot cell or shielded glove box facilities to reduce man-rem problem associated with 232U daughter radionuclides. This technique is being investigated to fabricate the fuel for Indian Advanced Heavy Water Reactor (AHWR). In the IAP process, ThO 2 is converted to free flowing spheroids by powder extrusion route in an unshielded facility which are then coated with uranyl nitrate solution in a shielded facility. The dried coated agglomerate is finally compacted and then sintered in oxidizing/reducing atmosphere to obtain high density (Th,U)O 2 pellets. In this study, fabrication of (Th,U)O 2 mixed oxide pellets containing 3-5 wt.% UO 2 was carried out by IAP process. The pellets obtained were characterized using optical microscopy, XRD and alpha autoradiography. The results obtained were compared with the results for the pellets fabricated by other routes such as Coated Agglomerate Pelletization (CAP) and Powder Oxide Pelletization (POP) route.

Advanced Electric Propulsion for Space Solar Power Satellites

NASA Technical Reports Server (NTRS)

Oleson, Steve

1999-01-01

The sun tower concept of collecting solar energy in space and beaming it down for commercial use will require very affordable in-space as well as earth-to-orbit transportation. Advanced electric propulsion using a 200 kW power and propulsion system added to the sun tower nodes can provide a factor of two reduction in the required number of launch vehicles when compared to in-space cryogenic chemical systems. In addition, the total time required to launch and deliver the complete sun tower system is of the same order of magnitude using high power electric propulsion or cryogenic chemical propulsion: around one year. Advanced electric propulsion can also be used to minimize the stationkeeping propulsion system mass for this unique space platform. 50 to 100 kW class Hall, ion, magnetoplasmadynamic, and pulsed inductive thrusters are compared. High power Hall thruster technology provides the best mix of launches saved and shortest ground to Geosynchronous Earth Orbital Environment (GEO) delivery time of all the systems, including chemical. More detailed studies comparing launch vehicle costs, transfer operations costs, and propulsion system costs and complexities must be made to down-select a technology. The concept of adding electric propulsion to the sun tower nodes was compared to a concept using re-useable electric propulsion tugs for Low Earth Orbital Environment (LEO) to GEO transfer. While the tug concept would reduce the total number of required propulsion systems, more launchers and notably longer LEO to GEO and complete sun tower ground to GEO times would be required. The tugs would also need more complex, longer life propulsion systems and the ability to dock with sun tower nodes.

Certification Testing Approach for Propulsion System Design

NASA Technical Reports Server (NTRS)

Rodriguez, Henry; Popp, Chris

2005-01-01

The Certification of Propulsion Systems is costly and complex which involves development and qualification testing. The desire of the certification process is to assure all requirements can be demonstrated to be compliant. The purpose of this paper is to address the technical design concerns of certifying a system for flight. The authors of this paper have experience the lessons learned from supporting the Shuttle Program for Main Propulsion and On Orbit Propulsions Systems. They have collaborated design concerns for certifying propulsion systems. Presented are Pressurization, Tankage, Feed System and Combustion Instability concerns. Propulsion System Engineers are challenged with the dilemma for testing new systems to specific levels to reduce risk yet maintain budgetary targets. A methodical approach is presented to define the types of test suitable to address the technical issues for qualifying systems for retiring the risk levels.

Centralized versus distributed propulsion

NASA Technical Reports Server (NTRS)

Clark, J. P.

1982-01-01

The functions and requirements of auxiliary propulsion systems are reviewed. None of the three major tasks (attitude control, stationkeeping, and shape control) can be performed by a collection of thrusters at a single central location. If a centralized system is defined as a collection of separated clusters, made up of the minimum number of propulsion units, then such a system can provide attitude control and stationkeeping for most vehicles. A distributed propulsion system is characterized by more numerous propulsion units in a regularly distributed arrangement. Various proposed large space systems are reviewed and it is concluded that centralized auxiliary propulsion is best suited to vehicles with a relatively rigid core. These vehicles may carry a number of flexible or movable appendages. A second group, consisting of one or more large flexible flat plates, may need distributed propulsion for shape control. There is a third group, consisting of vehicles built up from multiple shuttle launches, which may be forced into a distributed system because of the need to add additional propulsion units as the vehicles grow. The effects of distributed propulsion on a beam-like structure were examined. The deflection of the structure under both translational and rotational thrusts is shown as a function of the number of equally spaced thrusters. When two thrusters only are used it is shown that location is an important parameter. The possibility of using distributed propulsion to achieve minimum overall system weight is also examined. Finally, an examination of the active damping by distributed propulsion is described.

Electric and hybrid vehicle system R/D

NASA Technical Reports Server (NTRS)

Schwartz, H. J.

1980-01-01

The work being done to characterize the level of current propulsion technology through component testing is described. Important interactions between the battery and the propulsion system will be discussed. Component development work, involving traction motors, motor controllers and transmissions are described and current results are presented. Studies of advanced electric and hybrid propulsion system studies are summarized and the status of propulsion system development work supported by the project is described. A strategy for fostering joint industry/government projects for commercialization of propulsion components and systems is described briefly.

YF-12 propulsion research program and results

NASA Technical Reports Server (NTRS)

Albers, J. A.; Olinger, F. V.

1976-01-01

The objectives and status of the propulsion program, along with the results acquired in the various technology areas, are discussed. The instrumentation requirements for and experience with flight testing the propulsion systems at high supersonic cruise are reported. Propulsion system performance differences between wind tunnel and flight are given. The effects of high frequency flow fluctuations (transients) on the stability of the propulsion system are described, and shock position control is evaluated.

Operationally efficient propulsion system study (OEPSS) data book. Volume 6; Space Transfer Propulsion Operational Efficiency Study Task of OEPSS

NASA Technical Reports Server (NTRS)

Harmon, Timothy J.

1992-01-01

This document is the final report for the Space Transfer Propulsion Operational Efficiency Study Task of the Operationally Efficient Propulsion System Study (OEPSS) conducted by the Rocketdyne Division of Rockwell International. This Study task studied, evaluated and identified design concepts and technologies which minimized launch and in-space operations and optimized in-space vehicle propulsion system operability.

The phosphotransferase system-dependent sucrose utilization regulon in enteropathogenic Escherichia coli strains is located in a variable chromosomal region containing iap sequences.

PubMed

Treviño-Quintanilla, Luis Gerardo; Escalante, Adelfo; Caro, Alma Delia; Martínez, Alfredo; González, Ricardo; Puente, José Luis; Bolívar, Francisco; Gosset, Guillermo

2007-01-01

The capacity to utilize sucrose as a carbon and energy source (Scr(+) phenotype) is a highly variable trait among Escherichia coli strains. In this study, seven enteropathogenic E. coli (EPEC) strains from different sources were studied for their capacity to grow using sucrose. Liquid media cultures showed that all analyzed strains have the Scr(+) phenotype and two distinct groups were defined: one of five and another of two strains displaying doubling times of 67 and 125 min, respectively. The genes conferring the Scr(+) phenotype in one of the fast-growing strains (T19) were cloned and sequenced. Comparative sequence analysis revealed that this strain possesses the scr regulon genes scrKYABR, encoding phosphoenolpyruvate:phosphotransferase system-dependent sucrose transport and utilization activities. Transcript level quantification revealed sucrose-dependent induction of scrK and scrR genes in fast-growing strains, whereas no transcripts were detected in slow-growing strains. Sequence comparison analysis revealed that the scr genes in strain T19 are almost identical to those present in the scr regulon of prototype EPEC E2348/69 and in both strains, the scr genes are inserted in the chromosomal intergenic region of hypothetical genes ygcE and ygcF. Comparison of the ygcE-ygcF intergenic region sequence of strains MG1655, enterohemorrhagic EDL933, uropathogenic ECFT073 and EPEC T19-E2348/69 revealed that the number of extragenic highly repeated iap sequences corresponded to nine, four, two and none, respectively. These results show that the iap sequence-containing chromosomal ygcE-ygcF intergenic region is highly variable in E. coli. Copyright (c) 2007 S. Karger AG, Basel.

Development of unified propulsion system for geostationary satellite

NASA Astrophysics Data System (ADS)

Murayama, S.; Kobayashi, H.; Masuda, I.; Kameishi, M.; Miyoshi, K.; Takahashi, M.

Japan's first Liquid Apogee Propulsion System (LAPS) has been developed for ETS-VI (Engineering Test Satellite - VI) 2-ton class geostationary satellite. The next largest (2-ton class) geostationary satellite, COMETS (Communication and Broadcasting Engineering Test Satellite), requires a more compact apogee propulsion system in order to increase the space for mission instruments. The study for such a propulsion system concluded with a Unified Propulsion System (UPS), which uses a common N2H4 propellant tank for both bipropellant apogee engines and monopropellant Reaction Control System (RCS) thrusters. This type of propulsion system has several significant advantages compared with popular nitrogen tetroxide/monomethyl hydrazine (NTO/MMH) bipropellant satellite propulsion systems: The NTO/N2H4 apogee engine has a high specific impulse, and N2H4 thrusters have high reliability. Residual of N2H4 caused by propellant utilization of apogee engine firing (AEF) can be consumed by N2H4 monopropellant thrusters; that means a considerably prolonged satellite life.

Propulsion System Dynamic Modeling for the NASA Supersonic Concept Vehicle: AeroPropulsoServoElasticity

NASA Technical Reports Server (NTRS)

Kopasakis, George; Connolly, Joseph; Seidel, Jonathan

2014-01-01

A summary of the propulsion system modeling under NASA's High Speed Project (HSP) AeroPropulsoServoElasticity (APSE) task is provided with a focus on the propulsion system for the low-boom supersonic configuration developed by Lockheed Martin and referred to as the N+2 configuration. This summary includes details on the effort to date to develop computational models for the various propulsion system components. The objective of this paper is to summarize the model development effort in this task, while providing more detail in the modeling areas that have not been previously published. The purpose of the propulsion system modeling and the overall APSE effort is to develop an integrated dynamic vehicle model to conduct appropriate unsteady analysis of supersonic vehicle performance. This integrated APSE system model concept includes the propulsion system model, and the vehicle structural-aerodynamics model. The development to date of such a preliminary integrated model will also be summarized in this report.propulsion system dynamics, the structural dynamics, and aerodynamics.

An Object Oriented Extensible Architecture for Affordable Aerospace Propulsion Systems

NASA Technical Reports Server (NTRS)

Follen, Gregory J.

2003-01-01

Driven by a need to explore and develop propulsion systems that exceeded current computing capabilities, NASA Glenn embarked on a novel strategy leading to the development of an architecture that enables propulsion simulations never thought possible before. Full engine 3 Dimensional Computational Fluid Dynamic propulsion system simulations were deemed impossible due to the impracticality of the hardware and software computing systems required. However, with a software paradigm shift and an embracing of parallel and distributed processing, an architecture was designed to meet the needs of future propulsion system modeling. The author suggests that the architecture designed at the NASA Glenn Research Center for propulsion system modeling has potential for impacting the direction of development of affordable weapons systems currently under consideration by the Applied Vehicle Technology Panel (AVT).

46 CFR 58.01-35 - Main propulsion auxiliary machinery.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 2 2011-10-01 2011-10-01 false Main propulsion auxiliary machinery. 58.01-35 Section 58... AUXILIARY MACHINERY AND RELATED SYSTEMS General Requirements § 58.01-35 Main propulsion auxiliary machinery. Auxiliary machinery vital to the main propulsion system must be provided in duplicate unless the system...

46 CFR 58.01-35 - Main propulsion auxiliary machinery.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 2 2010-10-01 2010-10-01 false Main propulsion auxiliary machinery. 58.01-35 Section 58... AUXILIARY MACHINERY AND RELATED SYSTEMS General Requirements § 58.01-35 Main propulsion auxiliary machinery. Auxiliary machinery vital to the main propulsion system must be provided in duplicate unless the system...

46 CFR 121.620 - Propulsion engine control systems.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 46 Shipping 4 2011-10-01 2011-10-01 false Propulsion engine control systems. 121.620 Section 121... Propulsion engine control systems. (a) A vessel must have two independent means of controlling each propulsion engine. Control must be provided for the engine speed, direction of shaft rotation, and engine...

46 CFR 58.01-35 - Main propulsion auxiliary machinery.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 2 2012-10-01 2012-10-01 false Main propulsion auxiliary machinery. 58.01-35 Section 58... AUXILIARY MACHINERY AND RELATED SYSTEMS General Requirements § 58.01-35 Main propulsion auxiliary machinery. Auxiliary machinery vital to the main propulsion system must be provided in duplicate unless the system...

46 CFR 121.620 - Propulsion engine control systems.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 46 Shipping 4 2012-10-01 2012-10-01 false Propulsion engine control systems. 121.620 Section 121... Propulsion engine control systems. (a) A vessel must have two independent means of controlling each propulsion engine. Control must be provided for the engine speed, direction of shaft rotation, and engine...

46 CFR 58.01-35 - Main propulsion auxiliary machinery.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 2 2013-10-01 2013-10-01 false Main propulsion auxiliary machinery. 58.01-35 Section 58... AUXILIARY MACHINERY AND RELATED SYSTEMS General Requirements § 58.01-35 Main propulsion auxiliary machinery. Auxiliary machinery vital to the main propulsion system must be provided in duplicate unless the system...

46 CFR 121.620 - Propulsion engine control systems.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 4 2014-10-01 2014-10-01 false Propulsion engine control systems. 121.620 Section 121... Propulsion engine control systems. (a) A vessel must have two independent means of controlling each propulsion engine. Control must be provided for the engine speed, direction of shaft rotation, and engine...

46 CFR 121.620 - Propulsion engine control systems.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 46 Shipping 4 2010-10-01 2010-10-01 false Propulsion engine control systems. 121.620 Section 121... Propulsion engine control systems. (a) A vessel must have two independent means of controlling each propulsion engine. Control must be provided for the engine speed, direction of shaft rotation, and engine...

46 CFR 58.01-35 - Main propulsion auxiliary machinery.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 46 Shipping 2 2014-10-01 2014-10-01 false Main propulsion auxiliary machinery. 58.01-35 Section 58... AUXILIARY MACHINERY AND RELATED SYSTEMS General Requirements § 58.01-35 Main propulsion auxiliary machinery. Auxiliary machinery vital to the main propulsion system must be provided in duplicate unless the system...

46 CFR 121.620 - Propulsion engine control systems.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 46 Shipping 4 2013-10-01 2013-10-01 false Propulsion engine control systems. 121.620 Section 121... Propulsion engine control systems. (a) A vessel must have two independent means of controlling each propulsion engine. Control must be provided for the engine speed, direction of shaft rotation, and engine...

Group B streptococcal infections in the newborn infant and the potential value of maternal vaccination.

PubMed

Berardi, Alberto; Cattelani, Chiara; Creti, Roberta; Berner, Reinhard; Pietrangiolillo, Zaira; Margarit, Immaculada; Maione, Domenico; Ferrari, Fabrizio

2015-01-01

Group B Streptococcus (GBS) is a leading cause of neonatal bacterial infections in developed countries. Early-onset disease (EOD) occurs at day 0-6 and late-onset disease occurs at day 7-89. Currently, the prevention of EOD relies upon intrapartum antibiotic prophylaxis (IAP) given to women who are GBS positive at prenatal screening or women with risk factors for EOD. Although successfully implemented, IAP has not fully eradicated EOD, and incidence rates of late-onset disease remain unchanged. Furthermore, antibiotic resistance may result from widespread antibiotic use. New prophylactic strategies are therefore of critical importance. A vaccine active against GBS, administered during pregnancy and combined with targeted IAP, could overcome these problems and reduce the mortality and morbidity associated with invasive diseases.

Preliminary study of propulsion systems and airplane wing parameters for a US Navy subsonic V/STOL aircraft

NASA Technical Reports Server (NTRS)

Zola, C. L.; Fishbach, L. H.; Allen, J. L.

1978-01-01

Two V/STOL propulsion concepts were evaluated in a common aircraft configuration. One propulsion system consists of cross coupled turboshaft engines driving variable pitch fans. The other system is a gas coupled combination of turbojet gas generators and tip turbine fixed pitch fans. Evaluations were made of endurance at low altitude, low speed loiter with equal takeoff fuel loads. Effects of propulsion system sizing, bypass ratio, and aircraft wing planform parameters were investigated and compared. Shaft driven propulsion systems appear to result in better overall performance, although at higher installed weight, than gas systems.

Performance analysis of the ascent propulsion system of the Apollo spacecraft

NASA Technical Reports Server (NTRS)

Hooper, J. C., III

1973-01-01

Activities involved in the performance analysis of the Apollo lunar module ascent propulsion system are discussed. A description of the ascent propulsion system, including hardware, instrumentation, and system characteristics, is included. The methods used to predict the inflight performance and to establish performance uncertainties of the ascent propulsion system are discussed. The techniques of processing the telemetered flight data and performing postflight performance reconstruction to determine actual inflight performance are discussed. Problems that have been encountered and results from the analysis of the ascent propulsion system performance during the Apollo 9, 10, and 11 missions are presented.

Advanced transportation system studies. Alternate propulsion subsystem concepts: Propulsion database

NASA Technical Reports Server (NTRS)

Levack, Daniel

1993-01-01

The Advanced Transportation System Studies alternate propulsion subsystem concepts propulsion database interim report is presented. The objective of the database development task is to produce a propulsion database which is easy to use and modify while also being comprehensive in the level of detail available. The database is to be available on the Macintosh computer system. The task is to extend across all three years of the contract. Consequently, a significant fraction of the effort in this first year of the task was devoted to the development of the database structure to ensure a robust base for the following years' efforts. Nonetheless, significant point design propulsion system descriptions and parametric models were also produced. Each of the two propulsion databases, parametric propulsion database and propulsion system database, are described. The descriptions include a user's guide to each code, write-ups for models used, and sample output. The parametric database has models for LOX/H2 and LOX/RP liquid engines, solid rocket boosters using three different propellants, a hybrid rocket booster, and a NERVA derived nuclear thermal rocket engine.

Solar System Exploration Augmented by In-Situ Resource Utilization: Human Planetary Base Issues for Mercury and Saturn

NASA Technical Reports Server (NTRS)

Palaszewski, Bryan A.

2017-01-01

Human and robotic missions to Mercury and Saturn are presented and analyzed with a range of propulsion options. Historical studies of space exploration, planetary spacecraft, and astronomy, in-situ resource utilization (ISRU), and industrialization all point to the vastness of natural resources in the solar system. Advanced propulsion benefitted from these resources in many ways. While advanced propulsion systems were proposed in these historical studies, further investigation of nuclear options using high power nuclear thermal and nuclear pulse propulsion as well as advanced chemical propulsion can significantly enhance these scenarios. Updated analyses based on these historical visions are presented. Nuclear thermal propulsion and ISRU enhanced chemical propulsion landers are assessed for Mercury missions. At Saturn, nuclear pulse propulsion with alternate propellant feed systems and Saturn moon exploration with chemical propulsion and nuclear electric propulsion options are discussed. Issues with using in-situ resource utilization on Mercury missions are discussed. At Saturn, the best locations for exploration and the use of the moons Titan and Enceladus as central locations for Saturn moon exploration is assessed.

Solar System Exploration Augmented by In-Situ Resource Utilization: Mercury and Saturn Propulsion Investigations

NASA Technical Reports Server (NTRS)

Palaszewski, Bryan

2016-01-01

Human and robotic missions to Mercury and Saturn are presented and analyzed with a range of propulsion options. Historical studies of space exploration, in-situ resource utilization (ISRU), and industrialization all point to the vastness of natural resources in the solar system. Advanced propulsion benefitted from these resources in many ways. While advanced propulsion systems were proposed in these historical studies, further investigation of nuclear options using high power nuclear thermal and nuclear pulse propulsion as well as advanced chemical propulsion can significantly enhance these scenarios. Updated analyses based on these historical visions will be presented. Nuclear thermal propulsion and ISRU enhanced chemical propulsion landers are assessed for Mercury missions. At Saturn, nuclear pulse propulsion with alternate propellant feed systems and Titan exploration with chemical propulsion options are discussed. In-situ resource utilization was found to be critical in making Mercury missions more amenable for human visits. At Saturn, refueling using local atmospheric mining was found to be difficult to impractical, while refueling the Saturn missions from Uranus was more practical and less complex.

Automated screening of propulsion system test data by neural networks, phase 1

NASA Technical Reports Server (NTRS)

Hoyt, W. Andes; Whitehead, Bruce A.

1992-01-01

The evaluation of propulsion system test and flight performance data involves reviewing an extremely large volume of sensor data generated by each test. An automated system that screens large volumes of data and identifies propulsion system parameters which appear unusual or anomalous will increase the productivity of data analysis. Data analysts may then focus on a smaller subset of anomalous data for further evaluation of propulsion system tests. Such an automated data screening system would give NASA the benefit of a reduction in the manpower and time required to complete a propulsion system data evaluation. A phase 1 effort to develop a prototype data screening system is reported. Neural networks will detect anomalies based on nominal propulsion system data only. It appears that a reasonable goal for an operational system would be to screen out 95 pct. of the nominal data, leaving less than 5 pct. needing further analysis by human experts.

Solar System Exploration Augmented by In-Situ Resource Utilization: Human Mercury and Saturn Exploration

NASA Technical Reports Server (NTRS)

Palaszewski, Bryan

2015-01-01

Human and robotic missions to Mercury and Saturn are presented and analyzed. Unique elements of the local planetary environments are discussed and included in the analyses and assessments. Using historical studies of space exploration, in-situ resource utilization (ISRU), and industrialization all point to the vastness of natural resources in the solar system. Advanced propulsion benefitted from these resources in many way. While advanced propulsion systems were proposed in these historical studies, further investigation of nuclear options using high power nuclear thermal and nuclear pulse propulsion as well as advanced chemical propulsion can significantly enhance these scenarios. Updated analyses based on these historical visions will be presented. Nuclear thermal propulsion and ISRU enhanced chemical propulsion landers are assessed for Mercury missions. At Saturn, nuclear pulse propulsion with alternate propellant feed systems and Titan exploration with chemical propulsion options are discussed.

Technology Area Roadmap for In Space Propulsion Technologies

NASA Technical Reports Server (NTRS)

Johnson, Les; Meyer, Mike; Coote, David; Goebel, Dan; Palaszewski, Bryan; White, Sonny

2010-01-01

This slide presentation reviews the technology area (TA) roadmap to develop propulsion technologies that will be used to enable further exploration of the solar system, and beyond. It is hoped that development of the technologies within this TA will result in technical solutions that will improve thrust levels, specific impulse, power, specific mass, volume, system mass, system complexity, operational complexity, commonality with other spacecraft systems, manufacturability and durability. Some of the propulsion technologies that are reviewed include: chemical and non-chemical propulsion, and advanced propulsion (i.e., those with a Technology Readiness level of less than 3). Examples of these advanced technologies include: Beamed Energy, Electric Sail, Fusion, High Energy Density Materials, Antimatter, Advanced Fission and Breakthrough propulsion technologies. Timeframes for development of some of these propulsion technologies are reviewed, and top technical challenges are reviewed. This roadmap describes a portfolio of in-space propulsion technologies that can meet future space science and exploration needs.

A novel Heart Rate Variability analysis using Lagged Poincaré plot: A study on hedonic visual elicitation.

PubMed

Nardelli, M; Greco, A; Valenza, G; Lanata, A; Bailon, R; Scilingo, E P

2017-07-01

This paper reports on a novel method for the analysis of Heart Rate Variability (HRV) through Lagged Poincaré Plot (LPP) theory. Specifically a hybrid method, LPP symb , including LPP quantifiers and related symbolic dynamics was proposed. LPP has been applied to investigate the autonomic response to pleasant and unpleasant pictures extracted from the International Affective Picture System (IAPS). IAPS pictures are standardized in terms of level of arousal, i.e. the intensity of the evoked emotion, and valence, i.e. the level of pleasantness/unpleasantness, according to the Circumplex model of Affects (CMA). Twenty-two healthy subjects were enrolled in the experiment, which comprised four sessions with increasing arousal level. Within each session valence increased from positive to negative. An ad-hoc pattern recognition algorithm using a Leave-One-Subject-Out (LOSO) procedure based on a Quadratic Discriminant Classifier (QDC) was implemented. Our pattern recognition system was able to classify pleasant and unpleasant sessions with an accuracy of 71.59%. Therefore, we can suggest the use of the LPP symb for emotion recognition.

Space station integrated propulsion and fluid systems study

NASA Technical Reports Server (NTRS)

Bicknell, B.; Wilson, S.; Dennis, M.; Shepard, D.; Rossier, R.

1988-01-01

The program study was performed in two tasks: Task 1 addressed propulsion systems and Task 2 addressed all fluid systems associated with the Space Station elements, which also included propulsion and pressurant systems. Program results indicated a substantial reduction in life cycle costs through integrating the oxygen/hydrogen propulsion system with the environmental control and life support system, and through supplying nitrogen in a cryogenic gaseous supercritical or subcritical liquid state. A water sensitivity analysis showed that increasing the food water content would substantially increase the amount of water available for propulsion use and in all cases, the implementation of the BOSCH CO2 reduction process would reduce overall life cycle costs to the station and minimize risk. An investigation of fluid systems and associated requirements revealed a delicate balance between the individual propulsion and fluid systems across work packages and a strong interdependence between all other fluid systems.

Engineering of the Magnetized Target Fusion Propulsion System

NASA Technical Reports Server (NTRS)

Statham, G.; White, S.; Adams, R. B.; Thio, Y. C. F.; Santarius, J.; Alexander, R.; Chapman, J.; Fincher, S.; Philips, A.; Polsgrove, T.

2003-01-01

Engineering details are presented for a magnetized target fusion (MTF) propulsion system designed to support crewed missions to the outer solar system. Basic operation of an MTF propulsion system is introduced. Structural, thermal, radiation-management and electrical design details are presented. The propellant storage and supply system design is also presented. A propulsion system mass estimate and associated performance figures are given. The advantages of helium-3 as a fusion fuel for an advanced MTF system are discussed.

Solar Electric Propulsion System Integration Technology (SEPSIT). Volume 2: Encke rendezvous mission and space vehicle functional description

NASA Technical Reports Server (NTRS)

Gardner, J. A.

1972-01-01

A solar electric propulsion system integration technology study is discussed. Detailed analyses in support of the solar electric propulsion module were performed. The thrust subsystem functional description is presented. The space vehicle and the space mission to which the propulsion system is applied are analyzed.

Feasibility of a responsive, hybrid propulsion augmented, Vertical-Takeoff-and-Landing, Single-Stage-to-Orbit launch system

NASA Astrophysics Data System (ADS)

Pelaccio, Dennis G.

1996-03-01

A novel, reusable, Vertical-Takeoff-and-Landing, Single-Stage-to-Orbit (VTOL/SSTO) launch system concept, named HYP-SSTO, is presented in this paper. This launch vehicle system concept uses a highly coupled, main high performance liquid oxygen/liquid hydrogen (LOX/LH2) propulsion system, that is used only for launch, with a hybrid auxiliary propulsion system which is used during final orbit insertion, major orbit maneuvering, and landing propulsive burn phases of flight. By using a hybrid propulsion system for major orbit maneuver burns and landing, this launch system concept has many advantages over conventional VTOL/SSTO concepts that use LOX/LH2 propulsion system(s) burns for all phases of flight. Because hybrid propulsion systems are relatively simple and inert by their nature, this concept has the potential to support short turnaround times between launches, be economical to develop, and be competitive in terms of overall system life-cycle cost. This paper provides a technical description of the novel, reusable HYP-SSTO launch system concept. Launch capability performance, as well as major design and operational system attributes, are identified and discussed.

Using Additive Manufacturing to Print a CubeSat Propulsion System

NASA Technical Reports Server (NTRS)

Marshall, William M.

2015-01-01

CubeSats are increasingly being utilized for missions traditionally ascribed to larger satellites CubeSat unit (1U) defined as 10 cm x 10 cm x 11 cm. Have been built up to 6U sizes. CubeSats are typically built up from commercially available off-the-shelf components, but have limited capabilities. By using additive manufacturing, mission specific capabilities (such as propulsion), can be built into a system. This effort is part of STMD Small Satellite program Printing the Complete CubeSat. Interest in propulsion concepts for CubeSats is rapidly gaining interest-Numerous concepts exist for CubeSat scale propulsion concepts. The focus of this effort is how to incorporate into structure using additive manufacturing. End-use of propulsion system dictates which type of system to develop-Pulse-mode RCS would require different system than a delta-V orbital maneuvering system. Team chose an RCS system based on available propulsion systems and feasibility of printing using a materials extrusion process. Initially investigated a cold-gas propulsion system for RCS applications-Materials extrusion process did not permit adequate sealing of part to make this a functional approach.

Rocket-Based Combined-Cycle (RBCC) Propulsion Technology Workshop. Tutorial session

NASA Technical Reports Server (NTRS)

1992-01-01

The goal of this workshop was to illuminate the nation's space transportation and propulsion engineering community on the potential of hypersonic combined cycle (airbreathing/rocket) propulsion systems for future space transportation applications. Four general topics were examined: (1) selections from the expansive advanced propulsion archival resource; (2) related propulsion systems technical backgrounds; (3) RBCC engine multimode operations related subsystem background; and (4) focused review of propulsion aspects of current related programs.

Advanced Chemical Propulsion

NASA Technical Reports Server (NTRS)

Alexander, Leslie, Jr.

2006-01-01

Advanced Chemical Propulsion (ACP) provides near-term incremental improvements in propulsion system performance and/or cost. It is an evolutionary approach to technology development that produces useful products along the way to meet increasingly more demanding mission requirements while focusing on improving payload mass fraction to yield greater science capability. Current activities are focused on two areas: chemical propulsion component, subsystem, and manufacturing technologies that offer measurable system level benefits; and the evaluation of high-energy storable propellants with enhanced performance for in-space application. To prioritize candidate propulsion technology alternatives, a variety of propulsion/mission analyses and trades have been conducted for SMD missions to yield sufficient data for investment planning. They include: the Advanced Chemical Propulsion Assessment; an Advanced Chemical Propulsion System Model; a LOx-LH2 small pumps conceptual design; a space storables propellant study; a spacecraft cryogenic propulsion study; an advanced pressurization and mixture ratio control study; and a pump-fed vs. pressure-fed study.

GPIM AF-M315E Propulsion System

NASA Technical Reports Server (NTRS)

Spores, Ronald A.; Masse, Robert; Kimbrel, Scott; McLean, Chris

2014-01-01

The NASA Space Technology mission Directorate's (STMD) Green Propellant Infusion Mission (GPIM) Technology Demonstration Mission (TDM) will demonstrate an operational AF-M315E green propellant propulsion system. Aerojet-Rocketdyne is responsible for the development of the propulsion system payload. This paper statuses the propulsion system module development, including thruster design and system design; Initial test results for the 1N engineering model thruster are presented. The culmination of this program will be high-performance, green AF-M315E propulsion system technology at TRL 7+, with components demonstrated to TRL 9, ready for direct infusion to a wide range of applications for the space user community.

Nuclear Propulsion Technical Interchange Meeting, volume 2

NASA Technical Reports Server (NTRS)

1993-01-01

The purpose of the meeting was to review the work performed in fiscal year 1992 in the areas of nuclear thermal and nuclear electric propulsion technology development. These proceedings are an accumulation of the presentations provided at the meeting along with annotations provided by authors. The proceedings cover system concepts, technology development, and system modeling for nuclear thermal propulsion (NTP) and nuclear electric propulsion (NEP). The test facilities required for the development of the nuclear propulsion systems are also discussed.

National Institute for Rocket Propulsion Systems (NIRPS): Solutions Facilitator

NASA Technical Reports Server (NTRS)

Brown, Tom

2011-01-01

National Institute for Rocket Propulsion Systems (NIRPS) "Solutions" plans to enable our nation's future in rocket propulsion systems by leveraging existing skills and capabilities to support industry's future needs

Hybrid rocket propulsion

NASA Technical Reports Server (NTRS)

Holzman, Allen L.

1993-01-01

Topics addressed are: (1) comparison of the theoretical impulses; (2) comparison of the density-specific impulses; (3) general propulsion system features comparison; (4) hybrid systems, booster applications; and (5) hybrid systems, upper stage propulsion applications.

Modeling of Spacecraft Advanced Chemical Propulsion Systems

NASA Technical Reports Server (NTRS)

Benfield, Michael P. J.; Belcher, Jeremy A.

2004-01-01

This paper outlines the development of the Advanced Chemical Propulsion System (ACPS) model for Earth and Space Storable propellants. This model was developed by the System Technology Operation of SAIC-Huntsville for the NASA MSFC In-Space Propulsion Project Office. Each subsystem of the model is described. Selected model results will also be shown to demonstrate the model's ability to evaluate technology changes in chemical propulsion systems.

Solar electric propulsion system technology

NASA Technical Reports Server (NTRS)

Masek, T. D.; Macie, T. W.

1971-01-01

Achievements in the solar electric propulsion system technology program (SEPST 3) are reported and certain propulsion system-spacecraft interaction problems are discussed. The basic solar electric propulsion system concept and elements are reviewed. Hardware is discussed only briefly, relying on detailed fabrication or assembly descriptions reported elsewhere. Emphasis is placed on recent performance data, which are presented to show the relationship between spacecraft requirements and present technology.

Mirror fusion propulsion system: A performance comparison with alternate propulsion systems for the manned Mars Mission

NASA Technical Reports Server (NTRS)

Schulze, Norman R.; Carpenter, Scott A.; Deveny, Marc E.; Oconnell, T.

1993-01-01

The performance characteristics of several propulsion technologies applied to piloted Mars missions are compared. The characteristics that are compared are Initial Mass in Low Earth Orbit (IMLEO), mission flexibility, and flight times. The propulsion systems being compared are both demonstrated and envisioned: Chemical (or Cryogenic), Nuclear Thermal Rocket (NTR) solid core, NTR gas core, Nuclear Electric Propulsion (NEP), and a mirror fusion space propulsion system. The proposed magnetic mirror fusion reactor, known as the Mirror Fusion Propulsion System (MFPS), is described. The description is an overview of a design study that was conducted to convert a mirror reactor experiment at Lawrence Livermore National Lab (LLNL) into a viable space propulsion system. Design principles geared towards minimizing mass and maximizing power available for thrust are identified and applied to the LLNL reactor design, resulting in the MFPS. The MFPS' design evolution, reactor and fuel choices, and system configuration are described. Results of the performance comparison shows that the MFPS minimizes flight time to 60 to 90 days for flights to Mars while allowing continuous return-home capability while at Mars. Total MFPS IMLEO including propellant and payloads is kept to about 1,000 metric tons.

Mirror fusion propulsion system - A performance comparison with alternate propulsion systems for the manned Mars mission

NASA Technical Reports Server (NTRS)

Deveny, M.; Carpenter, S.; O'Connell, T.; Schulze, N.

1993-01-01

The performance characteristics of several propulsion technologies applied to piloted Mars missions are compared. The characteristics that are compared are Initial Mass in Low Earth Orbit (IMLEO), mission flexibility, and flight times. The propulsion systems being compared are both demonstrated and envisioned: Chemical (or Cryogenic), Nuclear Thermal Rocket (NTR) solid core, NTR gas core, Nuclear Electric Propulsion (NEP), and a mirror fusion space propulsion system. The proposed magnetic mirror fusion reactor, known as the Mirror Fusion Propulsion System (MFPS), is described. The description is an overview of a design study that was conducted to convert a mirror reactor experiment at Lawrence Livermore National Lab (LLNL) into a viable space propulsion system. Design principles geared towards minimizing mass and maximizing power available for thrust are identified and applied to the LLNL reactor design, resulting in the MFPS. The MFPS' design evolution, reactor and fuel choices, and system configuration are described. Results of the performance comparison shows that the MFPS minimizes flight time to 60 to 90 days for flights to Mars while allowing continuous return-home capability while at Mars. Total MFPS IMLEO including propellant and payloads is kept to about 1,000 metric tons.

Indoor air pollution and the risk of orofacial clefts in a rural population in Shanxi province, China.

PubMed

Liu, Yingying; Wang, Bin; Li, Zhiwen; Zhang, Le; Liu, Jufen; Ren, Aiguo

2016-08-01

Shanxi Province is a region in China with a high incidence of orofacial clefts (OFCs). Our objective is to investigate the effect of maternal exposure to indoor air pollution (IAP) from coal combustion and tobacco smoke on the risk of an infant being born with orofacial clefts. Data were derived from an ongoing population-based case-control study of major external structural birth defects in Shanxi Province. Subjects included 213 cases with OFCs and 1319 healthy babies born between November 2002 and December 2014 in four rural counties. Exposure information was collected by face-to-face interview with mothers within 1 week of delivery or pregnancy termination. The authors derived an exposure index by integrating a series of IAP-related characteristics concerning dwelling and lifestyle. Increased odds of OFC were associated with IAP exposure from heating (adjusted odds ratio [aOR] = 2.4; 95% confidence interval [CI], 1.2-4.5) and from smoking (aOR = 1.8; 95% CI: 1.3, 2.5), but not with exposure from cooking (aOR = 0.9; 95% CI, 0.6-1.4). Compared with women without IAP exposure, the aORs of OFC for children of women with exposure indices of 1, 2, 3 and ≥ 4 were 1.1 (95% CI, 0.6-1.8), 1.4 (95% CI, 0.8-2.4), 1.8 (95% CI, 1.0-3.2), and 3.4 (95% CI, 1.6-7.4), respectively, demonstrating a clear dose-response trend (p < 0.001). Periconceptional exposure to IAP from coal combustion and tobacco smoking may increase the risk of OFCs in offsprings of women in Shanxi Province. Birth Defects Research (Part A) 106:708-715, 2016. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

A novel SMAC mimetic APG-1387 exhibits dual antitumor effect on HBV-positive hepatocellular carcinoma with high expression of cIAP2 by inducing apoptosis and enhancing innate anti-tumor immunity.

PubMed

Pan, Wentao; Luo, Qiuyun; Yan, Xianglei; Yuan, Luping; Yi, Hanjie; Zhang, Lin; Li, Baoxia; Zhang, Yuxin; Sun, Jian; Qiu, Miao-Zhen; Yang, Da-Jun

2018-04-18

Check point inhibitor anti-PD1 antibody produced some efficacy in Hepatocellular Carcinoma (HCC) patients previously treated with sorafenib. Unfortunately, HCC patients with hepatitis B virus (HBV) infection did not respond as well as uninfected patients. Previously, Second mitochondria-derived activator of caspases (SMAC) mimetics-the antagonist for inhibitor of apoptosis proteins (IAPs) can rapidly reduce serum hepatitis B virus DNA in animal model. APG-1387 is a novel SMAC-mimetic, small molecule inhibitor targeting inhibitor of apoptosis proteins (IAPs). In our study, firstly, we found that HCC patients with copy number alteration of cIAP1, cIAP2, and XIAP had a dismal prognosis. Then, we discovered that APG-1387 alone could induce apoptosis of PLC/PRF/5 which was HBV positive both in-vitro and in-vivo. Furthermore, we found that APG-1387 significantly up-regulated the expression of calreticulin and HLA-DR in PLC/PRF/5 via activating non-classic NF-κB pathway. Also, compared to vehicle group, APG-1387 increased NK cell counts by 5 folds in PLC/PRF/5 xenograft model. In-vitro, APG-1387 positively regulated T cells by reducing Treg differentiation and down-regulating PD1 expression in CD4 T cell. Moreover, APG-1387 had no impact on memory T cells. Consequently, our results suggest that APG1387 could be a good candidate to combine with anti-PD1 antibody treatment to overcome low responds of check point inhibitors in HBV positive HCC. Copyright © 2018 Elsevier Inc. All rights reserved.

Novel smac mimetic APG-1387 elicits ovarian cancer cell killing through TNF-alpha, Ripoptosome and autophagy mediated cell death pathway.

PubMed

Li, Bao-Xia; Wang, Heng-Bang; Qiu, Miao-Zhen; Luo, Qiu-Yun; Yi, Han-Jie; Yan, Xiang-Lei; Pan, Wen-Tao; Yuan, Lu-Ping; Zhang, Yu-Xin; Xu, Jian-Hua; Zhang, Lin; Yang, Da-Jun

2018-03-12

Ovarian cancer is a deadly disease. Inhibitors of apoptosis proteins (IAPs) are key regulators of apoptosis and are frequently dysregulated in ovarian cancer. Overexpression of IAPs proteins has been correlated with tumorigenesis, treatment resistance and poor prognosis. Reinstalling functional cell death machinery by pharmacological inhibition of IAPs proteins may represent an attractive therapeutic strategy for treatment of ovarian cancer. CCK-8 and colony formation assay was performed to examine cytotoxic activity. Apoptosis was analyzed by fluorescence microscopy, flow cytometry and TUNEL assay. Elisa assay was used to determine TNFα protein. Caspase activity assay was used for caspase activation evaluation. Immunoprecipitation and siRNA interference were carried out for functional analysis. Western blotting analysis were carried out to test protein expression. Ovarian cancer cell xenograft nude mice model was used for in vivo efficacy evaluation. APG-1387 demonstrated potent inhibitory effect on ovarian cancer cell growth and clonogenic cell survival. APG-1387 induced RIP1- and TNFα-dependent apoptotic cell death in ovarian cancer through downregulation of IAPs proteins and induction of caspase-8/FADD/RIP1 complex, which drives caspase-8 activation. NF-κB signaling pathway was activated upon APG-1387 treatment and RIP1 contributed to NF-κB activation. APG-1387 induced cytoprotective autophagy while triggering apoptosis in ovarian cancer cells and inhibition of autophagy enhanced APG-1387-induced apoptotic cell death. APG-1387 exhibited potent antitumor activity against established human ovarian cancer xenografts. Our results demonstrate that APG-1387 targets IAPs proteins to potently elicit apoptotic cell death in vitro and in vivo, and provide mechanistic and applicable rationale for future clinical evaluation of APG-1387 in ovarian cancer.

The contribution of posterior circulation to memory function during the intracarotid amobarbital procedure.

PubMed

Zijlmans, M; Huibers, C J A; Huiskamp, G J; de Kort, G A P; Alpherts, W C J; Leijten, F S S; Hendrikse, J

2012-08-01

The purpose of this study was to evaluate the contribution of posterior circulation to memory function by comparing memory scores between patients with and without a foetal-type posterior cerebral artery (FTP) during the intracarotid amobarbital procedure (IAP) in epilepsy patients. Patients undergoing bilateral IAP between January 2004 and January 2010 were retrospectively included. Pre-test angiograms were assessed for the presence of a FTP. Memory function scores (% correct) after right and left injections were obtained. Functional significance of FTP was affirmed by relative occipital versus parietal EEG slow-wave increase during IAP. Memory and EEG scores were compared between patients with and without FTP (Mann-Whitney U test). A total of 106 patients were included, 73 with posterior cerebral arteries (PCA) without FTP ('non-FTP'), 28 patients with unilateral FTP and 5 with a bilateral FTP. Memory scores were lower when amytal was injected to the hemisphere contralateral to the presumed seizure focus (on the right decreasing from 98.3 to 59.1, and on the left decreasing from 89.1 to 72.4; p < 0.001). When IAP was performed on the side of FTP memory scores were significantly lower (70.8) compared to non-FTP (82.0; p = 0.02). Relative occipital EEG changes were 0.44 for FTP cases and 0.36 for non-FTP patients (p = 0.01). A relationship between vasculature and brain function was demonstrated by lower memory scores and more slow-wave activity on occipital EEG during IAP in patients with foetal-type PCA compared to patients with non-FTP. This suggests an important contribution of brain areas supplied by the PCA to memory function.

Indoor air pollution from solid fuel use, chronic lung diseases and lung cancer in Harbin, Northeast China

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

Galeone, C.; Pelucchi, C.; La Vecchia, C.

In some areas of China, indoor air pollution (IAP) originating principally from the combustion of solid fuels has a relevant role in lung cancer. Most previous studies focused on the female population and only a few on both the sexes. We analyzed the relationship between IAP from solid fuel use and selected chronic lung diseases and lung cancer risk in Harbin, Northeast China, an area with a very high base line risk of lung cancer for both the sexes. We used data from a case-control study conducted between 1987 and 1990, including 218 patients with incident, histologically confirmed lung cancermore » and 436 controls admitted to the same hospitals as cases. We calculated an index of IAP from solid fuel use exposure using data on heating type, cooking fuel used, and house measurements. Cases reported more frequently than controls on exposure to coal fuel for house heating and/or cooking, and the odds ratio (OR) for ever versus never exposed was 2.19 (95% confidence interval (CI): 1.08-4.46). The ORs of lung cancer according to subsequent tertiles of IAP exposure index were 1.82 (95% CI: 1.14-2.89) and 1.99 (95% CI: 1.26-3.15) as compared with the lowest tertile. The ORs of lung cancer for participants with a history of chronic bronchitis and tuberculosis were 3.79 (95% CI: 2.38-6.02) and 3.82 (95% CI: 1.97-7.41), respectively. This study gives further support and quantification of the positive association between IAP, history of selected nonmalignant lung diseases, and lung cancer risk for both the sexes.« less

Operationally Efficient Propulsion System Study (OEPSS) data book. Volume 4: OEPSS design concepts

NASA Technical Reports Server (NTRS)

Wong, George S.; Ziese, James M.; Farhangi, Shahram

1990-01-01

This study was initiated to identify operations problems and cost drivers for current propulsion systems and to identify technology and design approaches to increase the operational efficiency and reduce operations costs for future propulsion systems. To provide readily usable data for the Advanced Launch System (ALS) program, the results of the OEPSS study have been organized into a series of OEPSS Data Books. This volume describes three propulsion concepts that will simplify the propulsion system design and significantly reduce operational requirements. The concepts include: (1) a fully integrated, booster propulsion module concept for the ALS that avoids the complex system created by using autonomous engines with numerous artificial interfaces; (2) an LOX tank aft concept which avoids potentially dangerous geysering in long LOX propellant lines; and (3) an air augmented, rocket engine nozzle afterburning propulsion concept that will significantly reduce LOX propellant requirements, reduce vehicle size and simplify ground operations and ground support equipment and facilities.

Impact of large volume paracentesis on respiratory parameters including transpulmonary pressure and on transpulmonary thermodilution derived hemodynamics: A prospective study

PubMed Central

Mayr, Ulrich; Karsten, Eugen; Lahmer, Tobias; Rasch, Sebastian; Thies, Philipp; Henschel, Benedikt; Fischer, Gerrit; Schmid, Roland M.

2018-01-01

Introduction Appropriate mechanical ventilation and prevention of alveolar collaps is mainly dependent on transpulmonary pressure TPP. TPP is assessed by measurement of esophageal pressure EP, largely influenced by pleural and intraabdominal pressure IAP. Consecutively, TPP-guided ventilation might be particularly useful in patients with high IAP. This study investigates the impact of large volume paracentesis LVP on TPP, EP, IAP as well as on hemodynamic and respiratory function in patients with liver cirrhosis and tense ascites. Material and methods We analysed 23 LVP-procedures in 11 cirrhotic patients ventilated with the AVEA Viasys respirator (CareFusion, USA) which is capable to measure EP via an esophageal tube. Results LVP of a mean volume of 4826±1276 mL of ascites resulted in marked increases in inspiratory (17.9±8.9 vs. 5.4±13.3 cmH2O; p<0.001) as well as expiratory TPP (-3.0±4.7 vs. -15.9±10.9 cmH2O; p<0.001; primary endpoint). In parallel, the inspiratory (2.4±8.7 vs. 14.1±14.5 cmH2O; p<0.001) and expiratory EP (12.4±6.0 vs. 24.9±11.3 cmH2O; p<0.001) significantly decreased. The effects were most pronounced for the release of the first 500 mL of ascites. LVP evoked substantial decreases in IAP and central venous pressure CVP. By contrast, mean arterial pressure, cardiac index, global end-diastolic volume index, extravascular lung water index and systemic vascular resistance index did not change. Among the respiratory parameters we observed an increase in paO2/FiO2 (247.7±60.9 vs. 208.3±46.8 mmHg; p<0.001) and a decrease in Oxygenation Index OI (4.8±2.0 vs. 5.8±3.1 cmH2O/mmHg; p = 0.002). Tidal volume (510±100 vs. 452±113 mL; p = 0.008) and dynamic respiratory system compliance Cdyn (46.8±15.9 vs. 35.1±14.6 mL/cmH20; p<0.001) increased, whereas paCO2 (47.3±10.7 vs. 51.2±12.3mmHg; p = 0.046) and the respiratory rate decreased (17.1±7.3 vs. 19.6±7.8 min-1; p = 0.010). Conclusions In mechanically ventilated patients with decompensated cirrhosis, intraabdominal hypertension resulted in a substantially decreased TPP despite PEEP-setting according to the ARDSNet. In these patients LVP markedly increased TPP and improved respiratory function in parallel with a decline of EP. Furthermore, LVP induced a decrease in IAP and CVP, while other hemodynamic parameters did not change. PMID:29538440

Visions of the Future: Hybrid Electric Aircraft Propulsion

NASA Technical Reports Server (NTRS)

Bowman, Cheryl L.

2016-01-01

The National Aeronautics and Space Administration (NASA) is investing continually in improving civil aviation. Hybridization of aircraft propulsion is one aspect of a technology suite which will transform future aircraft. In this context, hybrid propulsion is considered a combination of traditional gas turbine propulsion and electric drive enabled propulsion. This technology suite includes elements of propulsion and airframe integration, parallel hybrid shaft power, turbo-electric generation, electric drive systems, component development, materials development and system integration at multiple levels.

Electric Propulsion Requirements and Mission Analysis Under NASA's In-Space Propulsion Technology Project

NASA Technical Reports Server (NTRS)

Dudzinski, Leonard a.; Pencil, Eric J.; Dankanich, John W.

2007-01-01

The In-Space Propulsion Technology Project (ISPT) is currently NASA's sole investment in electric propulsion technologies. This project is managed at NASA Glenn Research Center (GRC) for the NASA Headquarters Science Mission Directorate (SMD). The objective of the electric propulsion project area is to develop near-term and midterm electric propulsion technologies to enhance or enable future NASA science missions while minimizing risk and cost to the end user. Systems analysis activities sponsored by ISPT seek to identify future mission applications in order to quantify mission requirements, as well as develop analytical capability in order to facilitate greater understanding and application of electric propulsion and other propulsion technologies in the ISPT portfolio. These analyses guide technology investments by informing decisions and defining metrics for technology development to meet identified mission requirements. This paper discusses the missions currently being studied for electric propulsion by the ISPT project, and presents the results of recent electric propulsion (EP) mission trades. Recent ISPT systems analysis activities include: an initiative to standardize life qualification methods for various electric propulsion systems in order to retire perceived risk to proposed EP missions; mission analysis to identify EP requirements from Discovery, New Frontiers, and Flagship classes of missions; and an evaluation of system requirements for radioisotope-powered electric propulsion. Progress and early results of these activities is discussed where available.

The Ion Propulsion System for the Solar Electric Propulsion Technology Demonstration Mission

NASA Technical Reports Server (NTRS)

Herman, Daniel A.; Santiago, Walter; Kamhawi, Hani; Polk, James E.; Snyder, John Steven; Hofer, Richard R.; Parker, J. Morgan

2015-01-01

The Asteroid Redirect Robotic Mission is a candidate Solar Electric Propulsion Technology Demonstration Mission whose main objectives are to develop and demonstrate a high-power solar electric propulsion capability for the Agency and return an asteroidal mass for rendezvous and characterization in a companion human-crewed mission. The ion propulsion system must be capable of operating over an 8-year time period and processing up to 10,000 kg of xenon propellant. This high-power solar electric propulsion capability, or an extensible derivative of it, has been identified as a critical part of an affordable, beyond-low-Earth-orbit, manned-exploration architecture. Under the NASA Space Technology Mission Directorate the critical electric propulsion and solar array technologies are being developed. The ion propulsion system being co-developed by the NASA Glenn Research Center and the Jet Propulsion Laboratory for the Asteroid Redirect Vehicle is based on the NASA-developed 12.5 kW Hall Effect Rocket with Magnetic Shielding (HERMeS0 thruster and power processing technologies. This paper presents the conceptual design for the ion propulsion system, the status of the NASA in-house thruster and power processing activity, and an update on flight hardware.

The NASA Electric Propulsion Program

NASA Technical Reports Server (NTRS)

Callahan, Lisa Wood; Curran, Francis M.

1996-01-01

Nearly all space missions require on-board propulsion systems and these systems typically have a major impact on spacecraft mass and cost. Electric propulsion systems offer major performance advantages over conventional chemical systems for many mission functions and the NASA Office of Space Access and Technology (OSAT) supports an extensive effort to develop the technology for high-performance, on-board electric propulsion system options to enhance and enable near- and far-term US space missions. This program includes research and development efforts on electrothermal, electrostatic, and electromagnetic propulsion system technologies to cover a wide range of potential applications. To maximize expectations of technology transfer, the program emphasizes strong interaction with the user community through a variety of cooperative and contracted approaches. This paper provides an overview of the OSAT electric propulsion program with an emphasis on recent progress and future directions.

Simulation model of the integrated flight/propulsion control system, displays, and propulsion system for ASTOVL lift-fan aircraft

NASA Technical Reports Server (NTRS)

Chung, W. Y. William; Borchers, Paul F.; Franklin, James A.

1995-01-01

A simulation model has been developed for use in piloted evaluations of takeoff, transition, hover, and landing characteristics of an advanced, short takeoff, vertical landing lift fan fighter aircraft. The flight/propulsion control system includes modes for several response types which are coupled to the aircraft's aerodynamic and propulsion system effectors through a control selector tailored to the lift fan propulsion system. Head-up display modes for approach and hover, tailored to their corresponding control modes are provided in the simulation. Propulsion system components modeled include a remote lift and a lift/cruise engine. Their static performance and dynamic response are represented by the model. A separate report describes the subsonic, power-off aerodynamics and jet induced aerodynamics in hover and forward flight, including ground effects.

Motor mapping of implied actions during perception of emotional body language.

PubMed

Borgomaneri, Sara; Gazzola, Valeria; Avenanti, Alessio

2012-04-01

Perceiving and understanding emotional cues is critical for survival. Using the International Affective Picture System (IAPS) previous TMS studies have found that watching humans in emotional pictures increases motor excitability relative to seeing landscapes or household objects, suggesting that emotional cues may prime the body for action. Here we tested whether motor facilitation to emotional pictures may reflect the simulation of the human motor behavior implied in the pictures occurring independently of its emotional valence. Motor-evoked potentials (MEPs) to single-pulse TMS of the left motor cortex were recorded from hand muscles during observation and categorization of emotional and neutral pictures. In experiment 1 participants watched neutral, positive and negative IAPS stimuli, while in experiment 2, they watched pictures depicting human emotional (joyful, fearful), neutral body movements and neutral static postures. Experiment 1 confirms the increase in excitability for emotional IAPS stimuli found in previous research and shows, however, that more implied motion is perceived in emotional relative to neutral scenes. Experiment 2 shows that motor excitability and implied motion scores for emotional and neutral body actions were comparable and greater than for static body postures. In keeping with embodied simulation theories, motor response to emotional pictures may reflect the simulation of the action implied in the emotional scenes. Action simulation may occur independently of whether the observed implied action carries emotional or neutral meanings. Our study suggests the need of controlling implied motion when exploring motor response to emotional pictures of humans. Copyright © 2012 Elsevier Inc. All rights reserved.

Positive erotic picture stimuli for emotion research in heterosexual females.

PubMed

Jacob, Gitta Anne; Arntz, Arnoud; Domes, Gregor; Reiss, Neele; Siep, Nicolette

2011-12-30

In most experimental studies, emotional pictures are widely used as stimulus material. However, there is still a lack of standardization of picture stimuli displaying erotic relationships, despite the association between a number of psychological problems and severe impairments and problems in intimate relationships. The aim of the study was to test a set of erotic stimuli, with the potential to be used in experimental studies, with heterosexual female subjects. Twenty International Affective Picture System (IAPS) pictures and an additional 100 pictures showing romantic but not explicitly sexual scenes and/or attractive single males were selected. All pictures were rated with respect to valence, arousal, and dominance by 41 heterosexual women and compared to pictures with negative, positive, and neutral emotional valence. Erotic IAPS pictures and our additional erotic pictures did not differ in any of the evaluation dimensions. Analyses of variance (ANOVAs) for valence, arousal, and dominance comparing different picture valence categories showed strong effects for category. However, valence was not significantly different between erotic and positive pictures, while arousal and control were not significantly different between positive and neutral pictures. The pictures of our new set are as positive for heterosexual women as highly positive IAPS pictures, but higher in arousal and dominance. The picture set can be used in experimental psychiatric studies requiring high numbers of stimuli per category. Limitations are the restriction of stimuli application to heterosexual females only and to self-report data. Copyright © 2011 Elsevier Ltd. All rights reserved.

Prophylactic treatment with alkaline phosphatase in cardiac surgery induces endogenous alkaline phosphatase release.

PubMed

Kats, Suzanne; Brands, Ruud; Hamad, Mohamed A Soliman; Seinen, Willem; Scharnhorst, Volkher; Wulkan, Raymond W; Schönberger, Jacques P; Oeveren, Wim van

2012-02-01

Laboratory and clinical data have implicated endotoxin as an important factor in the inflammatory response to cardiopulmonary bypass. We assessed the effects of the administration of bovine intestinal alkaline phosphatase (bIAP), an endotoxin detoxifier, on alkaline phosphatase levels in patients undergoing coronary artery bypass grafting. A total of 63 patients undergoing coronary artery bypass grafting were enrolled and prospectively randomized. Bovine intestinal alkaline phosphatase (n=32) or placebo (n=31) was administered as an intravenous bolus followed by continuous infusion for 36 hours. The primary endpoint was to evaluate alkaline phosphatase levels in both groups and to find out if administration of bIAP to patients undergoing CABG would lead to endogenous alkaline phosphatase release. No significant adverse effects were identified in either group. In all the 32 patients of the bIAP-treated group, we found an initial rise of plasma alkaline phosphatase levels due to bolus administration (464.27±176.17 IU/L). A significant increase of plasma alkaline phosphatase at 4-6 hours postoperatively was observed (354.97±95.00 IU/L) as well. Using LHA inhibition, it was shown that this second peak was caused by the generation of tissue non specific alkaline phosphatase (TNSALP-type alkaline phosphatase). Intravenous bolus administration plus 8 hours continuous infusion of alkaline phosphatase in patients undergoing coronary artery bypass grafting with cardiopulmonary bypass results in endogenous alkaline phosphatase release. This endogenous alkaline phosphatase may play a role in the immune defense system.

A review of electric propulsion systems and mission applications

NASA Technical Reports Server (NTRS)

Vondra, R.; Nock, K.; Jones, R.

1984-01-01

The satisfaction of growing demands for access to space resources will require new developments related to advanced propulsion and power technologies. A key technology in this context is concerned with the utilization of electric propulsion. A brief review of the current state of development of electric propulsion systems on an international basis is provided, taking into account advances in the USSR, the U.S., Japan, West Germany, China and Brazil. The present investigation, however, is mainly concerned with the U.S. program. The three basic types of electric thrusters are considered along with the intrinsic differences between chemical and electric propulsion, the resistojet, the augmented hydrazine thruster, the arcjet, the ion auxiliary propulsion system flight test, the pulsed plasma thruster, magnetoplasmadynamic propulsion, a pulsed inductive thruster, and rail accelerators. Attention is also given to the applications of electric propulsion.

New Propulsion Technologies For Exploration of the Solar System and Beyond

NASA Technical Reports Server (NTRS)

Johnson, Les; Cook, Stephen (Technical Monitor)

2001-01-01

In order to implement the ambitious science and exploration missions planned over the next several decades, improvements in in-space transportation and propulsion technologies must be achieved. For robotic exploration and science missions, increased efficiencies of future propulsion systems are critical to reduce overall life-cycle costs. Future missions will require 2 to 3 times more total change in velocity over their mission lives than the NASA Solar Electric Technology Application Readiness (NSTAR) demonstration on the Deep Space 1 mission. Rendezvous and return missions will require similar investments in in-space propulsion systems. New opportunities to explore beyond the outer planets and to the stars will require unparalleled technology advancement and innovation. The Advanced Space Transportation Program (ASTP) is investing in technologies to achieve a factor of 10 reduction in the cost of Earth orbital transportation and a factor of 2 reduction in propulsion system mass and travel time for planetary missions within the next 15 years. Since more than 70% of projected launches over the next 10 years will require propulsion systems capable of attaining destinations beyond Low Earth Orbit, investment in in-space technologies will benefit a large percentage of future missions. The ASTP technology portfolio includes many advanced propulsion systems. From the next generation ion propulsion system operating in the 5 - 10 kW range, to fission-powered multi-kilowatt systems, substantial advances in spacecraft propulsion performance are anticipated. Some of the most promising technologies for achieving these goals use the environment of space itself for energy and propulsion and are generically called, "propellantless" because they do not require on-board fuel to achieve thrust. An overview of the state-of-the-art in propellantless propulsion technologies such as solar and plasma sails, electrodynamic and momentum transfer tethers, and aeroassist and aerocapture will also be described. Results of recent earth-based technology demonstrations and space tests for many of these new propulsion technologies will be discussed.

NASA In-Space Propulsion Technologies and Their Infusion Potential

NASA Technical Reports Server (NTRS)

Anderson, David J.; Pencil,Eric J.; Peterson, Todd; Vento, Daniel; Munk, Michelle M.; Glaab, Louis J.; Dankanich, John W.

2012-01-01

The In-Space Propulsion Technology (ISPT) program has been developing in-space propulsion technologies that will enable or enhance NASA robotic science missions. The ISPT program is currently developing technology in four areas that include Propulsion System Technologies (Electric and Chemical), Entry Vehicle Technologies (Aerocapture and Earth entry vehicles), Spacecraft Bus and Sample Return Propulsion Technologies (components and ascent vehicles), and Systems/Mission Analysis. Three technologies are ready for flight infusion: 1) the high-temperature Advanced Material Bipropellant Rocket (AMBR) engine providing higher performance; 2) NASA s Evolutionary Xenon Thruster (NEXT) ion propulsion system, a 0.6-7 kW throttle-able gridded ion system; and 3) Aerocapture technology development with investments in a family of thermal protection system (TPS) materials and structures; guidance, navigation, and control (GN&C) models of blunt-body rigid aeroshells; and aerothermal effect models. Two component technologies that will be ready for flight infusion in the near future will be Advanced Xenon Flow Control System, and ultra-lightweight propellant tank technologies. Future focuses for ISPT are sample return missions and other spacecraft bus technologies like: 1) Mars Ascent Vehicles (MAV); 2) multi-mission technologies for Earth Entry Vehicles (MMEEV) for sample return missions; and 3) electric propulsion for sample return and low cost missions. These technologies are more vehicle-focused, and present a different set of technology infusion challenges. While the Systems/Mission Analysis area is focused on developing tools and assessing the application of propulsion technologies to a wide variety of mission concepts. These in-space propulsion technologies are applicable, and potentially enabling for future NASA Discovery, New Frontiers, and sample return missions currently under consideration, as well as having broad applicability to potential Flagship missions. This paper provides a brief overview of the ISPT program, describing the development status and technology infusion readiness of in-space propulsion technologies in the areas of electric propulsion, aerocapture, Earth entry vehicles, propulsion components, Mars ascent vehicle, and mission/systems analysis.

Clustered engine study

NASA Technical Reports Server (NTRS)

Shepard, Kyle; Sager, Paul; Kusunoki, Sid; Porter, John; Campion, AL; Mouritzan, Gunnar; Glunt, George; Vegter, George; Koontz, Rob

1993-01-01

Several topics are presented in viewgraph form which together encompass the preliminary assessment of nuclear thermal rocket engine clustering. The study objectives, schedule, flow, and groundrules are covered. This is followed by the NASA groundrules mission and our interpretation of the associated operational scenario. The NASA reference vehicle is illustrated, then the four propulsion system options are examined. Each propulsion system's preliminary design, fluid systems, operating characteristics, thrust structure, dimensions, and mass properties are detailed as well as the associated key propulsion system/vehicle interfaces. A brief series of systems analysis is also covered including: thrust vector control requirements, engine out possibilities, propulsion system failure modes, surviving system requirements, and technology requirements. An assessment of vehicle/propulsion system impacts due to the lessons learned are presented.

NASA's In-Space Propulsion Technology Program: Overview and Status

NASA Technical Reports Server (NTRS)

Johnson, Les; Alexander, Leslie; Baggett, Randy; Bonometti, Joe; Herrmann, Melody; James, Bonnie; Montgomery, Sandy

2004-01-01

NASA's In-Space Propulsion Technology Program is investing in technologies that have the potential to revolutionize the robotic exploration of deep space. For robotic exploration and science missions, increased efficiencies of future propulsion systems are critical to reduce overall life-cycle costs and, in some cases, enable missions previously considered impossible. Continued reliance on conventional chemical propulsion alone will not enable the robust exploration of deep space - the maximum theoretical efficiencies have almost been reached and they are insufficient to meet needs for many ambitious science missions currently being considered. The In-Space Propulsion Technology Program s technology portfolio includes many advanced propulsion systems. From the next generation ion propulsion system operating in the 5 - 10 kW range, to advanced cryogenic propulsion, substantial advances in spacecraft propulsion performance are anticipated. Some of the most promising technologies for achieving these goals use the environment of space itself for energy and propulsion and are generically called, 'propellantless' because they do not require onboard fuel to achieve thrust. Propellantless propulsion technologies include scientific innovations such as solar sails, electrodynamic and momentum transfer tethers, aeroassist, and aerocapture. This paper will provide an overview of both propellantless and propellant-based advanced propulsion technologies, and NASA s plans for advancing them as part of the $60M per year In-Space Propulsion Technology Program.

Additive Manufacturing a Liquid Hydrogen Rocket Engine

NASA Technical Reports Server (NTRS)

Jones, Carl P.; Robertson, Elizabeth H.; Koelbl, Mary Beth; Singer, Chris

2016-01-01

Space Propulsion is a 5 day event being held from 2nd May to the 6th May 2016 at the Rome Marriott Park Hotel in Rome, Italy. This event showcases products like Propulsion sub-systems and components, Production and manufacturing issues, Liquid, Solid, Hybrid and Air-breathing Propulsion Systems for Launcher and Upper Stages, Overview of current programmes, AIV issues and tools, Flight testing and experience, Technology building blocks for Future Space Transportation Propulsion Systems : Launchers, Exploration platforms & Space Tourism, Green Propulsion for Space Transportation, New propellants, Rocket propulsion & global environment, Cost related aspects of Space Transportation propulsion, Modelling, Pressure-Thrust oscillations issues, Impact of new requirements and regulations on design etc. in the Automotive, Manufacturing, Fabrication, Repair & Maintenance industries.

Economic effects of propulsion system technology on existing and future transport aircraft

NASA Technical Reports Server (NTRS)

Sallee, G. P.

1974-01-01

The results of an airline study of the economic effects of propulsion system technology on current and future transport aircraft are presented. This report represents the results of a detailed study of propulsion system operating economics. The study has four major parts: (1) a detailed analysis of current propulsion system maintenance with respect to the material and labor costs encountered versus years in service and the design characteristics of the major elements of the propulsion system of the B707, b727, and B747. (2) an analysis of the economic impact of a future representative 1979 propulsion system is presented with emphasis on depreciation of investment, fuel costs and maintenance costs developed on the basis of the analysis of the historical trends observed. (3) recommendations concerning improved methods of forecasting the maintenance cost of future propulsion systems are presented. A detailed method based on the summation of the projected labor and material repair costs for each major engine module and its installation along with a shorter form suitable for quick, less detailed analysis are presented, and (4) recommendations concerning areas where additional technology is needed to improve the economics of future commercial propulsion systems are presented along with the suggested economic benefits available from such advanced technology efforts.

Status and Mission Applicability of NASA's In-Space Propulsion Technology Project

NASA Technical Reports Server (NTRS)

Anderson, David J.; Munk, Michelle M.; Dankanich, John; Pencil, Eric; Liou, Larry

2009-01-01

The In-Space Propulsion Technology (ISPT) project develops propulsion technologies that will enable or enhance NASA robotic science missions. Since 2001, the ISPT project developed and delivered products to assist technology infusion and quantify mission applicability and benefits through mission analysis and tools. These in-space propulsion technologies are applicable, and potentially enabling for flagship destinations currently under evaluation, as well as having broad applicability to future Discovery and New Frontiers mission solicitations. This paper provides status of the technology development, near-term mission benefits, applicability, and availability of in-space propulsion technologies in the areas of advanced chemical thrusters, electric propulsion, aerocapture, and systems analysis tools. The current chemical propulsion investment is on the high-temperature Advanced Material Bipropellant Rocket (AMBR) engine providing higher performance for lower cost. Investments in electric propulsion technologies focused on completing NASA's Evolutionary Xenon Thruster (NEXT) ion propulsion system, a 0.6-7 kW throttle-able gridded ion system, and the High Voltage Hall Accelerator (HiVHAC) thruster, which is a mid-term product specifically designed for a low-cost electric propulsion option. Aerocapture investments developed a family of thermal protections system materials and structures; guidance, navigation, and control models of blunt-body rigid aeroshells; atmospheric models for Earth, Titan, Mars and Venus; and models for aerothermal effects. In 2009 ISPT started the development of propulsion technologies that would enable future sample return missions. The paper describes the ISPT project's future focus on propulsion for sample return missions. The future technology development areas for ISPT is: Planetary Ascent Vehicles (PAV), with a Mars Ascent Vehicle (MAV) being the initial development focus; multi-mission technologies for Earth Entry Vehicles (MMEEV) needed for sample return missions from many different destinations; propulsion for Earth Return Vehicles (ERV), transfer stages to the destination, and Electric Propulsion for sample return and low cost missions; and Systems/Mission Analysis focused on sample return propulsion. The ISPT project is funded by NASA's Science Mission Directorate (SMD).

Real-time fault diagnosis for propulsion systems

NASA Technical Reports Server (NTRS)

Merrill, Walter C.; Guo, Ten-Huei; Delaat, John C.; Duyar, Ahmet

1991-01-01

Current research toward real time fault diagnosis for propulsion systems at NASA-Lewis is described. The research is being applied to both air breathing and rocket propulsion systems. Topics include fault detection methods including neural networks, system modeling, and real time implementations.

Physiologically based pharmacokinetic and pharmacodynamic modeling of an antagonist (SM-406/AT-406) of multiple inhibitor of apoptosis proteins (IAPs) in a mouse xenograft model of human breast cancer.

PubMed

Zhang, Tao; Li, Yanyan; Zou, Peng; Yu, Jing-yu; McEachern, Donna; Wang, Shaomeng; Sun, Duxin

2013-09-01

The inhibitors of apoptosis proteins (IAPs) are a class of key apoptosis regulators overexpressed or dysregulated in cancer. SM-406/AT-406 is a potent and selective small molecule mimetic of Smac that antagonizes the inhibitor of apoptosis proteins (IAPs). A physiologically based pharmacokinetic and pharmacodynamic (PBPK-PD) model was developed to predict the tissue concentration-time profiles of SM-406, the related onco-protein levels in tumor, and the tumor growth inhibition in a mouse model bearing human breast cancer xenograft. In the whole body physiologically based pharmacokinetic (PBPK) model for pharmacokinetics characterization, a well stirred (perfusion rate-limited) model was used to describe SM-406 pharmacokinetics in the lung, heart, kidney, intestine, liver and spleen, and a diffusion rate-limited (permeability limited) model was used for tumor. Pharmacodynamic (PD) models were developed to correlate the SM-406 concentration in tumor to the cIAP1 degradation, pro-caspase 8 decrease, CL-PARP accumulation and tumor growth inhibition. The PBPK-PD model well described the experimental pharmacokinetic data, the pharmacodynamic biomarker responses and tumor growth. This model may be helpful to predict tumor and plasma SM-406 concentrations in the clinic. Copyright © 2013 John Wiley & Sons, Ltd.

CpG methylation of a silent controlling element in the murine Avy allele is incomplete and unresponsive to methyl donor supplementation.

PubMed

Cropley, Jennifer E; Suter, Catherine M; Beckman, Kenneth B; Martin, David I K

2010-02-04

The viable yellow allele of agouti (A(vy)) is remarkable for its unstable and partially heritable epigenetic state, which produces wide variation in phenotypes of isogenic mice. In the A(vy) allele an inserted intracisternal A particle (IAP) acts as a controlling element which deregulates expression of agouti by transcription from the LTR of the IAP; the phenotypic state has been linked to CpG methylation of the LTR. Phenotypic variation between A(vy) mice indicates that the epigenetic state of the IAP is unstable in the germline. We have made a detailed examination of somatic methylation of the IAP using bisulphite allelic sequencing, and find that the promoter is incompletely methylated even when it is transcriptionally silent. In utero exposure to supplementary methyl donors, which alters the spectrum of A(vy) phenotypes, does not increase the density of CpG methylation in the silent LTR. Our findings suggest that, contrary to previous supposition, methyl donor supplementation acts through an indirect mechanism to silence A(vy). The incomplete cytosine methylation we observe at the somatically silent A(vy) allele may reflect its unstable germline state, and the influence of epigenetic modifications underlying CpG methylation.

CpG Methylation of a Silent Controlling Element in the Murine Avy Allele Is Incomplete and Unresponsive to Methyl Donor Supplementation

PubMed Central

Cropley, Jennifer E.; Suter, Catherine M.; Beckman, Kenneth B.; Martin, David I. K.

2010-01-01

Background The viable yellow allele of agouti (Avy) is remarkable for its unstable and partially heritable epigenetic state, which produces wide variation in phenotypes of isogenic mice. In the Avy allele an inserted intracisternal A particle (IAP) acts as a controlling element which deregulates expression of agouti by transcription from the LTR of the IAP; the phenotypic state has been linked to CpG methylation of the LTR. Phenotypic variation between Avy mice indicates that the epigenetic state of the IAP is unstable in the germline. Principal Findings We have made a detailed examination of somatic methylation of the IAP using bisulphite allelic sequencing, and find that the promoter is incompletely methylated even when it is transcriptionally silent. In utero exposure to supplementary methyl donors, which alters the spectrum of Avy phenotypes, does not increase the density of CpG methylation in the silent LTR. Conclusions Our findings suggest that, contrary to previous supposition, methyl donor supplementation acts through an indirect mechanism to silence Avy. The incomplete cytosine methylation we observe at the somatically silent Avy allele may reflect its unstable germline state, and the influence of epigenetic modifications underlying CpG methylation. PMID:20140227

Advanced Space Fission Propulsion Systems

NASA Technical Reports Server (NTRS)

Houts, Michael G.; Borowski, Stanley K.

2010-01-01

Fission has been considered for in-space propulsion since the 1940s. Nuclear Thermal Propulsion (NTP) systems underwent extensive development from 1955-1973, completing 20 full power ground tests and achieving specific impulses nearly twice that of the best chemical propulsion systems. Space fission power systems (which may eventually enable Nuclear Electric Propulsion) have been flown in space by both the United States and the Former Soviet Union. Fission is the most developed and understood of the nuclear propulsion options (e.g. fission, fusion, antimatter, etc.), and fission has enjoyed tremendous terrestrial success for nearly 7 decades. Current space nuclear research and technology efforts are focused on devising and developing first generation systems that are safe, reliable and affordable. For propulsion, the focus is on nuclear thermal rockets that build on technologies and systems developed and tested under the Rover/NERVA and related programs from the Apollo era. NTP Affordability is achieved through use of previously developed fuels and materials, modern analytical techniques and test strategies, and development of a small engine for ground and flight technology demonstration. Initial NTP systems will be capable of achieving an Isp of 900 s at a relatively high thrust-to-weight ratio. The development and use of first generation space fission power and propulsion systems will provide new, game changing capabilities for NASA. In addition, development and use of these systems will provide the foundation for developing extremely advanced power and propulsion systems capable of routinely and affordably accessing any point in the solar system. The energy density of fissile fuel (8 x 10(exp 13) Joules/kg) is more than adequate for enabling extensive exploration and utilization of the solar system. For space fission propulsion systems, the key is converting the virtually unlimited energy of fission into thrust at the desired specific impulse and thrust-to-weight ratio. This presentation will discuss potential space fission propulsion options ranging from first generation systems to highly advanced systems. Ongoing research that shows promise for enabling second generation NTP systems with Isp greater than 1000 s will be discussed, as will the potential for liquid, gas, or plasma core systems. Space fission propulsion systems could also be used in conjunction with simple (water-based) propellant depots to enable routine, affordable missions to various destinations (e.g. moon, Mars, asteroids) once in-space infrastructure is sufficiently developed. As fuel and material technologies advance, very high performance Nuclear Electric Propulsion (NEP) systems may also become viable. These systems could enable sophisticated science missions, highly efficient cargo delivery, and human missions to numerous destinations. Commonalities between NTP, fission power systems, and NEP will be discussed.

Operationally Efficient Propulsion System Study (OEPSS) data book. Volume 3: Operations technology

NASA Technical Reports Server (NTRS)

Vilja, John O.

1990-01-01

The study was initiated to identify operational problems and cost drivers for current propulsion systems and to identify technology and design approaches to increase the operational efficiency and reduce operations costs for future propulsion systems. To provide readily usable data for the Advanced Launch System (ALS) program, the results of the OEPSS study were organized into a series of OEPSS Data Books. This volume describes operations technologies that will enhance operational efficiency of propulsion systems. A total of 15 operations technologies were identified that will eliminate or mitigate operations problems described in Volume 2. A recommended development plan is presented for eight promising technologies that will simplify the propulsion system and reduce operational requirements.

LO2/LH2 propulsion for outer planet orbiter spacecraft

NASA Technical Reports Server (NTRS)

Garrison, P. W.; Sigurdson, K. B.

1983-01-01

Galileo class orbiter missions (750-1500 kg) to the outer planets require a large postinjection delta-V for improved propulsion performance. The present investigation shows that a pump-fed low thrust LO2/LH2 propulsion system can provide a significantly larger net on-orbit mass for a given delta-V than a state-of-the-art earth storable, N2O4/monomethylhydrazine pressure-fed propulsion system. A description is given of a conceptual design for a LO2/LH2 pump-fed propulsion system developed for a Galileo class mission to the outer planets. Attention is given to spacecraft configuration, details regarding the propulsion system, the thermal control of the cryogenic propellants, and aspects of mission performance.

Children's Subjective Emotional Reactivity to Affective Pictures: Gender Differences and Their Antisocial Correlates in an Unselected Sample of 7-11-Year-Olds

ERIC Educational Resources Information Center

Sharp, Carla; Van Goozen, Stephanie; Goodyer, Ian

2006-01-01

Background: Differential responses in terms of gender and antisocial behaviour in emotional reactivity to affective pictures using the International Affective Picture System (IAPS) have been demonstrated in adult and adolescent samples. Moreover, a quadratic relationship between the arousal (intensity) and valence (degree of unpleasantness) has…

Comparative performance evaluation of advanced AC and DC EV propulsion systems

NASA Astrophysics Data System (ADS)

MacDowall, R. D.; Crumley, R. L.

Idaho National Engineering Laboratory (INEL) evaluates EV propulsion systems and components for the U.S. Department of Energy (DOE) Electric and Hybrid Vehicle (EHV) Program. In this study, experimental data were used to evaluate the relative performances of the benchmark Chrysler/GE ETV-1 DC and the Ford/GE First Generation Single-Shaft AC (ETX-I) propulsion systems. Tests were conducted on the INEL's chassis dynamometer using identical aerodynamic and rolling resistance road-load coefficients and vehicle test weights. The results allowed a direct comparison of selected efficiency and performance characteristics for the two propulsion system technologies. The ETX-I AC system exhibited slightly lower system efficiency during constant speed testing than the ETV-1 DC propulsion system.

The Nuclear Cryogenic Propulsion Stage

NASA Technical Reports Server (NTRS)

Houts, Michael G.; Kim, Tony; Emrich, William J.; Hickman, Robert R.; Broadway, Jeramie W.; Gerrish, Harold P.; Doughty, Glen; Belvin, Anthony; Borowski, Stanley K.; Scott, John

2014-01-01

The fundamental capability of Nuclear Thermal Propulsion (NTP) is game changing for space exploration. A first generation Nuclear Cryogenic Propulsion Stage (NCPS) based on NTP could provide high thrust at a specific impulse above 900 s, roughly double that of state of the art chemical engines. Characteristics of fission and NTP indicate that useful first generation systems will provide a foundation for future systems with extremely high performance. The role of the NCPS in the development of advanced nuclear propulsion systems could be analogous to the role of the DC-3 in the development of advanced aviation. Progress made under the NCPS project could help enable both advanced NTP and advanced Nuclear Electric Propulsion (NEP). Nuclear propulsion can be affordable and viable compared to other propulsion systems and must overcome a biased public fear due to hyper-environmentalism and a false perception of radiation and explosion risk.

Implementation of an Online Database for Chemical Propulsion Systems

NASA Technical Reports Server (NTRS)

David B. Owen, II; McRight, Patrick S.; Cardiff, Eric H.

2009-01-01

The Johns Hopkins University, Chemical Propulsion Information Analysis Center (CPIAC) has been working closely with NASA Goddard Space Flight Center (GSFC); NASA Marshall Space Flight Center (MSFC); the University of Alabama at Huntsville (UAH); The Johns Hopkins University, Applied Physics Laboratory (APL); and NASA Jet Propulsion Laboratory (JPL) to capture satellite and spacecraft propulsion system information for an online database tool. The Spacecraft Chemical Propulsion Database (SCPD) is a new online central repository containing general and detailed system and component information on a variety of spacecraft propulsion systems. This paper only uses data that have been approved for public release with unlimited distribution. The data, supporting documentation, and ability to produce reports on demand, enable a researcher using SCPD to compare spacecraft easily, generate information for trade studies and mass estimates, and learn from the experiences of others through what has already been done. This paper outlines the layout and advantages of SCPD, including a simple example application with a few chemical propulsion systems from various NASA spacecraft.

An integral nuclear power and propulsion system concept

NASA Astrophysics Data System (ADS)

Choong, Phillip T.; Teofilo, Vincent L.; Begg, Lester L.; Dunn, Charles; Otting, William

An integral space power concept provides both the electrical power and propulsion from a common heat source and offers superior performance capabilities over conventional orbital insertion using chemical propulsion systems. This paper describes a hybrid (bimodal) system concept based on a proven, inherently safe solid fuel form for the high temperature reactor core operation and rugged planar thermionic energy converter for long-life steady state electric power production combined with NERVA-based rocket technology for propulsion. The integral system is capable of long-life power operation and multiple propulsion operations. At an optimal thrust level, the integral system can maintain the minimal delta-V requirement while minimizing the orbital transfer time. A trade study comparing the overall benefits in placing large payloads to GEO with the nuclear electric propulsion option shows superiority of nuclear thermal propulsion. The resulting savings in orbital transfer time and the substantial reduction of overall lift requirement enables the use of low-cost launchers for several near-term military satellite missions.

The Propulsion Center at MSFC

NASA Technical Reports Server (NTRS)

Gerrish, Harold; Schmidt, George R. (Technical Monitor)

2000-01-01

The Propulsion Research Center at MSFC serves as a national resource for research of advanced, revolutionary propulsion technologies. Our mission is to move the nation's capabilities beyond the confines of conventional chemical propulsion into an era of aircraft like access to earth-orbit, rapid travel throughout the solar system, and exploration of interstellar space. Current efforts cover a wide range of exciting areas, including high-energy plasma thrusters, advanced fission and fusion engines, antimatter propulsion systems, beamed energy rockets and sails, and fundamental motive physics. Activities involve concept investigation, proof-of-concept demonstration, and breadboard validation of new propulsion systems. The Propulsion Research Center at MSFC provides an environment where NASA, national laboratories, universities, and industry researchers can pool their skills together to perform landmark propulsion achievements. We offer excellent educational opportunities to students and young researchers-fostering a wellspring of innovation that will revolutionize space transportation.

Beamed energy for space craft propulsion - Conceptual status and development potential

NASA Technical Reports Server (NTRS)

Sercel, Joel C.; Frisbee, Robert H.

1987-01-01

This paper outlines the results of a brief study that sought to identify and characterize beamed energy spacecraft propulsion concepts that may have positive impact on the economics of space industrialization. It is argued that the technology of beamed energy propulsion systems may significantly improve the prospects for near-term colonization of outer space. It is tentatively concluded that, for space industrialization purposes, the most attractive near-term beamed energy propulsion systems are based on microwave technology. This conclusion is reached based on consideration of the common features that exist between beamed microwave propulsion and the Solar Power Satellite (SPS) concept. Laser power beaming also continues to be an attractive option for spacecraft propulsion due to the reduced diffraction-induced beam spread afforded by laser radiation wavelengths. The conceptual status and development potential of a variety of beamed energy propulsion concepts are presented. Several alternative space transportation system concepts based on beamed energy propulsion are described.

MW-Class Electric Propulsion System Designs

NASA Technical Reports Server (NTRS)

LaPointe, Michael R.; Oleson, Steven; Pencil, Eric; Mercer, Carolyn; Distefano, Salvador

2011-01-01

Electric propulsion systems are well developed and have been in commercial use for several years. Ion and Hall thrusters have propelled robotic spacecraft to encounters with asteroids, the Moon, and minor planetary bodies within the solar system, while higher power systems are being considered to support even more demanding future space science and exploration missions. Such missions may include orbit raising and station-keeping for large platforms, robotic and human missions to near earth asteroids, cargo transport for sustained lunar or Mars exploration, and at very high-power, fast piloted missions to Mars and the outer planets. The Advanced In-Space Propulsion Project, High Efficiency Space Power Systems Project, and High Power Electric Propulsion Demonstration Project were established within the NASA Exploration Technology Development and Demonstration Program to develop and advance the fundamental technologies required for these long-range, future exploration missions. Under the auspices of the High Efficiency Space Power Systems Project, and supported by the Advanced In-Space Propulsion and High Power Electric Propulsion Projects, the COMPASS design team at the NASA Glenn Research Center performed multiple parametric design analyses to determine solar and nuclear electric power technology requirements for representative 300-kW class and pulsed and steady-state MW-class electric propulsion systems. This paper describes the results of the MW-class electric power and propulsion design analysis. Starting with the representative MW-class vehicle configurations, and using design reference missions bounded by launch dates, several power system technology improvements were introduced into the parametric COMPASS simulations to determine the potential system level benefits such technologies might provide. Those technologies providing quantitative system level benefits were then assessed for technical feasibility, cost, and time to develop. Key assumptions and primary results of the COMPASS MW-class electric propulsion power system study are reported, and discussion is provided on how the analysis might be used to guide future technology investments as NASA moves to more capable high power in-space propulsion systems.

State-of-the-Art for Small Satellite Propulsion Systems

NASA Technical Reports Server (NTRS)

Parker, Khary I.

2016-01-01

SmallSats are a low cost access to space with an increasing need for propulsion systems. NASA, and other organizations, will be using SmallSats that require propulsion systems to: a) Conduct high quality near and far reaching on-orbit research and b) Perform technology demonstrations. Increasing call for high reliability and high performing for SmallSat components. Many SmallSat propulsion technologies are currently under development: a) Systems at various levels of maturity and b) Wide variety of systems for many mission applications.

Directions in propulsion control

NASA Technical Reports Server (NTRS)

Lorenzo, Carl F.

1990-01-01

Discussed here is research at NASA Lewis in the area of propulsion controls as driven by trends in advanced aircraft. The objective of the Lewis program is to develop the technology for advanced reliable propulsion control systems and to integrate the propulsion control with the flight control for optimal full-system control.

Heat transfer in aerospace propulsion

NASA Technical Reports Server (NTRS)

Simoneau, Robert J.; Hendricks, Robert C.; Gladden, Herbert J.

1988-01-01

Presented is an overview of heat transfer related research in support of aerospace propulsion, particularly as seen from the perspective of the NASA Lewis Research Center. Aerospace propulsion is defined to cover the full spectrum from conventional aircraft power plants through the Aerospace Plane to space propulsion. The conventional subsonic/supersonic aircraft arena, whether commercial or military, relies on the turbine engine. A key characteristic of turbine engines is that they involve fundamentally unsteady flows which must be properly treated. Space propulsion is characterized by very demanding performance requirements which frequently push systems to their limits and demand tailored designs. The hypersonic flight propulsion systems are subject to severe heat loads and the engine and airframe are truly one entity. The impact of the special demands of each of these aerospace propulsion systems on heat transfer is explored.

Selection and Prioritization of Advanced Propulsion Technologies for Future Space Missions

NASA Technical Reports Server (NTRS)

Eberle, Bill; Farris, Bob; Johnson, Les; Jones, Jonathan; Kos, Larry; Woodcock, Gordon; Brady, Hugh J. (Technical Monitor)

2002-01-01

The exploration of our solar system will require spacecraft with much greater capability than spacecraft which have been launched in the past. This is particularly true for exploration of the outer planets. Outer planet exploration requires shorter trip times, increased payload mass, and ability to orbit or land on outer planets. Increased capability requires better propulsion systems, including increased specific impulse. Chemical propulsion systems are not capable of delivering the performance required for exploration of the solar system. Future propulsion systems will be applied to a wide variety of missions with a diverse set of mission requirements. Many candidate propulsion technologies have been proposed but NASA resources do not permit development of a] of them. Therefore, we need to rationally select a few propulsion technologies for advancement, for application to future space missions. An effort was initiated to select and prioritize candidate propulsion technologies for development investment. The results of the study identified Aerocapture, 5 - 10 KW Solar Electric Ion, and Nuclear Electric Propulsion as high priority technologies. Solar Sails, 100 Kw Solar Electric Hall Thrusters, Electric Propulsion, and Advanced Chemical were identified as medium priority technologies. Plasma sails, momentum exchange tethers, and low density solar sails were identified as high risk/high payoff technologies.

Powersail High Power Propulsion System Design Study

NASA Astrophysics Data System (ADS)

Gulczinski, Frank S., III

2000-11-01

A desire by the United States Air Force to exploit the space environment has led to a need for increased on-orbit electrical power availability. To enable this, the Air Force Research Laboratory Space Vehicles Directorate (AFRL/ VS) is developing Powersail: a two-phased program to demonstrate high power (100 kW to 1 MW) capability in space using a deployable, flexible solar array connected to the host spacecraft using a slack umbilical. The first phase will be a proof-of-concept demonstration at 50 kW, followed by the second phase, an operational system at full power. In support of this program, the AFRL propulsion Directorate's Spacecraft Propulsion Branch (AFRL/PRS ) at Edwards AFB has commissioned a design study of the Powersail High Power Propulsion System. The purpose of this study, the results of which are summarized in this paper, is to perform mission and design trades to identify potential full-power applications (both near-Earth and interplanetary) and the corresponding propulsion system requirements and design. The design study shall farther identify a suitable low power demonstration flight that maximizes risk reduction for the fully operational system. This propulsion system is expected to be threefold: (1) primary propulsion for moving the entire vehicle, (2) a propulsion unit that maintains the solar array position relative to the host spacecraft, and (3) control propulsion for maintaining proper orientation for the flexible solar array.

NASA In-Space Propulsion Technology Program: Overview and Update

NASA Technical Reports Server (NTRS)

Johnson, Les; Alexander, Leslie; Baggett, Randy M.; Bonometti, Joseph A.; Herrmann, Melody; James, Bonnie F.; Montgomery, Sandy E.

2004-01-01

NASA's In-Space Propulsion Technology Program is investing in technologies that have the potential to revolutionize the robotic exploration of deep space. For robotic exploration and science missions, increased efficiencies of future propulsion systems are critical to reduce overall life-cycle costs and, in some cases, enable missions previously considered impossible. Continued reliance on conventional chemical propulsion alone will not enable the robust exploration of deep space - the maximum theoretical efficiencies have almost been reached and they are insufficient to meet needs for many ambitious science missions currently being considered. The In-Space Propulsion Technology Program's technology portfolio includes many advanced propulsion systems. From the next-generation ion propulsion system operating in the 5- to 10-kW range to aerocapture and solar sails, substantial advances in - spacecraft propulsion performance are anticipated. Some of the most promising technologies for achieving these goals use the environment of space itself for energy and propulsion and are generically called 'propellantless' because they do not require onboard fuel to achieve thrust. Propellantless propulsion technologies include scientific innovations such as solar sails, electrodynamic and momentum transfer.tethers, aeroassist and aerocapture. This paper will provide an overview of both propellantless and propellant-based advanced propulsion technologies, as well as NASA's plans for advancing them as part of the In-Space Propulsion Technology Program.

NASA's In-Space Propulsion Technology Program: Overview and Update

NASA Technical Reports Server (NTRS)

Johnson, Les; Alexander, Leslie; Baggett, Randy M.; Bonometti, Joseph A.; Herrmann, Melody; James, Bonnie F.; Montgomery, Sandy E.

2004-01-01

NASA's In-Space Propulsion Technology Program is investing in technologies that have the potential to revolutionize the robotic exploration of deep space. For robotic exploration and science missions, increased efficiencies of future propulsion systems are critical to reduce overall life-cycle costs and, in some cases, enable missions previously considered impossible. Continued reliance on conventional chemical propulsion alone will not enable the robust exploration of deep space - the maximum theoretical efficiencies have almost been reached and they are insufficient to meet needs for many ambitious science missions currently being considered. The In-Space Propulsion Technology Program s technology portfolio includes many advanced propulsion systems. From the next-generation ion propulsion system operating in the 5- to 10-kW range to aerocapture and solar sails, substantial advances in spacecraft propulsion performance are anticipated. Some of the most promising technologies for achieving these goals ase the environment of space itself for energy and propulsion and are generically called 'propellantless' because they do not require onboard fuel to achieve thrust. Propellantless propulsion technologies include scientific innovations such as solar sails, electrodynamic and momentum transfer tethers, aeroassist, and aerocapture. This paper will provide an overview of both propellantless and propellant-based advanced propulsion technologies, as well as NASA s plans for advancing them as part of the In-Space Propulsion Technology Program.

The need for expanded exploration of matter-antimatter annihilation for propulsion application

NASA Technical Reports Server (NTRS)

Massier, P. F.

1982-01-01

The use of matter-antimatter annihilation as a propulsion application for interstellar travel is discussed. The physical basis for the superior energy release in such a system is summarized, and the problems associated with antimatter production, collection and storage are assessed. Advances in devising a workable propulsion system are reported, and the parameters of an antimatter propulsion system are described.

Hybrid rocket propulsion systems for outer planet exploration missions

NASA Astrophysics Data System (ADS)

Jens, Elizabeth T.; Cantwell, Brian J.; Hubbard, G. Scott

2016-11-01

Outer planet exploration missions require significant propulsive capability, particularly to achieve orbit insertion. Missions to explore the moons of outer planets place even more demanding requirements on propulsion systems, since they involve multiple large ΔV maneuvers. Hybrid rockets present a favorable alternative to conventional propulsion systems for many of these missions. They typically enjoy higher specific impulse than solids, can be throttled, stopped/restarted, and have more flexibility in their packaging configuration. Hybrids are more compact and easier to throttle than liquids and have similar performance levels. In order to investigate the suitability of these propulsion systems for exploration missions, this paper presents novel hybrid motor designs for two interplanetary missions. Hybrid propulsion systems for missions to Europa and Uranus are presented and compared to conventional in-space propulsion systems. The hybrid motor design for each of these missions is optimized across a range of parameters, including propellant selection, O/F ratio, nozzle area ratio, and chamber pressure. Details of the design process are described in order to provide guidance for researchers wishing to evaluate hybrid rocket motor designs for other missions and applications.

Overview of the Development of the Advanced Electric Propulsion System (AEPS)

NASA Technical Reports Server (NTRS)

Herman, Daniel; Tofil, Todd; Santiago, Walter; Kamhawi, Hani; Polk, James; Snyder, John Steven; Hofer, Richard; Picha, Frank; Schmidt, George

2017-01-01

NASA is committed to the demonstration and application of high-power solar electric propulsion to meet its future mission needs. It is continuing to develop the 14 kW Advanced Electric Propulsion System (AEPS) under a project that recently completed an Early Integrated System Test (EIST) and System Preliminary Design Review (PDR). In addition, NASA is pursuing external partnerships in order to demonstrate Solar Electric Propulsion (SEP) technology and the advantages of high-power electric propulsion-based spacecraft. The recent announcement of a Power and Propulsion Element (PPE) as the first major piece of an evolvable human architecture to Mars has replaced the Asteroid Redirect Robotic Mission (ARRM) as the most likely first application of the AEPS Hall thruster system. This high-power SEP capability, or an extensible derivative of it, has been recognized as a critical part of a new, affordable human exploration architecture for missions beyond-low-Earth-orbit. This paper presents the status of AEPS development activities, and describes how AEPS hardware will be integrated into the PPE ion propulsion system.

Preliminary Assessment of Thrust Augmentation of NEP Based Missions

NASA Technical Reports Server (NTRS)

Chew, Gilbert; Pelaccio, Dennis G.; Chiroux, Robert; Pervan, Sherry; Rauwolf, Gerald A.; White, Charles

2005-01-01

Science Applications International Corporation (SAIC), with support from NASA Marshall Space Flight Center, has conducted a preliminary study to compare options for augmenting the thrust of a conventional nuclear electric propulsion (NEP) system. These options include a novel nuclear propulsion system concept known as Hybrid Indirect Nuclear Propulsion (HINP) and conventional chemical propulsion. The utility and technical feasibility of the HINP concept are assessed, and features and potential of this new in-space propulsion system concept are identified. As part of the study, SAIC developed top-level design tools to model the size and performance of an HINP system, as well as for several chemical propulsion options, including liquid and gelled propellants. A mission trade study was performed to compare a representative HINP system with chemical propulsion options for thrust augmentation of NEP systems for a mission to Saturn's moon Titan. Details pertaining to the approach, features, initial demonstration results for HINP model development, and the mission trade study are presented. Key technology and design issues associated with the HINP concept and future work recommendations are also identified.

Factors Influencing Solar Electric Propulsion Vehicle Payload Delivery for Outer Planet Missions

NASA Technical Reports Server (NTRS)

Cupples, Michael; Green, Shaun; Coverstone, Victoria

2003-01-01

Systems analyses were performed for missions utilizing solar electric propulsion systems to deliver payloads to outer-planet destinations. A range of mission and systems factors and their affect on the delivery capability of the solar electric propulsion system was examined. The effect of varying the destination, the trip time, the launch vehicle, and gravity-assist boundary conditions was investigated. In addition, the affects of selecting propulsion system and power systems characteristics (including primary array power variation, number of thrusters, thruster throttling mode, and thruster Isp) on delivered payload was examined.

Development of technology for creating intelligent control systems for power plants and propulsion systems for marine robotic systems

NASA Astrophysics Data System (ADS)

Iakovleva, E. V.; Momot, B. A.

2017-10-01

The object of this study is to develop a power plant and an electric propulsion control system for autonomous remotely controlled vessels. The tasks of the study are as follows: to assess remotely controlled vessels usage reasonability, to define the requirements for this type of vessel navigation. In addition, the paper presents the analysis of technical diagnostics systems. The developed electric propulsion control systems for vessels should provide improved reliability and efficiency of the propulsion complex to ensure the profitability of remotely controlled vessels.

A Titan Explorer Mission Utilizing Solar Electric Propulsion and Chemical Propulsion Systems

NASA Technical Reports Server (NTRS)

Cupples, Michael; Coverstone, Vicki

2003-01-01

Mission and Systems analyses were performed for a Titan Explorer Mission scenario utilizing medium class launch vehicles, solar electric propulsion system (SEPS) for primary interplanetary propulsion, and chemical propulsion for capture at Titan. An examination of a range of system factors was performed to determine their affect on the payload delivery capability to Titan. The effect of varying the launch vehicle, solar array power, associated number of SEPS thrusters, chemical propellant combinations, tank liner thickness, and tank composite overwrap stress factor was investigated. This paper provides a parametric survey of the aforementioned set of system factors, delineating their affect on Titan payload delivery, as well as discussing aspects of planetary capture methodology.

Propulsion Options for the LISA Mission

NASA Technical Reports Server (NTRS)

Cardiff, Eric H.; Marr, Gregory C.

2004-01-01

The LISA mission is a constellation of three spacecraft operating at 1 AU from the Sun in a position trailing the Earth. After launch, a propulsion module provides the AV necessary to reach this operational orbit, and separates from the spacecraft. A second propulsion system integrated with the spacecraft maintains the operational orbit and reduces nongravitational disturbances on the instruments. Both chemical and electrical propulsion systems were considered for the propulsion module, and this trade is presented to show the possible benefits of an EP system. Several options for the orbit maintenance and disturbance reduction system are also briefly discussed, along with several important requirements that suggest the use of a FEEP thruster system.

Design of Electrical Systems for Rocket Propulsion Test Facilities at the John C. Stennis Space Center

NASA Technical Reports Server (NTRS)

Hughes, Mark S.; Davis, Dawn M.; Bakker, Henry J.; Jensen, Scott L.

2007-01-01

This viewgraph presentation reviews the design of the electrical systems that are required for the testing of rockets at the Rocket Propulsion Facility at NASA Stennis Space Center (NASA SSC). NASA/SSC s Mission in Rocket Propulsion Testing Is to Acquire Test Performance Data for Verification, Validation and Qualification of Propulsion Systems Hardware. These must be accurate reliable comprehensive and timely. Data acquisition in a rocket propulsion test environment is challenging: severe temporal transient dynamic environments, large thermal gradients, vacuum to 15 ksi pressure regimes SSC has developed and employs DAS, control systems and control systems and robust instrumentation that effectively satisfies these challenges.

The Altitude Wind Tunnel (AWT): A unique facility for propulsion system and adverse weather testing

NASA Technical Reports Server (NTRS)

Chamberlin, R.

1985-01-01

A need has arisen for a new wind tunnel facility with unique capabilities for testing propulsion systems and for conducting research in adverse weather conditions. New propulsion system concepts, new aircraft configurations with an unprecedented degree of propulsion system/aircraft integration, and requirements for aircraft operation in adverse weather dictate the need for a new test facility. Required capabilities include simulation of both altitude pressure and temperature, large size, full subsonic speed range, propulsion system operation, and weather simulation (i.e., icing, heavy rain). A cost effective rehabilitation of the NASA Lewis Research Center's Altitude Wind Tunnel (AWT) will provide a facility with all these capabilities.

SSTAC/ARTS Review of the Draft Integrated Technology Plan (ITP). Volume 2: Propulsion Systems

NASA Technical Reports Server (NTRS)

1991-01-01

The topics addressed are: (1) space propulsion technology program overview; (2) space propulsion technology program fact sheet; (3) low thrust propulsion; (4) advanced propulsion concepts; (5) high-thrust chemical propulsion; (6) cryogenic fluid management; (7) NASA CSTI earth-to-orbit propulsion; (8) advanced main combustion chamber program; (9) earth-to-orbit propulsion turbomachinery; (10) transportation technology; (11) space chemical engines technology; (12) nuclear propulsion; (13) spacecraft on-board propulsion; and (14) low-cost commercial transport.

Intrasystem Analysis Program (IAP) Structural Design Study.

DTIC Science & Technology

1981-06-01

accuracy constraints, and user competence . This report is designed to serve as a guide in con- structing procedures and identifying those aspects of the...parameters. 3.3.3 Userability The term "Userability" refers here to the level of competence assumed for an IAP analyst in need of a procedure. There...media the wires pass through is homogeneous along the length of the wires. Under these assumptions the wave propagation is predominantly tranverse

A Novel 6'-N-Aminoglycoside Acetyltransferase, AAC(6')-Ial, from a Clinical Isolate of Serratia marcescens.

PubMed

Tada, Tatsuya; Miyoshi-Akiyama, Tohru; Shimada, Kayo; Dahal, Rajan K; Mishra, Shyam K; Ohara, Hiroshi; Kirikae, Teruo; Pokhrel, Bharat M

2016-03-01

Serratia marcescens IOMTU115 has a novel 6'-N-aminoglycoside acetyltransferase-encoding gene, aac(6')-Ial. The encoded protein AAC(6')-Ial has 146 amino acids, with 91.8% identity to the amino acid sequence of AAC(6')-Ic in S. marcescens SM16 and 97.3% identity to the amino acid sequence of AAC(6')-Iap in S. marcescens WW4. The minimum inhibitory concentrations of aminoglycosides for Escherichia coli expressing AAC(6')-Ial were similar to those for E. coli expressing AAC(6')-Ic or AAC(6')-Iap. Thin-layer chromatography showed that AAC(6')-Ial, AAC(6')-Ic, or AAC(6')-Iap acetylated all the aminoglycosides tested, except for apramycin, gentamicin, and lividomycin. Kinetics assays revealed that AAC(6')-Ial is a functional acetyltransferase against aminoglycosides. The aac(6')-Ial gene was located on chromosomal DNA.

Engineering of the Magnetized Target Fusion Propulsion System

NASA Technical Reports Server (NTRS)

Statham, G.; White, S.; Adams, R. B.; Thio, Y. C. F.; Santarius, J.; Alexander, R.; Fincher, S.; Polsgrove, T.; Chapman, J.; Philips, A.

2002-01-01

Engineering details are presented for a magnetized target fusion (MTF) propulsion system designed to support crewed missions to the outer solar system. Structural, thermal and radiation-management design details are presented. Propellant storage and supply options are also discussed and a propulsion system mass estimate is given.

Mission Options for an Electric Propulsion Demonstration Flight Test

NASA Technical Reports Server (NTRS)

Garner, Charles

1989-01-01

Several mission options are discussed for an electric propulsion space test which provides operational and performance data for ion and arcjet propulsion systems and testing of APSA arrays and a super power system. The results of these top-level studies are considered preliminary. Ion propulsion system design and architecture for the purposes of performing orbit raising missions for payloads in the range of 2400 to 2700 kg are described. Focus was placed on a design which can be characterized by simplicity, reliability, and performance. Systems of this design are suitable for an electric propulsion precursor flight which would provide proof of principle data necessary for more ambitious and complex missions.

Nuclear Thermal Propulsion: A Joint NASA/DOE/DOD Workshop

NASA Technical Reports Server (NTRS)

Clark, John S. (Editor)

1991-01-01

Papers presented at the joint NASA/DOE/DOD workshop on nuclear thermal propulsion are compiled. The following subject areas are covered: nuclear thermal propulsion programs; Rover/NERVA and NERVA systems; Low Pressure Nuclear Thermal Rocket (LPNTR); particle bed reactor nuclear rocket; hybrid propulsion systems; wire core reactor; pellet bed reactor; foil reactor; Droplet Core Nuclear Rocket (DCNR); open cycle gas core nuclear rockets; vapor core propulsion reactors; nuclear light bulb; Nuclear rocket using Indigenous Martian Fuel (NIMF); mission analysis; propulsion and reactor technology; development plans; and safety issues.

An Overview of the NASA Aviation Safety Program Propulsion Health Monitoring Element

NASA Technical Reports Server (NTRS)

Simon, Donald L.

2000-01-01

The NASA Aviation Safety Program (AvSP) has been initiated with aggressive goals to reduce the civil aviation accident rate, To meet these goals, several technology investment areas have been identified including a sub-element in propulsion health monitoring (PHM). Specific AvSP PHM objectives are to develop and validate propulsion system health monitoring technologies designed to prevent engine malfunctions from occurring in flight, and to mitigate detrimental effects in the event an in-flight malfunction does occur. A review of available propulsion system safety information was conducted to help prioritize PHM areas to focus on under the AvSP. It is noted that when a propulsion malfunction is involved in an aviation accident or incident, it is often a contributing factor rather than the sole cause for the event. Challenging aspects of the development and implementation of PHM technology such as cost, weight, robustness, and reliability are discussed. Specific technology plans are overviewed including vibration diagnostics, model-based controls and diagnostics, advanced instrumentation, and general aviation propulsion system health monitoring technology. Propulsion system health monitoring, in addition to engine design, inspection, maintenance, and pilot training and awareness, is intrinsic to enhancing aviation propulsion system safety.

Propulsion System Dynamic Modeling of the NASA Supersonic Concept Vehicle for AeroPropulsoServoElasticity

NASA Technical Reports Server (NTRS)

Kopasakis, George; Connolly, Joseph W.; Seiel, Jonathan

2016-01-01

A summary of the propulsion system modeling under NASA's High Speed Project (HSP) AeroPropulsoServoElasticity (APSE) task is provided with a focus on the propulsion system for the low-boom supersonic configuration developed by Lockheed Martin and referred to as the N+2 configuration. This summary includes details on the effort to date to develop computational models for the various propulsion system components. The objective of this paper is to summarize the model development effort in this task, while providing more detail in the modeling areas that have not been previously published. The purpose of the propulsion system modeling and the overall APSE effort is to develop an integrated dynamic vehicle model to conduct appropriate unsteady analysis of supersonic vehicle performance. This integrated APSE system model concept includes the propulsion system model, and the vehicle structural aerodynamics model. The development to date of such a preliminary integrated model will also be summarized in this report

Propulsion System Dynamic Modeling of the NASA Supersonic Concept Vehicle for AeroPropulsoServoElasticity

NASA Technical Reports Server (NTRS)

Kopasakis, George; Connolly, Joseph W.; Seidel, Jonathan

2014-01-01

A summary of the propulsion system modeling under NASA's High Speed Project (HSP) AeroPropulsoServoElasticity (APSE) task is provided with a focus on the propulsion system for the lowboom supersonic configuration developed by Lockheed Martin and referred to as the N+2 configuration. This summary includes details on the effort to date to develop computational models for the various propulsion system components. The objective of this paper is to summarize the model development effort in this task, while providing more detail in the modeling areas that have not been previously published. The purpose of the propulsion system modeling and the overall APSE effort is to develop an integrated dynamic vehicle model to conduct appropriate unsteady analysis of supersonic vehicle performance. This integrated APSE system model concept includes the propulsion system model, and the vehicle structural-aerodynamics model. The development to date of such a preliminary integrated model will also be summarized in this report.

Propulsion Investigation for Zero and Near-Zero Emissions Aircraft

NASA Technical Reports Server (NTRS)

Snyder, Christopher A.; Berton, Jeffrey J.; Brown, Gerald v.; Dolce, James L.; Dravid, Marayan V.; Eichenberg, Dennis J.; Freeh, Joshua E.; Gallo, Christopher A.; Jones, Scott M.; Kundu, Krishna P.;

Advanced supersonic propulsion study. [with emphasis on noise level reduction

NASA Technical Reports Server (NTRS)

Sabatella, J. A. (Editor)

1974-01-01

A study was conducted to determine the promising propulsion systems for advanced supersonic transport application, and to identify the critical propulsion technology requirements. It is shown that noise constraints have a major effect on the selection of the various engine types and cycle parameters. Several promising advanced propulsion systems were identified which show the potential of achieving lower levels of sideline jet noise than the first generation supersonic transport systems. The non-afterburning turbojet engine, utilizing a very high level of jet suppression, shows the potential to achieve FAR 36 noise level. The duct-heating turbofan with a low level of jet suppression is the most attractive engine for noise levels from FAR 36 to FAR 36 minus 5 EPNdb, and some series/parallel variable cycle engines show the potential of achieving noise levels down to FAR 36 minus 10 EPNdb with moderate additional penalty. The study also shows that an advanced supersonic commercial transport would benefit appreciably from advanced propulsion technology. The critical propulsion technology needed for a viable supersonic propulsion system, and the required specific propulsion technology programs are outlined.

Propulsive Efficiencies of Magnetohydrodynamic Submerged Vehicular Propulsors

DTIC Science & Technology

1990-04-01

TERMS (Con’we on mrae . neoaay and kWerty by back nLt.) FIELD GROUP SUB-GROUP Magnetohydrodynamic propulsion, marine propulsion, seawater pump ...propelling a vehicular structure by a seawater elec- tromagnetic pump . This propulsion system can be applied to a surface ship or a submerged vehicle; however...structure by a seawater electromagnetic pump . This propulsion system can be applied to a surface ship or a submerged vehicle; however, in this work only

Test facilities for high power electric propulsion

NASA Technical Reports Server (NTRS)

Sovey, James S.; Vetrone, Robert H.; Grisnik, Stanley P.; Myers, Roger M.; Parkes, James E.

1991-01-01

Electric propulsion has applications for orbit raising, maneuvering of large space systems, and interplanetary missions. These missions involve propulsion power levels from tenths to tens of megawatts, depending upon the application. General facility requirements for testing high power electric propulsion at the component and thrust systems level are defined. The characteristics and pumping capabilities of many large vacuum chambers in the United States are reviewed and compared with the requirements for high power electric propulsion testing.

Options For Development of Space Fission Propulsion Systems

NASA Technical Reports Server (NTRS)

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

2001-01-01

Fission technology can enable rapid, affordable access to any point in the solar system. Potential fission-based transportation options include high specific power continuous impulse propulsion systems and bimodal nuclear thermal rockets. Despite their tremendous potential for enhancing or enabling deep space and planetary missions, to date space fission system have only been used in Earth orbit. The first step towards utilizing advanced fission propulsion systems is development of a safe, near-term, affordable fission system that can enhance or enable near-term missions of interest. An evolutionary approach for developing space fission propulsion systems is proposed.

46 CFR 127.110 - Plans and specifications required for new construction.

Code of Federal Regulations, 2011 CFR

2011-10-01

.... (v) Fluid-driven power and control systems. (vi) Through-hull penetrations and shell connections...) Steering and steering-control systems. (4) Propulsion and propulsion-control systems. (5) Piping diagrams... personnel in the control and observation of the propulsion systems and machinery spaces, or to reduce the...

Volume Dynamics Propulsion System Modeling for Supersonics Vehicle Research

NASA Technical Reports Server (NTRS)

Kopasakis, George; Connolly, Joseph W.; Paxson, Daniel E.; Ma, Peter

2010-01-01

Under the NASA Fundamental Aeronautics Program the Supersonics Project is working to overcome the obstacles to supersonic commercial flight. The proposed vehicles are long slim body aircraft with pronounced aero-servo-elastic modes. These modes can potentially couple with propulsion system dynamics; leading to performance challenges such as aircraft ride quality and stability. Other disturbances upstream of the engine generated from atmospheric wind gusts, angle of attack, and yaw can have similar effects. In addition, for optimal propulsion system performance, normal inlet-engine operations are required to be closer to compressor stall and inlet unstart. To study these phenomena an integrated model is needed that includes both airframe structural dynamics as well as the propulsion system dynamics. This paper covers the propulsion system component volume dynamics modeling of a turbojet engine that will be used for an integrated vehicle Aero-Propulso-Servo-Elastic model and for propulsion efficiency studies.

Volume Dynamics Propulsion System Modeling for Supersonics Vehicle Research

NASA Technical Reports Server (NTRS)

Kopasakis, George; Connolly, Joseph W.; Paxson, Daniel E.; Ma, Peter

2008-01-01

Under the NASA Fundamental Aeronautics Program, the Supersonics Project is working to overcome the obstacles to supersonic commercial flight. The proposed vehicles are long slim body aircraft with pronounced aero-servo-elastic modes. These modes can potentially couple with propulsion system dynamics; leading to performance challenges such as aircraft ride quality and stability. Other disturbances upstream of the engine generated from atmospheric wind gusts, angle of attack, and yaw can have similar effects. In addition, for optimal propulsion system performance, normal inlet-engine operations are required to be closer to compressor stall and inlet unstart. To study these phenomena an integrated model is needed that includes both airframe structural dynamics as well as the propulsion system dynamics. This paper covers the propulsion system component volume dynamics modeling of a turbojet engine that will be used for an integrated vehicle Aero-Propulso-Servo-Elastic model and for propulsion efficiency studies.

Volume Dynamics Propulsion System Modeling for Supersonics Vehicle Research

NASA Technical Reports Server (NTRS)

Kopasakis, George; Connolly, Joseph W.; Paxson, Daniel E.; Ma, Peter

2008-01-01

Under the NASA Fundamental Aeronautics Program the Supersonics Project is working to overcome the obstacles to supersonic commercial flight. The proposed vehicles are long slim body aircraft with pronounced aero-servo-elastic modes. These modes can potentially couple with propulsion system dynamics; leading to performance challenges such as aircraft ride quality and stability. Other disturbances upstream of the engine generated from atmospheric wind gusts, angle of attack, and yaw can have similar effects. In addition, for optimal propulsion system performance, normal inlet-engine operations are required to be closer to compressor stall and inlet unstart. To study these phenomena an integrated model is needed that includes both airframe structural dynamics as well as the propulsion system dynamics. This paper covers the propulsion system component volume dynamics modeling of a turbojet engine that will be used for an integrated vehicle Aero- Propulso-Servo-Elastic model and for propulsion efficiency studies.

Resource Prospector Propulsion Cold Flow Test

NASA Technical Reports Server (NTRS)

Williams, Hunter; Pederson, Kevin; Dervan, Melanie; Holt, Kimberly; Jernigan, Frankie; Trinh, Huu; Flores, Sam

2014-01-01

For the past year, NASA Marshall Space Flight Center and Johnson Space Center have been working on a government version of a lunar lander design for the Resource Prospector Mission. A propulsion cold flow test system, representing an early flight design of the propulsion system, has been fabricated. The primary objective of the cold flow test is to simulate the Resource Prospector propulsion system operation through water flow testing and obtain data for anchoring analytical models. This effort will also provide an opportunity to develop a propulsion system mockup to examine hardware integration to a flight structure. This paper will report the work progress of the propulsion cold flow test system development and test preparation. At the time this paper is written, the initial waterhammer testing is underway. The initial assessment of the test data suggests that the results are as expected and have a similar trend with the pretest prediction. The test results will be reported in a future conference.

A High Power Solar Electric Propulsion - Chemical Mission for Human Exploration of Mars

NASA Technical Reports Server (NTRS)

Burke, Laura M.; Martini, Michael C.; Oleson, Steven R.

2014-01-01

Recently Solar Electric Propulsion (SEP) as a main propulsion system has been investigated as an option to support manned space missions to near-Earth destinations for the NASA Gateway spacecraft. High efficiency SEP systems are able to reduce the amount of propellant long duration chemical missions require, ultimately reducing the required mass delivered to Low Earth Orbit (LEO) by a launch vehicle. However, for long duration interplanetary Mars missions, using SEP as the sole propulsion source alone may not be feasible due to the long trip times to reach and insert into the destination orbit. By combining an SEP propulsion system with a chemical propulsion system the mission is able to utilize the high-efficiency SEP for sustained vehicle acceleration and deceleration in heliocentric space and the chemical system for orbit insertion maneuvers and trans-earth injection, eliminating the need for long duration spirals. By capturing chemically instead of with low-thrust SEP, Mars stay time increases by nearly 200 days. Additionally, the size the of chemical propulsion system can be significantly reduced from that of a standard Mars mission because the SEP system greatly decreases the Mars arrival and departure hyperbolic excess velocities (V(sub infinity)).

Subsonic flight test evaluation of a propulsion system parameter estimation process for the F100 engine

NASA Technical Reports Server (NTRS)

Orme, John S.; Gilyard, Glenn B.

1992-01-01

Integrated engine-airframe optimal control technology may significantly improve aircraft performance. This technology requires a reliable and accurate parameter estimator to predict unmeasured variables. To develop this technology base, NASA Dryden Flight Research Facility (Edwards, CA), McDonnell Aircraft Company (St. Louis, MO), and Pratt & Whitney (West Palm Beach, FL) have developed and flight-tested an adaptive performance seeking control system which optimizes the quasi-steady-state performance of the F-15 propulsion system. This paper presents flight and ground test evaluations of the propulsion system parameter estimation process used by the performance seeking control system. The estimator consists of a compact propulsion system model and an extended Kalman filter. The extended Laman filter estimates five engine component deviation parameters from measured inputs. The compact model uses measurements and Kalman-filter estimates as inputs to predict unmeasured propulsion parameters such as net propulsive force and fan stall margin. The ability to track trends and estimate absolute values of propulsion system parameters was demonstrated. For example, thrust stand results show a good correlation, especially in trends, between the performance seeking control estimated and measured thrust.

Fusion for Space Propulsion and Plasma Liner Driven MTF

NASA Technical Reports Server (NTRS)

Thio, Y.C. Francis; Rodgers, Stephen L. (Technical Monitor)

2001-01-01

The need for fusion propulsion for interplanetary flights is discussed. For a propulsion system, there are three important system attributes: (1) The absolute amount of energy available, (2) the propellant exhaust velocity, and (3) the jet power per unit mass of the propulsion system (specific power). For human exploration and development of the solar system, propellant exhaust velocity in excess of 100 km/s and specific power in excess of 10 kW/kg are required. Chemical combustion cannot meet the requirement in propellant exhaust velocity. Nuclear fission processes typically result in producing energy in the form of heat that needs to be manipulated at temperatures limited by materials to about 2,800 K. Using the energy to heat a low atomic weight propellant cannot overcome the problem. Alternatively the energy can be converted into electricity which is then used to accelerate particles to high exhaust velocity. The necessary power conversion and conditioning equipment, however, increases the mass of the propulsion system for the same jet power by more than two orders of magnitude over chemical system, thus greatly limits the thrust-to-weight ratio attainable. If fusion can be developed, fusion appears to have the best of all worlds in terms of propulsion - it can provide the absolute amount, the propellant exhaust velocity, and the high specific jet power. An intermediate step towards pure fusion propulsion is a bimodal system in which a fission reactor is used to provide some of the energy to drive a fusion propulsion unit. The technical issues related to fusion for space propulsion are discussed. There are similarities as well as differences at the system level between applying fusion to propulsion and to terrestrial electrical power generation. The differences potentially provide a wider window of opportunities for applying fusion to propulsion. For example, pulsed approaches to fusion may be attractive for the propulsion application. This is particularly so in the light of significant development of the enabling pulsed power component technologies that have occurred in the last two decades because of defense and other energy requirements. The extreme states of matter required to produce fusion reactions may be more readily realizable in the pulsed states with less system mass than in steady states. Significant saving in system mass may result in pulsed fusion systems using plasmas in the appropriate density regimes. Magnetized target fusion, which attempts to combine the favorable attributes of magnetic confinement and inertial compression-containment into one single integrated fusion scheme, appears to have benefits that are worth exploring for propulsion application.

In-Space Propulsion Technologies for Robotic Exploration of the Solar System

NASA Technical Reports Server (NTRS)

Johnson, Les; Meyer, Rae Ann; Frame, Kyle

2006-01-01

Supporting NASA's Science Mission Directorate, the In-Space Propulsion Technology Program is developing the next generation of space propulsion technologies for robotic, deep-space exploration. Recent technological advancements and demonstrations of key, high-payoff propulsion technologies have been achieved and will be described. Technologies under development and test include aerocapture, solar electric propulsion, solar sail propulsion, and advanced chemical propulsion.

LOX/LH2 propulsion system for launch vehicle upper stage, test results

NASA Technical Reports Server (NTRS)

Ikeda, T.; Imachi, U.; Yuzawa, Y.; Kondo, Y.; Miyoshi, K.; Higashino, K.

1984-01-01

The test results of small LOX/LH2 engines for two propulsion systems, a pump fed system and a pressure fed system are reported. The pump fed system has the advantages of higher performances and higher mass fraction. The pressure fed system has the advantages of higher reliability and relative simplicity. Adoption of these cryogenic propulsion systems for upper stage of launch vehicle increases the payload capability with low cost. The 1,000 kg thrust class engine was selected for this cryogenic stage. A thrust chamber assembly for the pressure fed propulsion system was tested. It is indicated that it has good performance to meet system requirements.

Propulsion Technology Needs for Exploration

NASA Technical Reports Server (NTRS)

Brown, Thomas

2007-01-01

The objectives of currently planned exploration efforts, as well as those further in the future, require significant advancements in propulsion technologies. The current Lunar exploration architecture has set goals and mission objectives that necessitate the use of new systems and the extension of existing technologies beyond present applications. In the near term, the majority of these technologies are the result of a need to apply high performing cryogenic propulsion systems to long duration in-space applications. Advancement of cryogenic propulsion to these applications is crucial to provide higher performing propulsion systems that reduce the vehicle masses; enhance the safety of vehicle systems and ground operations; and provide a path for In-situ Resource Utilization (ISRU).Use of a LOX/LH2 main propulsion system for Lunar Lander Descent is a top priority because more conventional storable propellants are far from meeting the performance needs of the current architecture. While LOX/LH2 pump feed engines have been used in flight applications for many years, these engines have limited throttle capabilities. Engines that are capable of much greater throttling while still meeting high performance goals are a necessity to achieving exploration goals. Applications of LOX/CH4 propulsion to Lander ascent propulsion systems and reaction control systems are also if interest because of desirable performance and operations improvements over conventional storable systems while being more suitable for use of in-situ produced propellants. Within the current lunar architecture, use of cryogenic propulsion for the Earth Departure Stage and Lunar Lander elements also necessitate the need for advanced Cryogenic Fluid Management technologies. These technologies include long duration propellant storage/distribution, low-gravity propellant management, cryogenic couplings and disconnects, light weight composite tanks and support structure, and subsystem integration. In addition to the propulsive and fluid management system technologies described, many component level technologies are also required to enable to the success if the integrated systems. The components include, but are not limited to, variable/throttling valves, variable position actuators, leak detectors, light weight cryogenic fluid pumps, sensor technology and others. NASA, partnering with the Aerospace Industry must endeavor to develop these, and other promising propulsion technologies, to enable the implements of the country's goals in exploration of the Moon, Mars and beyond.

Modeling indoor air pollution from cookstove emissions in developing countries using a Monte Carlo single-box model

NASA Astrophysics Data System (ADS)

Johnson, Michael; Lam, Nick; Brant, Simone; Gray, Christen; Pennise, David

2011-06-01

A simple Monte Carlo single-box model is presented as a first approach toward examining the relationship between emissions of pollutants from fuel/cookstove combinations and the resulting indoor air pollution (IAP) concentrations. The model combines stove emission rates with expected distributions of kitchen volumes and air exchange rates in the developing country context to produce a distribution of IAP concentration estimates. The resulting distribution can be used to predict the likelihood that IAP concentrations will meet air quality guidelines, including those recommended by the World Health Organization (WHO) for fine particulate matter (PM2.5) and carbon monoxide (CO). The model can also be used in reverse to estimate the probability that specific emission factors will result in meeting air quality guidelines. The modeled distributions of indoor PM2.5 concentration estimated that only 4% of homes using fuelwood in a rocket-style cookstove, even under idealized conditions, would meet the WHO Interim-1 annual PM2.5 guideline of 35 μg m-3. According to the model, the PM2.5 emissions that would be required for even 50% of homes to meet this guideline (0.055 g MJ-delivered-1) are lower than those for an advanced gasifier fan stove, while emissions levels similar to liquefied petroleum gas (0.018 g MJ-delivered-1) would be required for 90% of homes to meet the guideline. Although the predicted distribution of PM concentrations (median = 1320 μg m-3) from inputs for traditional wood stoves was within the range of reported values for India (108-3522 μg m-3), the model likely overestimates IAP concentrations. Direct comparison with simultaneously measured emissions rates and indoor concentrations of CO indicated the model overestimated IAP concentrations resulting from charcoal and kerosene emissions in Kenyan kitchens by 3 and 8 times respectively, although it underestimated the CO concentrations resulting from wood-burning cookstoves in India by approximately one half. The potential overestimation of IAP concentrations is thought to stem from the model's assumption that all stove emissions enter the room and are completely mixed. Future versions of the model may be improved by incorporating these factors into the model, as well as more comprehensive and representative data on stove emissions performance, daily cooking energy requirements, and kitchen characteristics.

Advanced Compatibility Characterization Of AF-M315E With Spacecraft Propulsion System Materials Project

NASA Technical Reports Server (NTRS)

McClure, Mark B.; Greene, Benjamin

2014-01-01

All spacecraft require propulsion systems for thrust and maneuvering. Propulsion systems can be chemical, nuclear, electrical, cold gas or combinations thereof. Chemical propulsion has proven to be the most reliable technology since the deployment of launch vehicles. Performance, storability, and handling are three important aspects of liquid chemical propulsion. Bipropellant systems require a fuel and an oxidizer for propulsion, but monopropellants only require a fuel and a catalyst for propulsion and are therefore simpler and lighter. Hydrazine is the state of the art propellant for monopropellant systems, but has drawbacks because it is highly hazardous to human health, which requires extensive care in handling, complex ground ops due to safety and environmental considerations, and lengthy turnaround times for reusable spacecraft. All users of hydrazine monopropellant must contend with these issues and their associated costs. The development of a new monopropellant, intended to replace hydrazine, has been in progress for years. This project will apply advanced techniques to characterize the engineering properties of materials used in AF-M315E propulsion systems after propellant exposure. AF-M315E monopropellant has been selected HQ's Green Propellant Infusion Mission (GPIM) to replace toxic hydrazine for improved performance and reduce safety and health issues that will shorten reusable spacecraft turn-around time. In addition, this project will fundamentally strengthen JSC's core competency to evaluate, use and infuse liquid propellant systems.

The Ion Propulsion System for the Solar Electric Propulsion Technology Demonstration Mission

NASA Technical Reports Server (NTRS)

Herman, Daniel A.; Santiago, Walter; Kamhawi, Hani; Polk, James E.; Snyder, John Steven; Hofer, Richard; Parker, J. Morgan

2015-01-01

The Asteroid Redirect Robotic Mission is a candidate Solar Electric Propulsion Technology Demonstration Mission whose main objectives are to develop and demonstrate a high-power solar electric propulsion capability for the Agency and return an asteroidal mass for rendezvous and characterization in a subsequent human-crewed mission. The ion propulsion subsystem must be capable of operating over an 8-year time period and processing up to 10,000 kg of xenon propellant. This high-power solar electric propulsion capability, or an extensible derivative of it, has been identified as an enabling element of an affordable beyond low-earth orbit human-crewed exploration architecture. Under the NASA Space Technology Mission Directorate the critical electric propulsion and solar array technologies are being developed. The ion propulsion system for the Asteroid Redirect Vehicle is based on the NASA-developed 12.5 kW Hall Effect Rocket with Magnetic Shielding thruster and power processing technologies. This paper presents the conceptual design for the ion propulsion system, a status on the NASA in-house thruster and power processing is provided, and an update on acquisition for flight provided.

Steady-state simulation program for attitude control propulsion systems

NASA Technical Reports Server (NTRS)

Heinmiller, P. J.

1973-01-01

The formulation and the engineering equations employed in the steady state attitude control propulsion system simulation program are presented. The objective of this program is to aid in the preliminary design and development of propulsion systems used for spacecraft attitude control. The program simulates the integrated operation of the many interdependent components typically comprising an attitude control propulsion system. Flexibility, generality, ease of operation, and speed consistent with adequate accuracy were overriding considerations during the development of this program. Simulation modules were developed representing the various types of fluid components typically encountered in an attitude control propulsion system. These modules are basically self-contained and may be arranged by the program user into desired configuration through the program input data.

Electromagnetic thrusters for spacecraft prime propulsion

NASA Technical Reports Server (NTRS)

Rudolph, L. K.; King, D. Q.

1984-01-01

The benefits of electromagnetic propulsion systems for the next generation of US spacecraft are discussed. Attention is given to magnetoplasmadynamic (MPD) and arc jet thrusters, which form a subset of a larger group of electromagnetic propulsion systems including pulsed plasma thrusters, Hall accelerators, and electromagnetic launchers. Mission/system study results acquired over the last twenty years suggest that for future prime propulsion applications high-power self-field MPD thrusters and low-power arc jets have the greatest potential of all electromagnetic thruster systems. Some of the benefits they are expected to provide include major reductions in required launch mass compared to chemical propulsion systems (particularly in geostationary orbit transfer) and lower life-cycle costs (almost 50 percent less). Detailed schematic drawings are provided which describe some possible configurations for the various systems.

Electric propulsion - Characteristics, applications, and status

NASA Technical Reports Server (NTRS)

Maloy, J. E.; Dulgeroff, C. R.; Poeschel, R. L.

1981-01-01

As chemical propulsion systems were achieving their ultimate capability for planetary exploration, space scientists were developing solar electric propulsion as the propulsion system need for future missions. This paper provides a comparative review of the principles of ion thruster and chemical rocket operations and discusses the current status of the 30-cm mercury ion thruster development and the specifications imposed on the 30-cm thruster by the Solar Electric Propulsion System program. The 30-cm thruster operating range, efficiency, wear out lifetime, and interface requirements are described. Finally, the areas of 30-cm thruster technology that remain to be refined are discussed.

NASA's In-Space Propulsion Technology Program: A Step Toward Interstellar Exploration

NASA Technical Reports Server (NTRS)

Johnson, Les; James, Bonnie; Baggett, Randy; Montgomery, Sandy

2005-01-01

NASA's In-Space Propulsion Technology Program is investing in technologies that have the potential to revolutionize the robotic exploration of deep space. For robotic exploration and science missions, increased efficiencies of future propulsion systems are critical to reduce overall life-cycle costs and, in some cases, enable missions previously considered impossible. Continued reliance on conventional chemical propulsion alone will not enable the robust exploration of deep space. The maximum theoretical efficiencies have almost been reached and are insufficient to meet needs for many ambitious science missions currently being considered. By developing the capability to support mid-term robotic mission needs, the program is laying the technological foundation for travel to nearby interstellar space. The In-Space Propulsion Technology Program s technology portfolio includes many advanced propulsion systems. From the next-generation ion propulsion systems operating in the 5-10 kW range, to solar sail propulsion, substantial advances in spacecraft propulsion performance are anticipated. Some of the most promising technologies for achieving these goals use the environment of space itself for energy and propulsion and are generically called "propellantless" because they do not require onboard fuel to achieve thrust. Propellantless propulsion technologies include scientific innovations, such as solar sails, electrodynamic and momentum transfer tethers, and aerocapture. This paper will provide an overview of those propellantless and propellant-based advanced propulsion technologies that will most significantly advance our exploration of deep space.

The Numerical Propulsion System Simulation: A Multidisciplinary Design System for Aerospace Vehicles

NASA Technical Reports Server (NTRS)

Lytle, John K.

1999-01-01

Advances in computational technology and in physics-based modeling are making large scale, detailed simulations of complex systems possible within the design environment. For example, the integration of computing, communications, and aerodynamics has reduced the time required to analyze ma or propulsion system components from days and weeks to minutes and hours. This breakthrough has enabled the detailed simulation of major propulsion system components to become a routine part of design process and to provide the designer with critical information about the components early in the design process. This paper describes the development of the Numerical Propulsion System Simulation (NPSS), a multidisciplinary system of analysis tools that is focussed on extending the simulation capability from components to the full system. This will provide the product developer with a "virtual wind tunnel" that will reduce the number of hardware builds and tests required during the development of advanced aerospace propulsion systems.

Approach to Modeling Boundary Layer Ingestion Using a Fully Coupled Propulsion-RANS Model

NASA Technical Reports Server (NTRS)

Gray, Justin S.; Mader, Charles A.; Kenway, Gaetan K. W.; Martins, Joaquim R. R. A.

2017-01-01

Airframe-propulsion integration concepts that use boundary layer ingestion have the potential to reduce aircraft fuel burn. One concept that has been recently explored is NASA's Starc-ABL aircraft configuration, which offers the potential for 12% mission fuel burn reduction by using a turbo-electric propulsion system with an aft-mounted electrically driven boundary layer ingestion propulsor. This large potential for improved performance motivates a more detailed study of the boundary layer ingestion propulsor design, but to date, analyses of boundary layer ingestion have used uncoupled methods. These methods account for only aerodynamic effects on the propulsion system or propulsion system effects on the aerodynamics, but not both simultaneously. This work presents a new approach for building fully coupled propulsive-aerodynamic models of boundary layer ingestion propulsion systems. A 1D thermodynamic cycle analysis is coupled to a RANS simulation to model the Starc-ABL aft propulsor at a cruise condition and the effects variation in propulsor design on performance are examined. The results indicates that both propulsion and aerodynamic effects contribute equally toward the overall performance and that the fully coupled model yields substantially different results compared to uncoupled. The most significant finding is that boundary layer ingestion, while offering substantial fuel burn savings, introduces throttle dependent aerodynamics effects that need to be accounted for. This work represents a first step toward the multidisciplinary design optimization of boundary layer ingestion propulsion systems.

Can Computer-Based Visual-Spatial Aids Lead to Increased Student Performance in Anatomy & Physiology?

ERIC Educational Resources Information Center

Kesner, Michael H.; Linzey, Alicia V.

2005-01-01

InterActive Physiology (IAP) is one of a new generation of anatomy and physiology learning aids with a broader range of sensory inputs than is possible from a static textbook or moderately dynamic lecture. This best-selling software has modules covering the muscular, respiratory, urinary, cardiovascular, and nervous systems plus a module on fluids…

The Status of Spacecraft Bus and Platform Technology Development Under the NASA ISPT Program

NASA Technical Reports Server (NTRS)

Anderson, David; Munk, Michelle M.; Pencil, Eric; Dankanich, John; Glaab, Louis; Peterson, Todd

2014-01-01

The In-Space Propulsion Technology (ISPT) program is developing spacecraft bus and platform technologies that will enable or enhance NASA robotic science missions. The ISPT program is currently developing technology in three areas that include Propulsion System Technologies, Entry Vehicle Technologies, and Systems Mission Analysis. ISPTs propulsion technologies include: 1) NASAs Evolutionary Xenon Thruster (NEXT) ion propulsion system, a 0.6-7 kW throttle-able gridded ion system; 2) a Hall-effect electric propulsion (HEP) system for sample return and low cost missions; 3) the Advanced Xenon Flow Control System (AXFS); ultra-lightweight propellant tank technologies (ULTT); and propulsion technologies for a Mars Ascent Vehicle (MAV). The AXFS and ULTT are two component technologies being developed with nearer-term flight infusion in mind, whereas NEXT and the HEP are being developed as EP systems. ISPTs entry vehicle technologies are: 1) Aerocapture technology development with investments in a family of thermal protection system (TPS) materials and structures; guidance, navigation, and control (GNC) models of blunt-body rigid aeroshells; and aerothermal effect models; and 2) Multi-mission technologies for Earth Entry Vehicles (MMEEV) for sample return missions. The Systems Mission Analysis area is focused on developing tools and assessing the application of propulsion, entry vehicle, and spacecraft bus technologies to a wide variety of mission concepts. Several of the ISPT technologies are related to sample return missions and other spacecraft bus technology needs like: MAV propulsion, MMEEV, and electric propulsion. These technologies, as well as Aerocapture, are more vehicle and mission-focused, and present a different set of technology development challenges. These in-space propulsion technologies are applicable, and potentially enabling for future NASA Discovery, New Frontiers, Flagship and sample return missions currently under consideration. This paper provides a brief overview of the ISPT program, describing the development status and technology infusion readiness.

Planetary mission applications for space storable propulsion

NASA Technical Reports Server (NTRS)

Chase, R. L.; Cork, M. J.; Young, D. L.

1974-01-01

This paper presents the results of a study to compare space-storable with earth-storable spacecraft propulsion systems, space-storable with solid kick stages, and several space-storable development options on the basis of benefits received for cost expenditures required. The results show that, for a launch vehicle with performance less than that of Shuttle/Centaur, space-storable spacecraft propulsion offers an incremental benefit/cost ratio between 1.0 and 5.5 when compared to earth-storable systems for three of the four missions considered. In the case of VOIR 83, positive benefits were apparent only for a specific launch vehicle-spacecraft propulsion combination. A space-storable propulsion system operating at thrust of 600 lbf, 355 units of specific impulse, and with blowdown pressurization, represents the best choice for the JO 81 mission on a Titan/Centaur if only spacecraft propulsion modifications are considered. For still higher performance, a new solid-propellant kick stage with space-storable spacecraft propulsion is preferred over a system which uses space-storable propellants for both the kick stage and the spacecraft system.

Space transportation systems, launch systems, and propulsion for the Space Exploration Initiative: Results from Project Outreach

NASA Technical Reports Server (NTRS)

Garber, T.; Hiland, J.; Orletsky, D.; Augenstein, B.; Miller, M.

1991-01-01

A number of transportation and propulsion options for Mars exploration missions are analyzed. As part of Project Outreach, RAND received and evaluated 350 submissions in the launch vehicle, space transportation, and propulsion areas. After screening submissions, aggregating those that proposed identical or nearly identical concepts, and eliminating from further consideration those that violated known physical princples, we had reduced the total number of viable submissions to 213. In order to avoid comparing such disparate things as launch vehicles and electric propulsion systems, six broad technical areas were selected to categorize the submissions: space transportation systems; earth-to-orbit (ETO) launch systems; chemical propulsion; nuclear propulsion; low-thrust propulsion; and other. To provide an appropriate background for analyzing the submissions, an extensive survey was made of the various technologies relevant to the six broad areas listed above. We discuss these technologies with the intent of providing the reader with an indication of the current state of the art, as well as the advances that might be expected within the next 10 to 20 years.

Memory recall in arousing situations - an emotional von Restorff effect?

PubMed

Wiswede, Daniel; Rüsseler, Jascha; Hasselbach, Simone; Münte, Thomas F

2006-07-24

Previous research has demonstrated a relationship between memory recall and P300 amplitude in list learning tasks, but the variables mediating this P300-recall relationship are not well understood. In the present study, subjects were required to recall items from lists consisting of 12 words, which were presented in front of pictures taken from the IAPS collection. One word per list is made distinct either by font color or by a highly arousing background IAPS picture. This isolation procedure was first used by von Restorff. Brain potentials were recorded during list presentation. Recall performance was enhanced for color but not for emotional isolates. Event-related brain potentials (ERP) showed a more positive P300-component for recalled non-isolated words and color-isolated words, compared to the respective non-remembered words, but not for words isolated by arousing background. Our findings indicate that it is crucial to take emotional mediator variables into account, when using the P300 to predict later recall. Highly arousing environments might force the cognitive system to interrupt rehearsal processes in working memory, which might benefit transfer into other, more stable memory systems. The impact of attention-capturing properties of arousing background stimuli is also discussed.

Development and Test of an Eddy-Current Clutch-Propulsion System

DOT National Transportation Integrated Search

1973-10-01

This report covers the Phase 1 effort which is to develop and to test an/AC-propulsion system for personal rapid- transit vehicles. This propulsion system incorporates an AC-induction motor in conjunction with an eddy-current clutch and brake. Also i...

Space station propulsion test bed

NASA Technical Reports Server (NTRS)

Briley, G. L.; Evans, S. A.

1989-01-01

A test bed was fabricated to demonstrate hydrogen/oxygen propulsion technology readiness for the intital operating configuration (IOC) space station application. The test bed propulsion module and computer control system were delivered in December 1985, but activation was delayed until mid-1986 while the propulsion system baseline for the station was reexamined. A new baseline was selected with hydrogen/oxygen thruster modules supplied with gas produced by electrolysis of waste water from the space shuttle and space station. As a result, an electrolysis module was designed, fabricated, and added to the test bed to provide an end-to-end simulation of the baseline system. Subsequent testing of the test bed propulsion and electrolysis modules provided an end-to-end demonstration of the complete space station propulsion system, including thruster hot firings using the oxygen and hydrogen generated from electrolysis of water. Complete autonomous control and operation of all test bed components by the microprocessor control system designed and delivered during the program was demonstrated. The technical readiness of the system is now firmly established.

Identification of the glucose transporter in mammalian cell membranes using an /sup 125/(I)-forskolin photoaffinity label

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

Ruoho, A.; Wadzinski, B.; Shanahan, M.

1987-05-01

The glucose transporter has been identified in a variety of mammlian cell membranes using a carrier-free photoactivatable radioiodinated derivative of forskolin, 3-iodo-4-azidophenethylamido-7-0-succinyldeacetyl-forskolin, (I-125)IAPS-Fsk, at 1-10 nM. The membranes which have been photolabeled with (I-125)IAPS-Fsk are: rat cardiac sarcolemmal membranes, rat cortex and cerebellum synaptic membranes, human placental membranes, and wild type S49 lymphoma cell membranes. The glucose transporter in rat cardiac sarcolemmal membranes and rat cortex and cerebellum synaptic membranes was determined to be 45 kDa by SDS-PAGE. Photolysis of human placental membranes and S49 lymphoma membranes with (I-125)IAPS-Fsk followed by SDS-PAGE indicated specific derivatization of a broad band (45-55more » kDa) in placental membranes and a narrower band (45 kDa) in the S49 lymphoma membranes. Digestion of the (I-125)IPAS-Fsk labelled placental and S49 lymphoma membranes with endo-B-galactosidase showed a reduction in the apparent molecular weight of the radiolabelled band to 40 kDa. Trypsinization of labelled placental and lymphoma membranes produced an 18 kDa radiolabelled proteolytic fragment. (I-125)IAPS-Fsk is a highly effective probe for identifying low levels of glucose transporters in mammalian tissues.« less

Status of indoor air pollution (IAP) through particulate matter (PM) emissions and associated health concerns in South Asia.

PubMed

Junaid, Muhammad; Syed, Jabir Hussain; Abbasi, Naeem Akhtar; Hashmi, Muhammad Zaffar; Malik, Riffat Naseem; Pei, De-Sheng

2018-01-01

Exposure to particulate emissions poses a variety of public health concerns worldwide, specifically in developing countries. This review summarized the documented studies on indoor particulate matter (PM) emissions and their major health concerns in South Asia. Reviewed literature illustrated the alarming levels of indoor air pollution (IAP) in India, Pakistan, Nepal, and Bangladesh, while Sri Lanka and Bhutan are confronted with relatively lower levels, albeit not safe. To our knowledge, data on this issue are absent from Afghanistan and Maldives. We found that the reported levels of PM 10 and PM 2.5 in Nepal, Pakistan, Bangladesh, and India were 2-65, 3-30, 4-22, 2-28 and 1-139, 2-180, 3-77, 1-40 fold higher than WHO standards for indoor PM 10 (50 μg/m 3 ) and PM 2.5 (25 μg/m 3 ), respectively. Regarding IAP-mediated health concerns, mortality rates and incidences of respiratory and non-respiratory diseases were increasing with alarming rates, specifically in India, Pakistan, Nepal, and Bangladesh. The major cause might be the reliance of approximately 80% population on conventional biomass burning in the region. Current review also highlighted the prospects of IAP reduction strategies, which in future can help to improve the status of indoor air quality and public health in South Asia. Copyright © 2017 Elsevier Ltd. All rights reserved.

Rocket Based Combined Cycle (RBCC) Propulsion Workshop, volume 2

NASA Technical Reports Server (NTRS)

Chojnacki, Kent T.

1992-01-01

The goal of the Rocket Based Combined Cycle (RBCC) Propulsion Technology Workshop, was to impart technology information to the propulsion community with respect to hypersonic combined cycle propulsion capabilities. The major recommendation resulting from this technology workshop was as follows: conduct a systems-level applications study to define the desired propulsion system and vehicle technology requirements for LEO launch vehicles. All SSTO and TSTO options using the various propulsion systems (airbreathing combined cycle, rocket-based combined cycle, and all rocket) must be considered. Such a study should be accomplished as soon as possible. It must be conducted with a consistent set of ground rules and assumptions. Additionally, the study should be conducted before any major expenditures on a RBCC technology development program occur.

Large Space Systems/Low-Thrust Propulsion Technology

NASA Technical Reports Server (NTRS)

1980-01-01

The potentially critical interactions that occur between propulsion, structures and materials, and controls for large spacecraft are considered, the technology impacts within these fields are defined and the net effect on large systems and the resulting missions is determined. Topical areas are systems/mission analysis, LSS static and dynamic characterization, and propulsion systems characterization.

Safe, Affordable, Nuclear Thermal Propulsion Systems

NASA Technical Reports Server (NTRS)

Houts, M. G.; Kim, T.; Emrich, W. J.; Hickman, R. R.; Broadway, J. W.; Gerrish, H. P.; Doughty, G. E.

2014-01-01

The fundamental capability of Nuclear Thermal Propulsion (NTP) is game changing for space exploration. A first generation Nuclear Cryogenic Propulsion Stage (NCPS) based on NTP could provide high thrust at a specific impulse above 900 s, roughly double that of state of the art chemical engines. Characteristics of fission and NTP indicate that useful first generation systems will provide a foundation for future systems with extremely high performance. The role of the NCPS in the development of advanced nuclear propulsion systems could be analogous to the role of the DC-3 in the development of advanced aviation. Progress made under the NCPS project could help enable both advanced NTP and advanced Nuclear Electric Propulsion (NEP).

Neptune Orbiters Utilizing Solar and Radioisotope Electric Propulsion

NASA Technical Reports Server (NTRS)

Fiehler, Douglas I.; Oleson, Steven R.

2004-01-01

In certain cases, Radioisotope Electric Propulsion (REP), used in conjunction with other propulsion systems, could be used to reduce the trip times for outer planetary orbiter spacecraft. It also has the potential to improve the maneuverability and power capabilities of the spacecraft when the target body is reached as compared with non-electric propulsion spacecraft. Current missions under study baseline aerocapture systems to capture into a science orbit after a Solar Electric Propulsion (SEP) stage is jettisoned. Other options under study would use all REP transfers with small payloads. Compared to the SEP stage/Aerocapture scenario, adding REP to the science spacecraft as well as a chemical capture system can replace the aerocapture system but with a trip time penalty. Eliminating both the SEP stage and the aerocapture system and utilizing a slightly larger launch vehicle, Star 48 upper stage, and a combined REP/Chemical capture system, the trip time can nearly be matched while providing over a kilowatt of science power reused from the REP maneuver. A Neptune Orbiter mission is examined utilizing single propulsion systems and combinations of SEP, REP, and chemical systems to compare concepts.

Investigation of Propulsion System Requirements for Spartan Lite

NASA Technical Reports Server (NTRS)

Urban, Mike; Gruner, Timothy; Morrissey, James; Sneiderman, Gary

1998-01-01

This paper discusses the (chemical or electric) propulsion system requirements necessary to increase the Spartan Lite science mission lifetime to over a year. Spartan Lite is an extremely low-cost (less than 10 M) spacecraft bus being developed at the NASA Goddard Space Flight Center to accommodate sounding rocket class (40 W, 45 kg, 35 cm dia by 1 m length) payloads. While Spartan Lite is compatible with expendable launch vehicles, most missions are expected to be tertiary payloads deployed by. the Space Shuttle. To achieve a one year or longer mission life from typical Shuttle orbits, some form of propulsion system is required. Chemical propulsion systems (characterized by high thrust impulsive maneuvers) and electrical propulsion systems (characterized by low-thrust long duration maneuvers and the additional requirement for electrical power) are discussed. The performance of the Spartan Lite attitude control system in the presence of large disturbance torques is evaluated using the Trectops(Tm) dynamic simulator. This paper discusses the performance goals and resource constraints for candidate Spartan Lite propulsion systems and uses them to specify quantitative requirements against which the systems are evaluated.

Simulation Propulsion System and Trajectory Optimization

NASA Technical Reports Server (NTRS)

Hendricks, Eric S.; Falck, Robert D.; Gray, Justin S.

2017-01-01

A number of new aircraft concepts have recently been proposed which tightly couple the propulsion system design and operation with the overall vehicle design and performance characteristics. These concepts include propulsion technology such as boundary layer ingestion, hybrid electric propulsion systems, distributed propulsion systems and variable cycle engines. Initial studies examining these concepts have typically used a traditional decoupled approach to aircraft design where the aerodynamics and propulsion designs are done a-priori and tabular data is used to provide inexpensive look ups to the trajectory ana-ysis. However the cost of generating the tabular data begins to grow exponentially when newer aircraft concepts require consideration of additional operational parameters such as multiple throttle settings, angle-of-attack effects on the propulsion system, or propulsion throttle setting effects on aerodynamics. This paper proposes a new modeling approach that eliminated the need to generate tabular data, instead allowing an expensive propulsion or aerodynamic analysis to be directly integrated into the trajectory analysis model and the entire design problem optimized in a fully coupled manner. The new method is demonstrated by implementing a canonical optimal control problem, the F-4 minimum time-to-climb trajectory optimization using three relatively new analysis tools: Open M-DAO, PyCycle and Pointer. Pycycle and Pointer both provide analytic derivatives and Open MDAO enables the two tools to be combined into a coupled model that can be run in an efficient parallel manner that helps to cost the increased cost of the more expensive propulsion analysis. Results generated with this model serve as a validation of the tightly coupled design method and guide future studies to examine aircraft concepts with more complex operational dependencies for the aerodynamic and propulsion models.

Propulsion Controls and Diagnostics Research at NASA Glenn Research Center

NASA Technical Reports Server (NTRS)

Garg, Sanjay

2007-01-01

With the increased emphasis on aircraft safety, enhanced performance and affordability, and the need to reduce the environmental impact of aircraft, there are many new challenges being faced by the designers of aircraft propulsion systems. Also the propulsion systems required to enable the National Aeronautics and Space Administration (NASA) Vision for Space Exploration in an affordable manner will need to have high reliability, safety and autonomous operation capability. The Controls and Dynamics Branch (CDB) at NASA Glenn Research Center (GRC) in Cleveland, Ohio, is leading and participating in various projects in partnership with other organizations within GRC and across NASA, the U.S. aerospace industry, and academia to develop advanced controls and health management technologies that will help meet these challenges through the concept of Intelligent Propulsion Systems. This paper describes the current activities of the CDB under the NASA Aeronautics Research and Exploration Systems Missions. The programmatic structure of the CDB activities is described along with a brief overview of each of the CDB tasks including research objectives, technical challenges, and recent accomplishments. These tasks include active control of propulsion system components, intelligent propulsion diagnostics and control for reliable fault identification and accommodation, distributed engine control, and investigations into unsteady propulsion systems.

50 CFR 218.170 - Specified activity and specified geographical area and effective dates.

Code of Federal Regulations, 2011 CFR

2011-10-01

... site QUTR site Test Vehicle Propulsion Thermal propulsion systemsElectric/Chemical propulsion systems..., classification and localization 05 4520 1510 Non-Navy testing 5 5 5 Acoustic & non-acoustic sensors (magnetic...

Green space propulsion: Opportunities and prospects

NASA Astrophysics Data System (ADS)

Gohardani, Amir S.; Stanojev, Johann; Demairé, Alain; Anflo, Kjell; Persson, Mathias; Wingborg, Niklas; Nilsson, Christer

2014-11-01

Currently, toxic and carcinogenic hydrazine propellants are commonly used in spacecraft propulsion. These propellants impose distinctive environmental challenges and consequential hazardous conditions. With an increasing level of future space activities and applications, the significance of greener space propulsion becomes even more pronounced. In this article, a selected number of promising green space propellants are reviewed and investigated for various space missions. In-depth system studies in relation to the aforementioned propulsion architectures further unveil possible approaches for advanced green propulsion systems of the future.

Unmanned planetary spacecraft chemical rocket propulsion.

NASA Technical Reports Server (NTRS)

Burlage, H., Jr.; Gin, W.; Riebling, R. W.

1972-01-01

Review of some chemical propulsion technology advances suitable for future unmanned spacecraft applications. Discussed system varieties include liquid space-storable propulsion systems, advanced liquid monopropellant systems, liquid systems for rendezvous and landing applications, and low-thrust high-performance solid-propellant systems, as well as hybrid space-storable systems. To optimize the performance and operational characteristics of an unmanned interplanetary spacecraft for a particular mission, and to achieve high cost effectiveness of the entire system, it is shown to be essential that the type of spacecraft propulsion system to be used matches, as closely as possible the various requirements and constraints. The systems discussed are deemed to be the most promising candidates for some of the anticipated interplanetary missions.

The Status of Spacecraft Bus and Platform Technology Development under the NASA ISPT Program

NASA Technical Reports Server (NTRS)

Anderson, David J.; Munk, Michelle M.; Pencil, Eric; Dankanich, John; Glaab, Louis; Peterson, Todd

2013-01-01

The In-Space Propulsion Technology (ISPT) program is developing spacecraft bus and platform technologies that will enable or enhance NASA robotic science missions. The ISPT program is currently developing technology in four areas that include Propulsion System Technologies (electric and chemical), Entry Vehicle Technologies (aerocapture and Earth entry vehicles), Spacecraft Bus and Sample Return Propulsion Technologies (components and ascent vehicles), and Systems/Mission Analysis. Three technologies are ready for near-term flight infusion: 1) the high-temperature Advanced Material Bipropellant Rocket (AMBR) engine providing higher performance; 2) NASA s Evolutionary Xenon Thruster (NEXT) ion propulsion system, a 0.6-7 kW throttle-able gridded ion system; and 3) Aerocapture technology development with investments in a family of thermal protection system (TPS) materials and structures; guidance, navigation, and control (GN&C) models of blunt-body rigid aeroshells; and aerothermal effect models. Two component technologies being developed with flight infusion in mind are the Advanced Xenon Flow Control System and ultralightweight propellant tank technologies. Future directions for ISPT are technologies that relate to sample return missions and other spacecraft bus technology needs like: 1) Mars Ascent Vehicles (MAV); 2) multi-mission technologies for Earth Entry Vehicles (MMEEV); and 3) electric propulsion. These technologies are more vehicles and mission-focused, and present a different set of technology development and infusion steps beyond those previously implemented. The Systems/Mission Analysis area is focused on developing tools and assessing the application of propulsion and spacecraft bus technologies to a wide variety of mission concepts. These inspace propulsion technologies are applicable, and potentially enabling for future NASA Discovery, New Frontiers, and sample return missions currently under consideration, as well as having broad applicability to potential Flagship missions. This paper provides a brief overview of the ISPT program, describing the development status and technology infusion readiness of in-space propulsion technologies in the areas of electric propulsion, Aerocapture, Earth entry vehicles, propulsion components, Mars ascent vehicle, and mission/systems analysis.

MOA: Magnetic Field Oscillating Amplified Thruster and its Application for Nuclear Electric and Thermal Propulsion

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

Frischauf, Norbert; Hettmer, Manfred; Grassauer, Andreas

More than 60 years after the later Nobel laureate Hannes Alfven had published a letter stating that oscillating magnetic fields can accelerate ionised matter via magneto-hydrodynamic interactions in a wave like fashion, the technical implementation of Alfven waves for propulsive purposes has been proposed, patented and examined for the first time by a group of inventors. The name of the concept, utilising Alfven waves to accelerate ionised matter for propulsive purposes, is MOA - Magnetic field Oscillating Amplified thruster. Alfven waves are generated by making use of two coils, one being permanently powered and serving also as magnetic nozzle, themore » other one being switched on and off in a cyclic way, deforming the field lines of the overall system. It is this deformation that generates Alfven waves, which are in the next step used to transport and compress the propulsive medium, in theory leading to a propulsion system with a much higher performance than any other electric propulsion system. Based on computer simulations, which were conducted to get a first estimate on the performance of the system, MOA is a highly flexible propulsion system, whose performance parameters might easily be adapted, by changing the mass flow and/or the power level. As such the system is capable to deliver a maximum specific impulse of 13116 s (12.87 mN) at a power level of 11.16 kW, using Xe as propellant, but can also be attuned to provide a thrust of 236.5 mN (2411 s) at 6.15 kW of power. While space propulsion is expected to be the prime application for MOA and is supported by numerous applications such as Solar and/or Nuclear Electric Propulsion or even as an 'afterburner system' for Nuclear Thermal Propulsion, other terrestrial applications can be thought of as well, making the system highly suited for a common space-terrestrial application research and utilisation strategy. (authors)« less

The status of spacecraft bus and platform technology development under the NASA ISPT program

NASA Astrophysics Data System (ADS)

Anderson, D. J.; Munk, M. M.; Pencil, E.; Dankanich, J.; Glaab, L.; Peterson, T.

The In-Space Propulsion Technology (ISPT) program is developing spacecraft bus and platform technologies that will enable or enhance NASA robotic science missions. The ISPT program is currently developing technology in four areas that include Propulsion System Technologies (electric and chemical), Entry Vehicle Technologies (aerocapture and Earth entry vehicles), Spacecraft Bus and Sample Return Propulsion Technologies (components and ascent vehicles), and Systems/Mission Analysis. Three technologies are ready for near-term flight infusion: 1) the high-temperature Advanced Material Bipropellant Rocket (AMBR) engine providing higher performance; 2) NASA's Evolutionary Xenon Thruster (NEXT) ion propulsion system, a 0.6-7 kW throttle-able gridded ion system; and 3) Aerocapture technology development with investments in a family of thermal protection system (TPS) materials and structures; guidance, navigation, and control (GN& C) models of blunt-body rigid aeroshells; and aerothermal effect models. Two component technologies being developed with flight infusion in mind are the Advanced Xenon Flow Control System and ultra-lightweight propellant tank technologies. Future directions for ISPT are technologies that relate to sample return missions and other spacecraft bus technology needs like: 1) Mars Ascent Vehicles (MAV); 2) multi-mission technologies for Earth Entry Vehicles (MMEEV); and 3) electric propulsion. These technologies are more vehicles and mission-focused, and present a different set of technology development and infusion steps beyond those previously implemented. The Systems/Mission Analysis area is focused on developing tools and assessing the application of propulsion and spacecraft bus technologies to a wide variety of mission concepts. These in-space propulsion technologies are applicable, and potentially enabling for future NASA Discovery, New Frontiers, and sample return missions currently under consideration, as well as having broad applicabilit- to potential Flagship missions. This paper provides a brief overview of the ISPT program, describing the development status and technology infusion readiness of in-space propulsion technologies in the areas of electric propulsion, Aerocapture, Earth entry vehicles, propulsion components, Mars ascent vehicle, and mission/systems analysis.

The Status of Spacecraft Bus and Platform Technology Development Under the NASA ISPT Program

NASA Technical Reports Server (NTRS)

Anderson, David J.; Munk, Michelle M.; Pencil, Eric J.; Dankanich, John; Glaab, Louis J.

2013-01-01

The In-Space Propulsion Technology (ISPT) program is developing spacecraft bus and platform technologies that will enable or enhance NASA robotic science missions. The ISPT program is currently developing technology in four areas that include Propulsion System Technologies (electric and chemical), Entry Vehicle Technologies (aerocapture and Earth entry vehicles), Spacecraft Bus and Sample Return Propulsion Technologies (components and ascent vehicles), and Systems/Mission Analysis. Three technologies are ready for near-term flight infusion: 1) the high-temperature Advanced Material Bipropellant Rocket (AMBR) engine providing higher performance 2) NASAs Evolutionary Xenon Thruster (NEXT) ion propulsion system, a 0.6-7 kW throttle-able gridded ion system and 3) Aerocapture technology development with investments in a family of thermal protection system (TPS) materials and structures guidance, navigation, and control (GN&C) models of blunt-body rigid aeroshells and aerothermal effect models. Two component technologies being developed with flight infusion in mind are the Advanced Xenon Flow Control System, and ultra-lightweight propellant tank technologies. Future direction for ISPT are technologies that relate to sample return missions and other spacecraft bus technology needs like: 1) Mars Ascent Vehicles (MAV) 2) multi-mission technologies for Earth Entry Vehicles (MMEEV) and 3) electric propulsion. These technologies are more vehicle and mission-focused, and present a different set of technology development and infusion steps beyond those previously implemented. The Systems/Mission Analysis area is focused on developing tools and assessing the application of propulsion and spacecraft bus technologies to a wide variety of mission concepts. These in-space propulsion technologies are applicable, and potentially enabling for future NASA Discovery, New Frontiers, and sample return missions currently under consideration, as well as having broad applicability to potential Flagship missions. This paper provides a brief overview of the ISPT program, describing the development status and technology infusion readiness of in-space propulsion technologies in the areas of electric propulsion, Aerocapture, Earth entry vehicles, propulsion components, Mars ascent vehicle, and mission/systems analysis.

Integrated null-flux suspension and multiphase propulsion system for magnetically-levitated vehicles

DOEpatents

Rote, Donald M.; He, Jianliang; Johnson, Larry R.

1994-01-01

A propulsion and stabilization system comprising a series of FIG. 8 coils mounted vertically on the walls of the guideway to provide suspension, lateral guidance and propulsion of a magnetically levitated vehicle. This system further allows for altering the magnetic field effects by changing the relative position of the loops comprising the FIG. 8 coils either longitudinally and/or vertically with resulting changes in the propulsion, the vertical stability, and the suspension.

Integrated null-flux suspension and multiphase propulsion system for magnetically-levitated vehicles

DOEpatents

Rote, D.M.; He, J.; Johnson, L.R.

1994-01-04

A propulsion and stabilization system are described comprising a series of coils mounted vertically on the walls of the guideway to provide suspension, lateral guidance, and propulsion of a magnetically levitated vehicle. This system further allows for altering the magnetic field effects by changing the relative position of the loops comprising the coils either longitudinally and/or vertically with resulting changes in the propulsion, the vertical stability, and the suspension. 8 figures.

Integrated null-flux suspension and multiphase propulsion system for magnetically-levitated vehicles

DOEpatents

Rote, D.M.; He, Jianliang; Johnson, L.R.

1992-01-01

This report discusses a propulsion and stabilization system comprising a series of figure 8 coils mounted vertically on the walls of the guideway to provide suspension, lateral guidance and propulsion of a magnetically levitated vehicle. This system further allows for altering the magnetic field effects by changing the relative position of the loops comprising the figure 8 coils either longitudinally and/or vertically with resulting changes in the propulsion, the vertical stability, and the suspension.

Generation of isolated attosecond pulses with enhancement cavities—a theoretical study

NASA Astrophysics Data System (ADS)

Högner, M.; Tosa, V.; Pupeza, I.

2017-03-01

The generation of extreme-ultraviolet (XUV) isolated attosecond pulses (IAPs) has enabled experimental access to the fastest phenomena in nature observed so far, namely the dynamics of electrons in atoms, molecules and solids. However, nowadays the highest repetition rates at which IAPs can be generated lies in the {kHz} range. This represents a rather severe restriction for numerous experiments involving the detection of charged particles, where the desired number of generated particles per shot is limited by space charge effects to ideally one. Here, we present a theoretical study on the possibility of efficiently producing IAPs at multi-{MHz} repetition rates via cavity-enhanced high-harmonic generation (HHG). To this end, we assume parameters of state-of-the-art Yb-based femtosecond laser technology to evaluate several time-gating methods which could generate IAPs in enhancement cavities. We identify polarization gating and a new method, employing non-collinear optical gating in a tailored transverse cavity mode, as suitable candidates and analyze these via extensive numerical modeling. The latter, which we dub transverse mode gating (TMG) promises the highest efficiency and robustness. Assuming 0.7 μ {{J}}, 5-cycle pulses from the seeding laser and a state-of-the-art enhancement cavity, we show that TMG bares the potential to generate IAPs with photon energies around 100 {eV} and a photon flux of at least {10}8 {photons} {{{s}}}-1 at repetition rates of 10 {MHz} and higher. This result reveals a roadmap towards a dramatic decrease in measurement time (and, equivalently, an increase in the signal-to-noise ratio) in photoelectron spectroscopy and microscopy. In particular, it paves the way to combining attosecond streaking with photoelectron emission microscopy, affording, for the first time, the spatially and temporally resolved observation of plasmonic fields in nanostructures. Furthermore, it promises the generation of frequency combs with an unprecedented bandwidth for XUV precision spectroscopy.

Listeria monocytogenes mutants with altered growth phenotypes at refrigeration temperature and high salt concentrations.

PubMed

Burall, Laurel S; Laksanalamai, Pongpan; Datta, Atin R

2012-02-01

Listeria monocytogenes can survive and grow in refrigerated temperatures and high-salt environments. In an effort to better understand the associated mechanisms, a library of ∼ 5,200 transposon mutants of LS411, a food isolate from the Jalisco cheese outbreak, were screened for their ability to grow in brain heart infusion (BHI) broth at 5°C or in the presence of 7% NaCl and two mutants with altered growth profiles were identified. The LS522 mutant has a transposon insertion between secA2 and iap and showed a significant reduction in growth in BHI broth at 5°C and in the presence of 7% NaCl. Reverse transcriptase quantitative PCR (RT-qPCR) revealed a substantial reduction in the expression of iap. Additionally, a hypothetical gene (met), containing a putative S-adenosylmethionine-dependent methyltransferase domain, downstream of iap had downregulated expression. In-frame deletion mutants of iap and met were created in LS411. The LS560 (LS411 Δiap) mutant showed reduced growth at 5°C and in the presence of 7% salt, confirming its role in cold and salt growth attenuation. Surprisingly, the LS655 (LS411 Δmet) mutant showed slightly increased growth during refrigeration, though no alteration was seen in salt growth relative to the wild-type strain. The LS527 mutant, containing an insertion 36 bp upstream of the gbu operon, showed reduced expression of the gbu transcript by RT-qPCR and also showed growth reduction at 5°C and in the presence of 7% salt. This attenuation was severely exacerbated when the mutant was grown under the combined stresses. Analysis of the gbu operon deletion mutant showed decreased growth in 7% salt and refrigeration, supporting the previously characterized role for this gene in cold and salt adaptation. These studies indicate the potential for an intricate relationship between environmental stress regulation and virulence in L. monocytogenes.

Listeria monocytogenes Mutants with Altered Growth Phenotypes at Refrigeration Temperature and High Salt Concentrations

PubMed Central

Burall, Laurel S.; Laksanalamai, Pongpan

2012-01-01

Listeria monocytogenes can survive and grow in refrigerated temperatures and high-salt environments. In an effort to better understand the associated mechanisms, a library of ∼ 5,200 transposon mutants of LS411, a food isolate from the Jalisco cheese outbreak, were screened for their ability to grow in brain heart infusion (BHI) broth at 5°C or in the presence of 7% NaCl and two mutants with altered growth profiles were identified. The LS522 mutant has a transposon insertion between secA2 and iap and showed a significant reduction in growth in BHI broth at 5°C and in the presence of 7% NaCl. Reverse transcriptase quantitative PCR (RT-qPCR) revealed a substantial reduction in the expression of iap. Additionally, a hypothetical gene (met), containing a putative S-adenosylmethionine-dependent methyltransferase domain, downstream of iap had downregulated expression. In-frame deletion mutants of iap and met were created in LS411. The LS560 (LS411 Δiap) mutant showed reduced growth at 5°C and in the presence of 7% salt, confirming its role in cold and salt growth attenuation. Surprisingly, the LS655 (LS411 Δmet) mutant showed slightly increased growth during refrigeration, though no alteration was seen in salt growth relative to the wild-type strain. The LS527 mutant, containing an insertion 36 bp upstream of the gbu operon, showed reduced expression of the gbu transcript by RT-qPCR and also showed growth reduction at 5°C and in the presence of 7% salt. This attenuation was severely exacerbated when the mutant was grown under the combined stresses. Analysis of the gbu operon deletion mutant showed decreased growth in 7% salt and refrigeration, supporting the previously characterized role for this gene in cold and salt adaptation. These studies indicate the potential for an intricate relationship between environmental stress regulation and virulence in L. monocytogenes. PMID:22179239

Proteasome inhibitor PS-341 limits macrophage necroptosis by promoting cIAPs-mediated inhibition of RIP1 and RIP3 activation.

PubMed

Zhang, Yuchen; Cheng, Junjun; Zhang, Junmeng; Wu, Xiaofan; Chen, Fang; Ren, Xuejun; Wang, Yunlong; Li, Quan; Li, Yu

2016-09-02

Apoptotic and necrotic macrophages have long been known for their existence in atherosclerotic lesions. However, the mechanisms underlying the choice of their death pattern have not been fully elucidated. Here, we report the effects of PS-341, a potent and specific proteasome inhibitor, on the cell death of primary bone marrow-derived macrophages (BMDMs) in vitro. The results showed that PS-341 could not induce macrophage apoptosis or promote TNF-induced macrophage apoptosis, on the other hand, PS-341 could significantly inhibit macrophage necroptosis induced by TNF and pan-caspase inhibitor z-VAD treatment. Remarkably, high-dose of PS-341 showed similar inhibitory effects on macrophage necroptosis comparable to that of kinase inhibition of RIP1 through specific inhibitor Nec-1 or inhibition of RIP3 via specific genetical ablation. Furthermore, the degradation of cellular inhibitor of apoptosis proteins (cIAPs) was suppressed by PS-341, which could antagonize the activation of RIP1 kinase via post-translational mechanism. Further evidences demonstrated reduced levels of both RIP1 and RIP 3 upon PS-341 treatment, concomitantly, a more strong association of RIP1 with cIAPs and less with RIP3 was found following PS-341 treatment, these findings suggested that PS-341 may disrupt the formation of RIP1-RIP3 complex (necrosome) through stabilizing cIAPs. Collectively, our results indicated that the proteasome-mediated degradation of cIAPs could be inhibited by PS-341 and followed by limited RIP1 and RIP3 kinase activities, which were indispensable for necroptosis, thus eliciting a significant necroptosis rescue in BMDMs in vitro. Overall, our study has identified a new role of PS-341 in the cell death of BMDMs and provided a novel insight into the atherosclerotic inflammation caused by proteasome-mediated macrophage necroptosis. Copyright © 2016 Elsevier Inc. All rights reserved.

Relationship between ventral hernia defect area and intra-abdominal pressure: dynamic in vivo measurement.

PubMed

Qandeel, Haitham; O'Dwyer, Patrick J

2016-04-01

It is an acceptable concept that the ventral hernia defect area will increase with a rise in intra-abdominal pressure (IAP). The literature lacks the evidence about how much this increase is in vivo. The aim of this study was to objectively measure the change in the ventral hernia defect area with increasing intra-abdominal pressure. In a prospective study of laparoscopic ventral hernia repair, the area of hernia defect was measured from inside the abdomen using a sterile paper ruler. The horizontal (width) and vertical (length) measurements of the defect were taken at two pressure points: (IAP = 8 mmHg) and (IAP = 15 mmHg). The hernia defect area was calculated as an oval shape using a standard formula. Eighteen consecutive patients with a ventral hernia were included in this study (8 males: 10 females). Median age was 60 years (30-81), body mass index (BMI) was 29.9 (22.6-37.6). Changing the IAP significantly, (P < 0.001) changed the values of horizontal and vertical measurements, and the calculated area of the ventral hernia defect. The median calculated defect area, as an oval shape, was 5.6 cm(2) (Q1-Q3 = 3.5-15.5) and 6.9 cm(2) (Q1-Q3 = 4.5-18.7) at 8 and 15 mmHg IAP, respectively. The calculated area of mesh required to cover the defect with a 5 cm overlap increased by a median of 5% (Q1-Q3 = 3-6%). The change in defect area did not differ significantly between obese and non-obese patients (P = 0.5). Dynamic, rather than static, measurements of ventral hernia area during laparoscopy provide a simple way of in vivo objective measurement that helps the surgeon choose the appropriate area of mesh. When choosing mesh area, we support the trend toward a larger overlap of at least 5 cm if less precise methods of measuring defect area are been used.

Propulsion and Cryogenics Advanced Development (PCAD) Project Propulsion Technologies for the Lunar Lander

NASA Technical Reports Server (NTRS)

Klem, Mark D.; Smith, Timothy D.

2008-01-01

The Propulsion and Cryogenics Advanced Development (PCAD) Project in the Exploration Technology Development Program is developing technologies as risk mitigation for Orion and the Lunar Lander. An integrated main and reaction control propulsion system has been identified as a candidate for the Lunar Lander Ascent Module. The propellants used in this integrated system are Liquid Oxygen (LOX)/Liquid Methane (LCH4) propellants. A deep throttle pump fed Liquid Oxygen (LOX)/Liquid Hydrogen (LH2) engine system has been identified for the Lunar Lander Descent Vehicle. The propellant combination and architecture of these propulsion systems are novel and would require risk reduction prior to detailed design and development. The PCAD Project addresses the technology requirements to obtain relevant and necessary test data to further the technology maturity of propulsion hardware utilizing these propellants. This plan and achievements to date will be presented.

Reconfiguration of NASA GRC's Vacuum Facility 6 for Testing of Advanced Electric Propulsion System (AEPS) Hardware

NASA Technical Reports Server (NTRS)

Peterson, Peter; Kamhawi, Hani; Huang, Wensheng; Yim, John; Haag, Tom; Mackey, Jonathan; McVetta, Mike; Sorrelle, Luke; Tomsik, Tom; Gilligan, Ryan;

Reconfiguration of NASA GRC's Vacuum Facility 6 for Testing of Advanced Electric Propulsion System (AEPS) Hardware

NASA Technical Reports Server (NTRS)

Peterson, Peter Y.; Kamhawi, Hani; Huang, Wensheng; Yim, John; Haag, Tom; Mackey, Jonathan; McVetta, Mike; Sorrelle, Luke; Tomsik, Tom; Gilligan, Ryan;

Reconfiguration of NASA GRC's Vacuum Facility 6 for Testing of Advanced Electric Propulsion System (AEPS) Hardware

NASA Technical Reports Server (NTRS)

Peterson, Peter Y.; Kamhawi, Hani; Huang, Wensheng; Yim, John T.; Haag, Thomas W.; Mackey, Jonathan A.; McVetta, Michael S.; Sorrelle, Luke T.; Tomsik, Thomas M.; Gilligan, Ryan P.;

A perspective on future directions in aerospace propulsion system simulation

NASA Technical Reports Server (NTRS)

Miller, Brent A.; Szuch, John R.; Gaugler, Raymond E.; Wood, Jerry R.

1989-01-01

The design and development of aircraft engines is a lengthy and costly process using today's methodology. This is due, in large measure, to the fact that present methods rely heavily on experimental testing to verify the operability, performance, and structural integrity of components and systems. The potential exists for achieving significant speedups in the propulsion development process through increased use of computational techniques for simulation, analysis, and optimization. This paper outlines the concept and technology requirements for a Numerical Propulsion Simulation System (NPSS) that would provide capabilities to do interactive, multidisciplinary simulations of complete propulsion systems. By combining high performance computing hardware and software with state-of-the-art propulsion system models, the NPSS will permit the rapid calculation, assessment, and optimization of subcomponent, component, and system performance, durability, reliability and weight-before committing to building hardware.

Definition of propulsion system for V/STOL research and technology aircraft

NASA Technical Reports Server (NTRS)

1977-01-01

Wind tunnel test support, aircraft contractor support, a propulsion system computer card deck, preliminary design studies, and propulsion system development plan are reported. The Propulsion system consists of two lift/cruise turbofan engines, one turboshaft engine and one lift fan connected together with shafting into a combiner gearbox. Distortion parameter levels from 40 x 80 test data were within the established XT701-AD-700 limits. The three engine-three fan system card deck calculates either vertical or conventional flight performance, installed or uninstalled. Design study results for XT701 engine modifications, bevel gear cross shaft location, fixed and tilt fan frames and propulsion system controls are described. Optional water-alcohol injection increased total net thrust 10.3% on a 90 F day. Engines have sufficient turbine life for 500 hours of the RTA duty cycle.

Test and Evaluation of an Eddy Current Clutch/Brake Propulsion System

DOT National Transportation Integrated Search

1975-01-01

This report covers the Phase II effort of a program to develop and test a 15 hp eddy-current clutch propulsion system. Included in the Phase 2 effort are the test and evaluation of the eddy-current clutch propulsion system on board a test vehicle. Th...

Research Technology

NASA Image and Video Library

1999-10-21

Pictured is an artist's concept of an advanced chemical propulsion system called Pulse Detonation. Long term technology research in this advanced propulsion system has the potential to dramatically change the way we think about space propulsion systems. This research is expected to significantly reduce the cost of space travel within the next 25 years.

Proceedings of the International Conference on the Performance of Off-Road Vehicles and Machines (8th). Volume 3. Held at Cambridge England, on August 5-11, 1984.

DTIC Science & Technology

1984-08-01

energy-savIng propulsion systems for tracked all- -terrain vehicles with extremely high mobility. Mong many proposed idea, Sthoeof hybrid -electric...propulsion system are dominant. Hybrid -electric propulsion system are hybrids In which at least one of the energy stores, sources or convertors can...Aer’teed b*.of I F~ Po ’edfJr* dema. 1046 Modern newly designed energy-saving hybrid -electric propulsion systems work on tracked all-terrain vehicles are

Large Liquid Rocket Testing: Strategies and Challenges

NASA Technical Reports Server (NTRS)

Rahman, Shamim A.; Hebert, Bartt J.

2005-01-01

Rocket propulsion development is enabled by rigorous ground testing in order to mitigate the propulsion systems risks that are inherent in space flight. This is true for virtually all propulsive devices of a space vehicle including liquid and solid rocket propulsion, chemical and non-chemical propulsion, boost stage and in-space propulsion and so forth. In particular, large liquid rocket propulsion development and testing over the past five decades of human and robotic space flight has involved a combination of component-level testing and engine-level testing to first demonstrate that the propulsion devices were designed to meet the specified requirements for the Earth to Orbit launchers that they powered. This was followed by a vigorous test campaign to demonstrate the designed propulsion articles over the required operational envelope, and over robust margins, such that a sufficiently reliable propulsion system is delivered prior to first flight. It is possible that hundreds of tests, and on the order of a hundred thousand test seconds, are needed to achieve a high-reliability, flight-ready, liquid rocket engine system. This paper overviews aspects of earlier and recent experience of liquid rocket propulsion testing at NASA Stennis Space Center, where full scale flight engines and flight stages, as well as a significant amount of development testing has taken place in the past decade. The liquid rocket testing experience discussed includes testing of engine components (gas generators, preburners, thrust chambers, pumps, powerheads), as well as engine systems and complete stages. The number of tests, accumulated test seconds, and years of test stand occupancy needed to meet varying test objectives, will be selectively discussed and compared for the wide variety of ground test work that has been conducted at Stennis for subscale and full scale liquid rocket devices. Since rocket propulsion is a crucial long-lead element of any space system acquisition or development, the appropriate plan and strategy must be put in place at the outset of the development effort. A deferment of this test planning, or inattention to strategy, will compromise the ability of the development program to achieve its systems reliability requirements and/or its development milestones. It is important for the government leadership and support team, as well as the vehicle and propulsion development team, to give early consideration to this aspect of space propulsion and space transportation work.

Solar Electric and Chemical Propulsion for a Titan Mission

NASA Technical Reports Server (NTRS)

Cupples, Michael; Green, Shaun E.; Donahue, Benjamin B.; Coverstone, Victoria L.

2005-01-01

Systems analyses were performed for a Titan Explorer Mission characterized by Earth-Saturn transfer stages using solar electric power generation and propulsion systems for primary interplanetary propulsion, and chemical propulsion for capture at Titan. An examination of a range of system factors was performed to determine their effect on the payload delivery capability to Titan. The effect of varying launch vehicle type, solar array power level, ion thruster number, specific impulse, trip time, and Titan capture stage chemical propellant choice was investigated. The major purpose of the study was to demonstrate the efficacy of applying advanced ion propulsion system technologies like NASA's Evolutionary Xenon Thruster (NEXT), coupled with state-of-the-art (SOA) and advanced chemical technologies to a Flagship class mission. This study demonstrated that a NASA Design Reference Mission (DRM) payload of 406 kg could be successfully delivered to Titan using the baseline advanced ion propulsion system in conjunction with SOA chemical propulsion for Titan capture. In addition, the SEPS/Chemical system of this study is compared to an all- chemical NASA DRM mission. Results showed that the NEXT- based SEPS/Chemical system was able to deliver the required payload to Titan in 5 years less transfer time and on a smaller launch vehicle than the SOA chemical option.

Hybrid propulsion systems for space exploration missions

NASA Technical Reports Server (NTRS)

Darooka, D. K.

1991-01-01

Combinations of nuclear thermal propulsion (NTP), nuclear electric propulsion (NEP), and chemical propulsion are discussed. Technical details are given in viewgraph form. The characteristics of each configuration are discussed, particularly thrust characteristics.

The NASA In-Space Propulsion Technology Project's Current Products and Future Directions

NASA Technical Reports Server (NTRS)

Anderson, David J.; Dankanich, John; Munk, Michelle M.; Pencil, Eric; Liou, Larry

2010-01-01

Since its inception in 2001, the objective of the In-Space Propulsion Technology (ISPT) project has been developing and delivering in-space propulsion technologies that enable or enhance NASA robotic science missions. These in-space propulsion technologies are applicable, and potentially enabling for future NASA flagship and sample return missions currently under consideration, as well as having broad applicability to future Discovery and New Frontiers mission solicitations. This paper provides status of the technology development, applicability, and availability of in-space propulsion technologies that recently completed, or will be completing within the next year, their technology development and are ready for infusion into missions. The paper also describes the ISPT project s future focus on propulsion for sample return missions. The ISPT technologies completing their development are: 1) the high-temperature Advanced Material Bipropellant Rocket (AMBR) engine providing higher performance for lower cost; 2) NASA s Evolutionary Xenon Thruster (NEXT) ion propulsion system, a 0.6-7 kW throttle-able gridded ion system; and 3) aerocapture technologies which include thermal protection system (TPS) materials and structures, guidance, navigation, and control (GN&C) models of blunt-body rigid aeroshells; and atmospheric and aerothermal effect models. The future technology development areas for ISPT are: 1) Planetary Ascent Vehicles (PAV); 2) multi-mission technologies for Earth Entry Vehicles (MMEEV) needed for sample return missions from many different destinations; 3) propulsion for Earth Return Vehicles (ERV) and transfer stages, and electric propulsion for sample return and low cost missions; 4) advanced propulsion technologies for sample return; and 5) Systems/Mission Analysis focused on sample return propulsion.

Trajectory correction propulsion for TOPS

NASA Technical Reports Server (NTRS)

Long, H. R.; Bjorklund, R. A.

1972-01-01

A blowdown-pressurized hydrazine propulsion system was selected to provide trajectory correction impulse for outer planet flyby spacecraft as the result of cost/mass/reliability tradeoff analyses. Present hydrazine component and system technology and component designs were evaluated for application to the Thermoelectric Outer Planet Spacecraft (TOPS); while general hydrazine technology was adequate, component design changes were deemed necessary for TOPS-type missions. A prototype hydrazine propulsion system was fabricated and fired nine times for a total of 1600 s to demonstrate the operation and performance of the TOPS propulsion configuration. A flight-weight trajectory correction propulsion subsystem (TCPS) was designed for the TOPS based on actual and estimated advanced components.

Space station onboard propulsion system: Technology study

NASA Technical Reports Server (NTRS)

Mcallister, J. G.; Rudland, R. S.; Redd, L. R.; Beekman, D. H.; Cuffin, S. M.; Beer, C. M.; Mccarthy, K. K.

1987-01-01

The objective was to prepare for the design of the space station propulsion system. Propulsion system concepts were defined and schematics were developed for the most viable concepts. A dual model bipropellant system was found to deliver the largest amount of payload. However, when resupply is considered, an electrolysis system with 10 percent accumulators requires less resupply propellant, though it is penalized by the amount of time required to fill the accumulators and the power requirements for the electrolyzer. A computer simulation was prepared, which was originally intended to simulate the water electrolysis propulsion system but which was expanded to model other types of systems such as cold gas, monopropellant and bipropellant storable systems.

Design, Integration, Certification and Testing of the Orion Crew Module Propulsion System

NASA Technical Reports Server (NTRS)

McKay, Heather; Freeman, Rich; Cain, George; Albright, John D.; Schoenberg, Rich; Delventhal, Rex

2014-01-01

The Orion Multipurpose Crew Vehicle (MPCV) is NASA's next generation spacecraft for human exploration of deep space. Lockheed Martin is the prime contractor for the design, development, qualification and integration of the vehicle. A key component of the Orion Crew Module (CM) is the Propulsion Reaction Control System, a high-flow hydrazine system used during re-entry to orient the vehicle for landing. The system consists of a completely redundant helium (GHe) pressurization system and hydrazine fuel system with monopropellant thrusters. The propulsion system has been designed, integrated, and qualification tested in support of the Orion program's first orbital flight test, Exploration Flight Test One (EFT-1), scheduled for 2014. A subset of the development challenges and lessons learned from this first flight test campaign will be discussed in this paper for consideration when designing future spacecraft propulsion systems. The CONOPS and human rating requirements of the CM propulsion system are unique when compared with a typical satellite propulsion reaction control system. The system requires a high maximum fuel flow rate. It must operate at both vacuum and sea level atmospheric pressure conditions. In order to meet Orion's human rating requirements, multiple parts of the system must be redundant, and capable of functioning after spacecraft system fault events.

Technology Roadmap for Dual-Mode Scramjet Propulsion to Support Space-Access Vision Vehicle Development

NASA Technical Reports Server (NTRS)

Cockrell, Charles E., Jr.; Auslender, Aaron H.; Guy, R. Wayne; McClinton, Charles R.; Welch, Sharon S.

2002-01-01

Third-generation reusable launch vehicle (RLV) systems are envisioned that utilize airbreathing and combined-cycle propulsion to take advantage of potential performance benefits over conventional rocket propulsion and address goals of reducing the cost and enhancing the safety of systems to reach earth orbit. The dual-mode scramjet (DMSJ) forms the core of combined-cycle or combination-cycle propulsion systems for single-stage-to-orbit (SSTO) vehicles and provides most of the orbital ascent energy. These concepts are also relevant to two-stage-to-orbit (TSTO) systems with an airbreathing first or second stage. Foundation technology investments in scramjet propulsion are driven by the goal to develop efficient Mach 3-15 concepts with sufficient performance and operability to meet operational system goals. A brief historical review of NASA scramjet development is presented along with a summary of current technology efforts and a proposed roadmap. The technology addresses hydrogen-fueled combustor development, hypervelocity scramjets, multi-speed flowpath performance and operability, propulsion-airframe integration, and analysis and diagnostic tools.

Coupled simulation of the propulsion system and vehicle using the ESPSS satellite library

NASA Astrophysics Data System (ADS)

Koppel, C. R.; Di Matteo, F.; Moral, J.; Steelant, J.

2018-06-01

The paper documents the implementation and validation of the coupled simulation of the propulsion system and vehicle performed during the 4th development phase of the ESPSS (European Space Propulsion System Simulation) library running on the existing platform EcosimPro®. This covers a significant update of the spacecraft propulsion system modeling: the Fluid flow, Tanks and Combustion chamber components are updated to allow coupling to the vehicle's motion, the Archimedes pressure coming from acceleration and rotations given by the vehicle or by any perturbation forces are taken into account, several new features are added to the Satellite library along with new components enabling full attitude control of a platform. A new powerful compact equation is presented for solving elegantly the Archimedes pressure coming from combined acceleration and rotation in the most general case (noncollinear). Eventually, a propulsion system is modeled to check the correct implementation of the new components especially those dealing with the effects of the mission on the propulsion subsystem.

Propulsion Research at the Propulsion Research Center of the NASA Marshall Space Flight Center

NASA Technical Reports Server (NTRS)

Blevins, John; Rodgers, Stephen

2003-01-01

The Propulsion Research Center of the NASA Marshall Space Flight Center is engaged in research activities aimed at providing the bases for fundamental advancement of a range of space propulsion technologies. There are four broad research themes. Advanced chemical propulsion studies focus on the detailed chemistry and transport processes for high-pressure combustion, and on the understanding and control of combustion stability. New high-energy propellant research ranges from theoretical prediction of new propellant properties through experimental characterization propellant performance, material interactions, aging properties, and ignition behavior. Another research area involves advanced nuclear electric propulsion with new robust and lightweight materials and with designs for advanced fuels. Nuclear electric propulsion systems are characterized using simulated nuclear systems, where the non-nuclear power source has the form and power input of a nuclear reactor. This permits detailed testing of nuclear propulsion systems in a non-nuclear environment. In-space propulsion research is focused primarily on high power plasma thruster work. New methods for achieving higher thrust in these devices are being studied theoretically and experimentally. Solar thermal propulsion research is also underway for in-space applications. The fourth of these research areas is advanced energetics. Specific research here includes the containment of ion clouds for extended periods. This is aimed at proving the concept of antimatter trapping and storage for use ultimately in propulsion applications. Another activity in this involves research into lightweight magnetic technology for space propulsion applications.

Embedded Wing Propulsion Conceptual Study

NASA Technical Reports Server (NTRS)

Kim, Hyun D.; Saunders, John D.

2003-01-01

As a part of distributed propulsion work under NASA's Revolutionary Aeropropulsion Concepts or RAC project, a new propulsion-airframe integrated vehicle concept called Embedded Wing Propulsion (EWP) is developed and examined through system and computational fluid dynamics (CFD) studies. The idea behind the concept is to fully integrate a propulsion system within a wing structure so that the aircraft takes full benefits of coupling of wing aerodynamics and the propulsion thrust stream. The objective of this study is to assess the feasibility of the EWP concept applied to large transport aircraft such as the Blended-Wing-Body aircraft. In this paper, some of early analysis and current status of the study are presented. In addition, other current activities of distributed propulsion under the RAC project are briefly discussed.

Potential propellant storage and feed systems for space station resistojet propulsion options

NASA Technical Reports Server (NTRS)

Bader, Clayton H.

1987-01-01

The resistojet system has been defined as part of the baseline propulsion system for the initial Operating Capability Space Station. The resistojet propulsion module will perform a reboost function using a wide variety of fluids as propellants. There are many optional propellants and propellant combinations for use in the resistojet including (but not limited to): hydrazine, hydrogen, oxygen, nitrogen, water, carbon dioxide, and methane. Many different types of propulsion systems have flown or have been conceptualized that may have application for use with resistojets. This paper describes and compares representative examples of these systems that may provide a basis for space station resistojet system design.

Use of high temperature superconductors in magnetoplasmadynamic systems

NASA Technical Reports Server (NTRS)

Reed, C. B.; Sovey, J. S.

1988-01-01

The use of Tesla-class high-temperature superconducting magnets may have an extremely large impact on critical development issues (erosion, heat transfer, and performance) related to magnetoplasmadynamic (MPD) thrusters and also may provide significant benefits in reducing the mass of magnetics used in the power processing system. These potential performance improvements, coupled with additional benefits of high-temperature superconductivity, provide a very strong motivation to develop high-temperature superconductivity (HTS) applied-field MPD thruster propulsion systems. The application of HTS to MPD thruster propulsion systems may produce an enabling technology for these electric propulsion systems. This paper summarizes the impact that HTS may have upon MPD propulsion systems.

Advanced Space Transportation Concepts and Propulsion Technologies for a New Delivery Paradigm

NASA Technical Reports Server (NTRS)

Robinson, John W.; McCleskey, Carey M.; Rhodes, Russel E.; Lepsch, Roger A.; Henderson, Edward M.; Joyner, Claude R., III; Levack, Daniel J. H.

2013-01-01

This paper describes Advanced Space Transportation Concepts and Propulsion Technologies for a New Delivery Paradigm. It builds on the work of the previous paper "Approach to an Affordable and Productive Space Transportation System". The scope includes both flight and ground system elements, and focuses on their compatibility and capability to achieve a technical solution that is operationally productive and also affordable. A clear and revolutionary approach, including advanced propulsion systems (advanced LOX rich booster engine concept having independent LOX and fuel cooling systems, thrust augmentation with LOX rich boost and fuel rich operation at altitude), improved vehicle concepts (autogeneous pressurization, turbo alternator for electric power during ascent, hot gases to purge system and keep moisture out), and ground delivery systems, was examined. Previous papers by the authors and other members of the Space Propulsion Synergy Team (SPST) focused on space flight system engineering methods, along with operationally efficient propulsion system concepts and technologies. This paper continues the previous work by exploring the propulsion technology aspects in more depth and how they may enable the vehicle designs from the previous paper. Subsequent papers will explore the vehicle design, the ground support system, and the operations aspects of the new delivery paradigm in greater detail.

The NASA In-Space Propulsion Technology Project, Products, and Mission Applicability

NASA Technical Reports Server (NTRS)

Anderson, David J.; Pencil, Eric; Liou, Larry; Dankanich, John; Munk, Michelle M.; Kremic, Tibor

2009-01-01

The In-Space Propulsion Technology (ISPT) Project, funded by NASA s Science Mission Directorate (SMD), is continuing to invest in propulsion technologies that will enable or enhance NASA robotic science missions. This overview provides development status, near-term mission benefits, applicability, and availability of in-space propulsion technologies in the areas of aerocapture, electric propulsion, advanced chemical thrusters, and systems analysis tools. Aerocapture investments improved: guidance, navigation, and control models of blunt-body rigid aeroshells; atmospheric models for Earth, Titan, Mars, and Venus; and models for aerothermal effects. Investments in electric propulsion technologies focused on completing NASA s Evolutionary Xenon Thruster (NEXT) ion propulsion system, a 0.6 to 7 kW throttle-able gridded ion system. The project is also concluding its High Voltage Hall Accelerator (HiVHAC) mid-term product specifically designed for a low-cost electric propulsion option. The primary chemical propulsion investment is on the high-temperature Advanced Material Bipropellant Rocket (AMBR) engine providing higher performance for lower cost. The project is also delivering products to assist technology infusion and quantify mission applicability and benefits through mission analysis and tools. In-space propulsion technologies are applicable, and potentially enabling for flagship destinations currently under evaluation, as well as having broad applicability to future Discovery and New Frontiers mission solicitations.

NASA's In-Space Propulsion Technology Project Overview, Near-term Products and Mission Applicability

NASA Technical Reports Server (NTRS)

Dankanich, John; Anderson, David J.

2008-01-01

The In-Space Propulsion Technology (ISPT) Project, funded by NASA's Science Mission Directorate (SMD), is continuing to invest in propulsion technologies that will enable or enhance NASA robotic science missions. This overview provides development status, near-term mission benefits, applicability, and availability of in-space propulsion technologies in the areas of aerocapture, electric propulsion, advanced chemical thrusters, and systems analysis tools. Aerocapture investments improved (1) guidance, navigation, and control models of blunt-body rigid aeroshells, 2) atmospheric models for Earth, Titan, Mars and Venus, and 3) models for aerothermal effects. Investments in electric propulsion technologies focused on completing NASA s Evolutionary Xenon Thruster (NEXT) ion propulsion system, a 0.6-7 kW throttle-able gridded ion system. The project is also concluding its High Voltage Hall Accelerator (HiVHAC) mid-term product specifically designed for a low-cost electric propulsion option. The primary chemical propulsion investment is on the high-temperature Advanced Material Bipropellant Rocket (AMBR) engine providing higher performance for lower cost. The project is also delivering products to assist technology infusion and quantify mission applicability and benefits through mission analysis and tools. In-space propulsion technologies are applicable, and potentially enabling for flagship destinations currently under evaluation, as well as having broad applicability to future Discovery and New Frontiers mission solicitations.

An Overview of Aerospace Propulsion Research at NASA Glenn Research Center

NASA Technical Reports Server (NTRS)

Reddy, D. R.

2007-01-01

NASA Glenn Research center is the recognized leader in aerospace propulsion research, advanced technology development and revolutionary system concepts committed to meeting the increasing demand for low noise, low emission, high performance, and light weight propulsion systems for affordable and safe aviation and space transportation needs. The technologies span a broad range of areas including air breathing, as well as rocket propulsion systems, for commercial and military aerospace applications and for space launch, as well as in-space propulsion applications. The scope of work includes fundamentals, components, processes, and system interactions. Technologies developed use both experimental and analytical approaches. The presentation provides an overview of the current research and technology development activities at NASA Glenn Research Center .

10 CFR 473.30 - Standards and criteria.

Code of Federal Regulations, 2014 CFR

2014-01-01

... DEPARTMENT OF ENERGY ENERGY CONSERVATION AUTOMOTIVE PROPULSION RESEARCH AND DEVELOPMENT Review and... if the research and development to be conducted— (a) Supplements the automotive propulsion system...) Is likely to produce an advanced automobile propulsion system suitable for steps toward technology...

10 CFR 473.30 - Standards and criteria.

Code of Federal Regulations, 2012 CFR

2012-01-01

... DEPARTMENT OF ENERGY ENERGY CONSERVATION AUTOMOTIVE PROPULSION RESEARCH AND DEVELOPMENT Review and... if the research and development to be conducted— (a) Supplements the automotive propulsion system...) Is likely to produce an advanced automobile propulsion system suitable for steps toward technology...

10 CFR 473.30 - Standards and criteria.

Code of Federal Regulations, 2013 CFR

2013-01-01

... DEPARTMENT OF ENERGY ENERGY CONSERVATION AUTOMOTIVE PROPULSION RESEARCH AND DEVELOPMENT Review and... if the research and development to be conducted— (a) Supplements the automotive propulsion system...) Is likely to produce an advanced automobile propulsion system suitable for steps toward technology...

Center for Advanced Space Propulsion

NASA Technical Reports Server (NTRS)

1995-01-01

The Center for Advanced Space Propulsion (CASP) is part of the University of Tennessee-Calspan Center for Aerospace Research (CAR). It was formed in 1985 to take advantage of the extensive research faculty and staff of the University of Tennessee and Calspan Corporation. It is also one of sixteen NASA sponsored Centers established to facilitate the Commercial Development of Space. Based on investigators' qualifications in propulsion system development, and matching industries' strong intent, the Center focused its efforts in the following technical areas: advanced chemical propulsion, electric propulsion, AI/Expert systems, fluids management in microgravity, and propulsion materials processing. This annual report focuses its discussion in these technical areas.

Space Transportation Propulsion Technology Symposium. Volume 1: Executive summary

NASA Technical Reports Server (NTRS)

1991-01-01

The Space Transportation Propulsion Technology Symposium was held to provide a forum for communication within the propulsion within the propulsion technology developer and user communities. Emphasis was placed on propulsion requirements and initiatives to support current, next generation, and future space transportation systems, with the primary objectives of discerning whether proposed designs truly meet future transportation needs and identifying possible technology gaps, overlaps, and other programmatic deficiencies. Key space transportation propulsion issues were addressed through four panels with government, industry, and academia membership. The panels focused on systems engineering and integration; development, manufacturing and certification; operational efficiency; and program development and cultural issues.

Software To Secure Distributed Propulsion Simulations

NASA Technical Reports Server (NTRS)

Blaser, Tammy M.

2003-01-01

Distributed-object computing systems are presented with many security threats, including network eavesdropping, message tampering, and communications middleware masquerading. NASA Glenn Research Center, and its industry partners, has taken an active role in mitigating the security threats associated with developing and operating their proprietary aerospace propulsion simulations. In particular, they are developing a collaborative Common Object Request Broker Architecture (CORBA) Security (CORBASec) test bed to secure their distributed aerospace propulsion simulations. Glenn has been working with its aerospace propulsion industry partners to deploy the Numerical Propulsion System Simulation (NPSS) object-based technology. NPSS is a program focused on reducing the cost and time in developing aerospace propulsion engines

Vehicle-Level Oxygen/Methane Propulsion System Hotfire Testing at Thermal Vacuum Conditions

NASA Technical Reports Server (NTRS)

Morehead, Robert L.; Melcher, J. C.; Atwell, Matthew J.; Hurlbert, Eric A.; Desai, Pooja; Werlink, Rudy

2017-01-01

A prototype integrated liquid oxygen/liquid methane propulsion system was hot-fire tested at a variety of simulated altitude and thermal conditions in the NASA Glenn Research Center Plum Brook Station In-Space Propulsion Thermal Vacuum Chamber (formerly B2). This test campaign served two purposes: 1) Characterize the performance of the Plum Brook facility in vacuum accumulator mode and 2) Collect the unique data set of an integrated LOX/Methane propulsion system operating in high altitude and thermal vacuum environments (a first). Data from this propulsion system prototype could inform the design of future spacecraft in-space propulsion systems, including landers. The test vehicle for this campaign was the Integrated Cryogenic Propulsion Test Article (ICPTA), which was constructed for this project using assets from the former Morpheus Project rebuilt and outfitted with additional new hardware. The ICPTA utilizes one 2,800 lbf main engine, two 28 lbf and two 7 lbf reaction control engines mounted in two pods, four 48-inch propellant tanks (two each for liquid oxygen and liquid methane), and a cold helium system for propellant tank pressurization. Several hundred sensors on the ICPTA and many more in the test cell collected data to characterize the operation of the vehicle and facility. Multiple notable experiments were performed during this test campaign, many for the first time, including pressure-fed cryogenic reaction control system characterization over a wide range of conditions, coil-on-plug ignition system demonstration at the vehicle level, integrated main engine/RCS operation, and a non-intrusive propellant mass gauging system. The test data includes water-hammer and thermal heat leak data critical to validating models for use in future vehicle design activities. This successful test campaign demonstrated the performance of the updated Plum Brook In-Space Propulsion thermal vacuum chamber and incrementally advanced the state of LOX/Methane propulsion technology through numerous system-level and subsystem experiments.

Modeling of Water-Breathing Propulsion Systems Utilizing the Aluminum-Seawater Reaction and Solid-Oxide Fuel Cells

DTIC Science & Technology

2011-01-01

ABSTRACT Title of Document: MODELING OF WATER-BREATHING PROPULSION SYSTEMS UTILIZING THE ALUMINUM-SEAWATER REACTION AND SOLID...Hybrid Aluminum Combustor (HAC): a novel underwater power system based on the exothermic reaction of aluminum with seawater. The system is modeled ...using a NASA-developed framework called Numerical Propulsion System Simulation (NPSS) by assembling thermodynamic models developed for each component

Revised Simulation Model of the Control System, Displays, and Propulsion System for a ASTOVL Lift Fan Aircraft

NASA Technical Reports Server (NTRS)

Franklin, James A.

1997-01-01

This report describes revisions to a simulation model that was developed for use in piloted evaluations of takeoff, transition, hover, and landing characteristics of an advanced short takeoff and vertical landing lift fan fighter aircraft. These revisions have been made to the flight/propulsion control system, head-up display, and propulsion system to reflect recent flight and simulation experience with short takeoff and vertical landing operations. They include nonlinear inverse control laws in all axes (eliminating earlier versions with state rate feedback), throttle scaling laws for flightpath and thrust command, control selector commands apportioned based on relative effectiveness of the individual controls, lateral guidance algorithms that provide more flexibility for terminal area operations, and a simpler representation of the propulsion system. The model includes modes tailored to the phases of the aircraft's operation, with several response types which are coupled to the aircraft's aerodynamic and propulsion system effectors through a control selector tailored to the propulsion system. Head-up display modes for approach and hover are integrated with the corresponding control modes. Propulsion system components modeled include a remote lift fan and a lift-cruise engine. Their static performance and dynamic responses are represented by the model. A separate report describes the subsonic, power-off aerodynamics and jet induced aerodynamics in hover and forward flight, including ground effects.

Hybrid drive for motor vehicles with a preponderantly intermittent method of operation

NASA Technical Reports Server (NTRS)

Schreck, H.

1977-01-01

A flywheel hybrid propulsion system is compared with a conventional propulsion system in a test vehicle under intermittent operation. An energy balance is presented for the conventional propulsion system. Results so far indicate especially high energy conversion of the gyro component under dynamic operation along with favorable internal combustion engine conditions.

Overview of the Development and Mission Application of the Advanced Electric Propulsion System (AEPS)

NASA Technical Reports Server (NTRS)

Herman, Daniel A.; Tofil, Todd; Santiago, Walter; Kamhawi, Hani; Polk, James E.; Snyder, John Steven; Hofer, Richard R.; Picha, Frank; Jackson, Jerry; Allen, May

2017-01-01

NASA remains committed to the development and demonstration of a high-power solar electric propulsion capability for the Agency. NASA is continuing to develop the 14 kilowatt Advanced Electric Propulsion System (AEPS), which has recently completed an Early Integrated System Test and System Preliminary Design Review. NASA continues to pursue Solar Electric Propulsion (SEP) Technology Demonstration Mission partners and mature high-power SEP mission concepts. The recent announcement of the development of a Power and Propulsion Element (PPE) as the first element of an evolvable human architecture to Mars has replaced the Asteroid Redirect Robotic Mission as the most probable first application of the AEPS Hall thruster system. This high-power SEP capability, or an extensible derivative of it, has been identified as a critical part of an affordable, beyond-low-Earth-orbit, manned-exploration architecture. This paper presents the status of the combined NASA and Aerojet AEPS development activities and updated mission concept for implementation of the AEPS hardware as part of the ion propulsion system for a PPE.

Overview of the Development and Mission Application of the Advanced Electric Propulsion System (AEPS)

NASA Technical Reports Server (NTRS)

Herman, Daniel A.; Tofil, Todd A.; Santiago, Walter; Kamhawi, Hani; Polk, James E.; Snyder, John S.; Hofer, Richard R.; Picha, Frank Q.; Jackson, Jerry; Allen, May

2018-01-01

NASA remains committed to the development and demonstration of a high-power solar electric propulsion capability for the Agency. NASA is continuing to develop the 14 kW Advanced Electric Propulsion System (AEPS), which has recently completed an Early Integrated System Test and System Preliminary Design Review. NASA continues to pursue Solar Electric Propulsion (SEP) Technology Demonstration Mission partners and mature high-power SEP mission concepts. The recent announcement of the development of a Power and Propulsion Element (PPE) as the first element of an evolvable human architecture to Mars has replaced the Asteroid Redirect Robotic Mission (ARRM) as the most probable first application of the AEPS Hall thruster system. This high-power SEP capability, or an extensible derivative of it, has been identified as a critical part of an affordable, beyond-low-Earth-orbit, manned exploration architecture. This paper presents the status of the combined NASA and Aerojet Rocketdyne AEPS development activities and updated mission concept for implementation of the AEPS hardware as part of the ion propulsion system for a PPE.

Loop Shaping Control Design for a Supersonic Propulsion System Model Using Quantitative Feedback Theory (QFT) Specifications and Bounds

NASA Technical Reports Server (NTRS)

Connolly, Joseph W.; Kopasakis, George

2010-01-01

This paper covers the propulsion system component modeling and controls development of an integrated mixed compression inlet and turbojet engine that will be used for an overall vehicle Aero-Propulso-Servo-Elastic (APSE) model. Using previously created nonlinear component-level propulsion system models, a linear integrated propulsion system model and loop shaping control design have been developed. The design includes both inlet normal shock position control and jet engine rotor speed control for a potential supersonic commercial transport. A preliminary investigation of the impacts of the aero-elastic effects on the incoming flow field to the propulsion system are discussed, however, the focus here is on developing a methodology for the propulsion controls design that prevents unstart in the inlet and minimizes the thrust oscillation experienced by the vehicle. Quantitative Feedback Theory (QFT) specifications and bounds, and aspects of classical loop shaping are used in the control design process. Model uncertainty is incorporated in the design to address possible error in the system identification mapping of the nonlinear component models into the integrated linear model.

Numerical simulation of the flow around a steerable propulsion unit

NASA Astrophysics Data System (ADS)

Pacuraru, F.; Lungu, A.; Ungureanu, C.; Marcu, O.

2010-08-01

Azimuth propulsion units have become during the last decade a more and more popular solution for all kinds of vessels. Azimuth thruster system, combining the propulsion and steering units of conventional ships replaces traditional propellers and lengthy drive shafts and rudders ensuring an excellent vessel steering. In many cases the interaction between the propeller and other components of the propulsion system strongly affects the inflow to the propeller and therefore its performance. The correct estimation of this influence is important for propulsion systems which consist of more than one element, such as pods (shaft, gondola and propeller), ducted propellers (duct, struts and propeller) or bow thrusters (ship form, tunnel, gondola and propeller). The paper proposes a numerical investigation based on RANS computation for solving the viscous flow around an azimuth thruster system to provide a detailed insight into the critical flow regions for determining the optimum inclination angle for struts, for studying the hydrodynamic interactions between various components of the system, for predicting the hydrodynamic performance of the propulsion system and to investigate regions with possible flow separations.

Propulsion IVHM Technology Experiment

NASA Technical Reports Server (NTRS)

Chicatelli, Amy K.; Maul, William A.; Fulton, Christopher E.

2006-01-01

The Propulsion IVHM Technology Experiment (PITEX) successfully demonstrated real-time fault detection and isolation of a virtual reusable launch vehicle (RLV) main propulsion system (MPS). Specifically, the PITEX research project developed and applied a model-based diagnostic system for the MPS of the X-34 RLV, a space-launch technology demonstrator. The demonstration was simulation-based using detailed models of the propulsion subsystem to generate nominal and failure scenarios during captive carry, which is the most safety-critical portion of the X-34 flight. Since no system-level testing of the X-34 Main Propulsion System (MPS) was performed, these simulated data were used to verify and validate the software system. Advanced diagnostic and signal processing algorithms were developed and tested in real time on flight-like hardware. In an attempt to expose potential performance problems, the PITEX diagnostic system was subjected to numerous realistic effects in the simulated data including noise, sensor resolution, command/valve talkback information, and nominal build variations. In all cases, the PITEX system performed as required. The research demonstrated potential benefits of model-based diagnostics, defined performance metrics required to evaluate the diagnostic system, and studied the impact of real-world challenges encountered when monitoring propulsion subsystems.

A minimum propellant solution to an orbit-to-orbit transfer using a low thrust propulsion system

NASA Technical Reports Server (NTRS)

Cobb, Shannon S.

1991-01-01

The Space Exploration Initiative is considering the use of low thrust (nuclear electric, solar electric) and intermediate thrust (nuclear thermal) propulsion systems for transfer to Mars and back. Due to the duration of such a mission, a low thrust minimum-fuel solution is of interest; a savings of fuel can be substantial if the propulsion system is allowed to be turned off and back on. This switching of the propulsion system helps distinguish the minimal-fuel problem from the well-known minimum-time problem. Optimal orbit transfers are also of interest to the development of a guidance system for orbital maneuvering vehicles which will be needed, for example, to deliver cargoes to the Space Station Freedom. The problem of optimizing trajectories for an orbit-to-orbit transfer with minimum-fuel expenditure using a low thrust propulsion system is addressed.

Reliability model of a monopropellant auxiliary propulsion system

NASA Technical Reports Server (NTRS)

Greenberg, J. S.

1971-01-01

A mathematical model and associated computer code has been developed which computes the reliability of a monopropellant blowdown hydrazine spacecraft auxiliary propulsion system as a function of time. The propulsion system is used to adjust or modify the spacecraft orbit over an extended period of time. The multiple orbit corrections are the multiple objectives which the auxiliary propulsion system is designed to achieve. Thus the reliability model computes the probability of successfully accomplishing each of the desired orbit corrections. To accomplish this, the reliability model interfaces with a computer code that models the performance of a blowdown (unregulated) monopropellant auxiliary propulsion system. The computer code acts as a performance model and as such gives an accurate time history of the system operating parameters. The basic timing and status information is passed on to and utilized by the reliability model which establishes the probability of successfully accomplishing the orbit corrections.

A rapid method for optimization of the rocket propulsion system for single-stage-to-orbit vehicles

NASA Technical Reports Server (NTRS)

Eldred, C. H.; Gordon, S. V.

1976-01-01

A rapid analytical method for the optimization of rocket propulsion systems is presented for a vertical take-off, horizontal landing, single-stage-to-orbit launch vehicle. This method utilizes trade-offs between propulsion characteristics affecting flight performance and engine system mass. The performance results from a point-mass trajectory optimization program are combined with a linearized sizing program to establish vehicle sizing trends caused by propulsion system variations. The linearized sizing technique was developed for the class of vehicle systems studied herein. The specific examples treated are the optimization of nozzle expansion ratio and lift-off thrust-to-weight ratio to achieve either minimum gross mass or minimum dry mass. Assumed propulsion system characteristics are high chamber pressure, liquid oxygen and liquid hydrogen propellants, conventional bell nozzles, and the same fixed nozzle expansion ratio for all engines on a vehicle.

Energy Efficient Engine Flight Propulsion System Preliminary Analysis and Design Report

NASA Technical Reports Server (NTRS)

Bisset, J. W.; Howe, D. C.

1983-01-01

The final design and analysis of the flight propulsion system is presented. This system is the conceptual study engine defined to meet the performance, economic and environmental goals established for the Energy Efficient Engine Program. The design effort included a final definition of the engine, major components, internal subsystems, and nacelle. Various analytical representations and results from component technology programs are used to verify aerodynamic and structural design concepts and to predict performance. Specific design goals and specifications, reflecting future commercial aircraft propulsion system requirements for the mid-1980's, are detailed by NASA and used as guidelines during engine definition. Information is also included which details salient results from a separate study to define a turbofan propulsion system, known as the maximum efficiency engine, which reoptimized the advanced fuel saving technologies for improved fuel economy and direct operating costs relative to the flight propulsion system.

Nonlinear Dynamic Modeling of a Supersonic Commercial Transport Turbo-Machinery Propulsion System for Aero-Propulso-Servo-Elasticity Research

NASA Technical Reports Server (NTRS)

Connolly, Joseph W.; Kopasakis, George; Carlson, Jan-Renee; Woolwine, Kyle

2015-01-01

This paper covers the development of an integrated nonlinear dynamic model for a variable cycle turbofan engine, supersonic inlet, and convergent-divergent nozzle that can be integrated with an aeroelastic vehicle model to create an overall Aero-Propulso-Servo-Elastic (APSE) modeling tool. The primary focus of this study is to provide a means to capture relevant thrust dynamics of a full supersonic propulsion system by using relatively simple quasi-one dimensional computational fluid dynamics (CFD) methods that will allow for accurate control algorithm development and capture the key aspects of the thrust to feed into an APSE model. Previously, propulsion system component models have been developed and are used for this study of the fully integrated propulsion system. An overview of the methodology is presented for the modeling of each propulsion component, with a focus on its associated coupling for the overall model. To conduct APSE studies the de- scribed dynamic propulsion system model is integrated into a high fidelity CFD model of the full vehicle capable of conducting aero-elastic studies. Dynamic thrust analysis for the quasi-one dimensional dynamic propulsion system model is presented along with an initial three dimensional flow field model of the engine integrated into a supersonic commercial transport.

Ion Beam Propulsion Study

NASA Technical Reports Server (NTRS)

2008-01-01

The Ion Beam Propulsion Study was a joint high-level study between the Applied Physics Laboratory operated by NASA and ASRC Aerospace at Kennedy Space Center, Florida, and Berkeley Scientific, Berkeley, California. The results were promising and suggested that work should continue if future funding becomes available. The application of ion thrusters for spacecraft propulsion is limited to quite modest ion sources with similarly modest ion beam parameters because of the mass penalty associated with the ion source and its power supply system. Also, the ion source technology has not been able to provide very high-power ion beams. Small ion beam propulsion systems were used with considerable success. Ion propulsion systems brought into practice use an onboard ion source to form an energetic ion beam, typically Xe+ ions, as the propellant. Such systems were used for steering and correction of telecommunication satellites and as the main thruster for the Deep Space 1 demonstration mission. In recent years, "giant" ion sources were developed for the controlled-fusion research effort worldwide, with beam parameters many orders of magnitude greater than the tiny ones of conventional space thruster application. The advent of such huge ion beam sources and the need for advanced propulsion systems for exploration of the solar system suggest a fresh look at ion beam propulsion, now with the giant fusion sources in mind.

Nonlinear Dynamic Modeling of a Supersonic Commercial Transport Turbo-Machinery Propulsion System for Aero-Propulso-Servo-Elasticity Research

NASA Technical Reports Server (NTRS)

Connolly, Joe; Carlson, Jan-Renee; Kopasakis, George; Woolwine, Kyle

2015-01-01

This paper covers the development of an integrated nonlinear dynamic model for a variable cycle turbofan engine, supersonic inlet, and convergent-divergent nozzle that can be integrated with an aeroelastic vehicle model to create an overall Aero-Propulso-Servo-Elastic (APSE) modeling tool. The primary focus of this study is to provide a means to capture relevant thrust dynamics of a full supersonic propulsion system by using relatively simple quasi-one dimensional computational fluid dynamics (CFD) methods that will allow for accurate control algorithm development and capture the key aspects of the thrust to feed into an APSE model. Previously, propulsion system component models have been developed and are used for this study of the fully integrated propulsion system. An overview of the methodology is presented for the modeling of each propulsion component, with a focus on its associated coupling for the overall model. To conduct APSE studies the described dynamic propulsion system model is integrated into a high fidelity CFD model of the full vehicle capable of conducting aero-elastic studies. Dynamic thrust analysis for the quasi-one dimensional dynamic propulsion system model is presented along with an initial three dimensional flow field model of the engine integrated into a supersonic commercial transport.

Invasive alien plant species dynamics in the Himalayan region under climate change.

PubMed

Lamsal, Pramod; Kumar, Lalit; Aryal, Achyut; Atreya, Kishor

2018-01-25

Climate change will impact the dynamics of invasive alien plant species (IAPS). However, the ability of IAPS under changing climate to invade mountain ecosystems, particularly the Himalayan region, is less known. This study investigates the current and future habitat of five IAPS of the Himalayan region using MaxEnt and two representative concentration pathways (RCPs). Two invasive species, Ageratum conyzoides and Parthenium hysterophorus, will lose overall suitable area by 2070, while Ageratina adenophora, Chromolaena odorata and Lantana camara will gain suitable areas and all of them will retain most of the current habitat as stable. The southern Himalayan foothills will mostly conserve species ecological niches, while suitability of all the five species will decrease with increasing elevation. Such invasion dynamics in the Himalayan region could have impacts on numerous ecosystems and their biota, ecosystem services and human well-being. Trans-boundary response strategies suitable to the local context of the region could buffer some of the likely invasion impacts.

Compensation of high order harmonic long quantum-path attosecond chirp

NASA Astrophysics Data System (ADS)

Guichard, R.; Caillat, J.; Lévêque, C.; Risoud, F.; Maquet, A.; Taïeb, R.; Zaïr, A.

2017-12-01

We propose a method to compensate for the extreme ultra violet (XUV) attosecond chirp associated with the long quantum-path in the high harmonic generation process. Our method employs an isolated attosecond pulse (IAP) issued from the short trajectory contribution in a primary target to assist the infrared driving field to produce high harmonics from the long trajectory in a secondary target. In our simulations based on the resolution of the time-dependent Schrödinger equation, the resulting high harmornics present a clear phase compensation of the long quantum-path contribution, near to Fourier transform limited attosecond XUV pulse. Employing time-frequency analysis of the high harmonic dipole, we found that the compensation is not a simple far-field photonic interference between the IAP and the long-path harmonic emission, but a coherent phase transfer from the weak IAP to the long quantum-path electronic wavepacket. Our approach opens the route to utilizing the long quantum-path for the production and applications of attosecond pulses.

Development of Protein Degradation Inducers of Androgen Receptor by Conjugation of Androgen Receptor Ligands and Inhibitor of Apoptosis Protein Ligands.

PubMed

Shibata, Norihito; Nagai, Katsunori; Morita, Yoko; Ujikawa, Osamu; Ohoka, Nobumichi; Hattori, Takayuki; Koyama, Ryokichi; Sano, Osamu; Imaeda, Yasuhiro; Nara, Hiroshi; Cho, Nobuo; Naito, Mikihiko

2018-01-25

Targeted protein degradation using small molecules is a novel strategy for drug development. We have developed hybrid molecules named specific and nongenetic inhibitor of apoptosis protein [IAP]-dependent protein erasers (SNIPERs) that recruit IAP ubiquitin ligases to degrade target proteins. Here, we show novel SNIPERs capable of inducing proteasomal degradation of the androgen receptor (AR). Through derivatization of the SNIPER(AR) molecule at the AR ligand and IAP ligand and linker, we developed 42a (SNIPER(AR)-51), which shows effective protein knockdown activity against AR. Consistent with the degradation of the AR protein, 42a inhibits AR-mediated gene expression and proliferation of androgen-dependent prostate cancer cells. In addition, 42a efficiently induces caspase activation and apoptosis in prostate cancer cells, which was not observed in the cells treated with AR antagonists. These results suggest that SNIPER(AR)s could be leads for an anticancer drug against prostate cancers that exhibit AR-dependent proliferation.

Plasmon-shaped polarization gating for high-order-harmonic generation

NASA Astrophysics Data System (ADS)

Wang, Feng; He, Lixin; Chen, Jiawei; Wang, Baoning; Zhu, Xiaosong; Lan, Pengfei; Lu, Peixiang

2017-12-01

We present a plasmon-shaped polarization gating for high-order-harmonic generation by using a linearly polarized laser field to illuminate two orthogonal bow-tie nanostructures. The results show that when these two bow-tie nanostructures have nonidentical geometrical sizes, the transverse and longitudinal components of the incident laser field will experience different phase responses, thus leading to a time-dependent ellipticity of laser field. For the polarizing angle of incident laser field in the range from 45∘ to 60∘, the dominant harmonic emission is gated within the few optical cycles where the laser ellipticity is below 0.3. Then sub-50-as isolated attosecond pulses (IAPs) can be generated. Such a plasmon-shaped polarization gating is robust for IAP generation against the variations of the carrier-envelope phases of the laser pulse. Moreover, by changing the geometrical size of one of the bow-tie nanostructures, the electron dynamics can be effectively controlled and the more efficient supercontinuum as well as IAP can be generated.

Field resonance propulsion concept

NASA Technical Reports Server (NTRS)

Holt, A. C.

1979-01-01

A propulsion concept was developed based on a proposed resonance between coherent, pulsed electromagnetic wave forms, and gravitational wave forms (or space-time metrics). Using this concept a spacecraft propulsion system potentially capable of galactic and intergalactic travel without prohibitive travel times was designed. The propulsion system utilizes recent research associated with magnetic field line merging, hydromagnetic wave effects, free-electron lasers, laser generation of megagauss fields, and special structural and containment metals. The research required to determine potential, field resonance characteristics and to evaluate various aspects of the spacecraft propulsion design is described.

Fusion for Space Propulsion

NASA Technical Reports Server (NTRS)

Thio, Y. C. Francis; Schmidt, George R.; Santarius, John F.; Turchi, Peter J.; Siemon, Richard E.; Rodgers, Stephen L. (Technical Monitor)

2002-01-01

The need for fusion propulsion for interplanetary flights is discussed. For a propulsion system, there are three important system attributes: (1) The absolute amount of energy available, (2) the propellant exhaust velocity, and (3) the jet power per unit mass of the propulsion system (specific power). For efficient and affordable human exploration of the solar system, propellant exhaust velocity in excess of 100 km/s and specific power in excess of 10 kW/kg are required. Chemical combustion obviously cannot meet the requirement in propellant exhaust velocity. Nuclear fission processes typically result in producing energy in the form of heat that needs to be manipulated at temperatures limited by materials to about 2,800 K. Using the fission energy to heat a low atomic weight propellant produces propellant velocity of the order of 10 kinds. Alternatively the fission energy can be converted into electricity that is used to accelerate particles to high exhaust velocity. However, the necessary power conversion and conditioning equipment greatly increases the mass of the propulsion system. Fundamental considerations in waste heat rejection and power conditioning in a fission electric propulsion system place a limit on its jet specific power to the order of about 0.2 kW/kg. If fusion can be developed for propulsion, it appears to have the best of all worlds - it can provide the largest absolute amount of energy, the propellant exhaust velocity (> 100 km/s), and the high specific jet power (> 10 kW/kg). An intermediate step towards fusion propulsion might be a bimodal system in which a fission reactor is used to provide some of the energy to drive a fusion propulsion unit. There are similarities as well as differences between applying fusion to propulsion and to terrestrial electrical power generation. The similarities are the underlying plasma and fusion physics, the enabling component technologies, the computational and the diagnostics capabilities. These physics and engineering capabilities have been demonstrated for a fusion reactor gain (Q) of the order of unity (TFTR: 0.25, JET: 0.65, JT-60: Q(sub eq) approx. 1.25). These technological advances made it compelling for considering fusion for propulsion.

A CubeSat Asteroid Mission: Design Study and Trade-Offs

NASA Technical Reports Server (NTRS)

Landis, Geoffrey A.; Oleson, Steven R.; McGuire, Melissa; Hepp, Aloysius; Stegeman, James; Bur, Mike; Burke, Laura; Martini, Michael; Fittje, James E.; Kohout, Lisa;

In-Space Propulsion for Science and Exploration

NASA Technical Reports Server (NTRS)

Bishop-Behel, Karen; Johnson, Les

2004-01-01

This paper presents viewgraphs on the development of In-Space Propulsion Technologies for Science and Exploration. The topics include: 1) In-Space Propulsion Technology Program Overview; 2) In-Space Propulsion Technology Project Status; 3) Solar Electric Propulsion; 4) Next Generation Electric Propulsion; 5) Aerocapture Technology Alternatives; 6) Aerocapture; 7) Advanced Thermal Protection Systems Developed and Being Tested; 8) Solar Sails; 9) Advanced Chemical Propulsion; 10) Momentum Exchange Tethers; and 11) Momentum-exchange/electrodynamic reboost (MXER) Tether Basic Operation.

Towards a smart glove: arousal recognition based on textile Electrodermal Response.

PubMed

Valenza, Gaetano; Lanata, Antonio; Scilingo, Enzo Pasquale; De Rossi, Danilo

2010-01-01

This paper investigates the possibility of using Electrodermal Response, acquired by a sensing fabric glove with embedded textile electrodes, as reliable means for emotion recognition. Here, all the essential steps for an automatic recognition system are described, from the recording of physiological data set to a feature-based multiclass classification. Data were collected from 35 healthy volunteers during arousal elicitation by means of International Affective Picture System (IAPS) pictures. Experimental results show high discrimination after twenty steps of cross validation.

A Combined Solar Electric and Storable Chemical Propulsion Vehicle for Piloted Mars Missions

NASA Technical Reports Server (NTRS)

Mercer, Carolyn R.; Oleson, Steven R.; Drake, Bret G.

2014-01-01

The Mars Design Reference Architecture (DRA) 5.0 explored a piloted Mars mission in the 2030 timeframe, focusing on architecture and technology choices. The DRA 5.0 focused on nuclear thermal and cryogenic chemical propulsion system options for the mission. Follow-on work explored both nuclear and solar electric options. One enticing option that was found in a NASA Collaborative Modeling for Parametric Assessment of Space Systems (COMPASS) design study used a combination of a 1-MW-class solar electric propulsion (SEP) system combined with storable chemical systems derived from the planned Orion crew vehicle. It was found that by using each propulsion system at the appropriate phase of the mission, the entire SEP stage and habitat could be placed into orbit with just two planned Space Launch System (SLS) heavy lift launch vehicles assuming the crew would meet up at the Earth-Moon (E-M) L2 point on a separate heavy-lift launch. These appropriate phases use high-thrust chemical propulsion only in gravity wells when the vehicle is piloted and solar electric propulsion for every other phase. Thus the SEP system performs the spiral of the unmanned vehicle from low Earth orbit (LEO) to E-M L2 where the vehicle meets up with the multi-purpose crew vehicle. From here SEP is used to place the vehicle on a trajectory to Mars. With SEP providing a large portion of the required capture and departure changes in velocity (delta V) at Mars, the delta V provided by the chemical propulsion is reduced by a factor of five from what would be needed with chemical propulsion alone at Mars. This trajectory also allows the SEP and habitat vehicle to arrive in the highly elliptic 1-sol parking orbit compatible with envisioned Mars landing concepts. This paper explores mission options using between SEP and chemical propulsion, the design of the SEP system including the solar array and electric propulsion systems, and packaging in the SLS shroud. Design trades of stay time, power level, specific impulse and propellant type are discussed.

A Combined Solar Electric and Storable Chemical Propulsion Vehicle for Piloted Mars Missions

NASA Technical Reports Server (NTRS)

Mercer, Carolyn R.; Oleson, Steven R.; Drake, Bret

2013-01-01

The Mars Design Reference Architecture (DRA) 5.0 explored a piloted Mars mission in the 2030 timeframe, focusing on architecture and technology choices. The DRA 5.0 focused on nuclear thermal and cryogenic chemical propulsion system options for the mission. Follow-on work explored both nuclear and solar electric options. One enticing option that was found in a NASA Collaborative Modeling for Parametric Assessment of Space Systems (COMPASS) design study used a combination of a 1-MW-class solar electric propulsion (SEP) system combined with storable chemical systems derived from the planned Orion crew vehicle. It was found that by using each propulsion system at the appropriate phase of the mission, the entire SEP stage and habitat could be placed into orbit with just two planned Space Launch System (SLS) heavy lift launch vehicles assuming the crew would meet up at the Earth-Moon (E-M) L2 point on a separate heavy-lift launch. These appropriate phases use high-thrust chemical propulsion only in gravity wells when the vehicle is piloted and solar electric propulsion for every other phase. Thus the SEP system performs the spiral of the unmanned vehicle from low Earth orbit (LEO) to E-M L2 where the vehicle meets up with the multi-purpose crew vehicle. From here SEP is used to place the vehicle on a trajectory to Mars. With SEP providing a large portion of the required capture and departure changes in velocity (delta V) at Mars, the delta V provided by the chemical propulsion is reduced by a factor of five from what would be needed with chemical propulsion alone at Mars. This trajectory also allows the SEP and habitat vehicle to arrive in the highly elliptic 1-sol parking orbit compatible with envisioned Mars landing concepts. This paper explores mission options using between SEP and chemical propulsion, the design of the SEP system including the solar array and electric propulsion systems, and packaging in the SLS shroud. Design trades of stay time, power level, specific impulse and propellant type are discussed.

NEXT Single String Integration Test Results

NASA Technical Reports Server (NTRS)

Soulas, George C.; Patterson, Michael J.; Pinero, Luis; Herman, Daniel A.; Snyder, Steven John

2010-01-01

As a critical part of NASA's Evolutionary Xenon Thruster (NEXT) test validation process, a single string integration test was performed on the NEXT ion propulsion system. The objectives of this test were to verify that an integrated system of major NEXT ion propulsion system elements meets project requirements, to demonstrate that the integrated system is functional across the entire power processor and xenon propellant management system input ranges, and to demonstrate to potential users that the NEXT propulsion system is ready for transition to flight. Propulsion system elements included in this system integration test were an engineering model ion thruster, an engineering model propellant management system, an engineering model power processor unit, and a digital control interface unit simulator that acted as a test console. Project requirements that were verified during this system integration test included individual element requirements ; integrated system requirements, and fault handling. This paper will present the results of these tests, which include: integrated ion propulsion system demonstrations of performance, functionality and fault handling; a thruster re-performance acceptance test to establish baseline performance: a risk-reduction PMS-thruster integration test: and propellant management system calibration checks.

Highlights from a Mach 4 Experimental Demonstration of Inlet Mode Transition for Turbine-Based Combined Cycle Hypersonic Propulsion

NASA Technical Reports Server (NTRS)

Foster, Lancert E.; Saunders, John D., Jr.; Sanders, Bobby W.; Weir, Lois J.

2012-01-01

NASA is focused on technologies for combined cycle, air-breathing propulsion systems to enable reusable launch systems for access to space. Turbine Based Combined Cycle (TBCC) propulsion systems offer specific impulse (Isp) improvements over rocket-based propulsion systems in the subsonic takeoff and return mission segments along with improved safety. Among the most critical TBCC enabling technologies are: 1) mode transition from the low speed propulsion system to the high speed propulsion system, 2) high Mach turbine engine development and 3) innovative turbine based combined cycle integration. To address these challenges, NASA initiated an experimental mode transition task including analytical methods to assess the state-of-the-art of propulsion system performance and design codes. One effort has been the Combined-Cycle Engine Large Scale Inlet Mode Transition Experiment (CCE-LIMX) which is a fully integrated TBCC propulsion system with flowpath sizing consistent with previous NASA and DoD proposed Hypersonic experimental flight test plans. This experiment was tested in the NASA GRC 10 by 10-Foot Supersonic Wind Tunnel (SWT) Facility. The goal of this activity is to address key hypersonic combined-cycle engine issues including: (1) dual integrated inlet operability and performance issues-unstart constraints, distortion constraints, bleed requirements, and controls, (2) mode-transition sequence elements caused by switching between the turbine and the ramjet/scramjet flowpaths (imposed variable geometry requirements), and (3) turbine engine transients (and associated time scales) during transition. Testing of the initial inlet and dynamic characterization phases were completed and smooth mode transition was demonstrated. A database focused on a Mach 4 transition speed with limited off-design elements was developed and will serve to guide future TBCC system studies and to validate higher level analyses.

LADEE Propulsion System Cold Flow Test

NASA Technical Reports Server (NTRS)

Williams, Jonathan Hunter; Chapman, Jack M.; Trinh, Hau, P.; Bell, James H.

2013-01-01

Lunar Atmosphere and Dust Environment Explorer (LADEE) is a NASA mission that will orbit the Moon. Its main objective is to characterize the atmosphere and lunar dust environment. The spacecraft development is being led by NASA Ames Research Center and scheduled for launch in 2013. The LADEE spacecraft will be operated with a bi-propellant hypergolic propulsion system using MMH and NTO as the fuel and oxidizer, respectively. The propulsion system utilizes flight-proven hardware on major components. The propulsion layout is composed of one 100-lbf main thruster and four 5-lbf RCS thrusters. The propellants are stored in four tanks (two parallel-connected tanks per propellant component). The propellants will be pressurized by regulated helium. A simulated propulsion system has been built for conducting cold flow test series to characterize the transient fluid flow of the propulsion system feed lines and to verify the critical operation modes, such as system priming, waterhammer, and crucial mission duty cycles. Propellant drainage differential between propellant tanks will also be assessed. Since the oxidizer feed line system has a higher flow demand than the fuel system does, the cold flow test focuses on the oxidizer system. The objective of the cold flow test is to simulate the LADEE propulsion fluid flow operation through water cold flow test and to obtain data for anchoring analytical models. The models will be used to predict the transient and steady state flow behaviors in the actual flight operations. The test activities, including the simulated propulsion test article, cold flow test, and analytical modeling, are being performed at NASA Marshall Space Flight Center. At the time of the abstract submission, the test article checkout is being performed. The test series will be completed by November, 2012

The impact of emerging technologies on an advanced supersonic transport

NASA Technical Reports Server (NTRS)

Driver, C.; Maglieri, D. J.

1986-01-01

The effects of advances in propulsion systems, structure and materials, aerodynamics, and systems on the design and development of supersonic transport aircraft are analyzed. Efficient propulsion systems with variable-cycle engines provide the basis for improved propulsion systems; the propulsion efficienies of supersonic and subsonic engines are compared. Material advances consist of long-life damage-tolerant structures, advanced material development, aeroelastic tailoring, and low-cost fabrication. Improvements in the areas of aerodynamics and systems are examined. The environmental problems caused by engine emissions, airport noise, and sonic boom are studied. The characteristics of the aircraft designed to include these technical advances are described.

Multi-disciplinary coupling effects for integrated design of propulsion systems

NASA Technical Reports Server (NTRS)

Chamis, C. C.; Singhal, S. N.

1993-01-01

Effective computational simulation procedures are described for modeling the inherent multi-disciplinary interactions which govern the accurate response of propulsion systems. Results are presented for propulsion system responses including multi-disciplinary coupling effects using coupled multi-discipline thermal, structural, and acoustic tailoring; an integrated system of multi-disciplinary simulators; coupled material behavior/fabrication process tailoring; sensitivities using a probabilistic simulator; and coupled materials, structures, fracture, and probabilistic behavior simulator. The results demonstrate that superior designs can be achieved if the analysis/tailoring methods account for the multi-disciplinary coupling effects. The coupling across disciplines can be used to develop an integrated coupled multi-discipline numerical propulsion system simulator.

Multi-disciplinary coupling for integrated design of propulsion systems

NASA Technical Reports Server (NTRS)

Chamis, C. C.; Singhal, S. N.

1993-01-01

Effective computational simulation procedures are described for modeling the inherent multi-disciplinary interactions for determining the true response of propulsion systems. Results are presented for propulsion system responses including multi-discipline coupling effects via (1) coupled multi-discipline tailoring, (2) an integrated system of multidisciplinary simulators, (3) coupled material-behavior/fabrication-process tailoring, (4) sensitivities using a probabilistic simulator, and (5) coupled materials/structures/fracture/probabilistic behavior simulator. The results show that the best designs can be determined if the analysis/tailoring methods account for the multi-disciplinary coupling effects. The coupling across disciplines can be used to develop an integrated interactive multi-discipline numerical propulsion system simulator.

NASA's Nuclear Thermal Propulsion Project

NASA Technical Reports Server (NTRS)

Houts, Michael G.; Mitchell, Doyce P.; Kim, Tony; Emrich, William J.; Hickman, Robert R.; Gerrish, Harold P.; Doughty, Glen; Belvin, Anthony; Clement, Steven; Borowski, Stanley K.;