The Aegis BMD Global Enterprise: A High End Maritime Partnership

DTIC Science & Technology

2016-04-13

have been dealing with ballistic-missile defense through the alliance’s Active Layered Theatre Ballistic Missile Defence (ALTBMD) program and, since...Defense Agency (MDA) budgets.18 The twenty-fifth test— designated Flight Test Mission (FTM) 15—occurred on 15 April 2011, when the MDA conducted the...original design , which focused on short- and medium-range threats. The LV-2 had flown in two previous BMD live-fire tests but had not been hit—until FTM

Panel Discussion on Multi-Disciplinary Analysis

NASA Technical Reports Server (NTRS)

Garcia, Robert

2002-01-01

The Marshall Space Flight Center (MSFC) is hosting the Thermal and Fluids Analysis Workshop (TFAWS) during the week of September 10, 2001. Included in this year's TFAWS is a panel session on Multidisciplinary Analysis techniques. The intent is to provide an opportunity for the users to gain information as to what product may be best suited for their applications environment and to provide feedback to you, the developers, on future desired developments. Potential users of multidisciplinary analysis (MDA) techniques are often overwhelmed by the number of choices available to them via commercial products and by the pace of new developments in this area. The purpose of this panel session is to provide a forum wherein MDA tools available and under development can be discussed, compared, and contrasted. The intent of this panel is to provide the end-user with the information necessary to make educated decisions on how to proceed with selecting their MDA tool. It is anticipated that the discussions this year will focus on MDA techniques that couple discipline codes or algorithms (as opposed to monolithic, unified MDA approaches). The MDA developers will be asked to prepare a product overview presentation addressing specific questions provided by the panel organizers. The purpose of these questions will be to establish the method employed by the particular MDA technique for communication between the discipline codes, to establish the similarities and differences amongst the various approaches, and to establish the range of experience and applications for each particular MDA approach.

Solid film lubricants and thermal control coatings flown aboard the EOIM-3 MDA sub-experiment

NASA Technical Reports Server (NTRS)

Murphy, Taylor J.; David, Kaia E.; Babel, Hank W.

1995-01-01

Additional experimental data were desired to support the selection of candidate thermal control coatings and solid film lubricants for the McDonnell Douglas Aerospace (MDA) Space Station hardware. The third Evaluation of Oxygen Interactions With Materials Mission (EOIM-3) flight experiment presented an opportunity to study the effects of the low Earth orbit environment on thermal control coatings and solid film lubricants. MDA provided five solid film lubricants and two anodic thermal control coatings for EOIM-3. The lubricant sample set consisted of three solid film lubricants with organic binders one solid film lubricant with an inorganic binder, and one solid film lubricant with no binder. The anodize coating sample set consisted of undyed sulfuric acid anodize and cobalt sulfide dyed sulfuric acid anodize, each on two different substrate aluminum alloys. The organic and inorganic binders in the solid film lubricants experienced erosion, and the lubricating pigments experienced oxidation. MDA is continuing to assess the effect of exposure to the low Earth orbit environment on the life and friction properties of the lubricants. Results to date support the design practice of shielding solid film lubricants from the low Earth orbit environment. Post-flight optical property analysis of the anodized specimens indicated that there were limited contamination effects and some atomic oxygen and ultraviolet radiation effects. These effects appeared to be within the values predicted by simulated ground testing and analysis of these materials, and they were different for each coating and substrate.

Differentially expressed proteins in ER+ MCF7 and ER- MDA- MB-231 human breast cancer cells by RhoGDI-α silencing and overexpression.

PubMed

Hooshmand, Somayeh; Ghaderi, Abbas; Yusoff, Khatijah; Thilakavathy, Karuppiah; Rosli, Rozita; Mojtahedi, Zahra

2014-01-01

The consequence of Rho GDP dissociation inhibitor alpha (RhoGDIα) activity on migration and invasion of estrogen receptor positive (ER+) and negative (ER-) breast cancer cells has not been studied using the proteomic approach. Changes in expression of RhoGDIα and other proteins interacting directly or indirectly with RhoGDIα in MCF7 and MDA-MB-231, with different metastatic potentials is of particular interest. ER+ MCF7 and ER- MDA-MB-231 cell lines were subjected to two-dimensional electrophoresis (2-DE) and spots of interest were identified by matrix-assisted laser desorption/ionization time of- flight/time- of-flight (MALDI-TOF/TOF) mass spectrometry (MS) analysis after downregulation of RhoGDIα using short interfering RNA (siRNA) and upregulated using GFP-tagged ORF clone of RhoGDIα. The results showed a total of 35 proteins that were either up- or down-regulated in these cells. Here we identifed 9 and 15 proteins differentially expressed with silencing of RhoGDIα in MCF-7 and the MDA-MB-231 cells, respectively. In addition, 10 proteins were differentially expressed in the upregulation of RhoGDIα in MCF7, while only one protein was identified in the upregulation of RhoGDIα in MDA-MB-231. Based on the biological functions of these proteins, the results revealed that proteins involved in cell migration are more strongly altered with RhoGDI-α activity. Although several of these proteins have been previously indicated in tumorigenesis and invasiveness of breast cancer cells, some ohave not been previously reported to be involved in breast cancer migration. Hence, these proteins may serve as useful candidate biomarkers for tumorigenesis and invasiveness of breast cancer cells. Future studies are needed to determine the mechanisms by which these proteins regulate cell migration. The combination of RhoGDIα with other potential biomarkers may be a more promising approach in the inhibition of breast cancer cell migration.

The BIMDA shuttle flight mission: a low cost microgravity payload.

PubMed

Holemans, J; Cassanto, J M; Moller, T W; Cassanto, V A; Rose, A; Luttges, M; Morrison, D; Todd, P; Stewart, R; Korszun, R Z; Deardorff, G

1991-01-01

This paper presents the design, operation and experiment protocol of the Bioserve sponsored flights of the ITA Materials Dispersion Apparatus Payload (BIMDA) flown on the Space Shuttle on STS-37. The BIMDA payload represents a joint effort between ITA (Instrumentation Technology Associates, Inc.) and Bioserve Space Technologies, a NASA Center for the Commercial Development of Space, to investigate the methods and commercial potential of biomedical and fluid science applications in the microgravity environment of space. The BIMDA payload, flown in a Refrigerator/Incubator Module (R/IM) in the Orbiter middeck, consists of three different devices designed to mix fluids in space; four Materials Dispersion Apparatus (MDA) Minilabs developed by ITA, six Cell Syringes, and six Bioprocessing Modules both developed by NASA JSC and Bioserve. The BIMDA design and operation reflect user needs for late access prior to launch (<24 h) and early access after landing (<2 h). The environment for the payload is temperature controlled by the R/IM. The astronaut crew operates the payload and documents its operation. The temperature of the payload is recorded automatically during flight. The flight of the BIMDA payload is the first of two development flights of the MDA on the Space Shuttle. Future commercial flights of ITA's Materials Dispersion Apparatus on the Shuttle will be sponsored by NASA's Office of Commercial Programs and will take place over the next three years. Experiments for the BIMDA payload include research into the following areas: protein crystal growth, thin film membrane casting, collagen formation, fibrin clot formation, seed germination, enzymatic catalysis, zeolite crystallization, studies of mixing effects of lymphocyte functions, and solute diffusion and transport.

Medical Data Architecture Project Status

NASA Technical Reports Server (NTRS)

Krihak, M.; Middour, C.; Lindsey, A.; Marker, N.; Wolfe, S.; Winther, S.; Ronzano, K.; Bolles, D.; Toscano, W.; Shaw, T.

2017-01-01

The Medical Data Architecture (MDA) project supports the Exploration Medical Capability (ExMC) risk to minimize or reduce the risk of adverse health outcomes and decrements in performance due to in-flight medical capabilities on human exploration missions. To mitigate this risk, the ExMC MDA project addresses the technical limitations identified in ExMC Gap Med 07: We do not have the capability to comprehensively process medically-relevant information to support medical operations during exploration missions. This gap identifies that the current International Space Station (ISS) medical data management includes a combination of data collection and distribution methods that are minimally integrated with on-board medical devices and systems. Furthermore, there are variety of data sources and methods of data collection. For an exploration mission, the seamless management of such data will enable an increasingly autonomous crew than the current ISS paradigm. The MDA will develop capabilities that support automated data collection, and the necessary functionality and challenges in executing a self-contained medical system that approaches crew health care delivery without assistance from ground support. To attain this goal, the first year of the MDA project focused on reducing technical risk, developing documentation and instituting iterative development processes that established the basis for the first version of MDA software (or Test Bed 1). Test Bed 1 is based on a nominal operations scenario authored by the ExMC Element Scientist. This narrative was decomposed into a Concept of Operations that formed the basis for Test Bed 1 requirements. These requirements were successfully vetted through the MDA Test Bed 1 System Requirements Review, which permitted the MDA project to begin software code development and component integration. This paper highlights the MDA objectives, development processes, and accomplishments, and identifies the fiscal year 2017 milestones and deliverables in the upcoming year.

Medical Data Architecture (MDA) Project Status

NASA Technical Reports Server (NTRS)

Krihak, M.; Middour, C.; Gurram, M.; Wolfe, S.; Marker, N.; Winther, S.; Ronzano, K.; Bolles, D.; Toscano, W.; Shaw, T.

2018-01-01

The Medical Data Architecture (MDA) project supports the Exploration Medical Capability (ExMC) risk to minimize or reduce the risk of adverse health outcomes and decrements in performance due to in-flight medical capabilities on human exploration missions. To mitigate this risk, the ExMC MDA project addresses the technical limitations identified in ExMC Gap Med 07: We do not have the capability to comprehensively process medically-relevant information to support medical operations during exploration missions. This gap identifies that the current in-flight medical data management includes a combination of data collection and distribution methods that are minimally integrated with on-board medical devices and systems. Furthermore, there are a variety of data sources and methods of data collection. For an exploration mission, the seamless management of such data will enable a more medically autonomous crew than the current paradigm. The medical system requirements are being developed in parallel with the exploration mission architecture and vehicle design. ExMC has recognized that in order to make informed decisions about a medical data architecture framework, current methods for medical data management must not only be understood, but an architecture must also be identified that provides the crew with actionable insight to medical conditions. This medical data architecture will provide the necessary functionality to address the challenges of executing a self-contained medical system that approaches crew health care delivery without assistance from ground support. Hence, the products supported by current prototype development will directly inform exploration medical system requirements.

Method for the elucidation of the elemental composition of low molecular mass chemicals using exact masses of product ions and neutral losses: application to environmental chemicals measured by liquid chromatography with hybrid quadrupole/time-of-flight mass spectrometry.

PubMed

Suzuki, Shigeru; Ishii, Tetsuko; Yasuhara, Akio; Sakai, Shinichi

2005-01-01

A method for elucidating the elemental compositions of low molecular weight chemicals, based primarily on mass measurements made using liquid chromatography (LC) with time-of-flight mass spectrometry (TOFMS) and quadrupole/time-of-flight mass spectrometry (LC/QTOFMS), was developed and tested for 113 chemicals of environmental interest with molecular masses up to approximately 400 Da. As the algorithm incorporating the method is not affected by differences in the instrument used, or by the ionization method and other ionization conditions, the method is useful not only for LC/TOFMS, but also for all kinds of mass spectra measured with higher accuracy and precision (uncertainties of a few mDa) employing all ionization methods and on-line separation techniques. The method involves calculating candidate compositions for intact ionized molecules (ionized forms of the sample molecule that have lost or gained no more than a proton, i.e., [M+H](+) or [M-H](-)) as well as for fragment ions and corresponding neutral losses, and eliminating those atomic compositions for the molecules that are inconsistent with the corresponding candidate compositions of fragment ions and neutral losses. Candidate compositions were calculated for the measured masses of the intact ionized molecules and of the fragment ions and corresponding neutral losses, using mass uncertainties of 2 and 5 mDa, respectively. Compositions proposed for the ionized molecule that did not correspond to the sum of the compositions of a candidate fragment ion and its corresponding neutral loss were discarded. One, 2-5, 6-10, 11-20, and >20 candidate compositions were found for 65%, 39%, 1%, 1%, and 0%, respectively, for the 124 ionized molecules formed from the 113 chemicals tested (both positive and negative ions were obtained from 11 of the chemicals). However, no candidate composition was found for 2% of the test cases (i.e., 3 chemicals), for each of which the measured mass of one of the product ions was in error by 5-6.7 mDa.

A systematic review of factors that shape implementation of mass drug administration for lymphatic filariasis in sub-Saharan Africa.

PubMed

Silumbwe, Adam; Zulu, Joseph Mumba; Halwindi, Hikabasa; Jacobs, Choolwe; Zgambo, Jessy; Dambe, Rosalia; Chola, Mumbi; Chongwe, Gershom; Michelo, Charles

2017-05-22

Understanding factors surrounding the implementation process of mass drug administration for lymphatic filariasis (MDA for LF) elimination programmes is critical for successful implementation of similar interventions. The sub-Saharan Africa (SSA) region records the second highest prevalence of the disease and subsequently several countries have initiated and implemented MDA for LF. Systematic reviews have largely focused on factors that affect coverage and compliance, with less attention on the implementation of MDA for LF activities. This review therefore seeks to document facilitators and barriers to implementation of MDA for LF in sub-Saharan Africa. A systematic search of databases PubMed, Science Direct and Google Scholar was conducted. English peer-reviewed publications focusing on implementation of MDA for LF from 2000 to 2016 were considered for analysis. Using thematic analysis, we synthesized the final 18 articles to identify key facilitators and barriers to MDA for LF programme implementation. The main factors facilitating implementation of MDA for LF programmes were awareness creation through innovative community health education programmes, creation of partnerships and collaborations, integration with existing programmes, creation of morbidity management programmes, motivation of community drug distributors (CDDs) through incentives and training, and management of adverse effects. Barriers to implementation included the lack of geographical demarcations and unregistered migrations into rapidly urbanizing areas, major disease outbreaks like the Ebola virus disease in West Africa, delayed drug deliveries at both country and community levels, inappropriate drug delivery strategies, limited number of drug distributors and the large number of households allocated for drug distribution. Mass drug administration for lymphatic filariasis elimination programmes should design their implementation strategies differently based on specific contextual factors to improve implementation outcomes. Successfully achieving this requires undertaking formative research on the possible constraining and inhibiting factors, and incorporating the findings in the design and implementation of MDA for LF.

Study protocol for a cluster randomised controlled factorial design trial to assess the effectiveness and feasibility of reactive focal mass drug administration and vector control to reduce malaria transmission in the low endemic setting of Namibia.

PubMed

Medzihradsky, Oliver F; Kleinschmidt, Immo; Mumbengegwi, Davis; Roberts, Kathryn W; McCreesh, Patrick; Dufour, Mi-Suk Kang; Uusiku, Petrina; Katokele, Stark; Bennett, Adam; Smith, Jennifer; Sturrock, Hugh; Prach, Lisa M; Ntuku, Henry; Tambo, Munyaradzi; Didier, Bradley; Greenhouse, Bryan; Gani, Zaahira; Aerts, Ann; Gosling, Roly; Hsiang, Michelle S

2018-01-27

To interrupt malaria transmission, strategies must target the parasite reservoir in both humans and mosquitos. Testing of community members linked to an index case, termed reactive case detection (RACD), is commonly implemented in low transmission areas, though its impact may be limited by the sensitivity of current diagnostics. Indoor residual spraying (IRS) before malaria season is a cornerstone of vector control efforts. Despite their implementation in Namibia, a country approaching elimination, these methods have been met with recent plateaus in transmission reduction. This study evaluates the effectiveness and feasibility of two new targeted strategies, reactive focal mass drug administration (rfMDA) and reactive focal vector control (RAVC) in Namibia. This is an open-label cluster randomised controlled trial with 2×2 factorial design. The interventions include: rfMDA (presumptive treatment with artemether-lumefantrine (AL)) versus RACD (rapid diagnostic testing and treatment using AL) and RAVC (IRS with Acellic 300CS) versus no RAVC. Factorial design also enables comparison of the combined rfMDA+RAVC intervention to RACD. Participants living in 56 enumeration areas will be randomised to one of four arms: rfMDA, rfMDA+RAVC, RACD or RACD+RAVC. These interventions, triggered by index cases detected at health facilities, will be targeted to individuals residing within 500 m of an index. The primary outcome is cumulative incidence of locally acquired malaria detected at health facilities over 1 year. Secondary outcomes include seroprevalence, infection prevalence, intervention coverage, safety, acceptability, adherence, cost and cost-effectiveness. Findings will be reported on clinicaltrials.gov, in peer-reviewed publications and through stakeholder meetings with MoHSS and community leaders in Namibia. NCT02610400; Pre-results. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Overview of MSFC's Applied Fluid Dynamics Analysis Group Activities

NASA Technical Reports Server (NTRS)

Garcia, Roberto; Griffin, Lisa; Williams, Robert

2002-01-01

This viewgraph report presents an overview of activities and accomplishments of NASA's Marshall Space Flight Center's Applied Fluid Dynamics Analysis Group. Expertise in this group focuses on high-fidelity fluids design and analysis with application to space shuttle propulsion and next generation launch technologies. Topics covered include: computational fluid dynamics research and goals, turbomachinery research and activities, nozzle research and activities, combustion devices, engine systems, MDA development and CFD process improvements.

Influence of the interaction between nodal fibroblast and breast cancer cells on gene expression

PubMed Central

Santos, Rosângela Portilho Costa; Benvenuti, Ticiana Thomazine; Honda, Suzana Terumi; Del Valle, Paulo Roberto; Katayama, Maria Lucia Hirata; Brentani, Helena Paula; Carraro, Dirce Maria; Rozenchan, Patrícia Bortman; Brentani, Maria Mitzi; de Lyra, Eduardo Carneiro; Torres, César Henrique; Salzgeber, Marcia Batista; Kaiano, Jane Haruko Lima; Góes, João Carlos Sampaio

2010-01-01

Our aim was to evaluate the interaction between breast cancer cells and nodal fibroblasts, by means of their gene expression profile. Fibroblast primary cultures were established from negative and positive lymph nodes from breast cancer patients and a similar gene expression pattern was identified, following cell culture. Fibroblasts and breast cancer cells (MDA-MB231, MDA-MB435, and MCF7) were cultured alone or co-cultured separated by a porous membrane (which allows passage of soluble factors) for comparison. Each breast cancer lineage exerted a particular effect on fibroblasts viability and transcriptional profile. However, fibroblasts from positive and negative nodes had a parallel transcriptional behavior when co-cultured with a specific breast cancer cell line. The effects of nodal fibroblasts on breast cancer cells were also investigated. MDA MB-231 cells viability and migration were enhanced by the presence of fibroblasts and accordingly, MDA-MB435 and MCF7 cells viability followed a similar pattern. MDA-MB231 gene expression profile, as evaluated by cDNA microarray, was influenced by the fibroblasts presence, and HNMT, COMT, FN3K, and SOD2 were confirmed downregulated in MDA-MB231 co-cultured cells with fibroblasts from both negative and positive nodes, in a new series of RT-PCR assays. In summary, transcriptional changes induced in breast cancer cells by fibroblasts from positive as well as negative nodes are very much alike in a specific lineage. However, fibroblasts effects are distinct in each one of the breast cancer lineages, suggesting that the inter-relationships between stromal and malignant cells are dependent on the intrinsic subtype of the tumor. Electronic supplementary material The online version of this article (doi:10.1007/s13277-010-0108-7) contains supplementary material, which is available to authorized users. PMID:20820980

Effects of flight activity and age on oxidative damage in the honey bee, Apis mellifera.

PubMed

Margotta, Joseph W; Roberts, Stephen P; Elekonich, Michelle M

2018-05-03

Frequent and highly aerobic behaviors likely contribute to naturally occurring stress, accelerate senescence, and limit lifespan. To understand how the physiological and cellular mechanisms that determine the onset and duration of senescence are shaped by behavioral development and behavioral duration, we exploited the tractability of the honey bee ( Apis mellifera ) model system. First, we determined if a cause-effect relationship exists between honey bee flight and oxidative stress by comparing oxidative damage accrued from intense flight bouts to damage accrued from D-galactose ingestion, which induces oxidative stress and limit lifespan in other insects. Second, we experimentally manipulated the duration of honey bee flight across a range of ages to determine their effects on reactive oxygen species (ROS) accumulation and associated enzymatic antioxidant protective mechanisms. In bees fed D-galactose, lipid peroxidation (MDA) was higher than in bees fed sucrose and age-matched bees with high and low flight experience collected from a colony. Bees with high amounts of flight experience exhibited elevated 8-OHdG, a marker of oxidative DNA damage, relative to bees with less flight experience. Bees with high amounts of flight experience also showed increased levels of pro-oxidants (superoxide and H 2 O 2 ) and decreased or unchanged levels of antioxidants (SOD and catalase). These data implicate an imbalance of pro- to antioxidants in flight-associated oxidative stress and reveal how behavior can damage a cell and consequently limit lifespan. © 2018. Published by The Company of Biologists Ltd.

MATRIX DISCRIMINANT ANALYSIS WITH APPLICATION TO COLORIMETRIC SENSOR ARRAY DATA

PubMed Central

Suslick, Kenneth S.

2014-01-01

With the rapid development of nano-technology, a “colorimetric sensor array” (CSA) which is referred to as an optical electronic nose has been developed for the identification of toxicants. Unlike traditional sensors which rely on a single chemical interaction, CSA can measure multiple chemical interactions by using chemo-responsive dyes. The color changes of the chemo-responsive dyes are recorded before and after exposure to toxicants and serve as a template for classification. The color changes are digitalized in the form of a matrix with rows representing dye effects and columns representing the spectrum of colors. Thus, matrix-classification methods are highly desirable. In this article, we develop a novel classification method, matrix discriminant analysis (MDA), which is a generalization of linear discriminant analysis (LDA) for the data in matrix form. By incorporating the intrinsic matrix-structure of the data in discriminant analysis, the proposed method can improve CSA’s sensitivity and more importantly, specificity. A penalized MDA method, PMDA, is also introduced to further incorporate sparsity structure in discriminant function. Numerical studies suggest that the proposed MDA and PMDA methods outperform LDA and other competing discriminant methods for matrix predictors. The asymptotic consistency of MDA is also established. R code and data are available online as supplementary material. PMID:26783371

Will mass drug administration eliminate lymphatic filariasis? Evidence from northern coastal Tanzania.

PubMed

Parker, Melissa; Allen, Tim

2013-07-01

This article documents understandings and responses to mass drug administration (MDA) for the treatment and prevention of lymphatic filariasis among adults and children in northern coastal Tanzania from 2004 to 2011. Assessment of village-level distribution registers, combined with self-reported drug uptake surveys of adults, participant observation and interviews, revealed that at study sites in Pangani and Muheza districts the uptake of drugs was persistently low. The majority of people living at these highly endemic locations either did not receive or actively rejected free treatment. A combination of social, economic and political reasons explain the low uptake of drugs. These include a fear of treatment (attributable, in part, to a lack of trust in international aid and a questioning of the motives behind the distribution); divergence between biomedical and local understandings of lymphatic filariasis; and limited and ineffective communication about the rationale for mass treatment. Other contributory factors are the reliance upon volunteers for distribution within villages and, in some locations, strained relationships between different groups of people within villages as well as between local leaders and government officials. The article also highlights a disjuncture between self-reported uptake of drugs by adults at a village level and the higher uptake of drugs recorded in official reports. The latter informs claims that elimination will be a possibility by 2020. This gives voice to a broader problem: there is considerable pressure for those implementing MDA to report positive results. The very real challenges of making MDA work are pushed to one side - adding to a rhetoric of success at the expense of engaging with local realities. It is vital to address the kind of issues raised in this article if current attempts to eliminate lymphatic filariasis in mainland coastal Tanzania are to achieve their goal.

Medical Data Architecture Project Status

NASA Technical Reports Server (NTRS)

Krihak, M.; Middour, C.; Gurram, M.; Wolfe, S.; Marker, N.; Winther, S.; Ronzano, K.; Bolles, D.; Toscano, W.; Shaw, T.

2018-01-01

The Medical Data Architecture (MDA) project supports the Exploration Medical Capability (ExMC) risk to minimize or reduce the risk of adverse health outcomes and decrements in performance due to in-flight medical capabilities on human exploration missions. To mitigate this risk, the ExMC MDA project addresses the technical limitations identified in ExMC Gap Med 07: We do not have the capability to comprehensively process medically-relevant information to support medical operations during exploration missions. This gap identifies that the current in-flight medical data management includes a combination of data collection and distribution methods that are minimally integrated with on-board medical devices and systems. Furthermore, there are a variety of data sources and methods of data collection. For an exploration mission, the seamless management of such data will enable a more medically autonomous crew than the current paradigm. The medical system requirements are being developed in parallel with the exploration mission architecture and vehicle design. ExMC has recognized that in order to make informed decisions about a medical data architecture framework, current methods for medical data management must not only be understood, but an architecture must also be identified that provides the crew with actionable insight to medical conditions. This medical data architecture will provide the necessary functionality to address the challenges of executing a self-contained medical system that approaches crew health care delivery without assistance from ground support. Hence, the products supported by current prototype development will directly inform exploration medical system requirements.

Flight test of a propulsion controlled aircraft system on the NASA F-15 airplane

NASA Technical Reports Server (NTRS)

Burcham, Frank W., Jr.; Maine, Trindel A.

1995-01-01

Flight tests of the propulsion controlled aircraft (PCA) system on the NASA F-15 airplane evolved as a result of a long series of simulation and flight tests. Initially, the simulation results were very optimistic. Early flight tests showed that manual throttles-only control was much more difficult than the simulation, and a flight investigation was flown to acquire data to resolve this discrepancy. The PCA system designed and developed by MDA evolved as these discrepancies were found and resolved, requiring redesign of the PCA software and modification of the flight test plan. Small throttle step inputs were flown to provide data for analysis, simulation update, and control logic modification. The PCA flight tests quickly revealed less than desired performance, but the extensive flexibility built into the flight PCA software allowed rapid evaluation of alternate gains, filters, and control logic, and within 2 weeks, the PCA system was functioning well. The initial objective of achieving adequate control for up-and-away flying and approaches was satisfied, and the option to continue to actual landings was achieved. After the PCA landings were accomplished, other PCA features were added, and additional maneuvers beyond those originally planned were flown. The PCA system was used to recover from extreme upset conditions, descend, and make approaches to landing. A heading mode was added, and a single engine plus rudder PCA mode was also added and flown. The PCA flight envelope was expanded far beyond that originally designed for. Guest pilots from the USAF, USN, NASA, and the contractor also flew the PCA system and were favorably impressed.

Efficacy studies of Sclerotium rolfsii lectin on breast cancer using NOD SCID mouse model.

PubMed

Hegde, Prajna; Narasimhappagari, Jagadeesh; Swamy, Bale M; Inamdar, Shashikala R

2018-04-20

Expression of altered glycans like TF, Tn and sTn antigens has been observed in a number of carcinomas which are targeted in cancer therapy. Sclerotium rolfsii lectin (SRL) is known to recognize TF and its substituted forms. Clinical potential of SRL has been demonstrated by studying its interaction with different types of cancer cells. Here we report, in vitro studies of SRL on breast cancer MDA-MB-468 cells and in vivo studies with MCF-7 xenografts. In vitro growth inhibitory studies of SRL on metastatic triple negative breast cancer MDA-MB-468 cells was performed by MTT assay, flow cytometry, adhesion and CAM assay. In vivo efficacy studies of SRL were performed using NOD SCID mice bearing MCF-7 xenografts. SRL has strong binding to MDA-MB-468 cells with MFI of 85.5 and has growth inhibitory effect with IC 50 of 32μg/mL at 48 h. SRL has anti angiogenesis effect and also anti adhesive effect with fibronectin and collagen at 20μg/mL by 36 and 42% respectively. In vivo efficacy studies of SRL on NOD SCID mice bearing MCF-7 xenogratfs revealed 61.77 and 75.71% tumor regressing effect respectively at 20 and 30mg/kg body weight without any toxicity. All these results substantiate clinical potential of SRL on breast cancer. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

CFD flowfield simulation of Delta Launch Vehicles in a power-on configuration

NASA Technical Reports Server (NTRS)

Pavish, D. L.; Gielda, T. P.; Soni, B. K.; Deese, J. E.; Agarwal, R. K.

1993-01-01

This paper summarizes recent work at McDonnell Douglas Aerospace (MDA) to develop and validate computational fluid dynamic (CFD) simulations of under expanded rocket plume external flowfields for multibody expendable launch vehicles (ELVs). Multi engine reacting gas flowfield predictions of ELV base pressures are needed to define vehicle base drag and base heating rates for sizing external nozzle and base region insulation thicknesses. Previous ELV design programs used expensive multibody power-on wind tunnel tests that employed chamber/nozzle injected high pressure cold or hot-air. Base heating and pressure measurements were belatedly made during the first flights of past ELV's to correct estimates from semi-empirical engineering models or scale model tests. Presently, CFD methods for use in ELV design are being jointly developed at the Space Transportation Division (MDA-STD) and New Aircraft Missiles Division (MDA-NAMD). An explicit three dimensional, zonal, finite-volume, full Navier-Stokes (FNS) solver with finite rate hydrocarbon/air and aluminum combustion kinetics was developed to accurately compute ELV power-on flowfields. Mississippi State University's GENIE++ general purpose interactive grid generation code was chosen to create zonal, finite volume viscous grids. Axisymmetric, time dependent, turbulent CFD simulations of a Delta DSV-2A vehicle with a MB-3 liquid main engine burning RJ-1/LOX were first completed. Hydrocarbon chemical kinetics and a k-epsilon turbulence model were employed and predictions were validated with flight measurements of base pressure and temperature. Zonal internal/external grids were created for a Delta DSV-2C vehicle with a MB-3 and three Castor-1 solid motors burning and a Delta-2 with an RS-27 main engine (LOX/RP-1) and 9 GEM's attached/6 burning. Cold air, time dependent FNS calculations were performed for DSV-2C during 1992. Single phase simulations that employ finite rate hydrocarbon and aluminum (solid fuel) combustion chemistry are currently in progress. Reliable and efficient Eulerian algorithms are needed to model two phase (solid-gas) momentum and energy transfer mechanisms for solid motor fuel combustion products.

CFD flowfield simulation of Delta Launch Vehicles in a power-on configuration

NASA Astrophysics Data System (ADS)

Pavish, D. L.; Gielda, T. P.; Soni, B. K.; Deese, J. E.; Agarwal, R. K.

1993-07-01

This paper summarizes recent work at McDonnell Douglas Aerospace (MDA) to develop and validate computational fluid dynamic (CFD) simulations of under expanded rocket plume external flowfields for multibody expendable launch vehicles (ELVs). Multi engine reacting gas flowfield predictions of ELV base pressures are needed to define vehicle base drag and base heating rates for sizing external nozzle and base region insulation thicknesses. Previous ELV design programs used expensive multibody power-on wind tunnel tests that employed chamber/nozzle injected high pressure cold or hot-air. Base heating and pressure measurements were belatedly made during the first flights of past ELV's to correct estimates from semi-empirical engineering models or scale model tests. Presently, CFD methods for use in ELV design are being jointly developed at the Space Transportation Division (MDA-STD) and New Aircraft Missiles Division (MDA-NAMD). An explicit three dimensional, zonal, finite-volume, full Navier-Stokes (FNS) solver with finite rate hydrocarbon/air and aluminum combustion kinetics was developed to accurately compute ELV power-on flowfields. Mississippi State University's GENIE++ general purpose interactive grid generation code was chosen to create zonal, finite volume viscous grids. Axisymmetric, time dependent, turbulent CFD simulations of a Delta DSV-2A vehicle with a MB-3 liquid main engine burning RJ-1/LOX were first completed. Hydrocarbon chemical kinetics and a k-epsilon turbulence model were employed and predictions were validated with flight measurements of base pressure and temperature. Zonal internal/external grids were created for a Delta DSV-2C vehicle with a MB-3 and three Castor-1 solid motors burning and a Delta-2 with an RS-27 main engine (LOX/RP-1) and 9 GEM's attached/6 burning. Cold air, time dependent FNS calculations were performed for DSV-2C during 1992. Single phase simulations that employ finite rate hydrocarbon and aluminum (solid fuel) combustion chemistry are currently in progress. Reliable and efficient Eulerian algorithms are needed to model two phase (solid-gas) momentum and energy transfer mechanisms for solid motor fuel combustion products.

The Industrial Base and National Security: A New Strategy

DTIC Science & Technology

1993-04-01

addresses this issue in her article entitled, " Managing Innovation on the Factory Floor": Manufacturing managers often buy the most advanced...Incentives Program." Government Contract Number MDA903-85-C-0139 Final Report, 1986. 31 11. Tyre, Marcie J. " Managing Innovation On The Factory Floor

Protective effect of royal jelly on fertility and biochemical parameters in bleomycin-‎induced male rats.

PubMed

Amirshahi, Tayebeh; Najafi, Gholamreza; Nejati, Vahid

2014-03-01

Bleomycin (BL) is a glycopeptide antibiotic obtained from the bacterium Streptomyces verticillus which is routinely used for treatment of human cancers. Royal jelly (RJ) is a production from the hypo pharyngeal, mandibular and post cerebral glands of nurse bees. RJ consists of 66% water, 15% sugars, 5% lipids, and 13% proteins, essential amino acids and vitamins. The aim of present study was to evaluate protective effect of royal jelly on sperm parameters and malondialdehyde (MDA) production in rat. Forty adult male wistar rats (220±20gr) were randomly divided into 4 groups (n=10). Control group (CG) received normal saline 10 ml/kg twice a week with Intraperitoneal (I.P) for 48 days (0.3 ml/rat(. Royal Jelly group (RJG) received jelly (100 mg/kg daily) for 48 days orally. Bleomycin group (BLG) received BL (10 mg/kg twice a week) with I.P for 48 days. Royal Jelly+ Bleomycin group (RJ+BLG) received royal Jelly (100 mg/kg /day) orally concomitant with BL administration. Sperm count, motility, and viability were investigated and chromatin quality and DNA integrity were also analyzed. Serum testosterone and MDA concentrations were measured as well. BL caused decline significantly (p<0.05) sperm count, sperm viability, motility as well as testosterone concentration compared to control group while significant (p<0.05) increases in immature sperm, sperm with damaged DNA and MDA concentration were announced in BL in comparison with CG and RJ+BLG. Royal jelly improved Bleomycin-induced toxicity on sperm parameters and testosterone and MDA concentrations. The present results support the idea that BL adversely affects sperm parameters and MDA and the RJ with antioxidant properties has positive effects on these parameters. This article extracted from M.Sc. thesis. (Tayebeh amirshahi).

Aerothermodynamic Insight From The HIFIRE Program

NASA Astrophysics Data System (ADS)

Kimmel, Roger L.; Adamczak, David; Dolvin, Douglas; Borg, Matthew; Stanfield, Scott

2011-05-01

The HIFiRE (Hypersonic International Flight Research and Experimentation) program is a joint venture of the United States Air Force Research Laboratory and Australian Defence Science and Technology Organisation to utilize economical flight research opportunities in the exploration of flight science issues for space access systems. Flights 1 and 5 focus on collecting high-resolution experimental data on critical aerothermodynamic phenomena, including laminar-turbulent transition and shock/boundary layer interactions. Flight 1, successfully flown in March 2010, employed a test article composed of a 7-deg right angle cone, followed by a cylinder and flare. The test article remained attached to the second-stage booster throughout the ballistic trajectory. Flight 5, to be launched in a similar fashion, will feature a 2:1 elliptic cross-section cone as the test article. For both flights significant resources have been invested in pre-flight aerothermodynamic analysis and testing. This manuscript will summarize the overall strategy of the HIFiRE program, review the pre-flight aerothermodynamic analysis for Flights 1 and 5, and present a brief look at preliminary results from the post-flight analysis of Flight 1.

Suppression of Transient Events by Levitation (STABLE): Results From the USML-2 Mission. Experiment 38

NASA Technical Reports Server (NTRS)

Nurre, Gerald S.; Edberg, Donald L.

1998-01-01

Microgravity science payloads can be extremely sensitive to vibrations from machinery, acoustics, ventilation, and crew activity. Suppression of Transient Acceleration by Levitation (STABLE) is an active vibration isolation system designed to protect payloads from these disturbances. This paper gives an account of results from the flight demonstration of the STABLE microgravity isolation system, which was developed and successfully flight tested in orbit during USML-2, with the participation of Astronaut Fred Leslie. Following a very brief description of the operational principles, the hardware and software design, and performance criteria, results of the analysis of measured flight data are presented to provide an evaluation of system performance parameters, including acceleration attenuation, assessment of sway space, system power consumption, and other factors critical to the performance of an isolation system. Lessons learned and potential design improvements and evolutions are discussed. Data reduction by Robert Boucher of McDonnell Douglas Aerospace (MDA) was substantially assisted by Kenneth Hrovat of Tal-Cut, Inc., under support from National Aeronautics and Space Administration/Lewis Research Center (LeRC), Cleveland, OH.

Characterization of the canine mda-7 gene, transcripts and expression patterns

PubMed Central

Sandey, Maninder; Bird, R. Curtis; Das, Swadesh K.; Sarkar, Devanand; Curiel, David T.; Fisher, Paul B.; Smith, Bruce F.

2014-01-01

Human melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24) displays potent growth suppressing and cell killing activity against a wide variety of human and rodent cancer cells. In this study, we identified a canine ortholog of the human mda-7/IL-24 gene located within a cluster of IL-10 family members on chromosome 7. The full-length mRNA sequence of canine mda-7 was determined, which encodes a 186-amino acid protein that has 66% similarity to human MDA-7/IL-24. Canine MDA-7 is constitutively expressed in cultured normal canine epidermal keratinocytes (NCEKs), and its expression levels are increased after lipopolysaccharide stimulation. In cultured NCEKs, the canine mda-7 pre-mRNA is differentially spliced, via exon skipping and alternate 5′-splice donor sites, to yield five splice variants (canine mda-7sv1, canine mda-7sv2, canine mda-7sv3, canine mda-7sv4 and canine mda-7sv5) that encode four protein isoforms of the canine MDA-7 protein. These protein isoforms have a conserved N-terminus (signal peptide sequence) and are dissimilar in amino acid sequences at their C-terminus. Canine MDA-7 is not expressed in primary canine tumor samples, and most tumor derived cancer cell lines tested, like its human counterpart. Unlike human MDA-7/IL-24, canine mda-7 mRNA is not expressed in unstimulated or lipopolysaccharide (LPS), concanavalin A (ConA) or phytohemagglutinin (PHA) stimulated canine peripheral blood mononuclear cells (PBMCs). Furthermore, in-silico analysis revealed that canonical canine MDA-7 has a potential 28 amino acid signal peptide sequence that can target it for active secretion. This data suggests that canine mda-7 is indeed an ortholog of human mda-7/IL-24, its protein product has high amino acid similarity to human MDA-7/IL-24 protein and it may possess similar biological properties to human MDA-7/IL-24, but its expression pattern is more restricted than its human ortholog. PMID:24865935

Myotonic Muscular Dystrophy

MedlinePlus

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Detection of malondialdehyde in processed meat products without interference from the ingredients.

PubMed

Jung, Samooel; Nam, Ki Chang; Jo, Cheorun

2016-10-15

Our aim was to develop a method for accurate quantification of malondialdehyde (MDA) in meat products. MDA content of uncured ground pork (Control); ground pork cured with sodium nitrite (Nitrite); and ground pork cured with sodium nitrite, sodium chloride, sodium pyrophosphate, maltodextrin, and a sausage seasoning (Mix) was measured by the 2-thiobarbituric acid (TBA) assay with MDA extraction by trichloroacetic acid (method A) and two high-performance liquid chromatography (HPLC) methods: i) HPLC separation of the MDA-dinitrophenyl hydrazine adduct (method B) and ii) HPLC separation of MDA (method C) after MDA extraction with acetonitrile. Methods A and B could not quantify MDA accurately in groups Nitrite and Mix. Nevertheless, MDA in groups Control, Nitrite, and Mix was accurately quantified by method C with good recovery. Therefore, direct MDA quantification by HPLC after MDA extraction with acetonitrile (method C) is useful for accurate measurement of MDA content in processed meat products. Copyright © 2016 Elsevier Ltd. All rights reserved.

Protective effect of royal jelly on fertility and biochemical parameters in bleomycin-‎induced male rats

PubMed Central

Amirshahi, Tayebeh; Najafi, Gholamreza; Nejati, Vahid

2014-01-01

Background: Bleomycin (BL) is a glycopeptide antibiotic obtained from the bacterium Streptomyces verticillus which is routinely used for treatment of human cancers. Royal jelly (RJ) is a production from the hypo pharyngeal, mandibular and post cerebral glands of nurse bees. RJ consists of 66% water, 15% sugars, 5% lipids, and 13% proteins, essential amino acids and vitamins. Objective: The aim of present study was to evaluate protective effect of royal jelly on sperm parameters and malondialdehyde (MDA) production in rat. Materials and Methods: Forty adult male wistar rats (220±20gr) were randomly divided into 4 groups (n=10). Control group (CG) received normal saline 10 ml/kg twice a week with Intraperitoneal (I.P) for 48 days (0.3 ml/rat(. Royal Jelly group (RJG) received jelly (100 mg/kg daily) for 48 days orally. Bleomycin group (BLG) received BL (10 mg/kg twice a week) with I.P for 48 days. Royal Jelly+ Bleomycin group (RJ+BLG) received royal Jelly (100 mg/kg /day) orally concomitant with BL administration. Sperm count, motility, and viability were investigated and chromatin quality and DNA integrity were also analyzed. Serum testosterone and MDA concentrations were measured as well. Results: BL caused decline significantly (p<0.05) sperm count, sperm viability, motility as well as testosterone concentration compared to control group while significant (p<0.05) increases in immature sperm, sperm with damaged DNA and MDA concentration were announced in BL in comparison with CG and RJ+BLG. Royal jelly improved Bleomycin-induced toxicity on sperm parameters and testosterone and MDA concentrations. Conclusion: The present results support the idea that BL adversely affects sperm parameters and MDA and the RJ with antioxidant properties has positive effects on these parameters. This article extracted from M.Sc. thesis. (Tayebeh amirshahi) PMID:24799882

A DN-mda5 transgenic zebrafish model demonstrates that Mda5 plays an important role in snakehead rhabdovirus resistance.

PubMed

Gabor, K A; Charette, J R; Pietraszewski, M J; Wingfield, D J; Shim, J S; Millard, P J; Kim, C H

2015-08-01

Melanoma Differentiation-Associated protein 5 (MDA5) is a member of the retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) family, which is a cytosolic pattern recognition receptor that detects viral nucleic acids. Here we show an Mda5-dependent response to rhabdovirus infection in vivo using a dominant-negative mda5 transgenic zebrafish. Dominant-negative mda5 zebrafish embryos displayed an impaired antiviral immune response compared to wild-type counterparts that can be rescued by recombinant full-length Mda5. To our knowledge, we have generated the first dominant-negative mda5 transgenic zebrafish and demonstrated a critical role for Mda5 in the antiviral response to rhabdovirus. Copyright © 2015 Elsevier Ltd. All rights reserved.

Materials Testing on the DC-X and DC-XA

NASA Technical Reports Server (NTRS)

Smith, Dane; Carroll, Carol; Marschall, Jochen; Pallix, Joan

1997-01-01

Flight testing of thermal protection materials has been carried out over a two year period on the base heat shield of the Delta Clipper (DC-X and DC-XA), as well on a body flap. The purpose was to use the vehicle as a test bed for materials and more efficient repair or maintenance processes which would be potentially useful for application on new entry vehicles (i.e., X-33, RLV, planetary probes), as well as on the existing space shuttle orbiters. Panels containing Thermal Protection Systems (TPS) and/or structural materials were constructed either at NASA Ames Research Center or at McDonnell Douglas Aerospace (MDA) and attached between two of the four thrusters in the base heat shield of the DC-X or DC-XA. Three different panels were flown on DC-X flights 6, 7, and 8. A total of 7 panels were flown on DC-XA flights 1, 2, and 3. The panels constructed at Ames contained a variety of ceramic TPS including flexible blankets, tiles with high emissivity coatings, lightweight ceramic ablators and other ceramic composites. The MDS test panels consisted primarily of a variety of metallic composites. This report focuses on the ceramic TPS test results.

The innate immune sensor LGP2 activates antiviral signaling by regulating MDA5-RNA interaction and filament assembly

PubMed Central

Bruns, Annie M.; Leser, George P.; Lamb, Robert A.; Horvath, Curt M.

2014-01-01

SUMMARY Cytoplasmic pattern recognition receptors detect non-self RNAs during virus infections and initiate antiviral signaling. One receptor, MDA5, possesses essential signaling domains, but weak RNA binding. A second receptor, LGP2, rapidly detects diverse dsRNA species, but lacks signaling domains. Accumulating evidence suggests LGP2 and MDA5 work together to detect viral RNA and generate a complete antiviral response, but the basis for their cooperation has been elusive. Experiments presented here address this gap in antiviral signaling, revealing that LGP2 assists MDA5-RNA interactions leading to enhanced MDA5-mediated antiviral signaling. LGP2 increases the initial rate of MDA5-RNA interaction and regulates MDA5 filament assembly, resulting in the formation of more numerous, shorter MDA5 filaments that are shown to generate equivalent or greater signaling activity in vivo than the longer filaments containing only MDA5. These findings provide a mechanism for LGP2 co-activation of MDA5 and a biological context for MDA5-RNA filaments in antiviral responses. PMID:25127512

MDA5 cooperatively forms dimers and ATP-sensitive filaments upon binding double-stranded RNA

PubMed Central

Berke, Ian C; Modis, Yorgo

2012-01-01

Melanoma differentiation-associated gene-5 (MDA5) detects viral double-stranded RNA in the cytoplasm. RNA binding induces MDA5 to activate the signalling adaptor MAVS through interactions between the caspase recruitment domains (CARDs) of the two proteins. The molecular mechanism of MDA5 signalling is not well understood. Here, we show that MDA5 cooperatively binds short RNA ligands as a dimer with a 16–18-basepair footprint. A crystal structure of the MDA5 helicase-insert domain demonstrates an evolutionary relationship with the archaeal Hef helicases. In X-ray solution structures, the CARDs in unliganded MDA5 are flexible, and RNA binds on one side of an asymmetric MDA5 dimer, bridging the two subunits. On longer RNA, full-length and CARD-deleted MDA5 constructs assemble into ATP-sensitive filaments. We propose a signalling model in which the CARDs on MDA5–RNA filaments nucleate the assembly of MAVS filaments with the same polymeric geometry. PMID:22314235

MDA5 assembles into a polar helical filament on dsRNA

PubMed Central

Berke, Ian C.; Yu, Xiong; Modis, Yorgo; Egelman, Edward H.

2012-01-01

Melanoma differentiation-associated protein 5 (MDA5) detects viral dsRNA in the cytoplasm. On binding of RNA, MDA5 forms polymers, which trigger assembly of the signaling adaptor mitochondrial antiviral-signaling protein (MAVS) into its active fibril form. The molecular mechanism of MDA5 signaling is not well understood, however. Here we show that MDA5 forms helical filaments on dsRNA and report the 3D structure of the filaments using electron microscopy (EM) and image reconstruction. MDA5 assembles into a polar, single-start helix around the RNA. Fitting of an MDA5 homology model into the structure suggests a key role for the MDA5 C-terminal domain in cooperative filament assembly. Our study supports a signal transduction mechanism in which the helical array of MDA5 within filaments nucleates the assembly of MAVS fibrils. We conclude that MDA5 is a polymerization-dependent signaling platform that uses the amyloid-like self-propagating properties of MAVS to amplify signaling. PMID:23090998

[Disasters and emergency situations: what have we learned from the past to prepare for the future?].

PubMed

Peleg, Kobi

2010-07-01

Israel has gained extensive experience in the mass casuaLty field, especially from dealing with terrorism events. This special issue of "Harefuah" includes articles that describe and analyze several aspects and approaches related to mass casualty event (MCE) preparedness and response strategies, based on Israel's experience. Feigenberg reports that Magen David Adom (MDA) was able to evacuate all urgent injuries during an MCE from the site to a hospital in 28 minutes, on average. Of the MCE casualties, 71% were evacuated directly to level 1 trauma centers. Rafalowski notes that the ability of MDA to implement organizational and operational Learning processes close to the time of the incident, as well as their modular operational approach, which allows flexibility in responding to simultaneous events, are probably among the reasons that have helped MDA reach a high Level of success in dealing with MCEs. Analysis of terrorism injury data demonstrates that these injuries, suffered by both children and adults, are characterized by increased complexity, with higher severity, higher in-patient mortality rates, and significantly greater use of precious hospital resources such as intensive care, operating rooms, CT, and days of hospitalization. Extensive experience dealing with MCEs has brought managerial insights to the entire health system, for instance in the hospitalization system and clinical management of injuries. In her article, Adini defines five major components for assessing the Israeli health system in emergencies. Shasha's article discusses the principles of hospital preparedness while working under fire. The importance of this subject has in recent years helped bring a more academic approach to emergency and disaster management in the world and in Israel, as enacted at Tel Aviv University's Multidisciplinary Master's Program in Emergency and Disaster Management, and also in other universities that focus on specific disciplines. In summary, achieving improvement requires continuous focus on preparedness, integration of new technologies, routine debriefings, and developing new coping strategies, education, training, and drills. These should all be part of daily preparedness routines. Only in this way can a high quality level of preparedness be maintained over time.

Manned remote work station development article. Volume 1, book 1: Flight article requirements. Appendix A: Mission requirements

NASA Technical Reports Server (NTRS)

1979-01-01

The requirements for several configurations of flight articles are presented. These requirements provide the basis to design manned remote work station development test articles and establish tests and simulation objectives for the resolution of development issues. Mission system and subsystem requirements for four MRWS configurations included: open cherry picker; closed cherry picker; crane turret; and free flyer.

Assessment of acquisition protocols for routine imaging of Y-90 using PET/CT

PubMed Central

2013-01-01

Background Despite the early theoretical prediction of the 0+-0+ transition of 90Zr, 90Y-PET underwent only recently a growing interest for the development of imaging radioembolization of liver tumors. The aim of this work was to determine the minimum detectable activity (MDA) of 90Y by PET imaging and the impact of time-of-flight (TOF) reconstruction on detectability and quantitative accuracy according to the lesion size. Methods The study was conducted using a Siemens Biograph® mCT with a 22 cm large axial field of view. An IEC torso-shaped phantom containing five coplanar spheres was uniformly filled to achieve sphere-to-background ratios of 40:1. The phantom was imaged nine times in 14 days over 30 min. Sinograms were reconstructed with and without TOF information. A contrast-to-noise ratio (CNR) index was calculated using the Rose criterion, taking partial volume effects into account. The impact of reconstruction parameters on quantification accuracy, detectability, and spatial localization of the signal was investigated. Finally, six patients with hepatocellular carcinoma and four patients included in different 90Y-based radioimmunotherapy protocols were enrolled for the evaluation of the imaging parameters in a clinical situation. Results The highest CNR was achieved with one iteration for both TOF and non-TOF reconstructions. The MDA, however, was found to be lower with TOF than with non-TOF reconstruction. There was no gain by adding TOF information in terms of CNR for concentrations higher than 2 to 3 MBq mL−1, except for infra-centimetric lesions. Recovered activity was highly underestimated when a single iteration or non-TOF reconstruction was used (10% to 150% less depending on the lesion size). The MDA was estimated at 1 MBq mL−1 for a TOF reconstruction and infra-centimetric lesions. Images from patients treated with microspheres were clinically relevant, unlike those of patients who received systemic injections of 90Y. Conclusions Only one iteration and TOF were necessary to achieve an MDA around 1 MBq mL−1 and the most accurate localization of lesions. For precise quantification, at least three iterations gave the best performance, using TOF reconstruction and keeping an MDA of roughly 1 MBq mL−1. One and three iterations were mandatory to prevent false positive results for quantitative analysis of clinical data. Trial registration http://IDRCB 2011-A00043-38 P101103 PMID:23414629

Impact of the Mass Drug Administration for malaria in response to the Ebola outbreak in Sierra Leone.

PubMed

Aregawi, Maru; Smith, Samuel J; Sillah-Kanu, Musa; Seppeh, John; Kamara, Anitta R Y; Williams, Ryan O; Aponte, John J; Bosman, Andrea; Alonso, Pedro

2016-09-20

As emergency response to the Ebola epidemic, the Government of Sierra Leone and its partners implemented a large-scale Mass Drug Administration (MDA) with artesunate-amodiaquine (ASAQ) covering >2.7 million people in the districts hardest hit by Ebola during December 2014-January 2015. The World Health Organization (WHO) and the National Malaria Control Programme (NMCP) evaluated the impact of the MDA on malaria morbidity at health facilities and the number of Ebola alerts received at District Ebola Command Centres. The coverage of the two rounds of MDA with ASAQ was estimated by relating the number anti-malarial medicines distributed to the estimated resident population. Segmented time-series analysis was applied to weekly data collected from 49 primary health units (PHUs) and 11 hospitals performing malaria parasitological testing during the study period, to evaluate trends of malaria cases and Ebola alerts during the post-MDA weeks compared to the pre-MDA weeks in MDA- and non-MDA-cheifdoms. After two rounds of the MDA, the number of suspected cases tested with rapid diagnostic test (RDT) decreased significantly by 43 % (95 % CI 38-48 %) at week 1 and remained low at week 2 and 3 post-first MDA and at week 1 and 3 post-second MDA; RDT positive cases decreased significantly by 47 % (41-52 %) at week 1 post-first and remained lower throughout all post-MDA weeks; and the RDT test positivity rate (TPR) declined by 35 % (32-38 %) at week 2 and stayed low throughout all post-MDA weeks. The total malaria (clinical + confirmed) cases decreased significantly by 45 % (39-52 %) at week 1 and were lower at week 2 and 3 post-first MDA; and week 1 post-second MDA. The proportion of confirmed malaria cases (out of all-outpatients) fell by 33 % (29-38 %) at week 1 post-first MDA and were lower during all post-MDA weeks. On the contrary, the non-malaria outpatient cases (cases due to other health conditions) either remained unchanged or fluctuated insignificantly. The Ebola alerts decreased by 30 % (13-46 %) at week 1 post-first MDA and much lower during all the weeks post-second MDA. The MDA achieved its goals of reducing malaria morbidity and febrile cases that would have been potentially diagnosed as suspected Ebola cases with increased risk of nosocomial infections. The intervention also helped reduce patient case-load to the severely strained health services at the peak of the Ebola outbreak and malaria transmission. As expected, the effect of the MDA waned in a matter of few weeks and malaria intensity returned to the pre-MDA levels. Nevertheless, the approach was an appropriate public health intervention in the context of the Ebola epidemic even in high malaria transmission areas of Sierra Leone.

Impact of electromagnetic radiation emitted by monitors on changes in the cellular membrane structure and protective antioxidant effect of vitamin A - In vitro study.

PubMed

Lewicka, Małgorzata; Henrykowska, Gabriela; Zawadzka, Magdalena; Rutkowski, Maciej; Pacholski, Krzysztof; Buczyński, Andrzej

2017-07-14

The increasing number of devices emitting electromagnetic radiation (EMR) in people's everyday life attracted the attention of researchers because of possible adverse effects of this factor on living organisms. One of the EMR effect may be peroxidation of lipid membranes formed as a result of free radical process. The article presents the results of in vitro studies aimed at identifying changes in malondialdehyde (MDA) concentration - a marker of lipid peroxidation and antioxidant role of vitamin A during the exposure of blood platelets to electromagnetic radiation generated by liquid-crystal-display (LCD) monitors. Electromagnetic radiation emitted by LCD monitors is characterized by parameters: 1 kHz frequency and 220 V/m intensity (15 cm from display screen). The time of exposure was 30 and 60 min. The study was conducted on porcine blood platelets. The samples were divided into 6 groups: unexposed to radiation, unexposed + vitamin A, exposed for 30 min, exposed for 30 min + vitamin A, exposed for 60 min, exposed for 60 min + vitamin A. The MDA concentration in blood platelets increases significantly as compared to control values after 60 min of exposure to EMR. A significant decrease in MDA concentration after the addition of vitamin A was noticed. In the blood samples exposed to EMR for 30 and 60 min the MDA concentration was significantly increased by addition of vitamin A. The results show the possibly negative effect of electromagnetic radiation on the cellular membrane structure manifested by changes in malondialdehyde concentration and indicate a possible protective role of vitamin A in this process. Int J Occup Med Environ Health 2017;30(5):695-703. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

MDA, MDMA, and other "mescaline-like" substances in the US military's search for a truth drug (1940s to 1960s).

PubMed

Passie, Torsten; Benzenhöfer, Udo

2018-01-01

This article describes the context in which 3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA) and other mescaline-like compounds were explored as hallucinogens for military and intelligence purposes from the 1940s to the 1960s. Germans first tested mescaline as a "truth drug" in a military context. In the 1940s, the United States military started testing hallucinogenic substances as truth drugs for interrogation and behavior manipulation. After tests carried out using mescaline and other drugs in 1950, some derivatives of mescaline were synthesized by the Army for the exploration of possible "speech-inducing" effects. After insufficient animal testing, the substances were given to patients at the New York State Psychiatric Institute (NYSPI). 3,4-Methylenedioxy-N-ethylamphetamine (MDE), a compound almost identical to MDMA, was among the compounds delivered for testing at the NYSPI. During tests with other derivatives (3,4-dimethoxyphenethylamine (DMA), 3,4-methylenedioxyphenethylamine (MDPEA), MDA) in 1952-53, an unwitting patient died in these tests, which was kept secret from the public. Research was interrupted and toxicological animal testing procedures were initiated. The secret animal studies run in 1953/1954 revealed that some of the "mescaline derivatives" tested (e.g. MDA, MDE, DMA, 3,4,5-trimethoxyamphetamine (TMA), MDMA) were considered for further testing in humans. In 1955, the military changed focus to lysergic acid diethylamide (LSD), but some interest in mescaline-like compounds remained for their ability to change mood and habit without interfering with cognition and sensory perception. Based on the known documents, it remains unclear (but probable) whether any of the mescaline derivatives tested were being used operationally. Copyright © 2017 John Wiley & Sons, Ltd.

Development of modified MDA (M-MDA), PWR fuel cladding tube for high duty operation in future

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

Watanabe, Seiichi; Kido, Toshiya; Arakawa, Yasushi

2007-07-01

A new cladding material of M-MDA has been developed in order to prepare for a strong growing demand for advanced fuel which can maintain its integrity even under high duties due to more efficient operation such as higher burnup, higher LHR, and longer operation cycle which will contribute the suppression of environmental burdens like CO{sub 2} emission. The main aim of M-MDA is to have excellent corrosion resistance while the other properties are inherited from MDA, which has been adopted to the step 2 fuel, instead of Zry-4, of Japanese PWR plant whose upper limit of assembly discharged burnup ismore » 55 MWd/kgU. And we could confirm that the main aim of M-MDA was achieved by means of out-of-pile tests. In order to confirm improvement of corrosion resistance of M-MDA in the actual operation, irradiation test of M-MDA in the commercial reactor of Vandellos II is ongoing. The latest results of on-site examination after every end of cycle showed that oxide thickness of M-MDA-SR was much smaller than that of MDA at rod discharged burnup of approximately 60 MWd/kgU. The final irradiation cycle was completed on April 2007 and then we will obtain corrosion data of M-MDA over 70 MWd/kgU. M-MDA is a candidate alloy for advanced fuel under higher duty usage. (authors)« less

Community Attitudes toward Mass Drug Administration for Control and Elimination of Neglected Tropical Diseases after the 2014 Outbreak of Ebola Virus Disease in Lofa County, Liberia

PubMed Central

Bogus, Joshua; Gankpala, Lincoln; Fischer, Kerstin; Krentel, Alison; Weil, Gary J.; Fischer, Peter U.; Kollie, Karsor; Bolay, Fatorma K.

2016-01-01

The recent outbreak of Ebola virus disease (EVD) interrupted mass drug administration (MDA) programs to control and eliminate neglected tropical diseases in Liberia. MDA programs treat entire communities with medication regardless of infection status to interrupt transmission and eliminate lymphatic filariasis and onchocerciasis. Following reports of hostilities toward health workers and fear that they might be spreading EVD, it was important to determine whether attitudes toward MDA might have changed after the outbreak. We surveyed 140 community leaders from 32 villages in Lofa County, Liberia, that had previously participated in MDA and are located in an area that was an early epicenter of the EVD outbreak. Survey respondents reported a high degree of community trust in the MDA program, and 97% thought their communities were ready to resume MDA. However, respondents predicted that fewer people would comply with MDA after the EVD epidemic than before. The survey also uncovered fears in the community that EVD and MDA might be linked. Respondents suggested that MDA programs emphasize to people that the medications are identical to those previously distributed and that MDA programs have nothing to do with EVD. PMID:26666700

Recurrent rhinovirus infections in a child with inherited MDA5 deficiency

PubMed Central

Lamborn, Ian T.; Jing, Huie; Zhang, Yu; Munir, Shirin; Bade, Sangeeta; Murdock, Heardley M.; Santos, Celia P.; Brock, Linda G.; Masutani, Evan; Matthews, Helen F.; Collins, Peter L.; Subbarao, Kanta; Gelfand, Erwin W.

2017-01-01

MDA5 is a cytosolic sensor of double-stranded RNA (ds)RNA including viral byproducts and intermediates. We studied a child with life-threatening, recurrent respiratory tract infections, caused by viruses including human rhinovirus (HRV), influenza virus, and respiratory syncytial virus (RSV). We identified in her a homozygous missense mutation in IFIH1 that encodes MDA5. Mutant MDA5 was expressed but did not recognize the synthetic MDA5 agonist/(ds)RNA mimic polyinosinic-polycytidylic acid. When overexpressed, mutant MDA5 failed to drive luciferase activity from the IFNB1 promoter or promoters containing ISRE or NF-κB sequence motifs. In respiratory epithelial cells or fibroblasts, wild-type but not knockdown of MDA5 restricted HRV infection while increasing IFN-stimulated gene expression and IFN-β/λ. However, wild-type MDA5 did not restrict influenza virus or RSV replication. Moreover, nasal epithelial cells from the patient, or fibroblasts gene-edited to express mutant MDA5, showed increased replication of HRV but not influenza or RSV. Thus, human MDA5 deficiency is a novel inborn error of innate and/or intrinsic immunity that causes impaired (ds)RNA sensing, reduced IFN induction, and susceptibility to the common cold virus. PMID:28606988

The need of adequate information to achieve total compliance of mass drug administration in Pekalongan

NASA Astrophysics Data System (ADS)

Ginandjar, Praba; Saraswati, Lintang Dian; Taufik, Opik; Nurjazuli; Widjanarko, Bagoes

2017-02-01

World Health Organization (WHO) initiated The Global Program to Eliminate Lymphatic Filariasis (LF) through mass drug administration (MDA). Pekalongan started MDA in 2011. Yet the LF prevalence in 2015 remained exceed the threshold (1%). This study aimed to describe the inhibiting factors related to the compliance of MDA in community level. This was a rapid survey with cross sectional approach. A two-stages random sampling was used in this study. In the first stage, 25 clusters were randomly selected from 27 villages with proportionate to population size (PPS) methods (C-Survey). In the second stage, 10 subjects were randomly selected from each cluster. Subject consisted of 250 respondents from 25 selected clusters. Variables consisted of MDA coverage, practice of taking medication during MDA, enabling and inhibiting factors to MDA in community level. The results showed most respondents had poor knowledge on filariasis, which influence awareness of the disease. Health-illness perception, did not receive the drugs, lactation, side effect, and size of the drugs were dominant factors of non-compliance to MDA. MDA information and community empowerment were needed to improve MDA coverage. Further study to explore the appropriate model of socialization will support the success of MDA program

Dermal uptake and excretion of 4,4'-methylenedianiline during rotor blade production in helicopter industry--an intervention study.

PubMed

Weiss, Tobias; Schuster, Hubert; Müller, Johannes; Schaller, Karl-Heinz; Drexler, Hans; Angerer, Jürgen; Käfferlein, Heiko U

2011-10-01

Workers using composite materials by fibre reinforced laminate technology are exposed to 4,4'-methylenedianiline (MDA), a liver toxicant and suspected human carcinogen, during the production of rotor blades in helicopter industry. The aim of the study presented here was to assess the internal dose of MDA and the suitability of various personal protection measures at the workplace. Ambient monitoring and biological monitoring was carried out by analysing MDA in air and urine samples in seven workers of a highly specialized workplace (rotor blade production). Three different concepts of personal protection measures were applied to study the route of uptake and to evaluate strategies in decreasing workplace exposure. In addition, elimination kinetics of MDA was studied in three workers who were exposed to MDA on three consecutive working days. Ambient monitoring consistently provided air levels at or below the limit of quantification of 0.1 μg m(-3). Nevertheless, MDA was detected in 89% of all post-shift urine samples and median concentration was 4.2 μg l(-1). MDA in urine were >20 times higher than expected on data from ambient monitoring alone. A significant decrease in exposure could be achieved when workers have worn MDA-protective overalls in combination with MDA-protective gloves and a splash protection shield (from 9.8 μg l(-1) down to 3.7 μg l(-1)). The results show that MDA is taken up primarily via the skin at the workplaces under study. The excretion of MDA in urine was observed to be delayed after dermal exposure. Exposure assessment of MDA should be carried out by biological monitoring rather than ambient monitoring. For this purpose, urine samples midweek or at the end of the week should be used based on the observed delay in the excretion of MDA after dermal absorption. Uptake of MDA via the skin could not be completely avoided even if state-of-the-art personal protection measures were applied.

Sierra Nevada Corporation's Dream Chaser Test Article Altitude T

NASA Image and Video Library

2017-08-30

Sierra Nevada Corporation’s Dream Chaser completed an important step toward orbital flight with a successful captive carry test at NASA’s Armstrong Flight Research Center in California, located on Edwards Air Force Base. A helicopter successfully carried a Dream Chaser test article, which has the same specifications as a flight-ready spacecraft, to the same altitude and flight conditions of an upcoming free flight test. The Dream Chaser is a lifting-body, winged spacecraft that will fly back to Earth in a manner similar to NASA’s space shuttles. The successful captive carry test clears the way for a free flight test of the spacecraft later this year in which the uncrewed Dream Chaser will be released to glide on its own and land.

MDA Establishes Effective Metrics for Energy Reduction and Other Environmental Performance Improvements

DTIC Science & Technology

2009-05-06

More Efficient Fuel, Electricity & Water Use (Cont’d.)  Energy and resource conservation campaign: beginning to implement an energy and resource...articles about energy conservation awareness and soliciting employee ideas  Reducing water temperature at MDIOC came from someone reporting the...issue after reading about conservation tips in the newsletter 12 Fuel, Electricity & Water Use Metrics  MDA’s objective is energy use reduction of 3

Nanobioinformatics: Emerging Computational Tools to Understand Nano-Bio Interaction

DTIC Science & Technology

2012-11-16

followed for using animals for toxicity studies, Organization for Economic Co- operation and Development ( OECD ) has set guidelines for toxicity studies...operation and Development ( OECD ) has set guidelines for toxicity studies in guideline number 420, which says that only dosages of 50-2000 mg/kg body weight...GSH, SOD, GSSH, MDA, ALK , ALT, LDH), Cell lines. Preprocessing: After collection of data from the published articles preprocessing of the data is

Effects of oxidative modification on thermal aggregation and gel properties of soy protein by malondialdehyde.

PubMed

Wu, Wei; Hua, Yufei; Lin, Qinlu

2014-03-01

Malondialdehyde (MDA) was selected as a representative of lipid peroxidation products to investigate the effects of oxidative modification on thermal aggregation and gel properties of soy protein by lipid peroxidation products. Incubation of soy protein with increasing concentration of MDA resulted in gradual decrease of particle size and content of thermal aggregates during heat denaturation. Oxidative modification by MDA resulted in a decrease in water holding capacity, gel hardness, and gel strength of soy protein gel. An increase in coarseness and interstice of MDA modified protein gel network was accompanied by uneven distribution of interstice as MDA concentration increased. The results showed that degree of thermal aggregation of MDA-modified soy protein gradually decreased as MDA concentration increased, which contributed to a decrease in water holding capacity, gel hardness, and gel strength of MDA-modified soy protein gel.

Antiviral function of grouper MDA5 against iridovirus and nodavirus.

PubMed

Huang, Youhua; Yu, Yepin; Yang, Ying; Yang, Min; Zhou, Linli; Huang, Xiaohong; Qin, Qiwei

2016-07-01

Melanoma differentiation-associated gene 5 (MDA5) is a critical member of retinoic acid-inducible gene I (RIG-I)-like receptor (RLR) family which can recognize viral RNA and enhances antiviral response in host cells. In this study, a MDA5 homolog from orange spotted grouper (Epinephelus coioides) (EcMDA5) was cloned, and its roles on grouper virus infection were characterized. The full-length EcMDA5 cDNA encoded a polypeptide of 982 amino acids with 74% identity with MDA5 homolog from rock bream (Oplegnathus fasciatus). Amino acid alignment analysis indicated that EcMDA5 contained three functional domains: two caspase activation and recruitment domain (CARDs), a DEAD box helicase-like (DExDc) domain, a helicase superfamily C-terminal domain (HELICc), and a C-terminal regulatory domain (RD). Upon challenge with Singapore grouper iridovirus (SGIV) or polyinosin-polycytidylic acid (poly I:C), the transcript of EcMDA5 was significantly up-regulated especially at the early stage post-injection. Under fluorescence microscopy, we observed that EcMDA5 mostly localized in the cytoplasm of grouper spleen (GS) cells. Interestingly, during virus infection, the distribution pattern of EcMDA5 was significantly altered in SGIV infected cells, but not in red spotted grouper nervous necrosis virus (RGNNV) infected cells, suggested that EcMDA5 might interact with viral proteins during SGIV infection. The ectopic expression of EcMDA5 in vitro obviously delayed virus infection induced cytopathic effect (CPE) progression and significantly inhibited viral gene transcription of RGNNV and SGIV. Moreover, overexpression of EcMDA5 not only significantly increased interferon (IFN) and IFN-stimulated response element (ISRE) promoter activities in a dose dependent manner, but also enhanced the expression of IRF3, IRF7 and TRAF6. In addition, the transcription level of the proinflammatory factors, including TNF-α, IL-6 and IL-8 were differently altered by EcMDA5 overexpression during SGIV or RGNNV infection, suggesting that the regulation on proinflammatory cytokines by EcMDA5 were also important for RGNNV infection. Together, our results demonstrated for the first time that the inhibitory effect of fish MDA5 on iridovirus replication might be mainly through the regulation of proinflammatory cytokines. Copyright © 2016 Elsevier Ltd. All rights reserved.

LFC leading edge glove flight: Aircraft modification design, test article development and systems integration

NASA Technical Reports Server (NTRS)

Etchberger, F. R.

1983-01-01

Reduction of skin friction drag by suction of boundary layer air to maintain laminar flow has been known since Prandtl's published work in 1904. The dramatic increases in fuel costs and the potential for periods of limited fuel availability provided the impetus to explore technologies to reduce transport aircraft fuel consumption. NASA sponsored the Aircraft Energy Efficiency (ACEE) program in 1976 to develop technologies to improve fuel efficiency. This report documents the Lockheed-Georgia Company accomplishments in designing and fabricating a leading-edge flight test article incorporating boundary layer suction slots to be flown by NASA on their modified JetStar aircraft. Lockheed-Georgia Company performed as the integration contractor to design the JetStar aircraft modification to accept both a Lockheed and a McDonnell Douglas flight test article. McDonnell Douglas uses a porous skin concept. The report describes aerodynamic analyses, fabrication techniques, JetStar modifications, instrumentation requirements, and structural analyses and testing for the Lockheed test article. NASA will flight test the two LFC leading-edge test articles in a simulated commercial environment over a 6 to 8 month period in 1984. The objective of the flight test program is to evaluate the effectiveness of LFC leading-edge systems in reducing skin friction drag and consequently improving fuel efficiency.

Exploring a model-driven architecture (MDA) approach to health care information systems development.

PubMed

Raghupathi, Wullianallur; Umar, Amjad

2008-05-01

To explore the potential of the model-driven architecture (MDA) in health care information systems development. An MDA is conceptualized and developed for a health clinic system to track patient information. A prototype of the MDA is implemented using an advanced MDA tool. The UML provides the underlying modeling support in the form of the class diagram. The PIM to PSM transformation rules are applied to generate the prototype application from the model. The result of the research is a complete MDA methodology to developing health care information systems. Additional insights gained include development of transformation rules and documentation of the challenges in the application of MDA to health care. Design guidelines for future MDA applications are described. The model has the potential for generalizability. The overall approach supports limited interoperability and portability. The research demonstrates the applicability of the MDA approach to health care information systems development. When properly implemented, it has the potential to overcome the challenges of platform (vendor) dependency, lack of open standards, interoperability, portability, scalability, and the high cost of implementation.

A methodology for the validated design space exploration of fuel cell powered unmanned aerial vehicles

NASA Astrophysics Data System (ADS)

Moffitt, Blake Almy

Unmanned Aerial Vehicles (UAVs) are the most dynamic growth sector of the aerospace industry today. The need to provide persistent intelligence, surveillance, and reconnaissance for military operations is driving the planned acquisition of over 5,000 UAVs over the next five years. The most pressing need is for quiet, small UAVs with endurance beyond what is capable with advanced batteries or small internal combustion propulsion systems. Fuel cell systems demonstrate high efficiency, high specific energy, low noise, low temperature operation, modularity, and rapid refuelability making them a promising enabler of the small, quiet, and persistent UAVs that military planners are seeking. Despite the perceived benefits, the actual near-term performance of fuel cell powered UAVs is unknown. Until the auto industry began spending billions of dollars in research, fuel cell systems were too heavy for useful flight applications. However, the last decade has seen rapid development with fuel cell gravimetric and volumetric power density nearly doubling every 2--3 years. As a result, a few design studies and demonstrator aircraft have appeared, but overall the design methodology and vehicles are still in their infancy. The design of fuel cell aircraft poses many challenges. Fuel cells differ fundamentally from combustion based propulsion in how they generate power and interact with other aircraft subsystems. As a result, traditional multidisciplinary analysis (MDA) codes are inappropriate. Building new MDAs is difficult since fuel cells are rapidly changing in design, and various competitive architectures exist for balance of plant, hydrogen storage, and all electric aircraft subsystems. In addition, fuel cell design and performance data is closely protected which makes validation difficult and uncertainty significant. Finally, low specific power and high volumes compared to traditional combustion based propulsion result in more highly constrained design spaces that are problematic for design space exploration. To begin addressing the current gaps in fuel cell aircraft development, a methodology has been developed to explore and characterize the near-term performance of fuel cell powered UAVs. The first step of the methodology is the development of a valid MDA. This is accomplished by using propagated uncertainty estimates to guide the decomposition of a MDA into key contributing analyses (CAs) that can be individually refined and validated to increase the overall accuracy of the MDA. To assist in MDA development, a flexible framework for simultaneously solving the CAs is specified. This enables the MDA to be easily adapted to changes in technology and the changes in data that occur throughout a design process. Various CAs that model a polymer electrolyte membrane fuel cell (PEMFC) UAV are developed, validated, and shown to be in agreement with hardware-in-the-loop simulations of a fully developed fuel cell propulsion system. After creating a valid MDA, the final step of the methodology is the synthesis of the MDA with an uncertainty propagation analysis, an optimization routine, and a chance constrained problem formulation. This synthesis allows an efficient calculation of the probabilistic constraint boundaries and Pareto frontiers that will govern the design space and influence design decisions relating to optimization and uncertainty mitigation. A key element of the methodology is uncertainty propagation. The methodology uses Systems Sensitivity Analysis (SSA) to estimate the uncertainty of key performance metrics due to uncertainties in design variables and uncertainties in the accuracy of the CAs. A summary of SSA is provided and key rules for properly decomposing a MDA for use with SSA are provided. Verification of SSA uncertainty estimates via Monte Carlo simulations is provided for both an example problem as well as a detailed MDA of a fuel cell UAV. Implementation of the methodology was performed on a small fuel cell UAV designed to carry a 2.2 kg payload with 24 hours of endurance. Uncertainty distributions for both design variables and the CAs were estimated based on experimental results and were found to dominate the design space. To reduce uncertainty and test the flexibility of the MDA framework, CAs were replaced with either empirical, or semi-empirical relationships during the optimization process. The final design was validated via a hardware-in-the loop simulation. Finally, the fuel cell UAV probabilistic design space was studied. A graphical representation of the design space was generated and the optima due to deterministic and probabilistic constraints were identified. The methodology was used to identify Pareto frontiers of the design space which were shown on contour plots of the design space. Unanticipated discontinuities of the Pareto fronts were observed as different constraints became active providing useful information on which to base design and development decisions.

Swine influenza virus vaccine serologic cross-reactivity to contemporary US swine H3N2 and efficacy in pigs infected with an H3N2 similar to 2011-2012 H3N2v.

PubMed

Kitikoon, Pravina; Gauger, Phillip C; Anderson, Tavis K; Culhane, Marie R; Swenson, Sabrina; Loving, Crystal L; Perez, Daniel R; Vincent, Amy L

2013-12-01

Swine influenza A virus (IAV) reassortment with 2009 H1N1 pandemic (H1N1pdm09) virus has been documented, and new genotypes and subclusters of H3N2 have since expanded in the US swine population. An H3N2 variant (H3N2v) virus with the H1N1pdm09 matrix gene and the remaining genes of swine triple reassortant H3N2 caused outbreaks at agricultural fairs in 2011-2012. To assess commercial swine IAV vaccines' efficacy against H3N2 viruses, including those similar to H3N2v, antisera to three vaccines were tested by hemagglutinin inhibition (HI) assay against contemporary H3N2. Vaccine 1, with high HI cross-reactivity, was further investigated for efficacy against H3N2 virus infection in pigs with or without maternally derived antibodies (MDA). In addition, efficacy of a vaccine derived from whole inactivated virus (WIV) was compared with live attenuated influenza virus (LAIV) against H3N2. Hemagglutinin inhibition cross-reactivity demonstrated that contemporary swine H3N2 viruses have drifted from viruses in current swine IAV vaccines. The vaccine with the highest level of HI cross-reactivity significantly protected pigs without MDA. However, the presence of MDA at vaccination blocked vaccine efficacy. The performance of WIV and LAIV was comparable in the absence of MDA. Swine IAV in the United States is complex and dynamic. Vaccination to minimize virus shedding can help limit transmission of virus among pigs and people. However, vaccines must be updated. A critical review of the use of WIV in sows is required in the context of the current IAV ecology and vaccine application in pigs with MDA. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

Mobile Aerial Tracking and Imaging System (MATRIS) for Aeronautical Research

NASA Technical Reports Server (NTRS)

Banks, Daniel W.; Blanchard, R. C.; Miller, G. M.

2004-01-01

A mobile, rapidly deployable ground-based system to track and image targets of aeronautical interest has been developed. Targets include reentering reusable launch vehicles (RLVs) as well as atmospheric and transatmospheric vehicles. The optics were designed to image targets in the visible and infrared wavelengths. To minimize acquisition cost and development time, the system uses commercially available hardware and software where possible. The conception and initial funding of this system originated with a study of ground-based imaging of global aerothermal characteristics of RLV configurations. During that study NASA teamed with the Missile Defense Agency/Innovative Science and Technology Experimentation Facility (MDA/ISTEF) to test techniques and analysis on two Space Shuttle flights.

Community Attitudes Toward Mass Drug Administration for Control and Elimination of Neglected Tropical Diseases After the 2014 Outbreak of Ebola Virus Disease in Lofa County, Liberia.

PubMed

Bogus, Joshua; Gankpala, Lincoln; Fischer, Kerstin; Krentel, Alison; Weil, Gary J; Fischer, Peter U; Kollie, Karsor; Bolay, Fatorma K

2016-03-01

The recent outbreak of Ebola virus disease (EVD) interrupted mass drug administration (MDA) programs to control and eliminate neglected tropical diseases in Liberia. MDA programs treat entire communities with medication regardless of infection status to interrupt transmission and eliminate lymphatic filariasis and onchocerciasis. Following reports of hostilities toward health workers and fear that they might be spreading EVD, it was important to determine whether attitudes toward MDA might have changed after the outbreak. We surveyed 140 community leaders from 32 villages in Lofa County, Liberia, that had previously participated in MDA and are located in an area that was an early epicenter of the EVD outbreak. Survey respondents reported a high degree of community trust in the MDA program, and 97% thought their communities were ready to resume MDA. However, respondents predicted that fewer people would comply with MDA after the EVD epidemic than before. The survey also uncovered fears in the community that EVD and MDA might be linked. Respondents suggested that MDA programs emphasize to people that the medications are identical to those previously distributed and that MDA programs have nothing to do with EVD. © The American Society of Tropical Medicine and Hygiene.

Analytical and Experimental Verification of a Flight Article for a Mach-8 Boundary-Layer Experiment

NASA Technical Reports Server (NTRS)

Richards, W. Lance; Monaghan, Richard C.

1996-01-01

Preparations for a boundary-layer transition experiment to be conducted on a future flight mission of the air-launched Pegasus(TM) rocket are underway. The experiment requires a flight-test article called a glove to be attached to the wing of the Mach-8 first-stage booster. A three-dimensional, nonlinear finite-element analysis has been performed and significant small-scale laboratory testing has been accomplished to ensure the glove design integrity and quality of the experiment. Reliance on both the analysis and experiment activities has been instrumental in the success of the flight-article design. Results obtained from the structural analysis and laboratory testing show that all glove components are well within the allowable thermal stress and deformation requirements to satisfy the experiment objectives.

Persistent 'hotspots' of lymphatic filariasis microfilaraemia despite 14 years of mass drug administration in Ghana.

PubMed

Biritwum, Nana-Kwadwo; Yikpotey, Paul; Marfo, Benjamin K; Odoom, Samuel; Mensah, Ernest O; Asiedu, Odame; Alomatu, Bright; Hervie, Edward T; Yeboah, Abednego; Ade, Serge; Hinderaker, Sven G; Reid, Anthony; Takarinda, Kudakwashe C; Koudou, Benjamin; Koroma, Joseph B

2016-12-01

Among the 216 districts in Ghana, 98 were declared endemic for lymphatic filariasis in 1999 after mapping. Pursuing the goal of elimination, WHO recommends annual treatment using mass drugs administration (MDA) for at least 5 years. MDA was started in the country in 2001 and reached national coverage in 2006. By 2014, 69 districts had 'stopped-MDA' (after passing the transmission assessment survey) while 29 others remained with persistent microfilaraemia (mf) prevalence (≥1%) despite more than 11 years of MDA and were classified as 'hotspots'. An ecological study was carried out to compare baseline mf prevalence and anti-microfilaria interventions between hotspot and stopped-MDA districts. Baseline mf prevalence was significantly higher in hotspots than stopped-MDA districts (p<0.001). After three years of MDA, there was a significant decrease in mf prevalence in hotspot districts, but it was still higher than in stopped-MDA districts. The number of MDA rounds was slightly higher in hotspot districts (p<0.001), but there were no differences in coverage of MDA or long-lasting-insecticide-treated nets. The main difference in hotspots and stopped-MDA districts was a high baseline mf prevalence. This finding indicates that the recommended 5-6 rounds annual treatment may not achieve interruption of transmission. © The Author 2017. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Effects of malondialdehyde modification on the in vitro digestibility of soy protein isolate.

PubMed

Chen, Nannan; Zhao, Qiangzhong; Sun, Weizheng; Zhao, Mouming

2013-12-11

Soy protein isolate (SPI) was modified by lipid peroxidation product malondialdehyde (MDA), and the in vitro digestibility of modified SPI was investigated. Results indicated that incubation with increasing MDA concentration resulted in significant carbonyl group generation and loss of free amino groups of SPI. Fluorescence loss of natural tryptophan and formation of Schiff base were observed. Noncovalent interaction between molecules was enhanced and became the main force that led to the solubility reduction of MDA-modified SPI. Differential scanning calorimetry (DSC) indicated that SPI had higher thermal stability and lower total calorimetric enthalpy after MDA pretreatment. Electrophoresis showed that β-conglycinin was more sensitive to MDA modification. In vitro digestion indicated that MDA could induce non-disulfide covalent polymer of SPI, which could not be digested by pepsin and pancreatin. β subunits of β-conglycinin became more resistant to digestion with increasing MDA concentration. Evaluation of the free amino acid profile in the digests indicated that MDA-modified SPI had deteriorating nutritive quality.

Pharmacokinetic modeling of 4,4'-methylenedianiline released from reused polyurethane dialyzer potting materials.

PubMed

Do Luu, H M; Hutter, J C

2000-01-01

4, 4'-Methylenedianiline (MDA) is a hydrolysis degradation product that can be released from polyurethanes commonly used in medical device applications. MDA is mutagenic and carcinogenic in animals. In humans, it is hepatotoxic, a known contact and respiratory allergen, and a suspected carcinogen. A physiologically based pharmacokinetic (PBPK) model was developed to estimate the absorption, distribution, metabolism, and excretion of MDA in patients exposed to MDA leached from the potting materials of hemodialyzers. A worst-case reuse situation and a single use case were investigated. The PBPK model included five tissue compartments: liver, kidney, gastrointestinal tract, slowly perfused tissues, and richly perfused tissues. Physiological and chemical parameters of a healthy individual used in the model were obtained from the literature. The model was calibrated using previously published kinetic studies of IV administered doses of (14) C-MDA to rats. The model was validated using independent data published for MDA-exposed workers. The PBPK results indicated that dialysis patients who are exposed to MDA released from dialyzers (new or reused) could accumulate low levels of MDA and metabolites (total MDA) over time. Copyright 2000 John Wiley & Sons, Inc.

How Can Onchocerciasis Elimination in Africa Be Accelerated? Modeling the Impact of Increased Ivermectin Treatment Frequency and Complementary Vector Control.

PubMed

Verver, Suzanne; Walker, Martin; Kim, Young Eun; Fobi, Grace; Tekle, Afework H; Zouré, Honorat G M; Wanji, Samuel; Boakye, Daniel A; Kuesel, Annette C; de Vlas, Sake J; Boussinesq, Michel; Basáñez, Maria-Gloria; Stolk, Wilma A

2018-06-01

Great strides have been made toward onchocerciasis elimination by mass drug administration (MDA) of ivermectin. Focusing on MDA-eligible areas, we investigated where the elimination goal can be achieved by 2025 by continuation of current practice (annual MDA with ivermectin) and where intensification or additional vector control is required. We did not consider areas hypoendemic for onchocerciasis with loiasis coendemicity where MDA is contraindicated. We used 2 previously published mathematical models, ONCHOSIM and EPIONCHO, to simulate future trends in microfilarial prevalence for 80 different settings (defined by precontrol endemicity and past MDA frequency and coverage) under different future treatment scenarios (annual, biannual, or quarterly MDA with different treatment coverage through 2025, with or without vector control strategies), assessing for each strategy whether it eventually leads to elimination. Areas with 40%-50% precontrol microfilarial prevalence and ≥10 years of annual MDA may achieve elimination with a further 7 years of annual MDA, if not achieved already, according to both models. For most areas with 70%-80% precontrol prevalence, ONCHOSIM predicts that either annual or biannual MDA is sufficient to achieve elimination by 2025, whereas EPIONCHO predicts that elimination will not be achieved even with complementary vector control. Whether elimination will be reached by 2025 depends on precontrol endemicity, control history, and strategies chosen from now until 2025. Biannual or quarterly MDA will accelerate progress toward elimination but cannot guarantee it by 2025 in high-endemicity areas. Long-term concomitant MDA and vector control for high-endemicity areas might be useful.

MDA-9/Syntenin regulates differentiation and angiogenesis programs in head and neck squamous cell carcinoma.

PubMed

Oyesanya, Regina A; Bhatia, Shilpa; Menezes, Mitchell E; Dumur, Catherine I; Singh, Karan P; Bae, Sejong; Troyer, Dean A; Wells, Robert B; Sauter, Edward R; Sidransky, David; Fisher, Paul B; Semmes, Oliver J; Dasgupta, Santanu

2014-01-01

Little is known about the molecular pathways regulating poor differentiation and invasion of head and neck squamous cell carcinoma (HNSCC). In the present study, we aimed to determine the role of MDA-9/Syntenin, a metastasis associated molecule in HNSCC tumorigenesis. Elevated MDA-9/Syntenin expression was evident in 67% (54/81) primary HNSCC tumors (p=0.001-0.002) and 69% (9/13) pre-neoplastic tissues (p=0.02-0.03). MDA-9/Syntenin overexpression was associated with the stage (p=0.001), grade (p=0.001) and lymph node metastasis (p=0.0001). Silencing of MDA-9/Syntenin in 3 poorly differentiated HNSCC cell lines induced squamous epithelial cell differentiation, disrupted angiogenesis and reduced tumor growth in vitro and in vivo. We confirmed SPRR1B and VEGFR1 as the key molecular targets of MDA-9/Syntenin on influencing HNSCC differentiation and angiogenesis respectively. MDA-9/Syntenin disrupted SPRR1B expression interacting through its PDZ1 domain and altered VEGFR1 expression in vitro and in vivo. VEGFR1 co-localized with MDA-9/Syntenin in HNSCC cell lines and primary tumor. Downregulation of growth regulatory molecules CyclinD1, CDK4, STAT3, PI3K and CTNNB1 was also evident in the MDA-9/Syntenin depleted cells, which was reversed following over-expression of MDA-9/Syntenin in immortalized oral epithelial cells. Our results suggest that early induction of MDA-9/Syntenin expression influences HNSCC progression and should be further evaluated for potential biomarker development.

MDA-9/Syntenin regulates differentiation and angiogenesis programs in head and neck squamous cell carcinoma

PubMed Central

Dumur, Catherine I.; Singh, Karan P; Bae, Sejong; Troyer, Dean A.; Wells, Robert B.; Sauter, Edward R.; Sidransky, David; Fisher, Paul B.; Semmes, Oliver J.; Dasgupta, Santanu

2014-01-01

Little is known about the molecular pathways regulating poor differentiation and invasion of head and neck squamous cell carcinoma (HNSCC). In the present study, we aimed to determine the role of MDA-9/Syntenin, a metastasis associated molecule in HNSCC tumorigenesis. Elevated MDA-9/Syntenin expression was evident in 67% (54/81) primary HNSCC tumors (p=0.001-0.002) and 69% (9/13) pre-neoplastic tissues (p=0.02-0.03). MDA-9/Syntenin overexpression was associated with the stage (p=0.001), grade (p=0.001) and lymph node metastasis (p=0.0001). Silencing of MDA-9/Syntenin in 3 poorly differentiated HNSCC cell lines induced squamous epithelial cell differentiation, disrupted angiogenesis and reduced tumor growth in vitro and in vivo. We confirmed SPRR1B and VEGFR1 as the key molecular targets of MDA-9/Syntenin on influencing HNSCC differentiation and angiogenesis respectively. MDA-9/Syntenin disrupted SPRR1B expression interacting through its PDZ1 domain and altered VEGFR1 expression in vitro and in vivo. VEGFR1 co-localized with MDA-9/Syntenin in HNSCC cell lines and primary tumor. Downregulation of growth regulatory molecules CyclinD1, CDK4, STAT3, PI3K and CTNNB1 was also evident in the MDA-9/Syntenin depleted cells, which was reversed following over-expression of MDA-9/Syntenin in immortalized oral epithelial cells. Our results suggest that early induction of MDA-9/Syntenin expression influences HNSCC progression and should be further evaluated for potential biomarker development. PMID:25593999

Acquisition/expulsion system for earth orbital propulsion system study. Volume 4: Flight test article

NASA Technical Reports Server (NTRS)

1973-01-01

Two orbital test plans were prepared to verify one of the passive cryogenic storage tank/feedline candidate designs. One plan considered the orbital test article to be launched as a dedicated payload using an Atlas F burner launching configuration. The second plan proposed to launch the orbital test article as a secondary payload on the Titan E/Centaur proof flight. The secondary payload concept was pursued until January 1973, when work to build the hardware for this phase of the contract was terminated for lack of a sponsor for the flight. The dedicated payload launched on an Atlas F is described.

MDA-9/Syntenin-Slug transcriptional complex promote epithelial-mesenchymal transition and invasion/metastasis in lung adenocarcinoma

PubMed Central

Wang, Lu-Kai; Pan, Szu-Hua; Chang, Yih-Leong; Hung, Pei-Fang; Kao, Shih-Han; Wang, Wen-Lung; Lin, Ching-Wen; Yang, Shuenn-Chen; Liang, Chen-Hsien; Wu, Chen-Tu; Hsiao, Tzu-Hung

2016-01-01

Melanoma differentiation-associated gene-9 (MDA-9)/Syntenin is a novel therapeutic target because it plays critical roles in cancer progression and exosome biogenesis. Here we show that Slug, a key epithelial-mesenchymal-transition (EMT) regulator, is a MDA-9/Syntenin downstream target. Mitogen EGF stimulation increases Slug expression and MDA-9/Syntenin nuclear translocation. MDA-9/Syntenin uses its PDZ1 domain to bind with Slug, and this interaction further leads to HDAC1 recruitment, up-regulation of Slug transcriptional repressor activity, enhanced Slug-mediated EMT, and promotion of cancer invasion and metastasis. The PDZ domains and nuclear localization of MDA-9/Syntenin are both required for promoting Slug-mediated cancer invasion. Clinically, patients with high MDA-9/Syntenin and high Slug expressions were associated with poor overall survival compared to those with low expression in lung adenocarcinomas. Our findings provide evidence that MDA-9/Syntenin acts as a pivotal adaptor of Slug and it transcriptionally enhances Slug-mediated EMT to promote cancer invasion and metastasis. PMID:26561205

Robotic Lunar Lander Development Status

NASA Technical Reports Server (NTRS)

Ballard, Benjamin; Cohen, Barbara A.; McGee, Timothy; Reed, Cheryl

2012-01-01

NASA Marshall Space Flight Center and John Hopkins University Applied Physics Laboratory have developed several mission concepts to place scientific and exploration payloads ranging from 10 kg to more than 200 kg on the surface of the moon. The mission concepts all use a small versatile lander that is capable of precision landing. The results to date of the lunar lander development risk reduction activities including high pressure propulsion system testing, structure and mechanism development and testing, and long cycle time battery testing will be addressed. The most visible elements of the risk reduction program are two fully autonomous lander flight test vehicles. The first utilized a high pressure cold gas system (Cold Gas Test Article) with limited flight durations while the subsequent test vehicle, known as the Warm Gas Test Article, utilizes hydrogen peroxide propellant resulting in significantly longer flight times and the ability to more fully exercise flight sensors and algorithms. The development of the Warm Gas Test Article is a system demonstration and was designed with similarity to an actual lunar lander including energy absorbing landing legs, pulsing thrusters, and flight-like software implementation. A set of outdoor flight tests to demonstrate the initial objectives of the WGTA program was completed in Nov. 2011, and will be discussed.

NASA's Robotic Lunar Lander Development Program

NASA Technical Reports Server (NTRS)

Ballard, Benjamin W.; Reed, Cheryl L. B.; Artis, David; Cole, Tim; Eng, Doug S.; Kubota, Sanae; Lafferty, Paul; McGee, Timothy; Morese, Brian J.; Chavers, Gregory;

Digital droplet multiple displacement amplification (ddMDA) for whole genome sequencing of limited DNA samples

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

Rhee, Minsoung; Light, Yooli K.; Meagher, Robert J.

Here, multiple displacement amplification (MDA) is a widely used technique for amplification of DNA from samples containing limited amounts of DNA (e.g., uncultivable microbes or clinical samples) before whole genome sequencing. Despite its advantages of high yield and fidelity, it suffers from high amplification bias and non-specific amplification when amplifying sub-nanogram of template DNA. Here, we present a microfluidic digital droplet MDA (ddMDA) technique where partitioning of the template DNA into thousands of sub-nanoliter droplets, each containing a small number of DNA fragments, greatly reduces the competition among DNA fragments for primers and polymerase thereby greatly reducing amplification bias. Consequently,more » the ddMDA approach enabled a more uniform coverage of amplification over the entire length of the genome, with significantly lower bias and non-specific amplification than conventional MDA. For a sample containing 0.1 pg/μL of E. coli DNA (equivalent of ~3/1000 of an E. coli genome per droplet), ddMDA achieves a 65-fold increase in coverage in de novo assembly, and more than 20-fold increase in specificity (percentage of reads mapping to E. coli) compared to the conventional tube MDA. ddMDA offers a powerful method useful for many applications including medical diagnostics, forensics, and environmental microbiology.« less

Digital droplet multiple displacement amplification (ddMDA) for whole genome sequencing of limited DNA samples

DOE PAGES

Rhee, Minsoung; Light, Yooli K.; Meagher, Robert J.; ...

2016-05-04

Here, multiple displacement amplification (MDA) is a widely used technique for amplification of DNA from samples containing limited amounts of DNA (e.g., uncultivable microbes or clinical samples) before whole genome sequencing. Despite its advantages of high yield and fidelity, it suffers from high amplification bias and non-specific amplification when amplifying sub-nanogram of template DNA. Here, we present a microfluidic digital droplet MDA (ddMDA) technique where partitioning of the template DNA into thousands of sub-nanoliter droplets, each containing a small number of DNA fragments, greatly reduces the competition among DNA fragments for primers and polymerase thereby greatly reducing amplification bias. Consequently,more » the ddMDA approach enabled a more uniform coverage of amplification over the entire length of the genome, with significantly lower bias and non-specific amplification than conventional MDA. For a sample containing 0.1 pg/μL of E. coli DNA (equivalent of ~3/1000 of an E. coli genome per droplet), ddMDA achieves a 65-fold increase in coverage in de novo assembly, and more than 20-fold increase in specificity (percentage of reads mapping to E. coli) compared to the conventional tube MDA. ddMDA offers a powerful method useful for many applications including medical diagnostics, forensics, and environmental microbiology.« less

MDA-9/Syntenin regulates protective autophagy in anoikis-resistant glioma stem cells.

PubMed

Talukdar, Sarmistha; Pradhan, Anjan K; Bhoopathi, Praveen; Shen, Xue-Ning; August, Laura A; Windle, Jolene J; Sarkar, Devanand; Furnari, Frank B; Cavenee, Webster K; Das, Swadesh K; Emdad, Luni; Fisher, Paul B

2018-05-14

Glioma stem cells (GSCs) comprise a small subpopulation of glioblastoma multiforme cells that contribute to therapy resistance, poor prognosis, and tumor recurrence. Protective autophagy promotes resistance of GSCs to anoikis, a form of programmed cell death occurring when anchorage-dependent cells detach from the extracellular matrix. In nonadherent conditions, GSCs display protective autophagy and anoikis-resistance, which correlates with expression of melanoma differentiation associated gene-9/Syntenin (MDA-9) (syndecan binding protein; SDCBP). When MDA-9 is suppressed, GSCs undergo autophagic death supporting the hypothesis that MDA-9 regulates protective autophagy in GSCs under anoikis conditions. MDA-9 maintains protective autophagy through phosphorylation of BCL2 and by suppressing high levels of autophagy through EGFR signaling. MDA-9 promotes these changes by modifying FAK and PKC signaling. Gain-of-function and loss-of-function genetic approaches demonstrate that MDA-9 regulates pEGFR and pBCL2 expression through FAK and pPKC. EGFR signaling inhibits autophagy markers (ATG5, Lamp1, LC3B), helping to maintain protective autophagy, and along with pBCL2 maintain survival of GSCs. In the absence of MDA-9, this protective mechanism is deregulated; EGFR no longer maintains protective autophagy, leading to highly elevated and sustained levels of autophagy and consequently decreased cell survival. In addition, pBCL2 is down-regulated in the absence of MDA-9, leading to cell death in GSCs under conditions of anoikis. Our studies confirm a functional link between MDA-9 expression and protective autophagy in GSCs and show that inhibition of MDA-9 reverses protective autophagy and induces anoikis and cell death in GSCs.

Phenolic profiling of the skin, pulp and seeds of Albariño grapes using hybrid quadrupole time-of-flight and triple-quadrupole mass spectrometry.

PubMed

Di Lecce, Giuseppe; Arranz, Sara; Jáuregui, Olga; Tresserra-Rimbau, Anna; Quifer-Rada, Paola; Lamuela-Raventós, Rosa M

2014-02-15

This paper describes for the first time a complete characterisation of the phenolic compounds in different anatomical parts of the Albariño grape. The application of high-performance liquid chromatography coupled with two complementary techniques, hybrid quadrupole time-of-flight and triple-quadrupole mass spectrometry, allowed the phenolic composition of the Albariño grape to be unambiguously identified and quantified. A more complete phenolic profile was obtained by product ion and precursor ion scans, while a neutral loss scan at 152 u enabled a fast screening of procyanidin dimers, trimers and their galloylated derivatives. The compounds were confirmed by accurate mass measurements in QqToF-MS and QqToF-MS/MS modes at high resolution, and good fits were obtained for all investigated ions, with errors ranging from 0.2 to 4.5 mDa. To the best of our knowledge, two flavanol monomer hexosides were detected in the grape berry for the first time. Copyright © 2013 Elsevier Ltd. All rights reserved.

MiR-34b-5p Suppresses Melanoma Differentiation-Associated Gene 5 (MDA5) Signaling Pathway to Promote Avian Leukosis Virus Subgroup J (ALV-J)-Infected Cells Proliferaction and ALV-J Replication

PubMed Central

Li, Zhenhui; Luo, Qingbin; Xu, Haiping; Zheng, Ming; Abdalla, Bahareldin Ali; Feng, Min; Cai, Bolin; Zhang, Xiaocui; Nie, Qinghua; Zhang, Xiquan

2017-01-01

Avian leukosis virus subgroup J (ALV-J) is an oncogenic retrovirus that has a similar replication cycle to multiple viruses and therefore can be used as a model system for viral entry into host cells. However, there are few reports on the genes or microRNAs (miRNAs) that are responsible for the replication of ALV-J. Our previous miRNA and RNA sequencing data showed that the expression of miR-34b-5p was significantly upregulated in ALV-J-infected chicken spleens compared to non-infected chicken spleens, but melanoma differentiation-associated gene 5 (MDA5) had the opposite expression pattern. In this study, a dual-luciferase reporter assay showed that MDA5 is a direct target of miR-34b-5p. In vitro, overexpression of miR-34b-5p accelerated the proliferation of ALV-J-infected cells by inducing the progression from G2 to S phase and it promoted cell migration. Ectopic expression of MDA5 inhibited ALV-J-infected cell proliferation, the cell cycle and cell migration, and knockdown of MDA5 promoted proliferation, the cell cycle and migration. In addition, during ALV-J infections, MDA5 can detect virus invasion and it triggers the MDA5 signaling pathway. MDA5 overexpression can activate the MDA5 signaling pathway, and thus it can inhibit the mRNA and protein expression of the ALV-J env gene and it can suppress virion secretion. In contrast, in response to the knockdown of MDA5 by small interfering RNA (siRNA) or an miR-34b-5p mimic, genes in the MDA5 signaling pathway were significantly downregulated (P < 0.05), but the mRNA and protein expression of ALV-J env and the sample-to-positive ratio of virion in the supernatants were increased. This indicates that miR-34b-5p is able to trigger the MDA5 signaling pathway and affect ALV-J infections. Together, these results suggest that miR-34b-5p targets MDA5 to accelerate the proliferation and migration of ALV-J-infected cells, and it promotes ALV-J replication, via the MDA5 signaling pathway. PMID:28194372

LncITPRIP-1 Positively Regulates Innate Immune Response through Promoting Oligomerization and Activation of MDA5.

PubMed

Xie, Qinya; Chen, Shengwen; Tian, Renyun; Huang, Xiang; Deng, Rilin; Xue, Binbin; Qin, Yuwen; Xu, Yan; Wang, Jingjing; Guo, Mengmeng; Chen, Jinwen; Tang, Songqing; Li, Guangdi; Zhu, Haizhen

2018-06-13

Emerging evidence indicates that long non-coding RNAs (lncRNAs) regulate various biological processes, especially innate and adaptive immunity. However, the relationship between lncRNAs and interferon (IFN) pathway remains largely unknown. Here, we report that lncRNA ITPRIP-1 (lncITPRIP-1) is involved in viral infection and plays a crucial role in virus-triggered IFN signaling pathway through targeting MDA5. LncITPRIP-1 can be induced by viral infection, which is not entirely dependent on IFN signal. Besides, there is no coding potential found in lncITPRIP-1 transcript. LncITPRIP-1 binds to the C-terminal of MDA5 and it possesses the ability to boost oligomerization of both full length and 2CARD domains of MDA5 in a K63-linked-polyubiquitination-independent manner. Amazingly, we also find that MDA5 could suppress HCV replication independent of IFN signaling through its C-terminal deficient domain bound to viral RNA, in which lncITPRIP-1 plays as an assistant. In addition, the expression of lncITPRIP-1 is highly consistent with MDA5 expression, indicating that lncITPRIP-1 may function as a cofactor of MDA5. All the data suggest that lncITPRIP-1 enhances innate immune response to viral infection through promoting oligomerization and activation of MDA5. Our study discovers the first lncRNA ITPRIP-1 involved in MDA5 activation. SIGNIFICANCE Hepatitis C virus infection causes a global health issue and there is still no available vaccine, which makes it urgent to reveal the underlying mechanisms of HCV and host factors. Although RIG-I has been recognized as the leading cytoplasmic sensor against HCV for a long time, recent findings of MDA5 regulating IFN response to HCV have emerged. Our work validates the significant role of MDA5 in IFN signaling and HCV infection, and proposes the first lncRNA inhibiting HCV replication by promoting the activation of MDA5 and mediating the association between MDA5 and HCV RNA, which may shed light on MDA5 function study and the treatment for hepatitis C patients. Our suggested model of how lncITPRIP-1 can orchestrate signal transduction for IFN production illustrates the essential role of lncRNAs in virus elimination. Copyright © 2018 American Society for Microbiology.

MiR-34b-5p Suppresses Melanoma Differentiation-Associated Gene 5 (MDA5) Signaling Pathway to Promote Avian Leukosis Virus Subgroup J (ALV-J)-Infected Cells Proliferaction and ALV-J Replication.

PubMed

Li, Zhenhui; Luo, Qingbin; Xu, Haiping; Zheng, Ming; Abdalla, Bahareldin Ali; Feng, Min; Cai, Bolin; Zhang, Xiaocui; Nie, Qinghua; Zhang, Xiquan

2017-01-01

Avian leukosis virus subgroup J (ALV-J) is an oncogenic retrovirus that has a similar replication cycle to multiple viruses and therefore can be used as a model system for viral entry into host cells. However, there are few reports on the genes or microRNAs (miRNAs) that are responsible for the replication of ALV-J. Our previous miRNA and RNA sequencing data showed that the expression of miR-34b-5p was significantly upregulated in ALV-J-infected chicken spleens compared to non-infected chicken spleens, but melanoma differentiation-associated gene 5 ( MDA5 ) had the opposite expression pattern. In this study, a dual-luciferase reporter assay showed that MDA5 is a direct target of miR-34b-5p. In vitro , overexpression of miR-34b-5p accelerated the proliferation of ALV-J-infected cells by inducing the progression from G2 to S phase and it promoted cell migration. Ectopic expression of MDA5 inhibited ALV-J-infected cell proliferation, the cell cycle and cell migration, and knockdown of MDA5 promoted proliferation, the cell cycle and migration. In addition, during ALV-J infections, MDA5 can detect virus invasion and it triggers the MDA5 signaling pathway. MDA5 overexpression can activate the MDA5 signaling pathway, and thus it can inhibit the mRNA and protein expression of the ALV-J env gene and it can suppress virion secretion. In contrast, in response to the knockdown of MDA5 by small interfering RNA (siRNA) or an miR-34b-5p mimic, genes in the MDA5 signaling pathway were significantly downregulated ( P < 0.05), but the mRNA and protein expression of ALV-J env and the sample-to-positive ratio of virion in the supernatants were increased. This indicates that miR-34b-5p is able to trigger the MDA5 signaling pathway and affect ALV-J infections. Together, these results suggest that miR-34b-5p targets MDA5 to accelerate the proliferation and migration of ALV-J-infected cells, and it promotes ALV-J replication, via the MDA5 signaling pathway.

Finite-Element Analysis of a Mach-8 Flight Test Article Using Nonlinear Contact Elements

NASA Technical Reports Server (NTRS)

Richards, W. Lance

1997-01-01

A flight test article, called a glove, is required for a Mach-8 boundary-layer experiment to be conducted on a flight mission of the air-launched Pegasus(reg) space booster. The glove is required to provide a smooth, three-dimensional, structurally stable, aerodynamic surface and includes instrumentation to determine when and where boundary-layer transition occurs during the hypersonic flight trajectory. A restraint mechanism has been invented to attach the glove to the wing of the space booster. The restraint mechanism securely attaches the glove to the wing in directions normal to the wing/glove interface surface, but allows the glove to thermally expand and contract to alleviate stresses in directions parallel to the interface surface. A finite-element analysis has been performed using nonlinear contact elements to model the complex behavior of the sliding restraint mechanism. This paper provides an overview of the glove design and presents details of the analysis that were essential to demonstrate the flight worthiness of the wing-glove test article. Results show that all glove components are well within the allowable stress and deformation requirements to satisfy the objectives of the flight research experiment.

Malondialdehyde-Derived Epitopes In Human Skin Result From Acute Exposure To Solar UV And Occur In Nonmelanoma Skin Cancer Tissue

PubMed Central

Williams, Joshua D.; Bermudez, Yira; Park, Sophia L.; Stratton, Steven P.; Uchida, Koji; Hurst, Craig A.; Wondrak, Georg T.

2014-01-01

Cutaneous exposure to solar ultraviolet radiation (UVR) is a causative factor in photoaging and photocarcinogenesis. In human skin, oxidative stress is widely considered a key mechanism underlying the detrimental effects of acute and chronic UVR exposure. The lipid peroxidation product malondialdehyde (MDA) accumulates in tissue under conditions of increased oxidative stress, and the occurrence of MDA-derived protein epitopes, including dihydropyridine-lysine (DHP), has recently been substantiated in human skin. Here we demonstrate for the first time that acute exposure to sub-apoptogenic doses of solar simulated UV light (SSL) causes the formation of free MDA and protein-bound MDA-derived epitopes in cultured human HaCaT keratinocytes and healthy human skin. Immunohistochemical staining revealed that acute exposure to SSL is sufficient to cause an almost twenty-fold increase in general MDA- and specific DHP-epitope content in human skin. When compared to dose-matched solar simulated UVA, complete SSL was more efficient generating both free MDA and MDA-derived epitopes. Subsequent tissue microarray (TMA) analysis revealed the prevalence of MDA- and DHP-epitopes in nonmelanoma skin cancer (NMSC). In squamous cell carcinoma tissue, both MDA- and DHP-epitopes were increased more than three-fold as compared to adjacent normal tissue. Taken together, these date demonstrate the occurrence of MDA-derived epitopes in both solar UVR-exposed healthy human skin and NMSC TMA tissue; however, the potential utility of these epitopes as novel biomarkers of cutaneous photodamage and a functional role in the process of skin photocarcinogenesis remain to be explored. PMID:24584085

MDA-9/Syntenin (SDCBP) modulates small GTPases RhoA and Cdc42 via transforming growth factor β1 to enhance epithelial-mesenchymal transition in breast cancer.

PubMed

Menezes, Mitchell E; Shen, Xue-Ning; Das, Swadesh K; Emdad, Luni; Sarkar, Devanand; Fisher, Paul B

2016-12-06

Epithelial-mesenchymal transition (EMT) is one of the decisive steps regulating cancer invasion and metastasis. However, the molecular mechanisms underlying this transition require further clarification. MDA-9/syntenin (SDCBP) expression is elevated in breast cancer patient samples as well as cultured breast cancer cells. Silencing expression of MDA-9 in mesenchymal metastatic breast cancer cells triggered a change in cell morphology in both 2D- and 3D-cultures to a more epithelial-like phenotype, along with changes in EMT markers, cytoskeletal rearrangement and decreased invasion. Conversely, over expressing MDA-9 in epithelial non-metastatic breast cancer cells instigated a change in morphology to a more mesenchymal phenotype with corresponding changes in EMT markers, cytoskeletal rearrangement and an increase in invasion. We also found that MDA-9 upregulated active levels of known modulators of EMT, the small GTPases RhoA and Cdc42, via TGFβ1. Reintroducing TGFβ1 in MDA-9 silenced cells restored active RhoA and cdc42 levels, modulated cytoskeletal rearrangement and increased invasion. We further determined that MDA-9 interacts with TGFβ1 via its PDZ1 domain. Finally, in vivo studies demonstrated that silencing the expression of MDA-9 resulted in decreased lung metastasis and TGFβ1 re-expression partially restored lung metastases. Our findings provide evidence for the relevance of MDA-9 in mediating EMT in breast cancer and support the potential of MDA-9 as a therapeutic target against metastatic disease.

Duck MDA5 functions in innate immunity against H5N1 highly pathogenic avian influenza virus infections

PubMed Central

2014-01-01

Melanoma differentiation-associated gene 5 (MDA5) is an important intracellular receptor that recognizes long molecules of viral double-stranded RNA in innate immunity. To understand the mechanism of duck MDA5-mediated innate immunity, we cloned the MDA5 cDNA from the Muscovy duck (Cairina moschata). Quantitative real-time PCR analysis indicates that duck MDA5 mRNA was constitutively expressed in all sampled tissues. A significant increase of MDA5 mRNA was detected in the brain, spleen and lungs of ducks after infection with an H5N1 highly pathogenic avian influenza virus (HPAIV). We investigated the role of the predicted functional domains of MDA5. The results indicate the caspase activation and recruitment domain (CARD) of duck MDA5 had a signal transmission function through IRF-7-dependent signaling pathway. Overexpression of the CARD strongly activated the chicken IFN-β promoter and upregulated the mRNA expression of antiviral molecules (such as OAS, PKR and Mx), proinflammatory cytokines (such as IL-2, IL-6, IFN-α and IFN-γ, but not IL-1β and IL-8) and retinoic acid-inducible gene I (RIG-I)-like receptors (RLR) (RIG-I and LGP2) without exogenous stimulation. We also demonstrate the NS1 of the H5N1 HPAIV inhibited the duck MDA5-mediated signaling pathway in vitro. These results suggest that duck MDA5 is an important receptor for inducing antiviral activity in the host immune response of ducks. PMID:24939427

The right wing of the LEFT airplane

NASA Technical Reports Server (NTRS)

Powell, Arthur G.

1987-01-01

The NASA Leading-Edge Flight Test (LEFT) program addressed the environmental issues which were potential problems in the application of Laminar Flow Control (LFC) to transport aircraft. These included contamination of the LFC surface due to dirt, rain, insect remains, snow, and ice, in the critical leading-edge region. Douglas Aircraft Company designed and built a test article which was mounted on the right wing of the C-140 JetStar aircraft. The test article featured a retractable leading-edge high-lift shield for contamination protection and suction through perforations on the upper surface for LFC. Following a period of developmental flight testing, the aircraft entered simulated airline service, which included exposure to airborne insects, heavy rain, snow, and icing conditions both in the air and on the ground. During the roughly 3 years of flight testing, the test article has consistently demonstrated laminar flow in cruising flight. The experience with the LEFT experiment was summarized with emphasis on significant test findings. The following items were discussed: test article design and features; suction distribution; instrumentation and transition point reckoning; problems and fixes; system performance and maintenance requirements.

Sensitive and selective quantification of free and total malondialdehyde in plasma using UHPLC-HRMS.

PubMed

Mendonça, Rute; Gning, Ophélie; Di Cesaré, Claudia; Lachat, Laurence; Bennett, Nigel C; Helfenstein, Fabrice; Glauser, Gaétan

2017-09-01

Quantification of malondialdehyde (MDA) as a marker of lipid peroxidation is relevant for many research fields. We describe a new sensitive and selective method to measure free and total plasmatic MDA using derivatization with 2,4-dinitrophenylhydrazine (DNPH) and ultra-HPLC-high-resolution MS. Free and total MDA were extracted from minute sample amounts (10 μl) using acidic precipitation and alkaline hydrolysis followed by acidic precipitation, respectively. Derivatization was completed within 10 min at room temperature, and the excess DNPH discarded by liquid-liquid extraction. Quantification was achieved by internal standardization using dideuterated MDA as internal standard. The method's lowest limit of quantification was 100 nM and linearity spanned greater than three orders of magnitude. Intra- and inter-day precisions for total MDA were 2.9% and 3.0%, respectively, and those for free MDA were 12.8% and 24.9%, respectively. Accuracy was 101% and 107% at low and high concentrations, respectively. In human plasma, free MDA levels were 120 nM (SD 36.26) and total MDA levels were 6.7 μM (SD 0.46). In addition, we show the applicability of this method to measure MDA plasma levels from a variety of animal species, making it invaluable to scientists in various fields. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

Improved quantification of a commercial enzyme-linked immunosorbent assay kit for measuring anti-MDA5 antibody.

PubMed

Gono, Takahisa; Okazaki, Yuka; Murakami, Akihiro; Kuwana, Masataka

2018-04-09

To compare the quantitative performance for measuring anti-MDA5 antibody titer of two enzyme-linked immunosorbent assay (ELISA) systems: an in-house ELISA and the commercial MESACUP TM anti-MDA5 test. Anti-MDA5 antibody titer was measured in sera from 70 patients with dermatomyositis using an in-house ELISA and the MESACUP TM anti-MDA5 test side-by-side. For the commercial ELISA kit, serum samples diluted 1:101 were used according to the manufacturer's protocol, but serial dilutions of sera were also examined to identify the optimal serum dilution for quantification. The anti-MDA5 antibody titers measured by the in-house and commercial ELISAs were positively correlated with each other (r = 0.53, p = .0001), but the antibody titer measured by the commercial ELISA was less sensitive to change after medical treatment, and 37 (80%) of 46 anti-MDA5-positive sera had antibody titer exceeding the quantification range specified by the manufacturer (≥150 index). Experiments using diluted serum samples revealed that diluting the sera 1:5050 improved the quantitative performance of the MESACUP TM anti-MDA5 test, including a better correlation with the in-house ELISA results and an increased sensitivity to change. We improved the ability of the commercial ELISA kit to quantify anti-MDA5 antibody titer by altering its protocol.

Impregnating magnetic components with MDA free epoxy

NASA Astrophysics Data System (ADS)

Sanchez, R. O.; Domeier, L.; Gunewardena, S.

1995-08-01

This paper describes the use of 'Formula 456' an aliphatic amine cured epoxy for impregnating coils. Methylene dianiline (MDA) has been used for more than 20 years as the curing agent for various epoxy formulations throughout the Department of Energy. Sandia National Laboratories began the process of replacing MDA with other formulations because of regulations imposed by OSHA on the use of MDA.

GO1 Inert Test Article Captive Carry

NASA Image and Video Library

2018-01-10

Generation Orbit Launch Services, Inc. (GO) completed the GO1 Inert Test Article captive carry flight test at NASA’s Armstrong Flight Research Center in December. Under a public-private partnership with NASA, GO developed the GO1-ITA, a mass properties and outer mold line simulator for the GO1 hypersonic flight testbed and earned NASA airworthiness approval for flight on NASA’s C-20a. NASA’s C-20a was originally modified to add a centerline hard point to carry the Uninhabited Aerial Vehicle Synthetic Aperture Radar (UAVSAR) pod. Together with the NASA Armstrong team, a campaign of three flight tests was conducted, successfully completing all test objectives including clearing the operational flight envelope of the C-20a with the GO1-ITA mounted to the centerline hard point, and demonstrated the unique launch maneuver designed for air launch of the GO1 on operational flights starting in 2019. Data collected during the campaign will be used to validate models and inform the ongoing design and development of GO1.

Aerothermal Assment Of The Expert Flap In The SCIROCCO Wind Tunnel

NASA Astrophysics Data System (ADS)

Walpot, L.; Di Clemente, M.; Vos, J.; Etchells, J.; Trifoni, E.; Thoemel, J.; Gavira, J.

2011-05-01

In the frame of the “In-Flight Test Measurement Techniques for Aerothermodynamics” activity of the EXPERT Program, the EXPERT Instrumented Open Flap Assembly experiment has the objective to verify the design/sensor integration and validate the CFD tools. Ground based measurements were made in Europe’s largest high enthalpy plasma facility, Scirocco in Italy. Two EXPERT flaps of the flight article, instrumented with 14 thermocouples, 5 pressure ports, a pyrometer and an IR camera mounted in the cavity instrumented flap will collect in-flight data. During the Scirocco experiment, an EXPERT flap model identical to the flight article was mounted at 45 deg on a holder including cavity and was subjected to a hot plasma flow at an enthalpy up to 11MJ/kg at a stagnation pressure of 7 bar. The test model sports the same pressure sensors as the flight article. Hypersonic state-of-the-art codes were then be used to perform code-to-code and wind tunnel-to-code comparisons, including thermal response of the flap as collected during the tests by the sensors and camera.

Prototyping and implementing flight qualifiable semicustom CMOS P-well bulk integrated circuits in the JPL environment

NASA Technical Reports Server (NTRS)

Olson, E. M.

1986-01-01

Presently, there are many difficulties associated with implementing application specific custom or semi-custom (standard cell based) integrated circuits (ICs) into JPL flight projects. One of the primary difficulties is developing prototype semi-custom integrated circuits for use and evaluation in engineering prototype flight hardware. The prototype semi-custom ICs must be extremely cost-effective and yet still representative of flight qualifiable versions of the design. A second difficulty is encountered in the transport of the design from engineering prototype quality to flight quality. Normally, flight quality integrated circuits have stringent quality standards, must be radiation resistant and should consume minimal power. It is often not necessary or cost effective, however, to impose such stringent quality standards on engineering models developed for systems analysis in controlled lab environments. This article presents work originally initiated for ground based applications that also addresses these two problems. Furthermore, this article suggests a method that has been shown successful in prototyping flight quality semi-custom ICs through the Metal Oxide Semiconductor Implementation Service (MOSIS) program run by the University of Southern California's Information Sciences Institute. The method has been used successfully to design and fabricate through the MOSIS three different semi-custom prototype CMOS p-well chips. The three designs make use of the work presented and were designed consistent with design techniques and structures that are flight qualifiable, allowing one hour transfer of the design from engineering model status to flight qualifiable foundry-ready status through methods outlined in this article.

Paramyxovirus V protein interaction with the antiviral sensor LGP2 disrupts MDA5 signaling enhancement but is not relevant to LGP2-mediated RLR signaling inhibition.

PubMed

Rodriguez, Kenny R; Horvath, Curt M

2014-07-01

The interferon antiviral system is a primary barrier to virus replication triggered upon recognition of nonself RNAs by the cytoplasmic sensors encoded by retinoic acid-inducible gene I (RIG-I), melanoma differentiation-associated gene 5 (MDA5), and laboratory of genetics and physiology gene 2 (LGP2). Paramyxovirus V proteins are interferon antagonists that can selectively interact with MDA5 and LGP2 through contact with a discrete helicase domain region. Interaction with MDA5, an activator of antiviral signaling, disrupts interferon gene expression and antiviral responses. LGP2 has more diverse reported roles as both a coactivator of MDA5 and a negative regulator of both RIG-I and MDA5. This functional dichotomy, along with the concurrent interference with both cellular targets, has made it difficult to assess the unique consequences of V protein interaction with LGP2. To directly evaluate the impact of LGP2 interference, MDA5 and LGP2 variants unable to be recognized by measles virus and parainfluenza virus 5 (PIV5) V proteins were tested in signaling assays. Results indicate that interaction with LGP2 specifically prevents coactivation of MDA5 signaling and that LGP2's negative regulatory capacity was not affected. V proteins only partially antagonize RIG-I at high concentrations, and their expression had no additive effects on LGP2-mediated negative regulation. However, conversion of RIG-I to a direct V protein target was accomplished by only two amino acid substitutions that allowed both V protein interaction and efficient interference. These results clarify the unique consequences of MDA5 and LGP2 interference by paramyxovirus V proteins and help resolve the distinct roles of LGP2 in both activation and inhibition of antiviral signal transduction. Importance: Paramyxovirus V proteins interact with two innate immune receptors, MDA5 and LGP2, but not RIG-I. V proteins prevent MDA5 from signaling to the beta interferon promoter, but the consequences of LGP2 targeting are poorly understood. As the V protein targets MDA5 and LGP2 simultaneously, and LGP2 is both a positive and negative regulator of both MDA5 and RIG-I, it has been difficult to evaluate the specific advantages conferred by LGP2 targeting. Experiments with V-insensitive proteins revealed that the primary outcome of LGP2 interference is suppression of its ability to synergize with MDA5. LGP2's negative regulation of MDA5 and RIG-I remains intact irrespective of V protein interaction. Complementary experiments demonstrate that RIG-I can be converted to V protein sensitivity by two amino acid substitutions. These findings clarify the functions of LGP2 as a positive regulator of MDA5 signaling, demonstrate the basis for V-mediated LGP2 targeting, and broaden our understanding of paramyxovirus-host interactions. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Paramyxovirus V Protein Interaction with the Antiviral Sensor LGP2 Disrupts MDA5 Signaling Enhancement but Is Not Relevant to LGP2-Mediated RLR Signaling Inhibition

PubMed Central

Rodriguez, Kenny R.

2014-01-01

ABSTRACT The interferon antiviral system is a primary barrier to virus replication triggered upon recognition of nonself RNAs by the cytoplasmic sensors encoded by retinoic acid-inducible gene I (RIG-I), melanoma differentiation-associated gene 5 (MDA5), and laboratory of genetics and physiology gene 2 (LGP2). Paramyxovirus V proteins are interferon antagonists that can selectively interact with MDA5 and LGP2 through contact with a discrete helicase domain region. Interaction with MDA5, an activator of antiviral signaling, disrupts interferon gene expression and antiviral responses. LGP2 has more diverse reported roles as both a coactivator of MDA5 and a negative regulator of both RIG-I and MDA5. This functional dichotomy, along with the concurrent interference with both cellular targets, has made it difficult to assess the unique consequences of V protein interaction with LGP2. To directly evaluate the impact of LGP2 interference, MDA5 and LGP2 variants unable to be recognized by measles virus and parainfluenza virus 5 (PIV5) V proteins were tested in signaling assays. Results indicate that interaction with LGP2 specifically prevents coactivation of MDA5 signaling and that LGP2's negative regulatory capacity was not affected. V proteins only partially antagonize RIG-I at high concentrations, and their expression had no additive effects on LGP2-mediated negative regulation. However, conversion of RIG-I to a direct V protein target was accomplished by only two amino acid substitutions that allowed both V protein interaction and efficient interference. These results clarify the unique consequences of MDA5 and LGP2 interference by paramyxovirus V proteins and help resolve the distinct roles of LGP2 in both activation and inhibition of antiviral signal transduction. IMPORTANCE Paramyxovirus V proteins interact with two innate immune receptors, MDA5 and LGP2, but not RIG-I. V proteins prevent MDA5 from signaling to the beta interferon promoter, but the consequences of LGP2 targeting are poorly understood. As the V protein targets MDA5 and LGP2 simultaneously, and LGP2 is both a positive and negative regulator of both MDA5 and RIG-I, it has been difficult to evaluate the specific advantages conferred by LGP2 targeting. Experiments with V-insensitive proteins revealed that the primary outcome of LGP2 interference is suppression of its ability to synergize with MDA5. LGP2's negative regulation of MDA5 and RIG-I remains intact irrespective of V protein interaction. Complementary experiments demonstrate that RIG-I can be converted to V protein sensitivity by two amino acid substitutions. These findings clarify the functions of LGP2 as a positive regulator of MDA5 signaling, demonstrate the basis for V-mediated LGP2 targeting, and broaden our understanding of paramyxovirus-host interactions. PMID:24829334

Improving Coverage and Compliance in Mass Drug Administration for the Elimination of LF in Two ‘Endgame’ Districts in Indonesia Using Micronarrative Surveys

PubMed Central

Krentel, Alison; Damayanti, Rita; Titaley, Christiana Rialine; Suharno, Nugroho; Bradley, Mark; Lynam, Timothy

2016-01-01

Background As the Global Programme to Eliminate Lymphatic Filariasis (LF) approaches its 2020 goal, an increasing number of districts will enter the endgame phase where drug coverage rates from mass drug administration (MDA) are used to assess whether MDA can be stopped. As reported, the gap between reported and actual drug coverage in some contexts has overestimated the true rates, thus causing premature administration of transmission assessment surveys (TAS) that detect ongoing LF transmission. In these cases, districts must continue with additional rounds of MDA. Two districts in Indonesia (Agam District, Depok City) fit this criteria—one had not met the pre-TAS criteria and the other, had not passed the TAS criteria. In both cases, the district health teams needed insight into their drug delivery programs in order to improve drug coverage in the subsequent MDA rounds. Methodology/Principal Findings To inform the subsequent MDA round, a micronarrative survey tool was developed to capture community members’ experience with MDA and the social realm where drug delivery and compliance occur. A baseline survey was implemented after the 2013 MDA in endemic communities in both districts using the EPI sampling criteria (n = 806). Compliance in the last MDA was associated with perceived importance of the LF drugs for health (p<0.001); perceived safety of the LF drugs (p<0.001) and knowing someone in the household has complied (p<0.001). Results indicated that specialized messages were needed to reach women and younger men. Both districts used these recommendations to implement changes to their MDA without additional financial support. An endline survey was performed after the 2014 MDA using the same sampling criteria (n = 811). Reported compliance in the last MDA improved in both districts from 57% to 77% (p<0.05). Those who reported having ever taken the LF drug rose from 79% to 90% (p<0.001) in both sites. Conclusions/Significance Micronarrative surveys were shown to be a valid and effective tool to detect operational issues within MDA programs. District health staff felt ownership of the results, implementing feasible changes to their programs that resulted in significant improvements to coverage and compliance in the subsequent MDA. This kind of implementation research using a micronarrative survey tool could benefit underperforming MDA programs as well as other disease control programs where a deeper understanding is needed to improve healthcare delivery. PMID:27812107

Aerothermodynamic Testing and Boundary Layer Trip Sizing of the HIFiRE Flight 1 Vehicle

NASA Technical Reports Server (NTRS)

Berger, Karen T.; Greene, Frank A.; Kimmel, Roger; Alba, Christopher; Johnson, Heath

2008-01-01

An experimental wind tunnel test was conducted in the NASA Langley Research Center s 20-Inch Mach 6 Air Tunnel in support of the Hypersonic International Flight Research Experimentation Program. The information in this article is focused on the Flight 1 configuration, the first in a series of flight experiments. The article documents experimental measurements made over a Reynolds numbers range of 2.1x10(exp 6)/ft to 5.6x10(exp 6)/ft and angles of attack of -5 to +5 deg on several scaled ceramic heat transfer models of the Flight 1 configuration. Global heat transfer was measured using phosphor thermography and the resulting images and heat transfer distributions were used to infer the state of the boundary layer on the vehicle windside and leeside surfaces. Boundary layer trips were used to force the boundary layer turbulent and the experimental data highlighted in this article were used to size and place the boundary layer trip for the flight vehicle. The required height of the flight boundary layer trip was determined to be 0.079 in and the trip was moved from the design location of 7.87 in to 20.47 in to ensure that augmented heating would not impact the laminar side of the vehicle. Allowable roughness was selected to be 3.2x10(exp -3) in.

Assessing the feasibility of interrupting the transmission of soil-transmitted helminths through mass drug administration: The DeWorm3 cluster randomized trial protocol.

PubMed

Ásbjörnsdóttir, Kristjana Hrönn; Ajjampur, Sitara S Rao; Anderson, Roy M; Bailey, Robin; Gardiner, Iain; Halliday, Katherine E; Ibikounle, Moudachirou; Kalua, Khumbo; Kang, Gagandeep; Littlewood, D Timothy J; Luty, Adrian J F; Means, Arianna Rubin; Oswald, William; Pullan, Rachel L; Sarkar, Rajiv; Schär, Fabian; Szpiro, Adam; Truscott, James E; Werkman, Marleen; Yard, Elodie; Walson, Judd L

2018-01-01

Current control strategies for soil-transmitted helminths (STH) emphasize morbidity control through mass drug administration (MDA) targeting preschool- and school-age children, women of childbearing age and adults in certain high-risk occupations such as agricultural laborers or miners. This strategy is effective at reducing morbidity in those treated but, without massive economic development, it is unlikely it will interrupt transmission. MDA will therefore need to continue indefinitely to maintain benefit. Mathematical models suggest that transmission interruption may be achievable through MDA alone, provided that all age groups are targeted with high coverage. The DeWorm3 Project will test the feasibility of interrupting STH transmission using biannual MDA targeting all age groups. Study sites (population ≥80,000) have been identified in Benin, Malawi and India. Each site will be divided into 40 clusters, to be randomized 1:1 to three years of twice-annual community-wide MDA or standard-of-care MDA, typically annual school-based deworming. Community-wide MDA will be delivered door-to-door, while standard-of-care MDA will be delivered according to national guidelines. The primary outcome is transmission interruption of the STH species present at each site, defined as weighted cluster-level prevalence ≤2% by quantitative polymerase chain reaction (qPCR), 24 months after the final round of MDA. Secondary outcomes include the endline prevalence of STH, overall and by species, and the endline prevalence of STH among children under five as an indicator of incident infections. Secondary analyses will identify cluster-level factors associated with transmission interruption. Prevalence will be assessed using qPCR of stool samples collected from a random sample of cluster residents at baseline, six months after the final round of MDA and 24 months post-MDA. A smaller number of individuals in each cluster will be followed with annual sampling to monitor trends in prevalence and reinfection throughout the trial. ClinicalTrials.gov NCT03014167.

A multi-center field study of two point-of-care tests for circulating Wuchereria bancrofti antigenemia in Africa

PubMed Central

Chesnais, Cédric B.; Awaca-Uvon, Naomi-Pitchouna; Bolay, Fatoma K.; Boussinesq, Michel; Fischer, Peter U.; Gankpala, Lincoln; Meite, Aboulaye; Missamou, François; Pion, Sébastien D.

2017-01-01

Background The Global Programme to Eliminate Lymphatic Filariasis uses point-of-care tests for circulating filarial antigenemia (CFA) to map endemic areas and for monitoring and evaluating the success of mass drug administration (MDA) programs. We compared the performance of the reference BinaxNOW Filariasis card test (ICT, introduced in 1997) with the Alere Filariasis Test Strip (FTS, introduced in 2013) in 5 endemic study sites in Africa. Methodology The tests were compared prior to MDA in two study sites (Congo and Côte d'Ivoire) and in three sites that had received MDA (DRC and 2 sites in Liberia). Data were analyzed with regard to % positivity, % agreement, and heterogeneity. Models evaluated potential effects of age, gender, and blood microfilaria (Mf) counts in individuals and effects of endemicity and history of MDA at the village level as potential factors linked to higher sensitivity of the FTS. Lastly, we assessed relationships between CFA scores and Mf in pre- and post-MDA settings. Principal findings Paired test results were available for 3,682 individuals. Antigenemia rates were 8% and 22% higher by FTS than by ICT in pre-MDA and in post-MDA sites, respectively. FTS/ICT ratios were higher in areas with low infection rates. The probability of having microfilaremia was much higher in persons with CFA scores >1 in untreated areas. However, this was not true in post-MDA settings. Conclusions/Significance This study has provided extensive new information on the performance of the FTS compared to ICT in Africa and it has confirmed the increased sensitivity of FTS reported in prior studies. Variability in FTS/ICT was related in part to endemicity level, history of MDA, and perhaps to the medications used for MDA. These results suggest that FTS should be superior to ICT for mapping, for transmission assessment surveys, and for post-MDA surveillance. PMID:28892473

Novel Role of MDA-9/Syntenin in Regulating Urothelial Cell Proliferation by Modulating EGFR Signaling

PubMed Central

Dasgupta, Santanu; Menezes, Mitchell E.; Das, Swadesh K.; Emdad, Luni; Janjic, Aleksandar; Bhatia, Shilpa; Mukhopadhyay, Nitai D; Shao, Chunbo; Sarkar, Devanand; Fisher, Paul B.

2013-01-01

Purpose Urothelial cell carcinoma (UCC) rapidly progresses from superficial to muscle-invasive tumors. The key molecules involved in metastatic progression and its early detection require clarification. The present study defines a seminal role of the metastasis-associated gene MDA-9/Syntenin in UCC progression. Experimental Design Expression pattern of MDA-9/Syntenin was examined in 44 primary UCC and the impact of its overexpression and knock down was examined in multiple cells lines and key findings were validated in primary tumors. Results Significantly higher (p= 0.002–0.003) expression of MDA-9/Syntenin was observed in 64% (28/44) of primary tumors and an association was evident with stage (p=0.01), grade (p=0.03) and invasion status (p=0.02). MDA-9/Syntenin overexpression in non-tumorigenic HUC-1 cells increased proliferation (p=0.0012), invasion (p=0.0001) and EGFR, AKT, PI3K and c-Src expression. Alteration of Beta-catenin, E-Cadherin, Vimentin, Claudin-1, ZO-1 and TCF4 expression were also observed. MDA-9/Syntenin knock down in 3 UCC cell lines reversed phenotypic and molecular changes observed in the HUC-1 cells and reduced in vivo metastasis. Key molecular changes observed in the cell lines were confirmed in primary tumors. A physical interaction and co-localization of MDA-9/Syntenin and EGFR was evident in UCC cell lines and primary tumors. A logistic regression model analysis revealed a significant correlation between MDA-9/Syntenin:EGFR and MDA-9/Syntenin: AKT expressions with stage (p=0.04, EGFR), (p=0.01, AKT). A correlation between MDA-9/Syntenin: β-catenin co-expression with stage (p=0.03) and invasion (p=0.04) was also evident. Conclusions Our findings indicate that MDA-9/Syntenin might provide an attractive target for developing detection, monitoring and therapeutic strategies for managing UCC. PMID:23873690

Novel role of MDA-9/syntenin in regulating urothelial cell proliferation by modulating EGFR signaling.

PubMed

Dasgupta, Santanu; Menezes, Mitchell E; Das, Swadesh K; Emdad, Luni; Janjic, Aleksandar; Bhatia, Shilpa; Mukhopadhyay, Nitai D; Shao, Chunbo; Sarkar, Devanand; Fisher, Paul B

2013-09-01

Urothelial cell carcinoma (UCC) rapidly progresses from superficial to muscle-invasive tumors. The key molecules involved in metastatic progression and its early detection require clarification. The present study defines a seminal role of the metastasis-associated gene MDA-9/Syntenin in UCC progression. Expression pattern of MDA-9/Syntenin was examined in 44 primary UCC and the impact of its overexpression and knockdown was examined in multiple cells lines and key findings were validated in primary tumors. Significantly higher (P=0.002-0.003) expression of MDA-9/Syntenin was observed in 64% (28 of 44) of primary tumors and an association was evident with stage (P=0.01), grade (P=0.03), and invasion status (P=0.02). MDA-9/Syntenin overexpression in nontumorigenic HUC-1 cells increased proliferation (P=0.0012), invasion (P=0.0001), and EGF receptor (EGFR), AKT, phosphoinositide 3-kinase (PI3K), and c-Src expression. Alteration of β-catenin, E-cadherin, vimentin, claudin-1, ZO-1, and T-cell factor-4 (TCF4) expression was also observed. MDA-9/Syntenin knockdown in three UCC cell lines reversed phenotypic and molecular changes observed in the HUC-1 cells and reduced in vivo metastasis. Key molecular changes observed in the cell lines were confirmed in primary tumors. A physical interaction and colocalization of MDA-9/Syntenin and EGFR was evident in UCC cell lines and primary tumors. A logistic regression model analysis revealed a significant correlation between MDA-9/Syntenin:EGFR and MDA-9/Syntenin:AKT expressions with stage (P=0.04, EGFR; P=0.01, AKT). A correlation between MDA-9/Syntenin:β-catenin coexpression with stage (P=0.03) and invasion (P=0.04) was also evident. Our findings indicate that MDA-9/Syntenin might provide an attractive target for developing detection, monitoring, and therapeutic strategies for managing UCC. ©2013 AACR.

A multi-center field study of two point-of-care tests for circulating Wuchereria bancrofti antigenemia in Africa.

PubMed

Chesnais, Cédric B; Awaca-Uvon, Naomi-Pitchouna; Bolay, Fatoma K; Boussinesq, Michel; Fischer, Peter U; Gankpala, Lincoln; Meite, Aboulaye; Missamou, François; Pion, Sébastien D; Weil, Gary J

2017-09-01

The Global Programme to Eliminate Lymphatic Filariasis uses point-of-care tests for circulating filarial antigenemia (CFA) to map endemic areas and for monitoring and evaluating the success of mass drug administration (MDA) programs. We compared the performance of the reference BinaxNOW Filariasis card test (ICT, introduced in 1997) with the Alere Filariasis Test Strip (FTS, introduced in 2013) in 5 endemic study sites in Africa. The tests were compared prior to MDA in two study sites (Congo and Côte d'Ivoire) and in three sites that had received MDA (DRC and 2 sites in Liberia). Data were analyzed with regard to % positivity, % agreement, and heterogeneity. Models evaluated potential effects of age, gender, and blood microfilaria (Mf) counts in individuals and effects of endemicity and history of MDA at the village level as potential factors linked to higher sensitivity of the FTS. Lastly, we assessed relationships between CFA scores and Mf in pre- and post-MDA settings. Paired test results were available for 3,682 individuals. Antigenemia rates were 8% and 22% higher by FTS than by ICT in pre-MDA and in post-MDA sites, respectively. FTS/ICT ratios were higher in areas with low infection rates. The probability of having microfilaremia was much higher in persons with CFA scores >1 in untreated areas. However, this was not true in post-MDA settings. This study has provided extensive new information on the performance of the FTS compared to ICT in Africa and it has confirmed the increased sensitivity of FTS reported in prior studies. Variability in FTS/ICT was related in part to endemicity level, history of MDA, and perhaps to the medications used for MDA. These results suggest that FTS should be superior to ICT for mapping, for transmission assessment surveys, and for post-MDA surveillance.

Space Station/Skylab Sketch

NASA Technical Reports Server (NTRS)

1966-01-01

Seldom in aerospace history has a major decision been as promptly and concisely recorded as with the Skylab shown in this sketch. At a meeting at the Marshall Space Flight Center on August 19, 1966, George E. Mueller, NASA Associate Administrator for Marned Space Flight, used a felt pen and poster paper to pin down the final conceptual layout for the budding space station's (established as the Skylab in 1970) major elements. General Davy Jones, first program director, added his initials and those of Dr. Mueller in the lower right corner. The goals of the Skylab were to enrich our scientific knowledge of the Earth, the Sun, the stars, and cosmic space; to study the effects of weightlessness on living organisms, including man; to study the effects of the processing and manufacturing of materials utilizing the absence of gravity; and to conduct Earth resource observations. The Skylab also conducted 19 selected experiments submitted by high school students. Skylab's 3 different 3-man crews spent up to 84 days in Earth orbit. The Marshall Space Flight Center (MSFC) had responsibility for developing and integrating most of the major components of the Skylab: the Orbital Workshop (OWS), Airlock Module (AM), Multiple Docking Adapter (MDA), Apollo Telescope Mount (ATM), Payload Shroud (PS), and most of the experiments. MSFC was also responsible for providing the Saturn IB launch vehicles for three Apollo spacecraft and crews and a Saturn V launch vehicle for the Skylab.

Skylab

NASA Image and Video Library

1966-01-01

Seldom in aerospace history has a major decision been as promptly and concisely recorded as with the Skylab shown in this sketch. At a meeting at the Marshall Space Flight Center on August 19, 1966, George E. Mueller, NASA Associate Administrator for Marned Space Flight, used a felt pen and poster paper to pin down the final conceptual layout for the budding space station's (established as the Skylab in 1970) major elements. General Davy Jones, first program director, added his initials and those of Dr. Mueller in the lower right corner. The goals of the Skylab were to enrich our scientific knowledge of the Earth, the Sun, the stars, and cosmic space; to study the effects of weightlessness on living organisms, including man; to study the effects of the processing and manufacturing of materials utilizing the absence of gravity; and to conduct Earth resource observations. The Skylab also conducted 19 selected experiments submitted by high school students. Skylab's 3 different 3-man crews spent up to 84 days in Earth orbit. The Marshall Space Flight Center (MSFC) had responsibility for developing and integrating most of the major components of the Skylab: the Orbital Workshop (OWS), Airlock Module (AM), Multiple Docking Adapter (MDA), Apollo Telescope Mount (ATM), Payload Shroud (PS), and most of the experiments. MSFC was also responsible for providing the Saturn IB launch vehicles for three Apollo spacecraft and crews and a Saturn V launch vehicle for the Skylab.

The effects of chronic radiation of gamma ray on protein expression and oxidative stress in Brachypodium distachyon.

PubMed

Kim, Dae Yeon; Hong, Min Jeong; Park, Cheong-Sool; Seo, Yong Weon

2015-05-01

To compare the effects of gamma-irradiation on biochemical responses and growth, six-week-old Brachypodium plants were chronically exposed to gamma-irradiation for 30 days at various dosages. Growth surveys of Brachypodium plants in response to different dosages of gamma-irradiation were conducted to compare physiological changes between irradiated and non-irradiated plants. Photosynthetic pigments, soluble sugar content, activities of antioxidant enzymes, and malonaldehyde (MDA) induced by reactive oxygen species (ROS) production were also measured. Gamma-irradiation had a negative influence on the average plant height, leaf length, leaf width, and fresh weight. Photosynthetic pigment levels decreased with increasing dosages of gamma-irradiation, while soluble sugar content slightly increased. Gamma-irradiation responsive proteins were detected and identified by two-dimensional gel electrophoresis (2D-PAGE) and matrix-assisted laser desorption ionization time-of-flight (MALDI-TOF). The proteins had a role in photosynthetic carbon fixation, anabolic pathway glycolysis, mitochondrial ATP production, and oxidative stress response regulation. MDA levels and activities of antioxidant enzymes such as superoxide dismutase (SOD), ascorbate peroxidase (APX), catalase (CAT), and peroxidase (POD) increased with the increase in gamma-irradiation dosage level. This study provides some basic information regarding responses to gamma-irradiation, and provides valuable physiological and biological data on the effects of different gamma-irradiation dosages on Triticeae species.

The Environmental Behavior of Methylene-4,4'-dianiline.

PubMed

Schupp, Thomas; Allmendinger, Hans; Boegi, Christian; Bossuyt, Bart T A; Hidding, Bjoern; Shen, Summer; Tury, Bernard; West, Robert J

2018-06-24

Methylene-4,4'-dianiline (MDA, CAS-No. 101-77-9) is a high production volume intermediate that is mainly processed to diisocyanates and finally polyurethanes. This review summarizes available data concerning the environmental behavior. When released into the environment, MDA distributes into water and subsequently sediment and soil compartments; the air is of little relevance, owed to the low vapor pressure and short atmospheric half-life, which renders MDA non-critical for long-range transport. Biodegradation data present a diverged picture; in some tests, MDA is not readily biodegradable or even not inherent biodegradable; in other tests, MDA turned out to be readily biodegradable (but failing the 10-d window). The history and composition of the inoculum used for testing seem to play an important role, which is underlined by good test results with adapted inoculum. In soil, initially a rapid mineralization is observed, which slows down within the first days due to competitive chemical absorption. The latter results in degradation rates comparable to that of natural organic matter. Under anaerobic conditions, mineralization is poor. Irreversible chemisorption occurs unless soils/sediments are highly reduced. Half-lives due to primary decay do not indicate MDA to be persistent according to the regulatory guidance used in then EU, Canada, or the USA; in Japan, however, due to test results in MITI degradation tests, MDA would be regarded as persistent. The identification of microbial MDA metabolites deserves further research. MDA is not bioaccumulative, but it is toxic to aquatic organisms and mammals. MDA in pore water of soils is rapidly adsorbed on the surface of plant roots. Test runs were too short to draw a final conclusion with regards to transport to stem, leaves, and fruits. Data from structurally similar compounds indicate that such transport would account for less than 1% of the root-adsorbed material.

A comparative study of biodegradability of a carcinogenic aromatic amine (4,4'-diaminodiphenylmethane) with OECD 301 test methods.

PubMed

Mei, Cheng-Fang; Liu, Yan-Zhen; Long, Wei-Nian; Sun, Guo-Ping; Zeng, Guo-Qu; Xu, Mei-Ying; Luan, Tian-Gang

2015-01-01

4,4'-Diaminodiphenylmethane (MDA) is a widely used compound in industries. Studies on the biodegradability of MDA are necessary for environmental hazard identification and risk assessment. Previous studies have suggested that MDA was not readily biodegradable. In the present study, three batches of biodegradation tests (OECD 301A, B, D and F tests) were performed on MDA in June, August and December of 2012. MDA was found to be readily biodegradable and produced colored intermediates in the 301A, B and F test systems. MDA biodegradation measurements were consistent among the three batches of tests. Differences in the extent of biodegradation determined in different methods originated from different test conditions and assessment endpoints. The 301D test has stringent test conditions and is usually performed on chemicals that are toxic to microorganisms, so the test results obtained from 301D tests are less meaningful for evaluating the biodegradability of MDA. The low MDA biodegradation measurements in the 301B tests compared to the 301A and F tests were due to the assessment method, which did not account for MDA incorporation into biomass in its calculation of CO2 formation rate. The differences in the biodegradation rates, as measured by the different OECD 301 test systems, could also be related to the structure and properties of the chemical. For test substances that can be assessed by all OECD 301 test methods, the highest biodegradation values may be obtained from the 301A and F test methods. This study provides new information to assess the environmental fate in the risk assessment of MDA. Copyright © 2014 Elsevier Inc. All rights reserved.

Malondialdehyde-derived epitopes in human skin result from acute exposure to solar UV and occur in nonmelanoma skin cancer tissue.

PubMed

Williams, Joshua D; Bermudez, Yira; Park, Sophia L; Stratton, Steven P; Uchida, Koji; Hurst, Craig A; Wondrak, Georg T

2014-03-05

Cutaneous exposure to solar ultraviolet radiation (UVR) is a causative factor in photoaging and photocarcinogenesis. In human skin, oxidative stress is widely considered a key mechanism underlying the detrimental effects of acute and chronic UVR exposure. The lipid peroxidation product malondialdehyde (MDA) accumulates in tissue under conditions of increased oxidative stress, and the occurrence of MDA-derived protein epitopes, including dihydropyridine-lysine (DHP), has recently been substantiated in human skin. Here we demonstrate for the first time that acute exposure to sub-apoptogenic doses of solar simulated UV light (SSL) causes the formation of free MDA and protein-bound MDA-derived epitopes in cultured human HaCaT keratinocytes and healthy human skin. Immunohistochemical staining revealed that acute exposure to SSL is sufficient to cause an almost twenty-fold increase in general MDA- and specific DHP-epitope content in human skin. When compared to dose-matched solar simulated UVA, complete SSL was more efficient generating both free MDA and MDA-derived epitopes. Subsequent tissue microarray (TMA) analysis revealed the prevalence of MDA- and DHP-epitopes in nonmelanoma skin cancer (NMSC). In squamous cell carcinoma tissue, both MDA- and DHP-epitopes were increased more than threefold as compared to adjacent normal tissue. Taken together, these date demonstrate the occurrence of MDA-derived epitopes in both solar UVR-exposed healthy human skin and NMSC TMA tissue; however, the potential utility of these epitopes as novel biomarkers of cutaneous photodamage and a functional role in the process of skin photocarcinogenesis remain to be explored. Copyright © 2014 Elsevier B.V. All rights reserved.

Modeling the Impact and Costs of Semiannual Mass Drug Administration for Accelerated Elimination of Lymphatic Filariasis

PubMed Central

de Vlas, Sake J.; Fischer, Peter U.; Weil, Gary J.; Goldman, Ann S.

2013-01-01

The Global Program to Eliminate Lymphatic Filariasis (LF) has a target date of 2020. This program is progressing well in many countries. However, progress has been slow in some countries, and others have not yet started their mass drug administration (MDA) programs. Acceleration is needed. We studied how increasing MDA frequency from once to twice per year would affect program duration and costs by using computer simulation modeling and cost projections. We used the LYMFASIM simulation model to estimate how many annual or semiannual MDA rounds would be required to eliminate LF for Indian and West African scenarios with varied pre-control endemicity and coverage levels. Results were used to estimate total program costs assuming a target population of 100,000 eligibles, a 3% discount rate, and not counting the costs of donated drugs. A sensitivity analysis was done to investigate the robustness of these results with varied assumptions for key parameters. Model predictions suggested that semiannual MDA will require the same number of MDA rounds to achieve LF elimination as annual MDA in most scenarios. Thus semiannual MDA programs should achieve this goal in half of the time required for annual programs. Due to efficiency gains, total program costs for semiannual MDA programs are projected to be lower than those for annual MDA programs in most scenarios. A sensitivity analysis showed that this conclusion is robust. Semiannual MDA is likely to shorten the time and lower the cost required for LF elimination in countries where it can be implemented. This strategy may improve prospects for global elimination of LF by the target year 2020. PMID:23301115

Impact of Six Rounds of Mass Drug Administration on Brugian Filariasis and Soil-Transmitted Helminth Infections in Eastern Indonesia

PubMed Central

Supali, Taniawati; Djuardi, Yenny; Bradley, Mark; Noordin, Rahmah; Rückert, Paul; Fischer, Peter U.

2013-01-01

Background The lymphatic filarial parasite Brugia timori occurs only in eastern Indonesia where it causes high morbidity. The absence of an animal reservoir, the inefficient transmission by Anopheles mosquitoes and the high sensitivity to DEC/albendazole treatment make this species a prime candidate for elimination by mass drug administration (MDA). Methodology/Principal Findings We evaluated the effect of MDA using DEC and albendazole on B. timori and soil transmitted helminths (STH) in a cross-sectional study of a sentinel village on Alor Island annually over a period of 10 years. Pre-MDA the microfilaria (MF) prevalence was 26% and 80% of the residents had filaria-specific IgG4 antibodies. In 2010, 34 months after the 6th round of MDA, MF and antibody rates were only 0.17% and 6.4%, respectively. The MDA campaign had also a beneficial effect on STH. Baseline prevalence rates for Ascaris, hookworm and Trichuris were 34%, 28%, and 11%, respectively; these rates were reduced to 27%, 4%, and 2% one year after the 5th round of MDA. Unfortunately, STH rates rebounded 34 months after cessation of MDA and approached pre-MDA rates. However, the intensity of STH infection in 2009 was still reduced, and no heavy infections were detected. Conclusions/Significance MDA with DEC/albendazole has had a major impact on B. timori MF and IgG4 antibody rates, providing a proof of principle that elimination is feasible. We also documented the value of annual DEC/albendazole as a mass de-worming intervention and the importance of continuing some form of STH control after cessation of MDA for filariasis. PMID:24349595

Impact of six rounds of mass drug administration on Brugian filariasis and soil-transmitted helminth infections in eastern Indonesia.

PubMed

Supali, Taniawati; Djuardi, Yenny; Bradley, Mark; Noordin, Rahmah; Rückert, Paul; Fischer, Peter U

2013-01-01

The lymphatic filarial parasite Brugia timori occurs only in eastern Indonesia where it causes high morbidity. The absence of an animal reservoir, the inefficient transmission by Anopheles mosquitoes and the high sensitivity to DEC/albendazole treatment make this species a prime candidate for elimination by mass drug administration (MDA). We evaluated the effect of MDA using DEC and albendazole on B. timori and soil transmitted helminths (STH) in a cross-sectional study of a sentinel village on Alor Island annually over a period of 10 years. Pre-MDA the microfilaria (MF) prevalence was 26% and 80% of the residents had filaria-specific IgG4 antibodies. In 2010, 34 months after the 6(th) round of MDA, MF and antibody rates were only 0.17% and 6.4%, respectively. The MDA campaign had also a beneficial effect on STH. Baseline prevalence rates for Ascaris, hookworm and Trichuris were 34%, 28%, and 11%, respectively; these rates were reduced to 27%, 4%, and 2% one year after the 5(th) round of MDA. Unfortunately, STH rates rebounded 34 months after cessation of MDA and approached pre-MDA rates. However, the intensity of STH infection in 2009 was still reduced, and no heavy infections were detected. MDA with DEC/albendazole has had a major impact on B. timori MF and IgG4 antibody rates, providing a proof of principle that elimination is feasible. We also documented the value of annual DEC/albendazole as a mass de-worming intervention and the importance of continuing some form of STH control after cessation of MDA for filariasis.

MDA-9/syntenin and IGFBP-2 promote angiogenesis in human melanoma.

PubMed

Das, Swadesh K; Bhutia, Sujit K; Azab, Belal; Kegelman, Timothy P; Peachy, Leyla; Santhekadur, Prasanna K; Dasgupta, Santanu; Dash, Rupesh; Dent, Paul; Grant, Steven; Emdad, Luni; Pellecchia, Maurizio; Sarkar, Devanand; Fisher, Paul B

2013-01-15

Melanoma differentiation-associated gene-9 (mda-9/syntenin) encodes an adapter scaffold protein whose expression correlates with and mediates melanoma progression and metastasis. Tumor angiogenesis represents an integral component of cancer metastasis prompting us to investigate a possible role of mda-9/syntenin in inducing angiogenesis. Genetic (gain-of-function and loss-of-function) and pharmacologic approaches were used to modify mda-9/syntenin expression in normal immortal melanocytes, early radial growth phase melanoma, and metastatic melanoma cells. The consequence of modifying mda-9/syntenin expression on angiogenesis was evaluated using both in vitro and in vivo assays, including tube formation assays using human vascular endothelial cells, chorioallantoic membrane (CAM) assays and xenograft tumor animal models. Gain-of-function and loss-of-function experiments confirm that MDA-9/syntenin induces angiogenesis by augmenting expression of several proangiogenic factors/genes. Experimental evidence is provided for a model of angiogenesis induction by MDA-9/syntenin in which MDA-9/syntenin interacts with the extracellular matrix (ECM), activating Src and FAK resulting in activation by phosphorylation of Akt, which induces hypoxia inducible factor 1-α (HIF-1α). The HIF-1α activates transcription of insulin growth factor-binding protein-2 (IGFBP-2), which is secreted thereby promoting angiogenesis and further induces endothelial cells to produce and secrete VEGF-A augmenting tumor angiogenesis. Our studies delineate an unanticipated cell nonautonomous function of MDA-9/syntenin in the context of angiogenesis, which may directly contribute to its metastasis-promoting properties. As a result, targeting MDA-9/syntenin or its downstream-regulated molecules may provide a means of simultaneously impeding metastasis by both directly inhibiting tumor cell transformed properties (autonomous) and indirectly by blocking angiogenesis (nonautonomous).

MDA-9/Syntenin and IGFBP-2 Promote Angiogenesis in Human Melanoma

PubMed Central

Das, Swadesh K.; Bhutia, Sujit K.; Azab, Belal; Kegelman, Timothy P.; Peachy, Leyla; Santhekadur, Prasanna K.; Dasgupta, Santanu; Dash, Rupesh; Dent, Paul; Grant, Steven; Emdad, Luni; Pellecchia, Maurizio; Sarkar, Devanand; Fisher, Paul B.

2012-01-01

Melanoma differentiation associated gene-9 (mda-9/syntenin) encodes an adapter scaffold protein whose expression correlates with and mediates melanoma progression and metastasis. Tumor angiogenesis represents an integral component of cancer metastasis prompting us to investigate a possible role of mda-9/syntenin in inducing angiogenesis. Genetic (gain-of-function and loss-of-function) and pharmacological approaches were employed to modify mda-9/syntenin expression in normal immortal melanocytes, early radial growth phase melanoma and metastatic melanoma cells. The consequence of modifying mda-9/syntenin expression on angiogenesis was evaluated using both in vitro and in vivo assays, including tube formation assays using human vascular endothelial cells, CAM assays and xenograft tumor animal models. Gain-of-function and loss-of-function experiments confirm that MDA-9/syntenin induces angiogenesis by augmenting expression of several pro-angiogenic factors/genes. Experimental evidence is provided for a model of angiogenesis induction by MDA-9/syntenin in which MDA-9/syntenin interacts with the ECM activating Src and FAK resulting in activation by phosphorylation of Akt, which induces HIF-1α. The HIF-1α activates transcription of Insulin Growth Factor Binding Protein-2 (IGFBP-2), which is secreted thereby promoting angiogenesis and further induces endothelial cells to produce and secrete VEGF-A augmenting tumor angiogenesis. Our studies delineate an unanticipated cell non-autonomous function of MDA-9/syntenin in the context of angiogenesis, which may directly contribute to its metastasis-promoting properties. As a result, targeting MDA-9/syntenin or its downstream-regulated molecules may provide a means of simultaneously impeding metastasis by both directly inhibiting tumor cell transformed properties (autonomous) and indirectly by blocking angiogenesis (non-autonomous). PMID:23233738

Anti-MDA5 autoantibodies in juvenile dermatomyositis identify a distinct clinical phenotype: a prospective cohort study

PubMed Central

2014-01-01

Introduction The aim of this study was to define the frequency and associated clinical phenotype of anti-MDA5 autoantibodies in a large UK based, predominantly Caucasian, cohort of patients with juvenile dermatomyositis (JDM). Methods Serum samples and clinical data were obtained from 285 patients with JDM recruited to the UK Juvenile Dermatomyositis Cohort and Biomarker Study. The presence of anti-MDA5 antibodies was determined by immunoprecipitation and confirmed by ELISA using recombinant MDA5 protein. Results were compared with matched clinical data, muscle biopsies (scored by an experienced paediatric neuropathologist) and chest imaging (reviewed by an experienced paediatric radiologist). Results Anti-MDA5 antibodies were identified in 7.4% of JDM patients and were associated with a distinct clinical phenotype including skin ulceration (P = 0.03) oral ulceration (P = 0.01), arthritis (P <0.01) and milder muscle disease both clinically (as determined by Childhood Myositis Assessment Score (P = 0.03)) and histologically (as determined by a lower JDM muscle biopsy score (P <0.01)) than patients who did not have anti-MDA5 antibodies. A greater proportion of children with anti-MDA5 autoantibodies achieved disease inactivity at two years post-diagnosis according to PRINTO criteria (P = 0.02). A total of 4 out of 21 children with anti-MDA5 had interstitial lung disease; none had rapidly progressive interstitial lung disease. Conclusions Anti-MDA5 antibodies can be identified in a small but significant proportion of patients with JDM and identify a distinctive clinical sub-group. Screening for anti-MDA5 autoantibodies at diagnosis would be useful to guide further investigation for lung disease, inform on prognosis and potentially confirm the diagnosis, as subtle biopsy changes could otherwise be missed. PMID:24989778

Evaluation of cloud detection instruments and performance of laminar-flow leading-edge test articles during NASA Leading-Edge Flight-Test Program

NASA Technical Reports Server (NTRS)

Davis, Richard E.; Maddalon, Dal V.; Wagner, Richard D.; Fisher, David F.; Young, Ronald

1989-01-01

Summary evaluations of the performance of laminar-flow control (LFC) leading edge test articles on a NASA JetStar aircraft are presented. Statistics, presented for the test articles' performance in haze and cloud situations, as well as in clear air, show a significant effect of cloud particle concentrations on the extent of laminar flow. The cloud particle environment was monitored by two instruments, a cloud particle spectrometer (Knollenberg probe) and a charging patch. Both instruments are evaluated as diagnostic aids for avoiding laminar-flow detrimental particle concentrations in future LFC aircraft operations. The data base covers 19 flights in the simulated airline service phase of the NASA Leading-Edge Flight-Test (LEFT) Program.

Periodic molybdenum disc array for light trapping in amorphous silicon layer

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

Wang, Jiwei; Deng, Changkai; Shanghai Advanced Research Institute, Chinese Academy of Sciences, 99 Haike Road, Shanghai, 201210 China

2016-05-15

We demonstrate the light trapping effect in amorphous silicon (a-Si:H) layer by inserting a layer of periodic molybdenum disc array (MDA) between the a-Si:H layer and the quartz substrate, which forms a three-layer structure of Si/MDA/SiO{sub 2}. The MDA layer was fabricated by a new cost-effective method based on nano-imprint technology. Further light absorption enhancement was realized through altering the topography of MDA by annealing it at 700°C. The mechanism of light absorption enhancement in a-Si:H interfaced with MDA was analyzed, and the electric field distribution and light absorption curve of the different layers in the Si/MDA structure under lightmore » illumination of different wavelengths were simulated by employing numerical finite difference time domain (FDTD) solutions.« less

Degree of neutrophil, atrophy, and metaplasia intestinal were associate with malondialdehyde level in gastritis patients

NASA Astrophysics Data System (ADS)

Siregar, G. A.; Sari, D. K.; Sungkar, T.

2018-03-01

The main pathogenesis of gastritis is inflammation that closely related to free radicals. Malondialdehyde (MDA) is a free radical biomarker and is found to increase in gastritis patients. However, these studies are generally performed on experimental animals as well as MDA examination in gastric mucosa. This study aim was to determine the association of degrees of gastritis (degree of lymphocyte infiltration, neutrophil activity, atrophy, and intestinal metaplasia) with plasma MDA level. A cross-sectional study of 80 consecutive gastritis patients who came to an endoscopic unit of Adam Malik General Hospital in Medan, Indonesia, from May–September 2017. Assessed for severity of chronic inflammatory, neutrophil activity, atrophy, and intestinal metaplasia refers to Updated Sydney System. Plasma MDA levels were examined using an HPLC MDA kit. Univariate analysis, bivariate (chi-square and Fisher exact test), and multivariate (binary logistic regression test) were programmed with SPSS version 22. There was no significant association between degree of lymphocyte infiltration with MDA level. There were significant associations between degree of neutrophil activity, atrophy, and intestinal metaplasia with MDA level (p=0.039, 0.003, 0.021; respectively). The moderate+severe degree of neutrophil activity, atrophy, and intestinal metaplasia were associated with high level of MDA.

Dissociation of Paramyxovirus Interferon Evasion Activities: Universal and Virus-Specific Requirements for Conserved V Protein Amino Acids in MDA5 Interference ▿

PubMed Central

Ramachandran, Aparna; Horvath, Curt M.

2010-01-01

The V protein of the paramyxovirus subfamily Paramyxovirinae is an important virulence factor that can interfere with host innate immunity by inactivating the cytosolic pathogen recognition receptor MDA5. This interference is a result of a protein-protein interaction between the highly conserved carboxyl-terminal domain of the V protein and the helicase domain of MDA5. The V protein C-terminal domain (CTD) is an evolutionarily conserved 49- to 68-amino-acid region that coordinates two zinc atoms per protein chain. Site-directed mutagenesis of conserved residues in the V protein CTD has revealed both universal and virus-specific requirements for zinc coordination in MDA5 engagement and has also identified other conserved residues as critical for MDA5 interaction and interference. Mutation of these residues produces V proteins that are specifically defective for MDA5 interference and not impaired in targeting STAT1 for proteasomal degradation via the VDC ubiquitin ligase complex. Results demonstrate that mutation of conserved charged residues in the V proteins of Nipah virus, measles virus, and mumps virus also abolishes MDA5 interaction. These findings clearly define molecular determinants for MDA5 inhibition by the paramyxovirus V proteins. PMID:20719949

Peroxyoxalate chemiluminescence detection of condensates of malondialdehyde with thiobarbituric acids using a flow system.

PubMed

Nakashima, K; Nagata, M; Takahashi, M; Akiyama, S

1992-01-01

The peroxyoxalate chemiluminescence(CL) detection method for the evaluation of the CL intensity of malondialdehyde(MDA) condensates with seven 2-thiobarbituric acid derivatives is described. The method consists of a flow injection technique together with a CL detection system using bis(2,4,6-trichlorophenyl) oxalate(TCPO) and hydrogen peroxide as chemiluminogenic reagents. Linear correlations between CL intensity and concentration are obtained for pmol levels of condensates. Among the condensates, 1,3-diethyl-2-thiobarbituric acid(DETBA)-MDA shows the largest CL intensity. High performance liquid chromatography (HPLC)/CL detection of DETBA-MDA and 1,3-diphenyl-2-thiobarbituric acid(DPTBA)-MDA using a mixture of TCPO and hydrogen peroxide in acetonitrile as a postcolumn reagent solution is also described. The detection limits for DETBA-MDA and DPTBA-MDA are 20 and 200 fmol, respectively, per 20 microL injection at a signal-to-noise ratio of 2. This HPLC/CL detection system was applied to the determination of MDA in rat brains by using DETBA as a fluorescent derivatizing reagent.

Malondialdehyde Suppresses Cerebral Function by Breaking Homeostasis between Excitation and Inhibition in Turtle Trachemys scripta

PubMed Central

Li, Fangxu; Yang, Zhilai; Lu, Yang; Wei, Yan; Wang, Jinhui; Yin, Dazhong; He, Rongqiao

2010-01-01

The levels of malondialdehyde (MDA) are high in the brain during carbonyl stress, such as following daily activities and sleep deprivation. To examine our hypothesis that MDA is one of the major substances in the brain leading to fatigue, the influences of MDA on brain functions and neuronal encodings in red-eared turtle (Trachemys scripta) were studied. The intrathecal injections of MDA brought about sleep-like EEG and fatigue-like behaviors in a dose-dependent manner. These changes were found associated with the deterioration of encoding action potentials in cortical neurons. In addition, MDA increased the ratio of γ-aminobutyric acid to glutamate in turtle's brain, as well as the sensitivity of GABAergic neurons to inputs compared to excitatory neurons. Therefore, MDA, as a metabolic product in the brain, may weaken cerebral function during carbonyl stress through breaking the homeostasis between excitatory and inhibitory neurons. PMID:21203547

Waterhammer Modeling for the Ares I Upper Stage Reaction Control System Cold Flow Development Test Article

NASA Technical Reports Server (NTRS)

Williams, Jonathan H.

2010-01-01

The Upper Stage Reaction Control System provides three-axis attitude control for the Ares I launch vehicle during active Upper Stage flight. The system design must accommodate rapid thruster firing to maintain the proper launch trajectory and thus allow for the possibility to pulse multiple thrusters simultaneously. Rapid thruster valve closure creates an increase in static pressure, known as waterhammer, which propagates throughout the propellant system at pressures exceeding nominal design values. A series of development tests conducted in the fall of 2009 at Marshall Space Flight Center were performed using a water-flow test article to better understand fluid performance characteristics of the Upper Stage Reaction Control System. A subset of the tests examined waterhammer along with the subsequent pressure and frequency response in the flight-representative system and provided data to anchor numerical models. This thesis presents a comparison of waterhammer test results with numerical model and analytical results. An overview of the flight system, test article, modeling and analysis are also provided.

Waterhammer modeling for the Ares I Upper Stage Reaction Control System cold flow development test article

NASA Astrophysics Data System (ADS)

Williams, Jonathan Hunter

The Upper Stage Reaction Control System provides in-flight three-axis attitude control for the Ares I Upper Stage. The system design must accommodate rapid thruster firing to maintain proper launch trajectory and thus allow for the possibility to pulse multiple thrusters simultaneously. Rapid thruster valve closure creates an increase in static pressure, known as waterhammer, which propagates throughout the propellant system at pressures exceeding nominal design values. A series of development tests conducted at Marshall Space Flight Center in 2009 were performed using a water-flow test article to better understand fluid characteristics of the Upper Stage Reaction Control System. A subset of the tests examined the waterhammer pressure and frequency response in the flight-representative system and provided data to anchor numerical models. This thesis presents a comparison of waterhammer test results with numerical model and analytical results. An overview of the flight system, test article, modeling and analysis are also provided.

mda-9/Syntenin protein positively regulates the activation of Akt protein by facilitating integrin-linked kinase adaptor function during adhesion to type I collagen.

PubMed

Hwangbo, Cheol; Park, Juhee; Lee, Jeong-Hyung

2011-09-23

The integrin-linked kinase (ILK)-PINCH1-α-parvin (IPP) complex functions as a signaling platform for integrins that modulates various cellular processes. ILK functions as a central adaptor for the assembly of IPP complex. We report here that mda-9/syntenin, a positive regulator of cancer metastasis, regulates the activation of Akt (also known as protein kinase B) by facilitating ILK adaptor function during adhesion to type I collagen (COL-I) in human breast cancer cells. COL-I stimulation induced the phosphorylation and plasma membrane translocation of Akt. Inhibition of mda-9/syntenin or expression of mutant ILK (E359K) significantly blocked the translocation of both ILK and Akt to the plasma membrane. mda-9/syntenin associated with ILK, and this association was increased at the plasma membrane by COL-I stimulation. Knockdown of mda-9/syntenin impaired COL-I-induced association of ILK with Akt and plasma membrane targeting of ILK-Akt complex. These results demonstrated that mda-9/syntenin regulates the activation of Akt by controlling the plasma membrane targeting of Akt via a mechanism that facilitates the association of Akt with ILK at the plasma membrane during adhesion to COL-I. On a striking note, inhibition of mda-9/syntenin impaired COL-I-induced plasma membrane translocation of the IPP complex and assembly of integrin β1-IPP signaling complexes. Thus, our study defines the role of mda-9/syntenin in ILK adaptor function and describes a new mechanism of mda-9/syntenin for regulation of cell migration.

Cascading Delay Risk of Airline Workforce Deployments with Crew Pairing and Schedule Optimization.

PubMed

Chung, Sai Ho; Ma, Hoi Lam; Chan, Hing Kai

2017-08-01

This article concerns the assignment of buffer time between two connected flights and the number of reserve crews in crew pairing to mitigate flight disruption due to flight arrival delay. Insufficient crew members for a flight will lead to flight disruptions such as delays or cancellations. In reality, most of these disruption cases are due to arrival delays of the previous flights. To tackle this problem, many research studies have examined the assignment method based on the historical flight arrival delay data of the concerned flights. However, flight arrival delays can be triggered by numerous factors. Accordingly, this article proposes a new forecasting approach using a cascade neural network, which considers a massive amount of historical flight arrival and departure data. The approach also incorporates learning ability so that unknown relationships behind the data can be revealed. Based on the expected flight arrival delay, the buffer time can be determined and a new dynamic reserve crew strategy can then be used to determine the required number of reserve crews. Numerical experiments are carried out based on one year of flight data obtained from 112 airports around the world. The results demonstrate that by predicting the flight departure delay as the input for the prediction of the flight arrival delay, the prediction accuracy can be increased. Moreover, by using the new dynamic reserve crew strategy, the total crew cost can be reduced. This significantly benefits airlines in flight schedule stability and cost saving in the current big data era. © 2016 Society for Risk Analysis.

Jets over Labrador and Quebec: noise effects on human health.

PubMed Central

Rosenberg, J

1991-01-01

OBJECTIVE: To determine whether the noise from low-level flights over Labrador and Quebec is harmful to human health. DATA SOURCE AND SELECTION: Search of MEDLINE for articles on the effect of noise, particularly impulse noise associated with low-level flights, and a search of the references from identified articles. DATA SYNTHESIS: The noise levels from low-level flights could affect hearing acuity. However, the more important consequences appear to be stress-mediated physiologic effects, especially cardiovascular ones, and psychologic distress, particularly in children. Subjective perception of control over the noise has been found to mitigate some physiologic effects. CONCLUSION: There is sufficient evidence to show that the noise from low-level flights is harmful to human health. PMID:2007238

The relationship of prenatal maternal depression or anxiety to maternal caregiving behavior and infant behavior self-regulation during infant heel lance: an ethological time-based study of behavior.

PubMed

Warnock, Fay F; Craig, Kenneth D; Bakeman, Roger; Castral, Thaila; Mirlashari, Jila

2016-09-07

Sensitive and responsive maternal caregiving behavior strengthens infant self-regulatory capacities (HL), but this regulatory role may be diminished in some mothers with second-trimester prenatal exposure to depression and/ or anxiety (MDA). This study examined maternal and infant behavior during infant heel lance (HL) when mothers had or did not have MDA. Ethological methods and micro-analytic approaches capable of distinguishing and comparing time-based patterning in maternal and infant behavior were used to clarify biological mechanisms, such as MDA, that may underlie observed behavior. Aims were to examine group differences in caregiving behavior between mothers with and without MDA 5 min Pre-HL and 5 min Post-H, and relationships between MDA, maternal caregiving behavior and infant pain behavior self-regulation, concurrently. At second trimester, mothers were assessed for symptoms of mild-severe depression or anxiety. Mothers whose scores exceeded predetermined cut-off scores on one or more of the mental health measures were allocated to the MDA-exposure group, those below to the non-MDA-exposure group. Reliable observers, blinded to MDA status and study phases, coded video records of the caregiving behavior of each study mother for the full duration of the 5 min Pre-HL and 5 min Post-HL study phases. Group differences and associations between mean measures of maternal mental health scores, time-based measures of maternal behavior, and time-based measures of infant pain behavior regulation (previously coded) were concurrently analyzed using comparative and correlational statistics. MDA-exposed mothers spent significantly more time not embracing, engaging or responding to infant cues than maternal controls Pre-HL and Post-HL. MDA was associated with atypical maternal caregiving behavior, which in turn was related to atypical infant pain behavior self-regulation during and after the HL. Our findings have implication for practice. We recommend inclusion of mothers with MDA and their infants in interventions that strengthen the early mother-infant interaction and mother's regulatory caregiving role. MDA and maternal caregiving behavior must be considered in future infant pain studies to examine if they confound effectiveness of mother driven caregiving interventions for neonatal pain. We highlight the importance of examining maternal mental health throughout the perinatal and postnatal trajectory, and particularly the newborn period.

Mechanisms underlying the growth inhibitory effects of the cyclo-oxygenase-2 inhibitor celecoxib in human breast cancer cells.

PubMed

Basu, Gargi D; Pathangey, Latha B; Tinder, Teresa L; Gendler, Sandra J; Mukherjee, Pinku

2005-01-01

Inhibitors of cyclo-oxygenase (COX)-2 are being extensively studied as anticancer agents. In the present study we evaluated the mechanisms by which a highly selective COX-2 inhibitor, celecoxib, affects tumor growth of two differentially invasive human breast cancer cell lines. MDA-MB-231 (highly invasive) and MDA-MB-468 (moderately invasive) cell lines were treated with varying concentrations of celecoxib in vitro, and the effects of this agent on cell growth and angiogenesis were monitored by evaluating cell proliferation, apoptosis, cell cycle arrest, and vasculogenic mimicry. The in vitro results of MDA-MB-231 cell line were further confirmed in vivo in a mouse xenograft model. The highly invasive MDA-MB-231 cells express higher levels of COX-2 than do the less invasive MDA-MB-468 cells. Celecoxib treatment inhibited COX-2 activity, indicated by prostaglandin E2 secretion, and caused significant growth arrest in both breast cancer cell lines. In the highly invasive MDA-MB-231 cells, the mechanism of celecoxib-induced growth arrest was by induction of apoptosis, associated with reduced activation of protein kinase B/Akt, and subsequent activation of caspases 3 and 7. In the less invasive MDA-MB-468 cells, growth arrest was a consequence of cell cycle arrest at the G0/G1 checkpoint. Celecoxib-induced growth inhibition was reversed by addition of exogenous prostaglandin E2 in MDA-MB-468 cells but not in MDA-MB-231 cells. Furthermore, MDA-MB-468 cells formed significantly fewer extracellular matrix associated microvascular channels in vitro than did the high COX-2 expressing MDA-MB-231 cells. Celecoxib treatment not only inhibited cell growth and vascular channel formation but also reduced vascular endothelial growth factor levels. The in vitro findings corroborated in vivo data from a mouse xenograft model in which daily administration of celecoxib significantly reduced tumor growth of MDA-MB-231 cells, which was associated with reduced vascularization and increased necrosis in the tumor mass. The disparate molecular mechanisms of celecoxib-induced growth inhibition in human breast cancer cells depends upon the level of COX-2 expression and the invasive potential of the cell lines examined. Data suggest a role for COX-2 not only in the growth of cancer cells but also in activating the angiogenic pathway through regulating levels of vascular endothelial growth factor.

Incorporating Manual and Autonomous Code Generation

NASA Technical Reports Server (NTRS)

McComas, David

1998-01-01

Code can be generated manually or using code-generated software tools, but how do you interpret the two? This article looks at a design methodology that combines object-oriented design with autonomic code generation for attitude control flight software. Recent improvements in space flight computers are allowing software engineers to spend more time engineering the applications software. The application developed was the attitude control flight software for an astronomical satellite called the Microwave Anisotropy Probe (MAP). The MAP flight system is being designed, developed, and integrated at NASA's Goddard Space Flight Center. The MAP controls engineers are using Integrated Systems Inc.'s MATRIXx for their controls analysis. In addition to providing a graphical analysis for an environment, MATRIXx includes an autonomic code generation facility called AutoCode. This article examines the forces that shaped the final design and describes three highlights of the design process: (1) Defining the manual to autonomic code interface; (2) Applying object-oriented design to the manual flight code; (3) Implementing the object-oriented design in C.

Advanced Teleprocessing Systems

DTIC Science & Technology

1983-09-30

Defenae AdTanced Research Projects Agency DAHC1S.C0368 DARPA rw M n*~ MDA 903.77.C-0272 A ^^ ^ 2490 MDA «)W3-C-0064 COMPUTER NETWORK...i -.% W-V."’ * - \\ ATV.VVV" ir*7 ADVANCED TELEPROCESSING SYSTEMS Semi-Annual Technical Report September 30, 1983 Contract Number: MDA 903-82...83 through 30 SEPT 83 6 PERFORMING ORG. REPORT NUMBER 7. AUTHORC«; Leonard Kleinrock 8 CONTRACT OR GRANT NUMBERr«; MDA 903-82-C-0064 9

Atheroprotective immunization with malondialdehyde-modified LDL is hapten specific and dependent on advanced MDA adducts: implications for development of an atheroprotective vaccine1[S

PubMed Central

Gonen, Ayelet; Hansen, Lotte F.; Turner, William W.; Montano, Erica N.; Que, Xuchu; Rafia, Apaїs; Chou, Meng-Yun; Wiesner, Philipp; Tsiantoulas, Dimitrios; Corr, Maripat; VanNieuwenhze, Michael S.; Tsimikas, Sotirios; Binder, Christoph J.; Witztum, Joseph L.; Hartvigsen, Karsten

2014-01-01

Immunization with homologous malondialdehyde (MDA)-modified LDL (MDA-LDL) leads to atheroprotection in experimental models supporting the concept that a vaccine to oxidation-specific epitopes (OSEs) of oxidized LDL could limit atherogenesis. However, modification of human LDL with OSE to use as an immunogen would be impractical for generalized use. Furthermore, when MDA is used to modify LDL, a wide variety of related MDA adducts are formed, both simple and more complex. To define the relevant epitopes that would reproduce the atheroprotective effects of immunization with MDA-LDL, we sought to determine the responsible immunodominant and atheroprotective adducts. We now demonstrate that fluorescent adducts of MDA involving the condensation of two or more MDA molecules with lysine to form malondialdehyde-acetaldehyde (MAA)-type adducts generate immunodominant epitopes that lead to atheroprotective responses. We further demonstrate that a T helper (Th) 2-biased hapten-specific humoral and cellular response is sufficient, and thus, MAA-modified homologous albumin is an equally effective immunogen. We further show that such Th2-biased humoral responses per se are not atheroprotective if they do not target relevant antigens. These data demonstrate the feasibility of development of a small-molecule immunogen that could stimulate MAA-specific immune responses, which could be used to develop a vaccine approach to retard or prevent atherogenesis. PMID:25143462

Measurement of free and bound malondialdehyde in plasma by high-performance liquid chromatography as the 2,4-dinitrophenylhydrazine derivative.

PubMed

Pilz, J; Meineke, I; Gleiter, C H

2000-06-09

We established a method for the detection of free and total (free and bound) malondialdehyde (MDA) in human plasma samples after derivatisation with 2,4-dinitrophenylhydrazine (DNPH). Free MDA was prepared by perchloric acid deproteinisation whereas an alkaline hydrolysation step for 30 min at 60 degrees C was introduced prior to protein precipitation for the determination of total MDA. Derivatisation was accomplished in 10 min at room temperature subsequently chromatographed by HPLC on a reversed-phase 3 microm C(18) column with UV detection (310 nm). The detection limit was 25 pmol/ml for free and 0.3 nmol/ml for total MDA. The recovery of MDA added to different human plasma samples was 93.6% (n=11; RSD 7.1%) for the hydrolysation procedure. In samples from 12 healthy volunteers who underwent a hypoxic treatment (13% O2 for 6 h) we estimated a baseline value of total MDA of 2.16 nmol/ml (SD 0.29) (ambient air) with a significant increase to 2.92 (nmol/ml, SD 0.57; P=0.01) after the end of this physiological oxidative stress challenge. Plasma values of free MDA in these samples were close to our detection limit. The presented technique can easily performed with an isocratic HPLC apparatus and provides highly specific results for MDA as do sophisticated GC-MS methods.

CpA/CpG methylation of CiMDA5 possesses tight association with the resistance against GCRV and negatively regulates mRNA expression in grass carp, Ctenopharyngodon idella.

PubMed

Shang, Xueying; Su, Jianguo; Wan, Quanyuan; Su, Juanjuan

2015-01-01

Melanoma differentiation-associated gene 5 (MDA5) plays a crucial role in recognizing intracellular viral infection, activating the interferon regulatory factor pathways as well as inducing antiviral response. While the antiviral regulatory mechanism of MDA5 remains unclear. In the present study, CiMDA5 (Ctenopharyngodon idella MDA5) against grass carp reovirus (GCRV) would be initially revealed from the perspective of DNA methylation, a pivotal epigenetic modification. Two CpG islands (CGIs) were predicted located in the first exon of CiMDA5, of which the first CpG island was 427 bp in length possessed 29 candidate CpG loci and 34 CpA loci, and the second one was 130 bp in length involving 7 CpG loci as well as 10 CpA loci. By bisulfite sequencing PCR (BSP), the methylation statuses were detected in spleen of 70 individuals divided into resistant/susceptible groups post challenge experiment, and the resistance-association analysis was performed with Chi-square test. Quantitative real-time RT-PCR (qRT-PCR) was carried out to explore the relationship between DNA methylation and gene expression in CiMDA5. Results indicated that the methylation levels of CpA/CpG sites at +200, +202, +204, +207 nt, which consisted of a putative densely methylated element (DME), were significantly higher in the susceptible group than those in the resistant group. Meanwhile, the average transcription of CiMDA5 was down-regulated in the susceptible individuals compared with the resistant individuals. Evidently, the DNA methylation may be the negative modulator of CiMDA5 antiviral expression. Collectively, the methylation levels of CiMDA5 demonstrated the tight association with the resistance against GCRV and the negative-regulated roles in mRNA expression. This study first discovered the resistance-associated gene modulated by DNA methylation in teleost, preliminary revealed the underlying regulatory mechanism of CiMDA5 transcription against GCRV as well as laid a theoretical foundation on molecular nosogenesis of hemorrhagic diseases in C. idella. Copyright © 2014 Elsevier Ltd. All rights reserved.

Population-based coverage survey results following the mass drug administration of azithromycin for the treatment of trachoma in Amhara, Ethiopia.

PubMed

Astale, Tigist; Sata, Eshetu; Zerihun, Mulat; Nute, Andrew W; Stewart, Aisha E P; Gessese, Demelash; Ayenew, Gedefaw; Melak, Berhanu; Chanyalew, Melsew; Tadesse, Zerihun; Callahan, E Kelly; Nash, Scott D

2018-02-01

Trachoma is the leading infectious cause of blindness worldwide. In communities where the district level prevalence of trachomatous inflammation-follicular among children ages 1-9 years is ≥5%, WHO recommends annual mass drug administration (MDA) of antibiotics with the aim of at least 80% coverage. Population-based post-MDA coverage surveys are essential to understand the effectiveness of MDA programs, yet published reports from trachoma programs are rare. In the Amhara region of Ethiopia, a population-based MDA coverage survey was conducted 3 weeks following the 2016 MDA to estimate the zonal prevalence of self-reported drug coverage in all 10 administrative zones. Survey households were selected using a multi-stage cluster random sampling design and all individuals in selected households were presented with a drug sample and asked about taking the drug during the campaign. Zonal estimates were weighted and confidence intervals were calculated using survey procedures. Self-reported drug coverage was then compared with regional reported administrative coverage. Region-wide, 24,248 individuals were enumerated, of which, 20,942 (86.4%) individuals were present. The regional self-reported antibiotic coverage was 76.8% (95%Confidence Interval (CI):69.3-82.9%) in the population overall and 77.4% (95%CI = 65.7-85.9%) among children ages 1-9 years old. Zonal coverage ranged from 67.8% to 90.2%. Five out of 10 zones achieved a coverage >80%. In all zones, the reported administrative coverage was greater than 90% and was considerably higher than self-reported MDA coverage. Main reasons reported for MDA campaign non-attendance included being physically unable to get to MDA site (22.5%), traveling (20.6%), and not knowing about the campaign (21.0%). MDA refusal was low (2.8%) in this population. Although self-reported MDA coverage in Amhara was greater than 80% in some zones, programmatic improvements are warranted throughout Amhara to achieve higher coverage. These results will be used to enhance community mobilization and improve training for MDA distributors and supervisors to improve coverage in future MDAs.

Assessing the feasibility of interrupting the transmission of soil-transmitted helminths through mass drug administration: The DeWorm3 cluster randomized trial protocol

PubMed Central

Ajjampur, Sitara S. Rao; Anderson, Roy M.; Bailey, Robin; Gardiner, Iain; Halliday, Katherine E.; Ibikounle, Moudachirou; Kalua, Khumbo; Kang, Gagandeep; Littlewood, D. Timothy J.; Luty, Adrian J. F.; Means, Arianna Rubin; Oswald, William; Pullan, Rachel L.; Sarkar, Rajiv; Schär, Fabian; Szpiro, Adam; Truscott, James E.; Werkman, Marleen; Yard, Elodie; Walson, Judd L.

2018-01-01

Current control strategies for soil-transmitted helminths (STH) emphasize morbidity control through mass drug administration (MDA) targeting preschool- and school-age children, women of childbearing age and adults in certain high-risk occupations such as agricultural laborers or miners. This strategy is effective at reducing morbidity in those treated but, without massive economic development, it is unlikely it will interrupt transmission. MDA will therefore need to continue indefinitely to maintain benefit. Mathematical models suggest that transmission interruption may be achievable through MDA alone, provided that all age groups are targeted with high coverage. The DeWorm3 Project will test the feasibility of interrupting STH transmission using biannual MDA targeting all age groups. Study sites (population ≥80,000) have been identified in Benin, Malawi and India. Each site will be divided into 40 clusters, to be randomized 1:1 to three years of twice-annual community-wide MDA or standard-of-care MDA, typically annual school-based deworming. Community-wide MDA will be delivered door-to-door, while standard-of-care MDA will be delivered according to national guidelines. The primary outcome is transmission interruption of the STH species present at each site, defined as weighted cluster-level prevalence ≤2% by quantitative polymerase chain reaction (qPCR), 24 months after the final round of MDA. Secondary outcomes include the endline prevalence of STH, overall and by species, and the endline prevalence of STH among children under five as an indicator of incident infections. Secondary analyses will identify cluster-level factors associated with transmission interruption. Prevalence will be assessed using qPCR of stool samples collected from a random sample of cluster residents at baseline, six months after the final round of MDA and 24 months post-MDA. A smaller number of individuals in each cluster will be followed with annual sampling to monitor trends in prevalence and reinfection throughout the trial. Trial registration ClinicalTrials.gov NCT03014167 PMID:29346377

Analysis of the effect on optical equipment caused by solar position in target flight measure

NASA Astrophysics Data System (ADS)

Zhu, Shun-hua; Hu, Hai-bin

2012-11-01

Optical equipment is widely used to measure flight parameters in target flight performance test, but the equipment is sensitive to the sun's rays. In order to avoid the disadvantage of sun's rays directly shines to the optical equipment camera lens when measuring target flight parameters, the angle between observation direction and the line which connects optical equipment camera lens and the sun should be kept at a big range, The calculation method of the solar azimuth and altitude to the optical equipment at any time and at any place on the earth, the equipment observation direction model and the calculating model of angle between observation direction and the line which connects optical equipment camera lens are introduced in this article. Also, the simulation of the effect on optical equipment caused by solar position at different time, different date, different month and different target flight direction is given in this article.

Sprague-Dawley rats display sex-linked differences in the pharmacokinetics of 3,4-methylenedioxymethamphetamine (MDMA) and its metabolite 3,4-methylenedioxyamphetamine (MDA)

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

Fonsart, Julien, E-mail: julien.fonsart@lrb.aphp.f; CNRS, UMR 7157, Paris F-75006; INSERM, U705, Paris F-75006

The use of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) has increased in recent years; it can lead to life-threatening hyperthermia and serotonin syndrome. Human and rodent males appear to be more sensitive to acute toxicity than are females. MDMA is metabolized to five main metabolites by the enzymes CYP1A2, CYP2D and COMT. Little is presently known about sex-dependent differences in the pharmacokinetics of MDMA and its metabolites. We therefore analyzed MDMA disposition in male and female rats by measuring the plasma and urine concentrations of MDMA and its metabolites using a validated LC-MS method. MDA AUC{sub last} and C{sub max} were 1.6- tomore » 1.7-fold higher in males than in females given MDMA (5 mg/kg sc), while HMMA C{sub max} and AUC{sub last} were 3.2- and 3.5-fold higher, respectively. MDMA renal clearance was 1.26-fold higher in males, and that of MDA was 2.2-fold higher. MDMA AUC{sub last} and t{sub 1/2} were 50% higher in females given MDMA (1 mg/kg iv). MDA C{sub max} and AUC{sub last} were 75-82% higher in males, with a 2.8-fold higher metabolic index. Finally, the AUC{sub last} of MDA was 0.73-fold lower in males given 1 mg/kg iv MDA. The volumes of distribution of MDMA and MDA at steady-state were similar in the two sexes. These data strongly suggest that differences in the N-demethylation of MDMA to MDA are major influences on the MDMA and MDA pharmacokinetics in male and female rats. Hence, males are exposed to significantly more toxic MDA, which could explain previously reported sexual dysmorphism in the acute effects and toxicity of MDMA in rats.« less

Widespread Increases in Malondialdehyde Immunoreactivity in Dopamine-Rich and Dopamine-Poor Regions of Rat Brain Following Multiple, High Doses of Methamphetamine

PubMed Central

Horner, Kristen A.; Gilbert, Yamiece E.; Cline, Susan D.

2011-01-01

Treatment with multiple high doses of methamphetamine (METH) can induce oxidative damage, including dopamine (DA)-mediated reactive oxygen species (ROS) formation, which may contribute to the neurotoxic damage of monoamine neurons and long-term depletion of DA in the caudate putamen (CPu) and substantia nigra pars compacta (SNpc). Malondialdehyde (MDA), a product of lipid peroxidation by ROS, is commonly used as a marker of oxidative damage and treatment with multiple high doses of METH increases MDA reactivity in the CPu of humans and experimental animals. Recent data indicate that MDA itself may contribute to the destruction of DA neurons, as MDA causes the accumulation of toxic intermediates of DA metabolism via its chemical modification of the enzymes necessary for the breakdown of DA. However, it has been shown that in human METH abusers there is also increased MDA reactivity in the frontal cortex, which receives relatively fewer DA afferents than the CPu. These data suggest that METH may induce neuronal damage regardless of the regional density of DA or origin of DA input. The goal of the current study was to examine the modification of proteins by MDA in the DA-rich nigrostriatal and mesoaccumbal systems, as well as the less DA-dense cortex and hippocampus following a neurotoxic regimen of METH treatment. Animals were treated with METH (10 mg/kg) every 2 h for 6 h, sacrificed 1 week later, and examined using immunocytochemistry for changes in MDA-adducted proteins. Multiple, high doses of METH significantly increased MDA immunoreactivity (MDA-ir) in the CPu, SNpc, cortex, and hippocampus. Multiple METH administration also increased MDA-ir in the ventral tegmental area and nucleus accumbens. Our data indicate that multiple METH treatment can induce persistent and widespread neuronal damage that may not necessarily be limited to the nigrostriatal DA system. PMID:21602916

Insight into Buffalo (Bubalus bubalis) RIG1 and MDA5 Receptors: A Comparative Study on dsRNA Recognition and In-Vitro Antiviral Response

PubMed Central

Singh, Manvender; Brahma, Biswajit; Maharana, Jitendra; Patra, Mahesh Chandra; Kumar, Sushil; Mishra, Purusottam; Saini, Megha; De, Bidhan Chandra; Mahanty, Sourav; Datta, Tirtha Kumar; De, Sachinandan

2014-01-01

RIG1 and MDA5 have emerged as important intracellular innate pattern recognition receptors that recognize viral RNA and mediate cellular signals controlling Type I interferon (IFN-I) response. Buffalo RIG1 and MDA5 genes were investigated to understand the mechanism of receptor induced antiviral response. Sequence analysis revealed that RIG1 and MDA5 maintain a domain arrangement that is common in mammals. Critical binding site residues of the receptors are evolutionary conserved among mammals. Molecular dynamics simulations suggested that RIG1 and MDA5 follow a similar, if not identical, dsRNA binding pattern that has been previously reported in human. Moreover, binding free energy calculation revealed that MDA5 had a greater affinity towards dsRNA compared to RIG1. Constitutive expressions of RLR genes were ubiquitous in different tissues without being specific to immune organs. Poly I:C stimulation induced elevated expressions of IFN-β and IFN-stimulated genes (ISGs) through interferon regulatory factors (IRFs) mediated pathway in buffalo foetal fibroblast cells. The present study provides crucial insights into the structure and function of RIG1 and MDA5 receptors in buffalo. PMID:24587036

Association between Pre-Transplant Serum Malondialdehyde Levels and Survival One Year after Liver Transplantation for Hepatocellular Carcinoma

PubMed Central

Lorente, Leonardo; Rodriguez, Sergio T.; Sanz, Pablo; Abreu-González, Pedro; Díaz, Dácil; Moreno, Antonia M.; Borja, Elisa; Martín, María M.; Jiménez, Alejandro; Barrera, Manuel A.

2016-01-01

Previous studies have found higher levels of serum malondialdehyde (MDA) in hepatocellular carcinoma (HCC) patients compared to healthy controls and higher MDA concentrations in tumoral tissue of HCC patients than in non-tumoral tissue. However, the association between pre-transplant serum levels of MDA and survival in HCC patients after liver transplantation (LT) has not been described, and the aim of the present study was to determine whether such an association exists. In this observational study we measured serum MDA levels in 127 patients before LT. We found higher pre-LT serum MDA levels in 15 non-surviving than in 112 surviving patients one year after LT (p = 0.02). Exact binary logistic regression analysis revealed that pre-LT serum levels of MDA over 3.37 nmol/mL were associated with mortality after one year of LT (Odds ratio = 5.38; 95% confidence interval (CI) = from 1.580 to infinite; p = 0.007) adjusting for age of the deceased donor. The main finding of our study was that there is an association between serum MDA levels before LT for HCC and 1-year survival after LT. PMID:27058525

Oral fluid and plasma 3,4-methylenedioxymethamphetamine (MDMA) and metabolite correlation after controlled oral MDMA administration.

PubMed

Desrosiers, Nathalie A; Barnes, Allan J; Hartman, Rebecca L; Scheidweiler, Karl B; Kolbrich-Spargo, Erin A; Gorelick, David A; Goodwin, Robert S; Huestis, Marilyn A

2013-05-01

Oral fluid (OF) offers a noninvasive sample collection for drug testing. However, 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) in OF has not been adequately characterized in comparison to plasma. We administered oral low-dose (1.0 mg/kg) and high-dose (1.6 mg/kg) MDMA to 26 participants and collected simultaneous OF and plasma specimens for up to 143 h after dosing. We compared OF/plasma (OF/P) ratios, time of initial detection (t first), maximal concentrations (C max), time of peak concentrations (t max), time of last detection (t last), clearance, and 3,4-methylenedioxyamphetamine (MDA)-to-MDMA ratios over time. For OF MDMA and MDA, C max was higher, t last was later, and clearance was slower compared to plasma. For OF MDA only, t first was later compared to plasma. Median (range) OF/P ratios were 5.6 (0.1-52.3) for MDMA and 3.7 (0.7-24.3) for MDA. OF and plasma concentrations were weakly but significantly correlated (MDMA: R(2) = 0.438, MDA: R(2) = 0.197, p < 0.0001). Median OF/P ratios were significantly higher following high dose administration: MDMA low = 5.2 (0.1-40.4), high = 6.0 (0.4-52.3, p < 0.05); MDA low = 3.3 (0.7-17.1), high = 4.1 (0.9-24.3, p < 0.001). There was a large inter-subject variation in OF/P ratios. The MDA/MDMA ratios in plasma were higher than those in OF (p < 0.001), and the MDA/MDMA ratios significantly increased over time in OF and plasma. The MDMA and MDA concentrations were higher in OF than in plasma. OF and plasma concentrations were correlated, but large inter-subject variability precludes the estimation of plasma concentrations from OF.

Microbial metabolites are associated with a high adherence to a Mediterranean dietary pattern using a 1H-NMR-based untargeted metabolomics approach.

PubMed

Almanza-Aguilera, Enrique; Urpi-Sarda, Mireia; Llorach, Rafael; Vázquez-Fresno, Rosa; Garcia-Aloy, Mar; Carmona, Francesc; Sanchez, Alex; Madrid-Gambin, Francisco; Estruch, Ramon; Corella, Dolores; Andres-Lacueva, Cristina

2017-10-01

The study of biomarkers of dietary patterns including the Mediterranean diet (MedDiet) is scarce and could improve the assessment of these patterns. Moreover, it could provide a better understanding of health benefits of dietary patterns in nutritional epidemiology. We aimed to determine a robust and accurate biomarker associated with a high adherence to a MedDiet pattern that included dietary assessment and its biological effect. In this cross-sectional study, we included 56 and 63 individuals with high (H-MDA) and low (L-MDA) MedDiet adherence categories, respectively, all from the Prevención con Dieta Mediterránea trial. A 1 H-NMR-based untargeted metabolomics approach was applied to urine samples. Multivariate statistical analyses were conducted to determine the metabolite differences between groups. A stepwise logistic regression and receiver operating characteristic curves were used to build and evaluate the prediction model for H-MDA. Thirty-four metabolites were identified as discriminant between H-MDA and L-MDA. The fingerprint associated with H-MDA included higher excretion of proline betaine and phenylacetylglutamine, among others, and decreased amounts of metabolites related to glucose metabolism. Three microbial metabolites - phenylacetylglutamine, p-cresol and 4-hydroxyphenylacetate - were included in the prediction model of H-MDA (95% specificity, 95% sensitivity and 97% area under the curve). The model composed of microbial metabolites was the biomarker that defined high adherence to a Mediterranean dietary pattern. The overall metabolite profiling identified reflects the metabolic modulation produced by H-MDA. The proposed biomarker may be a better tool for assessing and aiding nutritional epidemiology in future associations between H-MDA and the prevention or amelioration of chronic diseases. Copyright © 2017 Elsevier Inc. All rights reserved.

Oral Fluid and Plasma 3,4-Methylenedioxymethamphetamine (MDMA) and Metabolite Correlation after Controlled Oral MDMA Administration

PubMed Central

Desrosiers, Nathalie A.; Barnes, Allan J.; Hartman, Rebecca L.; Scheidweiler, Karl B.; Kolbrich-Spargo, Erin A.; Gorelick, David A.; Goodwin, Robert S.; Huestis, Marilyn A.

2013-01-01

Oral fluid (OF) offers a non-invasive sample collection for drug testing. However, 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) in OF has not been adequately characterized in comparison to plasma. We administered oral low (1.0 mg/kg) and high (1.6 mg/kg) dose MDMA to 26 participants and collected simultaneous OF and plasma specimens for up to 143 h after dosing. We compared OF/plasma (OF/P) ratios, time of initial detection (tfirst), maximal concentrations (Cmax), time of peak concentrations (tmax), time of last detection (tlast), clearance, and 3,4-methylenedioxyamphetamine (MDA) to MDMA ratios over time. For OF MDMA and MDA, Cmax was higher, tlast was later, and clearance was slower compared to plasma. For OF MDA only, tfirst was later compared to plasma. Median (range) OF/P ratios were 5.6 (0.1-52.3) for MDMA and 3.7 (0.7-24.3) for MDA. OF and plasma concentrations were weakly but significantly correlated (MDMA R2= 0.438, MDA R2= 0.197, p<0.0001). Median OF/P ratios were significantly higher following high dose: MDMA low 5.2 (0.1-40.4) and high 6.0 (0.4-52.3) (p<0.05); MDA low 3.3 (0.7-17.1) and high 4.1 (0.9-24.3) (p<0.001). There was large inter-subject variation in OF/P ratios. MDA/MDMA ratios in plasma were higher than those in OF (p<0.001), and MDA/MDMA ratios significantly increased over time in OF and plasma. MDMA and MDA concentrations were higher in OF than in plasma. OF and plasma concentrations were correlated, but large inter-subject variability precludes estimation of plasma concentrations from OF. PMID:23471370

The Mediterranean diet adherence by pregnant women delivering prematurely: association with size at birth and complications of prematurity.

PubMed

Parlapani, Elisavet; Agakidis, Charalampos; Karagiozoglou-Lampoudi, Thomais; Sarafidis, Kosmas; Agakidou, Eleni; Athanasiadis, Apostolos; Diamanti, Elisavet

2017-11-13

The Mediterranean diet (MD) is associated with decreased risk of metabolic syndrome and gestational diabetes due to the anti-inflammatory and antioxidative properties of its components. The aim was to investigate the potential association of MD adherence (MDA) during pregnancy by mothers delivering prematurely, with intrauterine growth as expressed by neonates' anthropometry at birth and complications of prematurity. This is a single-center, prospective, observational cohort study of 82 women who delivered preterm singletons at post conceptional age (PCA) ≤ 34 weeks and their live-born neonates. Maternal and neonatal demographic and clinical data were recorded. All mothers filled in a food frequency questionnaire, and the MDA score was calculated. Based on 50th centile of MD score, participants were classified into high-MDA and low-MDA groups. The low-MDA mothers had significantly higher pregestational BMI and rates of overweight/obesity (odd ratios (OR) 3.5) and gestational hypertension/preeclampsia (OR 3.8). Neonates in the low-MDA group had significantly higher incidence of intrauterine growth restriction (IUGR) (OR 3.3) and lower z-scores of birth weight and BMI. Regarding prematurity-related complications, the low MDA-group was more likely to develop necrotizing enterocolitis, bronchopulmonary dysplasia, and retinopathy of prematurity (OR 3.2, 1.3, and 1.6, respectively), while they were less likely to develop respiratory distress syndrome (OR 0.49), although the differences were not statistically significant. However, adjustment for confounders revealed MDA as a significant independent predictor of hypertension/preeclampsia, IUGR, birth weight z-score, necrotizing enterocolitis, and bronchopulmonary dysplasia. High MDA during pregnancy may favorably affect intrauterine growth and certain acute and chronic complications of prematurity as well as maternal hypertension/preeclampsia.

Low expression of Mda-7/IL-24 and high expression of C-myb in tumour tissues are predictors of poor prognosis for Burkitt lymphoma patients.

PubMed

Ma, Ming; Zhao, Riyang; Yang, Xingxiao; Zhao, Lianmei; Liu, Lihua; Zhang, Cong; Wang, Xuexiao; Shan, Baoen

2018-02-08

Burkitt lymphoma is one of the most common types of haematopoietic malignancy in children and adolescents. Mda-7/IL-24 had been identified as a differentiation inducer of Burkitt lymphoma cells. Previous studies have revealed that knockdown of C-myb can also lead to the terminal differentiation of Burkitt lymphoma cells. The aim of the present study was to investigate the correlation between the expression of Mda-7/IL-24 and C-myb, as well as their prognostic significance, for Burkitt lymphoma patients. The tumour tissues were collected from 59 cases of Burkitt lymphoma patients and detected with Western blotting and immunohistochemistry. The results showed that the expression of Mda-7/IL-24 was lower, whereas the expression of C-myb was higher in Burkitt lymphoma tissues compared to specimens of normal lymph node tissues. Furthermore, C-myb expression was negatively correlated with Mda-7/IL-24 expression at the protein level in Burkitt lymphoma tissues and cell lines. Both the expression of Mda-7/IL-24 and C-myb in Burkitt lymphoma tissues was associated with some clinicopathological parameters, such as clinical stage, infiltration in the bone marrow, Ki67 and overall survival rates. These results indicated that low expression of Mda-7/IL-24 along with high expression of C-myb are predictors for poor prognosis of Burkitt lymphoma patients; this outcome suggests that Mda-7/IL-24 and C-myb might be potential targets for clinical treatment of Burkitt lymphoma. Mda-7/IL-24: melanoma differentiation associated gene7/interleukin 24; FCM: flow cytometry; Ecog: Eastern Cooperative Oncology Group; IPI: International lymphoma prognosis index.

Manned remote work station development article

NASA Technical Reports Server (NTRS)

1978-01-01

The two prime objectives of the Manned Remote Work Station (MRWS) Development Article Study are to first, evaluate the MRWS flight article roles and associated design concepts for fundamental requirements and embody key technology developments into a simulation program; and to provide detail manufacturing drawings and schedules for a simulator development test article. An approach is outlined which establishes flight article requirements based on past studies of Solar Power Satellite, orbital construction support equipments, construction bases and near term shuttle operations. Simulation objectives are established for those technology issues that can best be addressed on a simulator. Concepts for full-scale and sub-scale simulators are then studied to establish an overall approach to studying MRWS requirements. Emphasis then shifts to design and specification of a full-scale development test article.

Amino Acid Requirements for MDA5 and LGP2 Recognition by Paramyxovirus V Proteins: a Single Arginine Distinguishes MDA5 from RIG-I

PubMed Central

Rodriguez, Kenny R.

2013-01-01

Paramyxovirus V proteins bind to MDA5 (melanoma differentiation-associated gene 5) and LGP2 (laboratory of genetics and physiology gene 2) but not RIG-I (retinoic acid-inducible gene I). The results demonstrate MDA5 R806 is essential for inhibition by diverse V proteins. Complementary substitution for the analogous RIG-I L714 confers V protein recognition. The analogous LGP2 R455 is required for recognition by measles V protein, but not other V proteins. These findings indicate that paramyxoviruses use a single amino acid to distinguish MDA5 from RIG-I and have evolved distinct contact sites for LGP2 interference. PMID:23269789

[Clinical and hygienic aspects of occupational neurosensory deafness in civil aviation flight personnel].

PubMed

Kruglikova, N V; Romeiko, V L; Bekeneva, T I; Kharitonova, O I

2015-01-01

The article covers implementation of regulatory and legal concepts in prevention of risk caused by hazardous effects of noise in civil aviation flight personnel. The authors analyzed case histories of civil aviation flight personnel patients examined in occupational diseases clinic, with first diagnosed occupational neurosensory deafness.

Improved Orbiter Waste Collection System Study, Appendix D

NASA Technical Reports Server (NTRS)

1984-01-01

Basic requirements for a space shuttle orbiter waste collection system are established. They are intended to be an aid in the development and procurement of a representative flight test article. Orbiter interface requirements, performance requirements, flight crew operational requirements, flight environmental requirements, and ground operational and environmental requirements are considered.

The Effect of Compliance on the Impact of Mass Drug Administration for Elimination of Lymphatic Filariasis in Egypt

PubMed Central

El-Setouhy, Maged; Abd Elaziz, Khaled M.; Helmy, Hanan; Farid, Hoda A.; Kamal, Hussein A.; Ramzy, Reda M. R.; Shannon, William D.; Weil, Gary J.

2008-01-01

We studied effects of compliance on the impact of mass drug administration (MDA) with diethylcarbamazine and albendazole for lymphatic filariasis (LF) in an Egyptian village. Baseline microfilaremia (mf) and filarial antigenemia rates were 11.5% and 19.0%, respectively. The MDA compliance rates were excellent (> 85%). However, individual compliance was highly variable; 7.4% of those surveyed after five rounds of MDA denied having ever taken the medications and 52.4% reported that they had taken all five doses. The mf and antigenemia rates were 0.2% and 2.7% in those who reported five doses of MDA and 8.3% and 13.8% in those who reported zero doses. There was no significant difference in residual infection rates among those who had taken two or more doses. These results underscore the importance of compliance for LF elimination programs based on MDA and suggest that two ingested doses of MDA are as effective as five doses for reducing filariasis infection rates. PMID:18165524

Measurement by reversed-phase high-performance liquid chromatography of malondialdehyde in normal human urine following derivatisation with 2,4-dinitrophenylhydrazine.

PubMed

Korchazhkina, Olga; Exley, Christopher; Andrew Spencer, Stephen

2003-09-05

A selective and sensitive method based on derivatisation with 2,4-dinitrophenylhydrazine (DNPH) and consecutive HPLC gradient separation is described for the determination of malondialdehyde (MDA) in urine. Preparation of urine samples involved a one-step derivatisation/extraction procedure. Separation was achieved using a Waters SymmetryC(18) column (3.9 x 150 mm) and linear gradient of acetonitrile in water (from 30% to 70% in 30 min). The overall detection limit of the method was 56 nM of MDA in urine. The recovery of MDA was 94.3+/-8.6%. MDA in urine of healthy volunteers, measured using the method of standard additions, was 0.019+/-0.012 microM/mmol creatinine. MDA in the same samples measured using the 2-thiobarbituric acid (TBA) assay was 0.181+/-0.063 microM/mmol creatinine. We demonstrate that the commonly used TBA assay in conjunction with HPLC may overestimate the MDA concentration in human urine by almost 10-fold.

The development and testing of the Lens Antenna Deployment Demonstration (LADD) test article

NASA Technical Reports Server (NTRS)

Pugh, Mark L.; Denton, Robert J., Jr.; Strange, Timothy J.

1993-01-01

The USAF Rome Laboratory and NASA Marshall Space Flight Center, through contract to Grumman Corporation, have developed a space-qualifiable test article for the Strategic Defense Initiative Organization to demonstrate the critical structural and mechanical elements of single-axis roll-out membrane deployment for Space Based Radar (SBR) applications. The Lens Antenna Deployment Demonstration (LADD) test article, originally designed as a shuttle-attached flight experiment, is a large precision space structure which is representative of operational designs for space-fed lens antennas. Although the flight experiment was cancelled due to funding constraints and major revisions in the Strategic Defense System (SDS) architecture, development of this test article was completed in June 1989. To take full advantage of the existence of this unique structure, a series of ground tests are proposed which include static, dynamic, and thermal measurements in a simulated space environment. An equally important objective of these tests is the verification of the analytical tools used to design and develop large precision space structures.

Mechanisms underlying the growth inhibitory effects of the cyclo-oxygenase-2 inhibitor celecoxib in human breast cancer cells

PubMed Central

Basu, Gargi D; Pathangey, Latha B; Tinder, Teresa L; Gendler, Sandra J; Mukherjee, Pinku

2005-01-01

Introduction Inhibitors of cyclo-oxygenase (COX)-2 are being extensively studied as anticancer agents. In the present study we evaluated the mechanisms by which a highly selective COX-2 inhibitor, celecoxib, affects tumor growth of two differentially invasive human breast cancer cell lines. Methods MDA-MB-231 (highly invasive) and MDA-MB-468 (moderately invasive) cell lines were treated with varying concentrations of celecoxib in vitro, and the effects of this agent on cell growth and angiogenesis were monitored by evaluating cell proliferation, apoptosis, cell cycle arrest, and vasculogenic mimicry. The in vitro results of MDA-MB-231 cell line were further confirmed in vivo in a mouse xenograft model. Results The highly invasive MDA-MB-231 cells express higher levels of COX-2 than do the less invasive MDA-MB-468 cells. Celecoxib treatment inhibited COX-2 activity, indicated by prostaglandin E2 secretion, and caused significant growth arrest in both breast cancer cell lines. In the highly invasive MDA-MB-231 cells, the mechanism of celecoxib-induced growth arrest was by induction of apoptosis, associated with reduced activation of protein kinase B/Akt, and subsequent activation of caspases 3 and 7. In the less invasive MDA-MB-468 cells, growth arrest was a consequence of cell cycle arrest at the G0/G1 checkpoint. Celecoxib-induced growth inhibition was reversed by addition of exogenous prostaglandin E2 in MDA-MB-468 cells but not in MDA-MB-231 cells. Furthermore, MDA-MB-468 cells formed significantly fewer extracellular matrix associated microvascular channels in vitro than did the high COX-2 expressing MDA-MB-231 cells. Celecoxib treatment not only inhibited cell growth and vascular channel formation but also reduced vascular endothelial growth factor levels. The in vitro findings corroborated in vivo data from a mouse xenograft model in which daily administration of celecoxib significantly reduced tumor growth of MDA-MB-231 cells, which was associated with reduced vascularization and increased necrosis in the tumor mass. Conclusion The disparate molecular mechanisms of celecoxib-induced growth inhibition in human breast cancer cells depends upon the level of COX-2 expression and the invasive potential of the cell lines examined. Data suggest a role for COX-2 not only in the growth of cancer cells but also in activating the angiogenic pathway through regulating levels of vascular endothelial growth factor. PMID:15987447

75 FR 60090 - Membership of the Performance Review Board

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-29

...: Missile Defense Agency (MDA), DoD. ACTION: Notice. SUMMARY: This notice announces the appointment of the members of the Performance Review Board (PRB) of the Missile Defense Agency (MDA). The publication of PRB... CONTACT: Jovey Martir, MDA SES Program Management, Missile Defense Agency, Arlington, Virginia, (703) 693...

Systematic assessment of the performance of whole-genome amplification for SNP/CNV detection and β-thalassemia genotyping.

PubMed

He, Fei; Zhou, Wanjun; Cai, Ren; Yan, Tizhen; Xu, Xiangmin

2018-04-01

In this study, we aimed to assess the performance of two whole-genome amplification methods, multiple displacement amplification (MDA), and multiple annealing and looping-based amplification cycle (MALBAC), for β-thalassemia genotyping and single-nucleotide polymorphism (SNP)/copy-number variant (CNV) detection using two DNA sequencing assays. We collected peripheral blood, cell lines, and discarded embryos, and carried out MALBAC and MDA on single-cell and five-cell samples. We detected and statistically analyzed differences in the amplification efficiency, positive predictive value, sensitivity, allele dropout (ADO) rate, SNPs, and CV values between the two methods. Through Sanger sequencing at the single-cell and five-cell levels, we showed that both the amplification rate and ADO rate of MDA were better than those using MALBAC, and the sensitivity and positive predictive value obtained from MDA were higher than those from MALBAC for β-thalassemia genotyping. Using next-generation sequencing (NGS) at the single-cell level, we confirmed that MDA has better properties than MALBAC for SNP detection. However, MALBAC was more stable and homogeneous than MDA using low-depth NGS at the single-cell level for CNV detection. We conclude that MALBAC is the better option for CNV detection, while MDA is better suited for SNV detection.

Relevance of plasma malondialdehyde level and severity of portal hypertension in cirrhotic patients.

PubMed

Wang, Sheng-Lan; Zhu, Xin-Yan; Zhang, Dong-Wei; Zhang, Zhao-Jie; Gao, Heng-Jun; Yang, Chang-Qing

2015-01-01

Portal hypertension is one of the death reasons for the liver cirrhosis patients. The oxidative stress is related to the occurrence and development of portal hypertension in cirrhosis. Malondialdehyde (MDA), one of the lipid peroxides, increases substantially in cirrhotic patients. To evaluate the relevance between the MDA level and portal hypertension in cirrhotic patients. 60 liver cirrhotic patients and 30 healthy controls were enrolled. The plasma MDA level and general blood tests including ALT, AST, ALB, total bilirubin, and platelet were measured. All people enrolled accepted endoscopic examination and B-Ultrasound check to evaluate the severity of portal hypertension. The MDA plasma level of cirrhotic patients was significantly higher than the controls (P<0.001) and increased significantly accompanied by the severity of liver fibrosis and portal hypertension (P<0.01). Further, the plasma MDA level of cirrhotic patients was significantly correlated with Child-Pugh classification of cirrhosis (r=0.820, P<0.001), the degree of esophageal varices (r=0.857, P<0.001) and the width of portal vein (r=0.652, P<0.001). The ROC curve analyses showed that the plasma MDA level is a strong predictor of liver cirrhosis and portal hypertension. Plasma MDA level may correlate with the severity of portal hypertension in cirrhotic patients.

The past matters: estimating intrinsic hookworm transmission intensity in areas with past mass drug administration to control lymphatic filariasis.

PubMed

Werkman, Marleen; Truscott, James E; Toor, Jaspreet; Wright, James E; Anderson, Roy M

2017-05-23

Current WHO guidelines for soil-transmitted helminth (STH) control focus on mass drug administration (MDA) targeting preschool-aged (pre-SAC) and school-aged children (SAC), with the goal of eliminating STH as a public health problem amongst children. Recently, attention and funding has turned towards the question whether MDA alone can result in the interruption of transmission for STH. The lymphatic filariasis (LF) elimination programme, have been successful in reaching whole communities. There is the possibility of building upon the infrastructure created for these LF-programmes to enhance the control of STH. Using hookworm as an example, we explore what further MDA coverage might be required to induce interruption of transmission for hookworm in the wake of a successful LF programme. Analyses based on the model of STH transmission and MDA impact predict the effects of previous LF control by MDA over five years, on a defined baseline prevalence of STH in an area with a defined transmission intensity (the basic reproductive number R 0 ). If the LF MDA programme achieved a high coverage (70, 70 and 60% for pre-SAC, SAC and adults, respectively) we expect that in communities with a hookworm prevalence of 15%, after 5 years of LF control, the intrinsic R 0 value in that setting is 2.47. By contrast, if lower LF coverages were achieved (40, 40 and 30% for pre-SAC, SAC and adults, respectively), with the same prevalence of 15% at baseline (after 5 years of LF MDA), the intrinsic hookworm R 0 value is predicted to be 1.67. The intrinsic R 0 value has a large effect on the expected successes of follow-up STH programmes post LF MDA. Consequently, the outcomes of identical programmes may differ between these communities. To design the optimal MDA intervention to eliminate STH infections, it is vital to have information on historical MDA programmes and baseline prevalence to estimate the intrinsic transmission intensity for the defined setting (R 0 ). The baseline prevalence alone is not sufficient to inform policy for the control of STH, post cessation of LF MDA, since this will be highly dependent on the intensity and effectiveness of past programmes and the intrinsic transmission intensity of the dominant STH species in any given setting.

Deployable antenna phase A study

NASA Technical Reports Server (NTRS)

Schultz, J.; Bernstein, J.; Fischer, G.; Jacobson, G.; Kadar, I.; Marshall, R.; Pflugel, G.; Valentine, J.

1979-01-01

Applications for large deployable antennas were re-examined, flight demonstration objectives were defined, the flight article (antenna) was preliminarily designed, and the flight program and ground development program, including the support equipment, were defined for a proposed space transportation system flight experiment to demonstrate a large (50 to 200 meter) deployable antenna system. Tasks described include: (1) performance requirements analysis; (2) system design and definition; (3) orbital operations analysis; and (4) programmatic analysis.

Full Motion Flight Simulator in the Classroom

ERIC Educational Resources Information Center

Christensen, Brad

2005-01-01

Virtual flight can be very entertaining, and computer-based simulators can also be educational, if organized and used correctly. When Berea College decided to find a flight simulator suited to the school's educational goals, the faculty settled on an ANT-18 Link trainer. This article begins with a discussion of Link trainers' history, and then…

Looking Up: Multimedia about Space and Flight.

ERIC Educational Resources Information Center

Walter, Virginia A.

1998-01-01

The best CD-ROMs for young people about space and flight exploit the promise of hypermedia to create informative simulations. This article provides an annotated bibliography of CD-ROMs on astronomy and flight for K-12 students; suggests book and Internet connections; and highlights poetry for astronomers, science fiction, a biography of Charles…

Metabolomics changes in a rat model of obstructive jaundice: mapping to metabolism of amino acids, carbohydrates and lipids as well as oxidative stress.

PubMed

Long, Yue; Dong, Xin; Yuan, Yawei; Huang, Jinqiang; Song, Jiangang; Sun, Yumin; Lu, Zhijie; Yang, Liqun; Yu, Weifeng

2015-07-01

The study examined the global metabolic and some biochemical changes in rats with cholestasis induced by bile duct ligation (BDL). Serum samples were collected in male Wistar rats with BDL (n = 8) and sham surgery (n = 8) at day 3 after surgery for metabolomics analysis using a combination of reversed phase chromatography and hydrophilic interaction chromatography (HILIC) and quadrupole-time-of-flight mass spectrometry (Q-TOF MS). The serum levels of malondialdehyde (MDA), total antioxidative capacity (T-AOC), glutathione (GSH) and glutathione disulfide (GSSG), the activities of superoxide dismutase (SOD) and glutathion peroxidase (GSH-Px) were measured to estimate the oxidative stress state. Key changes after BDL included increased levels of l-phenylalanine, l-glutamate, l-tyrosine, kynurenine, l-lactic acid, LysoPC(c) (14:0), glycine and succinic acid and decreased levels of l-valine, PC(b) (19:0/0:0), taurine, palmitic acid, l-isoleucine and citric acid metabolism products. And treatment with BDL significantly decreased the levels of GSH, T-AOC as well as SOD, GSH-Px activities, and upregulated MDA levels. The changes could be mapped to metabolism of amino acids and lipids, Krebs cycle and glycolysis, as well as increased oxidative stress and decreased antioxidant capability. Our study indicated that BDL induces major changes in the metabolism of all 3 major energy substances, as well as oxidative stress.

Utilization survey of prototype structural test article

NASA Technical Reports Server (NTRS)

Baber, S.; Mcdaniel, H. M.; Berry, M. J.

1974-01-01

A survey was conducted of six aerospace companies and two NASA agencies to determine how prototype structural test articles are used in flight operations. The prototype structures are airframes and similar devices which are used for testing and generally are not flown. The survey indicated the following: (1) prototype test articles are not being discarded after development testing is complete, but are used for other purposes, (2) only two cases of prototypes being refurbished and flown were identified, (3) protective devices and inspection techniques are available to prevent or minimize test article damage, (4) substitute programs from design verification are availabel in lieu of using prototype structural articles, and (5) there is a trend away from dedicated test articles. Four options based on these study results were identified to reduce test and hardware costs without compromising reliability of the flight program.

Knowledge sifters in MDA technologies

NASA Astrophysics Data System (ADS)

Kravchenko, Yuri; Kursitys, Ilona; Bova, Victoria

2018-05-01

The article considers a new approach to efficient management of information processes on the basis of object models. With the help of special design tools, a generic and application-independent application model is created, and then the program is implemented in a specific development environment. At the same time, the development process is completely based on a model that must contain all the information necessary for programming. The presence of a detailed model provides the automatic creation of typical parts of the application, the development of which is amenable to automation.

Chemoprevention gene therapy (CGT) of pancreatic cancer using perillyl alcohol and a novel chimeric serotype cancer terminator virus.

PubMed

Sarkar, S; Azab, B; Quinn, B A; Shen, X; Dent, P; Klibanov, A L; Emdad, L; Das, S K; Sarkar, D; Fisher, P B

2014-01-01

Conditionally replication competent adenoviruses (Ads) that selectively replicate in cancer cells and simultaneously express a therapeutic cytokine, such as melanoma differentiation associated gene- 7/Interleukin-24 (mda-7/IL-24), a Cancer Terminator Virus (CTV-M7), hold potential for treating human cancers. To enhance the efficacy of the CTV-M7, we generated a chimeric Ad.5 and Ad.3 modified fiber bipartite CTV (Ad.5/3-CTV-M7) that can infect tumor cells in a Coxsackie Adenovirus receptor (CAR) independent manner, while retaining high infectivity in cancer cells containing high CAR. Although mda-7/IL-24 displays broad-spectrum anticancer properties, pancreatic ductal adenocarcinoma (PDAC) cells display an intrinsic resistance to mda-7/IL-24-mediated killing due to an mda-7/IL-24 mRNA translational block. However, using a chemoprevention gene therapy (CGT) approach with perillyl alcohol (POH) and a replication incompetent Ad to deliver mda-7/IL-24 (Ad.mda-7) there is enhanced conversion of mda-7/IL-24 mRNA into protein resulting in pancreatic cancer cell death in vitro and in vivo in nude mice containing human PDAC xenografts. This combination synergistically induces mda-7/IL-24-mediated cancer-specific apoptosis by inhibiting anti-apoptotic Bcl-xL and Bcl-2 protein expression and inducing an endoplasmic reticulum (ER) stress response through induction of BiP/GRP-78, which is most evident in chimeric-modified non-replicating Ad.5/3- mda-7- and CTV-M7-infected PDAC cells. Moreover, Ad.5/3-CTV-M7 in combination with POH sensitizes therapy-resistant MIA PaCa-2 cell lines over-expressing either Bcl-2 or Bcl-xL to mda-7/IL-24-mediated apoptosis. Ad.5/3-CTV-M7 plus POH also exerts a significant antitumor 'bystander' effect in vivo suppressing both primary and distant site tumor growth, confirming therapeutic utility of Ad.5/3-CTV-M7 plus POH in PDAC treatment, where all other current treatment strategies in clinical settings show minimal efficacy.

Clinical Utility of an Enzyme-Linked Immunosorbent Assay for Detecting Anti-Melanoma Differentiation-Associated Gene 5 Autoantibodies

PubMed Central

Sato, Shinji; Murakami, Akihiro; Kuwajima, Akiko; Takehara, Kazuhiko; Mimori, Tsuneyo; Kawakami, Atsushi; Mishima, Michiaki; Suda, Takafumi; Seishima, Mariko; Fujimoto, Manabu; Kuwana, Masataka

2016-01-01

Objective Autoantibodies to melanoma differentiation-associated gene 5 (MDA5) are specifically expressed in patients with dermatomyositis (DM) and are associated with a subset of DM patients with rapidly progressive interstitial lung disease (RP-ILD). Here, we examined the clinical utility of a newly developed enzyme-linked immunosorbent assay (ELISA) system for detecting these antibodies. Methods Here we developed an improved ELISA for detecting anti-MDA5 antibodies. We then performed a multicenter clinical study involving 8 medical centers and enrolled 242 adult patients with polymyositis (PM)/DM, 190 with non-PM/DM connective tissue disease (CTD), 154 with idiopathic interstitial pneumonia (IIP), and 123 healthy controls. Anti-MDA5 antibodies in the patients’ serum samples were quantified using our newly developed ELISA, and the results were compared to those obtained using the gold-standard immunoprecipitation (IP) assay. In addition, correlations between the ELISA-quantified anti-MDA5 antibodies and clinical characteristics were evaluated. Results In patients with PM/DM, the anti-MDA5 antibody measurements obtained from the ELISA and IP assay were highly concordant; the ELISA exhibited an analytical sensitivity of 98.2%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 99.5% (compared to the IP assay). Anti-MDA5 antibodies were detected in 22.7% of the DM patients, but not in any of the patients with PM, non-PM/DM CTD, or IIP. Clinically amyopathic DM, RP-ILD, arthritis, and fever were more prevalent in DM patients who were anti-MDA5 antibody-positive than in those who were antibody-negative (P ≤ 0.0002 for all comparisons). In addition, anti-MDA5 antibody-positive patients with RP-ILD exhibited higher antibody levels than those without RP-ILD (P = 0.006). Conclusion Our newly developed ELISA can detect anti-MDA5 antibodies as efficiently as the gold standard IP assay and has the potential to facilitate the routine clinical measurement of anti-MDA5 antibodies in patients who suspected to have DM. PMID:27115353

Clinical Utility of an Enzyme-Linked Immunosorbent Assay for Detecting Anti-Melanoma Differentiation-Associated Gene 5 Autoantibodies.

PubMed

Sato, Shinji; Murakami, Akihiro; Kuwajima, Akiko; Takehara, Kazuhiko; Mimori, Tsuneyo; Kawakami, Atsushi; Mishima, Michiaki; Suda, Takafumi; Seishima, Mariko; Fujimoto, Manabu; Kuwana, Masataka

2016-01-01

Autoantibodies to melanoma differentiation-associated gene 5 (MDA5) are specifically expressed in patients with dermatomyositis (DM) and are associated with a subset of DM patients with rapidly progressive interstitial lung disease (RP-ILD). Here, we examined the clinical utility of a newly developed enzyme-linked immunosorbent assay (ELISA) system for detecting these antibodies. Here we developed an improved ELISA for detecting anti-MDA5 antibodies. We then performed a multicenter clinical study involving 8 medical centers and enrolled 242 adult patients with polymyositis (PM)/DM, 190 with non-PM/DM connective tissue disease (CTD), 154 with idiopathic interstitial pneumonia (IIP), and 123 healthy controls. Anti-MDA5 antibodies in the patients' serum samples were quantified using our newly developed ELISA, and the results were compared to those obtained using the gold-standard immunoprecipitation (IP) assay. In addition, correlations between the ELISA-quantified anti-MDA5 antibodies and clinical characteristics were evaluated. In patients with PM/DM, the anti-MDA5 antibody measurements obtained from the ELISA and IP assay were highly concordant; the ELISA exhibited an analytical sensitivity of 98.2%, specificity of 100%, positive predictive value of 100%, and negative predictive value of 99.5% (compared to the IP assay). Anti-MDA5 antibodies were detected in 22.7% of the DM patients, but not in any of the patients with PM, non-PM/DM CTD, or IIP. Clinically amyopathic DM, RP-ILD, arthritis, and fever were more prevalent in DM patients who were anti-MDA5 antibody-positive than in those who were antibody-negative (P ≤ 0.0002 for all comparisons). In addition, anti-MDA5 antibody-positive patients with RP-ILD exhibited higher antibody levels than those without RP-ILD (P = 0.006). Our newly developed ELISA can detect anti-MDA5 antibodies as efficiently as the gold standard IP assay and has the potential to facilitate the routine clinical measurement of anti-MDA5 antibodies in patients who suspected to have DM.

Comparison of community-wide, integrated mass drug administration strategies for schistosomiasis and soil-transmitted helminthiasis: a cost-effectiveness modelling study.

PubMed

Lo, Nathan C; Bogoch, Isaac I; Blackburn, Brian G; Raso, Giovanna; N'Goran, Eliézer K; Coulibaly, Jean T; Becker, Sören L; Abrams, Howard B; Utzinger, Jürg; Andrews, Jason R

2015-10-01

More than 1·5 billion people are affected by schistosomiasis or soil-transmitted helminthiasis. WHO's recommendations for mass drug administration (MDA) against these parasitic infections emphasise treatment of school-aged children, using separate treatment guidelines for these two helminthiases groups. We aimed to evaluate the cost-effectiveness of expanding integrated MDA to the entire community in four settings in Côte d'Ivoire. We extended previously published, dynamic, age-structured models of helminthiases transmission to simulate costs and disability averted with integrated MDA (of praziquantel and albendazole) for schistosomiasis and soil-transmitted helminthiasis. We calibrated the model to data for prevalence and intensity of species-specific helminth infection from surveys undertaken in four communities in Côte d'Ivoire between March, 1997, and September, 2010. We simulated a 15-year treatment programme with 75% coverage in only school-aged children; school-aged children and preschool-aged children; adults; and the entire community. Treatment costs were estimated at US$0·74 for school-aged children and $1·74 for preschool-aged children and adults. The incremental cost-effectiveness ratio (ICER) was calculated in 2014 US dollars per disability-adjusted life-year (DALY) averted. Expanded community-wide treatment was highly cost effective compared with treatment of only school-aged children (ICER $167 per DALY averted) and WHO guidelines (ICER $127 per DALY averted), and remained highly cost effective even if treatment costs for preschool-aged children and adults were ten times greater than those for school-aged children. Community-wide treatment remained highly cost effective even when elimination of helminth infections was not achieved. These findings were robust across the four diverse communities in Côte d'Ivoire, only one of which would have received annual MDA for both schistosomiasis and soil-transmitted helminthiasis under the latest WHO guidelines. Treatment every 6 months was also highly cost effective in three out of four communities. Integrated, community-wide MDA programmes for schistosomiasis and soil-transmitted helminthiasis can be highly cost effective, even in communities with low disease burden in any helminth group. These results support an urgent need to re-evaluate current global guidelines for helminthiases control programmes to include community-wide treatment, increased treatment frequency, and consideration for lowered prevalence thresholds for integrated treatment. Stanford University Medical Scholars Programme, Mount Sinai Hospital-University Health Network AMO Innovation Fund. Copyright © 2015 Lo et al. Open Access article distributed under the terms of CC BY. Published by Elsevier Ltd.. All rights reserved.

In-flight medical incapacitation and impairment of airline pilots.

PubMed

DeJohn, Charles A; Wolbrink, Alex M; Larcher, Julie G

2006-10-01

Medical incapacitation in the cockpit is rare, although it is a concern that has been the subject of several investigations over the years. With recent heightened interest in this problem, it seemed worthwhile to review all relevant scientific literature on the topic. Medline, PsychLit, the Aerospace Database, and other online databases were searched for studies of pilot in-flight medical incapacitation and impairment. The search revealed 13 articles during the years from 1968 to 2000. The studies represented several different approaches and were divided into five categories as follows: in-flight medical events, career termination, simulator data, questionnaires, and epidemiological analysis. The articles based on in-flight medical events showed that the leading causes of those episodes were myocardial infarctions, cardiac arrhythmias, and epileptic seizures. Few of the other types of studies used data from actual in-flight medical occurrences, instead relying on indirect measures such as career termination due to permanent medical grounding, loss of licensure insurance, or general epidemiological data to estimate the frequency of in-flight medical events. The reviewed studies provided only limited information on the frequency and categories of in-flight medical events and did not include incapacitation rates, making meaningful comparison between studies difficult. Future research needs to be based on actual in-flight medical events, and should be normalized to a useful denominator, such as flight time, to allow for meaningful comparison between studies.

In Vivo Ligands of MDA5 and RIG-I in Measles Virus-Infected Cells

PubMed Central

Hembach, Katharina; Baum, Alina; García-Sastre, Adolfo; Söding, Johannes; Conzelmann, Karl-Klaus

2014-01-01

RIG-I-like receptors (RLRs: RIG-I, MDA5 and LGP2) play a major role in the innate immune response against viral infections and detect patterns on viral RNA molecules that are typically absent from host RNA. Upon RNA binding, RLRs trigger a complex downstream signaling cascade resulting in the expression of type I interferons and proinflammatory cytokines. In the past decade extensive efforts were made to elucidate the nature of putative RLR ligands. In vitro and transfection studies identified 5′-triphosphate containing blunt-ended double-strand RNAs as potent RIG-I inducers and these findings were confirmed by next-generation sequencing of RIG-I associated RNAs from virus-infected cells. The nature of RNA ligands of MDA5 is less clear. Several studies suggest that double-stranded RNAs are the preferred agonists for the protein. However, the exact nature of physiological MDA5 ligands from virus-infected cells needs to be elucidated. In this work, we combine a crosslinking technique with next-generation sequencing in order to shed light on MDA5-associated RNAs from human cells infected with measles virus. Our findings suggest that RIG-I and MDA5 associate with AU-rich RNA species originating from the mRNA of the measles virus L gene. Corresponding sequences are poorer activators of ATP-hydrolysis by MDA5 in vitro, suggesting that they result in more stable MDA5 filaments. These data provide a possible model of how AU-rich sequences could activate type I interferon signaling. PMID:24743923

Sensitization and cross-reactivity patterns of contact allergy to diisocyanates and corresponding amines: investigation of diphenylmethane-4,4'-diisocyanate, diphenylmethane-4,4'-diamine, dicyclohexylmethane-4,4'-diisocyanate, and dicylohexylmethane-4,4'-diamine.

PubMed

Hamada, Haneen; Bruze, Magnus; Zimerson, Erik; Isaksson, Marléne; Engfeldt, Malin

2017-10-01

Isocyanates are used in polyurethane production. Dermal exposure to isocyanates can induce contact allergy. The most common isocyanate is diphenylmethane diisocyanate used for industrial purposes. The isomer diphenylmethane-4,4'-diisocyanate (4,4'-MDI) is used in patch testing. Diphenylmethane-4,4'-diamine (4,4'-MDA) is its corresponding amine. Concurrent reactions to 4,4'-MDI and 4,4'-MDA have been reported, as have concurrent reactions to 4,4'-MDI and dicyclohexylmethane-4,4'-diisocyanate (4,4'-DMDI). To investigate the sensitization capacities and the cross-reactivity of 4,4'-MDI, 4,4'-MDA, 4,4'-DMDI, and dicyclohexylmethane-4,4'-diamine (4,4'-DMDA). The guinea-pig maximization test (GPMT) was used. The GPMT showed sensitizing capacities for all investigated substances: 4,4'-MDI, 4,4'-MDA, 4,4'-DMDI, and 4,4'-DMDA (all p < 0.001). 4,4'-MDI-sensitized animals showed cross-reactivity to 4,4'-MDA (p < 0.001) and 4,4'-DMDI (all p < 0.05). 4,4'-MDA-sensitized animals showed cross-reactivity to 4,4'-DMDA (p = 0.008). All of the investigated substances were shown to be strong sensitizers. Animals sensitized to 4,4'-MDI showed cross-reactivity to 4,4'-MDA and 4,4'-DMDI, supporting previous findings in the literature. The aromatic amine 4,4'-MDA showed cross-reactivity to the aliphatic amine 4,4'-DMDA. © 2017 The Authors. Contact Dermatitis published by John Wiley & Sons Ltd.

Proapoptotic signaling induced by RIG-I and MDA-5 results in type I interferon–independent apoptosis in human melanoma cells

PubMed Central

Besch, Robert; Poeck, Hendrik; Hohenauer, Tobias; Senft, Daniela; Häcker, Georg; Berking, Carola; Hornung, Veit; Endres, Stefan; Ruzicka, Thomas; Rothenfusser, Simon; Hartmann, Gunther

2009-01-01

The retinoic acid–inducible gene I (RIG-I) and melanoma differentiation–associated antigen 5 (MDA-5) helicases sense viral RNA in infected cells and initiate antiviral responses such as the production of type I IFNs. Here we have shown that RIG-I and MDA-5 also initiate a proapoptotic signaling pathway that is independent of type I IFNs. In human melanoma cells, this signaling pathway required the mitochondrial adapter Cardif (also known as IPS-1) and induced the proapoptotic BH3-only proteins Puma and Noxa. RIG-I– and MDA-5–initiated apoptosis required Noxa but was independent of the tumor suppressor p53. Triggering this pathway led to efficient activation of mitochondrial apoptosis, requiring caspase-9 and Apaf-1. Surprisingly, this proapoptotic signaling pathway was also active in nonmalignant cells, but these cells were much less sensitive to apoptosis than melanoma cells. Endogenous Bcl-xL rescued nonmalignant, but not melanoma, cells from RIG-I– and MDA-5–mediated apoptosis. In addition, we confirmed the results of the in vitro studies, demonstrating that RIG-I and MDA-5 ligands both reduced human tumor lung metastasis in immunodeficient NOD/SCID mice. These results identify an IFN-independent antiviral signaling pathway initiated by RIG-I and MDA-5 that activates proapoptotic signaling and, unless blocked by Bcl-xL, results in apoptosis. Due to their immunostimulatory and proapoptotic activity, RIG-I and MDA-5 ligands have therapeutic potential due to their ability to overcome the characteristic resistance of melanoma cells to apoptosis. PMID:19620789

Preimplantation genetic diagnosis for Duchenne muscular dystrophy by multiple displacement amplification.

PubMed

Ren, Zi; Zeng, Hai-tao; Xu, Yan-wen; Zhuang, Guang-lun; Deng, Jie; Zhang, Cheng; Zhou, Can-quan

2009-02-01

To evaluate the use of multiple displacement amplification (MDA) in preimplantation genetic diagnosis (PGD) for female carriers with Duchenne muscular dystrophy (DMD). MDA was used to amplify a whole genome of single cells. Following the setup on single cells, the test was applied in two clinical cases of PGD. One mutant exon, six short tandem repeats (STR) markers within the dystrophin gene, and amelogenin were incorporated into singleplex polymerase chain reaction (PCR) assays on MDA products of single blastomeres. Center for reproductive medicine in First Affiliated Hospital, Sun Yat-sen University, China. Two female carriers with a duplication of exons 3-11 and a deletion of exons 47-50, respectively. The MDA of single cells and fluorescent PCR assays for PGD. The ability to analyze single blastomeres for DMD using MDA. The protocol setup previously allowed for the accurate diagnosis of each embryo. Two clinical cases resulted in a healthy girl, which was the first successful clinical application of MDA in PGD for DMD. We suggest that this protocol is reliable to increase the accuracy of the PGD for DMD.

Assembly Test Article (ATA)

NASA Technical Reports Server (NTRS)

Ricks, Glen A.

1988-01-01

The assembly test article (ATA) consisted of two live loaded redesigned solid rocket motor (RSRM) segments which were assembled and disassembled to simulate the actual flight segment stacking process. The test assembly joint was flight RSRM design, which included the J-joint insulation design and metal capture feature. The ATA test was performed mid-November through 24 December 1987, at Kennedy Space Center (KSC), Florida. The purpose of the test was: certification that vertical RSRM segment mating and separation could be accomplished without any damage; verification and modification of the procedures in the segment stacking/destacking documents; and certification of various GSE to be used for flight assembly and inspection. The RSRM vertical segment assembly/disassembly is possible without any damage to the insulation, metal parts, or seals. The insulation J-joint contact area was very close to the predicted values. Numerous deviations and changes to the planning documents were made to ensure the flight segments are effectively and correctly stacked. Various GSE were also certified for use on flight segments, and are discussed in detail.

Mass Spectrometric Evidence of Malonaldehyde and 4-Hydroxynonenal Adductions to Radical-Scavenging Soy Peptides

PubMed Central

Zhao, Jing; Chen, Jing; Zhu, Haining; Xiong, Youling L.

2012-01-01

Antioxidative peptides in food systems are potential targets of lipid oxidation-generated reactive aldehydes, such as malonaldehyde (MDA) and 4-hydroxynonenal (HNE). In this study, covalent modifications on radical-scavenging peptides prepared from soy protein hydrolysate by MDA and HNE were characterized by liquid chromatography–electrospray ionization-mass spectrometry (LC-ESI-MS/MS). MS/MS analyses detected the formation of Schiff base type adducts of MDA on the side chain groups of lysine, histidine, arginine, glutamine, and asparagine residues as well as the N-termini of peptides. MDA also formed a fluorescent product with lysine residues. HNE adducted on lysine residues through Schiff base formation and on histidine, arginine, glutamine, and asparagine residues mainly through Michael addition. In spite of the extensive MDA modification, peptide cross-linking by this potential mechanism was undetectable. PMID:22946674

Quantification of malondialdehyde and 4-hydroxynonenal adducts to lysine residues in native and oxidized human low-density lipoprotein.

PubMed Central

Requena, J R; Fu, M X; Ahmed, M U; Jenkins, A J; Lyons, T J; Baynes, J W; Thorpe, S R

1997-01-01

Malondialdehyde (MDA) and 4-hydroxynonenal (HNE) are major end-products of oxidation of polyunsaturated fatty acids, and are frequently measured as indicators of lipid peroxidation and oxidative stress in vivo. MDA forms Schiff-base adducts with lysine residues and cross-links proteins in vitro; HNE also reacts with lysines, primarily via a Michael addition reaction. We have developed methods using NaBH4 reduction to stabilize these adducts to conditions used for acid hydrolysis of protein, and have prepared reduced forms of lysine-MDA [3-(N epsilon-lysino)propan-1-ol (LM)], the lysine-MDA-lysine iminopropene cross-link [1,3-di(N epsilon-lysino)propane (LML)] and lysine-HNE [3-(N epsilon-lysino)-4-hydroxynonan-l-ol (LHNE)]. Gas chromatography/MS assays have been developed for quantification of the reduced compounds in protein. RNase incubated with MDA or HNE was used as a model for quantification of the adducts by gas chromatography/MS. There was excellent agreement between measurement of MDA bound to RNase as LM and LML, and as thiobarbituric acid-MDA adducts measured by HPLC; these adducts accounted for 70-80% of total lysine loss during the reaction with MDA. LM and LML (0.002-0.12 mmol/ mol of lysine) were also found in freshly isolated low-density lipoprotein (LDL) from healthy subjects. LHNE was measured in RNase treated with HNE, but was not detectable in native LDL. LM, LML and LHNE increased in concert with the formation of conjugated dienes during the copper-catalysed oxidation of LDL, but accounted for modification of < 1% of lysine residues in oxidized LDL. These results are the first report of direct chemical measurement of MDA and HNE adducts to lysine residues in LDL. LM, LML and LHNE should be useful as biomarkers of lipid peroxidative modification of protein and of oxidative stress in vitro and in vivo. PMID:9078279

Activation of β-catenin signaling in androgen receptor-negative prostate cancer cells.

PubMed

Wan, Xinhai; Liu, Jie; Lu, Jing-Fang; Tzelepi, Vassiliki; Yang, Jun; Starbuck, Michael W; Diao, Lixia; Wang, Jing; Efstathiou, Eleni; Vazquez, Elba S; Troncoso, Patricia; Maity, Sankar N; Navone, Nora M

2012-02-01

To study Wnt/β-catenin in castrate-resistant prostate cancer (CRPC) and understand its function independently of the β-catenin-androgen receptor (AR) interaction. We carried out β-catenin immunocytochemical analysis, evaluated TOP-flash reporter activity (a reporter of β-catenin-mediated transcription), and sequenced the β-catenin gene in MDA prostate cancer 118a, MDA prostate cancer 118b, MDA prostate cancer 2b, and PC-3 prostate cancer cells. We knocked down β-catenin in AR-negative MDA prostate cancer 118b cells and carried out comparative gene-array analysis. We also immunohistochemically analyzed β-catenin and AR in 27 bone metastases of human CRPCs. β-Catenin nuclear accumulation and TOP-flash reporter activity were high in MDA prostate cancer 118b but not in MDA prostate cancer 2b or PC-3 cells. MDA prostate cancer 118a and MDA prostate cancer 118b cells carry a mutated β-catenin at codon 32 (D32G). Ten genes were expressed differently (false discovery rate, 0.05) in MDA prostate cancer 118b cells with downregulated β-catenin. One such gene, hyaluronan synthase 2 (HAS2), synthesizes hyaluronan, a core component of the extracellular matrix. We confirmed HAS2 upregulation in PC-3 cells transfected with D32G-mutant β-catenin. Finally, we found nuclear localization of β-catenin in 10 of 27 human tissue specimens; this localization was inversely associated with AR expression (P = 0.056, Fisher's exact test), suggesting that reduced AR expression enables Wnt/β-catenin signaling. We identified a previously unknown downstream target of β-catenin, HAS2, in prostate cancer, and found that high β-catenin nuclear localization and low or no AR expression may define a subpopulation of men with bone metastatic prostate cancer. These findings may guide physicians in managing these patients.

Investigation into Hybrid Rockets and Other Cost-Effective Propulsion System Options for Small Satellites

DTIC Science & Technology

1996-05-01

8-7 COMPLETE TEXT OF THESIS ROCKET PROPULSION FUNDEMENTALS EXPERIMENTAL DATA (MICROSOFT EXCEL FILES) 4 ANALYSIS WORKSHEETS (MATHSOFT MATHCAD FILES...up and running. At ~413,000, this represents a very small investment considering it encompasses the entire program. Similar programs run at... investment would be -needed along with over two man-years of effort. However, this is for the first flight article. Subsequent flight articles of identical

Methyl malondialdehyde is not suitable as an internal standard for malondialdehyde detection in urine after derivatisation with 2,4-dinitrophenylhydrazine.

PubMed

Korchazhkina, Olga; Yang, Ying

2004-07-05

A previously described method of measurement of malondialdehyde (MDA) in human urine after derivatisation with 2,4-dinitrophenylhydrazine (DNPH) was tested for a possibility of using methyl malondialdehyde (MeMDA) as an internal standard. Despite structural similarity, those compounds were found to produce different yields of derivatisation under the same conditions depending on urine matrix. We conclude, that MeMDA is not suitable as an internal standard for the measurement of MDA in urine under previously reported conditions when DNPH is used as a deriviatising agent.

Technical publications of the NASA Wallops Flight Facility, 1980 through 1983

NASA Technical Reports Server (NTRS)

Foster, J. N.

1984-01-01

This bibliography lists the publications sponsored by the NASA Wallops Flight Center/NASA Goddard Space Flight Center, Wallops Flight Facility during the period 1980 through 1983. The compilation contains citations listed by type of publication; i.e., NASA formal report, NASA contractor report, journal article, or presentation; by contract/grant number; and by accession number. Oceanography, astrophysics, artificial satellites, fluid mechanics, and sea ice are among the topics covered.

Ionizing Radiation Enhances Adenoviral Vector Expressing mda-7/IL-24-mediated Apoptosis in Human Ovarian Cancer

PubMed Central

EMDAD, LUNI; SARKAR, DEVANAND; LEBEDEVA, IRINA V.; SU, ZAO-ZHONG; GUPTA, PANKAJ; MAHASRESHTI, PARAMESHWAR J.; DENT, PAUL; CURIEL, DAVID T.; FISHER, PAUL B.

2007-01-01

Ovarian cancer is the fifth most common cause of cancer-related death in women. Current interventional approaches, including debulking surgery, chemotherapy, and/or radiation have proven minimally effective in preventing the recurrence and/or mortality associated with this malignancy. Subtraction hybridization applied to terminally differentiating human melanoma cells identified melanoma differentiation associated gene-7/interleukin-24 (mda-7/IL-24), whose unique properties include the ability to selectively induce growth suppression, apoptosis, and radiosensitization in diverse cancer cells, without causing any harmful effects in normal cells. Previously, it has been shown that adenovirus-mediated mda-7/IL-24 therapy (Ad.mda-7) induces apoptosis in ovarian cancer cells, however, the apoptosis induction was relatively low. We now document that apoptosis can be enhanced by treating ovarian cancer cells with ionizing radiation (IR) in combination with Ad.mda-7. Additionally, we demonstrate that mda-7/IL-24 gene delivery, under the control of a minimal promoter region of progression elevated gene-3 (PEG-3), which functions selectively in diverse cancer cells with minimal activity in normal cells, displays a selective radiosensitization effect in ovarian cancer cells. The present studies support the use of IR in combination with mda-7/IL-24 as a means of augmenting the therapeutic benefit of this gene in ovarian cancer, particularly in the context of tumors displaying resistance to radiation therapy. PMID:16646087

Chromobacterium haemolyticum sp. nov., a strongly haemolytic species.

PubMed

Han, Xiang Y; Han, Faye S; Segal, Jonathan

2008-06-01

A Gram-negative bacterium, strain MDA0585(T), isolated from a sputum culture, was characterized by a polyphasic approach. The 16S rRNA gene and a conserved portion of the DNA gyrase A gene were sequenced and analysed phylogenetically. Strain MDA0585(T) showed the closest relationships with Chromobacterium violaceum ATCC 12472(T) and Chromobacterium subtsugae PRAA4-1(T) (96.1 % and 96.3 % 16S rRNA gene sequence similarity, respectively). The cellular fatty acids of strain MDA0585(T) consisted mainly of C(16 : 0), C(16 : 1)omega7c and C(16 : 1)omega6c (summed feature 3) and C(18 : 1)omega7c and C(18 : 1)omega6c (summed feature 8), a profile that was similar to, but distinguishable from, those of C. violaceum ATCC 12472(T) and C. subtsugae PRAA4-1(T). In culture, strain MDA0585(T) differed from C. violaceum and C. subtsugae in several ways: lack of violet pigmentation, the ability to haemolyse sheep blood, differences in several biochemical reactions and higher resistance to antibiotics. The culture supernatant of strain MDA0585(T) also caused remarkable haemolysis of human erythrocytes. These results suggest that strain MDA0585(T) represents a novel species within the genus Chromobacterium, for which the name Chromobacterium haemolyticum sp. nov. is proposed. The type strain is MDA0585(T) (=CCUG 53230(T)=JCM 14163(T)=DSM 19808(T)).

Controlled formation of emulsion gels stabilized by salted myofibrillar protein under malondialdehyde (MDA)-induced oxidative stress.

PubMed

Zhou, Feibai; Sun, Weizheng; Zhao, Mouming

2015-04-15

This study presented the cold-set gelation of emulsions stabilized by salted myofibrillar protein (MP) under oxidative stress originated from malondialdehyde (MDA). Gel properties were compared over a range of MDA/NaCl concentrations including gel viscoelastic properties, strength, water-holding capacity (WHC), amount of protein entrapped, and microstructure. The oxidative stability of emulsion gels as indicated by lipid hydroperoxide was further determined and compared. Results indicated that emulsion stabilized by MP at swollen state under certain ionic strengths (0.2-0.6 M) was the premise of gel formation under MDA. In the presence of intermediate MDA concentrations (2.5-10 mM), the emulsion gels showed an improved elasticity, strength, WHC, and oxidative stability. This improvement should be mainly attributed to the enhanced protein-protein cross-linkings via MDA, which were homogeneously formed among absorbed and/or unabsorbed proteins, entrapping a greater amount and fractions of protein within network. Therefore, the oil droplets were better adherent to the gel matrix. Nevertheless, addition of high MDA concentrations (25-50 mM) led to the formation of excessive covalent bonds, which might break protein-protein bonds and trigger the desorption of protein from the interface. This ultimately caused "oil leak" phenomena as well as the collapse of gel structure and, thus, overall decreased gel properties and oxidative stability.

Knowledge, attitudes and perceptions regarding lymphatic filariasis: study on systematic noncompliance with mass drug administration

PubMed Central

Cabral, Silvia; Bonfim, Cristine; Oliveira, Rosalira; Oliveira, Paula; Guimarães, Terezinha; Brandão, Eduardo; Aguiar-Santos, Ana Maria; Medeiros, Zulma

2017-01-01

ABSTRACT The aim of this study was to investigate the epidemiological characteristics, antigenic profile, perceptions, attitudes and practices of individuals who have been systematically non-compliant in mass drug administration (MDA) campaigns targeting lymphatic filariasis, in the municipality of Olinda, State of Pernambuco, Northeastern Brazil. A pretested questionnaire was used to obtain information on socioenvironmental demographics, perceptions of lymphatic filariasis and MDA, and reasons for systematic noncompliance with treatment. A rapid immunochromatographic test (ICT) was performed during the survey to screen for filariasis. It was found that the survey subjects knew about filariasis and MDA. Filariasis was identified as a disease (86.2%) and 74.4% associated it with the presence of swelling in the legs. About 80% knew about MDA, and the main source of information was healthcare workers (68.3%). For men the main reasons for systematic noncompliance with MDA were that “the individual had not received the medication” (p=0.03) and for women “the individual either feared experiencing adverse reactions”. According to the ICT, the prevalence of lymphatic filariasis was 2%. The most important causes of systematic noncompliance were not receiving the drug and fear of side-effects. For successful implementation of MDA programs, good planning, educational campaigns promoting the benefits of MDA, adoption of measures to minimize the impact of adverse effects and improvement of drug distribution logistics are needed. PMID:28443941

Caught in the middle with multiple displacement amplification: the myth of pooling for avoiding multiple displacement amplification bias in a metagenome.

PubMed

Marine, Rachel; McCarren, Coleen; Vorrasane, Vansay; Nasko, Dan; Crowgey, Erin; Polson, Shawn W; Wommack, K Eric

2014-01-30

Shotgun metagenomics has become an important tool for investigating the ecology of microorganisms. Underlying these investigations is the assumption that metagenome sequence data accurately estimates the census of microbial populations. Multiple displacement amplification (MDA) of microbial community DNA is often used in cases where it is difficult to obtain enough DNA for sequencing; however, MDA can result in amplification biases that may impact subsequent estimates of population census from metagenome data. Some have posited that pooling replicate MDA reactions negates these biases and restores the accuracy of population analyses. This assumption has not been empirically tested. Using mock viral communities, we examined the influence of pooling on population-scale analyses. In pooled and single reaction MDA treatments, sequence coverage of viral populations was highly variable and coverage patterns across viral genomes were nearly identical, indicating that initial priming biases were reproducible and that pooling did not alleviate biases. In contrast, control unamplified sequence libraries showed relatively even coverage across phage genomes. MDA should be avoided for metagenomic investigations that require quantitative estimates of microbial taxa and gene functional groups. While MDA is an indispensable technique in applications such as single-cell genomics, amplification biases cannot be overcome by combining replicate MDA reactions. Alternative library preparation techniques should be utilized for quantitative microbial ecology studies utilizing metagenomic sequencing approaches.

IL-1β produced by aggressive breast cancer cells is one of the factors that dictate their interactions with mesenchymal stem cells through chemokine production.

PubMed

Escobar, Pauline; Bouclier, Céline; Serret, Julien; Bièche, Ivan; Brigitte, Madly; Caicedo, Andres; Sanchez, Elodie; Vacher, Sophie; Vignais, Marie-Luce; Bourin, Philippe; Geneviève, David; Molina, Franck; Jorgensen, Christian; Lazennec, Gwendal

2015-10-06

The aim of this work was to understand whether the nature of breast cancer cells could modify the nature of the dialog of mesenchymal stem cells (MSCs) with cancer cells. By treating MSCs with the conditioned medium of metastatic Estrogen-receptor (ER)-negative MDA-MB-231, or non-metastatic ER-positive MCF-7 breast cancer cells, we observed that a number of chemokines were produced at higher levels by MSCs treated with MDA-MB-231 conditioned medium (CM). MDA-MB-231 cells were able to induce NF-κB signaling in MSC cells. This was shown by the use of a NF-kB chemical inhibitor or an IκB dominant negative mutant, nuclear translocation of p65 and induction of NF-κB signature. Our results suggest that MDA-MB-231 cells exert their effects on MSCs through the secretion of IL-1β, that activates MSCs and induces the same chemokines as the MDA-MB-231CM. In addition, inhibition of IL-1β secretion in the MDA-MB-231 cells reduces the induced production of a panel of chemokines by MSCs, as well the motility of MDA-MB-231 cells. Our data suggest that aggressive breast cancer cells secrete IL-1β, which increases the production of chemokines by MSCs.

IL-1β produced by aggressive breast cancer cells is one of the factors that dictate their interactions with mesenchymal stem cells through chemokine production

PubMed Central

Serret, Julien; Bièche, Ivan; Brigitte, Madly; Caicedo, Andres; Sanchez, Elodie; Vacher, Sophie; Vignais, Marie-Luce; Bourin, Philippe; Geneviève, David; Molina, Franck; Jorgensen, Christian; Lazennec, Gwendal

2015-01-01

The aim of this work was to understand whether the nature of breast cancer cells could modify the nature of the dialog of mesenchymal stem cells (MSCs) with cancer cells. By treating MSCs with the conditioned medium of metastatic Estrogen-receptor (ER)-negative MDA-MB-231, or non-metastatic ER-positive MCF-7 breast cancer cells, we observed that a number of chemokines were produced at higher levels by MSCs treated with MDA-MB-231 conditioned medium (CM). MDA-MB-231 cells were able to induce NF-κB signaling in MSC cells. This was shown by the use of a NF-kB chemical inhibitor or an IκB dominant negative mutant, nuclear translocation of p65 and induction of NF-κB signature. Our results suggest that MDA-MB-231 cells exert their effects on MSCs through the secretion of IL-1β, that activates MSCs and induces the same chemokines as the MDA-MB-231CM. In addition, inhibition of IL-1β secretion in the MDA-MB-231 cells reduces the induced production of a panel of chemokines by MSCs, as well the motility of MDA-MB-231 cells. Our data suggest that aggressive breast cancer cells secrete IL-1β, which increases the production of chemokines by MSCs. PMID:26362269

Anti and Androgenic Activities in MDA-KB2 Cells: A Comparison of Performance in 96 Well Versus HTS Assays

EPA Science Inventory

We developed the MDA-kb2 cell line to screen androgen agonists/antagonists (Wilson et al., ToxSci 66:69, 2002). MDA-kb2 has been used to quantify anti- and androgenic activities of chemicals, mixtures, combustion by-products, oil dispersants and waste, source and drinking water s...

Celebrating 100 Years of Flight: Testing Wing Designs in Aircraft

ERIC Educational Resources Information Center

Pugalee, David K.; Nusinov, Chuck; Giersch, Chris; Royster, David; Pinelli, Thomas E.

2005-01-01

This article describes an investigation involving several designs of airplane wings in trial flight simulations based on a NASA CONNECT program. Students' experiences with data collection and interpretation are highlighted. (Contains 5 figures.)

Controlling Taenia solium and soil transmitted helminths in a northern Lao PDR village: Impact of a triple dose albendazole regime.

PubMed

Ash, Amanda; Okello, Anna; Khamlome, Boualam; Inthavong, Phouth; Allen, John; Thompson, R C Andrew

2017-10-01

Taenia solium taeniasis-cysticercosis and soil-transmitted helminths (STHs) are parasitic Neglected Tropical Diseases endemic throughout Southeast Asia. Within Lao PDR, a remote northern hill tribe village had previously been identified as a hyper endemic focus for T. solium. To reduce this observed prevalence, a One Health intervention covering both pigs and humans was implemented, which included two Mass drug administrations (MDA1 and MDA2) for village residents using a triple dose albendazole 400mg treatment regime. In addition to the effect on T. solium levels, the dual impact of this anthelmintic regime on STHs within the community was also monitored. Faecal samples were collected pre and post MDA1 and MDA2 and analysed for the presence of Taenia species and the STHs Ascaris lumbricoides, Trichuris trichiura and hookworm species. The McMaster technique was used to measure the changes in both prevalence and intensity of infection. Molecular characterisation of Taenia and hookworm species was conducted to detect zoonotic species. The level of taeniasis within the sampled population decreased by 79.4% after MDA1, remained steady during the five month inter-treatment interval and decreased again by 100% after MDA2. The prevalence of STHs decreased by 65.5% and 62.8% after MDA1 and MDA2 respectively; however an increase to 62.1% of pre MDA1 levels was detected during the inter-treatment interval. Individually, hookworm prevalence decreased by 83.4% (MDA1) and 84.5% (MDA2), A. lumbricoides by 95.6% and 93.5% and T. trichiura by 69.2% and 61%. The intensity of infection within the sampled population also decreased, with egg reduction rates of 94.4% and 97.8% for hookworm, 99.4% and 99.3% for A. lumbricoides and 77.2% and 88.5% for T. trichiura. Molecular characterisation identified a T. solium tapeworm carrier from 21.6% (13/60) of households in the village. T. saginata was identified in 5% (3/60) of households. The zoonotic hookworm A. ceylanicum was detected in the resident dog population. These results suggest that the triple dose albendazole 400mg treatment regime achieved a significant reduction in the level of taeniasis whilst simultaneously reducing the STH burden within the village. The increased STH prevalence detected between MDAs reflects the need for behavioural changes and a sustained chemotherapy programme, which may also need to include the resident dog population. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.

Iron chelation as a possible mechanism for aspirin-induced malondialdehyde production by mouse liver microsomes and mitochondria.

PubMed Central

Schwarz, K B; Arey, B J; Tolman, K; Mahanty, S

1988-01-01

To investigate the possibility that lipid peroxidation is the mechanism responsible for aspirin-induced liver damage, pure neutralized acetylsalicylic acid (ASA), 0.6-90.9 mM, was added to calcium-aggregated mouse liver microsomes followed by incubation in NADPH buffer at 37 degrees C for 60 min and subsequent measurement of malondialdehyde (MDA). MDA production at ASA concentrations from 1.2 to 4.6 mM was greater than control (P less than 0.004). Peak MDA values were observed with 4.6 mM ASA, 39.58 +/- 6.73 nmol MDA/mg protein vs. 16.16 +/- 2.85 (P less than 0.004). Higher concentrations of ASA were inhibitory compared with the value at 4.6 mM (P less than 0.001). Aspirin had similar effects on MDA production by mouse liver mitochondria. MDA production with either ASA or buffer was completely suppressed by the potent iron-chelating agents desferrioxamine and alpha,alpha' dipyridyl when these were added to the microsomal preparations. Since MDA production in this system is known to be affected by iron-chelating agents (enhanced at low concentration, inhibited at higher concentration), the iron-chelating properties of ASA were investigated. Conductivity titration curves of Fe(OH)3 added to water or ASA suggested that the ASA was complexing with iron. The presence of an iron-ASA complex was established by high pressure liquid chromatographic analysis of the solution from this study. We conclude that aspirin enhances MDA production by hepatic microsomes and mitochondria via an aspirin-iron chelate and that this represents at least one mechanism by which aspirin may produce liver damage. PMID:3335633

All-trans-retinoic acid activates the pro-invasive Src-YAP-Interleukin 6 axis in triple-negative MDA-MB-231 breast cancer cells while cerivastatin reverses this action.

PubMed

Mezquita, Belén; Mezquita, Pau; Pau, Montserrat; Gasa, Laura; Navarro, Lourdes; Samitier, Mireia; Pons, Miquel; Mezquita, Cristóbal

2018-05-04

All-trans-retinoic acid (RA), the active metabolite of vitamin A, can reduce the malignant phenotype in some types of cancer and paradoxically also can promote cancer growth and invasion in others. For instance, it has been reported that RA induces tumor suppression in tumor xenografts of MDA-MB-468 breast cancer cells while increasing tumor growth and metastases in xenografts of MDA-MB-231 breast cancer cells. The signaling pathways involved in the pro-invasive action of retinoic acid remain mostly unknown. We show here that RA activates the pro-invasive axis Src-YAP-Interleukin 6 (Src-YAP-IL6) in triple negative MDA-MB-231 breast cancer cells, yielding to increased invasion of these cells. On the contrary, RA inhibits the Src-YAP-IL6 axis of triple-negative MDA-MB-468 cells, which results in decreased invasion phenotype. In both types of cells, inhibition of the Src-YAP-IL6 axis by the Src inhibitor PP2 drastically reduces migration and invasion. Src inhibition also downregulates the expression of a pro-invasive isoform of VEGFR1 in MDA-MB-231 breast cancer cells. Furthermore, interference of YAP nuclear translocation using the statin cerivastatin reverses the upregulation of Interleukin 6 (IL-6) and the pro-invasive effect of RA on MDA-MB-231 breast cancer cells and also decreases invasion and viability of MDA-MB-468 breast cancer cells. These results altogether suggest that RA induces pro-invasive or anti-invasive actions in two triple-negative breast cancer cell lines due to its ability to activate or inhibit the Src-YAP-IL6 axis in different cancer cells. The pro-invasive effect of RA can be reversed by the statin cerivastatin.

Activation of Beta-Catenin Signaling in Androgen Receptor–Negative Prostate Cancer Cells

PubMed Central

Wan, Xinhai; Liu, Jie; Lu, Jing-Fang; Tzelepi, Vassiliki; Yang, Jun; Starbuck, Michael W.; Diao, Lixia; Wang, Jing; Efstathiou, Eleni; Vazquez, Elba S.; Troncoso, Patricia; Maity, Sankar N.; Navone, Nora M.

2012-01-01

Purpose To study Wnt/beta-catenin in castrate-resistant prostate cancer (CRPC) and understand its function independently of the beta-catenin–androgen receptor (AR) interaction. Experimental Design We performed beta-catenin immunocytochemical analysis, evaluated TOP-flash reporter activity (a reporter of beta-catenin–mediated transcription), and sequenced the beta-catenin gene in MDA PCa 118a, MDA PCa 118b, MDA PCa 2b, and PC-3 prostate cancer (PCa) cells. We knocked down beta-catenin in AR-negative MDA PCa 118b cells and performed comparative gene-array analysis. We also immunohistochemically analyzed beta-catenin and AR in 27 bone metastases of human CRPCs. Results Beta-catenin nuclear accumulation and TOP-flash reporter activity were high in MDA PCa 118b but not in MDA PCa 2b or PC-3 cells. MDA PCa 118a and 118b cells carry a mutated beta-catenin at codon 32 (D32G). Ten genes were expressed differently (false discovery rate, 0.05) in MDA PCa 118b cells with downregulated beta-catenin. One such gene, hyaluronan synthase 2 (HAS2), synthesizes hyaluronan, a core component of the extracellular matrix. We confirmed HAS2 upregulation in PC-3 cells transfected with D32G-mutant beta-catenin. Finally, we found nuclear localization of beta-catenin in 10 of 27 human tissue specimens; this localization was inversely associated with AR expression (P = 0.056, Fisher’s exact test), suggesting that reduced AR expression enables Wnt/beta-catenin signaling. Conclusion We identified a previously unknown downstream target of beta-catenin, HAS2, in PCa, and found that high beta-catenin nuclear localization and low or no AR expression may define a subpopulation of men with bone-metastatic PCa. These findings may guide physicians in managing these patients. PMID:22298898

Intratumoral injection of INGN 241, a nonreplicating adenovector expressing the melanoma-differentiation associated gene-7 (mda-7/IL24): biologic outcome in advanced cancer patients.

PubMed

Tong, Alex W; Nemunaitis, John; Su, Dan; Zhang, Yuan; Cunningham, Casey; Senzer, Neil; Netto, George; Rich, Dawn; Mhashilkar, Abner; Parker, Karen; Coffee, Keith; Ramesh, Rajagopal; Ekmekcioglu, Suhendan; Grimm, Elizabeth A; van Wart Hood, Jill; Merritt, James; Chada, Sunil

2005-01-01

The mda-7 gene (approved gene symbol IL24) is a novel tumor suppressor gene with tumor-apoptotic and immune-activating properties. We completed a Phase I dose-escalation clinical trial, in which a nonreplicating adenoviral construct expressing the mda-7 transgene (INGN 241; Ad-mda7) was administered intratumorally to 22 patients with advanced cancer. Excised tumors were evaluated for vector-specific DNA and RNA, transgenic MDA-7 expression, and biological effects. Successful gene transfer as assessed by DNA- and RT-PCR was demonstrated in 100% of patients evaluated. DNA analyses demonstrated a dose-dependent penetration of INGN 241 (up to 4 x 10(8) copies/mug DNA at the 2 x 10(12) vp dose). A parallel distribution of vector DNA, vector RNA, MDA-7 protein expression, and apoptosis induction was observed in all tumors, with signals decreasing with distance away from the injection site. Additional evidence for bioactivity of INGN 241 was illustrated via regulation of the MDA-7 target genes beta-catenin, iNOS, and CD31. Transient increases (up to 20-fold) of serum IL-6, IL-10, and TNF-alpha were observed. Significantly higher elevations of IL-6 and TNF-alpha were observed in patients who responded clinically to INGN 241. Patients also showed marked increases of CD3+CD8+ T cells posttreatment, suggesting that INGN 241 increased systemic TH1 cytokine production and mobilized CD8+ T cells. Intratumoral delivery of INGN 241 induced apoptosis in a large volume of tumor and elicited tumor-regulatory and immune-activating events that are consistent with the preclinical features of MDA-7/IL-24.

Formation of malondialdehyde (MDA), 4-hydroxy-2-hexenal (HHE) and 4-hydroxy-2-nonenal (HNE) in fish and fish oil during dynamic gastrointestinal in vitro digestion.

PubMed

Larsson, Karin; Harrysson, Hanna; Havenaar, Robert; Alminger, Marie; Undeland, Ingrid

2016-02-01

Marine lipids contain a high proportion of polyunsaturated fatty acids (PUFA), including the characteristic long chain (LC) n-3 PUFA. Upon peroxidation these lipids generate reactive products, such as malondialdehyde (MDA), 4-hydroxy-2-hexenal (HHE) and 4-hydroxy-2-nonenal (HNE), which can form covalent adducts with biomolecules and thus are regarded as genotoxic and cytotoxic. PUFA peroxidation can occur both before and after ingestion. The aim of this study was to determine what levels of MDA, HHE and HNE can evolve in the gastric and intestinal lumen after ingesting meals containing fish or fish oil using a dynamic gastrointestinal (GI) model (TIM). The impact of the fish muscle matrix, lipid content, fish species, and oven baking on GI oxidation was evaluated. MDA and HHE concentrations in gastric lumen increased for all meals during digestion, with the highest level found with herring mince; ∼ 25 μM MDA and ∼ 850 nM HHE. Aldehyde concentrations reached in intestinal lumen during digestion of fish containing meals were generally lower than in gastric lumen, while isolated herring oils (bulk and emulsified) generated higher MDA and HHE values in intestinal lumen compared to gastric lumen. Based on aldehyde levels in gastric lumen, meals containing herring lipids were ranked: raw herring (17% lipid) = baked herring (4% lipid) > raw herring (4% lipid) ≫ herring oil emulsion > herring oil. Herring developed higher concentrations of MDA and HHE during gastric digestion compared to salmon, which initially contained lower levels of oxidation products. Cooked salmon generated higher MDA concentrations during digestion than raw salmon. Low levels of HNE were observed during digestion of all test meals, in accordance with the low content of n-6 PUFA in fish lipids.

What is a "Maison des Adolescents"? A history of integrated youth health care services in France.

PubMed

Benoit, Laelia; Cottin, Patrick; Moro, Marie R

2018-06-13

Since 1999, the development of more than 100 "Maisons des Adolescents" (MDAs) has enabled young persons to gain access to specific care in integrated youth-friendly facilities in France. To contribute to the development and standardization of international youth-friendly health care services, this review provides insight into the French MDA facilities. This socio-historical analysis includes a systematic review of articles referring to the MDAs (selection through title and/or abstract), ministry reports and newspaper articles, from 1999 to 2018. If the various medical programmes of MDAs depend on the priorities of local teams rather as well as on official regulations, all MDAs offer the following essential services: a "Health and Prevention Space" open daily; multidisciplinary consultations; a mobile team visiting youth hospitalized in medical units; a mobile team able to meet adolescents at their homes; an open centre for art workshops; refresher and remedial courses for school work; network meetings and parent support groups. The MDAs from the start addressed an age group (young people aged 11-21 years) rather than an illness. They thus provide primary prevention for adolescents according to the World Health Organization definition of health as "a state of complete physical, mental and social well-being." This medical and political movement was shaped by the epistemological background of its first leaders. Although more cohort studies to evaluate their early interventions would be useful, the success of the MDA network is already widely acknowledged by users, professionals and policy makers. © 2018 John Wiley & Sons Australia, Ltd.

Endogenous sulfur dioxide aggravates myocardial injury in isolated rat heart with ischemia and reperfusion.

PubMed

Zhang, Suqing; Du, Junbao; Jin, Hongfang; Li, Wei; Liang, Yinfang; Geng, Bin; Li, Shukui; Zhang, Chunyu; Tang, Chaoshu

2009-02-27

Ischemia-reperfusion (I/R) injury is an important clinical problem. This article investigated the role of sulfur dioxide (SO2) in the regulation of cardiac function and in the pathogenesis of cardiac I/R injury in isolated rat heart. Rat hearts isolated on a Langendorff apparatus were divided into control, I/R, I/R+SO2, and I/R+hydroxamate groups. Hydroxamate is an inhibitor of SO2 synthetase. I/R treatment was ischemia for 2 hr in hypothermic solution (4 degrees C), then reperfusion/rewarming (37 degrees C) for 60 min. Cardiac function was monitored by MacLab analog to a digital converter. Determination of sulfite content involved reverse-phase high performance liquid chromatography with fluorescence detection. Myoglobin content of coronary perfusate was determined at 410 nm. Myocardial malondialdehyde (MDA) was determined by thiobarbituric acid method, and conjugated diene (CD) was extracted by chloroform. 5,50-Dithiobis-2-nitrobenzoic acid was used to determine glutathione (GSH). The results showed that I/R treatment obviously increased myocardial sulfite content, and sulfite content of myocardium was negatively correlated with the recovery rate of left-ventricle developed pressure and positively correlated with the leakage of myoglobin. In postreperfusion, myocardial function recovery was decreased by SO2. During reperfusion, myocardium-released enzymes, MDA and CD level were increased but myocardial GSH content was depressed with the treatment of SO2 donor. Incubation of myocardial tissue with SO2 significantly increased MDA and CD generation. Endogenous SO2 might be involved in the pathogenesis of myocardial I/R injury, and its mechanism might be associated with an increase in lipid peroxide level and a decrease in GSH generation.

Biomechanics and biomimetics in insect-inspired flight systems.

PubMed

Liu, Hao; Ravi, Sridhar; Kolomenskiy, Dmitry; Tanaka, Hiroto

2016-09-26

Insect- and bird-size drones-micro air vehicles (MAV) that can perform autonomous flight in natural and man-made environments are now an active and well-integrated research area. MAVs normally operate at a low speed in a Reynolds number regime of 10(4)-10(5) or lower, in which most flying animals of insects, birds and bats fly, and encounter unconventional challenges in generating sufficient aerodynamic forces to stay airborne and in controlling flight autonomy to achieve complex manoeuvres. Flying insects that power and control flight by flapping wings are capable of sophisticated aerodynamic force production and precise, agile manoeuvring, through an integrated system consisting of wings to generate aerodynamic force, muscles to move the wings and a control system to modulate power output from the muscles. In this article, we give a selective review on the state of the art of biomechanics in bioinspired flight systems in terms of flapping and flexible wing aerodynamics, flight dynamics and stability, passive and active mechanisms in stabilization and control, as well as flapping flight in unsteady environments. We further highlight recent advances in biomimetics of flapping-wing MAVs with a specific focus on insect-inspired wing design and fabrication, as well as sensing systems.This article is part of the themed issue 'Moving in a moving medium: new perspectives on flight'. © 2016 The Author(s).

Biomechanics and biomimetics in insect-inspired flight systems

PubMed Central

Liu, Hao; Ravi, Sridhar; Kolomenskiy, Dmitry; Tanaka, Hiroto

2016-01-01

Insect- and bird-size drones—micro air vehicles (MAV) that can perform autonomous flight in natural and man-made environments are now an active and well-integrated research area. MAVs normally operate at a low speed in a Reynolds number regime of 104–105 or lower, in which most flying animals of insects, birds and bats fly, and encounter unconventional challenges in generating sufficient aerodynamic forces to stay airborne and in controlling flight autonomy to achieve complex manoeuvres. Flying insects that power and control flight by flapping wings are capable of sophisticated aerodynamic force production and precise, agile manoeuvring, through an integrated system consisting of wings to generate aerodynamic force, muscles to move the wings and a control system to modulate power output from the muscles. In this article, we give a selective review on the state of the art of biomechanics in bioinspired flight systems in terms of flapping and flexible wing aerodynamics, flight dynamics and stability, passive and active mechanisms in stabilization and control, as well as flapping flight in unsteady environments. We further highlight recent advances in biomimetics of flapping-wing MAVs with a specific focus on insect-inspired wing design and fabrication, as well as sensing systems. This article is part of the themed issue ‘Moving in a moving medium: new perspectives on flight’. PMID:27528780

Aviation dentistry: current concepts and practice.

PubMed

Zadik, Y

2009-01-10

With the growing number of air passengers, flight attendants, leisure pilots as well as military and airline pilots, dentists may increasingly encounter flight-related oral conditions requiring treatment. Moreover, dentists should prevent the creation of in-flight hazards when treating aircrew members. The aim of this article is to introduce the concepts of aviation (aerospace) medicine and dentistry. Data were gathered to cover the following issues: head and facial barotraumas (barotrauma-related headache, external otitic barotrauma, barosinusitis and barotitis-media), dental barotrauma (barometric pressure-related tooth injury), barodontalgia (barometric pressure-related oro-dental pain), and dental care for aircrews. Special considerations have to be made when planning restorative, endodontic, prosthodontic and surgical treatment to an aircrew patient. This article supplies the dental practitioner with some diagnostic tools as well as treatment guidelines. Principles of prevention, periodic examination, dental-related flight restriction (grounding) and dental documentation (for forensic purposes) are described as well.

Connected Component Model for Multi-Object Tracking.

PubMed

He, Zhenyu; Li, Xin; You, Xinge; Tao, Dacheng; Tang, Yuan Yan

2016-08-01

In multi-object tracking, it is critical to explore the data associations by exploiting the temporal information from a sequence of frames rather than the information from the adjacent two frames. Since straightforwardly obtaining data associations from multi-frames is an NP-hard multi-dimensional assignment (MDA) problem, most existing methods solve this MDA problem by either developing complicated approximate algorithms, or simplifying MDA as a 2D assignment problem based upon the information extracted only from adjacent frames. In this paper, we show that the relation between associations of two observations is the equivalence relation in the data association problem, based on the spatial-temporal constraint that the trajectories of different objects must be disjoint. Therefore, the MDA problem can be equivalently divided into independent subproblems by equivalence partitioning. In contrast to existing works for solving the MDA problem, we develop a connected component model (CCM) by exploiting the constraints of the data association and the equivalence relation on the constraints. Based upon CCM, we can efficiently obtain the global solution of the MDA problem for multi-object tracking by optimizing a sequence of independent data association subproblems. Experiments on challenging public data sets demonstrate that our algorithm outperforms the state-of-the-art approaches.

A fast and validated method for the determination of malondialdehyde in fish liver using high-performance liquid chromatography with a photodiode array detector.

PubMed

Faizan, Mohammad; Esatbeyoglu, Tuba; Bayram, Banu; Rimbach, Gerald

2014-04-01

Malondialdehyde (MDA) is a biomarker of lipid peroxidation and is present in foods and biological samples such as plasma. A high-performance liquid chromatography (HPLC) method was applied to determine MDA in fish liver samples after derivatization with 2,4-dinitrophenylhydrazine (DNPH) using a ODS2 column (10 cm × 4.6 mm, 3 μm) and a photodiode array detector. The mobile phase consisted of 0.2% acetic acid (v/v) in distilled water and acetonitrile (42:58, v/v). The present method was validated in terms of linearity, lower limit of quantification, lower limit of detection, precision, accuracy, recovery, and stability of MDA according to U.S. Food and Drug Administration (FDA) guidelines. The limit of quantification of MDA was 0.39 μmol/L, which is comparable to other methods. The recovery of the spiked MDA liver samples was in the range of 92.4% to 104.2%. This newly modified HPLC method is specific, sensitive, and accurate and allows the analysis of MDA within 4 min in fish liver but also in other tissues and plasma. © 2014 Institute of Food Technologists®

Glomerular malondialdehyde levels in patients with focal and segmental glomerulosclerosis and minimal change disease.

PubMed

Nezhad, Simin Torabi; Momeni, Babak; Basiratnia, Mitra

2010-09-01

Minimal change disease (MCD) and focal and segmental glomerulosclerosis (FSGS) are often studied together, because both present with heavy proteinuria and the nephrotic syndrome. The precise distinction between MCD and FSGS is sometimes difficult because of inadequate number of glomeruli for definite diagnosis. Some evidence suggests that markers of lipid peroxidation, such as malondialdehyde (MDA) is an index of free radical mediated injury and may be involved in the pathogenesis of FSGS. In this study, we assessed the immunoreactivity of MDA, the end product of lipid peroxidation in glomeruli of patients with idiopathic FSGS, MCD as well as normal controls (NC). Our results showed that the immunostaining level of MDA was significantly higher in patients with FSGS (mean = 1.5) than in either patients with MCD (mean = 0.16) or normal controls (mean = 0.11) with P value < 0.001. Glomerular MDA level correlated well with the degree of glomerulosclerosis in patients with idiopathic FSGS. Our data demonstrates that the glomerular level of MDA is higher in idiopathic FSGS than MCD. We suggest that MDA immunostaining can be helpful in differentiating between FSGS and MCD in problematic cases and when we do not have enough glomeruli for definite and correct diagnosis.

Anti-proliferative and apoptosis inducing potential of hydroalcoholic Achillea wilhelmsii C. Koch extract on human breast adenocarcinoma cell lines MCF-7 and MDA-Mb-468.

PubMed

Galavi, Hamid Reza; Saravani, Ramin; Shahraki, Ali; Ashtiani, Mojtaba

2016-11-01

Achillea wilhelmsii C. Koch contains a variety of components such as flavonoid. The previous studies showed that flavonoid has anti-cancer properties. The aim of the present study was to determine the anti-proliferative and apoptosis-inducing potential of hydroalcoholic Achillea wilhelmsii C. Koch extract (HAWE) on MCF-7 and MDA-Mb-468 human breast carcinoma cell lines. The anti-proliferative activity of HAWE was evaluated using MTT, flowcytometry by annexin V/PI double staining, and caspase-3 activity. The results of MTT showed that the ED50 of MCF-7 and MDA-Mb-468 was 25μg/ml of HAWE, 48h after treatment. Flowcytometry by annexin V/PI showed that HAWE induced late apoptosis in MCF-7 and early apoptosis in MDA-Mb-468. In addition, the caspase-3 colorimetric method showed that caspase-3 increased in the MDA-Mb-468 after treatment with HAWE. This study found that the hydroalcoholic extract of Achillea wilhelmsii C. Koch induced apoptosis in both the MCF-7 and MDA-Mb-468 human breast carcinoma cell lines.

The 6th Meeting of the Global Alliance to Eliminate Lymphatic Filariasis: A half-time review of lymphatic filariasis elimination and its integration with the control of other neglected tropical diseases

PubMed Central

2010-01-01

The 6th Meeting of the Global Alliance to Eliminate Lymphatic Filariasis (GAELF6) was held 1-3 June, 2010 in Seoul, Korea, with 150 participants from 38 countries. The year 2010 marks the midpoint between the first GAELF meeting, in 2000, and the World Health Organization (WHO) 2020 goal of global elimination of lymphatic filariasis (LF) as a public health problem. The theme of the meeting, "Half-time in LF Elimination: Teaming Up with Neglected Tropical Diseases (NTDs)," reflected significant integration of LF elimination programmes into a comprehensive initiative to control NTDs. Presentations on LF epidemiology, treatment, research, and programmes highlighted both accomplishments and remaining challenges. The WHO strategy to interrupt LF transmission is based on annual mass drug administration (MDA) using two-drug combinations. After mapping the geographic distribution of LF, MDA is implemented for ≥ 5 years, followed by a period of post-MDA surveillance, and, ultimately, verification of LF elimination. Morbidity management further reduces disease burden. Of 81 countries considered LF-endemic in 2000, 52 (64.2%) have begun MDA; 10 (12.3%) others with low-level transmission are unlikely to require MDA. In 2008, ~695 million people were offered treatment (51.7% of the at-risk population); ~496 million participated. Approximately 22 million people have been protected from LF infection and disease, with savings of ~US $24.2 billion. Morbidity management programmes have been implemented in 27 (33.3%) countries. Significant challenges to LF elimination remain. These include: initiating MDA in the remaining 19 countries that require it; achieving full geographic coverage in countries where MDA has started; finding alternative strategies to address the problem of Loa loa co-endemicity in Central Africa; developing strategies to treat urban populations; initiating and sustaining MDA in settings of armed conflict; developing refined guidelines and procedures for stopping MDA, for post-MDA surveillance, and for verifying the elimination of LF; and integrating morbidity management into all LF elimination programmes. Scientific research and enhanced advocacy for NTDs remain critical for addressing these challenges. GAELF6 was characterized by enthusiasm and recognition that "teaming up with NTDs" offers opportunities for new partnerships, fresh perspectives, enhanced advocacy, and greater programmatic integration in a rapidly changing global health environment. PMID:20961435

The effect of L-thyroxine replacement therapy on ischemia-modified albümin and malondialdehyde levels in patients with overt and subclinical hypothyroidism.

PubMed

Erem, Cihangir; Suleyman, Akile Karacin; Civan, Nadim; Mentese, Ahmet; Nuhoglu, İrfan; Uzun, Aysegul; Coskun, Hulya; Deger, Orhan

2016-11-01

The main objective of this study was to evaluate the levels of ischemia-modified albumin (IMA) and malondialdehyde (MDA) in patients with subclinical (SHypo) and overt hypothyroidism (OHypo), and to assess the effects of levothyroxine (LT 4 ) therapy on the oxidative stress (OS) parameters. We also investigated the relationships among serum thyroid hormones, lipid parameters, and IMA and MDA in these patients. Thirty untreated patients with OHypo, 25 untreated patients with Shypo, and 30 age- and sex-matched healthy controls were prospectively included in the study. Biochemical and hormonal parameters including IMA and MDA were evaluated in all patients just before and one month after the maintenance of euthyroidism. Compared with the control subjects, the levels of MDA and triglycerides (TG) significantly increased in patients with SHypo (p < 0.001 and p < 0.05, respectively), whereas high density lipoprotein cholesterol (HDL-C) levels significantly decreased (p = 0.01). Patients with OHypo showed significantly high MDA, total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), and TG levels (p = 0.001, p < 0.01, p = 0.01, and p < 0.01, respectively), and significantly low HDL-C levels compared with the controls (p < 0.05). MDA levels and lipid profile were not significantly different in the patients with OHypo when compared with the patients with SHypo. Serum IMA levels did not significantly change in patients with OHypo and SHypo compared with the controls. In the pre-treatment period, MDA levels were inversely correlated with HDL-C levels in patients with OHypo (r: -0.471, p = 0.009). Plasma MDA and LDL-C levels significantly decreased and HDL-C levels significantly increased in the groups of OHypo and SHypo after LT 4 treatment. Serum IMA levels did not significantly change with the therapy in all patient groups. Increased MDA levels in both patient groups represent increased lipid peroxidation which might play an important role in the pathogenesis of the atherosclerosis seen in these patients. Increased OS in patients with SHypo and OHypo could be improved by LT 4 treatment. Also, MDA can be used as a reliable marker of OS and oxidative damage, while IMA is considered to be inappropriate.

Mass drug administration for malaria

PubMed Central

Poirot, Eugenie; Skarbinski, Jacek; Sinclair, David; Kachur, S Patrick; Slutsker, Laurence; Hwang, Jimee

2013-01-01

Background Mass drug administration (MDA), defined as the empiric administration of a therapeutic antimalarial regimen to an entire population at the same time, has been a historic component of many malaria control and elimination programmes, but is not currently recommended. With renewed interest in MDA and its role in malaria elimination, this review aims to summarize the findings from existing research studies and program experiences of MDA strategies for reducing malaria burden and transmission. Objectives To assess the impact of antimalarial MDA on population asexual parasitaemia prevalence, parasitaemia incidence, gametocytaemia prevalence, anaemia prevalence, mortality and MDA-associated adverse events. Search methods We searched the Cochrane Infectious Disease Group Specialized Register, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE+, EMBASE, to February 2013. We also searched CABS Abstracts, LILACS, reference lists, and recent conference proceedings. Selection criteria Cluster-randomized trials and non-randomized controlled studies comparing therapeutic MDA versus placebo or no MDA, and uncontrolled before-and-after studies comparing post-MDA to baseline data were selected. Studies administering intermittent preventive treatment (IPT) to sub-populations (for example, pregnant women, children or infants) were excluded. Data collection and analysis Two authors independently reviewed studies for inclusion, extracted data and assessed risk of bias. Studies were stratified by study design and then subgrouped by endemicity, by co-administration of 8-aminoquinoline plus schizonticide drugs and by plasmodium species. The quality of evidence was assessed using the GRADE approach. Main results Two cluster-randomized trials, eight non-randomized controlled studies and 22 uncontrolled before-and-after studies are included in this review. Twenty-two studies (29 comparisons) compared MDA to placebo or no intervention of which two comparisons were conducted in areas of low endemicity (≤5%), 12 in areas of moderate endemicity (6-39%) and 15 in areas of high endemicity (≥ 40%). Ten studies evaluated MDA plus other vector control measures. The studies used a wide variety of MDA regimens incorporating different drugs, dosages, timings and numbers of MDA rounds. Many of the studies are now more than 30 years old. Areas of low endemicity (≤5%) Within the first month post-MDA, a single uncontrolled before-and-after study conducted in 1955 on a small Taiwanese island reported a much lower prevalence of parasitaemia following a single course of chloroquine compared to baseline (1 study, very low quality evidence). This lower parasite prevalence was still present after more than 12 months (one study, very low quality evidence). In addition, one cluster-randomized trial evaluating MDA in a low endemic setting reported zero episodes of parasitaemia at baseline, and throughout five months of follow-up in both the control and intervention arms (one study, very low quality evidence). Areas of moderate endemicity (6-39%) Within the first month post-MDA, the prevalence of parasitaemia was much lower in three non-randomized controlled studies from Kenya and India in the 1950s (RR 0.03, 95% CI 0.01 to 0.08, three studies, moderate quality evidence), and in three uncontrolled before-and-after studies conducted between 1954 and 1961 (RR 0.29, 95% CI 0.17 to 0.48, three studies,low quality evidence). The longest follow-up in these settings was four to six months. At this time point, the prevalence of parasitaemia remained substantially lower than controls in the two non-randomized controlled studies (RR 0.18, 95% CI 0.10 to 0.33, two studies, low quality evidence). In contrast, the two uncontrolled before-and-after studies found mixed results: one found no difference and one found a substantially higher prevalence compared to baseline (not pooled, two studies, very low quality evidence). Areas of high endemicity (≥40%) Within the first month post-MDA, the single cluster-randomized trial from the Gambia in 1999 found no significant difference in parasite prevalence (one study, low quality evidence). However, prevalence was much lower during the MDA programmes in three non-randomized controlled studies conducted in the 1960s and 1970s (RR 0.17, 95% CI 0.11 to 0.27, three studies, moderate quality evidence), and within one month of MDA in four uncontrolled before-and-after studies (RR 0.37, 95% CI 0.28 to 0.49, four studies,low quality evidence). Four trials reported changes in prevalence beyond three months. In the Gambia, the single cluster-randomized trial found no difference at five months (one trial, moderate quality evidence). The three uncontrolled before-and-after studies had mixed findings with large studies from Palestine and Cambodia showing sustained reductions at four months and 12 months, respectively, and a small study from Malaysia showing no difference after four to six months of follow-up (three studies,low quality evidence). 8-aminoquinolines We found no studies directly comparing MDA regimens that included 8-aminoquinolines with regimens that did not. In a crude subgroup analysis with a limited number of studies, we were unable to detect any evidence of additional benefit of primaquine in moderate- and high-transmission settings. Plasmodium species In studies that reported species-specific outcomes, the same interventions resulted in a larger impact on Plasmodium falciparum compared to P. vivax. Authors' conclusions MDA appears to reduce substantially the initial risk of malaria parasitaemia. However, few studies showed sustained impact beyond six months post-MDA, and those that did were conducted on small islands or in highland settings. To assess whether there is an impact of MDA on malaria transmission in the longer term requires more quasi experimental studies with the intention of elimination, especially in low- and moderate-transmission settings. These studies need to address any long-term outcomes, any potential barriers for community uptake, and contribution to the development of drug resistance. PLAIN LANGUAGE SUMMARY Administration of antimalarial drugs to whole populations Malaria is the most important mosquito-borne disease caused by a parasite, accounting for an estimated 660,000 deaths annually. Fortunately, malaria is both preventable and treatable. Several malaria control tools currently exist, and new and innovative approaches are continually under development. The administration of drugs against malaria to whole populations, termed mass drug administration (MDA), was a component of many malaria elimination programmes in the 1950s, and is once again attracting interest as a malaria elimination tool. As a consequence, it is important to review the currently available literature in order to assess the potential for this strategy to reduce malaria burden and transmission, and to identify gaps in our understanding. This review assessed the impact of MDA on several malaria-specific outcome measures. Thirty-two studies were included in this review, from sites in Asia, Africa, Europe and the Americas. The review found that although MDA can reduce the initial risk of malaria-specific outcomes, these reductions are often not sustained. However, a few studies conducted on small islands or in highland areas did show sustained impact more than six months after MDA. Adverse events were inadequately addressed in most studies. Notable severe drug reactions, including haemolysis, haemoglobinuria, severe anaemia and death, were reported with 8-aminoquinoline plus schizonticide drug co-administration, while severe skin reactions were reported with sulphadoxine-pyrimethamine plus artesunate plus primaquine. Assessing the true impact of MDA programmes can be a challenge due to the heterogeneity of the study methods employed. Nonetheless, this review can help guide future antimalarial MDA interventions and their evaluation. PMID:24318836

Advanced Stirling Radioisotope Generator Engineering Unit 2 (ASRG EU2) Final Assembly

NASA Technical Reports Server (NTRS)

Oriti, Salvatore M.

2015-01-01

NASA Glenn Research Center (GRC) has recently completed the assembly of a unique Stirling generator test article for laboratory experimentation. Under the Advanced Stirling Radioisotope Generator (ASRG) flight development contract, NASA GRC initiated a task to design and fabricate a flight-like generator for in-house testing. This test article was given the name ASRG Engineering Unit 2 (EU2) as it was effectively the second engineering unit to be built within the ASRG project. The intent of the test article was to duplicate Lockheed Martin's qualification unit ASRG design as much as possible to enable system-level tests not previously possible at GRC. After the cancellation of the ASRG flight development project, the decision was made to continue the EU2 build, and make use of a portion of the hardware from the flight development project. GRC and Lockheed Martin engineers collaborated to develop assembly procedures, leveraging the valuable knowledge gathered by Lockheed Martin during the ASRG development contract. The ASRG EU2 was then assembled per these procedures at GRC with Lockheed Martin engineers on site. The assembly was completed in August 2014. This paper details the components that were used for the assembly, and the assembly process itself.

The π-Tetrel Bond and its Influence on Hydrogen Bonding and Proton Transfer.

PubMed

Wei, Yuanxin; Li, Qingzhong; Scheiner, Steve

2018-03-19

The positive region that lies above the plane of F 2 TO (T=C and Si) interacts with malondialdehyde (MDA), which contains an intramolecular H-bond. The T atom of F 2 TO can lie either in the MDA molecular plane, forming a T⋅⋅⋅O tetrel bond, or F 2 TO can stack directly above MDA in a parallel arrangement. The former structure is more stable than the latter, and in either case, F 2 SiO engages in a much stronger interaction than does F 2 CO, reaching nearly 200 kJ mol -1 . The π-tetrel bond strengthens/weakens the MDA H-bond when the bond is formed to the hydroxyl/carbonyl group of MDA, and causes an accompanying inhibition/promotion of proton transfer within this H-bond; this effect is stronger for F 2 SiO. These same aspects can be tuned by substituents placed on any of the C atoms of MDA, although their effects are not fully correlated with the electron-withdrawing or electron-releasing properties of the substituent. A new type of π-π tetrel bond occurs when the π-hole on the T atom of F 2 TO approaches the middle carbon atom of MDA from above, and a similar configuration is also found between F 2 TO and benzene. Evidence for extensive C⋅⋅⋅C π-π tetrel bonding in crystal materials is presented. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

A stochastic model for the probability of malaria extinction by mass drug administration.

PubMed

Pemberton-Ross, Peter; Chitnis, Nakul; Pothin, Emilie; Smith, Thomas A

2017-09-18

Mass drug administration (MDA) has been proposed as an intervention to achieve local extinction of malaria. Although its effect on the reproduction number is short lived, extinction may subsequently occur in a small population due to stochastic fluctuations. This paper examines how the probability of stochastic extinction depends on population size, MDA coverage and the reproduction number under control, R c . A simple compartmental model is developed which is used to compute the probability of extinction using probability generating functions. The expected time to extinction in small populations after MDA for various scenarios in this model is calculated analytically. The results indicate that mass drug administration (Firstly, R c must be sustained at R c  < 1.2 to avoid the rapid re-establishment of infections in the population. Secondly, the MDA must produce effective cure rates of >95% to have a non-negligible probability of successful elimination. Stochastic fluctuations only significantly affect the probability of extinction in populations of about 1000 individuals or less. The expected time to extinction via stochastic fluctuation is less than 10 years only in populations less than about 150 individuals. Clustering of secondary infections and of MDA distribution both contribute positively to the potential probability of success, indicating that MDA would most effectively be administered at the household level. There are very limited circumstances in which MDA will lead to local malaria elimination with a substantial probability.

Characterization and immune response expression of the Rig-I-like receptor mda5 in common carp Cyprinus carpio.

PubMed

Zhu, Y Y; Xing, W X; Shan, S J; Zhang, S Q; Li, Y Q; Li, T; An, L; Yang, G W

2016-06-01

In this study, the full-length complementary (c)DNA of common carp Cyprinus carpio melanoma differentiation-associated gene 5 (mda5) was cloned. The complete open reading frame of C. carpio mda5 contained 2982 bp and encodes 993 amino acids. The deduced amino acids contained six functional domains: two caspase activation and recruitment domains (CARD), a conserved restriction domain of bacterial type III restriction enzyme (ResIII), a DExD/H box-containing domain (DEXDc), a helicase super family C-terminal domain (HELICc) and a C-terminal regulatory domain (RD). The mda5 gene was expressed in all tested tissues, with high levels in the gills and spleen, while lower expressed in gonad and blood. The copy numbers of mda5 were increased in the liver, spleen, head kidney and the mucosal-associated immune tissues such as the foregut, hindgut, gills and skin after stimulation with polyinosinic polycytidylic [poly(I:C)] and Aeromonas hydrophila. The myxovirus resistance gene (mx) messenger (m)RNA levels in the spleen, head kidney, foregut and gills were significantly up-regulated after poly(I:C) injection. When injected with poly(I:C), mda5 and mx transcripts were also significantly induced in vitro. These results implied that mda5 might be involved in both antiviral and antibacterial innate immune processes in C. carpio. © 2016 The Authors. Journal of Fish Biology © 2016 The Fisheries Society of the British Isles. © 2016 The Fisheries Society of the British Isles.

NASA's Space Launch System: Progress Report

NASA Technical Reports Server (NTRS)

Cook, Jerry; Lyles, Garry

2017-01-01

NASA and its commercial industry team achieved significant progress in 2016 in manufacturing and testing of the Block 1 vehicle for the first launch of the Space Launch System (SLS). Test and flight article hardware for the liquid hydrogen fuel tank as well as the engine section for the core stage were completed at Michoud Assembly Facility (MAF) in New Orleans. Test stands neared completion at Marshall Space Flight Center for the propellant tanks, engine section, intertank and payload section. Stennis Space Center completed major structural renovations on the B2 test stand, where the core stage "green run" test program will be conducted. The SLS team completed a hotfire test series at Stennis to successfully demonstrate the ability of the RS-25 engine to operate under SLS environments and performance conditions. The team also test fired the second qualification five-segment solid rocket motor and cast the first six motor segments for the first SLS mission. The Interim Cryogenic Propulsion Stage (ICPS) test article was delivered to Marshall for structural tests, and work is nearly finished on the flight stage. Flight software testing completed at Marshall included power quality and command and data handling. In 2017, that work continues. SLS completed Preliminary Design Review (PDR) on the Exploration Upper Stage (EUS), a powerful, human-rated spacecraft that will propel explorers to cis-lunar space. In 2017, hardware will continue to be integrated at MAF for core stage structural test articles and the first two operational flights. RS-25 hotfire testing will continue to explore engine performance, as well as test flight-like software and four new Engine Controller Units (ECUs) for the first mission. Production of development components for a more affordable RS-25 design is underway. Core stage structural test articles have begun arriving at Marshall. While engineering challenges typical of a new development are possible, SLS is working toward launch readiness in late 2018. This paper will discuss these and other technical and programmatic successes and challenges over the past year and provide a preview of work ahead before first flight

Revitalization of Nuclear Powered Flight

DTIC Science & Technology

2016-05-01

1 AU/ACSC/2016 AIR COMMAND AND STAFF COLLEGE AIR UNIVERSITY Revitalization of Nuclear Powered Flight by Todd C...Aviation History On-Line Museum . August 6, 2007. Accessed February 16, 2016. http://www.aviation-history.com/articles/nuke-american.htm. Courtland

Costs of testing for ocular Chlamydia trachomatis infection compared to mass drug administration for trachoma in the Gambia: application of results from the PRET study.

PubMed

Harding-Esch, Emma; Jofre-Bonet, Mireia; Dhanjal, Jaskiran K; Burr, Sarah; Edwards, Tansy; Holland, Martin; Sillah, Ansumana; West, Sheila; Lietman, Tom; Keenan, Jeremy; Mabey, David; Bailey, Robin

2015-04-01

Mass drug administration (MDA) treatment of active trachoma with antibiotic is recommended to be initiated in any district where the prevalence of trachoma inflammation, follicular (TF) is ≥ 10% in children aged 1-9 years, and then to continue for at least three annual rounds before resurvey. In The Gambia the PRET study found that discontinuing MDA based on testing a sample of children for ocular Chlamydia trachomatis(Ct) infection after one MDA round had similar effects to continuing MDA for three rounds. Moreover, one round of MDA reduced disease below the 5% TF threshold. We compared the costs of examining a sample of children for TF, and of testing them for Ct, with those of MDA rounds. The implementation unit in PRET The Gambia was a census enumeration area (EA) of 600-800 people. Personnel, fuel, equipment, consumables, data entry and supervision costs were collected for census and treatment of a sample of EAs and for the examination, sampling and testing for Ct infection of 100 individuals within them. Programme costs and resource savings from testing and treatment strategies were inferred for the 102 EAs in the study area, and compared. Census costs were $103.24 per EA plus initial costs of $108.79. MDA with donated azithromycin cost $227.23 per EA. The mean cost of examining and testing 100 children was $796.90 per EA, with Ct testing kits costing $4.80 per result. A strategy of testing each EA for infection is more expensive than two annual rounds of MDA unless the kit cost is less than $1.38 per result. However stopping or deciding not to initiate treatment in the study area based on testing a sample of EAs for Ct infection (or examining children in a sample of EAs) creates savings relative to further unnecessary treatments. Resources may be saved by using tests for chlamydial infection or clinical examination to determine that initial or subsequent rounds of MDA for trachoma are unnecessary.

Costs of Testing for Ocular Chlamydia trachomatis Infection Compared to Mass Drug Administration for Trachoma in The Gambia: Application of Results from the PRET Study

PubMed Central

Harding-Esch, Emma; Jofre-Bonet, Mireia; Dhanjal, Jaskiran K.; Burr, Sarah; Edwards, Tansy; Holland, Martin; Sillah, Ansumana; West, Sheila; Lietman, Tom; Keenan, Jeremy; Mabey, David; Bailey, Robin

2015-01-01

Background Mass drug administration (MDA) treatment of active trachoma with antibiotic is recommended to be initiated in any district where the prevalence of trachoma inflammation, follicular (TF) is ≥10% in children aged 1–9 years, and then to continue for at least three annual rounds before resurvey. In The Gambia the PRET study found that discontinuing MDA based on testing a sample of children for ocular Chlamydia trachomatis(Ct) infection after one MDA round had similar effects to continuing MDA for three rounds. Moreover, one round of MDA reduced disease below the 5% TF threshold. We compared the costs of examining a sample of children for TF, and of testing them for Ct, with those of MDA rounds. Methods The implementation unit in PRET The Gambia was a census enumeration area (EA) of 600–800 people. Personnel, fuel, equipment, consumables, data entry and supervision costs were collected for census and treatment of a sample of EAs and for the examination, sampling and testing for Ct infection of 100 individuals within them. Programme costs and resource savings from testing and treatment strategies were inferred for the 102 EAs in the study area, and compared. Results Census costs were $103.24 per EA plus initial costs of $108.79. MDA with donated azithromycin cost $227.23 per EA. The mean cost of examining and testing 100 children was $796.90 per EA, with Ct testing kits costing $4.80 per result. A strategy of testing each EA for infection is more expensive than two annual rounds of MDA unless the kit cost is less than $1.38 per result. However stopping or deciding not to initiate treatment in the study area based on testing a sample of EAs for Ct infection (or examining children in a sample of EAs) creates savings relative to further unnecessary treatments. Conclusion Resources may be saved by using tests for chlamydial infection or clinical examination to determine that initial or subsequent rounds of MDA for trachoma are unnecessary. PMID:25901349

Biological measure of compliance to Artesunate plus Amodiaquine association: interest in a Mono-Desethyl-Amodiaquine blood assay?

PubMed

Sarrassat, Sophie; Sakho, Madiagne; Le Hesran, Jean Yves

2009-04-01

The deployment of Artemisinin-based Combination Therapy for treating uncomplicated malaria poses problems in the patient compliance to these new treatments. The aim of our study was to investigate the relationship between compliance to 3 days treatment with Artesunate plus Amodiaquine (AS+AQ) and the Mono-Desethyl-Amodiaquine (MDA) blood concentration on the fourth day. A reference scale of mean MDA blood concentrations was constructed in 40 healthy adults. Each concentration corresponded to the MDA level on day 3 in a subject having one of the seven compliance degrees defined by the number and sequence of drug intakes from day 0 to day 2: one single dose on day 0, day 1 or day 2; two single doses separated by 24h, on day 0 and day 1 or on day 1 and day 2; two single doses separated by 48 h, on day 0 and day 2; three single doses, on day 0, day 1 and day 2. MDA was assayed in whole blood samples by HPLC. Non-parametric Mann and Whitney U tests were used for the comparison of two means. Our results demonstrated no clear relationship between the mean MDA blood concentrations on day 3 and compliance degrees, according to neither the number nor the sequence of doses taken. In particular, even though the differences were not significant, the mean concentration after three doses, expected to be the maximum, was unexpectedly lower than after two doses, on day 0 and day 1 or on day 1 and day 2. The high inter-individual variability of MDA concentrations attributed to the different rates of hepatic metabolism of each individual appears to have a greater effect on MDA levels than the number or timing of doses. Therefore, it seems that the role of a MDA blood assay is limited in use to discerning if none or one or more doses have been taken. A MDA assay do not allow to measure the compliance degree of one patient to AS+AQ association. Presently, interview and pill count following treatment seem to be the only tools available that may permit differentiation between degrees of compliance.

Study of oxidative stress biomarkers in chronic obstructive pulmonary disease and their correlation with disease severity in north Indian population cohort

PubMed Central

Bajpai, Jyoti; Prakash, Ved; Kant, Surya; Verma, Ajay Kumar; Srivastava, Anand; Bajaj, Darshan K; Ahmad, MK; Agarwal, Avinash

2017-01-01

Background: Oxidant-antioxidant imbalance forms a prime component in pathogenesis of chronic obstructive pulmonary disease (COPD). Studies of oxidative stress markers in South Asians were sparse. Methods: One hundred and eighty COPD patients and eighty healthy nonsmokers were enrolled in the study. Serum malondialdehyde (MDA) and iron levels were estimated for oxidative stress. Three antioxidant markers evaluated-catalase, superoxide dismutase (SOD), and serum copper. Patients on antioxidant therapy and with sepsis and chronic illness were excluded from the study. Results: The mean age of COPD patients was 59.29 ± 10.3 years. Serum levels of MDA and iron were significantly higher in COPD patients compared to controls (5.21 ± 1.9 vs. 0.71 ± 0.29 nmol MDA/ml, P = 0.0001 and 69.85 ± 85.49 vs. 79.32 ± 24.39 μg/dl, P = 0.0001, respectively). Mean level of all antioxidant enzymes catalase, SOD, and copper were significantly diminished in cases when compared to control population (P = 0.001). Levels of MDA and iron were found to be significantly elevated in higher Global Initiative for Chronic Obstructive Lung Disease (GOLD) classes (III, IV) when compared to lower GOLD Classes (I, II). The levels of serum antioxidants were significantly depleted in higher GOLD grades too. COPD patients who were male and smoked had significantly higher levels of oxidants and depleted antioxidant levels compared to female and nonsmoking compatriots. Serum MDA levels negatively correlated with forced expiratory volume 1 s and forced vital capacity (r = −0.19 and r = −0.21, P ≤ 0.01). The presence of a cough significantly correlated with higher levels of MDA and iron (P = 0.001). The levels of MDA negatively correlated with SOD and catalase levels. Conclusion: Oxidative markers (MDA and iron) are higher whereas antioxidants (catalase, copper, and SOD) are significantly reduced in patients of COPD. Serum MDA levels correlate with lung functions and disease severity. PMID:28671162

Context dependent reversion of tumor phenotype by connexin-43 expression in MDA-MB231 cells and MCF-7 cells: Role of β-catenin/connexin43 association

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

Talhouk, Rabih S., E-mail: rtalhouk@aub.edu.lb; Fares, Mohamed-Bilal; Rahme, Gilbert J.

Connexins (Cx), gap junction (GJ) proteins, are regarded as tumor suppressors, and Cx43 expression is often down regulated in breast tumors. We assessed the effect of Cx43 over-expression in 2D and 3D cultures of two breast adenocarcinoma cell lines: MCF-7 and MDA-MB-231. While Cx43 over-expression decreased proliferation of 2D and 3D cultures of MCF-7 by 56% and 80% respectively, MDA-MB-231 growth was not altered in 2D cultures, but exhibited 35% reduction in 3D cultures. C-terminus truncated Cx43 did not alter proliferation. Untransfected MCF-7 cells formed spherical aggregates in 3D cultures, and MDA-MB-231 cells formed stellar aggregates. However, MCF-7 cells over-expressingmore » Cx43 formed smaller sized clusters and Cx43 expressing MDA-MB-231 cells lost their stellar morphology. Extravasation ability of both MCF-7 and MDA-MB-231 cells was reduced by 60% and 30% respectively. On the other hand, silencing Cx43 in MCF10A cells, nonneoplastic human mammary cell line, increased proliferation in both 2D and 3D cultures, and disrupted acinar morphology. Although Cx43 over-expression did not affect total levels of β-catenin, α-catenin and ZO-2, it decreased nuclear levels of β-catenin in 2D and 3D cultures of MCF-7 cells, and in 3D cultures of MDA-MB-231 cells. Cx43 associated at the membrane with α-catenin, β-catenin and ZO-2 in 2D and 3D cultures of MCF-7 cells, and only in 3D conditions in MDA-MB-231 cells. This study suggests that Cx43 exerts tumor suppressive effects in a context-dependent manner where GJ assembly with α-catenin, β-catenin and ZO-2 may be implicated in reducing growth rate, invasiveness, and, malignant phenotype of 2D and 3D cultures of MCF-7 cells, and 3D cultures of MDA-MB-231 cells, by sequestering β-catenin away from nucleus. - Highlights: • Cx43 over-expressing MCF-7 and MDA-MB-231 were grown in 2D and 3D cultures. • Proliferation and growth morphology were affected in a context dependent manner. • Extravasation ability of both MCF-7 and MDA-MB-231 cells was reduced. • Cx43-mediated gap junction complex assembly correlated with observed changes. • We propose that membranous Cx43 sequesters β-catenin away from the nucleus.« less

Thermal performance demonstration of a prototype internally cooled nose tip/forebody/window assembly

NASA Astrophysics Data System (ADS)

Wojciechowski, Carl J.; Brooks, Lori C.; Teal, Gene; Karu, Zain; Kalin, David A.; Jones, Gregory W.; Romero, Harold

1996-11-01

Internally liquid cooled apertures (windows) installed in a full size forebody have been characterized under high heat flux conditions representative of endoatmospheric flight. Analysis and test data obtained in the laboratory and at arc heater test facilities at Arnold Engineering Development Center and NASA Ames are presented in this paper. Data for several types of laboratory bench tests are presented: transmission interferometry and imaging, coolant pressurization effects on optical quality, and coolant flow rate calibrations for both the window and other internally cooled components. Initially, using heat transfer calibration models identical in shape to the flight test articles, arc heater facility thermal test environments were obtained at several conditions representative of full flight thermal environments. Subsequent runs tested the full-up flight article including nosetip, forebody and aperture for full flight duplication of surface heating rates and exposure ties. Pretest analyses compared will to test measurements. These data demonstrate a very efficient internal liquid cooling design which can be applied to other applications such as cooled mirrors for high heat flux applications.

Non-destructive determination of Malondialdehyde (MDA) distribution in oilseed rape leaves by laboratory scale NIR hyperspectral imaging

NASA Astrophysics Data System (ADS)

Kong, Wenwen; Liu, Fei; Zhang, Chu; Zhang, Jianfeng; Feng, Hailin

2016-10-01

The feasibility of hyperspectral imaging with 400-1000 nm was investigated to detect malondialdehyde (MDA) content in oilseed rape leaves under herbicide stress. After comparing the performance of different preprocessing methods, linear and nonlinear calibration models, the optimal prediction performance was achieved by extreme learning machine (ELM) model with only 23 wavelengths selected by competitive adaptive reweighted sampling (CARS), and the result was RP = 0.929 and RMSEP = 2.951. Furthermore, MDA distribution map was successfully achieved by partial least squares (PLS) model with CARS. This study indicated that hyperspectral imaging technology provided a fast and nondestructive solution for MDA content detection in plant leaves.

Celebrating 100 Years of Flight.

ERIC Educational Resources Information Center

Reese, Susan

2003-01-01

In honor of the Wright brothers' first flight, the article profiles aviation and aerospace technology programs that are training workers in aviation safety and explorations. Looks at programs from Eastern New Mexico University-Roswell, Pima Community College, and Olathe Northwest High School. (JOW)

International Space Station (ISS)

NASA Image and Video Library

2000-07-01

The 45-foot, port-side (P1) truss segment flight article for the International Space Station is being transported to the Redstone Airfield, Marshall Space Flight Center. The truss will be loaded aboard NASA's Super Guppy cargo plane for shipment to the Kennedy Space Center.

HyBoLT Flight Experiment

NASA Technical Reports Server (NTRS)

Chen, Fang-Jeng (Frank); Berry, Scott A.

2010-01-01

HyBoLT was a Hypersonic Boundary Layer Transition flight experiment funded by the Hypersonics Project of the Fundamental Aeronautics Program in NASA's Aeronautics Research Mission Directorate. The HyBoLT test article mounted on the top of the ALV X-1 rocket was launched from Virginia's Wallops Island on August 22, 2008. Unfortunately a problem in the rocket's flight control system caused the vehicle to veer off the designed flight course. Launch officials activated a self-destruct mechanism in the rocket's nose cone after 20 seconds into flight. This report is a closeout document about the HyBoLT flight experiment. Details are provided of the objectives and approach associated with this experimental program as well as the 20 seconds flight data acquired before the vehicle was destroyed.

Satellite Power Systems (SPS). LSST systems and integration task for SPS flight test article

NASA Technical Reports Server (NTRS)

Greenberg, H. S.

1981-01-01

This research activity emphasizes the systems definition and resulting structural requirements for the primary structure of two potential SPS large space structure test articles. These test articles represent potential steps in the SPS research and technology development.

Prophylactic surgery prior to extended-duration space flight: Is the benefit worth the risk?

PubMed Central

Ball, Chad G.; Kirkpatrick, Andrew W.; Williams, David R.; Jones, Jeffrey A.; Polk, J.D.; Vanderploeg, James M.; Talamini, Mark A.; Campbell, Mark R.; Broderick, Timothy J.

2012-01-01

This article explores the potential benefits and defined risks associated with prophylactic surgical procedures for astronauts before extended-duration space flight. This includes, but is not limited to, appendectomy and cholecystesctomy. Furthermore, discussion of treatment during space flight, potential impact of an acute illness on a defined mission and the ethical issues surrounding this concept are debated in detail. PMID:22564516

Community health workers' experiences and perspectives on mass drug administration for schistosomiasis control in western Kenya: the SCORE Project.

PubMed

Omedo, Martin O; Matey, Elizabeth J; Awiti, Alphonce; Ogutu, Michael; Alaii, Jane; Karanja, Diana M S; Montgomery, Susan P; Secor, W Evan; Mwinzi, Pauline N M

2012-12-01

Abstract. The Schistosomiasis Consortium for Operational Research and Evaluation (SCORE) includes communitywide treatment in areas with ≥ 25% prevalence of schistosomiasis along the shores of Lake Victoria using community health workers (CHWs). The CHWs are key drivers in community-owned mass drug administration (MDA) intervention programs. We explored their experiences and perceptions after initial MDA participation. Unstructured open-ended group discussions were conducted after completion of MDA activities. Narratives were obtained from CHWs using a digital audio recorder during the group discussion, transcribed verbatim and translated into English where applicable. Thematic decomposition of data was done using ATLAS.t.i. software. From the perspective of the CHWs, factors influencing MDA compliance included drug side effects, food supply stability, and conspiracy theories about the "real" purpose of treatment. The interest of CHWs to serve as community drug distributors stemmed from both intrinsic and extrinsic factors. Feedback from CHWs can promote more effective MDA in rural Kenyan communities.

Coverage and Awareness of and Compliance with Mass Drug Administration for Elimination of Lymphatic Filariasis in Burdwan District, West Bengal, India

PubMed Central

Sarkar, Aditya Prasad; Misra, Raghunath; Chakroborty, Amitava; Mondal, Tusar Kanti; Bag, Kanad

2013-01-01

India adopted WHO's strategy of repeated rounds of mass drug administration (MDA) with diethylcarbamazine to eliminate lymphatic filariasis. The present study attempted to assess the coverage and awareness of and compliance with MDA for elimination of lymphatic filariasis in Burdwan district of India, following MDA round in July 2010. A cross-sectional study was conducted among the four randomly-selected clusters in the district of Burdwan, West Bengal, India, covering 603 individuals from 154 households, using a predesigned pretested schedule. The drug distribution coverage, compliance, and effective coverage were 48.76 %, 70.07%, and 34.16% respectively. Only 41.4% of the study population was aware of the MDA activity. This evaluation study noted that MDA is restricted to tablet distribution only. There is an urgent need to improve compliance with drug intake through strengthening of the awareness programme involving both government health workers and community volunteers. PMID:23930334

Acute and subacute toxicities effect of oxytetracycline pharmaceutical wastewater on Zebrafish

NASA Astrophysics Data System (ADS)

Wu, Pengpeng; Shen, Hong-Yan

2018-02-01

Oxytetracycline wastewater is a major category of pharmaceutical wastewater, and its toxic effects on aquatic organisms have aroused people’s attention. In this study, Zebrafish were separately exposed to four Oxytetracycline wastewater treatments (20%, 40%, 60%, 80%) and a control group were sampled on days 3, 6, 9, 12, and 15. Superoxide dismutase (SOD) activities showed significant inhibition, but the highest SOD activity was found in 20% and 40% the treatment groups (195.12U/mgprot, 187.43U/mgprot, respectively) on the 12th day. MDA contents increased significantly compared with control group. MDA contents showed that the higher the volume concentration, the higher the contents of MDA with the increase of exposure time. The highest MDA content shown in 60% exposure group (5.49nmol/mgprot) on the 12th day. And SOD activities and MDA contents showed a trend of “Λ” type. In conclusion, Oxytetracycline wastewater induced oxidative stress and toxicity in Zebrafish muscle tissue.

Effects of maternally-derived antibodies on serologic responses to vaccination in kittens.

PubMed

Digangi, Brian A; Levy, Julie K; Griffin, Brenda; Reese, Michael J; Dingman, Patricia A; Tucker, Sylvia J; Dubovi, Edward J

2012-02-01

The optimal vaccination protocol to induce immunity in kittens with maternal antibodies is unknown. The objective of this study was to determine the effects of maternally-derived antibody (MDA) on serologic responses to vaccination in kittens. Vaccination with a modified live virus (MLV) product was more effective than an inactivated (IA) product at inducing protective antibody titers (PAT) against feline panleukopenia virus (FPV). IA vaccination against feline herpesvirus-1 (FHV) and feline calicivirus (FCV) was more effective in the presence of low MDA than high MDA. Among kittens with low MDA, MLV vaccination against FCV was more effective than IA vaccination. A total of 15%, 44% and 4% of kittens had insufficient titers against FPV, FHV and FCV, respectively, at 17 weeks of age. Serologic response to vaccination of kittens varies based on vaccination type and MDA level. In most situations, MLV vaccination should be utilized and protocols continued beyond 14 weeks of age to optimize response by all kittens.

Free trade and occupational health policy: an argument for health and safety across the North American workplace.

PubMed

McGuinness, M J

1994-01-01

This article considers the argument that the North American Free Trade Agreement (NAFTA) would encourage US and Canadian industry to relocate their hazardous manufacturing operations to Mexico. Proponents of this view believe that this industrial flight south would worsen working conditions in Mexico as well as lower occupational health and safety standards in the US and Canada. In evaluating this argument, the article examines working conditions in US-owned factories in the Mexican maquiladora zone, reviews the current occupational health and safety regulatory structure in Mexico, and considers those institutions established by the European Community to protect workers against the flight of hazardous industries. The article concludes that the harmonization of labor norms throughout North American and the establishment of a functional North American regulatory structure following the precedents set by the European Community are necessary steps to ensure that NAFTA does not produce the feared flight of hazardous industries to Mexico nor degrade the health of workers in Mexico, Canada, or the US.

microRNA-145 regulates the RLR signaling pathway in miiuy croaker after poly(I:C) stimulation via targeting MDA5.

PubMed

Han, Jingjing; Sun, Yuena; Song, Weihua; Xu, Tianjun

2017-03-01

MicroRNAs (miRNAs) are endogenous small non-coding RNAs that participate in diverse biological processes via degrading the target mRNAs or repressing translation. In this study, the regulation of miRNA to the RLR (RIG-I-like receptor) signaling pathway by degrading the target mRNAs was researched in miiuy croaker. MDA5, a microRNA-145-5p (miR-145-5p) putative target gene, was predicted by bioinformatics, and the target sites from the 3'untranslated region of MDA5 transcripts were confirmed using luciferase reporter assays. Pre-miR-145 was more effective in inhibiting MDA5 than miR-145-5p mimic, and the effect was dose- and time-dependent. The expression patterns of miR-145-5p and MDA5 were analyzed in liver and kidney from miiuy croaker. Results implied that miR-145-5p may function via degrading the MDA5 mRNAs, thereby regulating the RLR signaling pathway. Studies on miR-145-5p will enrich knowledge of its functions in immune response regulation in fish, as well as offer a basis for regulatory networks that are composed of numerous miRNAs. Copyright © 2016 Elsevier Ltd. All rights reserved.

Malondialdehyde epitopes as targets of immunity and the implications for atherosclerosis

PubMed Central

Binder, Christoph J.

2018-01-01

Accumulating evidence suggests that oxidation-specific epitopes (OSEs) constitute a novel class of damage-associated molecular patterns (DAMPs) generated during high oxidative stress but also in the physiological process of apoptosis. To deal with the potentially harmful consequences of such epitopes, the immune system has developed several mechanisms to protect from OSEs and to orchestrate their clearance, including IgM natural antibodies and both cellular and membrane-bound receptors. Here, we focus on malondialdehyde (MDA) epitopes as prominent examples of OSEs that trigger both innate and adaptive immune responses. First, we review the mechanism of MDA generation, the different types of adducts on various biomolecules and provide relevant examples for physiological carriers of MDA such as apoptotic cells, microvesicles (MV) or oxidized low-density lipoproteins (LDL). Based on recent insights, we argue that MDA epitopes contribute to the maintenance of homeostatic functions by acting as markers of elevated oxidative stress and tissue damage. We discuss multiple lines of evidence that MDA epitopes are pro-inflammatory and thus important targets of innate and adaptive immune responses. Finally, we illustrate the relevance of MDA epitopes in human pathologies by describing their capacity to drive inflammatory processes in atherosclerosis and highlighting protective mechanisms of immunity that could be exploited for therapeutic purposes. PMID:27235680

Use of Multiple Displacement Amplification as Pre-polymerase Chain Reaction (Pre-PCR) to amplify genomic DNA of siphonapterids preserved for long periods in scientific collections.

PubMed

Avelar, Daniel M; Linardi, Pedro M

2010-09-15

The recently developed Multiple Displacement Amplification technique (MDA) allows for the production of a large quantity of high quality genomic DNA from low amounts of the original DNA. The goal of this study was to evaluate the performance of the MDA technique to amplify genomic DNA of siphonapterids that have been stored for long periods in 70% ethanol at room temperature. We subjected each DNA sample to two different methodologies: (1) amplification of mitochondrial 16S sequences without MDA; (2) amplification of 16S after MDA. All the samples obtained from these procedures were then sequenced. Only 4 samples (15.4%) subjected to method 1 showed amplification. In contrast, the application of MDA (method 2) improved the performance substantially, with 24 samples (92.3%) showing amplification, with significant difference. Interestingly, one of the samples successfully amplified with this method was originally collected in 1909. All of the sequenced samples displayed satisfactory results in quality evaluations (Phred ≥ 20) and good similarities, as identified with the BLASTn tool. Our results demonstrate that the use of MDA may be an effective tool in molecular studies involving specimens of fleas that have traditionally been considered inadequately preserved for such purposes.

Use of Multiple Displacement Amplification as Pre-polymerase Chain Reaction (Pre-PCR) to amplify genomic DNA of siphonapterids preserved for long periods in scientific collections

PubMed Central

2010-01-01

The recently developed Multiple Displacement Amplification technique (MDA) allows for the production of a large quantity of high quality genomic DNA from low amounts of the original DNA. The goal of this study was to evaluate the performance of the MDA technique to amplify genomic DNA of siphonapterids that have been stored for long periods in 70% ethanol at room temperature. We subjected each DNA sample to two different methodologies: (1) amplification of mitochondrial 16S sequences without MDA; (2) amplification of 16S after MDA. All the samples obtained from these procedures were then sequenced. Only 4 samples (15.4%) subjected to method 1 showed amplification. In contrast, the application of MDA (method 2) improved the performance substantially, with 24 samples (92.3%) showing amplification, with significant difference. Interestingly, one of the samples successfully amplified with this method was originally collected in 1909. All of the sequenced samples displayed satisfactory results in quality evaluations (Phred ≥ 20) and good similarities, as identified with the BLASTn tool. Our results demonstrate that the use of MDA may be an effective tool in molecular studies involving specimens of fleas that have traditionally been considered inadequately preserved for such purposes. PMID:20840790

Patient-centered communication of community treatment assistants in Tanzania predicts coverage of future mass drug administration for trachoma.

PubMed

Jenson, Alexander; Roter, Debra L; Mkocha, Harran; Munoz, Beatriz; West, Sheila

2018-06-01

Prevention of Trachoma, the leading cause of infectious blindness, requires community treatment assistants (CTAs) to perform mass drug administration (MDA) of azithromycin. Previous research has shown that female CTAs have higher MDA coverage, but no studies have focused on the content of conversation. We hypothesize that female CTAs had more patient-centered communication and higher MDA coverage. In 2011, CTAs from 23 distribution sites undergoing MDA as part of the Partnership for Rapid Elimination of Trachoma were selected. CTA - villager interactions were audio recorded. Audio was analyzed using an adaptation of the Roter Interaction Analysis System. The outcome of interest was the proportion of adults receiving MDA in 2011 who returned in 2012. 58 CTAs and 3122 interactions were included. Sites with female CTAs had significantly higher patient-centeredness ratio (0.548 vs 0.400) when compared to sites with male CTAs. Sites with more patient-centered interactions had higher proportion of patients return (p = 0.009). Female CTAs had higher proportion of patient-centered communication. Patient centered communication was associated with higher rates of return for MDA. Greater patient-centered connection with health care providers affects participation in public health efforts, even when those providers are lay health workers. Copyright © 2018 Elsevier B.V. All rights reserved.

Analysis of a carcinogen, 4,4'-methylenedianiline, from thermosetting polyurethane during sterilization.

PubMed

Shintani, H; Nakamura, A

1989-01-01

Polyurethane (PU) is widely used in medical devices such as potting material in artificial dialysis devices, plasma separators, etc. Gamma-ray irradiation is frequently used for the sterilization of such devices. This paper reports that a carcinogen, 4,4'-methylenedianiline (MDA, p,p'-diaminodiphenylmethane), is produced from medical thermosetting PU by gamma-ray irradiation. Gamma-ray irradiated PU was immersed in methanol or equine serum. The serum was treated with a mixture of 5N HCIO4:acetonitrile (1:10) in order to deproteinate and recover MDA. It was found that MDA is formed from thermosetting PU at around a few ppm in the original sample. The production of MDA increased with increasing irradiation dose. The MDA amount formed was related to the irradiation dose by a second order equation. Results of methanol and serum extraction were similar. Pressurized steam (autoclave) sterilization in place of gamma-ray sterilization was also examined. MDA production was not found in autoclave sterilization procedures. Gel permeation chromatography (GPC) of methanol or N,N-dimethylformamide (DMF) extract of irradiated PU showed that the PU oligomers eluted. Time course of methanol extract of irradiated PU was detected at 245.5 nm. This showed an exponential decline regardless of doses of irradiation.

[Inhibitory effect of exogenous insulin-like growth factor binding protein 7 on proliferation of human breast cancer cell line MDA-MB-453 and its mechanism].

PubMed

Yuan, Lei; Fan, Wen-Juan; Yang, Xu-Guang; Rao, Shu-Mei; Song, Jin-Ling; Song, Guo-Hua

2013-10-25

The present study was to investigate the effects of exogenous insulin-like growth factor binding protein 7 (IGFBP7) on the proliferation of human breast cancer cell line MDA-MB-453 and its possible mechanism. By means of MTT method in vitro, the results showed exogenous IGFBP7 inhibited the growth of MDA-MB-453 cells (IC50 of IGFBP7 = 8.49 μg/mL) in time- and concentration-dependent manner. SB203580, p38(MAPK) inhibitor, blocked the anti-proliferative effect of exogenous IGFBP7. The flow cytometry assay showed that exogenous IGFBP7 remarkably induced G0/G1 arrest in MDA-MB-453 cells. The Western blot showed that exogenous IGFBP7 promoted phosphorylation of p38(MAPK), up-regulated expression of p21(CIP1/WAF1), and inhibited phosphorylation of Rb. SB203580 restrained exogenous IGFBP7-induced regulation of p21(CIP1/WAF1) and p-Rb in MDA-MB-453 cells. In conclusion, the present study suggests that exogenous IGFBP7 could activate the p38(MAPK) signaling pathway, upregulate p21(CIP1/WAF1) expression, inhibit phosphorylation of Rb, and finally induce G0/G1 arrest in MDA-MB-453 cells.

Metabolically Generated Stable Isotope-Labeled Deoxynucleoside Code for Tracing DNA N6-Methyladenine in Human Cells.

PubMed

Liu, Baodong; Liu, Xiaoling; Lai, Weiyi; Wang, Hailin

2017-06-06

DNA N 6 -methyl-2'-deoxyadenosine (6mdA) is an epigenetic modification in both eukaryotes and bacteria. Here we exploited stable isotope-labeled deoxynucleoside [ 15 N 5 ]-2'-deoxyadenosine ([ 15 N 5 ]-dA) as an initiation tracer and for the first time developed a metabolically differential tracing code for monitoring DNA 6mdA in human cells. We demonstrate that the initiation tracer [ 15 N 5 ]-dA undergoes a specific and efficient adenine deamination reaction leading to the loss the exocyclic amine 15 N, and further utilizes the purine salvage pathway to generate mainly both [ 15 N 4 ]-dA and [ 15 N 4 ]-2'-deoxyguanosine ([ 15 N 4 ]-dG) in mammalian genomes. However, [ 15 N 5 ]-dA is largely retained in the genomes of mycoplasmas, which are often found in cultured cells and experimental animals. Consequently, the methylation of dA generates 6mdA with a consistent coding pattern, with a predominance of [ 15 N 4 ]-6mdA. Therefore, mammalian DNA 6mdA can be potentially discriminated from that generated by infecting mycoplasmas. Collectively, we show a promising approach for identification of authentic DNA 6mdA in human cells and determine if the human cells are contaminated with mycoplasmas.

Salivary Lipid Peroxidation and Total Sialic Acid Levels in Smokers and Smokeless Tobacco Users as Maraş Powder

PubMed Central

Kurtul, Naciye; Gökpınar, Engin

2012-01-01

Maraş powder (MP), a different type of smokeless tobacco (ST) and prepared from a tobacco of species Nicotiana rustica Linn, is widely used in Turkey. We aimed to investigate the effects of MP on salivary total sialic acid (TSA) and malondialdehyde (MDA) levels and to compare these parameters in smokers and MP users (MPUs). The salivary TSA and MDA concentrations were significantly higher in the smokers and MPU than those of control subjects and also in MPU than that of smokers. We have also observed that as the number of cigarettes consumed and MP amount increases, TSA and MDA levels increase too. In smokers, MDA values were significantly correlated with the number of cigarettes smoked and the duration of smoking. In MPU, both MDA and TSA levels were significantly correlated with the duration of MP use and the amount of daily consumed MP. We have concluded increased salivary TSA and MDA levels associated in MPU and smokers. Results can help to evaluate harmful effects of these habits. It is important to point out that bigger change in the measured parameters has been observed for MP use. This observation may be an important indication of harmful effects of ST use as MP. PMID:22577253

P16-positive continuous minimal deviation adenocarcinoma and gastric type adenocarcinoma in a patient with Peutz-Jeghers syndrome.

PubMed

Peng, Wei-Xia; Kure, Shoko; Ishino, Kousuke; Kurose, Keisuke; Yoneyama, Koichi; Wada, Ryuichi; Naito, Zenya

2015-01-01

We report a case of Peutz-Jeghers syndrome (PJS) in a 33-year-old female patient with synchronous uterine cervical minimal deviation adenocarcinoma (MDA) and gastric type adenocarcinoma (GTA). The patient was diagnosed with PJS at the age of 10. At the time of consultation, she complained of watery discharge. Magnetic resonance imaging of the pelvis showed a poorly circumscribed mass in the uterine cervix. Histologically, both MDA and GTA components, as well as their transitional area, were observed. Both components were diffusely positive for MUC6, CK7 and, robustly, for p16. Moreover, the components were negative for ER, PgR and CEA, while HIK1083 and CK20 positive cells were found focally. Ki-67 labeling index in the MDA component was 5% while that in the GTA component was 50%. This case of GTA accompanied by MDA in a patient with PJS is distinct from the single previously-reported comparable case of which we are aware, with respect to the overexpression of p16 protein, an event considered rare in these tumors, and the continuity between the MDA and GTA components. This continuity favors the hypothesis that GTA arises from the dedifferentiation of MDA.

P16-positive continuous minimal deviation adenocarcinoma and gastric type adenocarcinoma in a patient with Peutz-Jeghers syndrome

PubMed Central

Peng, Wei-Xia; Kure, Shoko; Ishino, Kousuke; Kurose, Keisuke; Yoneyama, Koichi; Wada, Ryuichi; Naito, Zenya

2015-01-01

We report a case of Peutz-Jeghers syndrome (PJS) in a 33-year-old female patient with synchronous uterine cervical minimal deviation adenocarcinoma (MDA) and gastric type adenocarcinoma (GTA). The patient was diagnosed with PJS at the age of 10. At the time of consultation, she complained of watery discharge. Magnetic resonance imaging of the pelvis showed a poorly circumscribed mass in the uterine cervix. Histologically, both MDA and GTA components, as well as their transitional area, were observed. Both components were diffusely positive for MUC6, CK7 and, robustly, for p16. Moreover, the components were negative for ER, PgR and CEA, while HIK1083 and CK20 positive cells were found focally. Ki-67 labeling index in the MDA component was 5% while that in the GTA component was 50%. This case of GTA accompanied by MDA in a patient with PJS is distinct from the single previously-reported comparable case of which we are aware, with respect to the overexpression of p16 protein, an event considered rare in these tumors, and the continuity between the MDA and GTA components. This continuity favors the hypothesis that GTA arises from the dedifferentiation of MDA. PMID:26191312

Malondialdehyde epitopes are sterile mediators of hepatic inflammation in hypercholesterolemic mice

PubMed Central

Weismann, David; Jäckel, Sven; Walenbergh, Sofie M. A.; Rendeiro, André F.; Weißer, Juliane; Puhm, Florian; Hladik, Anastasiya; Göderle, Laura; Papac-Milicevic, Nikolina; Haas, Gerald; Millischer, Vincent; Subramaniam, Saravanan; Knapp, Sylvia; Bennett, Keiryn L.; Bock, Christoph; Reinhardt, Christoph; Shiri-Sverdlov, Ronit; Binder, Christoph J.

2018-01-01

Background and Rationale Diet-related health issues such as non-alcoholic fatty liver disease and cardiovascular disorders are known to have a major inflammatory component. However, the exact pathways linking diet-induced changes e.g. hyperlipidemia, and the ensuing inflammation have remained elusive so far. Main Results We identified biological processes related to innate immunity and oxidative stress as prime response pathways in livers of Ldlr-/- mice on Western-type diet using RNA sequencing and in silico functional analyses of transcriptome data. The observed changes were independent of the presence of microbiota and thus indicative of a role for sterile triggers. We further show that MDA epitopes, products of lipid peroxidation and markers for enhanced oxidative stress, are detectable in hepatic inflammation predominantly on dying cells and stimulate cytokine secretion as well as leukocyte recruitment in vitro and in vivo. MDA-induced cytokine secretion in vitro was dependent on the presence of scavenger receptors CD36 and MSR1. Moreover, in vivo neutralization of endogenously generated MDA epitopes by intravenous injection of a specific MDA antibody results in decreased hepatic inflammation in Ldlr-/- mice on Western-type diet. Conclusions Accumulation of MDA epitopes plays a major role during diet-induced hepatic inflammation and can be ameliorated by administration of an anti-MDA antibody. PMID:27981604

Automated UAV-based video exploitation using service oriented architecture framework

NASA Astrophysics Data System (ADS)

Se, Stephen; Nadeau, Christian; Wood, Scott

2011-05-01

Airborne surveillance and reconnaissance are essential for successful military missions. Such capabilities are critical for troop protection, situational awareness, mission planning, damage assessment, and others. Unmanned Aerial Vehicles (UAVs) gather huge amounts of video data but it is extremely labour-intensive for operators to analyze hours and hours of received data. At MDA, we have developed a suite of tools that can process the UAV video data automatically, including mosaicking, change detection and 3D reconstruction, which have been integrated within a standard GIS framework. In addition, the mosaicking and 3D reconstruction tools have also been integrated in a Service Oriented Architecture (SOA) framework. The Visualization and Exploitation Workstation (VIEW) integrates 2D and 3D visualization, processing, and analysis capabilities developed for UAV video exploitation. Visualization capabilities are supported through a thick-client Graphical User Interface (GUI), which allows visualization of 2D imagery, video, and 3D models. The GUI interacts with the VIEW server, which provides video mosaicking and 3D reconstruction exploitation services through the SOA framework. The SOA framework allows multiple users to perform video exploitation by running a GUI client on the operator's computer and invoking the video exploitation functionalities residing on the server. This allows the exploitation services to be upgraded easily and allows the intensive video processing to run on powerful workstations. MDA provides UAV services to the Canadian and Australian forces in Afghanistan with the Heron, a Medium Altitude Long Endurance (MALE) UAV system. On-going flight operations service provides important intelligence, surveillance, and reconnaissance information to commanders and front-line soldiers.

Advanced glycation end products and antioxidant status in type 2 diabetic patients with and without peripheral artery disease.

PubMed

Lapolla, Annunziata; Piarulli, Francesco; Sartore, Giovanni; Ceriello, Antonio; Ragazzi, Eugenio; Reitano, Rachele; Baccarin, Lorenzo; Laverda, Barbara; Fedele, Domenico

2007-03-01

Advanced glycation end products (AGEs), pentosidine and malondialdehyde (MDA), are elevated in type 2 diabetic subjects with coronary and carotid angiopathy. We investigated the relationship of AGEs, MDA, total reactive antioxidant potentials (TRAPs), and vitamin E in type 2 diabetic patients with and without peripheral artery disease (PAD). AGEs, pentosidine, MDA, TRAP, vitamin E, and ankle-brachial index (ABI) were measured in 99 consecutive type 2 diabetic subjects and 20 control subjects. AGEs, pentosidine, and MDA were higher and vitamin E and TRAP were lower in patients with PAD (ABI <0.9) than in patients without PAD (ABI >0.9) (P < 0.001). After multiple regression analysis, a correlation between AGEs and pentosidine, as independent variables, and ABI, as the dependent variable, was found in both patients with and without PAD (r = 0.9198, P < 0.001 and r = 0.5764, P < 0.001, respectively) but not in control subjects. When individual regression coefficients were evaluated, only that due to pentosidine was confirmed as significant. For patients with PAD, considering TRAP, vitamin E, and MDA as independent variables and ABI as the dependent variable produced an overall significant regression (r = 0.6913, P < 0.001). The regression coefficients for TRAP and vitamin E were not significant, indicating that the model is best explained by a single linear regression between MDA and ABI. These findings were also confirmed by principal component analysis. Results show that pentosidine and MDA are strongly associated with PAD in type 2 diabetic patients.

Apigenin inhibits the inducible expression of programmed death ligand 1 by human and mouse mammary carcinoma cells.

PubMed

Coombs, Melanie R Power; Harrison, Megan E; Hoskin, David W

2016-10-01

Programmed death ligand 1 (PD-L1) is expressed by many cancer cell types, as well as by activated T cells and antigen-presenting cells. Constitutive and inducible PD-L1 expression contributes to immune evasion by breast cancer (BC) cells. We show here that the dietary phytochemical apigenin inhibited interferon (IFN)-γ-induced PD-L1 upregulation by triple-negative MDA-MB-468 BC cells, HER2(+) SK-BR-3 BC cells, and 4T1 mouse mammary carcinoma cells, as well as human mammary epithelial cells, but did not affect constitutive PD-L1 expression by triple-negative MDA-MB-231 BC cells. IFN-β-induced expression of PD-L1 by MDA-MB-468 cells was also inhibited by apigenin. In addition, luteolin, the major metabolite of apigenin, inhibited IFN-γ-induced PD-L1 expression by MDA-MB-468 cells. Apigenin-mediated inhibition of IFN-γ-induced PD-L1 expression by MDA-MB-468 and 4T1 cells was associated with reduced phosphorylation of STAT1, which was early and transient at Tyr701 and sustained at Ser727. Apigenin-mediated inhibition of IFN-γ-induced PD-L1 expression by MDA-MB-468 cells also increased proliferation and interleukin-2 synthesis by PD-1-expressing Jurkat T cells that were co-cultured with MDA-MB-468 cells. Apigenin therefore has the potential to increase the vulnerability of BC cells to T cell-mediated anti-tumor immune responses. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

[Extensive digital necrosis during dermatomyositis associated with MDA-5 antibodies].

PubMed

Charbit, L; Bursztejn, A-C; Mohamed, S; Kaminsky, P; Lerondeau, B; Barbaud, A; Deibener-Kaminsky, J; Schmutz, J-L

2016-01-01

Dermatomyositis (DM) is an inflammatory disease associated with auto-antibodies in 50 to 70% of cases. A new antibody, anti MDA-5, has been described in association with a specific type of DM involving severe interstitial lung disease and minimal muscle disease. We report the first case of DM with MDA-5 antibodies and with interstitial lung disease and rapidly extensive digital necrosis. A 28-year-old male was hospitalized for asthenia, myalgia and subacute dyspnea. Examination demonstrated skin lesions with edema on every digit associated with purpuric and cyanotic lesions, as well as erythematous papules on the helix and the elbows, and Gottron's papules. Systemic corticosteroid therapy was initiated. The immunoprecipitation results indicated the presence of anti-MDA-5 antibodies. Despite corticosteroid therapy, the patient's respiratory status gradually deteriorated towards pulmonary fibrosis and rapidly extensive necrosis appeared on all fingers and toes. Theses effects were resistant to cyclophosphamide and immunoglobulin but were stabilized by cyclosporine. Anti-MDA-5 antibodies are specific to DM and constitute a risk factor for severe interstitial lung disease (70% of cases) with a higher risk of mortality (40%). The cutaneous presentation of this DM is specific with palmar papules and mucocutaneous ulceration. Rapidly extensive digital necrosis has not been previously reported. No treatment has demonstrated superiority. We report the first case of DM with anti-MDA-5 antibodies involving interstitial lung disease and massive digital necrosis. Because of the pulmonary risk, in the presence of clinical lesions containing anti-MDA-5 DM, screening for these antibodies should be carried out. Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Wasabi-derived 6-(methylsulfinyl)hexyl isothiocyanate induces apoptosis in human breast cancer by possible involvement of the NF-κB pathways.

PubMed

Fuke, Yoko; Hishinuma, Madoka; Namikawa, Mayumi; Oishi, Yoshie; Matsuzaki, Takeshi

2014-01-01

6-(methylsulfinyl)hexyl isothiocyanate (6-MSITC) is a bioactive ingredient of wasabi (Wasabia japonica), which is a popular spice in Japan. 6-MSITC has been reported to inhibit the proliferation of breast cancer and melanoma cell lines. We inoculated 30 female Balb-nu/nu mice with MDA-MB-231 or -453 cells, and orally administered varying concentrations of 6-MSITC for 12 days following tumor growth. The tumor volumes and tumor weights from mice inoculated with MDA-MB-231 cells, and the tumor volumes of MDA-MB-453 cells were significantly inhibited by 6-MSITC on Days 9 and 11 after drug administration. DNA fragmentation, DNA ladder, and caspase 3/7 activity performed in vitro revealed that 6-MSITC induced apoptosis of MDA-MB-231, MDA-MB-453, and MCF-7 cells. Furthermore, nuclear factor-κB (NF-κB) expression in the nuclei and phosphorylation of inhibitor κBα (IκBα) was downregulated by 6-MSITC in a concentration-dependent manner; however, this activity was not observed in MCF-7 cells. Moreover, this downregulation of phosphorylated IκBα by 6-MSITC in MDA-MB-231 and -453 cells supports its inhibitory effects on NF-κB activity. The expression of phosphorylated AKT (pAKT) reduced by 6-MSITC was confirmed in MDA-MB-231 cells. Thus, we conclude that 6-MITC promotes apoptosis of breast cancer cells by inhibiting NF-kB and therefore releasing its control of the PI3K/AKT pathway.

Accuracy of Coverage Survey Recall following an Integrated Mass Drug Administration for Lymphatic Filariasis, Schistosomiasis, and Soil-Transmitted Helminthiasis.

PubMed

Budge, Philip J; Sognikin, Edmond; Akosa, Amanda; Mathieu, Els M; Deming, Michael

2016-01-01

Achieving target coverage levels for mass drug administration (MDA) is essential to elimination and control efforts for several neglected tropical diseases (NTD). To ensure program goals are met, coverage reported by drug distributors may be validated through household coverage surveys that rely on respondent recall. This is the first study to assess accuracy in such surveys. Recall accuracy was tested in a series of coverage surveys conducted at 1, 6, and 12 months after an integrated MDA in Togo during which three drugs (albendazole, ivermectin, and praziquantel) were distributed. Drug distribution was observed during the MDA to ensure accurate recording of persons treated during the MDA. Information was obtained for 506, 1131, and 947 persons surveyed at 1, 6, and 12 months, respectively. Coverage (defined as the percentage of persons taking at least one of the MDA medications) within these groups was respectively 88.3%, 87.4%, and 80.0%, according to the treatment registers; it was 87.9%, 91.4% and 89.4%, according to survey responses. Concordance between respondents and registers on swallowing at least one pill was >95% at 1 month and >86% at 12 months; the lower concordance at 12 months was more likely due to difficulty matching survey respondents with the year-old treatment register rather than inaccurate responses. Respondents generally distinguished between pills similar in appearance; concordance for recall of which pills were taken was over 80% in each survey. In this population, coverage surveys provided remarkably consistent coverage estimates for up to one year following an integrated MDA. It is not clear if similar consistency will be seen in other settings, however, these data suggest that in some settings coverage surveys might be conducted as much as one year following an MDA without compromising results. This might enable integration of post-MDA coverage measurement into large, multipurpose, periodic surveys, thereby conserving resources.

Artemisinin combination therapy mass drug administration in a setting of low malaria endemicity: programmatic coverage and adherence during an observational study in Zanzibar.

PubMed

Ali, Abdullah S; Thawer, Narjis G; Khatib, Bakar; Amier, Haji H; Shija, Joseph; Msellem, Mwinyi; Al-Mafazy, Abdul-Wahid; Garimo, Issa A; Mkali, Humphrey; Ramsan, Mahdi M; Kafuko, Jessica M; Paxton, Lynn A; Reithinger, Richard; Ngondi, Jeremiah M

2017-08-14

Mass drug administration (MDA) appears to be effective in reducing the risk of malaria parasitaemia. This study reports on programmatic coverage and compliance of MDA using artemisinin-based combination therapy (ACT) in four shehias (smallest administration unit) that had been identified as hotspots through Zanzibar's malaria case notification surveillance system. Mass drug administration was done in four shehias selected on the basis of: being an established malaria hot spot; having had mass screening and treatment (MSaT) 2-6 weeks previously; and exceeding the epidemic alert threshold of 5 cases within a week even after MSaT. Communities were sensitized and MDA was conducted using a house-to-house approach. All household members, except pregnant women and children aged less than 2 months, were provided with ACT medicine. Two weeks after the MDA campaign, a survey was undertaken to investigate completion of ACT doses. A total of 8816 [97.1% of eligible; 95% confidence interval (CI) 96.8-97.5] people received ACT. During post MDA surveys, 2009 people were interviewed: 90.2% reported having completed MDA doses; 1.9% started treatment but did not complete dosage; 4.7% did not take treatment; 2.0% were absent during MDA and 1.2% were ineligible (i.e. infants <2 months and pregnant women). Main reasons for failure to complete treatment were experience of side-effects and forgetting to take subsequent doses. Failure to take treatment was mainly due to fear of side-effects, reluctance due to lack of malaria symptoms and caregivers forgetting to give medication to children. Mass drug administration for malaria was well accepted by communities at high risk of malaria in Zanzibar, with high participation and completion rates. Further work to investigate the potential of MDA in accelerating Zanzibar's efforts towards malaria elimination should be pursued.

Effects of Chinese medicinal herbs on expression of brain-derived Neurotrophic factor (BDNF) and its interaction with human breast cancer MDA-MB-231 cells and endothelial HUVECs.

PubMed

Chiu, Jen-Hwey; Chen, Fang-Pey; Tsai, Yi-Fang; Lin, Man-Ting; Tseng, Ling-Ming; Shyr, Yi-Ming

2017-08-12

Our previous study demonstrated that an up-regulation of the Brain-Derived Neurotrophic Factor (BDNF) signaling pathway is involved the mechanism causing the recurrence of triple negative breast cancer. The aim of this study is to investigate the effects of commonly used Chinese medicinal herbs on MDA-MB-231 and HUVEC cells and how they interact with BDNF. Human TNBC MDA-MB-231 cells and human endothelial HUVEC cells were used to explore the effect of commonly used Chinese herbal medicines on cancer cells alone, on endothelial cells alone and on cancer cell/endothelial cell interactions; this was done via functional studies, including migration and invasion assays. Furthermore, Western blot analysis and real-time PCR investigations were also used to investigate migration signal transduction, invasion signal transduction, and angiogenic signal transduction in these systems. Finally, the effect of the Chinese medicinal herbs on cancer cell/endothelial cell interactions was assessed using co-culture and ELISA. In terms of autoregulation, BDNF up-regulated TrkB gene expression in both MDA-MB-231 and HUVEC cells. Furthermore, BDNF enhanced migration by MDA-MB-231 cells via Rac, Cdc42 and MMP, while also increasing the migration of HUVEC cells via MMP and COX-2 expression. As measured by ELISA, the Chinese herbal medicinal herbs A. membranaceus, P. lactiflora, L. chuanxiong, P. suffruticosa and L. lucidum increased BDNF secretion by MDA-MB-231 cells. Similarly, using a co-culture system with MDA-MB-231 cells, A. membranaceus and L. lucidum modulated BDNF-TrkB signaling by HUVEC cells. We conclude that BDNF plays an important role in the metastatic interaction between MDA-MB-231 and HUVEC cells. Some Chinese medicinal herbs are able to enhance the BDNF-related metastatic potential of the interaction between cancer cells and endothelial cells. These findings provide important information that should help with the development of integrated medical therapies for breast cancer patients.

Progress and Impact of 13 Years of the Global Programme to Eliminate Lymphatic Filariasis on Reducing the Burden of Filarial Disease

PubMed Central

Ramaiah, K. D.; Ottesen, Eric A.

2014-01-01

Background A Global Programme to Eliminate Lymphatic Filariasis was launched in 2000, with mass drug administration (MDA) as the core strategy of the programme. After completing 13 years of operations through 2012 and with MDA in place in 55 of 73 endemic countries, the impact of the MDA programme on microfilaraemia, hydrocele and lymphedema is in need of being assessed. Methodology/Principal findings During 2000–2012, the MDA programme made remarkable achievements – a total of 6.37 billion treatments were offered and an estimated 4.45 billion treatments were consumed by the population living in endemic areas. Using a model based on empirical observations of the effects of treatment on clinical manifestations, it is estimated that 96.71 million LF cases, including 79.20 million microfilaria carriers, 18.73 million hydrocele cases and a minimum of 5.49 million lymphedema cases have been prevented or cured during this period. Consequently, the global prevalence of LF is calculated to have fallen by 59%, from 3.55% to 1.47%. The fall was highest for microfilaraemia prevalence (68%), followed by 49% in hydrocele prevalence and 25% in lymphedema prevalence. It is estimated that, currently, i.e. after 13 years of the MDA programme, there are still an estimated 67.88 million LF cases that include 36.45 million microfilaria carriers, 19.43 million hydrocele cases and 16.68 million lymphedema cases. Conclusions/Significance The MDA programme has resulted in significant reduction of the LF burden. Extension of MDA to all at-risk countries and to all regions within those countries where MDA has not yet reached 100% geographic coverage is imperative to further reduce the number of microfilaraemia and chronic disease cases and to reach the global target of interrupting transmission of LF by 2020. PMID:25412180

The effect of a low carotenoid diet on malondialdehyde-thiobarbituric acid (MDA-TBA) concentrations in women: a placebo-controlled double-blind study.

PubMed

Dixon, Z R; Shie, F S; Warden, B A; Burri, B J; Neidlinger, T R

1998-02-01

The purpose of the study was to evaluate the effect of a low carotenoid diet (83 micrograms Beta-carotene) on malondialdehyde-thiobarbituric acid (MDA-TBA) concentrations of nine pre-menopausal women. Subjects lived on the metabolic research unit of the Western Human Nutrition Research Center (WHNRC), where diet, exercise and other activities were controlled. Five subjects (Group C, control group) consumed a low carotenoid diet and received an additional 0.5 mg/day of Beta-carotene while four subjects (Group P, placebo group) received only the low carotenoid diet during days 1 to 60 (period 1). All subjects received 0.5 mg/day of Beta-carotene during days 60 to 100 (period 2), plus three capsules/day mixed carotenoid supplement (Neo-Life Company) during study days 100 to 120. Changes in MDA-TBA concentrations were analyzed during the study periods and between the groups. At the start of the study (day 1), no significant difference in the MDA-TBA concentration was observed between the control (Group C) and the placebo (Group P) subjects. During period 1 (days 2 to 60), when Group P subjects consumed the low carotenoid diet without supplementation, the MDA-TBA values for Group P rose markedly and were significantly (p < 0.05) higher than the MDA-TBA values for Group C subjects who were receiving carotenoid supplementation. During period 2 (days 60 to 100) when both groups received carotenoid supplementation, the MDA-TBA values of Group P subjects were significantly (p < 0.05) reduced to the point where they were similar to the MDA-TBA values for Group C subjects. These findings provide evidence to support the beneficial effects of carotenoids in preventing lipid peroxidation in the cells. Further studies are needed to identify the exact mechanism by which carotenoids prevent lipid peroxidation and the amount needed for normal activity.

A Review of Factors That Influence Individual Compliance with Mass Drug Administration for Elimination of Lymphatic Filariasis

PubMed Central

Krentel, Alison; Fischer, Peter U.; Weil, Gary J.

2013-01-01

Background The success of programs to eliminate lymphatic filariasis (LF) depends in large part on their ability to achieve and sustain high levels of compliance with mass drug administration (MDA). This paper reports results from a comprehensive review of factors that affect compliance with MDA. Methodology/Principal Findings Papers published between 2000 and 2012 were considered, and 79 publications were included in the final dataset for analysis after two rounds of selection. While results varied in different settings, some common features were associated with successful programs and with compliance by individuals. Training and motivation of drug distributors is critically important, because these people directly interact with target populations, and their actions can affect MDA compliance decisions by families and individuals. Other important programmatic issues include thorough preparation of personnel, supplies, and logistics for implementation and preparation of the population for MDA. Demographic factors (age, sex, income level, and area of residence) are often associated with compliance by individuals, but compliance decisions are also affected by perceptions of the potential benefits of participation versus the risk of adverse events. Trust and information can sometimes offset fear of the unknown. While no single formula can ensure success MDA in all settings, five key ingredients were identified: engender trust, tailor programs to local conditions, take actions to minimize the impact of adverse events, promote the broader benefits of the MDA program, and directly address the issue of systematic non-compliance, which harms communities by prolonging their exposure to LF. Conclusions/Significance This review has identified factors that promote coverage and compliance with MDA for LF elimination across countries. This information may be helpful for explaining results that do not meet expectations and for developing remedies for ailing MDA programs. Our review has also identified gaps in understanding and suggested priority areas for further research. PMID:24278486

HLA-DRB1 Alleles as Genetic Risk Factors for the Development of Anti-MDA5 Antibodies in Patients with Dermatomyositis.

PubMed

Chen, Zhiyong; Wang, Yan; Kuwana, Masataka; Xu, Xue; Hu, Wei; Feng, Xuebing; Wang, Hong; Kimura, Akinori; Sun, Lingyun

2017-09-01

Patients with polymyositis/dermatomyositis (PM/DM) who express anti-melanoma differentiation associated protein 5 (anti-MDA5) antibodies frequently present with interstitial lung disease (ILD). The aim of this study was to investigate the association of HLA-DRB1 with anti-MDA5 expression in PM/DM. The frequency of DRB1 alleles was compared among 70 patients with PM, 104 patients with DM, and 400 healthy controls in a Han Chinese population. Frequencies of DRB1*04:01 [17.0% vs 1.3%, corrected p value (p c ) = 3.8 × 10 -8 , OR 16.2, 95% CI 6.6-39.7] and *12:02 (42.6% vs 19.3%, p c = 0.008, OR 3.1, 95% CI 1.7-5.7) were significantly higher in anti-MDA5-positive patients with PM/DM compared with the controls. The frequencies of DRB1*04:01 (p = 5.2 × 10 -6 , OR 17.1, 95% CI 5.3-54.9) and *12:02 (p = 3.8 × 10 -4 , OR 3.1, 95% CI 1.7-5.7) in anti-MDA5-positive patients with DM-ILD were higher than in the controls, whereas the frequencies of DRB1*04:01 and *12:02 did not differ between the anti-MDA5-negative patients with DM-ILD and controls. No difference in the frequency of DRB1 alleles, other than *04:01, carrying the "shared epitope" (SE), i.e., *01:01, *01:02, *04:05, and *10:01, was observed between the controls and patients with DM stratified by the presence of anti-MDA5 and ILD. DRB1*04:01 and *12:02 confer susceptibility to anti-MDA5 antibody production in DM, which cannot be explained by the SE hypothesis.

Altered lipid peroxidation markers are related to post-traumatic stress disorder (PTSD) and not trauma itself in earthquake survivors.

PubMed

Atli, Abdullah; Bulut, Mahmut; Bez, Yasin; Kaplan, İbrahim; Özdemir, Pınar Güzel; Uysal, Cem; Selçuk, Hilal; Sir, Aytekin

2016-06-01

The traumatic life events, including earthquakes, war, and interpersonal conflicts, cause a cascade of psychological and biological changes known as post-traumatic stress disorder (PTSD). Malondialdehyde (MDA) is a reliable marker of lipid peroxidation, and paraoxonase is a known antioxidant enzyme. The aims of this study were to investigate the relationship between earthquake trauma, PTSD effects on oxidative stress and the levels of serum paraoxonase 1 (PON1) enzyme activity, and levels of serum MDA. The study was carried out on three groups called: the PTSD group, the traumatized with earthquake exercise group, and healthy control group, which contained 32, 31, and 38 individuals, respectively. Serum MDA levels and PON1 enzyme activities from all participants were measured, and the results were compared across all groups. There were no significant differences between the PTSD patients and non-PTSD earthquake survivors in terms of the study variables. The mean PON1 enzyme activity from PTSD patients was significantly lower, while the mean MDA level was significantly higher than that of the healthy control group (p < 0.01 for both measurements). Similarly, earthquake survivors who did not develop PTSD showed higher MDA levels and lower PON1 activity when compared to healthy controls. However, the differences between these groups did not reach a statistically significant level. Increased MDA level and decreased PON1 activity measured in PTSD patients after earthquake and may suggest increased oxidative stress in these patients. The nonsignificant trends that are observed in lipid peroxidation markers of earthquake survivors may indicate higher impact of PTSD development on these markers than trauma itself. For example, PTSD diagnosis seems to add to the effect of trauma on serum MDA levels and PON1 enzyme activity. Thus, serum MDA levels and PON1 enzyme activity may serve as biochemical markers of PTSD diagnosis.

Accuracy of Coverage Survey Recall following an Integrated Mass Drug Administration for Lymphatic Filariasis, Schistosomiasis, and Soil-Transmitted Helminthiasis

PubMed Central

Budge, Philip J.; Sognikin, Edmond; Akosa, Amanda; Mathieu, Els M.; Deming, Michael

2016-01-01

Background Achieving target coverage levels for mass drug administration (MDA) is essential to elimination and control efforts for several neglected tropical diseases (NTD). To ensure program goals are met, coverage reported by drug distributors may be validated through household coverage surveys that rely on respondent recall. This is the first study to assess accuracy in such surveys. Methodology/Principal Findings Recall accuracy was tested in a series of coverage surveys conducted at 1, 6, and 12 months after an integrated MDA in Togo during which three drugs (albendazole, ivermectin, and praziquantel) were distributed. Drug distribution was observed during the MDA to ensure accurate recording of persons treated during the MDA. Information was obtained for 506, 1131, and 947 persons surveyed at 1, 6, and 12 months, respectively. Coverage (defined as the percentage of persons taking at least one of the MDA medications) within these groups was respectively 88.3%, 87.4%, and 80.0%, according to the treatment registers; it was 87.9%, 91.4% and 89.4%, according to survey responses. Concordance between respondents and registers on swallowing at least one pill was >95% at 1 month and >86% at 12 months; the lower concordance at 12 months was more likely due to difficulty matching survey respondents with the year-old treatment register rather than inaccurate responses. Respondents generally distinguished between pills similar in appearance; concordance for recall of which pills were taken was over 80% in each survey. Significance In this population, coverage surveys provided remarkably consistent coverage estimates for up to one year following an integrated MDA. It is not clear if similar consistency will be seen in other settings, however, these data suggest that in some settings coverage surveys might be conducted as much as one year following an MDA without compromising results. This might enable integration of post-MDA coverage measurement into large, multipurpose, periodic surveys, thereby conserving resources. PMID:26766287

Detection of increased 64Cu uptake by human copper transporter 1 gene overexpression using PET with 64CuCl2 in human breast cancer xenograft model.

PubMed

Kim, Kwang Il; Jang, Su Jin; Park, Ju Hui; Lee, Yong Jin; Lee, Tae Sup; Woo, Kwang Sun; Park, Hyun; Choe, Jae Gol; An, Gwang Il; Kang, Joo Hyun

2014-10-01

Copper is an essential cofactor for a variety of biochemical processes including oxidative phosphorylation, cellular antioxidant activity, and elimination of free radicals. The copper transporter 1 is known to be involved in cellular uptake of copper ions. In this study, we evaluated the utility of human copper transporter 1 (hCTR1) gene as a new reporter gene for (64)Cu PET imaging. Human breast cancer cells (MDA-MB-231) were infected with a lentiviral vector constitutively expressing the hCTR1 gene under super cytomegalovirus promoter, and positive clones (MDA-MB-231-hCTR1) were selected. The expression of hCTR1 gene in MDA-MB-231-hCTR1 cells was measured by reverse transcription polymerase chain reaction, Western blot, and (64)Cu uptake assay. To evaluate the cytotoxic effects induced by hCTR1 expression, the dose-dependent cell survival rate after treatment with cisplatin (Cis-diaminedichloroplatinum (II) [CDDP]) was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and trypan blue dye exclusion. Small-animal PET images were acquired in tumor-bearing mice from 2 to 48 h after an intravenous injection of (64)Cu. The hCTR1 gene expression in MDA-MB-231-hCTR1 cells was confirmed at the RNA and protein expression and the cellular (64)Cu uptake level. MTT assay and trypan blue dye exclusion showed that the cell viability of MDA-MB-231-hCTR1 cells decreased more rapidly than that of MDA-MB-231 cells after treatment with CDDP for 96 or 72 h, respectively. Small-animal PET imaging revealed a higher accumulation of (64)Cu in MDA-MB-231-hCTR1 tumors than in MDA-MB-231 tumors. With respect to the biodistribution data, the percentage injected dose per gram of (64)Cu in the MDA-MB-231 tumors and MDA-MB-231-hCTR1 tumors at 48 h after (64)Cu injection was 2.581 ± 0.254 and 5.373 ± 1.098, respectively. An increase in (64)Cu uptake induced by the expression of hCTR1 gene was demonstrated in vivo and in vitro, suggesting the potential use of hCTR1 gene as a new imaging reporter gene for PET with (64)CuCl2. © 2014 by the Society of Nuclear Medicine and Molecular Imaging, Inc.

Skylab

NASA Image and Video Library

1971-01-01

This illustration depicts the Skylab-1 and Skylab-2 mission sequence. The goals of the Skylab were to enrich our scientific knowledge of the Earth, the Sun, the stars, and cosmic space; to study the effects of weightlessness on living organisms, including man; to study the effects of the processing and manufacturing of materials utilizing the absence of gravity; and to conduct Earth resource observations. The Skylab also conducted 19 selected experiments submitted by high school students. Skylab's 3 different 3-man crews spent up to 84 days in Earth orbit. The Marshall Space Flight Center (MSFC) had responsibility for developing and integrating most of the major components of the Skylab: the Orbital Workshop (OWS), Airlock Module (AM), Multiple Docking Adapter (MDA), Apollo Telescope Mount (ATM), Payload Shroud (PS), and most of the experiments. MSFC was also responsible for providing the Saturn IB launch vehicles for three Apollo spacecraft and crews and a Saturn V launch vehicle for the Skylab.

RMS upper boom framed by aft flight deck viewing window W10

NASA Technical Reports Server (NTRS)

1983-01-01

Remote Manipulator System (RMS) upper arm boom (tear in multilayer beta cloth) deployed during dynamic interaction test using Payload Flight Test Article (PFTA) is visible outside aft viewing window W10. RMS 'Canada' insignia or logo appears on boom.

Non-destructive determination of Malondialdehyde (MDA) distribution in oilseed rape leaves by laboratory scale NIR hyperspectral imaging

PubMed Central

Kong, Wenwen; Liu, Fei; Zhang, Chu; Zhang, Jianfeng; Feng, Hailin

2016-01-01

The feasibility of hyperspectral imaging with 400–1000 nm was investigated to detect malondialdehyde (MDA) content in oilseed rape leaves under herbicide stress. After comparing the performance of different preprocessing methods, linear and nonlinear calibration models, the optimal prediction performance was achieved by extreme learning machine (ELM) model with only 23 wavelengths selected by competitive adaptive reweighted sampling (CARS), and the result was RP = 0.929 and RMSEP = 2.951. Furthermore, MDA distribution map was successfully achieved by partial least squares (PLS) model with CARS. This study indicated that hyperspectral imaging technology provided a fast and nondestructive solution for MDA content detection in plant leaves. PMID:27739491

INTERIM CRYOGENIC PROPULSION STAGE TEST ARTICLE UNLOADED PRIOR T

NASA Image and Video Library

2016-06-20

TWO CRANES LIFT THE APPROXIMATELY 8,000-POUND INTERIM CRYOGENIC PROPULSION STAGE TEST ARTICLE OUT OF ITS CRATE AT MARSHALL. THE TEST ARTICLE ARRIVED AT MARSHALL SPACE FLIGHT CENTER VIA BARGE ON THE TENNESSEE RIVER AND WAS TRANSPORTED TO BUILDING 4649 WHERE TESTING WILL BEGIN.

Mechanisms for vestibular disorders in space flight. Facts and hypotheses

NASA Technical Reports Server (NTRS)

Matsnev, E. I.

1980-01-01

This article discusses the vestibular disorders associated with space flight. It is found there is still no complete understanding of the changes occurring in the sensory systems of the body during weightlessness. Results of studies are presented, including results of a ground model.

Safety Versus Passenger Service: The Flight Attendants’ Dilemma

PubMed Central

Damos, Diane L.; Boyett, Kimberly S.; Gibbs, Patt

2013-01-01

After 9/11, new security duties were instituted at many U.S. air carriers and existing safety and security duties received increased emphasis. Concurrently, in-flight services were changed and in many cases, cabin crews were reduced. This article examines the post-9/11 conflict between passenger service and the timely performance of safety and security duties at 1 major U.S. air carrier. In-flight data were obtained on both international and domestic flights. The data suggest that the prompt performance of the safety and security duties is adversely affected by the number of service duties occurring in the later part of both international and domestic flights. PMID:23667300

[Peculiarities of pilot's perception of flight information presented on on-board liquid crystal displays].

PubMed

Lemeshchenko, N A; Ivanov, A I; Lapa, V V; Davydov, V V; Zhelonkin, V I; Riabinin, V A; Golosov, S Iu

2014-01-01

The article deals with results of experimental studies conducted on flight testing desk and covering peculiarities of pilot's perception of flight information presented on on-board liquid crystal display in dependence on changes speed and update rate of the screen. The authors determine frequency characteristics of information update rate, that achieve acceptable quality of the flight parameters perception in accordance with the changes speed. Vigorous maneuvering with high angular velocities of changed parameters of roll and pitch causes visual distortions that are connected with poor frequency of information update rate, deteriorate piloting quality and can cause flight unsafety.

Assessing the effectiveness of household-level focal mass drug administration and community-wide mass drug administration for reducing malaria parasite infection prevalence and incidence in Southern Province, Zambia: study protocol for a community randomized controlled trial.

PubMed

Eisele, Thomas P; Silumbe, Kafula; Finn, Timothy; Chalwe, Victor; Kamuliwo, Mukalwa; Hamainza, Busiku; Moonga, Hawela; Bennett, Adam; Yukich, Josh; Keating, Joseph; Steketee, Richard W; Miller, John M

2015-08-13

Mass drug administration (MDA) and focal MDA (fMDA) using dihydroartemisinin plus piperaquine (DHAp), represent two strategies to maximize the use of existing information to achieve greater clearance of human infection and reduce the parasite reservoir, and provide longer chemoprophylactic protection against new infections. The primary aim of this study is to quantify the relative effectiveness of MDA and fMDA with DHAp against no mass treatment (standard of care) for reducing Plasmodium falciparum prevalence and incidence. The study will be conducted along Lake Kariba in Southern Province, Zambia; an area of low to moderate malaria transmission and high coverage of vector control. A community randomized controlled trial (CRCT) of 60 health facility catchment areas (HFCAs) will be used to evaluate the impact of two rounds of MDA and fMDA interventions, relative to a control of no mass treatment, stratified by high and low transmission. Community residents in MDA HFCAs will be treated with DHAp at the end of the dry season (round one: November to December 2014) and the beginning of the rainy season (round two: February to March 2015). Community residents in fMDA HFCAs will be tested during the same two rounds for malaria parasites with a rapid diagnostic test; all positive individuals and all individuals living in their household will be treated with DHAp. Primary outcomes include malaria parasite prevalence (n = 5,640 children aged one month to under five-years-old), as measured by pre- and post-surveys, and malaria parasite infection incidence (n = 2,250 person-years among individuals aged three months and older), as measured by a monthly longitudinal cohort. The study is powered to detect approximately a 50 % relative reduction in these outcomes between each intervention group versus the control. Strengths of this trial include: a robust study design (CRCT); cross-sectional parasite surveys as well as a longitudinal cohort; and stratification of high and low transmission areas. Primary limitations include: statistical power to detect only a 50 % reduction in primary outcomes within high and low transmission strata; potential for contamination; and potential for misclassification of exposure. Identifier: Clinicaltrials.gov: NCT02329301 . Registration date: 30 December 2014.

Morbillivirus Control of the Interferon Response: Relevance of STAT2 and mda5 but Not STAT1 for Canine Distemper Virus Virulence in Ferrets

PubMed Central

Svitek, Nicholas; Gerhauser, Ingo; Goncalves, Christophe; Grabski, Elena; Döring, Marius; Kalinke, Ulrich; Anderson, Danielle E.; Cattaneo, Roberto

2014-01-01

ABSTRACT The V proteins of paramyxoviruses control the innate immune response. In particular, the V protein of the genus Morbillivirus interferes with the signal transducer and activator of transcription 1 (STAT1), STAT2, and melanoma differentiation-associated protein 5 (mda5) signaling pathways. To characterize the contributions of these pathways to canine distemper virus (CDV) pathogenesis, we took advantage of the knowledge about the mechanisms of interaction between the measles virus V protein with these key regulators of innate immunity. We generated recombinant CDVs with V proteins unable to properly interact with STAT1, STAT2, or mda5. A virus with combined STAT2 and mda5 deficiencies was also generated, and available wild-type and V-protein-knockout viruses were used as controls. Ferrets infected with wild-type and STAT1-blind viruses developed severe leukopenia and loss of lymphocyte proliferation activity and succumbed to the disease within 14 days. In contrast, animals infected with viruses with STAT2 or mda5 defect or both STAT2 and mda5 defects developed a mild self-limiting disease similar to that associated with the V-knockout virus. This study demonstrates the importance of interference with STAT2 and mda5 signaling for CDV immune evasion and provides a starting point for the development of morbillivirus vectors with reduced immunosuppressive properties. IMPORTANCE The V proteins of paramyxoviruses interfere with the recognition of the virus by the immune system of the host. For morbilliviruses, the V protein is known to interact with the signal transducer and activator of transcription 1 (STAT1) and STAT2 and the melanoma differentiation-associated protein 5 (mda5), which are involved in interferon signaling. Here, we examined the contribution of each of these signaling pathways to the pathogenesis of the carnivore morbillivirus canine distemper virus. Using viruses selectively unable to interfere with the respective signaling pathway to infect ferrets, we found that inhibition of STAT2 and mda5 signaling was critical for lethal disease. Our findings provide new insights in the mechanisms of morbillivirus immune evasion and may lead to the development of new vaccines and oncolytic vectors. PMID:24371065

Action of hexachlorobenzene on tumor growth and metastasis in different experimental models

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

Pontillo, Carolina Andrea, E-mail: caroponti@hotmail.com; Rojas, Paola, E-mail: parojas2010@gmail.com; Chiappini, Florencia, E-mail: florenciachiappini@hotmail.com

Hexachlorobenzene (HCB) is a widespread organochlorine pesticide, considered a possible human carcinogen. It is a dioxin-like compound and a weak ligand of the aryl hydrocarbon receptor (AhR). We have found that HCB activates c-Src/HER1/STAT5b and HER1/ERK1/2 signaling pathways and cell migration, in an AhR-dependent manner in MDA-MB-231 breast cancer cells. The aim of this study was to investigate in vitro the effect of HCB (0.005, 0.05, 0.5, 5 μM) on cell invasion and metalloproteases (MMPs) 2 and 9 activation in MDA-MB-231 cells. Furthermore, we examined in vivo the effect of HCB (0.3, 3, 30 mg/kg b.w.) on tumor growth, MMP2more » and MMP9 expression, and metastasis using MDA-MB-231 xenografts and two syngeneic mouse breast cancer models (spontaneous metastasis using C4-HI and lung experimental metastasis using LM3). Our results show that HCB (5 μM) enhances MMP2 expression, as well as cell invasion, through AhR, c-Src/HER1 pathway and MMPs. Moreover, HCB increases MMP9 expression, secretion and activity through a HER1 and AhR-dependent mechanism, in MDA-MB-231 cells. HCB (0.3 and 3 mg/kg b.w.) enhances subcutaneous tumor growth in MDA-MB-231 and C4-HI in vivo models. In vivo, using MDA-MB-231 model, the pesticide (0.3, 3 and 30 mg/kg b.w.) activated c-Src, HER1, STAT5b, and ERK1/2 signaling pathways and increased MMP2 and MMP9 protein levels. Furthermore, we observed that HCB stimulated lung metastasis regardless the tumor hormone-receptor status. Our findings suggest that HCB may be a risk factor for human breast cancer progression. - Highlights: ► HCB enhances MMP2 and MMP9 expression and cell invasion in MDA-MB-231, in vitro. ► HCB-effects are mediated through AhR, HER1 and/or c-Src. ► HCB increases subcutaneous tumor growth in MDA-MB-231 and C4-HI in vivo models. ► HCB activates c-Src/HER1 pathway and increases MMPs levels in MDA-MB-231 tumors. ► HCB stimulates lung metastasis in C4-HI and LM3 in vivo models.« less

Improved multiple displacement amplification (iMDA) and ultraclean reagents.

PubMed

Motley, S Timothy; Picuri, John M; Crowder, Chris D; Minich, Jeremiah J; Hofstadler, Steven A; Eshoo, Mark W

2014-06-06

Next-generation sequencing sample preparation requires nanogram to microgram quantities of DNA; however, many relevant samples are comprised of only a few cells. Genomic analysis of these samples requires a whole genome amplification method that is unbiased and free of exogenous DNA contamination. To address these challenges we have developed protocols for the production of DNA-free consumables including reagents and have improved upon multiple displacement amplification (iMDA). A specialized ethylene oxide treatment was developed that renders free DNA and DNA present within Gram positive bacterial cells undetectable by qPCR. To reduce DNA contamination in amplification reagents, a combination of ion exchange chromatography, filtration, and lot testing protocols were developed. Our multiple displacement amplification protocol employs a second strand-displacing DNA polymerase, improved buffers, improved reaction conditions and DNA free reagents. The iMDA protocol, when used in combination with DNA-free laboratory consumables and reagents, significantly improved efficiency and accuracy of amplification and sequencing of specimens with moderate to low levels of DNA. The sensitivity and specificity of sequencing of amplified DNA prepared using iMDA was compared to that of DNA obtained with two commercial whole genome amplification kits using 10 fg (~1-2 bacterial cells worth) of bacterial genomic DNA as a template. Analysis showed >99% of the iMDA reads mapped to the template organism whereas only 0.02% of the reads from the commercial kits mapped to the template. To assess the ability of iMDA to achieve balanced genomic coverage, a non-stochastic amount of bacterial genomic DNA (1 pg) was amplified and sequenced, and data obtained were compared to sequencing data obtained directly from genomic DNA. The iMDA DNA and genomic DNA sequencing had comparable coverage 99.98% of the reference genome at ≥1X coverage and 99.9% at ≥5X coverage while maintaining both balance and representation of the genome. The iMDA protocol in combination with DNA-free laboratory consumables, significantly improved the ability to sequence specimens with low levels of DNA. iMDA has broad utility in metagenomics, diagnostics, ancient DNA analysis, pre-implantation embryo screening, single-cell genomics, whole genome sequencing of unculturable organisms, and forensic applications for both human and microbial targets.

Cellular effect of styrene substituted biscoumarin caused cellular apoptosis and cell cycle arrest in human breast cancer cells.

PubMed

Perumalsamy, Haribalan; Sankarapandian, Karuppasamy; Kandaswamy, Narendran; Balusamy, Sri Renukadevi; Periyathambi, Dhaiveegan; Raveendiran, Nanthini

2017-11-01

Coumarins occurs naturally across plant kingdoms exhibits significant pharmacological properties and pharmacokinetic activity. The conventional, therapeutic agents are often associated with poor stability, absorption and increased side effects. Therefore, identification of a drug that has little or no-side effect on humans is consequential. Here, we investigated the antiproliferative activity of styrene substituted biscoumarin against various human breast cancer cell lines, such as MCF-7, (ER-) MDA-MB-231 and (AR+) MDA-MB-453. Styrene substituted biscoumarin induced cell death by apoptosis in MDA-MB-231 cell line was analyzed. Antiproliferative activity of Styrene substituted biscoumarin was performed by using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Styrene substituted biscoumarin induced apoptosis was assessed by Hoechst staining, Annexin V-fluorescein isothiocyanate/propidium iodide (Annexin V-FITC/PI) staining and flow cytometric analysis. Migratory and proliferating characteristic of breast cancer cell line MDA-MB-231 was also analyzed by wound healing and colony formation assay. Furthermore, mRNA expression of BAX and BCL-2 were quantified using qRT-PCR and protein expression level analyzed by Western blot. The inhibition concentration (IC 50 ) of styrene substituted biscoumarin was assayed against three breast cancer cell lines. The inhibition concentration (IC 50 ) value of styrene substituted biscoumarin toward MDA-MB-231, MDA-MB-453 and MCF-7 cell lines was 5.63, 7.30 and 10.84μg/ml respectively. Styrene substituted biscoumarin induced apoptosis was detected by Hoechst staining, DAPI/PI analysis and flow-cytometric analysis. The migration and proliferative efficiency of MDA-MB-231 cells were completely arrested upon styrene substituted biscoumarin treatment. Also, mRNA gene expression and protein expression of pro-apoptotic (BAX) and anti-apoptotic (BCL-2) genes were analyzed by qRT-PCR and western blot analysis upon styrene substituted biscoumarin treatment to MDA-MB-231 cells. Our results showed that styrene substituted biscoumarin downregulated BCL-2 gene expression and upregulated BAX gene expression to trigger apoptotic process. Styrene substituted biscoumarin could induce apoptosis through intrinsic mitochondrial pathway in breast cancer cell lines, particularly in MDA-MB-231. Our data suggest that styrene substituted biscoumarin may act as a potential chemotherapeutic agent against breast cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.

Relationship between the degree of antioxidant protection and the level of malondialdehyde in high-performance Polish Holstein-Friesian cows in peak of lactation

PubMed Central

2018-01-01

Lipid peroxidation can be described as a process under which free radicals attack carbon double bonds of omega-3 and omega-6 fatty acids. Whereas the end products of this process are reactive aldehydes, such as malondialdehyde (MDA). Lipid peroxidation leads to adverse changes in the nutritional value of milk; therefore, higher degree of antioxidant protection (DAP) ensures higher stability of dairy products by effecting their high antioxidative potential. Therefore, the purpose of this study was to demonstrate the relationship between the DAP and the level of MDA in high-performance Polish Holstein-Friesian cows in peak of lactation. Sixty-three Polish Holstein-Friesian cows were selected to the experiment according to: parity (all in the 2nd lactation), phase of lactation (peak of lactation), cytological quality of milk (somatic cell count < 150 thousand/ml) and without diagnosed metabolic diseases. The data obtained were analyzed statistically by two–way ANOVA, and Tukey’s post-hoc test. After analysis of performance the cows were divided into 3 groups (twenty one cows in each group) based on milk yield and MDA concentration. The study revealed a significant effect of the lactation performance of cows on MDA levels in milk (P ≤ 0.01). The highest concentration of MDA (61.137 nM/mL) was shown in milk of cows yielding between 50.00 and 55.80 kg/day. The highest concentration of fat was found in milk in which the MDA level ranged from 48 to 86 nM/mL. Whereas, the inverse relationship was demonstrated in case of protein concentration. The highest level of protein was found in cows with MDA levels in the range of 18–28 nM/mL (P ≤ 0.01). The lowest MDA level (in the range of 18–28 nM/mL) was associated with the highest concentration of vitamin E, β-carotene, total antioxidant status (TAS) and DAP, measured in both milk and plasma. The obtained results show that lipid peroxidation leads to adverse changes in the nutritional value of milk; the highest DAP (7.89 x 10−3) was found in the cows with the lowest MDA concentration in milk. PMID:29494660

Morbillivirus control of the interferon response: relevance of STAT2 and mda5 but not STAT1 for canine distemper virus virulence in ferrets.

PubMed

Svitek, Nicholas; Gerhauser, Ingo; Goncalves, Christophe; Grabski, Elena; Döring, Marius; Kalinke, Ulrich; Anderson, Danielle E; Cattaneo, Roberto; von Messling, Veronika

2014-03-01

The V proteins of paramyxoviruses control the innate immune response. In particular, the V protein of the genus Morbillivirus interferes with the signal transducer and activator of transcription 1 (STAT1), STAT2, and melanoma differentiation-associated protein 5 (mda5) signaling pathways. To characterize the contributions of these pathways to canine distemper virus (CDV) pathogenesis, we took advantage of the knowledge about the mechanisms of interaction between the measles virus V protein with these key regulators of innate immunity. We generated recombinant CDVs with V proteins unable to properly interact with STAT1, STAT2, or mda5. A virus with combined STAT2 and mda5 deficiencies was also generated, and available wild-type and V-protein-knockout viruses were used as controls. Ferrets infected with wild-type and STAT1-blind viruses developed severe leukopenia and loss of lymphocyte proliferation activity and succumbed to the disease within 14 days. In contrast, animals infected with viruses with STAT2 or mda5 defect or both STAT2 and mda5 defects developed a mild self-limiting disease similar to that associated with the V-knockout virus. This study demonstrates the importance of interference with STAT2 and mda5 signaling for CDV immune evasion and provides a starting point for the development of morbillivirus vectors with reduced immunosuppressive properties. The V proteins of paramyxoviruses interfere with the recognition of the virus by the immune system of the host. For morbilliviruses, the V protein is known to interact with the signal transducer and activator of transcription 1 (STAT1) and STAT2 and the melanoma differentiation-associated protein 5 (mda5), which are involved in interferon signaling. Here, we examined the contribution of each of these signaling pathways to the pathogenesis of the carnivore morbillivirus canine distemper virus. Using viruses selectively unable to interfere with the respective signaling pathway to infect ferrets, we found that inhibition of STAT2 and mda5 signaling was critical for lethal disease. Our findings provide new insights in the mechanisms of morbillivirus immune evasion and may lead to the development of new vaccines and oncolytic vectors.

Integrated System Test Approaches for the NASA Ares I Crew Launch Vehicle

NASA Technical Reports Server (NTRS)

Cockrell, Charles

2008-01-01

NASA is maturing test and evaluation plans leading to flight readiness of the Ares I crew launch vehicle. Key development, qualification, and verification tests are planned . Upper stage engine sea-level and altitude testing. First stage development and qualification motors. Upper stage structural and thermal development and qualification test articles. Main Propulsion Test Article (MPTA). Upper stage green run testing. Integrated Vehicle Ground Vibration Testing (IVGVT). Aerodynamic characterization testing. Test and evaluation supports initial validation flights (Ares I-Y and Orion 1) and design certification.

Multidimensional assessment of severe asthma: A systematic review and meta-analysis.

PubMed

Clark, Vanessa L; Gibson, Peter G; Genn, Grayson; Hiles, Sarah A; Pavord, Ian D; McDonald, Vanessa M

2017-10-01

The management of severe asthma is complex. Multidimensional assessment (MDA) of specific traits has been proposed as an effective strategy to manage severe asthma, although it is supported by few prospective studies. We aimed to systematically review the literature published on MDA in severe asthma, to identify the traits included in MDA and to determine the effect of MDA on asthma-related outcomes. We identified 26 studies and classified these based on study type (cohort/cross-sectional studies; experimental/outcome studies; and severe asthma disease registries). Study type determined the comprehensiveness of the assessment. Assessed traits were classified into three domains (airways, co-morbidities and risk factors). The airway domain had the largest number of traits assessed (mean ± SD = 4.2 ± 1.7) compared with co-morbidities (3.6 ± 2.2) and risk factors (3.9 ± 2.1). Bronchodilator reversibility and airflow limitation were assessed in 92% of studies, whereas airway inflammation was only assessed in 50%. Commonly assessed co-morbidities were psychological dysfunction, sinusitis (both 73%) and gastro-oesophageal reflux disease (GORD; 69%). Atopic and smoking statuses were the most commonly assessed risk factors (85% and 86%, respectively). There were six outcome studies, of which five concluded that MDA is effective at improving asthma-related outcomes. Among these studies, significantly more traits were assessed than treated. MDA studies have assessed a variety of different traits and have shown evidence of improved outcomes. This promising model of care requires more research to inform which traits should be assessed, which traits should be treated and what effect MDA has on patient outcomes. © 2017 Asian Pacific Society of Respirology.

Evaluation of drug incorporation into hair segments and nails by enantiomeric analysis following controlled single MDMA intakes.

PubMed

Madry, Milena M; Steuer, Andrea E; Hysek, Cédric M; Liechti, Matthias E; Baumgartner, Markus R; Kraemer, Thomas

2016-01-01

Incorporation rates of the enantiomers of 3,4-methylenedioxymethamphetamine (MDMA) and its metabolite 3,4-methylenedioxyamphetamine (MDA) into hair and nails were investigated after controlled administration. Fifteen subjects without MDMA use received two doses of 125 mg of MDMA. Hair, nail scrapings, and nail clippings were collected 9-77 days after the last administration (median 20 days). Hair samples were analyzed in segments of 1- to 2-cm length. After chiral derivatization with N-(2,4-dinitro-5-fluorophenyl)-L-valinamide, MDMA and MDA diastereomers were analyzed by liquid chromatography-tandem mass spectrometry. Highest concentrations in hair segments corresponded to the time of MDMA intake. They ranged from 101 to 3200 pg/mg and 71 to 860 pg/mg for R- and S-MDMA, and from 3.2 to 116 pg/mg and 4.4 to 108 pg/mg for R- and S-MDA, respectively. MDMA and MDA concentrations in nail scrapings and clippings were significantly lower than in hair samples. There was no significant difference between enantiomeric ratios of R/S-MDMA and R/S-MDA in hair and nail samples (medians 2.2-2.4 for MDMA and 0.85-0.95 for MDA). Metabolite ratios of MDA to MDMA were in the same range in hair and nail samples (medians 0.044-0.055). Our study demonstrates that administration of two representative doses of MDMA was detected in the hair segments corresponding to the time of intake based on average hair growth rates. MDMA was detected in all nail samples regardless of time passed after intake. Comparable R/S ratios in hair and nail samples may indicate that incorporation mechanisms into both matrices are comparable.

Electrophysiological Correlates of Amnestic Mild Cognitive Impairment in a Simon Task

PubMed Central

Cespón, Jesús; Galdo-Álvarez, Santiago; Díaz, Fernando

2013-01-01

Amnestic mild cognitive impairment (aMCI) represents a prodromal stage of Alzheimer`s disease (AD), especially when additional cognitive domains are affected (Petersen et al., 2009). Thus, single-domain amnestic MCI (sdaMCI) and multiple-domain-amnestic MCI (mdaMCI) biomarkers are important for enabling early interventions to help slow down progression of the disease. Recording event-related potentials (ERPs) is a non-invasive and inexpensive measure of brain activity associated with cognitive processes, and it is of interest from a clinical point of view. The ERP technique may also be useful for obtaining early sdaMCI and mdaMCI biomarkers because ERPs are sensitive to impairment in processes that are not manifested at behavioral or clinical levels. In the present study, EEG activity was recorded in 25 healthy participants and 30 amnestic MCI patients (17 sdaMCI and 13 mdaMCI) while they performed a Simon task. The ERPs associated with visuospatial (N2 posterior-contralateral – N2pc -) and motor (lateralized readiness potential – LRP –) processes were examined. The N2pc amplitude was smaller in participants with mdaMCI than in healthy participants, which indicated a decline in the correlates of allocation of attentional resources to the target stimulus. In addition, N2pc amplitude proved to be a moderately good biomarker of mdaMCI subtype (0.77 sensitivity, 0.76 specificity). However, the LRP amplitude was smaller in the two MCI groups (sdaMCI and mdaMCI) than in healthy participants, revealing a reduction in the motor resources available to execute the response in sdaMCI and mdaMCI patients. Furthermore, the LRP amplitude proved to be a valid biomarker (0.80 sensitivity, 0.92 specificity) of both amnestic MCI subtypes. PMID:24339941

Oxidative status in different settings and with different methodological approaches compared by Receiver Operating Characteristic curve analysis.

PubMed

Cighetti, Giuliana; Bamonti, Fabrizia; Aman, Caroline S; Gregori, Dario; De Giuseppe, Rachele; Novembrino, Cristina; de Liso, Federica; Maiavacca, Rita; Paroni, Rita

2015-01-01

To test the performance of different analytical approaches in highlighting the occurrence of deregulated redox status in various physio-pathological situations. 35 light and 61 heavy smokers, 19 chronic renal failure, 59 kidney transplanted patients, and 87 healthy controls were retrospectively considered for the study. Serum oxidative stress and antioxidant status, assessed by spectrophotometric Reactive Oxygen Metabolites (d-ROMs) and Total Antioxidant Capacity (TAC) tests, respectively, were compared with plasma free (F-MDA) and total (T-MDA) malondialdehyde, both quantified by isotope-dilution-gas chromatography-mass spectrometry (ID-GC-MS). Sensitivity, specificity and cut-off points of T-MDA, F-MDA, d-ROMs and TAC were evaluated by both Receiver Operating Characteristic (ROC) analyses and area under the ROC curve (AUC). Only T-MDA assay showed a clear absence of oxidative stress in controls and significant increase in all patients (AUC 1.00, sensitivity and specificity 100%). Accuracy was good for d-ROMs (AUC 0.87, sensitivity 72.8%, specificity 100%) and F-MDA (AUC 0.82, sensitivity 74.7%, specificity 83.9%), but not high enough for TAC to show in patients impaired antioxidant defense (AUC 0.66, sensitivity 52.0%, specificity 92.9%). This study reveals T-MDA as the best marker to detect oxidative stress, shows the ability of d-ROMs to identify modified oxidative status particularly in the presence of high damages, and evidences the poor TAC performance. d-ROMs and TAC assays could be useful for routine purposes; however, for an accurate clinical data evaluation, their comparison versus a "gold standard method" is required. Copyright © 2014 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Ischemia-modified albümin and malondialdehyde levels in patients with overt and subclinical hyperthyroidism: effects of treatment on oxidative stress.

PubMed

Erem, Cihangir; Suleyman, Akile Karacin; Civan, Nadim; Mentese, Ahmet; Nuhoglu, İrfan; Uzun, Aysegul; Ersoz, Halil Onder; Deger, Orhan

2015-01-01

The main purpose of this study was to evaluate the levels of ischemia-modified albumin (IMA) and malondialdehyde (MDA) in patients with OHyper and SHyper, to assess the effects of antithyroid drug (ATD) therapy on the oxidative stress (OS) parameters. Forty-five untreated patients with overt hyperthyroidism (OHyper), 20 untreated patients with subclinical hyperthyroidism (SHyper) and 30 age-and sex-matched healthy controls were prospectively included in the study. Biochemical and hormonal parameters were evaluated in all patients before and after treatment. Compared with the control subjects, the levels of MDA, glucose and TG were significantly increased in patients with SHyper (p<0.05), whereas LDL-C levels were significantly decreased (p<0.01). Patients with OHyper showed significantly elevated MDA and glucose levels (p<0.001) and significantly decreased LDL-C and HDL-C levels compared with the controls (p<0.01). In patients with Graves' disease, serum TSH levels were inversely correlated with plasma MDA levels (r: -0.42, p<0.05). Plasma MDA levels significantly decreased and levels of TC, LDL-C and HDL-C significantly increased in the groups of OHyper and SHyper after treatment. Serum IMA levels did not significantly change at baseline and with the therapy in all subjects. In conclusion, increased MDA levels in both patient groups represent increased lipid peroxidation which might play an important role in the pathogenesis of the atherosclerosis in these patients. Increased oxidative stress in patients with SHyper and OHyper could be improved by ATD therapy. Also, MDA can be used as a reliable marker of OS and oxidative damage, while IMA is considered to be inappropriate.

Disruption of endothelial adherens junction by invasive breast cancer cells is mediated by reactive oxygen species and is attenuated by AHCC.

PubMed

Haidari, Mehran; Zhang, Wei; Wakame, Koji

2013-12-18

The effect of antioxidants on treatment of cancer is still controversial. Previously, we demonstrated that interaction of breast cancer cells with endothelial cells leads to tyrosine phosphorylation of VE-cadherin and disruption of endothelial adherens junction (EAJ). The molecular mechanism underlying the anti-metastatic effects of mushroom-derived active hexode correlated compound (AHCC) remains elusive. Several cellular and biochemical techniques were used to determine the contribution of oxidative stress in the disruption of EAJ and to test this hypothesis that AHCC inhibits the breast cancer cell-induced disruption of EAJ. Interaction of breast cancer cells (MDA-MB-231 cells) with human umbilical vein endothelial cells (HUVECs) leads to an increase in generation of reactive oxygen species (ROS). Treatment of HUVECs with H2O2 or phorbol myristate acetate (PMA) led to tyrosine phosphorylation of VE-cadherin, dissociation of β-catenin from VE-cadherin complex and increased transendothelial migration (TEM) of MDA-MB-231 cells. Induction of VE-cadherin tyrosine phosphorylation by PMA or by interaction of MDA-MB-231 cells with HUVECs was mediated by HRas and protein kinase C-α signaling pathways. Disruption of EAJ and phosphorylation of VE-cadherin induced by interaction of MDA-MB-231 cells with HUVECs were attenuated when HUVECs were pretreated with an antioxidant, N-acetylcysteine (NAC) or AHCC. AHCC inhibited TEM of MDA-MB-231 cells and generation of ROS induced by interaction of MDA-MB-231 cells with HUVECs. Our studies suggest that ROS contributes to disruption of EAJ induced by interaction of MDA-MB-231 cells with HUVECs and AHCC attenuates this alteration. Copyright © 2013 Elsevier Inc. All rights reserved.

Increased levels of urinary biomarkers of lipid peroxidation products among workers occupationally exposed to diesel engine exhaust.

PubMed

Bin, Ping; Shen, Meili; Li, Haibin; Sun, Xin; Niu, Yong; Meng, Tao; Yu, Tao; Zhang, Xiao; Dai, Yufei; Gao, Weimin; Gu, Guizhen; Yu, Shanfa; Zheng, Yuxin

2016-08-01

Diesel engine exhaust (DEE) was found to induce lipid peroxidation (LPO) in animal exposure studies. LPO is a class of oxidative stress and can be reflected by detecting the levels of its production, such as malondialdehyde (MDA) and 4-hydroxynonenal (4-HNE), and etheno-DNA adducts including 1,N(6)-etheno-2'-deoxyadenosine (ɛdA) and 3,N(4)-etheno-2'-deoxycytidine (ɛdC). However, the impact of DEE exposure on LPO has not been explored in humans. In this study, we evaluated urinary MDA, 4-HNE, ɛdA, and ɛdC levels as biomarkers of LPO among 108 workers with exclusive exposure to DEE and 109 non-DEE-exposed workers. Results showed that increased levels of urinary MDA and ɛdA were observed in subjects occupationally exposed to DEE before and after age, body mass index (BMI), smoking status, and alcohol use were adjusted (all p < 0.001). There was a statistically significant relationship between the internal exposure dose (urinary ΣOH-PAHs) and MDA, 4-HNE, and ɛdA (all p < 0.001). Furthermore, significant increased relations between urinary etheno-DNA adduct and MDA, 4-HNE were observed (all p < 0.05). The findings of this study suggested that the level of LPO products (MDA and ɛdA) was increased in DEE-exposed workers, and urinary MDA and ɛdA might be feasible biomarkers for DEE exposure. LPO induced DNA damage might be involved and further motivated the genomic instability could be one of the pathogeneses of cancer induced by DEE-exposure. However, additional investigations should be performed to understand these observations.

Killing of Human Melanoma Cells Induced by Activation of Class I Interferon–Regulated Signaling Pathways via MDA-7/IL-24

PubMed Central

Ekmekcioglu, Suhendan; Mumm, John B.; Udtha, Malini; Chada, Sunil; Grimm, Elizabeth A.

2008-01-01

Restoration of the tumor-suppression function by gene transfer of the melanoma differentiation-associated gene 7 (MDA7)/interleukin 24 (IL-24) successfully induces apoptosis in melanoma tumors in vivo. To address the molecular mechanisms involved, we previously revealed that MDA7/IL-24 treatment of melanoma cells down-regulates interferon regulatory factor (IRF)-1 expression and concomitantly up-regulates IRF-2 expression, which competes with the activity of IRF-1 and reverses the induction of IRF-1–regulated inducible nitric oxide synthase (iNOS). Interferons (IFNs) influence melanoma cell survival by modulating apoptosis. A class I IFN (IFN alfa) has been approved for the treatment of advanced melanoma with some limited success. A class II IFN (IFN gamma), on the other hand, supports melanoma cell survival, possibly through constitutive activation of iNOS expression. We therefore conducted this study to explore the molecular pathways of MDA7/IL-24 regulation of apoptosis via the intracellular induction of IFNs in melanoma. We hypothesized that the restoration of the MDA7/IL-24 axis leads to upregulation of Class I IFNs and induction of the apoptotic cascade. We found that MDA7/IL-24 induces the secretion of endogenous IFN beta, another class I IFN, leading to the arrest of melanoma cell growth and apoptosis. We also identified a series of apoptotic markers that play a role in this pathway, including the regulation of tumor necrosis factor–related apoptosis-inducing ligand (TRAIL) and Fas-FasL. In summary, we described a novel pathway of MDA7/IL-24 regulation of apoptosis in melanoma tumors via endogenous IFN beta induction followed by IRF regulation and TRAIL/FasL system activation. PMID:18511292

COMMUNITY MEMBERS' PERCEPTIONS OF MASS DRUG ADMINISTRATION FOR CONTROL OF LYMPHATIC FILARIASIS IN RURAL AND URBAN TANZANIA.

PubMed

Kisoka, William J; Tersbøl, Britt Pinkowsky; Meyrowitsch, Dan W; Simonsen, Paul E; Mushi, Declare L

2016-01-01

Lymphatic filariasis is one of several neglected tropical diseases with severely disabling and stigmatizing manifestations that are referred to as 'neglected diseases of poverty'. It is a mosquito-borne disease found endemically and exclusively in low-income contexts where, concomitantly, general public health care is often deeply troubled and fails to meet the basic health needs of impoverished populations. This presents particular challenges for the implementation of mass drug administration (MDA), which currently is the principal means of control and eventual elimination. Several MDA programmes face the dilemma that they are unable to attain and maintain the required drug coverage across target groups. In recognition of this, a qualitative study was conducted in the Morogoro and Lindi regions of Tanzania to gain an understanding of community experiences with, and perceptions of, the MDA campaign implemented in 2011 by the National Lymphatic Filariasis Elimination Programme. The study revealed a wide variation of perceptions and experiences regarding the aim, rationale and justification of MDA. There were positive sentiments about the usefulness of the drugs, but many study participants were sceptical about the manner in which MDA is implemented. People were particularly disappointed with the limited attempts by implementers to share information and mobilize residents. In addition, negative sentiments towards MDA for lymphatic filariasis reflected a general feeling of desertion and marginalization by the health care system and political authorities. However, the results suggest that if the communities are brought on board with genuine respect for their integrity and informed self-determination, there is scope for major improvements in community support for MDA-based control activities.

Exhaled breath malondialdehyde, spirometric results and dust exposure assessment in ceramics production workers.

PubMed

Sakhvidi, Mohammad Javad Zare; Biabani Ardekani, Javad; Firoozichahak, Ali; Zavarreza, Javad; Hajaghazade, Mohammad; Mostaghaci, Mehrdad; Mehrparvar, Amirhooshang; Barkhordari, Abolfazl

2015-01-01

The study aimed at measuring exhaled breath malondialdehyde (EBC-MDA) in workers exposed to dust containing silica and at its comparison with the non-exposed control group. The cross sectional, case-control study (N = 50) was performed in a tile and ceramics production factory in Yazd, Iran. EBC-MDA was quantified in exhaled breath of the participants by a lab made breath sampler. Exposure intensity was measured according to the NIOSH 0600 method in selected homogeneous exposure groups. Additionally, spirometry test was conducted to investigate a correlation between EBC-MDA and spirometric findings in the exposed workers. There was no difference in the observed exposure intensities of silica containing dust in different units. However, "coating preparation" was the unit with the highest concentration of dust. Although, the level of EBC-MDA in the cases was slightly higher than in the controls, the difference was not statistically significant (U = 252, p = 0.464). A significant and positive correlation was found between dust exposure intensity in working units and the measured EBC-MDA of workers (r = 0.467, N = 25, p = 0.027). There were also no statistically significant differences among job categories in the exposed group for the values of FEV1% (F(3, 44) = 0.656, p = 0.584), FVC% (F(3, 44) = 1.417, p = 0.172), and FEV1/FVC% (F(3, 44) = 1.929, p = 0.139). The results showed a significant correlation between respirable dust exposure intensity and the level of EBC-MDA of the exposed subjects. However, our results did not show a significant correlation between lung function decreases and EBC-MDA. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

Mass drug administration of azithromycin for trachoma reduces the prevalence of genital Chlamydia trachomatis infection in the Solomon Islands.

PubMed

Marks, M; Bottomley, C; Tome, H; Pitakaka, R; Butcher, R; Sokana, O; Kako, H; Solomon, A W; Mabey, D C

2016-06-01

Chlamydia trachomatis is the most common bacterial sexually transmitted infection and is frequently asymptomatic; ocular C. trachomatis strains cause trachoma. Mass drug administration (MDA) of azithromycin for trachoma might also reduce the prevalence of genital C. trachomatis. In a survey conducted in the Solomon Islands in 2014, prior to MDA, the prevalence of genital C. trachomatis was 20.3% (95% CI 15.9% to 25.4%). We conducted a survey to establish the impact of MDA with azithromycin on genital C. trachomatis. Women attending three community outpatient clinics, predominantly for antenatal care, 10 months after MDA with azithromycin given for trachoma elimination, were enrolled in this survey. Self-taken high vaginal swabs were for C. trachomatis and Neisseria gonorrhoeae using the BD Probetec strand displacement assay. 298 women were enrolled. C. trachomatis infection was diagnosed in 43 women (14.4%, 95% CI 10.6% to 18.9%) and N. gonorrhoeae in 9 (3%, 95% CI 1.4% to 5.7%). The age-adjusted OR for C. trachomatis infection was consistent with a significant decrease in the prevalence of C. trachomatis following MDA (OR 0.58, 95% CI 0.37 to 0.94, p=0.027). There was no change in the prevalence of N. gonorrhoeae between following MDA (OR 0.51, 95% CI 0.22 to 1.22, p=0.13). This study demonstrated a 40% reduction in the age-adjusted prevalence of genital C. trachomatis infection following azithromycin MDA for trachoma elimination. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Missile Defense: Assessment of DODs Reports on Status of Efforts and Options for Improving Homeland Missile Defense

DTIC Science & Technology

2016-02-17

However, MDA may encounter challenges with the RKV’s contract strategy, industry collaboration efforts, and schedule because MDA has not yet...negotiated the terms of the RKV modification with the prime contractor, is relying on potential industry competitors to collaborate on developing the RKV...interfaces and standards for its subsystems, called modules. Under the DSC, MDA plans to form a cross industry team consisting of Boeing, Raytheon, and

Novel Therapeutic Approach for Breast Cancer

DTIC Science & Technology

2006-06-01

replication, mda-7/IL-24 expression, growth inhibition and apoptosis induction. Injecting Ad.PEG-E1A-mda-7 into human breast cancer xenografts in athymic nude...CLASSIFICATION OF: 18 . NUMBER OF PAGES 19a. NAME OF RESPONSIBLE PERSON USAMRMC a. REPORT U b. ABSTRACT U c. THIS PAGE U UU 62 19b...breast cancer xenografts in athymic nude mice in vivo. Infection of this CRCA (designated Ad.PEG-E1A-mda-7) in normal mammary epithelial cells and

Characterization of metabolic profile of intact non-tumor and tumor breast cells by high-resolution magic angle spinning nuclear magnetic resonance spectroscopy.

PubMed

Maria, Roberta M; Altei, Wanessa F; Andricopulo, Adriano D; Becceneri, Amanda B; Cominetti, Márcia R; Venâncio, Tiago; Colnago, Luiz A

2015-11-01

(1)H high-resolution magic angle spinning nuclear magnetic resonance ((1)H HR-MAS NMR) spectroscopy was used to analyze the metabolic profile of an intact non-tumor breast cell line (MCF-10A) and intact breast tumor cell lines (MCF-7 and MDA-MB-231). In the spectra of MCF-10A cells, six metabolites were assigned, with glucose and ethanol in higher concentrations. Fifteen metabolites were assigned in MCF-7 and MDA-MB-231 (1)H HR-MAS NMR spectra. They did not show glucose and ethanol, and the major component in both tumor cells was phosphocholine (higher in MDA-MB-231 than in MCF-7), which can be considered as a tumor biomarker of breast cancer malignant transformation. These tumor cells also show acetone signal that was higher in MDA-MB-231 cells than in MCF-7 cells. The high acetone level may be an indication of high demand for energy in MDA-MB-231 to maintain cell proliferation. The higher acetone and phosphocholine levels in MDA-MB-231 cells indicate the higher malignance of the cell line. Therefore, HR-MAS is a rapid reproducible method to study the metabolic profile of intact breast cells, with minimal sample preparation and contamination, which are critical in the analyses of slow-growth cells. Copyright © 2015 Elsevier Inc. All rights reserved.

Utilizing wide area maritime domain awareness (MDA) data to cue a remote surveillance system

NASA Astrophysics Data System (ADS)

Isenor, Anthony W.; Cross, Richard; Webb, Sean; Lapinski, Anna-Liesa S.

2013-10-01

Defence Research and Development Canada - Atlantic (DRDC Atlantic) is currently involved in research on the topic of northern Maritime Domain Awareness (MDA). One project, entitled Situational Information for Enabling Development of Northern Awareness (SEDNA), includes research on the exploitation of MDA data in northern areas. One aspect of this research is to utilize wide area MDA data to provide awareness to an unattended, land-based system. Wide area MDA is attained through the use of space-based AIS (SAIS) data, a data feed used by the Canadian Department of National Defence and supplied by the commercial provider exactEarth Ltd. The land-based surveillance system used is the remote northern system constructed within the DRDC Northern Watch Technology Demonstration Project. Northern Watch is a multi-year project intended to show state-of-the-art, unattended, surveillance capabilities in the Canadian north. The link between the SAIS and Northern Watch is provided by a research infrastructure that consists of an assembly of data sources, users, applications, and product management techniques that collectively support research in areas such as information management and MDA data exploitation. High-level descriptions of the systems are provided along with elaboration on the alerting algorithm, the notifications that would be sent to the Northern Watch southern command site, and the resulting actions that could be taken by the Northern Watch surveillance system.

Decursin exerts anti-cancer activity in MDA-MB-231 breast cancer cells via inhibition of the Pin1 activity and enhancement of the Pin1/p53 association.

PubMed

Kim, Ji-Hyun; Jung, Ji Hoon; Kim, Sung-Hoon; Jeong, Soo-Jin

2014-02-01

The peptidyl-prolyl cis/trans isomerase Pin1 is overexpressed in a wide variety of cancer cells and thus considered as an important target molecule for cancer therapy. This study demonstrates that decursin, a bioactive compound from Angelica gigas, exert the anti-cancer effect against breast cancer cells via regulation of Pin1 and its related signaling molecules. We observed that decursin induced G1 arrest with decrease in cyclin D1 level in Pin1-expressing breast cancer cells MDA-MB-231, but not Pin1-non-expressing breast cancer cells MDA-MB-157. In addition, decursin significantly reduced protein expression and enzymatic activity of Pin1 in MDA-MB-231 cells. Further, we found that decursin treatment enhanced the p53 expression level and failed to down-regulate Pin1 in the cells transfected with p53 siRNA, indicating the importance of p53 in the decursin-mediated Pin1 inhibition in MDA-MB-231 cells. Decursin stimulated association between Pin1 to p53. Moreover, decursin facilitated p53 transcription in MDA-MB-231 cells. Overall, our current study suggests the potential of decursin as an attractive cancer therapeutic agent for breast cancer by targeting Pin1 protein. Copyright © 2013 John Wiley & Sons, Ltd.

Multiple displacement amplification on single cell and possible PGD applications.

PubMed

Hellani, Ali; Coskun, Serdar; Benkhalifa, Moncef; Tbakhi, Abelghani; Sakati, Nadia; Al-Odaib, Ali; Ozand, Pinar

2004-11-01

Multiple displacement amplification (MDA) is a technique used in the amplification of very low amounts of DNA and reported to yield large quantities of high-quality DNA. We used MDA to amplify the whole genome directly from a single cell. The most common techniques used in PGD are PCR and fluorescent in-situ hybridization (FISH). There are many limitations to these techniques including, the number of chromosomes diagnosed for FISH or the quality of DNA issued from a single cell PCR. This report shows, for the first time, use of MDA for single cell whole genome amplification. A total of 16 short tandem repeats (STRs) were amplified successfully with a similar pattern to the genomic DNA. Furthermore, allelic drop out (ADO) derived from MDA was assessed in 40 single cells by analysing (i) heterozygosity for a known beta globin mutation (IVSI-5 C-G) and by studying (ii) the heterozygous loci present in the STRs. ADO turned out to be 10.25% for the beta globin gene sequencing and 5% for the fluorescent PCR analysis of STRs. Moreover, the amplification accuracy of MDA permitted the detection of trisomy 21 on a single cell using comparative genome hybridization-array. Altogether, these data suggest that MDA can be used for single cell molecular karyotyping and the diagnosis of any single gene disorder in PGD.

Oxidative stress and genetic damage among workers exposed primarily to organophosphate and pyrethroid pesticides.

PubMed

Zepeda-Arce, Rigoberto; Rojas-García, Aurora Elizabeth; Benitez-Trinidad, Alma; Herrera-Moreno, José Francisco; Medina-Díaz, Irma Martha; Barrón-Vivanco, Briscia S; Villegas, Germán Pier; Hernández-Ochoa, Isabel; Sólis Heredia, María de Jesús; Bernal-Hernández, Yael Y

2017-06-01

The indiscriminate use of pesticides in agriculture and public health campaigns has been associated with an increase of oxidative stress and DNA damage, resulting in health outcomes. Some defense mechanisms against free radical-induced oxidative damage include the antioxidant enzyme systems. The aim of this study was to determine the levels of malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPx), glutathione reductase (GR), and the relationship of antioxidant enzyme levels with DNA damage among sprayers (workers) occupationally exposed to pesticides. The determinations of MDA and antioxidant enzymes were performed spectrophotometrically. The genotoxic effects were evaluated using the comet assay. The results showed a marginally significant decrease in SOD and CAT activities in the high exposure group compared to the control group. For MDA, statistically significant differences were found among people working long term vs. those working temporarily (P = 0.02) as sprayers. In the moderate exposure group, a positive correlation was observed between MDA levels and GPx activity. In the high exposure group, a negative correlation was observed between GR and CAT activities, and between MDA levels and GPx activities. Furthermore, in the high exposure group, a positive correlation between DNA damage parameters and MDA levels was observed. The results suggest an important role of antioxidant enzymes for the protection of DNA damage caused by occupational exposure to pesticides. © 2017 Wiley Periodicals, Inc.

Migration and invasion induced by linoleic acid are mediated through fascin in MDA-MB-231 breast cancer cells.

PubMed

Gonzalez-Reyes, Christian; Marcial-Medina, Cleofas; Cervantes-Anaya, Nancy; Cortes-Reynosa, Pedro; Salazar, Eduardo Perez

2018-06-01

Epidemiological studies strongly suggest an association between high levels of dietary fat intake and an increased risk of developing breast cancer. Linoleic acid (LA) is an essential omega-6 PUFA and the major fatty acid in occidental diets. In breast cancer cells, LA induces expression of plasminogen activator inhibitor-1, proliferation, migration, and invasion. Fascin is an actin crosslinker globular protein that generates actin bundles made of parallel actin filaments, which mediate formation and stability of microspikes, stress fibers, membrane ruffles, and filopodia. However, the role of fascin in migration and invasion induced by LA in MDA-MB-231 breast cancer cells remains to be studied. We demonstrate here that LA induces an increase of fascin expression in MDA-MB-231 and MCF12A mammary epithelial cells. Particularly, LA induces the formation of filopodia and lamellipodia and the localization of fascin in these actin structures in MDA-MB-231 breast cancer cells. However, LA only induces formation of microspikes and the localization of fascin in these actin structures in mammary non-tumorigenic epithelial cells MCF12A. In addition, LA induces migration, invasion, and matrix metalloproteinase-9 secretion through a fascin-dependent pathway in MDA-MB-231 cells. In summary, our findings demonstrate that fascin is required for migration and invasion induced by LA in MDA-MB-231 breast cancer cells.

Dissecting the role of Engrailed in adult dopaminergic neurons--Insights into Parkinson disease pathogenesis.

PubMed

Rekaik, Hocine; Blaudin de Thé, François-Xavier; Prochiantz, Alain; Fuchs, Julia; Joshi, Rajiv L

2015-12-21

The homeoprotein Engrailed (Engrailed-1/Engrailed-2, collectively En1/2) is not only a survival factor for mesencephalic dopaminergic (mDA) neurons during development, but continues to exert neuroprotective and physiological functions in adult mDA neurons. Loss of one En1 allele in the mouse leads to progressive demise of mDA neurons in the ventral midbrain starting from 6 weeks of age. These mice also develop Parkinson disease-like motor and non-motor symptoms. The characterization of En1 heterozygous mice have revealed striking parallels to central mechanisms of Parkinson disease pathogenesis, mainly related to mitochondrial dysfunction and retrograde degeneration. Thanks to the ability of homeoproteins to transduce cells, En1/2 proteins have also been used to protect mDA neurons in various experimental models of Parkinson disease. This neuroprotection is partly linked to the ability of En1/2 to regulate the translation of certain nuclear-encoded mitochondrial mRNAs for complex I subunits. Other transcription factors that govern mDA neuron development (e.g. Foxa1/2, Lmx1a/b, Nurr1, Otx2, Pitx3) also continue to function for the survival and maintenance of mDA neurons in the adult and act through partially overlapping but also diverse mechanisms. Copyright © 2015 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

THE USE OF MULTIPLE DISPLACEMENT AMPLIFICATION TO INCREASE THE DETECTION AND GENOTYPING OF TRYPANOSOMA SPECIES SAMPLES IMMOBILISED ON FTA FILTERS

PubMed Central

MORRISON, LIAM J.; McCORMACK, GILLIAN; SWEENEY, LINDSAY; LIKEUFACK, ANNE C. L.; TRUC, PHILIPPE; TURNER, C. MICHAEL; TAIT, ANDY; MacLEOD, ANNETTE

2007-01-01

Whole genome amplification methods are a recently developed tool for amplifying DNA from limited template. We report its application in trypanosome infections, characterised by low parasitaemias. Multiple Displacement Amplification (MDA) amplifies DNA with a simple in vitro step, and was evaluated on mouse blood samples on FTA filter cards with known numbers of Trypanosoma brucei parasites. The data showed a twenty-fold increase in the number of PCRs possible per sample, using primers diagnostic for the multi-copy ribosomal ITS region or 177 bp repeats, and a twenty-fold increase in sensitivity over nested PCR against a single copy microsatellite. Using MDA for microsatellite genotyping caused allele dropout at low DNA concentrations, which was overcome by pooling multiple MDA reactions. The validity of using MDA was established with samples from Human African Trypanosomiasis patients. The use of MDA allows maximal use of finite DNA samples and may prove a valuable tool in studies where multiple reactions are necessary, such as population genetic analyses. PMID:17556624

Pharbilignan C induces apoptosis through a mitochondria-mediated intrinsic pathway in human breast cancer cells.

PubMed

Park, Yong Joo; Choi, Chang-Ik; Chung, Kyu Hyuck; Kim, Ki Hyun

2016-10-01

Pharbitidis Semen, the seed of Morning glory (Pharbitis nil), is a medicinal agent that has traditionally been used as a purgative in Korea. Pharbilignan C (PLC) is a dihydro[b]-benzofuran-type neolignan from Pharbitidis Semen, which reportedly exhibited the most potent cytotoxicity against human tumor cells. To further study the antiproliferative activity of PLC, its molecular mechanisms of action in two breast adenocarcinoma cells, MCF-7 and MDA-MB 231 cells were investigated. PLC inhibited the proliferation of MDA-MB 231 and MCF-7 cells, in order of sensitivity (IC50 of MDA-MB 231 cells: 7.0±2.0μM). PLC induced apoptosis in MDA-MB 231 cells with down regulation of Bcl-2 and up-regulation of Bax expression. It also decreased mitochondrial membrane potential accompanied with increasing initiator caspase, caspase-9 activation and executioner caspase, caspase-3 activation. This study demonstrates that PLC inhibited proliferation of MDA-MB 231 cells by inducing apoptosis via the mitochondria-mediated intrinsic pathway. Copyright © 2016 Elsevier Ltd. All rights reserved.

Manned remote work station development article, executive summary

NASA Technical Reports Server (NTRS)

1979-01-01

The mission requirements for the manned remote work station (MRWS) flight article and the manned remote work station open cherry picker development test article is defined. Considerations are given for the near, mid, and far term use of the MRWS with emphasis on its ultimate application: constructing the Solar Power Satellite.

28 CFR 105.10 - Definitions, purpose, and scope.

Code of Federal Regulations, 2010 CFR

2010-07-01

... foreign pilot or flight engineer license issued by a member of the Assembly of the International Civil Aviation Organization, as established by Article 43 of the Convention on International Civil Aviation..., and flight schools. Virtually all private providers of instruction in the operation of aircraft with a...

A Flight Simulator Program Takes Off

ERIC Educational Resources Information Center

McMahon, Don

2003-01-01

Aviation concepts, including forces acting on an airplane, navigation, correct aircraft terminology, and general aviation vocabulary, are often part of a comprehensive fifth-grade aviation curriculum. But in one school district, students also learned about flying planes and even trained in a flight simulator. This article describes how industry…

Changes in thrombin-stimulated platelet malondialdehyde production during the menstrual cycle.

PubMed Central

Tindall, H; Zuzel, M; Paton, R C; McNicol, G P

1981-01-01

Forty normal women had thrombin-stimulated platelet malondialdehyde (MDA) production measured during their menstrual cycle. Twenty women in this group were taking the combined oral contraceptive pill (OCP). Platelet MDA production was found to fall by 30% during normal menstruation and the week when the subjects were not taking a combined OCP, but it remained constant throughout the remainder of the cycle. No significant change in initial platelet aggregation response to stimulation by thrombin, change in plasma thrombin clotting time, plasma heparin neutralising activity (HNA), or plasma antithrombin III (AT-III) activity was seen when the platelet MDA production was reduced. The bleeding time results showed some variation throughout the menstrual cycle but these did not appear to be related to the variation in platelet MDA production. PMID:7251901

Oppenheimer's Box of Chocolates: Remediation of the Manhattan Project Landfill at Los Alamos National Laboratory - 12283

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

Allen, Donald L.; Ramsey, Susan S.; Finn, Kevin P.

2012-07-01

Material Disposal Area B (MDA B) is the oldest radioactive waste disposal facility at Los Alamos National Laboratory. Operated from 1944-48, MDA B was the disposal facility for the Manhattan Project. Recognized as one of the most challenging environmental remediation projects at Los Alamos, the excavation of MDA B received $110 million from the American Recovery and Reinvestment Act of 2009 to accelerate this complex remediation work. Several factors combined to create significant challenges to remediating the landfill known in the 1940's as the 'contaminated dump'. The secrecy surrounding the Manhattan Project meant that no records were kept of radiologicalmore » materials and chemicals disposed or of the landfill design. An extensive review of historical documents and interviews with early laboratory personnel resulted in a list of hundreds of hazardous chemicals that could have been buried in MDA B. Also, historical reports of MDA B spontaneously combusting on three occasions -with 50-foot flames and pink smoke spewing across the mesa during the last incident in 1948-indicated that hazardous materials were likely present in MDA B. To complicate matters further, though MDA B was located on an isolated mesa in the 1940's, the landfill has since been surrounded by a Los Alamos commercial district. The local newspaper, hardware store and a number of other businesses are located directly across the street from MDA B. This close proximity to the public and the potential for hazardous materials in MDA B necessitated conducting remediation work within protective enclosures. Potential chemical hazards and radiological inventory were better defined using a minimally intrusive sampling method called direct push technology (DPT) prior to excavation. Even with extensive sampling and planning the project team encountered many surprises and challenges during the project. The one area where planning did not fail to meet reality was safety. There were no serious worker injuries and the minor injuries recorded were those common to construction type activities. Extensive monitoring along the site boundary demonstrated that no hazardous chemicals were released and radiological dose to the public was within administrative limits. More than three years of effort by the LANL project team went into the planning for remediation of Material Disposal Area B. Hundreds of historical documents were reviewed; retired personnel were extensively interviewed and noninvasive techniques were used to characterize the site. The information collected was incorporated into the safety requirements, cost estimate, schedule and primary execution plan for the project. Ultimately the waste volume managed by the project approached 40000 m{sup 3}, more than double the original project estimate. This increase had a major impact on both project cost and schedule. Nuclear safety requirements for the project were based on an estimated MDA B radionuclide inventory of 12 PE-Ci. When excavation was complete over 123 PE-Ci had been removed from the trenches. The radionuclide inventory at MDA B was an order of magnitude higher than estimated. Work at MDA B could not have proceeded without the safety basis exemption from DOE-HQ. The one area where planning did not fail to meet reality was safety. There were no serious worker injuries and the minor injuries recorded were those common to construction type activities. Extensive monitoring along the site boundary demonstrated that no hazardous chemicals were released and radiological dose to the public was within administrative limits. (authors)« less

Polymyositis: Medical Management

MedlinePlus

... Donate Search MDA.org Close Polymyositis (PM) Medical Management Polymyositis (PM) is a highly treatable disease. Some ... PM) Signs and Symptoms Diagnosis Causes/Inheritance Medical Management Research Find your MDA Care Center Grants at ...

International cooperation in space transportation

NASA Astrophysics Data System (ADS)

Carlson, C. R.

1997-01-01

International cooperation in the field of Space Transportation has become an accepted norm as companies and countries have come to understand the necessity of lower costs for launch services. Many different approaches have been attempted, some of which are more successful than others. This paper discusses the history of McDonnell Douglas Aerospace (MDA) launch vehicle cooperation with Japan, as well as how MDA developed Mitsubishi Heavy Industries (MHI) as a supplier for the Delta III program, and how MDA became a supplier for the Japanese H-2 vehicle.

Polymyositis: Diagnosis

MedlinePlus

... Association (MDA) is a qualified 501(c)(3) tax-exempt organization. ©2018, Muscular Dystrophy Association Inc. All ... Association (MDA) is a qualified 501(c)(3) tax-exempt organization. ©2018, Muscular Dystrophy Association Inc. All ...

Dermatomyositis: Diagnosis

MedlinePlus

... Association (MDA) is a qualified 501(c)(3) tax-exempt organization. ©2018, Muscular Dystrophy Association Inc. All ... Association (MDA) is a qualified 501(c)(3) tax-exempt organization. ©2018, Muscular Dystrophy Association Inc. All ...

Characterization and optimization of the magnetron directional amplifier

NASA Astrophysics Data System (ADS)

Hatfield, Michael Craig

Many applications of microwave wireless power transmission (WPT) are dependent upon a high-powered electronically-steerable phased array composed of many radiating modules. The phase output from the high-gain amplifier in each module must be accurately controlled if the beam is to be properly steered. A highly reliable, rugged, and inexpensive design is essential for making WPT applications practical. A conventional microwave oven magnetron may be combined with a ferrite circulator and other external circuitry to create such a system. By converting it into a two-port amplifier, the magnetron is capable of delivering at least 30 dB of power gain while remaining phase-locked to the input signal over a wide frequency range. The use of the magnetron in this manner is referred to as a MDA (Magnetron Directional Amplifier). The MDA may be integrated with an inexpensive slotted waveguide array (SWA) antenna to form the Electronically-Steerable Phased Array Module (ESPAM). The ESPAM provides a building block approach to creating phased arrays for WPT. The size and shape of the phased array may be tailored to satisfy a diverse range of applications. This study provided an in depth examination into the capabilities of the MDA/ESPAM. The basic behavior of the MDA was already understood, as well as its potential applicability to WPT. The primary objective of this effort was to quantify how well the MDA could perform in this capacity. Subordinate tasks included characterizing the MDA behavior in terms of its system inputs, optimizing its performance, performing sensitivity analyses, and identifying operating limitations. A secondary portion of this study examined the suitability of the ESPAM in satisfying system requirements for the solar power satellite (SPS). Supporting tasks included an analysis of SPS requirements, modeling of the SWA antenna, and the demonstration of a simplified phased array constructed of ESPAM elements. The MDA/ESPAM is well suited for use as an amplifier or an element in a WPT phased array, providing over 75% efficiency and a fractional bandwidth exceeding 1.7% at 2.45 GHz. The results of this effort provide the WPT design engineer with tools to predict the MDA's optimum performance and limitations.

Melanoma Differentiation-associated Gene 7/IL-24 Exerts Cytotoxic Effects by Altering the Alternative Splicing of Bcl-x Pre-mRNA via the SRC/PKCδ Signaling Axis*

PubMed Central

Shapiro, Brian A.; Vu, Ngoc T.; Shultz, Michael D.; Shultz, Jacqueline C.; Mietla, Jennifer A.; Gouda, Mazen M.; Yacoub, Adly; Dent, Paul; Fisher, Paul B.; Park, Margaret A.; Chalfant, Charles E.

2016-01-01

Melanoma differentiation-associated gene 7 (MDA-7/IL-24) exhibits cytotoxic effects on tumor cells while sparing untransformed cells, and Bcl-x(L) is reported to efficiently block the induction of cell death by MDA-7/IL-24. The expression of Bcl-x(L) is regulated at the level of RNA splicing via alternative 5′ splice site selection within exon 2 to produce either the pro-apoptotic Bcl-x(s) or the anti-apoptotic Bcl-x(L). Our laboratory previously reported that Bcl-x RNA splicing is dysregulated in a large percentage of human non-small cell lung cancer (NSCLC) tumors. Therefore, we investigated whether the alternative RNA splicing of Bcl-x pre-mRNA was modulated by MDA-7/IL-24, which would suggest that specific NSCLC tumors are valid targets for this cytokine therapy. Adenovirus-delivered MDA-7/IL-24 (Ad.mda-7) reduced the viability of NSCLC cells of varying oncogenotypes, which was preceded by a decrease in the ratio of Bcl-x(L)/Bcl-x(s) mRNA and Bcl-x(L) protein expression. Importantly, both the expression of Bcl-x(L) and the loss of cell viability were “rescued” in Ad.mda-7-treated cells incubated with Bcl-x(s) siRNA. In addition, NSCLC cells ectopically expressing Bcl-x(s) exhibited significantly reduced Bcl-x(L) expression, which was again restored by Bcl-x(s) siRNA, suggesting the existence of a novel mechanism by which Bcl-x(s) mRNA restrains the expression of Bcl-x(L). In additional mechanistic studies, inhibition of SRC and PKCδ completely ablated the ability of MDA-7/IL-24 to reduce the Bcl-x(L)/(s) mRNA ratio and cell viability. These findings show that Bcl-x(s) expression is an important mediator of MDA-7/IL-24-induced cytotoxicity requiring the SRC/PKCδ signaling axis in NSCLC cells. PMID:27519412

Epidermal growth factor promotes a mesenchymal over an amoeboid motility of MDA-MB-231 cells embedded within a 3D collagen matrix

NASA Astrophysics Data System (ADS)

Geum, Dongil T.; Kim, Beum Jun; Chang, Audrey E.; Hall, Matthew S.; Wu, Mingming

2016-01-01

The receptor of epidermal growth factor (EGFR) critically regulates tumor cell invasion and is a potent therapeutic target for treatment of many types of cancers, including carcinomas and glioblastomas. It is known that EGF regulates cell motility when tumor cells are embedded within a 3D biomatrix. However, roles of EGF in modulating tumor cell motility phenotype are largely unknown. In this article, we report that EGF promotes a mesenchymal over an amoeboid motility phenotype using a malignant breast tumor cell line, MDA-MB-231, embedded within a 3D collagen matrix. Amoeboid cells are rounded in shape, while mesenchymal cells are elongated, and their migrations are governed by a distinctly different set of biomolecules. Using single cell tracking analysis, we also show that EGF promotes cell dissemination through a significant increase in cell persistence along with a moderate increase of speed. The increase of persistence is correlated with the increase of the percentage of the mesenchymal cells within the population. Our work reveals a novel role of microenvironmental cue, EGF, in modulating heterogeneity and plasticity of tumor cell motility phenotype. In addition, it suggests a potential visual cue for diagnosing invasive states of breast cancer cells. This work can be easily extended beyond breast cancer cells.

Where dentistry stands in light of health care reform.

PubMed

Collignon, B H

1994-01-01

The hot topic from Capitol Hill in Washington to Capitol Hill in Jefferson City is health care reform. President Clinton started the ball rolling during the campaign in 1992 by including health care reform in his platform. He continued the effort after his election by appointing his wife, Hillary, to chair a task force to present an outline for federal legislation. Since the package was presented to Congress, there has been much discussion, lobbying, and rumoring about the implications of health care reform and what it could mean to all of us as dentists. On the home front, Governor Carnahan has introduced legislation in Missouri to reform the health care system. This effort is known as the Missouri Health Assurance Plan (H.B. 1622). Missouri Dental Association members are vitally concerned about the impact of health care reform on their practice, their taxes, their relationship with their patients and employees, and on their ability to seek out health care services since each member is also a consumer of health care. This article represents answers to some of the questions being asked by MDA members in order that they might be more aware of the activities by the MDA, the ADA, and other levels of organized dentistry relating to health care reform.

Lipid Peroxidation: Production, Metabolism, and Signaling Mechanisms of Malondialdehyde and 4-Hydroxy-2-Nonenal

PubMed Central

Muñoz, Mario F.; Argüelles, Sandro

2014-01-01

Lipid peroxidation can be described generally as a process under which oxidants such as free radicals attack lipids containing carbon-carbon double bond(s), especially polyunsaturated fatty acids (PUFAs). Over the last four decades, an extensive body of literature regarding lipid peroxidation has shown its important role in cell biology and human health. Since the early 1970s, the total published research articles on the topic of lipid peroxidation was 98 (1970–1974) and has been increasing at almost 135-fold, by up to 13165 in last 4 years (2010–2013). New discoveries about the involvement in cellular physiology and pathology, as well as the control of lipid peroxidation, continue to emerge every day. Given the enormity of this field, this review focuses on biochemical concepts of lipid peroxidation, production, metabolism, and signaling mechanisms of two main omega-6 fatty acids lipid peroxidation products: malondialdehyde (MDA) and, in particular, 4-hydroxy-2-nonenal (4-HNE), summarizing not only its physiological and protective function as signaling molecule stimulating gene expression and cell survival, but also its cytotoxic role inhibiting gene expression and promoting cell death. Finally, overviews of in vivo mammalian model systems used to study the lipid peroxidation process, and common pathological processes linked to MDA and 4-HNE are shown. PMID:24999379

Water and Energy Dietary Requirements and Endocrinology of Human Space Flight

NASA Technical Reports Server (NTRS)

Lane, Helen W.; Feeback, Daniel L.

2002-01-01

Fluid and energy metabolism and related endocrine changes have been studied nearly from the beginning of human space flight in association with short- and long-duration flights. Fluid and electrolyte nutrition status is affected by many factors including the microgravity environment, stress, changes in body composition, diet, exercise habits, sleep cycles, and ambient temperature and humidity conditions. Space flight exposes astronauts to all these factors and consequently poses significant challenges to establishing dietary water, sodium, potassium, and energy recommendations. The purpose of this article is to review the results of ground-based and space flight research studies that have led to current water, electrolyte, and energy dietary requirements for humans during space flight and to give an overview of related endocrinologic changes that have been observed in humans during short- and long-duration space flight.

Signs and Symptoms

MedlinePlus

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Autonomous mission management for UAVs using soar intelligent agents

NASA Astrophysics Data System (ADS)

Gunetti, Paolo; Thompson, Haydn; Dodd, Tony

2013-05-01

State-of-the-art unmanned aerial vehicles (UAVs) are typically able to autonomously execute a pre-planned mission. However, UAVs usually fly in a very dynamic environment which requires dynamic changes to the flight plan; this mission management activity is usually tasked to human supervision. Within this article, a software system that autonomously accomplishes the mission management task for a UAV will be proposed. The system is based on a set of theoretical concepts which allow the description of a flight plan and implemented using a combination of Soar intelligent agents and traditional control techniques. The system is capable of automatically generating and then executing an entire flight plan after being assigned a set of objectives. This article thoroughly describes all system components and then presents the results of tests that were executed using a realistic simulation environment.

Skylab

NASA Image and Video Library

1972-01-01

This photograph depicts the flight article of the Airlock Module (AM) Flight Article being mated to the Fixed Airlock Shroud and aligned in a clean room of the McDornell Douglas Plant in St. Louis, Missouri. The AM enabled crew members to conduct extravehicular activities outside Skylab as required for experiment support. Separated from the Workshop and the Multiple Docking Adapter by doors, the AM could be evacuated for egress or ingress of a space-suited astronaut through a side hatch. Oxygen and nitrogen storage tanks needed for Skylab's life support system were mounted on the external truss work of the AM. Major components in the AM included Skylab's electric power control and distribution station, environmental control system, communication system, and data handling and recording systems. The Marshall Space Flight Center was responsible for the design and development of the Skylab hardware and experiment management.

Optical isomer analysis of 3,4-methylene-dioxyamphetamine analogues and their stereoselective disposition in rats.

PubMed

Matsushima, K; Nagai, T; Kamiyama, S

1998-01-01

Identification of the optical activity and simultaneous analysis of racemates (+/-) of three hallucinogens, 3,4-methylenedioxy-amphetamine (MDA), 3,4-methylenedioxymethamphetamine (MDMA), and 3,4-methylenedioxyethylamphetamine (MDEA), and the urinary excretion of their optical isomers in rats was performed by high-performance liquid chromatographic analysis. Analysis of optical enantiomers of three N-alkyl MDA derivatives was performed within 50 min using two different detectors, polarimetry (OR) and ultraviolet spectroscopy (UV). The OR detector proved suitable for identification of the optically active forms, whereas the UV detector was suitable for simultaneous analysis of the enantiomers in urine. After the administration of each of the three N-alkylated derivatives, rat urine specimens were collected over four intervals, 0-4, 4-12, 12-20, and 20-24 h. After the administration of 30 mg/kg of racemic MDA and MDMA, somewhat less of the S(+)-forms of unchanged MDA and MDMA than of the R(-)-forms in each urine specimen were detected, which gave R/S ratios greater than 1.00 (p < 0.01). Conversely, after the administration of 30 mg/kg of racemic MDEA, more of the S(+)-form than the R(-)-form was found in the urine, thus giving R/S ratios less than 1.00 (p < 0.01). The percentage of the dose excreted up to 24 h was approximately 29.4% of the administered dose for MDA [S(+) 13.40% and R(-) 15.98%], 5.8% for MDMA [S(+) 1.96% and R(-) 3.79%], and 7.3% for MDEA [S(+) 3.89% and R(-) 3.43%]. Urinary excretion of optical isomers of N-dealkylated MDA from MDMA and MDEA origin were the opposite of those of the unchanged forms, and their R/S ratios up to 24 h were 0.48 to 0.72 (p < 0.01) and 1.31 to 1.50 (p < 0.01), respectively. The urinary excretion rates up to 24 h were approximately 4.3% for N-dealkylated MDA from MDMA origin [S(+) 2.72% and R(-) 1.63%] and 0.8% for N-dealkylated MDA from MDEA origin [S(+) 0.36% and R(-) 0.47%]. The total percent of unchanged forms and N-dealkylated MDA was approximately 10.1% for MDMA [S(+) 4.68% and R(-) 5.42%] and 8.2% for MDEA [S(+) 4.25% and R(-) 3.91%]. The total R/S ratio of MDMA was found to be 1.95 (p < 0.01), whereas that of MDEA was 0.88 (p < 0.01). The total R/S ratio of MDA was 1.20 (p < 0.01 ), which was comparable with that of MDMA. These three R/S ratios did not conform to the theoretical values for three N-alkyl derivatives used and neither did the R/S ratios of urine specimens collected at the four interval. These results suggested the stereoselective disposition of three N-alkyl MDA analogues in rat. The method would be suitable for the forensic chemistry and toxicology analysis of specimens obtained from hallucinogen abusers.

Inclusion-Body Myositis: Diagnosis

MedlinePlus

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Learn About Neuromuscular Disease

MedlinePlus

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Limb-Girdle Muscular Dystrophy (LGMD)

MedlinePlus

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Dermatomyositis: Signs and Symptoms

MedlinePlus

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Genetics Home Reference: MDA5 deficiency

MedlinePlus

... the protein recognizes a molecule called double-stranded RNA (a chemical cousin of DNA), which certain viruses, ... When the MDA5 protein recognizes pieces of viral RNA inside the cell, it helps turn on the ...

Herbal Extract SH003 Suppresses Tumor Growth and Metastasis of MDA-MB-231 Breast Cancer Cells by Inhibiting STAT3-IL-6 Signaling

PubMed Central

Woo, Sang-Mi; Park, Sunju; Shin, Yong Cheol; Ko, Seong-Gyu

2014-01-01

Cancer inflammation promotes cancer progression, resulting in a high risk of cancer. Here, we demonstrate that our new herbal extract, SH003, suppresses both tumor growth and metastasis of MDA-MB-231 breast cancer cells via inhibiting STAT3-IL-6 signaling path. Our new herbal formula, SH003, mixed extract from Astragalus membranaceus, Angelica gigas, and Trichosanthes kirilowii Maximowicz, suppressed MDA-MB-231 tumor growth and lung metastasis in vivo and reduced the viability and metastatic abilities of MDA-MB-231 cells in vitro. Furthermore, SH003 inhibited STAT3 activation, which resulted in a reduction of IL-6 production. Therefore, we conclude that SH003 suppresses highly metastatic breast cancer growth and metastasis by inhibiting STAT3-IL-6 signaling path. PMID:24976685

Multidrug-resistant malaria and the impact of mass drug administration.

PubMed

Zuber, Janie Anne; Takala-Harrison, Shannon

2018-01-01

Based on the emergence and spread throughout the Greater Mekong Subregion (GMS) of multiple artemisinin-resistant lineages, the prevalence of multidrug resistance leading to high rates of artemisinin-based combination treatment failure in parts of the GMS, and the declining malaria burden in the region, the World Health Organization has recommended complete elimination of falciparum malaria from the GMS. Mass drug administration (MDA) is being piloted as one elimination intervention to be employed as part of this effort. However, concerns remain as to whether MDA might exacerbate the already prevalent problem of multidrug resistance in the region. In this review, we briefly discuss challenges of MDA, the use of MDA in the context of multidrug-resistant malaria, and the potential of different drug combinations and drug-based elimination strategies for mitigating the emergence and spread of resistance.

LGP2 Synergy with MDA5 in RLR-Mediated RNA Recognition and Antiviral Signaling

PubMed Central

Bruns, Annie M.; Horvath, Curt M.

2015-01-01

Mammalian cells have the ability to recognize virus infection and mount a powerful antiviral response. Pattern recognition receptor proteins detect molecular signatures of virus infection and activate antiviral signaling. The RIG-I-like receptor (RLR) proteins are expressed in the cytoplasm of nearly all cells and specifically recognize virus-derived RNA species as a molecular feature discriminating the pathogen from the host. The RLR family is composed of three homologous proteins, RIG-I, MDA5, and LGP2. All RLRs have the ability to detect virus-derived dsRNA and hydrolyze ATP, but display individual differences in enzymatic activity, intrinsic ability to recognize RNA, and mechanisms of activation. Emerging evidence suggests that MDA5 and RIG-I utilize distinct mechanisms to form oligomeric complexes along dsRNA. Aligning of their signaling domains creates a platform capable of propagating and amplifying antiviral signaling responses. LGP2 with intact ATP hydrolysis is critical for the MDA5-mediated antiviral response, but LGP2 lacks the domains essential for activation of antiviral signaling, leaving the role of LGP2 in antiviral signaling unclear. Recent studies revealed a mechanistic basis of synergy between LGP2 and MDA5 leading to enhanced antiviral signaling. This review briefly summarizes the RLR system, and focuses on the relationship between LGP2 and MDA5, describing in detail how these two proteins work together to detect foreign RNA and generate a fully functional antiviral response. PMID:25794939

[Knock-down of BCL11A expression in breast cancer cells promotes MDA-MB-231 cell apoptosis].

PubMed

Li, Hongli; Gui, Chen; Yan, Lijun

2016-11-01

Objective To detect the expression and pathological significance of B-cell CLL/lymphoma 11A (BCL11A) in breast cancer and investigate the effect of its silencing on the apoptosis of human MDA-MB-231 breast cancer cells. MethodsImmunohistochemistry was used to detect the expression of BCL11A in 62 cases of human breast cancer tissues and 8 cases of normal tissues. We synthesized siRNA targeting BCL11A, and then siRNA was transfected into MDA-MB-231 cells. Forty-eight hours later, the suppression effect of siRNA on BCL11A was determined by quantitative real-time PCR and Western blotting. The apoptosis of MDA-MB-231 cells was detected by flow cytometry. Results The BCL11A protein was mainly expressed in cytoplasm. The expression level of BCL11A in breast cancer tissues was higher than that in paracancerous tissues. The expression had correlations with tumor grade, tumor stage, while it had no correlations with the patients' age and tumor size. BCL11A-siRNA significantly suppressed the expression of BCL11A mRNA and protein as compared with the control group. MDA-MB-231 cells transfected with BCL11A-siRNA had higher apoptosis rate compared with the control group. Conclusion The BCL11A protein is highly expressed in breast cancer and knock-down of BCL11A promotes the apoptosis of MDA-MB-231 cells.

Recognition of Porphyromonas gingivalis Gingipain Epitopes by Natural IgM Binding to Malondialdehyde Modified Low-Density Lipoprotein

PubMed Central

Turunen, S. Pauliina; Kummu, Outi; Harila, Kirsi; Veneskoski, Marja; Soliymani, Rabah; Baumann, Marc; Pussinen, Pirkko J.; Hörkkö, Sohvi

2012-01-01

Objective Increased risk for atherosclerosis is associated with infectious diseases including periodontitis. Natural IgM antibodies recognize pathogen-associated molecular patterns on bacteria, and oxidized lipid and protein epitopes on low-density lipoprotein (LDL) and apoptotic cells. We aimed to identify epitopes on periodontal pathogen Porphyromonas gingivalis recognized by natural IgM binding to malondialdehyde (MDA) modified LDL. Methods and Results Mouse monoclonal IgM (MDmAb) specific for MDA-LDL recognized epitopes on P. gingivalis on flow cytometry and chemiluminescence immunoassays. Immunization of C57BL/6 mice with P. gingivalis induced IgM, but not IgG, immune response to MDA-LDL and apoptotic cells. Immunization of LDLR−/− mice with P. gingivalis induced IgM, but not IgG, immune response to MDA-LDL and diminished aortic lipid deposition. On Western blot MDmAb bound to P. gingivalis fragments identified as arginine-specific gingipain (Rgp) by mass spectrometry. Recombinant domains of Rgp produced in E. coli were devoid of phosphocholine epitopes but contained epitopes recognized by MDmAb and human serum IgM. Serum IgM levels to P. gingivalis were associated with anti-MDA-LDL levels in humans. Conclusion Gingipain of P. gingivalis is recognized by natural IgM and shares molecular identity with epitopes on MDA-LDL. These findings suggest a role for natural antibodies in the pathogenesis of two related inflammatory diseases, atherosclerosis and periodontitis. PMID:22496875

Ziyuglycoside I Inhibits the Proliferation of MDA-MB-231 Breast Carcinoma Cells through Inducing p53-Mediated G2/M Cell Cycle Arrest and Intrinsic/Extrinsic Apoptosis.

PubMed

Zhu, Xue; Wang, Ke; Zhang, Kai; Zhang, Ting; Yin, Yongxiang; Xu, Fei

2016-11-22

Due to the aggressive clinical behavior, poor outcome, and lack of effective specific targeted therapies, triple-negative breast cancer (TNBC) has currently been recognized as one of the most malignant types of tumors. In the present study, we investigated the cytotoxic effect of ziyuglycoside I, one of the major components extracted from Chinese anti-tumor herbal Radix Sanguisorbae , on the TNBC cell line MDA-MB-231. The underlying molecular mechanism of the cytotoxic effect ziyuglycoside I on MDA-MB-231 cells was investigated with cell viability assay, flow cytometric analysis and Western blot. Compared to normal mammary gland Hs 578Bst cells, treatment of ziyuglycoside I resulted in a significant growth inhibitory effect on MDA-MB-231 cells. Ziyuglycoside I induced the G2/M phase arrest and apoptosis of MDA-MB-231 cells in a dose-dependent manner. These effects were found to be partially mediated through the up-regulation of p53 and p21 WAF1 , elevated Bax/Bcl-2 ratio, and the activation of both intrinsic (mitochondrial-initiated) and extrinsic (Fas/FasL-initiated) apoptotic pathways. Furthermore, the p53 specific siRNA attenuated these effects. Our study suggested that ziyuglycoside I-triggered MDA-MB-231 cell cycle arrest and apoptosis were probably mediated by p53. This suggests that ziyuglycoside I might be a potential drug candidate for treating TNBC.

Curcumin blocks RON tyrosine kinase-mediated invasion of breast carcinoma cells.

PubMed

Narasimhan, Madhusudhanan; Ammanamanchi, Sudhakar

2008-07-01

We have recently shown that macrophage-stimulating protein (MSP) promotes the invasion of recepteur d'origine nantais (RON), a tyrosine kinase receptor-positive MDA-MB-231, MDA-MB-468 breast cancer cells, and also identified the regulatory elements required for RON gene expression. In this report, we have analyzed the efficacy of a chemopreventive agent, curcumin, in blocking RON tyrosine kinase-mediated invasion of breast cancer cells. Reverse transcription-PCR and Western analysis indicated the down-regulation of the RON message and protein, respectively, in MDA-MB-231 and MDA-MB-468 cells. Significantly, curcumin-mediated inhibition of RON expression resulted in the blockade of RON ligand, MSP-induced invasion of breast cancer cells. We have identified two putative nuclear factor-kappaB p65 subunit binding sites on the RON promoter. Using chromatin immunoprecipitation analysis and site-directed mutagenesis of the RON promoter, we have confirmed the binding of p65 to the RON promoter. Our data show that curcumin reduces RON expression by affecting p65 protein expression and transcriptional activity. Treatment of MDA-MB-231 cells with pyrrolidine dithiocarbamate, an inhibitor of p65, or small interfering RNA knockdown of p65, blocked RON gene expression and MSP-mediated invasion of MDA-MB-231 cells. This is the first report showing the regulation of human RON gene expression by nuclear factor-kappaB and suggests a potential therapeutic role for curcumin in blocking RON tyrosine kinase-mediated invasion of carcinoma cells.

The contribution of mass drug administration to global health: past, present and future.

PubMed

Webster, Joanne P; Molyneux, David H; Hotez, Peter J; Fenwick, Alan

2014-01-01

Mass drug administration (MDA) is a means of delivering safe and inexpensive essential medicines based on the principles of preventive chemotherapy, where populations or sub-populations are offered treatment without individual diagnosis. High-coverage MDA in endemic areas aims to prevent and alleviate symptoms and morbidity on the one hand and can reduce transmission on the other, together improving global health. MDA is the recommended strategy of the World Health Organisation to control or eliminate several neglected tropical diseases (NTDs). More than 700 million people now receive these essential NTD medicines annually. The combined cost of integrated NTD MDA has been calculated to be in the order of $0.50 per person per year. Activities have recently been expanded due, in part, to the proposed attempt to eliminate certain NTDs in the coming two decades. More than 1.9 billion people need to receive MDA annually across several years if these targets are to be met. Such extensive coverage will require additional avenues of financial support, expanded monitoring and evaluation focusing on impact and drug efficacy, as well as new diagnostic tools and social science strategies to encourage adherence. MDA is a means to help reduce the burden of disease, and hence poverty, among the poorest sector of populations. It has already made significant improvements to global health and productivity and has the potential for further successes, particularly where incorporated into sanitation and education programmes. However logistical, financial and biological challenges remain.

In vivo visualization and attenuation of oxidized lipid accumulation in hypercholesterolemic zebrafish

PubMed Central

Fang, Longhou; Green, Simone R.; Baek, Ji Sun; Lee, Sang-Hak; Ellett, Felix; Deer, Elena; Lieschke, Graham J.; Witztum, Joseph L.; Tsimikas, Sotirios; Miller, Yury I.

2011-01-01

Oxidative modification of LDL is an early pathological event in the development of atherosclerosis. Oxidation events such as malondialdehyde (MDA) formation may produce specific, immunogenic epitopes. Indeed, antibodies to MDA-derived epitopes are widely used in atherosclerosis research and have been demonstrated to enable cardiovascular imaging. In this study, we engineered a transgenic zebrafish with temperature-inducible expression of an EGFP-labeled single-chain human monoclonal antibody, IK17, which binds to MDA-LDL, and used optically transparent zebrafish larvae for imaging studies. Feeding a high-cholesterol diet (HCD) supplemented with a red fluorescent lipid marker to the transgenic zebrafish resulted in vascular lipid accumulation, quantified in live animals using confocal microscopy. After heat shock–induced expression of IK17-EGFP, we measured the time course of vascular accumulation of IK17-specific MDA epitopes. Treatment with either an antioxidant or a regression diet resulted in reduced IK17 binding to vascular lesions. Interestingly, homogenates of IK17-EGFP–expressing larvae bound to MDA-LDL and inhibited MDA-LDL binding to macrophages. Moreover, sustained expression of IK17-EGFP effectively prevented HCD-induced lipid accumulation in the vascular wall, suggesting that the antibody itself may have therapeutic effects. Thus, we conclude that HCD-fed zebrafish larvae with conditional expression of EGFP-labeled oxidation-specific antibodies afford an efficient method of testing dietary and/or other therapeutic antioxidant strategies that may ultimately be applied to humans. PMID:22105168

[Effects of trimetazidine on serum oxygen free radicals in congestive heart failure].

PubMed

Ma, Qi-lin; Xie, Yong; Zhang, Sai-dan

2002-12-28

To investigate the level of serum superoxide dismutase (SOD) and maiondialdehyde (MDA) and left ventricular systolic function in congestive heart failure (CHF) and to evaluate the influence of trimetazidine on them. Serum SOD and MDA were measured in 50 patients with heart function from grade two to four and 15 normal subjects. All the persons underwent echocardiography to determine the left ventricular end-systolic volume index (LVESVI) and the left ventricular ejection fraction (EF). The patients with CHF were randomly treated with trimetazidine plus routine therapy (n = 25) or routine therapy only (n = 25) for 8 weeks with evaluations made before and after the treatment. The SOD level and EF in the patients with CHF significantly decreased and the MDA level and LVESVI in those patients significantly increased compared with the normal subjects (P < 0.05); the severer the CHF, the greater the changes. After the treatment, the SOD level and EF increased significantly and MDA and LVESVI decreased significantly (P < 0.01) in both the trimetazidine and the conventional groups. And these changes were more obvious in the trimetazidine group than in the conventional group(P < 0.01). Oxygen free radicals play an important role in the pathophysiologic changes of CHF. The level of serum SOD and MDA can indicate the degree of CHF. Trimetazidine not only increases the level of SOD and decreases the level of MDA, but also improves the left ventricular systolic function.

Monodisperse Picoliter Droplets for Low-Bias and Contamination-Free Reactions in Single-Cell Whole Genome Amplification

PubMed Central

Maruyama, Toru; Yamagishi, Keisuke; Mori, Tetsushi; Takeyama, Haruko

2015-01-01

Whole genome amplification (WGA) is essential for obtaining genome sequences from single bacterial cells because the quantity of template DNA contained in a single cell is very low. Multiple displacement amplification (MDA), using Phi29 DNA polymerase and random primers, is the most widely used method for single-cell WGA. However, single-cell MDA usually results in uneven genome coverage because of amplification bias, background amplification of contaminating DNA, and formation of chimeras by linking of non-contiguous chromosomal regions. Here, we present a novel MDA method, termed droplet MDA, that minimizes amplification bias and amplification of contaminants by using picoliter-sized droplets for compartmentalized WGA reactions. Extracted DNA fragments from a lysed cell in MDA mixture are divided into 105 droplets (67 pL) within minutes via flow through simple microfluidic channels. Compartmentalized genome fragments can be individually amplified in these droplets without the risk of encounter with reagent-borne or environmental contaminants. Following quality assessment of WGA products from single Escherichia coli cells, we showed that droplet MDA minimized unexpected amplification and improved the percentage of genome recovery from 59% to 89%. Our results demonstrate that microfluidic-generated droplets show potential as an efficient tool for effective amplification of low-input DNA for single-cell genomics and greatly reduce the cost and labor investment required for determination of nearly complete genome sequences of uncultured bacteria from environmental samples. PMID:26389587

Review of the Ecotoxicological Properties of the Methylenedianiline Substances.

PubMed

Schupp, T; Allmendinger, H; Bossuyt, B T A; Hidding, B; Tury, B; West, R J

Concerning chronic toxicity, D. magna is the most sensitive species tested against MDA aquatic exposures, with a 21 days-NOEC of 0.00525 mg/L. Exposure of daphnids takes place via the aquatic phase. Other species of the same phylum (Arthropoda) appear to be less sensitive albeit with exposures via soil or sediment, with a 28 days-NOEC of 562 mg/kg d. w. soil (F. candida) and 41.3 mg/kg d. w. sediment (Hyalella azteca), for reproductive and survival endpoints, respectively. Also for acute toxicity, D. magna is more sensitive than the other species, with an 48 h-EC50 that spreads over two orders of magnitude, ranging from 0.019 to 2.7 mg/L. Fish show a more uniform reaction to MDA, with 96 h-LC50 ranging from about 20 to 60 mg/L; chronic data for fish are not available. Acute toxicity data for algae and cyanobacteria are in the range of 1-10 mg/L; based on growth rate, the 72 h-NOEC r or E r C 10 of MDA to algae is 0.3-9.3 mg/L.For sediment organisms, the black worm L. variegatus shows the highest sensitivity against MDA with a NOEC between ≤3.75 mg/kg and 30 mg/kg d. w., followed by the amphipod H. azteca. The lower sensitivity of L. variegatus in the second study compared to the first study is obviously attributable to the different feeding regimes (semi-continuous feeding against pre-spiked sediment). One argument might be that semi-continuous feeding allows the organisms to avoid the contaminated food. However, a change from semi-continuous feeding to sediment pre-spiked with nettle powder (Urtica sp.) results in an earlier and much stronger increase in ammonia concentration in the system. This became apparent after both studies on the blackworm were finalized. The ammonia 96 h-EC50 for the blackworm is 0.69 mg/L at pH = 8.2, and the 96 h-EC10 at pH = 8.2 is 0.33 mg/L (Hickey and Vickers, Arch Environ Contam Toxicol 26:292-298, 1994). As a result, the lower NOEC and LOEC in the second study with L. variegatus are probably attributable to interference by ammonia.MDA binds irreversibly to soil and sediment which may explain the general, but not uniform lower sensitivity of soil and sediment organisms against aquatic organisms. However, species with intense soil or sediment contact (L. variegatus and E. fetida) show in general lower NOEC values than those organisms with less direct contact (3.75 and 11.2 mg/kg d. w., respectively). On the one hand it may be hypothesized that this intense contact to soil bound MDA is one reason for the higher sensitivity; on the other hand, metabolic capacity against MDA of the organisms tested is unknown at this point in time and might as well explain differences in species sensitivity. For plants there are only acute data available, and in respect to acute toxicity L. sativa is more sensitive to MDA than E. fetida.Limited aquatic data available so far do not indicate that the toxicity of pMDA is different to MDA. In addition, the limited set of data generated with the marine M. macrocopa (crustacean), N. fustulum (diatom) and V. fisheri (bacteria) do not indicate that sea water organisms are more sensitive to MDA than fresh water organisms.In mammals, MDA is unlikely to interact with the endocrine sexual system; interaction with the adrenergic system cannot be ruled out, and effects of MDA on the thyroid hormone system have been demonstrated. MDA inhibits the thyroid peroxidase which might contribute to the thyroid gland tumors observed in chronic studies with rats and mice. Some anti-androgenic activity in in vitro studies with yeast cell did not prevail in in vivo studies with rats and mice.

Air & Space, Volume 2, Number 4, March-April, 1979.

ERIC Educational Resources Information Center

Forbush, Julie, Ed.

This newsletter, produced by the National Air and Space Museum of the Smithsonian Institution, contains an article on the Apollo 11 spaceflight, an article on hypersonic and supersonic flight which compares the Concorde, the X-15, and the Shuttle Orbiter, an article presenting photographs of the construction of the Shuttle Orbiter, and an article…

Evaluation of Hypolipidemic and Antioxidant Effects in Phenolrich Fraction of Crataegus pinnatifida Fruit in Hyperlipidemia Rats and Identification of Chemical Composition by Ultra-performance Liquid Chromatography Coupled with Quadropole Time-of-flight Mass Spectrometry

PubMed Central

Shao, Feng; Gu, Lifei; Chen, Huijuan; Liu, Ronghua; Huang, Huilian; Chen, Lanying; Yang, Ming

2017-01-01

Background: Hawthorn (Crataegus pinnatifida) fruit has enjoyed a great popularity as a pleasant-tasting food associated with hypolipidemic and antioxidant effects. Objective: Our aim was to screen the effective fraction of hawthorn fruit in the treatment of hyperlipidemia rats. Materials and Methods: In this study, ethanol extract of hawthorn fruit (Fr.1) and four fractionated extracts (Fr.2, Fr.3, Fr.4, and Fr.5) were compared to total phenol content evaluated using Folin–Ciocalteu method, and hypolipidemic and antioxidant effects were assessed in hyperlipidemic rats. Results: Total phenol content of Fr.4 was higher than other fractions by at least 2 fold. Furthermore, this fraction possessed the strongest hypolipidemic and antioxidant effects in hyperlipidemic rats. On this basis, 15 phenolic compounds and four organic acids in Fr.4 were positively or tentatively identified using ultra-performance liquid chromatography coupled with quadropole time-of-flight mass spectrometry. In addition, 5-O-caffeoyl quinic acid butyl ester was first reported in hawthorn fruit. Conclusion: Phenol-rich fraction in hawthorn fruit exhibited satisfactory hypolipidemic and antioxidant effects, and this could be exploited for further promotion of functional foods. SUMMARY Phenol-rich fraction in hawthorn fruit possesses most potent hypolipidemic and antioxidant effects in hyperlidemia rats. Abbreviations used: UPLC-Q-TOF-MS/MS: Ultra performance liquid chromatography coupled with quadropole time-of-flight mass spectrometry; TC: Total cholesterol; TG: Triglyceride; LDL-C: Low-density lipoprotein-cholesterol; HDL-C: High-density lipoprotein-cholesterol; GSH-Px: Glutathione peroxidase; SOD: Superoxide dismutase; MDA: Malondialdehyde; CAT: Catalase; NO: Nitric oxide; NOS: Nitric oxide synthase; ROS: Reactive oxygen species; •OOH: Superoxide anions, •OH: Hydroxyl radicals. PMID:29200740

Evaluation of Hypolipidemic and Antioxidant Effects in Phenolrich Fraction of Crataegus pinnatifida Fruit in Hyperlipidemia Rats and Identification of Chemical Composition by Ultra-performance Liquid Chromatography Coupled with Quadropole Time-of-flight Mass Spectrometry.

PubMed

Shao, Feng; Gu, Lifei; Chen, Huijuan; Liu, Ronghua; Huang, Huilian; Chen, Lanying; Yang, Ming

2017-01-01

Hawthorn ( Crataegus pinnatifida ) fruit has enjoyed a great popularity as a pleasant-tasting food associated with hypolipidemic and antioxidant effects. Our aim was to screen the effective fraction of hawthorn fruit in the treatment of hyperlipidemia rats. Materials and Methods: In this study, ethanol extract of hawthorn fruit (Fr.1) and four fractionated extracts (Fr.2, Fr.3, Fr.4, and Fr.5) were compared to total phenol content evaluated using Folin-Ciocalteu method, and hypolipidemic and antioxidant effects were assessed in hyperlipidemic rats. Total phenol content of Fr.4 was higher than other fractions by at least 2 fold. Furthermore, this fraction possessed the strongest hypolipidemic and antioxidant effects in hyperlipidemic rats. On this basis, 15 phenolic compounds and four organic acids in Fr.4 were positively or tentatively identified using ultra-performance liquid chromatography coupled with quadropole time-of-flight mass spectrometry. In addition, 5-O-caffeoyl quinic acid butyl ester was first reported in hawthorn fruit. Phenol-rich fraction in hawthorn fruit exhibited satisfactory hypolipidemic and antioxidant effects, and this could be exploited for further promotion of functional foods. Phenol-rich fraction in hawthorn fruit possesses most potent hypolipidemic and antioxidant effects in hyperlidemia rats. Abbreviations used: UPLC-Q-TOF-MS/MS: Ultra performance liquid chromatography coupled with quadropole time-of-flight mass spectrometry; TC: Total cholesterol; TG: Triglyceride; LDL-C: Low-density lipoprotein-cholesterol; HDL-C: High-density lipoprotein-cholesterol; GSH-Px: Glutathione peroxidase; SOD: Superoxide dismutase; MDA: Malondialdehyde; CAT: Catalase; NO: Nitric oxide; NOS: Nitric oxide synthase; ROS: Reactive oxygen species; •OOH: Superoxide anions, •OH: Hydroxyl radicals.

Background Oriented Schlieren (BOS) of a Supersonic Aircraft in Flight

NASA Technical Reports Server (NTRS)

Heineck, James T.; Banks, Daniel W.; Schairer, Edward T.; Haering, Edward A.; Bean, Paul S.

2016-01-01

This article describes the development and use of Background Oriented Schlieren on a full-scale supersonic jet in flight. A series of flight tests was performed in October, 2014 and February 2015 using the flora of the desert floor in the Supersonic Flight Corridor on the Edwards Air Force Base as a background. Flight planning was designed based on the camera resolution, the mean size and color of the predominant plants, and the navigation and coordination of two aircraft. Software used to process the image data was improved with additional utilities. The planning proved to be effective and the vast majority of the passes of the target aircraft were successfully recorded. Results were obtained that are the most detailed schlieren imagery of an aircraft in flight to date.

Transient Pressure Test Article Test Program

NASA Technical Reports Server (NTRS)

Vibbart, Charles M.

1989-01-01

The Transient Pressure Test Article (TPTA) test program is being conducted at a new test facility located in the East Test Area at the National Aeronautics and Space Administration's (NASA's) Marshall Space Flight Center (MSFC) in Huntsville, Alabama. This facility, along with the special test equipment (STE) required for facility support, was constructed specifically to test and verify the sealing capability of the Redesigned Solid Rocket Motor (RSRM) field, igniter, and nozzle joints. The test article consists of full scale RSRM hardware loaded with inert propellant and assembled in a short stack configuration. The TPTA is pressurized by igniting a propellant cartridge capable of inducing a pressure rise rate which stimulates the ignition transient that occurs during launch. Dynamic loads are applied during the pressure cycle to simulate external tank attach (ETA) strut loads present on the ETA ring. Sealing ability of the redesigned joints is evaluated under joint movement conditions produced by these combined loads since joint sealing ability depends on seal resilience velocity being greater than gap opening velocity. Also, maximum flight dynamic loads are applied to the test article which is either pressurized to 600 psia using gaseous nitrogen (GN2) or applied to the test article as the pressure decays inside the test article on the down cycle after the ignition transient cycle. This new test facility is examined with respect to its capabilities. In addition, both the topic of test effectiveness versus space vehicle flight performance and new aerospace test techniques, as well as a comparison between the old SRM design and the RSRM are presented.

[Impact of siRNA-mediated down-regulation of CD147 on human breast cancer cells].

PubMed

Li, Zhenqian; Li, Daoming; Li, Jiangwei; Huang, Pei; Qin, Hui

2015-10-01

To investigate the influence of siRNA-mediated down-regulation of CD147 on growth, proliferation and movement of human breast cancer cell line MDA-MB-231. The protein expression of CD147, MMP-2 and TIMP-2 of the MDA-MB-231 cells were analyzed by ABC. Lentiviral expression vector of CD147 gene was constructed and transfected into MDA-MB-231 cells. RT-PCR and Western blot were used to detect the mRNA and protein level changes of CD147 genes to identify the optimal time point, followed by detection of changes of mRNA and protein expression of MMP-2 and TIMP-2 genes. CCK-8 reagent method and cell scratch test were used to detect the proliferation and migration change of MDA-MB-231 cells. The nude mouse model of breast cancer by hypodermic injection with MDA-MB-231 cells was established to document the effect of CD147 siRNA on the tumor transplants. After transfection of lentiviral expression vector of CD147 gene, protein of CD147, MMP-2 and TIMP-2 were weakly or negative expressed, significantly weaker than those of control group (P < 0.01). After 72 hours of transfection, average down-regulation rate of CD147 and MMP-2 were 96.03% ± 0.84% and 96.03% ± 0.84%, respectively. Both CD147 mRNA and MMP-2 mRNA expression were down-regulated (P < 0.05), while TIMP-2 mRNA expression showed no significant deference (P > 0.05). No less than 2 days after transfection, cell growth of MDA-MB-231 cell line was found significantly inhibited (P < 0.05). After 24 hours of transection, average migration distance of MDA-MB-231 cell line and control group were (0.64 ± 0.12) mm and (4.69 ± 0.85) mm, respectively, which indicated a lower migrate speed. Down regulation of CD147 led to reduction of volume and mass of nude mouses. The growth of the carcinoma transplant was inhibited upon siRNA-mediated down-regulation of CD147 (P < 0.05), with an average tumor mass of (1.85 ± 0.98) g and both reduction of tumor size and tumor mass. CD147 may alter the MMP-2/TIMP-2 balance in MDA-MB-231 cells. CD147 gene silencing inhibits the proliferation and migration of MDA-MB-231 cells and the growth of carcinoma transplants in nude mice.

Association between activities of SOD, MDA and Na+-K+-ATPase in peripheral blood of patients with acute myocardial infarction and the complication of varying degrees of arrhythmia.

PubMed

Yin, Yu; Han, Wei; Cao, Ying

2018-04-24

To investigate the changes of ambulatory electrocardiography and peripheral blood SOD, MDA and Na+-K+-ATP enzymes in patients of acute myocardial infarction (AMI) complicated with arrhythmia. From January 2012 to March 2015, 135 cases AMI complicated with arrhythmia in our hospital were divided into 2 groups: 70 cases in the AMI uncomplicated with arrhythmia and 65 cases in the AMI complicated with arrhythmia. 62 cases volunteers accepted physical examination in our hospital in the same period were collected as the control group. 24 hour-electrocardiogram detected by ambulatory electrocardiogram (AECG), SOD and MDA in peripheral blood detected by diagnostic reagent kit and Na+-K+-ATP enzymes in peripheral blood detected by malachite green Kit Method phosphate determination method were collected. ROC curve was used to evaluate the prognostic value of SOD, MDA and Na+-K+-ATP enzymes in AMI patients. Compared with the control group, the patients had unusual ambulatory electrocardiography had increased (P <0.05), peripheral blood SOD and Na+-K+-ATP enzymes had decreased, peripheral blood MDA had increased in 2 AMI groups (P <0.05). Compared with AMI uncomplicated with arrhythmia group, the patients had unusual ambulatory electrocardiography had increased (P <0.05), peripheral blood SOD and Na+-K+-ATP enzymes had decreased, peripheral blood MDA had increased in AMI complicated with arrhythmia group (P <0.05). Among 135 cases AMI patients, 120 (88.9%) survived and 15 (11.1%) died, of whom 11 cases were AMI complicated with arrhythmia group, 4 cases were AMI uncomplicated with arrhythmia group. Compared with the AMI uncomplicated with arrhythmia group, the dead patients were more in the AMI complicated with arrhythmia group (c2 = 4.287, P = 0.038). Compared with the survival group, the SOD and Na+-K+-ATP enzymes were significantly lower (P <0.05) and MDA significantly higher (P <0.05) in the death group. The area under the ROC curve of SOD, MDA and Na+-K+-ATP enzymes were 0.958, 0.954 and 0.993 respectively, and the cut-off values were 30.66 ng/ml, 576.70 nmol/ml and 57.42 nmol/mgh, respectively. Ambulatory electrocardiography has a close relationship with the peripheral blood SOD, MDA and Na+-K+-ATP enzymes in AMI patients complicated with arrhythmia, which might predict AMI condition. Copyright © 2018 Hellenic Society of Cardiology. Published by Elsevier B.V. All rights reserved.

Design and Manufacture of Structurally Efficient Tapered Struts

NASA Technical Reports Server (NTRS)

Brewster, Jebediah W.

2009-01-01

Composite materials offer the potential of weight savings for numerous spacecraft and aircraft applications. A composite strut is just one integral part of the node-to-node system and the optimization of the shut and node assembly is needed to take full advantage of the benefit of composites materials. Lockheed Martin designed and manufactured a very light weight one piece composite tapered strut that is fully representative of a full scale flight article. In addition, the team designed and built a prototype of the node and end fitting system that will effectively integrate and work with the full scale flight articles.

Ferrous ion induced photon emission as a method to quantify oxidative stress in stored boar spermatozoa.

PubMed

Gogol, Piotr; Pieszka, Marek

2008-01-01

The aim of the study was to evaluate the effect of semen storage on ferrous ion induced luminescence of boar spermatozoa and to determine the relationship between parameters of this luminescence and lipid peroxidation as measured by malondialdehyde (MDA) contents. Boar semen samples were diluted in Biosolwens extender and stored for 12 days at 15 degrees C. Luminescence and MDA were measured directly after dilution (day 0) and at 6 and 12 days of semen storage. Luminescence was measured at 20 degrees C using a luminometer equipped with a cooled photomultiplier with a spectral response range from 370 to 620 nm. Emission was induced by adding FeSO4 solution (final concentration 0.05 mM). MDA content was measured by the HPLC method. The day of storage had a significant effect on some luminescence parameters and MDA content in spermatozoa. A significant correlation was observed between luminescence parameters and MDA concentration. The results of the study confirm that induced luminescence is strictly related to lipid peroxidation in spermatozoa that occur during boar semen storage. Parameters of luminescence treated as a holistic response of cells to oxidative stress can be useful for monitoring spermatozoa quality during semen preservation.

The relative safety of gamma-ray, autoclave, and ethylene oxide gas sterilization of thermosetting polyurethane.

PubMed

Shintani, H

1995-01-01

Sterilization of polyurethane (PU) produces 4,4'-methylenedianiline (MDA), a known carcinogen, and various other compounds. The relationships of the components of PU to the formation of these compounds by sterilization were studied. Specimens of PU fabricated from different combinations of isocyanates and polyols were obtained from dialyzers. The molecular weight of the particular polyol was found to influence the production of MDA by sterilization. Sterilization also produced many unidentified compounds. MDA production was not always associated with the production of the other compounds. Compared with gamma-ray irradiation and ethylene oxide gas (EOG) sterilization, autoclave sterilization eluted more hydrophilic compounds. This phenomenon was significant for PUs produced from smaller-molecular-weight polyols. The combination of autoclave sterilization and a PU produced from a larger-molecular-weight polyol is recommended to minimize the production of potentially toxic compounds. Of the techniques studied, EOG sterilization produced the least amounts of MDA and the other compounds, but the residue of EOG is itself problematic. The risk posed by the amounts of MDA extracted was not significant, but the biological safety of the other compounds remains to be determined.

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

Sanchez, R.O.; Archer, W.E.

This paper describes the use of Formula 456, an aliphatic amine cured epoxy for impregnating coils and high voltage transformers. Sandia has evaluated a number of MDA-free epoxy encapsulants which relied on either anhydride or other aromatic amine curing agents. The use of aliphatic amine curing agents was more recently evaluated and has resulted in the definition of Formula 456 resin. Methylene dianiline (MDA) has been used for more than 20 years as the curing agent for various epoxy formulations throughout the Department of Energy and much of industry. Sandia National Laboratories began the process of replacing MDA with othermore » formulations because of regulations imposed by OSHA on the use of MDA. OSHA has regulated MDA because it is a suspect carcinogen. Typically the elimination of OSHA-regulated materials provides a rare opportunity to qualify new formulations in a range of demanding applications. It was important to take full advantage of that opportunity, although the associated materials qualification effort was costly. Small high voltage transformers are one of those demanding applications. The successful implementation of the new formulation for high reliability transformers will be described. The test results that demonstrate the parts are qualified for use in DOE weapon systems will be presented.« less

Phenylpropanoids isolated from Piper sarmentosum Roxb. induce apoptosis in breast cancer cells through reactive oxygen species and mitochondrial-dependent pathways.

PubMed

Hematpoor, Arshia; Paydar, Mohammadjavad; Liew, Sook Yee; Sivasothy, Yasodha; Mohebali, Nooshin; Looi, Chung Yeng; Wong, Won Fen; Azirun, Mohd Sofian; Awang, Khalijah

2018-01-05

The aim of the present study is to isolate bioactive compounds from the roots of Piper sarmentosum and examine the mechanism of action using human breast cancer cell line (MDA-MB-231). Bioassay guided-fractionation of methanolic extract led to the isolation of asaricin (1) and isoasarone (2). Asaricin (1) and isoasarone (2) had significant cytotoxicity towards MDA-MB-231. MCF-10A (human normal breast epithelial cells) cells are less sensitive than MDA-MB-231, but they respond to the treatment with the same unit of measurement. Both compounds increase reactive oxygen species (ROS), decrease mitochondrial membrane potential (MMP) and enhance cytochrome c release in treated MDA-MB-231 cells. Isoasarone (2) markedly elevated caspase -8 and -3/7 activities and caused a decline in nuclear NF-κB translocation, suggesting extrinsic, death receptor-linked apoptosis pathway. Quantitative PCR results of MDA-MB-231 treated with asaricin (1) and isoasarone (2) showed altered expression of Bcl-2: Bax level. The inhibitory potency of these isolates may support the therapeutic uses of these compounds in breast cancer. Copyright © 2017 Elsevier B.V. All rights reserved.

Decreased paraoxonase1 activity and increased malondialdehyde and oxidative DNA damage levels in primary open angle glaucoma

PubMed Central

Mumcu, Ugur Yilmaz; Kocer, Ibrahim; Ates, Orhan; Alp, H. Hakan

2016-01-01

To investigate the malondialdehyde (MDA) levels, paraoxonase1 (PON1) activity and 8-hydroxy 2-deoxyguanosine (8-OHdG) levels in the primary open angle glaucoma (POAG) patient. Blood samples from 52 healthy individuals and 53 patients with POAG were analyzed for MDA and 8-OHdG by HPLC (high-performance liquid chromatography) and PON1 by spectrophotometry. The data obtained were analyzed statistically. MDA levels were 10.46±8.4 and 4.70±1.79 µmol; PON1 levels were 121±39.55 and 161.62±60.22 U/mL; and 8-OHdG values were 1.32±0.53/106 dG and 0.47±0.27/106 dG in the POAG patients and the control group, respectively. The difference was significant in MDA levels, 8-OHdG levels and PON1 activity in POAG patients in comparison with controls (P<0.001). We concluded that the observed increase in MDA and 8-OHdG levels may be correlated with decreased PON1 activity. Oxidative stress plays an important role in glaucoma development. PMID:27803873

Investigations on the human hepatic cytochrome P450 isozymes involved in the metabolism of 3,4-methylenedioxy-amphetamine (MDA) and benzodioxolyl-butanamine (BDB) enantiomers.

PubMed

Meyer, Markus R; Peters, Frank T; Maurer, Hans H

2009-10-08

3,4-Methylenedioxy-amphetamine (MDA) and benzodioxolyl-butanamine (BDB) are chiral designer drugs distributed on the illicit drug market and they are also N-dealkyl metabolites of 3,4-methylenedioxymethamphetamine (MDMA, Ecstasy, Adam), 3,4-methylenedioxyethylamphetamine (MDEA, Eve), and N-methyl-benzodioxolyl-butanamine (MBDB, Eden), respectively. MDA and BDB are mainly metabolized via demethylenation to the corresponding catecholamines. The aim of the present work was to elucidate the contribution of the relevant human P450s in the demethylenation of the MDA and BDB enantiomers. They were incubated using heterologously expressed human P450s and the corresponding metabolites dihydroxyamphetamine and 1,2-dihydroxy-4-[2-amino-butyl]benzene were determined. Highest contributions to the demethylenation as calculated from the enzyme kinetic data were obtained for CYP2D6 (MDA and BDB) and additionally CYP3A4 in the case of BDB at substrate concentrations corresponding to plasma concentrations of recreational users. A preferred transformation of the S-enantiomer could be observed for the CYP2D6- and CYP3A4-catalyzed reactions.

Oxidative stress markers in patients with primary open-angle glaucoma.

PubMed

Ghanem, Asaad A; Arafa, Lamiaa F; El-Baz, Ayman

2010-04-01

To investigate the levels of antioxidant enzymes catalase (CAT), glutathione peroxidase (GPO), superoxide dismutase (SOD), and malondialdehyde (MDA) in human eyes with primary open-angle glaucoma (POAG) and to correlate their concentrations with severity of glaucoma. A prospective cases control study. Thirty patients with primary open-angle glaucoma and twenty-five patients with senile cataracts of matched age and gender were included in the study prospectively. Aqueous humor samples were obtained by paracentesis at the time of elective surgery for glaucomatous and cataractous patients. Aqueous humor were analyzed for CAT, GPO, SOD, and MDA status. GPO, SOD, and MDA enzyme levels revealed a high significant increase in aqueous humor of POAG patients with respect to the comparative group of cataract patients (P < 0.001). No significant difference in the activity of CAT enzyme in aqueous humor of POAG and cataract patient (P = 0.201). Significant correlation was found between the MDA enzyme level and severe visual field loss (P < 0.001) in POAG patients. Increased levels of aqueous humor GPO, SOD, and MDA may be associated with POAG. In addition, they may be useful antioxidant enzyme levels in aqueous humor of POAG patients as a result of glaucoma disease and not a cause.

Hotspot Selective Preference of the Chimeric Sequences Formed in Multiple Displacement Amplification.

PubMed

Tu, Jing; Lu, Na; Duan, Mengqin; Huang, Mengting; Chen, Liang; Li, Junji; Guo, Jing; Lu, Zuhong

2017-02-24

Multiple displacement amplification (MDA) is considered to be a conventional approach to comprehensive amplification from low input DNA. The chimeric reads generated in MDA lead to severe disruption in some studies, including those focusing on heterogeneity, structural variation, and genetic recombination. Meanwhile, the generation of by-products gives a new approach to gain insights into the reaction process of φ29 polymerase. Here, we analyzed 36.7 million chimeras and screened 196 billion chimeric hotspots in the human genome, as well as evaluating the hotspot selective preference of chimeras. No significant preference was captured in the distributions of chimeras and hotspots among chromosomes. Hotspots with overlaps for 12-13 nucleotides (nt) were most likely to be selected as templates in chimera generation. Meanwhile, a regularly selective preference was noticed in overlap GC content. The preferences in overlap length and GC content was shown to be pertinent to the sequence denaturation temperature, which pointed out the optimization direction for reducing chimeras. Distance preference between two segments of chimeras was 80-280 nt. The analysis is beneficial for reducing the chimeras in MDA, and the characterization of MDA chimeras is helpful in distinguishing MDA chimeras from chimeric sequences caused by disease.

Hotspot Selective Preference of the Chimeric Sequences Formed in Multiple Displacement Amplification

PubMed Central

Tu, Jing; Lu, Na; Duan, Mengqin; Huang, Mengting; Chen, Liang; Li, Junji; Guo, Jing; Lu, Zuhong

2017-01-01

Multiple displacement amplification (MDA) is considered to be a conventional approach to comprehensive amplification from low input DNA. The chimeric reads generated in MDA lead to severe disruption in some studies, including those focusing on heterogeneity, structural variation, and genetic recombination. Meanwhile, the generation of by-products gives a new approach to gain insights into the reaction process of φ29 polymerase. Here, we analyzed 36.7 million chimeras and screened 196 billion chimeric hotspots in the human genome, as well as evaluating the hotspot selective preference of chimeras. No significant preference was captured in the distributions of chimeras and hotspots among chromosomes. Hotspots with overlaps for 12–13 nucleotides (nt) were most likely to be selected as templates in chimera generation. Meanwhile, a regularly selective preference was noticed in overlap GC content. The preferences in overlap length and GC content was shown to be pertinent to the sequence denaturation temperature, which pointed out the optimization direction for reducing chimeras. Distance preference between two segments of chimeras was 80–280 nt. The analysis is beneficial for reducing the chimeras in MDA, and the characterization of MDA chimeras is helpful in distinguishing MDA chimeras from chimeric sequences caused by disease. PMID:28245591

Mass drug administration and the global control of schistosomiasis: successes, limitations and clinical outcomes.

PubMed

Olveda, David U; McManus, Donald P; Ross, Allen G P

2016-12-01

Preventive chemotherapy is advocated for the global control and elimination of schistosomiasis. Despite the well known short-term benefits of treating patients for schistosomiasis, the impact of mass drug administration (MDA) campaigns to control the disease in the long term remains unresolved. Many studies have advocated the success of MDA programs in order to attract donor funds for elimination efforts but such successes are often short-lived given the drug does not alter the life cycle of the organism or prevent reinfection. Within a matter of months to years after halting treatment, the prevalence, intensity of infection and morbidity of disease return to baseline levels. Other mitigating factors contribute to the failings of MDA campaigns namely: poverty, poor drug coverage, poor drug compliance, and, in the case of Asiatic schistosomiasis, zoonotic transmission. Genetic and innate and acquired immunologic mechanisms complicate the epidemiologic picture of schistosomiasis globally, and may contribute indirectly to MDA shortcomings. The possibility of drug resistance is an ever present concern because of the sole reliance on one drug, praziquantel. Preventive chemotherapy is advocated for the global control and elimination of schistosomiasis. The short-term benefits of MDA campaigns are well documented but the long-term benefits are questionable.

Small real time detection satellites for MDA using hyperspectral imaging

NASA Astrophysics Data System (ADS)

Nakaya, Daiki; Yanagida, Hiroki; Shin, Satori; Ito, Tomonori; Takeuchi, Yusuke

2017-10-01

Hyperspectral Images are now used in the field of agriculture, cosmetics, and space exploring. Behind this fact, there is a result of efforts to contrive miniaturization and decrease in costs. This paper describes low-cost and small Hyperspectral Camera (HSC) under development and a method of utilizing it. Real Time Detection System for MDA is that government agencies put those cameras in small satellites and use them for MDA (Maritime Domain Awareness). We assume early detection of unidentified floating objects to find out disguised fishing ships and submarines.

[Studies on primary aromatic amines (PAAs) migration from multi-layer plastic food packaging by HPLC method].

PubMed

Cwiek-Ludwicka, Kazimiera; Pawlicka, Marzena; Starski, Andrzej; Półtorak, Hanna; Karłowski, Kazimierz

2011-01-01

The aim of this study was to identify of primary aromatic amines (PAAs) and to determine their migration from plastic food packaging. The magnitude of the migration of these substances from plastic food packaging consists a base for the evaluation of their compliance with the requirements of EU legislation and hazard for human health taking into account their migration into food. The unprinted and printed multi-layer plastic packaging (laminates), domestic and imported, were examined in these studies. PAAs migration tests from the laminates into food simulant (3% acetic acid) was performed according to the appropriate procedures recommended in the EU for testing migration from food contact articles under standard conditions reflecting the real use of laminates (10 days, 40 degrees C) and under ,, worst case scenario" conditions (2 h, 70 degrees C). PAAs present in migration solutions were concentrated on SPE columns and then seven PAAs (aniline, 1,3-phenylenediamine, 2, 6-toluenediamine, 2,4-toluenediamine, 4,4'-oxydianiline, 4,4'-methylenedianiline and 3,3 '-dimethylbenzidyne) were identified and determined by previously validated HPLC-DAD method. Depending on the migration conditions the PAAs content was different. When the "worst case scenario" conditions were applied the migration of 4,4 '-methylenedianiline (4,4 '-MDA) ranged from below detection limit (LOD = 0.51 microg/kg) up to 9.86 microg/kg, and aniline was released in the range from below detection limit (LOD = 0,98 microg/kg) up to 7.04 microg/kg. In two laminate samples of eight examined, the sum of PAAs (aniline and 4,4'-MDA) was 13.32 microg/kg and 14.72 microg/kg showing that the permitted limit (10 microg/kg) was exceeded. In the standard conditions, the migration of aniline and 4,4'-MDA was significantly lower Regarding the carcinogenic potential of PAAs, the laminates causing the amines migration above the permitted limit should not be used as food packaging.

Aircraft Flight Modeling During the Optimization of Gas Turbine Engine Working Process

NASA Astrophysics Data System (ADS)

Tkachenko, A. Yu; Kuz'michev, V. S.; Krupenich, I. N.

2018-01-01

The article describes a method for simulating the flight of the aircraft along a predetermined path, establishing a functional connection between the parameters of the working process of gas turbine engine and the efficiency criteria of the aircraft. This connection is necessary for solving the optimization tasks of the conceptual design stage of the engine according to the systems approach. Engine thrust level, in turn, influences the operation of aircraft, thus making accurate simulation of the aircraft behavior during flight necessary for obtaining the correct solution. The described mathematical model of aircraft flight provides the functional connection between the airframe characteristics, working process of gas turbine engines (propulsion system), ambient and flight conditions and flight profile features. This model provides accurate results of flight simulation and the resulting aircraft efficiency criteria, required for optimization of working process and control function of a gas turbine engine.

The Flight of the Phoenix: Interpersonal Aspects of Project Management

ERIC Educational Resources Information Center

Huffman, Brian J.; Kilian, Claire McCarty

2012-01-01

Although many classroom exercises use movies to focus on management and organizational behavior issues, none of those do so in the context of project management. This article presents such an exercise using "The Flight of the Phoenix", an incredibly rich story for any management class, which provides clear examples of organizational behavior…

NASA Report to Educators, Volume 3, Number 2, June 1975.

ERIC Educational Resources Information Center

National Aeronautics and Space Administration, Washington, DC.

In this document, a historical development of the space exploration activities of the United States and of the Soviet Union is provided. In particular, communications leading to the cooperative space agreement developed in 1972 are described. The article describes in detail the flight plan for the Apollo-Soyuz space flight. (CP)

The Size of Earth from Seven Miles Up

NASA Astrophysics Data System (ADS)

Mottmann, J.

2013-12-01

While on a vacation flight from Hawaii to California, I observed sunset occurring on clouds far below. The view triggered a vague memory about a fun article published more than three decades earlier on the topic of "Doubling Your Sunsets." Simple observations from my flight made it possible to compute the Earth's radius.

Skylab

NASA Image and Video Library

1971-01-01

This 1971 photograph was taken during the assembly of the Flight Article of the Skylab Airlock Module (AM). The Am, fabricated by McDornell Douglas under the direction of the Marshall Flight Center, allowed Skylab crew members an exit to perform extravehicular activities. The Module also contained many of the supplies and control panels for electrical power distribution and internal environment.

The Wright Stuff: Examining the Centennial of Flight

ERIC Educational Resources Information Center

Groce, Robin D.; Groce, Eric C.; Stooksberry, Lisa M.

2004-01-01

Several new books detailing various aspects of the lives and accomplishments of Wilbur and Orville Wright were written to mark the centennial of their famous 1902 entry into manned flight. This article describes eight books that are appropriate for early- to intermediate-level readers: (1) "Touching the Sky. The Flying Adventures of Wilbur and…

Biological monitoring of workers exposed to 4,4'-methylenediphenyl diisocyanate (MDI) in 19 French polyurethane industries.

PubMed

Robert, A; Ducos, P; Francin, J M; Marsan, P

2007-04-01

To study the range of urinary levels of 4,4'-methylenedianiline (MDA), a metabolite of methylenediphenyl diisocyanate (MDI), across factories in the polyurethane industries and to evaluate the validity of this biomarker to assess MDI occupational exposure. Workers exposed to MDI, as well as non-occupationally exposed subjects, were studied and pre- and post-shift urine samples were collected from 169 workers of 19 French factories and 120 controls. Details on work activities and practices were collected by a questionnaire and workers were classified into three job categories. The identification and quantification of the total urinary MDA were performed by high-performance liquid chromatography with electrochemical detection (HPLC/EC). For all the factories, MDA was detectable in 73% of the post-shift urine samples. These post-shift values, in the range of <0.10 (detection limit)-23.60 microg/l, were significantly higher than those of the pre-shift samples. Urinary MDA levels in the control group were in the range of < 0.10-0.80 microg/l. The degree of automation of the mixing operation (polyols and MDI) appears as a determinant in the extent of exposure levels. The highest amounts of MDA in urine were found in the spraying or hot processes. The excretion levels of the workers directly exposed to the hardener containing the MDI monomer were significantly higher than those of the other workers. In addition, skin exposure to MDI monomer or to polyurethane resin during the curing step were always associated with significant MDA levels in urine. Total MDA in post-shift urine samples is a reliable biomarker to assess occupational exposure to MDI in various industrial applications and to help factories to improve their manufacturing processes and working practices. A biological guiding value not exceeding 7 microg/l (5 microg/g creatinine) could be proposed in France.

Blueberry Phytochemicals Inhibit Growth and Metastatic Potential of MDA-MB-231 Breast Cancer Cells Through Modulation of the Phosphatidylinositol 3-Kinase Pathway

PubMed Central

Adams, Lynn S.; Phung, Sheryl; Yee, Natalie; Seeram, Navindra P.; Li, Liya; Chen, Shiuan

2010-01-01

Dietary phytochemicals are known to exhibit a variety of anti-carcinogenic properties. This study investigated the chemopreventive activity of blueberry extract in triple negative breast cancer cell lines in vitro and in vivo. Blueberry decreased cell proliferation in HCC38, HCC1937 and MDA-MB-231 cells with no effect on the non-tumorigenic MCF-10A cell line. Decreased metastatic potential of MDA-MB-231 cells by blueberry was shown through inhibition of cell motility using wound healing assays and migration through a PET membrane. Blueberry treatment decreased the activity of matrix metalloproteinase 9 and the secretion of urokinase-type plasminogen activator while increasing tissue inhibitor of metalloproteinase-1 and plasminogen activator inhibitor-1 secretion in MDA-MB-231 conditioned medium as shown by western blotting. Cell signaling pathways that control the expression/activation of these processes were investigated via western blotting and reporter gene assay. Treatment with blueberry decreased phosphatidylinositol 3-kinase (PI3K)/AKT and nuclear factor kappa-B (NFκB) activation in MDA-MB-231 cells where protein kinase C (PKC) and extracellular regulated kinase (ERK) were not affected. In vivo, the efficacy of blueberry to inhibit triple negative breast tumor growth was evaluated using the MDA-MB-231 xenograft model. Tumor weight and proliferation (Ki-67 expression) were decreased in blueberry treated mice, where apoptosis (caspase-3 expression) was increased compared to controls. Immunohistochemical analysis of tumors from blueberry-fed mice showed decreased activation of AKT and p65 NFκB signaling proteins with no effect on the phosphorylation of ERK. These data illustrate the inhibitory effect of blueberry phytochemicals on the growth and metastatic potential of MDA-MB-231 cells through modulation of the PI3K/AKT/NFκB pathway. PMID:20388778

The cost of antibiotic mass drug administration for trachoma control in a remote area of South Sudan.

PubMed

Kolaczinski, Jan H; Robinson, Emily; Finn, Timothy P

2011-10-01

Mass drug administration (MDA) of antibiotics is a key component of the so-called "SAFE" strategy for trachoma control, while MDA of anthelminthics provides the cornerstone for control of a number of other neglected tropical diseases (NTDs). Simultaneous delivery of two or more of these drugs, renowned as "integrated NTD control," is being promoted to reduce costs and expand intervention coverage. A cost analysis was conducted alongside an MDA campaign in a remote trachoma endemic area, to inform budgeting for NTD control in South Sudan. A first round of antibiotic MDA was conducted in the highly trachoma endemic county of Mayom, Unity state, from June to August 2010. A core team of seven staff delivered the intervention, including recruitment and training of 44 supervisors and 542 community drug distributors. Using an ingredients approach, financial and economic costs were captured from the provider perspective in a detailed costing database. Overall, 123,760 individuals were treated for trachoma, resulting in an estimated treatment coverage of 94%. The economic cost per person treated was USD 1.53, excluding the cost of the antibiotic azithromycin. Ninety four per cent of the delivery costs were recurrent costs, with personnel and travel/transport costs taking up the largest share. In a remote setting and for the initial round, MDA of antibiotics was considerably more expensive than USD 0.5 per person treated, an estimate frequently quoted to advocate for integrated NTD control. Drug delivery costs in South Sudan are unlikely to decrease substantially during subsequent MDA rounds, as the major cost drivers were recurrent costs. MDA campaigns for delivery of one or more drugs in South Sudan should thus be budgeted at around USD 1.5 per person treated, at least until further costing data for delivery of other NTD drugs, singly or in combination, are available.

3,4-Methylenedioxyamphetamine (MDA) analogues exhibit differential effects on synaptosomal release of 3H-dopamine and 3H-5-hydroxytryptamine

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

McKenna, D.J.; Guan, X.M.; Shulgin, A.T.

1991-03-01

The effect of various analogues of the neurotoxic amphetamine derivative, MDA (3,4-methylenedioxyamphetamine) on carrier-mediated, calcium-independent release of 3H-5-HT and 3H-DA from rat brain synaptosomes was investigated. Both enantiomers of the neurotoxic analogues MDA and MDMA (3,4-methylenedioxymethamphetamine) induce synaptosomal release of 3H-5-HT and 3H-DA in vitro. The release of 3H-5-HT induced by MDMA is partially blocked by 10(-6) M fluoxetine. The (+) enantiomers of both MDA and MDMA are more potent than the (-) enantiomers as releasers of both 3H-5-HT and 3H-DA. Eleven analogues, differing from MDA with respect to the nature and number of ring and/or side chain substituents, alsomore » show some activity in the release experiments, and are more potent as releasers of 3H-5-HT than of 3H-DA. The amphetamine derivatives {plus minus}fenfluramine, {plus minus}norfenfluramine, {plus minus}MDE, {plus minus}PCA, and d-methamphetamine are all potent releasers of 3H-5-HT and show varying degrees of activity as 3H-DA releasers. The hallucinogen DOM does not cause significant release of either 3H-monoamine. Possible long-term serotonergic neurotoxicity was assessed by quantifying the density of 5-HT uptake sites in rats treated with multiple doses of selected analogues using 3H-paroxetine to label 5-HT uptake sites. In the neurotoxicity study of the compounds investigated, only (+)MDA caused a significant loss of 5-HT uptake sites in comparison to saline-treated controls. These results are discussed in terms of the apparent structure-activity properties affecting 3H-monoamine release and their possible relevance to neurotoxicity in this series of MDA congeners.« less

Salivary thiobarbituric acid reacting substances and malondialdehyde--their relationship to reported smoking and to parodontal status described by the papillary bleeding index.

PubMed

Celec, Peter; Hodosy, Július; Celecová, Viera; Vodrázka, Ján; Cervenka, Tomás; Halcák, Lukác; Bozek, Peter; Kopáni, Martin; Kúdela, Matús

2005-01-01

Thiobarbituric reacting substances (TBARS) are markers of lipoperoxidation. The best-known specific TBARS is malondialdehyde (MDA). Results from our previous studies have shown that TBARS can be measured in saliva and are increased in patients with gingivitis. Whether MDA is the main TBARS in saliva from patients with altered parodontal status is unknown. Aim. To observe the relationship between the parodontal status and TBARS, MDA and the number of epithelial cells in saliva. In Study I saliva and plasma samples of 15 patients (8F, 7M) suffering from inflammatory periodontal diseases were gathered and TBARS levels were measured in these samples. In Study II saliva samples from 217 consecutive stomatologic patients were collected and analysed for TBARS spectrofluorometrically, MDA by high-performance liquid chromatography and epithelial cell count by light microscopy. Papillary bleeding index (PBI) was determined in standard stomatologic examination. In Study I results from our previous studies showing no correlation between salivary and plasma TBARS levels were confirmed. This indicates that the local salivary level of TBARS is unlikely to be directly affected by systemic oxidative stress. In Study II higher PBI was associated independently (adjusted for age and sex) tightly with higher TBARS (p<0.001) and with lower number of epithelial cells in saliva (p<0.05). Smokers had higher salivary MDA levels (p<0.003) and lower number of epithelial cells in saliva (p<0.01). Salivary TBARS are a simple parameter that partially reflects the parodontal status with a potential usefulness in the clinical stomatology. We show herein that salivary MDA is dependent on age and smoking, but there is no correlation between MDA and PBI. Further studies should uncover the main salivary TBARS compound in patients with altered parodontal status and trace the origin of these salivary lipoperoxidation markers.

Modeling the Economic and Epidemiologic Impact of Hookworm Vaccine and Mass Drug Administration (MDA) in Brazil, a High Transmission Setting

PubMed Central

Bartsch, Sarah M.; Hotez, Peter J.; Hertenstein, Daniel L.; Diemert, David J.; Zapf, Kristina M.; Bottazzi, Maria Elena; Bethony, Jeffrey M.; Brown, Shawn T.; Lee, Bruce Y.

2017-01-01

Background Although mass drug administration (MDA) has helped reduce morbidity attributed to soil-transmitted helminth infections in children, its limitations for hookworm infection have motivated the development of a human hookworm vaccine to both improve morbidity control and ultimately help block hookworm transmission leading to elimination. However, the potential economic and epidemiologic impact of a preventive vaccine has not been fully evaluated. Methods We developed a dynamic compartment model coupled to a clinical and economics outcomes model representing both the human and hookworm populations in a high transmission region of Brazil. Experiments simulated different implementation scenarios of MDA and vaccination under varying circumstances. Results Considering only intervention costs, both annual MDA and vaccination were highly cost-effective (ICERs ≤$790/DALY averted) compared to no intervention, with vaccination resulting in lower incremental cost-effectiveness ratios (ICERs ≤$444/DALY averted). From the societal perspective, vaccination was economically dominant (i.e., less costly and more effective) than annual MDA in all tested scenarios, except when vaccination was less efficacious (20% efficacy, 5 year duration) and MDA coverage was 75%. Increasing the vaccine's duration of protection and efficacy, and including a booster injection in adulthood all increased the benefits of vaccination (i.e., resulted in lower hookworm prevalence, averted more disability-adjusted life years, and saved more costs). Assuming its target product profile, a pediatric hookworm vaccine drastically decreased hookworm prevalence in children to 14.6% after 20 years, compared to 57.2% with no intervention and 54.1% with MDA. The addition of a booster in adulthood further reduced the overall prevalence from 68.0% to 36.0%, nearly eliminated hookworm infection in children. Conclusion Using a human hookworm vaccine would be cost-effective and in many cases economically dominant, providing both health benefits and cost-savings. It could become a key technology in effecting control and elimination efforts for hookworm globally. PMID:27002501

Sprague-Dawley rats display metabolism-mediated sex differences in the acute toxicity of 3,4-methylenedioxymethamphetamine (MDMA, ecstasy)

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

Fonsart, Julien; Menet, Marie-Claude; Decleves, Xavier

The use of the amphetamine derivative 3,4-methylenedioxymethamphetamine (MDMA, ecstasy) has been associated with unexplained deaths. Male humans and rodents are more sensitive to acute toxicity than are females, including a potentially lethal hyperthermia. MDMA is highly metabolized to five main metabolites, by the enzymes CYP1A2 and CYP2D. The major metabolite in rats, 3,4-methylenedioxyamphetamine (MDA), also causes hyperthermia. We postulated that the reported sex difference in rats is due to a sexual dimorphism(s). We therefore determined (1) the LD50 of MDMA and MDA, (2) their hyperthermic effects, (3) the activities of liver CYP1A2 and CYP2D, (4) the liver microsomal metabolism ofmore » MDMA and MDA, (5) and the plasma concentrations of MDMA and its metabolites 3 h after giving male and female Sprague-Dawley (SD) rats MDMA (5 mg.kg{sup -1} sc). The LD50 of MDMA was 2.4-times lower in males than in females. MDMA induced greater hyperthermia (0.9 deg. C) in males. The plasma MDA concentration was 1.3-fold higher in males, as were CYP1A2 activity (twice) and N-demethylation to MDA (3.3-fold), but the plasma MDMA concentration (1.4-fold) and CYP2D activity (1.3-fold) were higher in females. These results suggest that male SD rats are more sensitive to MDMA acute toxicity than are females, probably because their CYP1A2 is more active, leading to higher N-demethylation and plasma MDA concentration. This metabolic pathway could be responsible for the lethality of MDMA, as the LD50 of MDA is the same in both sexes. These data strongly suggest that the toxicity of amphetamine-related drugs largely depends on metabolic differences.« less

Elimination of lymphatic filariasis as a public health problem from the Cook Islands.

PubMed

Ave, Charlie; Kapa, D Ramaiah; Ottesen, Eric

2018-01-01

The Cook Islands has a long history of high-endemicity lymphatic filariasis (LF) transmitted by Aedes vector mosquitoes. Though the infection prevalence had declined between 1975 and 1999 following episodic treatment activities, still infection was widespread with pockets of persistent infection. Beginning in 1999, the Cook Islands embarked on a national program, in partnership with Pacific Programme to Eliminate LF (PacELF), to eliminate LF as a public health problem. All 12 inhabited islands were identified as endemic, and six rounds of mass drug administration (MDA) with once-yearly, single-dose albendazole plus diethylcarbamazine (DEC) were implemented during 2000-2006 to interrupt transmission of LF. Surveys carried out at the baseline, mid-term, stop-MDA, and post-MDA periods assessed LF antigen (Ag) prevalence in children and adults. Historical data, health workers' observations, and hospital records were used to assess the trend and burden of chronic disease. The baseline Ag prevalence (1999) ranged from 2.0% in Manihiki to > 18.0% in Aitutaki, Mitiaro, and Pukapuka, and the national average Ag prevalence was 8.6%. MDA, carried out with a national treatment coverage over six annual rounds of MDA ranging from 63.5 to 96.7% in different years, was stopped in 2007. By then, the national Ag prevalence had declined to 0.27%. The post-MDA surveillance survey results (2013-2014) showed that Ag prevalence had fallen to 0% in 11/12 islands, and the national prevalence was only 0.03%. Chronic filarial disease had almost entirely disappeared. The Cook Islands met all the criteria required for the World Health Organization (WHO) to acknowledge elimination of LF as a public health problem, as it did officially in 2016. This success also confirms that LF, even when transmitted by Aedes mosquitoes that are recognized to be more efficient than other vector species, can be eliminated as a public health problem by six rounds of MDA.

Modeling the economic and epidemiologic impact of hookworm vaccine and mass drug administration (MDA) in Brazil, a high transmission setting.

PubMed

Bartsch, Sarah M; Hotez, Peter J; Hertenstein, Daniel L; Diemert, David J; Zapf, Kristina M; Bottazzi, Maria Elena; Bethony, Jeffrey M; Brown, Shawn T; Lee, Bruce Y

2016-04-27

Although mass drug administration (MDA) has helped reduce morbidity attributed to soil-transmitted helminth infections in children, its limitations for hookworm infection have motivated the development of a human hookworm vaccine to both improve morbidity control and ultimately help block hookworm transmission leading to elimination. However, the potential economic and epidemiologic impact of a preventive vaccine has not been fully evaluated. We developed a dynamic compartment model coupled to a clinical and economics outcomes model representing both the human and hookworm populations in a high transmission region of Brazil. Experiments simulated different implementation scenarios of MDA and vaccination under varying circumstances. Considering only intervention costs, both annual MDA and vaccination were highly cost-effective (ICERs ≤ $790/DALY averted) compared to no intervention, with vaccination resulting in lower incremental cost-effectiveness ratios (ICERs ≤ $444/DALY averted). From the societal perspective, vaccination was economically dominant (i.e., less costly and more effective) versus annual MDA in all tested scenarios, except when vaccination was less efficacious (20% efficacy, 5 year duration) and MDA coverage was 75%. Increasing the vaccine's duration of protection and efficacy, and including a booster injection in adulthood all increased the benefits of vaccination (i.e., resulted in lower hookworm prevalence, averted more disability-adjusted life years, and saved more costs). Assuming its target product profile, a pediatric hookworm vaccine drastically decreased hookworm prevalence in children to 14.6% after 20 years, compared to 57.2% with no intervention and 54.1% with MDA. The addition of a booster in adulthood further reduced the overall prevalence from 68.0% to 36.0% and nearly eliminated hookworm infection in children. Using a human hookworm vaccine would be cost-effective and in many cases economically dominant, providing both health benefits and cost-savings. It could become a key technology in effecting control and elimination efforts for hookworm globally. Copyright © 2016 Elsevier Ltd. All rights reserved.

Atorvastatin reduces malondialdehyde concentrations in patients with polycystic ovary syndrome.

PubMed

Sathyapalan, Thozhukat; Shepherd, John; Coady, Anne-Marie; Kilpatrick, Eric S; Atkin, Stephen L

2012-11-01

It has been shown that there is an increase in oxidative stress in polycystic ovary syndrome (PCOS). Statins are considered to have a pleiotropic effect other than their lipid-lowering effect. These effects may be mediated in part by reducing oxidative stress. This randomized, double-blind, placebo-controlled study was conducted to assess the effect of atorvastatin on serum malondialdehyde (MDA) concentrations as a marker of oxidative stress in patients with PCOS. Forty medication-naïve patients with PCOS were randomized to either atorvastatin 20 mg daily or placebo for 3 months. A 3-month extension study for both groups of patients was undertaken with metformin 1500 mg daily after completing initial 3 months of atorvastatin or placebo. There was a significant decrease of MDA concentrations with atorvastatin [mean (sem)] [0.29 (0.04) vs. 0.25 (0.02) μmol/liter; P < 0.01] compared with placebo [0.28 (0.02) vs. 0.29 (0.12) μmol/liter; P = 0.52]. Three months treatment with metformin resulted in further reduction of MDA levels with atorvastatin compared with baseline [0.25 (0.02) baseline vs. 0.23 (0.03) μmol/liter for atorvastatin treated; P = 0.02]. There was also a significant correlation between the reduction in MDA with a reduction in high-sensitivity C-reactive protein (r = 0.71, P < 0.01), an increase in 25-hydroxyvitamin D (25OHD; r = -0.68, P = 0.02), and a reduction in testosterone levels (r = 0.63, P = 0.01). Multiple linear regression analysis revealed Δ25OHD, ΔC-reactive protein, and Δtestosterone were independent predictors of changes in MDA after atorvastatin treatment. No correlation was observed between the reductions in serum MDA concentrations with changes in the lipid parameters. Twelve weeks of atorvastatin led to a significant reduction in oxidative stress as determined by MDA concentrations among patients with polycystic ovary syndrome that was independently predicted by changes in testosterone, 25OHD, and high-sensitivity C-reactive protein.

Space flight nutrition research: platforms and analogs

NASA Technical Reports Server (NTRS)

Smith, Scott M.; Uchakin, Peter N.; Tobin, Brian W.

2002-01-01

Conducting research during actual or simulated weightlessness is a challenging endeavor, where even the simplest activities may present significant challenges. This article reviews some of the potential obstacles associated with performing research during space flight and offers brief descriptions of current and previous space research platforms and ground-based analogs, including those for human, animal, and cell-based research. This review is intended to highlight the main issues of space flight research analogs and leave the specifics for each physiologic system for the other papers in this section.

Design, Integration, Certification and Testing of the Orion Crew Module Propulsion System

NASA Technical Reports Server (NTRS)

McKay, Heather; Coffman, Eric; May, Sarah; Freeman, Rich; Cain, George; Albright, John; Schoenberg, Rich; Delventhal, Rex

2014-01-01

The Orion Crew Module Propulsion Reaction Control System is currently complete and ready for flight as part of the Orion program's first flight test, Exploration Flight Test One (EFT-1). As part of the first article design, build, test, and integration effort, several key lessons learned have been noted and are planned for incorporation into the next build of the system. This paper provides an overview of those lessons learned and a status on the Orion propulsion system progress to date.

Assay to detect lipid peroxidation upon exposure to nanoparticles.

PubMed

Potter, Timothy M; Neun, Barry W; Stern, Stephan T

2011-01-01

This chapter describes a method for the analysis of human hepatocarcinoma cells (HEP G2) for lipid peroxidation products, such as malondialdehyde (MDA), following treatment with nanoparticle formulations. Oxidative stress has been identified as a likely mechanism of nanoparticle toxicity, and cell-based in vitro systems for evaluation of nanoparticle-induced oxidative stress are widely considered to be an important component of biocompatibility screens. The products of lipid peroxidation, lipid hydroperoxides, and aldehydes, such as MDA, can be measured via a thiobarbituric acid reactive substances (TBARS) assay. In this assay, which can be performed in cell culture or in cell lysate, MDA combines with thiobarbituric acid (TBA) to form a fluorescent adduct that can be detected at an excitation wavelength of 530 nm and an emission wavelength of 550 nm. The results are then expressed as MDA equivalents, normalized to total cellular protein (determined by Bradford assay).

Non-destructive inspections of illicit drugs in envelope using terahertz time-domain spectroscopy

NASA Astrophysics Data System (ADS)

Li, Ning; Shen, Jingling; Lu, Meihong; Jia, Yan; Sun, Jinhai; Liang, Laishun; Shi, Yanning; Xu, Xiaoyu; Zhang, Cunlin

2006-09-01

The absorption spectra of two illicit drugs, methylenedioxyamphetarnine (MDA) and methamphetamine (MA), within and without two conventional envelopes are studied using terahertz time-domain spectroscopy technique. The characteristic absorption spectra of MDA and MA are obtained in the range of 0.2 THz to 2.5 THz. MDA has an obvious absorption peak at 1.41 THz while MA has obvious absorption peaks at 1.23 THz, 1.67 THz, 1.84 THz and 2.43 THz. We find that the absorption peaks of MDA and MA within the envelopes are almost the same as those without the envelopes respectively although the two envelopes have some different absorption in THz waveband. This result indicates that the type of illicit drugs in envelopes can be determined by identifying their characteristic absorption peaks, and THz time-domain spectroscopy is one of the most powerful candidates for illicit drugs inspection.

Whole-genome multiple displacement amplification from single cells.

PubMed

Spits, Claudia; Le Caignec, Cédric; De Rycke, Martine; Van Haute, Lindsey; Van Steirteghem, André; Liebaers, Inge; Sermon, Karen

2006-01-01

Multiple displacement amplification (MDA) is a recently described method of whole-genome amplification (WGA) that has proven efficient in the amplification of small amounts of DNA, including DNA from single cells. Compared with PCR-based WGA methods, MDA generates DNA with a higher molecular weight and shows better genome coverage. This protocol was developed for preimplantation genetic diagnosis, and details a method for performing single-cell MDA using the phi29 DNA polymerase. It can also be useful for the amplification of other minute quantities of DNA, such as from forensic material or microdissected tissue. The protocol includes the collection and lysis of single cells, and all materials and steps involved in the MDA reaction. The whole procedure takes 3 h and generates 1-2 microg of DNA from a single cell, which is suitable for multiple downstream applications, such as sequencing, short tandem repeat analysis or array comparative genomic hybridization.

Duration of detection of anti-BmR1 IgG4 antibodies after mass-drug administration (MDA) in Sarawak, Malaysia.

PubMed

Noordin, R; Muhi, J; Md Idris, Z; Arifin, N; Kiyu, A

2012-03-01

The detection rates of brugian filariasis in three regions of Sarawak namely Central, North and South after three courses of mass drug administration (MDA) from year 2004 to 2006 was investigated. A recombinant BmR1 antigen-based IgG4 detection test, named Brugia Rapid and night blood smear for microfilaria (mf) detection were used. All three regions recorded a sharp fall in mf positive rates after a year post-MDA. Meanwhile Brugia Rapid positive rates declined more gradually to 3.8% and 5.6% of the pre-MDA levels in the Central and North regions, respectively. This study showed that in filariasis endemic areas in Sarawak, anti-filarial IgG4 antibodies to BmR1, as detected by the Brugia Rapid test, were positive for one to two years after mf disappearance.

International Space Station (ISS)

NASA Image and Video Library

1997-06-01

This Boeing photograph shows the Node 1, Unity module, Flight Article (at right) and the U.S. Laboratory module, Destiny, Flight Article for the International Space Station (ISS) being manufactured in the High Bay Clean Room of the Space Station Manufacturing Facility at the Marshall Space Flight Center. The Node 1, or Unity, serves as a cornecting passageway to Space Station modules. The U.S. built Unity module was launched aboard the orbiter Endeavour (STS-88 mission) on December 4, 1998 and connected to the Zarya, the Russian-built Functional Energy Block (FGB). The U.S. Laboratory (Destiny) module is the centerpiece of the ISS, where science experiments will be performed in the near-zero gravity of space. The U.S. Laboratory/Destiny was launched aboard the orbiter Atlantis (STS-98 mission) on February 7, 2001. The ISS is a multidisciplinary laboratory, technology test bed, and observatory that will provide unprecedented undertakings in scientific, technological, and international experimentation.

Robust high-performance nanoliter-volume single-cell multiple displacement amplification on planar substrates.

PubMed

Leung, Kaston; Klaus, Anders; Lin, Bill K; Laks, Emma; Biele, Justina; Lai, Daniel; Bashashati, Ali; Huang, Yi-Fei; Aniba, Radhouane; Moksa, Michelle; Steif, Adi; Mes-Masson, Anne-Marie; Hirst, Martin; Shah, Sohrab P; Aparicio, Samuel; Hansen, Carl L

2016-07-26

The genomes of large numbers of single cells must be sequenced to further understanding of the biological significance of genomic heterogeneity in complex systems. Whole genome amplification (WGA) of single cells is generally the first step in such studies, but is prone to nonuniformity that can compromise genomic measurement accuracy. Despite recent advances, robust performance in high-throughput single-cell WGA remains elusive. Here, we introduce droplet multiple displacement amplification (MDA), a method that uses commercially available liquid dispensing to perform high-throughput single-cell MDA in nanoliter volumes. The performance of droplet MDA is characterized using a large dataset of 129 normal diploid cells, and is shown to exceed previously reported single-cell WGA methods in amplification uniformity, genome coverage, and/or robustness. We achieve up to 80% coverage of a single-cell genome at 5× sequencing depth, and demonstrate excellent single-nucleotide variant (SNV) detection using targeted sequencing of droplet MDA product to achieve a median allelic dropout of 15%, and using whole genome sequencing to achieve false and true positive rates of 9.66 × 10(-6) and 68.8%, respectively, in a G1-phase cell. We further show that droplet MDA allows for the detection of copy number variants (CNVs) as small as 30 kb in single cells of an ovarian cancer cell line and as small as 9 Mb in two high-grade serous ovarian cancer samples using only 0.02× depth. Droplet MDA provides an accessible and scalable method for performing robust and accurate CNV and SNV measurements on large numbers of single cells.

Effects of Agaricus blazei Murill Polysaccharide on Cadmium Poisoning on the MDA5 Signaling Pathway and Antioxidant Function of Chicken Peripheral Blood Lymphocytes.

PubMed

Lv, Ai; Ge, Ming; Hu, Xuequan; Liu, Wenjing; Li, Guangxing; Zhang, Ruili

2018-01-01

This experimental study investigated the effect of Agaricus blazei Murill polysaccharide (ABP) on cadmium (Cd) poisoning on the melanoma differentiation-associated gene 5 (MDA5) signaling pathway and antioxidant function of peripheral blood lymphocytes (PBLs) in chickens. The experiments were divided into four groups: 7-day-old chickens with normal saline (0.2 mL single/day), Cd (140 mg/kg), ABP (30 mg/mL, 0.2 mL single/day), and Cd + ABP(140 mg/kg/day + 0.2 mL ABP). Peripheral blood was collected on the 20th, 40th, and 60th days for each group, and PBLs were separated. We attempted to detect the expression of MDA5, downstream signaling molecules, and convergence protein (interferon promoter-stimulating factor 1); transcription factors (IRF3 and NF-κB); the content of cytokines (IL-1β, IL-6, TNF-α, and IFN-β) in PBLs; and the antioxidant index of superoxide dismutase (SOD), malondialdhyde (MDA), and glutathione peroxidase (GSH-Px). The results showed that ABP can reduce the accumulation of Cd in the peripheral blood of chickens; reduce the expression of MDA5 and downstream signaling molecules; and reduce the content of IL-1β, IL-6, TNF-α, and IFN-β in PBLs of chickens. The activity of antioxidant enzymes (SOD and GSH-Px) significantly increased, and the content of MDA decreased. These results showed that they have a certain protective effect of ABP on Cd poisoning in chicken PBLs caused by injury.

Geospatial Distribution and Clustering of Chlamydia trachomatis in Communities Undergoing Mass Azithromycin Treatment

PubMed Central

Yohannan, Jithin; He, Bing; Wang, Jiangxia; Greene, Gregory; Schein, Yvette; Mkocha, Harran; Munoz, Beatriz; Quinn, Thomas C.; Gaydos, Charlotte; West, Sheila K.

2014-01-01

Purpose. We detected spatial clustering of households with Chlamydia trachomatis infection (CI) and active trachoma (AT) in villages undergoing mass treatment with azithromycin (MDA) over time. Methods. We obtained global positioning system (GPS) coordinates for all households in four villages in Kongwa District, Tanzania. Every 6 months for a period of 42 months, our team examined all children under 10 for AT, and tested for CI with ocular swabbing and Amplicor. Villages underwent four rounds of annual MDA. We classified households as having ≥1 child with CI (or AT) or having 0 children with CI (or AT). We calculated the difference in the K function between households with and without CI or AT to detect clustering at each time point. Results. Between 918 and 991 households were included over the 42 months of this analysis. At baseline, 306 households (32.59%) had ≥1 child with CI, which declined to 73 households (7.50%) at 42 months. We observed borderline clustering of households with CI at 12 months after one round of MDA and statistically significant clustering with growing cluster sizes between 18 and 24 months after two rounds of MDA. Clusters diminished in size at 30 months after 3 rounds of MDA. Active trachoma did not cluster at any time point. Conclusions. This study demonstrates that CI clusters after multiple rounds of MDA. Clusters of infection may increase in size if the annual antibiotic pressure is removed. The absence of growth after the three rounds suggests the start of control of transmission. PMID:24906862

Crosstalk between stromal components and tumor cells of TNBC via secreted factors enhances tumor growth and metastasis

PubMed Central

Jin, Kideok; Pandey, Niranjan B.; Popel, Aleksander S.

2017-01-01

Triple negative breast cancer (TNBC) as a metastatic disease is currently incurable. Reliable and reproducible methods for testing drugs against metastasis are not available. Stromal cells may play a critical role in tumor progression and metastasis. In this study, we determined that fibroblasts and macrophages secreted IL-8 upon induction by tumor cell-conditioned media (TCM) from MDA-MB-231 cancer cells. Our data showed that the proliferation of MDA-MB-231 cells co-cultured with fibroblasts or macrophages was enhanced compared to the monoculture. Furthermore, TNBC cell migration, a key step in tumor metastasis, was promoted by conditioned media (CM) from TCM-induced fibroblasts or macrophages. Knockdown of the IL-8 receptor CXCR2 by CRISPR-Cas9 reduces MDA-MB-231 cell proliferation and migration compared to wild type. In a mouse xenograft tumor model, the growth of MDA-MB-231-CXCR2−/− tumor was significantly decreased compared to the growth of tumors from wild-type cells. In addition, the incidence of thoracic metastasis of MDA-MB-231-CXCR2−/− tumors was reduced compared to wild type. We found that the auto- and paracrine loop exists between TNBC cells and stroma, which results in enhanced IL-8 secretion from the stromal components. Significantly, inhibition of the IL-8 signaling pathway by reparixin, an inhibitor of the IL-8 receptor, CXCR1/2, reduced MDA-MB-231 tumor growth and metastasis. Taken together, these findings implicate IL-8 signaling as a critical event in TNBC tumor growth and metastasis via crosstalk with stromal components. PMID:28947965

Selenium Nanoparticles Induce the Chemo-Sensitivity of Fluorouracil Nanoparticles in Breast and Colon Cancer Cells.

PubMed

Abd-Rabou, Ahmed A; Shalby, Aziza B; Ahmed, Hanaa H

2018-05-11

Drug resistance is a major challenge of breast and colon cancer therapies leading to treatment failure. The main objective of the current study is to investigate whether selenium nanoparticles (nano-Se) can induce the chemo-sensitivity of 5-fluorouracil (FU)-encapsulated poly (D, L-lactide-co-glycolide) nanoparticles (nano-FU) in breast and colon cancer cell lines. Nano-Se and nano-FU were synthesized and characterized, then applied individually or in combination upon MCF7, MDA-MB-231, HCT 116, and Caco-2 cancerous cell lines. Cytotoxicity, cellular glucose uptake, and apoptosis, as well as malondialdehyde (MDA), nitric oxide (NO), and zinc (Zn) levels, were investigated upon the different treatments. We have resulted that nano-FU induced cell death in MCF7 and Caco-2 more effectively than MDA-MB-231 and HCT 116 cell lines. Moreover, nano-FU plus nano-Se potentiate MCF7 and Caco-2 chemo-sensitivity were higher than MDA-MB-231 and HCT 116 cancerous cell lines. It is relevant to note that Se and FU nano-formulations inhibited cancer cell bioenergetics via glucose uptake slight blockage. Furthermore, nano-FU increased the levels of NO and MDA in media over cancer cells, while their combinations with nano-Se rebalance the redox status with Zn increment. We noticed that MCF7 cell line is sensitive, while MDA-MB-231 cell line is resistant to Se and nano-Se. This novel approach could be of great potential to enhance the chemo-sensitivity in breast and colon cancer cells.

3,4-Methylenedioxymethamphetamine and 3,4-methylenedioxyamphetamine destroy serotonin terminals in rat brain: quantification of neurodegeneration by measurement of (/sup 3/H)paroxetine-labeled serotonin uptake sites

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

Battaglia, G.; Yeh, S.Y.; O'Hearn, E.

1987-09-01

This study examines the effects of repeated systemic administration (20 mg/kg s.c., twice daily for 4 days) of 3,4-methylenedioxymethamphetamine (MDMA) and 3,4-methylenedioxyamphetamine (MDA) on levels of brain monoamines, their metabolites and on the density of monoamine uptake sites in various regions of rat brain. Marked reductions (30-60%) in the concentration of 5-hydroxyindoleacetic acid were observed in cerebral cortex, hippocampus, striatum, hypothalamus and midbrain at 2 weeks after a 4-day treatment regimen of MDMA or MDA; less consistent reductions in serotonin (5-HT) content were observed in these brain regions. In addition, both MDMA and MDA caused comparable and substantial reductions (50-75%)more » in the density of (/sup 3/H)paroxetine-labeled 5-HT uptake sites in all brain regions examined. In contrast, neither MDMA nor MDA caused any widespread or long-term changes in the content of the catecholaminergic markers (i.e., norepinephrine, dopamine, 3,4 dihydroxyphenylacetic acid and homovanillic acid) or in the number of (/sup 3/H)mazindol-labeled norepinephrine or dopamine uptake sites in the brain regions examined. These data demonstrate that MDMA and MDA cause long-lasting neurotoxic effects with respect to both the functional and structural integrity of serotonergic neurons in brain. Furthermore, our measurement of reductions in the density of 5-HT uptake sites provides a means for quantification of the neurodegenerative effects of MDMA and MDA on presynaptic 5-HT terminals.« less

The Effect of Astaxanthin and Regular Training on Dynamic Pattern of Oxidative Stress on Male under Strenuous Exercise

NASA Astrophysics Data System (ADS)

Sylviana, N.; Gunawan, H.; Lesmana, R.; Purba, A.; Akbar, I. B.

2017-03-01

Strenuous physical activity will induced higher Reactive Oxygen Species (ROS) level in human body that can be measured by serum Malondialdehyde (MDA) level. Malondialdehyde is product of lipid peroxidation process that define as oxidative damage of lipid biomolecule by reactivity of reactive oxygen species. Still, the dynamic pattern of Malondialdehyde (MDA) level under strenuous exercise is not fully understood. Potent antioxidant such as Astaxanthin and training may be altered the level of MDA. Thus, purpose of this study is to understand effect of astaxanthin to MDA dynamic pattern on training male after strenuous physical activity. It was a double blind, experimental study, conducted on thirty young male age, divided into untrained and trained groups. Supplement Astaxanthin was given to 15 subject as well as placebo for one week after supplementation, Subjects were tested with anaerobic strenuous physical activity. The values were analyzed with ANOVA test followed by Duncan test showed that in every groups, mean of MDA before test was similar, start increase significantly after tested, begin decrease at 6th hour post test and back to baseline at 24th hour post-test ( p<0.05), except for group of untrained male with placebo still increase twice from baseline. The lowest mean of MDA was found on group of trained male with Astaxanthin supplementation and the highest was found on group of untrained male with placebo (p<0.05). These findings support that Astaxanthin and training might has positive effect to oxidative stress condition without altered its dynamic pattern in male after strenuous physical activity

Hydroxyl free radical production during torsional phacoemulsification.

PubMed

Aust, Steven D; Hebdon, Thomas; Humbert, Jordan; Dimalanta, Ramon

2010-12-01

To quantitate free radical generation during phacoemulsification using an ultrasonic phacoemulsification device that includes a torsional mode and evaluate tip designs specific to the torsional mode. Chemistry and Biochemistry Department, Utah State University, Logan, Utah, USA. Experimental study. Experiments were performed using the Infiniti Vision System and OZil handpiece. Hydroxyl radical concentrations in the aspirated irrigation solution during torsional phacoemulsification were quantitated as nanomolar malondialdehyde (nM MDA) and determined spectrophotometrically using the deoxyribose assay. The mean free radical production during phacoemulsification with torsional modality at 100% amplitude was 30.1 nM MDA ± 5.1 (SD) using a 0.9 mm 45-degree Kelman tapered ABS tip. With other tip designs intended for use with the torsional modality, free radical production was further reduced when fitted with the 0.9 mm 45-degree Kelman mini-flared ABS tip (13.2 ± 5.6 nM MDA) or the 0.9 mm 45-degree OZil-12 mini-flared ABS tip (14.3 ± 6.7 nM MDA). Although the measurements resulting from the use of the latter 2 tips were not statistically significantly different (P ≈ .25), they were different from those of the tapered tip (P<.0001). The MDA concentration in the aspirated irrigation solution using the torsional modality was approximately one half that reported for the handpiece's longitudinal modality in a previous study using the same bent-tip design (Kelman tapered, P<.0001). The level of MDA was further reduced approximately one half with torsional-specific tips. Copyright © 2010 ASCRS and ESCRS. Published by Elsevier Inc. All rights reserved.

Pentameric procyanidin from Theobroma cacao selectively inhibits growth of human breast cancer cells.

PubMed

Ramljak, Danica; Romanczyk, Leo J; Metheny-Barlow, Linda J; Thompson, Nicole; Knezevic, Vladimir; Galperin, Mikhail; Ramesh, Arun; Dickson, Robert B

2005-04-01

A naturally occurring, cocoa-derived pentameric procyanidin (pentamer) was previously shown to cause G0/G1 cell cycle arrest in human breast cancer cells by an unknown molecular mechanism. Here, we show that pentamer selectively inhibits the proliferation of human breast cancer cells (MDA MB-231, MDA MB-436, MDA MB-468, SKBR-3, and MCF-7) and benzo(a)pyrene-immortalized 184A1N4 and 184B5 cells. In contrast, normal human mammary epithelial cells in primary culture and spontaneously immortalized MCF-10A cells were significantly resistant. We evaluated whether this differential response to pentamer may involve depolarization of the mitochondrial membrane. Pentamer caused significant depolarization of mitochondrial membrane in MDA MB231 cells but not the more normal MCF-10A cells, whereas other normal and tumor cell lines tested gave variable results. Further investigations, using a proteomics approach with pentamer-treated MDA MB-231, revealed a specific dephosphorylation, without changes in protein expression, of several G1-modulatory proteins: Cdc2 (at Tyr15), forkhead transcription factor (at Ser256, the Akt phosphorylation site) and p53 (Ser392). Dephosphorylation of p53 (at Ser392) by pentamer was confirmed in MDA MB-468 cells. However, both expression and phosphorylation of retinoblastoma protein were decreased after pentamer treatment. Our results show that breast cancer cells are selectively susceptible to the cytotoxic effects of pentameric procyanidin, and suggest that inhibition of cellular proliferation by this compound is associated with the site-specific dephosphorylation or down-regulation of several cell cycle regulatory proteins.

Pain and mobility improvement and MDA plasma levels in degenerative osteoarthritis, low back pain, and rheumatoid arthritis after infrared A-irradiation.

PubMed

Siems, Werner; Bresgen, Nikolaus; Brenke, Rainer; Siems, Renate; Kitzing, Manfred; Harting, Heike; Eckl, Peter M

2010-01-01

Infrared (IR)-A irradiation can be useful in back and musculoskeletal pain therapy. In this study joint and vertebral column pain and mobility were measured during two weeks of IR-A irradiation treatment of patients suffering from degenerative osteoarthritis of hip and knee, low back pain, or rheumatoid arthritis. Additionally, before and after IR-A treatment MDA serum levels were measured to check if MDA variations accompany changes in pain intensity and mobility. Two-hundred and seven patients were divided into verum groups getting IR-irradiation, placebo groups getting visible, but not IR irradiation, and groups getting no irradiation. In osteoarthritis significant pain reduction according to Visual Analogue Scale and mobility improvements occurred in the verum group. Even though beneficial mean value changes occurred in the placebo group, the improvements in the placebo and No Irradiation groups were without statistical significance. In low back pain, pain and mobility improvements (by 35-40%) in the verum group were found, too. A delayed (2nd week) mobility improvement in rheumatoid arthritis was seen. However, pain relief was seen immediately. In patients suffering from low back pain or rheumatoid arthritis, the pain and mobility improvements were accompanied by significant changes of MDA serum levels. However, MDA appears not a sensitive biofactor for changes of the pain intensity in degenerative osteoarthritis. Nevertheless, unaffected or lowered MDA levels during intensive IR-A therapy argue against previous reports on free radical formation upon infrared. In conclusion, rapid beneficial effects of IR-A towards musculoskeletal pain and joint mobility loss were demonstrated.

Circulating and myometrial markers of oxidative stress in pregnant women with fetal growth restriction.

PubMed

Biberoglu, Ebru; Biberoglu, Kutay; Kirbas, Ayse; Daglar, Korkut; Genc, Metin; Avci, Aslihan; Danisman, Nuri

2016-01-01

The objective of this study was to identify the relationship between fetal growth restriction (FGR) and oxidative stress. The mechanisms that protect against oxidative stress in the local microenvironment were investigated by comparing the activities of the markers, both in the circulation and myometrium. Myometrial tissue and serum levels of malondialdehyde (MDA), xanthine oxidase (XO), catalase (CAT) and superoxide dismutase (SOD) markers were measured in 20 FGR and 20 healthy pregnancies. The mean duration of gestation at delivery was shorter (P = 0003) and the mean birthweight was lower P < 0001) in the FGR study group compared with the control group, as expected. While MDA and CAT concentrations were higher in the serum (P < 0.02 and P < 0.01, respectively), but lower in the myometrial samples (P < 0.01) in the FGR versus the control group, XO and myometrial SOD values were comparable in both groups. Although our data demonstrated that FGR is associated with oxidative stress, the exact role and mechanism of the oxidant and antioxidant imbalance is obscure. We speculate that despite limited local synthesis of CAT, effective and efficient removal of MDA in the uterine environment explains high MDA and CAT serum concentrations in women with FGR. Alternatively, a well-functioning myometrial system could rescue the fetus from reactive oxygen species, as demonstrated by lowered MDA and depleted CAT resulting from hyperconsumption. Elevated serum MDA and CAT levels in the serum may reflect the 'spillover' of these markers from the uterus to the circulation. © 2015 Japan Society of Obstetrics and Gynecology.

Are Alternative Strategies Required to Accelerate the Global Elimination of Lymphatic Filariasis? Insights From Mathematical Models

PubMed Central

Stolk, Wilma A; Prada, Joaquin M; Smith, Morgan E; Kontoroupis, Periklis; de Vos, Anneke S; Touloupou, Panayiota; Irvine, Michael A; Brown, Paul; Subramanian, Swaminathan; Kloek, Marielle; Michael, E; Hollingsworth, T Deirdre; de Vlas, Sake J

2018-01-01

Abstract Background With the 2020 target year for elimination of lymphatic filariasis (LF) approaching, there is an urgent need to assess how long mass drug administration (MDA) programs with annual ivermectin + albendazole (IA) or diethylcarbamazine + albendazole (DA) would still have to be continued, and how elimination can be accelerated. We addressed this using mathematical modeling. Methods We used 3 structurally different mathematical models for LF transmission (EPIFIL, LYMFASIM, TRANSFIL) to simulate trends in microfilariae (mf) prevalence for a range of endemic settings, both for the current annual MDA strategy and alternative strategies, assessing the required duration to bring mf prevalence below the critical threshold of 1%. Results Three annual MDA rounds with IA or DA and good coverage (≥65%) are sufficient to reach the threshold in settings that are currently at mf prevalence <4%, but the required duration increases with increasing mf prevalence. Switching to biannual MDA or employing triple-drug therapy (ivermectin, diethylcarbamazine, and albendazole [IDA]) could reduce program duration by about one-third. Optimization of coverage reduces the time to elimination and is particularly important for settings with a history of poorly implemented MDA (low coverage, high systematic noncompliance). Conclusions Modeling suggests that, in several settings, current annual MDA strategies will be insufficient to achieve the 2020 LF elimination targets, and programs could consider policy adjustment to accelerate, guided by recent monitoring and evaluation data. Biannual treatment and IDA hold promise in reducing program duration, provided that coverage is good, but their efficacy remains to be confirmed by more extensive field studies. PMID:29860286

Are Alternative Strategies Required to Accelerate the Global Elimination of Lymphatic Filariasis? Insights From Mathematical Models.

PubMed

Stolk, Wilma A; Prada, Joaquin M; Smith, Morgan E; Kontoroupis, Periklis; de Vos, Anneke S; Touloupou, Panayiota; Irvine, Michael A; Brown, Paul; Subramanian, Swaminathan; Kloek, Marielle; Michael, E; Hollingsworth, T Deirdre; de Vlas, Sake J

2018-06-01

With the 2020 target year for elimination of lymphatic filariasis (LF) approaching, there is an urgent need to assess how long mass drug administration (MDA) programs with annual ivermectin + albendazole (IA) or diethylcarbamazine + albendazole (DA) would still have to be continued, and how elimination can be accelerated. We addressed this using mathematical modeling. We used 3 structurally different mathematical models for LF transmission (EPIFIL, LYMFASIM, TRANSFIL) to simulate trends in microfilariae (mf) prevalence for a range of endemic settings, both for the current annual MDA strategy and alternative strategies, assessing the required duration to bring mf prevalence below the critical threshold of 1%. Three annual MDA rounds with IA or DA and good coverage (≥65%) are sufficient to reach the threshold in settings that are currently at mf prevalence <4%, but the required duration increases with increasing mf prevalence. Switching to biannual MDA or employing triple-drug therapy (ivermectin, diethylcarbamazine, and albendazole [IDA]) could reduce program duration by about one-third. Optimization of coverage reduces the time to elimination and is particularly important for settings with a history of poorly implemented MDA (low coverage, high systematic noncompliance). Modeling suggests that, in several settings, current annual MDA strategies will be insufficient to achieve the 2020 LF elimination targets, and programs could consider policy adjustment to accelerate, guided by recent monitoring and evaluation data. Biannual treatment and IDA hold promise in reducing program duration, provided that coverage is good, but their efficacy remains to be confirmed by more extensive field studies.

Advanced space-based InSAR risk analysis of planned and existing transportation infrastructure.

DOT National Transportation Integrated Search

2017-03-21

The purpose of this document is to summarize activities by Stanford University and : MDA Geospatial Services Inc. (MDA) to estimate surface deformation and associated : risk to transportation infrastructure using SAR Interferometric methods for the :...

Mass drug administration of ivermectin in south-eastern Senegal reduces the survivorship of wild-caught, blood fed malaria vectors

PubMed Central

2010-01-01

Background In south-eastern Senegal, malaria and onchocerciasis are co-endemic. Onchocerciasis in this region has been controlled by once or twice yearly mass drug administration (MDA) with ivermectin (IVM) for over fifteen years. Since laboratory-raised Anopheles gambiae s.s. are susceptible to ivermectin at concentrations found in human blood post-ingestion of IVM, it is plausible that a similar effect could be quantified in the field, and that IVM might have benefits as a malaria control tool. Methods In 2008 and 2009, wild-caught blood fed An. gambiae s.l. mosquitoes were collected from huts of three pairs of Senegalese villages before and after IVM MDAs. Mosquitoes were held in an insectary to assess their survival rate, subsequently identified to species, and their blood meals were identified. Differences in mosquito survival were statistically analysed using a Glimmix model. Lastly, changes in the daily probability of mosquito survivorship surrounding IVM MDAs were calculated, and these data were inserted into a previously developed, mosquito age-structured model of malaria transmission. Results Anopheles gambiae s.s. (P < 0.0001) and Anopheles arabiensis (P = 0.0191) from the treated villages had significantly reduced survival compared to those from control villages. Furthermore, An gambiae s.s. caught 1-6 days after MDA in treated villages had significantly reduced survival compared to control village collections (P = 0.0003), as well as those caught pre-MDA (P < 0.0001) and >7 days post-MDA (P < 0.0001). The daily probability of mosquito survival dropped >10% for the six days following MDA. The mosquito age-structured model of malaria transmission demonstrated that a single IVM MDA would reduce malaria transmission (Ro) below baseline for at least eleven days, and that repeated IVM MDAs would result in a sustained reduction in malaria Ro. Conclusions Ivermectin MDA significantly reduced the survivorship of An. gambiae s.s. for six days past the date of the MDA, which is sufficient to temporarily reduce malaria transmission. Repeated IVM MDAs could be a novel and integrative malaria control tool in areas with seasonal transmission, and which would have simultaneous impacts on neglected tropical diseases in the same villages. PMID:21171970

Neurotoxicity profiles of substituted amphetamines in the C57BL/6J mouse.

PubMed

O'Callaghan, J P; Miller, D B

1994-08-01

Dopaminergic (DA) and serotonergic (5-HT) projections to striatum and cortex have been implicated as the primary targets of substituted amphetamine (AMP)-induced neurotoxicity, largely on the basis of the propensity of these compounds to cause protracted decrements in DA and 5-HT rather than on the basis of AMP-induced alterations of indices linked to neural damage. Moreover, most studies of AMP-induced neurotoxicity, regardless of the endpoints assessed, have been conducted using a rat model; relatively little attention has been focused on the effects of these compounds in the mouse. Here, we evaluated the potential neurotoxic effects of d-methamphetamine (d-METH), d-methylenedioxyamphetamine (d-MDA), d-methylene-dioxymethamphetamine (d-MDMA) and d-fenfluramine (d-FEN) in the C57BL6/J mouse. Astrogliosis, assessed by quantification of glial fibrillary acidic protein (GFAP), was taken as the main index of AMP-induced neural damage. A silver degeneration stain also was used to obtain direct evidence of AMP-induced neuronal damage. Assays of tyrosine hydroxylase (TH), DA and 5-HT were used to assess effects on DA and 5-HT systems. Mice received d-METH (10 mg/kg), d-MDA (20 mg/kg), d-MDMA (20 mg/kg) or d-FEN (25 mg/kg) every 2 hr for a total of four s.c. injections. d-METH, d-MDA and d-MDMA caused a large (300%) increase in striatal GFAP that resolved by 3 weeks and a 50 to 75% decrease in TH and DA that did not resolve. d-METH, d-MDA and d-MDMA also caused fiber and terminal degeneration in striatum as revealed by silver staining. d-FEN did not affect any parameters in striatum. d-METH, d-MDA and d-MDMA also increased GFAP in cortex, effects that were associated with small (10-25%) and transient decrements in cortical 5-HT. d-FEN caused prolonged (weeks) decrements (20%) in cortical 5-HT but did not affect cortical GFAP. The effects of d-METH, d-MDA and d-MDMA were stereoselective and were blocked by pretreatment with MK-801. Core temperature was slightly elevated by d-METH, d-MDA and d-MDMA but was dramatically lowered by d-FEN. The data suggest that d-METH, d-MDA and d-MDMA, but not d-FEN, produce damage to neural elements of mouse striatum and cortex.

Spatiotemporal prediction of daily ambient ozone levels across China using random forest for human exposure assessment.

PubMed

Zhan, Yu; Luo, Yuzhou; Deng, Xunfei; Grieneisen, Michael L; Zhang, Minghua; Di, Baofeng

2018-02-01

In China, ozone pollution shows an increasing trend and becomes the primary air pollutant in warm seasons. Leveraging the air quality monitoring network, a random forest model is developed to predict the daily maximum 8-h average ozone concentrations ([O 3 ] MDA8 ) across China in 2015 for human exposure assessment. This model captures the observed spatiotemporal variations of [O 3 ] MDA8 by using the data of meteorology, elevation, and recent-year emission inventories (cross-validation R 2  = 0.69 and RMSE = 26 μg/m 3 ). Compared with chemical transport models that require a plenty of variables and expensive computation, the random forest model shows comparable or higher predictive performance based on only a handful of readily-available variables at much lower computational cost. The nationwide population-weighted [O 3 ] MDA8 is predicted to be 84 ± 23 μg/m 3 annually, with the highest seasonal mean in the summer (103 ± 8 μg/m 3 ). The summer [O 3 ] MDA8 is predicted to be the highest in North China (125 ± 17 μg/m 3 ). Approximately 58% of the population lives in areas with more than 100 nonattainment days ([O 3 ] MDA8 >100 μg/m 3 ), and 12% of the population are exposed to [O 3 ] MDA8 >160 μg/m 3 (WHO Interim Target 1) for more than 30 days. As the most populous zones in China, the Beijing-Tianjin Metro, Yangtze River Delta, Pearl River Delta, and Sichuan Basin are predicted to be at 154, 141, 124, and 98 nonattainment days, respectively. Effective controls of O 3 pollution are urgently needed for the highly-populated zones, especially the Beijing-Tianjin Metro with seasonal [O 3 ] MDA8 of 140 ± 29 μg/m 3 in summer. To the best of the authors' knowledge, this study is the first statistical modeling work of ambient O 3 for China at the national level. This timely and extensively validated [O 3 ] MDA8 dataset is valuable for refining epidemiological analyses on O 3 pollution in China. Copyright © 2017 Elsevier Ltd. All rights reserved.

Methanol extract of Codium fragile inhibits tumor necrosis factor-α-induced matrix metalloproteinase-9 and invasiveness of MDA-MB-231 cells by suppressing nuclear factor-κB activation.

PubMed

Dilshara, Matharage Gayani; Jayasooriya, Rajapaksha Gedara Prasad Tharanga; Kang, Chang-Hee; Choi, Yung-Hyun; Kim, Gi-Young

2016-06-01

To evaluate whether the methanol extract of Codium fragile (MECF) regulates tumor necrosis factor-α (TNF-α)-induced invasion of human breast cancer MDA-MB-231 cells by suppressing matrix metalloproteinase-9 (MMP-9). Reverse transcription-polymerase chain reaction (RT-PCR) and western blot analysis were performed to analyze the expression of MMP-9 and nuclear factor-κB (NF-κB) subunits, p65 and p50, and IκB in MDA-MB-231 cells. 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay was used for cell viability. MMP-9 activity and invasion were measured by gelatin zymography and a matrigel invasion assay, respectively. NF-κB activity was measured by an electrophoretic mobility shift assay and luciferase activity. MECF had no effect on cell viability up to a concentration of 100 μg/mL in human breast cancer MDA-MB-231 cells regardless of the presence of TNF-α. MDA-MB-231 cells that were stimulated with TNF-α showed a marked increase of invasion compared to the untreated control, whereas pretreatment with MECF downregulated the TNF-α-induced invasion of MDA-MB-231 cells. Additionally, zymography, western blot analysis, and RT-PCR confirmed that MECF decreased TNF-α-induced MMP-9 expression and activity which is a key regulator for cancer invasion. According to an electrophoretic morbidity shift assay, pretreatment with MECF in MDA-MB-231 cells significantly decreased the TNF-α-induced DNA-binding activity of NF-κB, which is an important transcription factor for regulating cancer invasion-related genes such as MMP-9. Furthermore, treatment with MECF sustained the expression of p65 and p50 in response to TNF-α in the cytosolic compartment. The luciferase assay demonstrated that MECF attenuated TNF-α-induced NF-κB luciferase activity. MECF exhibited its anti-invasive capability by downregulating TNF-α-induced MMP-9 expression, resulting from the suppression of NF-κB activity in the human breast cancer cell line MDA-MB-231. Copyright © 2016 Hainan Medical College. Production and hosting by Elsevier B.V. All rights reserved.

Development flight tests of JetStar LFC leading-edge flight test experiment

NASA Technical Reports Server (NTRS)

Fisher, David F.; Fischer, Michael C.

1987-01-01

The overall objective of the flight tests on the JetStar aircraft was to demonstrate the effectiveness and reliability of laminar flow control under representative flight conditions. One specific objective was to obtain laminar flow on the JetStar leading-edge test articles for the design and off-design conditions. Another specific objective was to obtain operational experience on a Laminar Flow Control (LFC) leading-edge system in a simulated airline service. This included operational experience with cleaning requirements, the effect of clogging, possible foreign object damage, erosion, and the effects of ice particle and cloud encounters. Results are summarized.

Replacing the weight of materials consumed on airships

NASA Technical Reports Server (NTRS)

Crocco, G A

1923-01-01

Two methods to replace the weight of gas lost on long airship flights are discussed: condensing the water of combustion and thermic sustentation. In the present article we will discuss the first method, leaving the second to be examined in a subsequent article.

The ISS flight of Richard Garriott: a template for medicine and science investigation on future spaceflight participant missions.

PubMed

Jennings, Richard T; Garriott, Owen K; Bogomolov, Valery V; Pochuev, Vladimir I; Morgun, Valery V; Garriott, Richard A

2010-02-01

A total of eight commercial spaceflight participants have launched to the International Space Station (ISS) on Soyuz vehicles. Based on an older mean age compared to career astronauts and an increased prevalence of medical conditions, spaceflight participants have provided the opportunity to learn about the effect of space travel on crewmembers with medical problems. The 12-d Soyuz TMA-13/12 ISS flight of spaceflight participant Richard Garriott included medical factors that required preflight intervention, risk mitigation strategies, and provided the opportunity for medical study on-orbit. Equally important, Mr. Garriott conducted extensive medical, scientific, and educational payload operations during the flight. These included 7 medical experiments and a total of 15 scientific projects such as protein crystal growth, Earth observations/photography, educational projects with schools, and amateur radio. The medical studies included the effect of microgravity on immune function, sleep, bone loss, corneal refractive surgery, low back pain, motion perception, and intraocular pressure. The overall mission success resulted from non-bureaucratic agility in mission planning, cooperation with investigators from NASA, ISS, International Partners, and the Korean Aerospace Research Institute, in-flight support and leadership from a team with spaceflight and Capcom experience, and overall mission support from the ISS program. This article focuses on science opportunities that suborbital and orbital spaceflight participant flights offer and suggests that the science program on Richard Garriott's flight be considered a model for future orbital and suborbital missions. The medical challenges are presented in a companion article.

The Size of Earth from Seven Miles Up

ERIC Educational Resources Information Center

Mottmann, J.

2013-01-01

While on a vacation flight from Hawaii to California, I observed sunset occurring on clouds far below. The view triggered a vague memory about a fun article 1 published more than three decades earlier on the topic of "Doubling Your Sunsets." Simple observations from my flight made it possible to compute the Earth's radius.

Flight data file: STS-4 crew activity plan

NASA Technical Reports Server (NTRS)

Pippert, E. B., Jr.

1982-01-01

The STS-4 Crew Activity Plan contains the on-orbit timeline, which is a flight data file article. Various time scales such as Mission Elapsed Time (MET), Greenwich Mean Time (GMT), and time until deorbit ignition as well as crew activities, day/night, orbit position, ground tracking, communication coverage, attitude, and maneuvers are presented in chart form.

Erratum: Correction to: The sTOF, a Favorable Geometry for a Time-of-Flight Analyzer

NASA Astrophysics Data System (ADS)

Murphy, Daniel M.

2018-05-01

In the article "The sTOF, a Favorable Geometry for a Time-of-Flight Analyzer", the electric sectors in the prototype analyzer used to generate the data in Figure 4 were mistakenly listed as having a radius of 165 mm. The correct size is a diameter of 165 mm.

The Physics of Flight: I. Fixed and Rotating Wings

ERIC Educational Resources Information Center

Linton, J. Oliver

2007-01-01

Almost all elementary textbook explanations of the theory of flight rely heavily on Bernoulli's principle and the fact that air travels faster over a wing than below it. In recent years the inadequacies and, indeed, fallacies in this explanation have been exposed (see Babinsky's excellent article in 2003 Phys. Educ. 38 497-503) and it is now…

Effect of 3-bromopyruvate acid on the redox equilibrium in non-invasive MCF-7 and invasive MDA-MB-231 breast cancer cells.

PubMed

Kwiatkowska, Ewa; Wojtala, Martyna; Gajewska, Agnieszka; Soszyński, Mirosław; Bartosz, Grzegorz; Sadowska-Bartosz, Izabela

2016-02-01

Novel approaches to cancer chemotherapy employ metabolic differences between normal and tumor cells, including the high dependence of cancer cells on glycolysis ("Warburg effect"). 3-Bromopyruvate (3-BP), inhibitor of glycolysis, belongs to anticancer drugs basing on this principle. 3-BP was tested for its capacity to kill human non-invasive MCF-7 and invasive MDA-MB-231 breast cancer cells. We found that 3-BP was more toxic for MDA-MB-231 cells than for MCF-7 cells. In both cell lines, a statistically significant decrease of ATP and glutathione was observed in a time- and 3-BP concentration-dependent manner. Transient increases in the level of reactive oxygen species and reactive oxygen species was observed, more pronounced in MCF-7 cells, followed by a decreasing tendency. Activities of glutathione peroxidase, glutathione reductase (GR) and glutathione S-transferase (GST) decreased in 3-BP treated MDA-MB-231 cells. For MCF-7 cells decreases of GR and GST activities were noted only at the highest concentration of 3-BP.These results point to induction of oxidative stress by 3-BP via depletion of antioxidants and inactivation of antioxidant enzymes, more pronounced in MDA-MB-231 cells, more sensitive to 3-BP.

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

Akhrymuk, Ivan; Frolov, Ilya; Frolova, Elena I., E-mail: evfrolova@UAB.edu

Alphaviruses are a family of positive-strand RNA viruses that circulate on all continents between mosquito vectors and vertebrate hosts. Despite a significant public health threat, their biology is not sufficiently investigated, and the mechanisms of alphavirus replication and virus–host interaction are insufficiently understood. In this study, we have applied a variety of experimental systems to further understand the mechanism by which infected cells detect replicating alphaviruses. Our new data strongly suggest that activation of the antiviral response by alphavirus-infected cells is determined by the integrity of viral genes encoding proteins with nuclear functions, and by the presence of two cellularmore » pattern recognition receptors (PRRs), RIG-I and MDA5. No type I IFN response is induced in their absence. The presence of either of these PRRs is sufficient for detecting virus replication. However, type I IFN activation in response to pathogenic alphaviruses depends on the basal levels of RIG-I or MDA5. - Highlights: • Both RIG-I and MDA5 detect alphavirus replication. • Alphavirus-induced transcriptional shutoff affects type I IFN induction. • Sensing of alphavirus replication by RIG-I and MDA5 depends on their concentrations. • High basal level of RIG-I and MDA5 allows IFN induction by pathogenic alphaviruses. • This dependence determines the discrepancy between the in vivo and in vitro data.« less

Activated protein C promotes breast cancer cell migration through interactions with EPCR and PAR-1

PubMed Central

Beaulieu, Lea M.; Church, Frank C.

2014-01-01

Activated protein C (APC) is a serine protease that regulates thrombin (IIa) production through inactivation of blood coagulation factors Va and VIIIa. APC also has non-hemostatic functions related to inflammation, proliferation, and apoptosis through various mechanisms. Using two breast cancer cell lines, MDA-MB-231 and MDA-MB-435, we investigated the role of APC in cell chemotaxis and invasion. Treatment of cells with increasing APC concentrations (1–50 μg/ml) increased invasion and chemotaxis in a concentration-dependent manner. Only the active form of APC increased invasion and chemotaxis of the MDA-MB-231 cells when compared to 3 inactive APC derivatives. Using a modified “checkerboard” analysis, APC was shown to only affect migration when plated with the cells; therefore, APC is not a chemoattractant. Blocking antibodies to endothelial protein C receptor (EPCR) and protease-activated receptor-1 (PAR-1) attenuated the effects of APC on chemotaxis in the MDA-MB-231 cells. Finally, treatment of the MDA-MB-231 cells with the proliferation inhibitor, Na butyrate, showed that APC did not increase migration by increasing cell number. Therefore, APC increases invasion and chemotaxis of cells by binding to the cell surface and activating specific signaling pathways through EPCR and PAR-1. PMID:17254565

Estimation of serum malondialdehyde and assessment of DNA damage using comet assay in patients with oral submucous fibrosis.

PubMed

Paulose, Swetha; Rangdhol, Vishwanath; Ramesh, Ramasamy; Jeelani, Siccandar Ali; Brooklyin, Sivakumar

2016-08-01

To quantify the level of serum malondialdehyde and extent of DNA damage using comet assay in patients with oral submucous fibrosis (SMF) in comparison to normal individuals and to correlate the extent of DNA damage with MDA levels. Study included 30 cases of SMF (n = 30) and equal number of healthy volunteers. Serum malondialdehyde was measured using the thiobarbituric-trichloroacetitic acid (TBA-TCA) method. Comet assay was used to assess the DNA damage. Association between the extent of DNA damage and serum MDA levels was analyzed in SMF statistically. Comet assay results showed that there was an increase in tail length, percentage of tail DNA and tail moment among SMF subjects (P < 0.05). Serum MDA levels were elevated in SMF patients compared with healthy subjects. A significant positive correlation was observed between serum MDA levels and comet tail length in SMF group (r = 0.56; P < 0.05). Patients with SMF have increased DNA damage and elevated levels of lipid peroxidation compared with healthy controls. Evaluation of MDA levels as an oxidative biomarker along with comet assay analysis will serve as a diagnostic tool to identify patients with high risk of malignant potential in SMF. © 2015 Wiley Publishing Asia Pty Ltd.

The prophylactic effect of vitamin C on oxidative stress indexes in rat eyes following exposure to radiofrequency wave generated by a BTS antenna model.

PubMed

Jelodar, Gholamali; Akbari, Abolfazl; Nazifi, Saeed

2013-02-01

This study was conducted to evaluate the effect of radiofrequency wave (RFW)-induced oxidative stress in the eye and the prophylactic effect of vitamin C on this organ by measuring the antioxidant enzymes activity including: glutathione peroxidase (GPx), superoxide dismutase (SOD) and catalase (CAT), and malondialdehyde (MDA). Thirty-two adult male Sprague-Dawley rats were randomly divided into four experimental groups and treated daily for 45 days as follows: Control, vitamin C (L-ascorbic acid 200 mg/kg of body weight/day by gavage), test (exposed to 900 MHz RFW) and the treated group (received vitamin C in addition to exposure to RFW). At the end of the experiment all animals were sacrificed, their eyes were removed and were used for measurement of antioxidant enzymes and MDA activity. The results indicate that exposure to RFW in the test group decreased antioxidant enzymes activity and increased MDA compared with the control groups (P < 0.05). In the treated group vitamin C improved antioxidant enzymes activity and reduced MDA compared to the test group (P < 0.05). It can be concluded that RFW causes oxidative stress in the eyes and vitamin C improves the antioxidant enzymes activity and decreases MDA.

Oxidative stress gradient in a medium during human corneal organ culture

PubMed Central

Johnsen-Soriano, Siv; Haug, Kristiane; Arnal, Emma; Peris-Martinez, Cristina; Moe, Morten C.

2012-01-01

Purpose Lipid peroxidation content was measured in an organ culture medium after one-week storage of human donor corneas. Moreover, the effects of the medium on oxidative stress, antioxidant capacity, and the proliferation of cultured human corneal cells were studied. Methods The medium was sampled from the upper and lower halves of storage vials and from controls (n=42). Malondialdehyde (MDA) was measured by high pressure liquid chromatography (HPLC). Cultured human corneal epithelium (CRL-11515) was exposed to different medium samples and monitored for changes in MDA (enzyme-linked immunosorbent assay [ELISA]), total antioxidant capacity (antioxidant assay kit), and proliferation (Ki-67). Results A significant increase in MDA was observed in the organ culture medium in the lower level of storage vials. The addition of this fraction to cultured cells increased MDA significantly after 3 days, and the medium from both levels significantly increased MDA after 7 days. The medium from both levels significantly decreased the total antioxidant capacity of the cells but did not affect proliferative activity. Conclusions An oxidative gradient with an evident biologic effect is established in the medium in vials during organ culture of human donor corneas. Donor tissue stored at the bottom or in lower levels of such vials is exposed to a significant amount of oxidative stress. PMID:22736949

Mitochondrial Ca{sup 2+} uniporter is critical for store-operated Ca{sup 2+} entry-dependent breast cancer cell migration

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

Tang, Shihao; Guangzhou No.12 Hospital, Guangzhou; Wang, Xubu

2015-02-27

Metastasis of cancer cells is a complicated multistep process requiring extensive and continuous cytosolic calcium modulation. Mitochondrial Ca{sup 2+} uniporter (MCU), a regulator of mitochondrial Ca{sup 2+} uptake, has been implicated in energy metabolism and various cellular signaling processes. However, whether MCU contributes to cancer cell migration has not been established. Here we examined the expression of MCU mRNA in the Oncomine database and found that MCU is correlated to metastasis and invasive breast cancer. MCU inhibition by ruthenium red (RuR) or MCU silencing by siRNA abolished serum-induced migration in MDA-MB-231 breast cancer cells and reduced serum- or thapsigargin (TG)-inducedmore » store-operated Ca2+ entry (SOCE). Serum-induced migrations in MDA-MB-231 cells were blocked by SOCE inhibitors. Our results demonstrate that MCU plays a critical role in breast cancer cell migration by regulating SOCE. - Highlights: • MCU is correlated to metastasis and invasive breast cancer. • MCU inhibition abolished serum-induced migration in MDA-MB-231 breast cancer cells and reduced serum- or TG-induced SOCE. • Serum-induced migrations in MDA-MB-231 cells were blocked by SOCE inhibitors. • MCU plays a critical role in MDA-MB-231 cell migration by regulating SOCE.« less

The effect of ILLLI on peripheral blood SOD, MDA in psoriasis treatment

NASA Astrophysics Data System (ADS)

Zhu, Jing; Nie, Fan

2005-07-01

Objective: To research the effect of Intravascular low level laser irradiation (ILLLI) on the SOD,MDA in the treatment of psoriasis. Method :47 patients suffering from psoriasis from five groups were treated by Intravascular low level laser irradiation (power:4-5mw,1h per day, period of treatment: 10 days) .We checked the change of SOD,MDA peripheral blood in 10 normal people between pre and post treatment. Group A were treated by He-Ne laser combined with drug, group B were treated by semi-conductor laser combined with drug, group C were treated only by He-Ne laser, group D were treated only by semiconductor laser, group E were treated only by drug . Results: The levels of SOD in red cell of psoriatic patients from five groups after treatment were significantly lower than that of controlled group. The levels of SOD of them were significantly increased and nearly closed to that of controlled group; the levels of MDA in red cell of psoriatic patients from five groups after treatment were significantly higher than that of controlled group; the levels of MDA of them are decreased ,however, they were still not recovered to normal levels. Conclusions: ILLLI, both He-Ne laser and semiconductor laser, can activate SOD in psoriasis patients and enhance their ability of anti-oxidation.

Integration of optical measurement methods with flight parameter measurement systems

NASA Astrophysics Data System (ADS)

Kopecki, Grzegorz; Rzucidlo, Pawel

2016-05-01

During the AIM (advanced in-flight measurement techniques) and AIM2 projects, innovative modern techniques were developed. The purpose of the AIM project was to develop optical measurement techniques dedicated for flight tests. Such methods give information about aircraft elements deformation, thermal loads or pressure distribution, etc. In AIM2 the development of optical methods for flight testing was continued. In particular, this project aimed at the development of methods that could be easily applied in flight tests in an industrial setting. Another equally important task was to guarantee the synchronization of the classical measuring system with cameras. The PW-6U glider used in flight tests was provided by the Rzeszów University of Technology. The glider had all the equipment necessary for testing the IPCT (image pattern correlation technique) and IRT (infrared thermometry) methods. Additionally, equipment adequate for the measurement of typical flight parameters, registration and analysis has been developed. This article describes the designed system, as well as presenting the system’s application during flight tests. Additionally, the results obtained in flight tests show certain limitations of the IRT method as applied.

Initial Flight Tests of the NASA F-15B Propulsion Flight Test Fixture

NASA Technical Reports Server (NTRS)

Palumbo, Nathan; Moes, Timothy R.; Vachon, M. Jake

2002-01-01

Flights of the F-15B/Propulsion Flight Test Fixture (PFTF) with a Cone Drag Experiment (CDE) attached have been accomplished at NASA Dryden Flight Research Center. Mounted underneath the fuselage of an F-15B airplane, the PFTF provides volume for experiment systems and attachment points for propulsion experiments. A unique feature of the PFTF is the incorporation of a six-degree-of-freedom force balance. The force balance mounts between the PFTF and experiment and measures three forces and moments. The CDE has been attached to the force balance for envelope expansion flights. This experiment spatially and inertially simulates a large propulsion test article. This report briefly describes the F-15B airplane, the PFTF, and the force balance. A detailed description of the CDE is provided. Force-balance ground testing and stiffness modifications are described. Flight profiles and selected flight data from the envelope expansion flights are provided and discussed, including force-balance data, the internal PFTF thermal and vibration environment, a handling qualities assessment, and performance capabilities of the F-15B airplane with the PFTF installed.

Overexpression of the miR-141/200c cluster promotes the migratory and invasive ability of triple-negative breast cancer cells through the activation of the FAK and PI3K/AKT signaling pathways by secreting VEGF-A.

PubMed

Choi, Sul Ki; Kim, Hoe Suk; Jin, Tiefeng; Hwang, Eun Hye; Jung, Minji; Moon, Woo Kyung

2016-08-02

The role of microRNA-200 (miR-200) family members in the migration and invasion of breast cancer is controversial. This study investigated the mechanisms by which the miR-200 family members modulated the migratory and invasive abilities of an aggressive triple-negative breast cancer (TNBC) cell line, MDA-MB-231. The miR-200 family (miR-200b/200a/429 and miR-141/200c clusters) and green fluorescence protein (GFP) were transduced into MDA-MB-231 cells using a lentiviral system. Stable cells highly expressing the miR-200 family and GFP were isolated by puromycin selection and fluorescence-activated cell sorting. Gene expression was evaluated using real-time polymerase chain reaction (PCR) and reverse transcriptase-PCR (RT-PCR). The migratory and invasive abilities were assessed using trans-well and wound-healing assays. The secreted cytokines and growth factors in cultured media were quantified using a Bio-Plex200 multiplex array system. Western blot assays and immunofluorescence staining were conducted to investigate miR-200 family-regulated signaling pathways. The entire dataset obtained in this study was statistically evaluated using a one-way ANOVA followed by a t-test. The stable overexpression of the miR-200b/200a/429 or miR-141/200c cluster suppressed cell growth and significantly increased migration and invasion of MDA-MB-231 cells. miR-141/200c overexpression was more effective in decreasing cell growth and promoting migration and invasion of MDA-MB-231 cells than was miR-200b/200a/429 overexpression. In addition, the overexpression of the miR-200b/200a/429 or miR-141/200c cluster led to an increase in the phosphorylation of focal adhesion kinase (FAK) and protein kinase B (AKT). Chemical inhibitors of FAK and phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/AKT suppressed the migration and invasion of MDA-MB-231 cells that was enhanced by the overexpression of the miR-200b/200a/429 or miR-141/200c cluster. Compared to the miR-200b/200a/429 cluster-transduced MDA-MB-231 cells, the miR-141/200c cluster-transduced MDA-MB-231 cells exhibited a significant increase in vascular endothelial growth factor (VEGF)-A secretion and integrin-alphaV (integrin-αV) expression. Treatment with an anti-VEGF-A-neutralizing antibody inhibited the increase in migration and invasion in both the miR-200b/200a/429- and miR-141/200c-transduced MDA-MB-231 cells but significantly reduced the phosphorylation of FAK and AKT in only the miR-141/200c cluster-transduced MDA-MB-231 cells. Taken together, our data demonstrate a mechanism in which the miR-141/200c cluster, through FAK- and PI3K/AKT-mediated signaling by means of increased VEGF-A secretion, promotes the migratory and invasive abilities of MDA-MB-231 cells.

Proteomic analysis of protective effects of polysaccharides from Salvia miltiorrhiza against immunological liver injury in mice.

PubMed

Sun, Xue-Gang; Fu, Xiu-Qiong; Cai, Hong-Bing; Liu, Qiang; Li, Chun-Hua; Liu, Ya-Wei; Li, Ying-Jia; Liu, Zhi-Feng; Song, Yu-Hong; Lv, Zhi-Ping

2011-07-01

This study was designed to investigate mechanisms of the protective effects of Salvia miltiorrhiza polysaccharide (SMPS) against lipopolysaccharide (LPS)-induced immunological liver injury (ILI) in Bacille Calmette-Guérin (BCG)-primed mice. Two-dimensional difference gel electrophoresis (2D-DIGE) and matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) analysis showed that three proteins are down-regulated and six proteins are up-regulated by SMPS. SMPS reduces the degree of liver injury by up-regulating the enzymes of the citric acid cycle, namely malate dehydrogenase (MDH) and 2-oxoglutarate dehydrogenase complex. LPS significantly increases nuclear factor kappa B (NF-κB) activation, inducible nitric oxide synthase (iNOS) expression and MDA level in BCG primed mice liver, whereas SMPS treatment protects against the immunological liver injury through inhibition of the NF-κB activation by up-regulation of PRDX6 and the subsequent attenuation of lipid peroxidation, iNOS expression and inflammation. Copyright © 2011 John Wiley & Sons, Ltd.

Biodegradable Eri silk nanoparticles as a delivery vehicle for bovine lactoferrin against MDA-MB-231 and MCF-7 breast cancer cells

PubMed Central

Roy, Kislay; Patel, Yogesh S; Kanwar, Rupinder K; Rajkhowa, Rangam; Wang, Xungai; Kanwar, Jagat R

2016-01-01

This study used the Eri silk nanoparticles (NPs) for delivering apo-bovine lactoferrin (Apo-bLf) (~2% iron saturated) and Fe-bLf (100% iron saturated) in MDA-MB-231 and MCF-7 breast cancer cell lines. Apo-bLf and Fe-bLf-loaded Eri silk NPs with sizes between 200 and 300 nm (±10 nm) showed a significant internalization within 4 hours in MDA-MB-231 cells when compared to MCF-7 cells. The ex vivo loop assay with chitosan-coated Fe-bLf-loaded silk NPs was able to substantiate its future use in oral administration and showed the maximum absorption within 24 hours by ileum. Both Apo-bLf and Fe-bLf induced increase in expression of low-density lipoprotein receptor-related protein 1 and lactoferrin receptor in epidermal growth factor (EGFR)-positive MDA-MB-231 cells, while transferrin receptor (TfR) and TfR2 in MCF-7 cells facilitated the receptor-mediated endocytosis of NPs. Controlled and sustained release of both bLf from silk NPs was shown to induce more cancer-specific cytotoxicity in MDA-MB-231 and MCF-7 cells compared to normal MCF-10A cells. Due to higher degree of internalization, the extent of cytotoxicity and apoptosis was significantly higher in MDA-MB-231 (EGFR+) cells when compared to MCF-7 (EGFR−) cells. The expression of a prominent anticancer target, survivin, was found to be downregulated at both gene and protein levels. Taken together, all the observations suggest the potential use of Eri silk NPs as a delivery vehicle for an anti-cancer milk protein, and indicate bLf for the treatment of breast cancer. PMID:26730188

National Mass Drug Administration Costs for Lymphatic Filariasis Elimination

PubMed Central

Goldman, Ann S.; Guisinger, Victoria H.; Aikins, Moses; Amarillo, Maria Lourdes E.; Belizario, Vicente Y.; Garshong, Bertha; Gyapong, John; Kabali, Conrad; Kamal, Hussein A.; Kanjilal, Sanjat; Kyelem, Dominique; Lizardo, Jefrey; Malecela, Mwele; Mubyazi, Godfrey; Nitièma, P. Abdoulaye; Ramzy, Reda M. R.; Streit, Thomas G.; Wallace, Aaron; Brady, Molly A.; Rheingans, Richard; Ottesen, Eric A.; Haddix, Anne C.

2007-01-01

Background Because lymphatic filariasis (LF) elimination efforts are hampered by a dearth of economic information about the cost of mass drug administration (MDA) programs (using either albendazole with diethylcarbamazine [DEC] or albendazole with ivermectin), a multicenter study was undertaken to determine the costs of MDA programs to interrupt transmission of infection with LF. Such results are particularly important because LF programs have the necessary diagnostic and treatment tools to eliminate the disease as a public health problem globally, and already by 2006, the Global Programme to Eliminate LF had initiated treatment programs covering over 400 million of the 1.3 billion people at risk. Methodology/Principal Findings To obtain annual costs to carry out the MDA strategy, researchers from seven countries developed and followed a common cost analysis protocol designed to estimate 1) the total annual cost of the LF program, 2) the average cost per person treated, and 3) the relative contributions of the endemic countries and the external partners. Costs per person treated ranged from $0.06 to $2.23. Principal reasons for the variation were 1) the age (newness) of the MDA program, 2) the use of volunteers, and 3) the size of the population treated. Substantial contributions by governments were documented – generally 60%–90% of program operation costs, excluding costs of donated medications. Conclusions/Significance MDA for LF elimination is comparatively inexpensive in relation to most other public health programs. Governments and communities make the predominant financial contributions to actual MDA implementation, not counting the cost of the drugs themselves. The results highlight the impact of the use of volunteers on program costs and provide specific cost data for 7 different countries that can be used as a basis both for modifying current programs and for developing new ones. PMID:17989784

Antioxidant Activity and ROS-Dependent Apoptotic Effect of Scurrula ferruginea (Jack) Danser Methanol Extract in Human Breast Cancer Cell MDA-MB-231

PubMed Central

Marvibaigi, Mohsen; Amini, Neda; Supriyanto, Eko; Abdul Majid, Fadzilah Adibah; Kumar Jaganathan, Saravana; Jamil, Shajarahtunnur; Hamzehalipour Almaki, Javad; Nasiri, Rozita

2016-01-01

Scurrula ferruginea (Jack) Danser is one of the mistletoe species belonging to Loranthaceae family, which grows on the branches of many deciduous trees in tropical countries. This study evaluated the antioxidant activities of S. ferruginea extracts. The cytotoxic activity of the selected extracts, which showed potent antioxidant activities, and high phenolic and flavonoid contents, were investigated in human breast cancer cell line (MDA-MB-231) and non-cancer human skin fibroblast cells (HSF-1184). The activities and characteristics varied depending on the different parts of S. ferruginea, solvent polarity, and concentrations of extracts. The stem methanol extract showed the highest amount of both phenolic (273.51 ± 4.84 mg gallic acid/g extract) and flavonoid contents (163.41 ± 4.62 mg catechin/g extract) and strong DPPH• radical scavenging (IC50 = 27.81 μg/mL) and metal chelation activity (IC50 = 80.20 μg/mL). The stem aqueous extract showed the highest ABTS•+ scavenging ability. The stem methanol and aqueous extracts exhibited dose-dependent cytotoxic activity against MDA-MB-231 cells with IC50 of 19.27 and 50.35 μg/mL, respectively. Furthermore, the extracts inhibited the migration and colony formation of MDA-MB-231 cells in a concentration-dependent manner. Morphological observations revealed hallmark properties of apoptosis in treated cells. The methanol extract induced an increase in ROS generation and mitochondrial depolarization in MDA-MB-231 cells, suggesting its potent apoptotic activity. The present study demonstrated that the S. ferruginea methanol extract mediated MDA-MB-231 cell growth inhibition via induction of apoptosis which was confirmed by Western blot analysis. It may be a potential anticancer agent; however, its in vivo anticancer activity needs to be investigated. PMID:27410459

Musculoskeletal Disease in MDA5-Related Type I Interferonopathy: A Mendelian Mimic of Jaccoud's Arthropathy.

PubMed

de Carvalho, Luciana Martins; Ngoumou, Gonza; Park, Ji Woo; Ehmke, Nadja; Deigendesch, Nikolaus; Kitabayashi, Naoki; Melki, Isabelle; Souza, Flávio Falcäo L; Tzschach, Andreas; Nogueira-Barbosa, Marcello H; Ferriani, Virgínia; Louzada-Junior, Paulo; Marques, Wilson; Lourenço, Charles M; Horn, Denise; Kallinich, Tilmann; Stenzel, Werner; Hur, Sun; Rice, Gillian I; Crow, Yanick J

2017-10-01

To define the molecular basis of a multisystem phenotype with progressive musculoskeletal disease of the hands and feet, including camptodactyly, subluxation, and tendon rupture, reminiscent of Jaccoud's arthropathy. We identified 2 families segregating an autosomal-dominant phenotype encompassing musculoskeletal disease and variable additional features, including psoriasis, dental abnormalities, cardiac valve involvement, glaucoma, and basal ganglia calcification. We measured the expression of interferon (IFN)-stimulated genes in the peripheral blood and skin, and undertook targeted Sanger sequencing of the IFIH1 gene encoding the cytosolic double-stranded RNA (dsRNA) sensor melanoma differentiation-associated protein 5 (MDA-5). We also assessed the functional consequences of IFIH1 gene variants using an in vitro IFNβ reporter assay in HEK 293T cells. We recorded an up-regulation of type I IFN-induced gene transcripts in all 5 patients tested and identified a heterozygous gain-of-function mutation in IFIH1 in each family, resulting in different substitutions of the threonine residue at position 331 of MDA-5. Both of these variants were associated with increased IFNβ expression in the absence of exogenous dsRNA ligand, consistent with constitutive activation of MDA-5. These cases highlight the significant musculoskeletal involvement that can be associated with mutations in MDA-5, and emphasize the value of testing for up-regulation of IFN signaling as a marker of the underlying molecular lesion. Our data indicate that both Singleton-Merten syndrome and neuroinflammation described in the context of MDA-5 gain-of-function constitute part of the same type I interferonopathy disease spectrum, and provide possible novel insight into the pathology of Jaccoud's arthropathy. © 2017, American College of Rheumatology.

Anti-Metastatic and Anti-Tumor Growth Effects of Origanum majorana on Highly Metastatic Human Breast Cancer Cells: Inhibition of NFκB Signaling and Reduction of Nitric Oxide Production

PubMed Central

Al Dhaheri, Yusra; Attoub, Samir; Arafat, Kholoud; AbuQamar, Synan; Viallet, Jean; Saleh, Alaaeldin; Al Agha, Hala; Eid, Ali; Iratni, Rabah

2013-01-01

Background We have recently reported that Origanum majorana exhibits anticancer activity by promoting cell cycle arrest and apoptosis of the metastatic MDA-MB-231 breast cancer cell line. Here, we extended our study by investigating the effect of O . majorana on the migration, invasion and tumor growth of these cells. Results We demonstrate that non-cytotoxic concentrations of O . majorana significantly inhibited the migration and invasion of the MDA-MB-231 cells as shown by wound-healing and matrigel invasion assays. We also show that O . majorana induce homotypic aggregation of MDA-MB-231 associated with an upregulation of E-cadherin protein and promoter activity. Furthermore, we show that O . majorana decrease the adhesion of MDA-MB-231 to HUVECs and inhibits transendothelial migration of MDA-MB-231 through TNF-α-activated HUVECs. Gelatin zymography assay shows that O . majorana suppresses the activities of matrix metalloproteinase-2 and -9 (MMP-2 and MMP-9). ELISA, RT-PCR and Western blot results revealed that O . majorana decreases the expression of MMP-2, MMP-9, urokinase plasminogen activator receptor (uPAR), ICAM-1 and VEGF. Further investigation revealed that O . majorana suppresses the phosphorylation of IκB, downregulates the nuclear level of NFκB and reduces Nitric Oxide (NO) production in MDA-MB-231 cells. Most importantly, by using chick embryo tumor growth assay, we also show that O . majorana promotes inhibition of tumor growth and metastasis in vivo. Conclusion Our findings identify Origanum majorana as a promising chemopreventive and therapeutic candidate that modulate breast cancer growth and metastasis. PMID:23874773

Elemental Zinc Is Inversely Associated with C-Reactive Protein and Oxidative Stress in Chronic Liver Disease.

PubMed

Uddin, Md Giash; Hossain, Mohammad Salim; Rahman, Md Atiqur; Uddin, A H M Mazbah; Bhuiyan, Md Shafiullah

2017-08-01

Chronic liver disease (CLD) is associated with the destruction of liver parenchyma cell. It is the main cause of morbidity and mortality in most of the developed countries. Oxidative stress and altered levels of different trace elements in serum have been documented for different diseases including inflammation and many liver diseases. This study aims to evaluate the serum level of malondialdehyde (MDA), nitric oxide (NO), antioxidant vitamin C, C-reactive protein (CRP), and zinc (Zn) in CLD patients and to establish a correlation among the study parameters with the severity of inflammatory conditions of CLD. In this study, CLD patients and healthy volunteers were recruited. Total cholesterol and triglyceride were determined by colorimeter using enzymatic method. Serum non-enzymatic antioxidant vitamin C, reactive oxygen species nitric oxide (NO), and malondialdehyde (MDA) were determined by UV-spectrophotometric method. Trace element (Zn) levels were determined by graphite furnace atomic absorption spectroscopy. Independent sample t test and Pearson's correlation test were performed for statistical analysis using the statistical software package SPSS, Version 20. Studies showed that the MDA (p < 0.001), NO (p < 0.001), and CRP levels were significantly higher in CLD patients than in control subjects. The antioxidant vitamin C (p < 0.001) and trace element zinc (p < 0.001) were comparatively lower in the CLD patients than in control subjects. Elemental Zn showed an inverse relationship with MDA, NO, and CRP but positively correlated with antioxidant capacity, whereas MDA showed a positive correlation with CRP level. Thus, we conclude that attenuated level of Zn and antioxidant in serum play an important role in the inflammatory status of CLD patients by elevating the concentration of MDA, NO, and CRP.

Accessory Factors of Cytoplasmic Viral RNA Sensors Required for Antiviral Innate Immune Response.

PubMed

Oshiumi, Hiroyuki; Kouwaki, Takahisa; Seya, Tsukasa

2016-01-01

Type I interferon (IFN) induces many antiviral factors in host cells. RIG-I-like receptors (RLRs) are cytoplasmic viral RNA sensors that trigger the signal to induce the innate immune response that includes type I IFN production. RIG-I and MDA5 are RLRs that form nucleoprotein filaments along viral double-stranded RNA, resulting in the activation of MAVS adaptor molecule. The MAVS protein forms a prion-like aggregation structure, leading to type I IFN production. RIG-I and MDA5 undergo post-translational modification. TRIM25 and Riplet ubiquitin ligases deliver a K63-linked polyubiquitin moiety to the RIG-I N-terminal caspase activation and recruitment domains (CARDs) and C-terminal region; the polyubiquitin chain then stabilizes the two-CARD tetramer structure required for MAVS assembly. MDA5 activation is regulated by phosphorylation. RIOK3 is a protein kinase that phosphorylates the MDA5 protein in a steady state, and PP1α/γ dephosphorylate this protein, resulting in its activation. RIG-I and MDA5 require cytoplasmic RNA helicases for their efficient activation. LGP2, another RLR, is an RNA helicase involved in RLR signaling. This protein does not possess N-terminal CARDs and, thus, cannot trigger downstream signaling by itself. Recent studies have revealed that this protein modulates MDA5 filament formation, resulting in enhanced type I IFN production. Several other cytoplasmic RNA helicases are involved in RLR signaling. DDX3, DHX29, DHX36, and DDX60 RNA helicases have been reported to be involved in RLR-mediated type I IFN production after viral infection. However, the underlying mechanism is largely unknown. Future studies are required to reveal the role of RNA helicases in the RLR signaling pathway.

The Effect of Oral Anthelmintics on the Survivorship and Re-feeding Frequency of Anthropophilic Mosquito Disease Vectors

PubMed Central

Kobylinski, Kevin C.; Deus, Kelsey M.; Butters, Matt T.; Hongyu, Tan; Gray, Meg; Silva, Ines Marques da; Sylla, Massamba; Foy, Brian D.

2010-01-01

In the Tropics, there is substantial temporal and spatial overlap of diseases propagated by anthropophilic mosquito vectors (such as malaria and dengue) and human helminth diseases (such as onchocerciasis and lymphatic filariasis) that are treated though mass drug administrations (MDA). This overlap will result in mosquito vectors imbibing significant quantities of these drugs when they blood feed on humans. Since many anthelmintic drugs have broad anti-invertebrate effects, the possibility of combined helminth control and mosquito-borne disease control through MDA is apparent. It has been previously shown that ivermectin can reduce mosquito survivorship when administered in a blood meal, but more detailed examinations are needed if MDA is to ever be developed into a tool for malaria or dengue control. We examined concentrations of drugs that follow human pharmacokinetics after MDA and that matched with mosquito feeding times, for effects against the anthropophilic mosquito vectors Anopheles gambiae s.s. and Aedes aegypti. Ivermectin was the only human-approved MDA drug we tested that affected mosquito survivorship, and only An. gambiae s.s. were affected at concentrations respecting human pharmacokinetics at indicated doses. Ivermectin also delayed An. gambiae s.s. re-feeding frequency and defecation rates, and two successive ivermectin-spiked blood meals following human pharmacokinetic concentrations compounded mortality effects compared to controls. These findings suggest that ivermectin MDA in Africa may be used to decrease malaria transmission if MDAs were administered more frequently. Such a strategy would broaden the current scope of polyparasitism control already afforded by MDAs, and which is needed in many African villages simultaneously burdened by many parasitic diseases. PMID:20540931

Influence of the interaction between nodal fibroblast and breast cancer cells on gene expression.

PubMed

Santos, Rosângela Portilho Costa; Benvenuti, Ticiana Thomazine; Honda, Suzana Terumi; Del Valle, Paulo Roberto; Katayama, Maria Lucia Hirata; Brentani, Helena Paula; Carraro, Dirce Maria; Rozenchan, Patrícia Bortman; Brentani, Maria Mitzi; de Lyra, Eduardo Carneiro; Torres, César Henrique; Salzgeber, Marcia Batista; Kaiano, Jane Haruko Lima; Góes, João Carlos Sampaio; Folgueira, Maria Aparecida Azevedo Koike

2011-02-01

Our aim was to evaluate the interaction between breast cancer cells and nodal fibroblasts, by means of their gene expression profile. Fibroblast primary cultures were established from negative and positive lymph nodes from breast cancer patients and a similar gene expression pattern was identified, following cell culture. Fibroblasts and breast cancer cells (MDA-MB231, MDA-MB435, and MCF7) were cultured alone or co-cultured separated by a porous membrane (which allows passage of soluble factors) for comparison. Each breast cancer lineage exerted a particular effect on fibroblasts viability and transcriptional profile. However, fibroblasts from positive and negative nodes had a parallel transcriptional behavior when co-cultured with a specific breast cancer cell line. The effects of nodal fibroblasts on breast cancer cells were also investigated. MDA MB-231 cells viability and migration were enhanced by the presence of fibroblasts and accordingly, MDA-MB435 and MCF7 cells viability followed a similar pattern. MDA-MB231 gene expression profile, as evaluated by cDNA microarray, was influenced by the fibroblasts presence, and HNMT, COMT, FN3K, and SOD2 were confirmed downregulated in MDA-MB231 co-cultured cells with fibroblasts from both negative and positive nodes, in a new series of RT-PCR assays. In summary, transcriptional changes induced in breast cancer cells by fibroblasts from positive as well as negative nodes are very much alike in a specific lineage. However, fibroblasts effects are distinct in each one of the breast cancer lineages, suggesting that the inter-relationships between stromal and malignant cells are dependent on the intrinsic subtype of the tumor.

The hyperthermic and neurotoxic effects of 'Ecstasy' (MDMA) and 3,4 methylenedioxyamphetamine (MDA) in the Dark Agouti (DA) rat, a model of the CYP2D6 poor metabolizer phenotype.

PubMed Central

Colado, M. I.; Williams, J. L.; Green, A. R.

1995-01-01

1. The effect of administration of 3,4-methylenedioxymethamphetamine (MDMA or 'Ecstasy') and its N-demethylated product, 3,4-methylenedioxyamphetamine (MDA) on both rectal temperature and long term neurotoxic loss of cerebral 5-hydroxytryptamine (5-HT) has been studied in male and female Dark Agouti (DA) rats. The female metabolizes debrisoquine more slowly than the male and its use has been suggested as a model of the human debrisoquine 4-hydroxylase poor metabolizer phenotype. 2. A novel h.p.l.c. method was developed and used to measure plasma MDMA and MDA concentrations in the DA rats. 3. The hyperthermic response following MDMA was enhanced in female rats. Plasma MDMA concentrations were also 57% higher than in males 45 min post-injection, while plasma concentrations of MDA were 48% lower. 4. Plasma concentrations of MDMA and MDA in male rats were unaffected by pretreatment with proadifen (15 mg kg-1) or quinidine (60 mg kg-1), but the hyperthermic response to MDMA (10 mg kg-1, i.p.) was enhanced by quinidine pretreatment. 5. The hyperthermic response following MDA was greater in male DA rats, despite plasma drug concentrations being 40% higher in females 60 min after injection. 6. Seven days after a single dose of MDMA (10 mg kg-1, i.p.) there was a substantial loss in the concentration of 5-HT and 5-hydroxyindoleacetic acid (5-HIA) in cortex and hippocampus. [3H]-paroxetine binding was also decreased by 27% in the cortex, indicating that the amine loss reflected a neurodegenerative change. MDMA (5 mg kg-1, i.p.) was without effect on brain 5-HT content.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7582557

P2Y2R activation by nucleotides released from the highly metastatic breast cancer cell contributes to pre-metastatic niche formation by mediating lysyl oxidase secretion, collagen crosslinking, and monocyte recruitment

PubMed Central

Joo, Young Nak; Jin, Hana; Eun, So Young; Park, Sang Won; Chang, Ki Churl; Kim, Hye Jung

2014-01-01

Tumor microenvironmental hypoxia induces hypoxia inducible factor-1α (HIF-1α) overexpression, leading to the release of lysyl oxidase (LOX), which crosslinks collagen at distant sites to facilitate environmental changes that allow cancer cells to easily metastasize. Our previous study showed that activation of the P2Y2 receptor (P2Y2R) by ATP released from MDA-MB-231 cells increased MDA-MB-231 cell invasion through endothelial cells. Therefore, in this study, we investigated the role of P2Y2R in breast cancer cell metastasis to distant sites. ATP or UTP released from hypoxia-treated MDA-MB-231 cells induced HIF-1α expression and LOX secretion by the activation of P2Y2R, and this phenomenon was significantly reduced in P2Y2R-depleted MDA-MB-231 cells. Furthermore, P2Y2R-mediated LOX release induced collagen crosslinking in an in vitro model. Finally, nude mice injected with MDA-MB-231 cells showed high levels of LOX secretion, crosslinked collagen and CD11b+ BMDC recruitment in the lung; however, mice that were injected with P2Y2R-depleted MDA-MB-231 cells did not exhibit these changes. These results demonstrate that P2Y2R plays an important role in activation of the HIF-1α–LOX axis, the induction of collagen crosslinking and the recruitment of CD11b+ BMDCs. Furthermore, P2Y2R activation by nucleotides recruits THP-1 monocytes, resulting in primary tumor progression and pre-metastatic niche formation. PMID:25238333

Impact and cost-effectiveness of snail control to achieve disease control targets for schistosomiasis.

PubMed

Lo, Nathan C; Gurarie, David; Yoon, Nara; Coulibaly, Jean T; Bendavid, Eran; Andrews, Jason R; King, Charles H

2018-01-23

Schistosomiasis is a parasitic disease that affects over 240 million people globally. To improve population-level disease control, there is growing interest in adding chemical-based snail control interventions to interrupt the lifecycle of Schistosoma in its snail host to reduce parasite transmission. However, this approach is not widely implemented, and given environmental concerns, the optimal conditions for when snail control is appropriate are unclear. We assessed the potential impact and cost-effectiveness of various snail control strategies. We extended previously published dynamic, age-structured transmission and cost-effectiveness models to simulate mass drug administration (MDA) and focal snail control interventions against Schistosoma haematobium across a range of low-prevalence (5-20%) and high-prevalence (25-50%) rural Kenyan communities. We simulated strategies over a 10-year period of MDA targeting school children or entire communities, snail control, and combined strategies. We measured incremental cost-effectiveness in 2016 US dollars per disability-adjusted life year and defined a strategy as optimally cost-effective when maximizing health gains (averted disability-adjusted life years) with an incremental cost-effectiveness below a Kenya-specific economic threshold. In both low- and high-prevalence settings, community-wide MDA with additional snail control reduced total disability by an additional 40% compared with school-based MDA alone. The optimally cost-effective scenario included the addition of snail control to MDA in over 95% of simulations. These results support inclusion of snail control in global guidelines and national schistosomiasis control strategies for optimal disease control, especially in settings with high prevalence, "hot spots" of transmission, and noncompliance to MDA. Copyright © 2018 the Author(s). Published by PNAS.

Impact and cost-effectiveness of snail control to achieve disease control targets for schistosomiasis

PubMed Central

Yoon, Nara; Coulibaly, Jean T.; Bendavid, Eran; Andrews, Jason R.; King, Charles H.

2018-01-01

Schistosomiasis is a parasitic disease that affects over 240 million people globally. To improve population-level disease control, there is growing interest in adding chemical-based snail control interventions to interrupt the lifecycle of Schistosoma in its snail host to reduce parasite transmission. However, this approach is not widely implemented, and given environmental concerns, the optimal conditions for when snail control is appropriate are unclear. We assessed the potential impact and cost-effectiveness of various snail control strategies. We extended previously published dynamic, age-structured transmission and cost-effectiveness models to simulate mass drug administration (MDA) and focal snail control interventions against Schistosoma haematobium across a range of low-prevalence (5–20%) and high-prevalence (25–50%) rural Kenyan communities. We simulated strategies over a 10-year period of MDA targeting school children or entire communities, snail control, and combined strategies. We measured incremental cost-effectiveness in 2016 US dollars per disability-adjusted life year and defined a strategy as optimally cost-effective when maximizing health gains (averted disability-adjusted life years) with an incremental cost-effectiveness below a Kenya-specific economic threshold. In both low- and high-prevalence settings, community-wide MDA with additional snail control reduced total disability by an additional 40% compared with school-based MDA alone. The optimally cost-effective scenario included the addition of snail control to MDA in over 95% of simulations. These results support inclusion of snail control in global guidelines and national schistosomiasis control strategies for optimal disease control, especially in settings with high prevalence, “hot spots” of transmission, and noncompliance to MDA. PMID:29301964

Characterization of hybrid cells derived from spontaneous fusion events between breast epithelial cells exhibiting stem-like characteristics and breast cancer cells.

PubMed

Dittmar, Thomas; Schwitalla, Sarah; Seidel, Jeanette; Haverkampf, Sonja; Reith, Georg; Meyer-Staeckling, Sönke; Brandt, Burkhard H; Niggemann, Bernd; Zänker, Kurt S

2011-01-01

Several data of the past years clearly indicated that the fusion of tumor cells and tumor cells or tumor cells and normal cells can give rise to hybrids cells exhibited novel properties such as an increased malignancy, drug resistance, or resistance to apoptosis. In the present study we characterized hybrid cells derived from spontaneous fusion events between the breast epithelial cell line M13SV1-EGFP-Neo and two breast cancer cell lines: HS578T-Hyg and MDA-MB-435-Hyg. Short-tandem-repeat analysis revealed an overlap of parental alleles in all hybrid cells indicating that hybrid cells originated from real cell fusion events. RealTime-PCR-array gene expression data provided evidence that each hybrid cell clone exhibited a unique gene expression pattern, resulting in a specific resistance of hybrid clones towards chemotherapeutic drugs, such as doxorubicin and paclitaxel, as well as a specific migratory behavior of hybrid clones towards EGF. For instance, M13MDA435-4 hybrids showed a marked resistance towards etoposide, doxorubicin and paclitaxel, whereas hybrid clones M13MDA-435-1 and -2 were only resistant towards etoposide. Likewise, all investigated M13MDA435 hybrids responded to EGF with an increased migratory activity, whereas the migration of parental MDA-MB-435-Hyg cells was blocked by EGF, suggesting that M13MDA435 hybrids may have acquired a new motility pathway. Similar findings have been obtained for M13HS hybrids. We conclude from our data that they further support the hypothesis that cell fusion could give rise to drug resistant and migratory active tumor (hybrid) cells in cancer.

Chrysin, Abundant in Morinda citrifolia Fruit Water-EtOAc Extracts, Combined with Apigenin Synergistically Induced Apoptosis and Inhibited Migration in Human Breast and Liver Cancer Cells.

PubMed

Huang, Cheng; Wei, Yu-Xuan; Shen, Ma-Ching; Tu, Yu-Hsuan; Wang, Chia-Chi; Huang, Hsiu-Chen

2016-06-01

The composition of Morinda citrifolia (M. citrifolia) was determined using high-performance liquid chromatography (HPLC), and the anticancer effects of M. citrifolia extract evaluated in HepG2, Huh7, and MDA-MB-231 cancer cells. M. citrifolia fruit extracts were obtained by using five different organic solvents, including hexane (Hex), methanol (MeOH), ethyl acetate (EtOAc), chloroform (CHCl3), and ethanol (EtOH). The water-EtOAc extracts from M. citrifolia fruits was found to have the highest anticancer activity. HPLC data revealed the predominance of chrysin in water-EtOAc extracts of M. citrifolia fruit. Furthermore, the combined effects of cotreatment with apigenin and chrysin on liver and breast cancer were investigated. Treatment with apigenin plus chrysin for 72-96 h reduced HepG2 and MDA-MB-231 cell viability and induced apoptosis through down-regulation of S-phase kinase-associated protein-2 (Skp2) and low-density lipoprotein receptor-related protein 6 (LRP6) expression. However, the combination treatment for 36 h synergistically decreased MDA-MB-231 cell motility but not cell viability through down-regulation of MMP2, MMP9, fibronectin, and snail in MDA-MB-231 cells. Additionally, chrysin combined with apigenin also suppressed tumor growth in human MDA-MB-231 breast cancer cells xenograft through down-regulation of ki-67 and Skp2 protein. The experimental results showed that chrysin combined with apigenin can reduce HepG2 and MDA-MB-231 proliferation and cell motility and induce apoptosis. It also offers opportunities for exploring new drug targets, and further investigations are underway in this regard.

Mechanism of chimera formation during the Multiple Displacement Amplification reaction.

PubMed

Lasken, Roger S; Stockwell, Timothy B

2007-04-12

Multiple Displacement Amplification (MDA) is a method used for amplifying limiting DNA sources. The high molecular weight amplified DNA is ideal for DNA library construction. While this has enabled genomic sequencing from one or a few cells of unculturable microorganisms, the process is complicated by the tendency of MDA to generate chimeric DNA rearrangements in the amplified DNA. Determining the source of the DNA rearrangements would be an important step towards reducing or eliminating them. Here, we characterize the major types of chimeras formed by carrying out an MDA whole genome amplification from a single E. coli cell and sequencing by the 454 Life Sciences method. Analysis of 475 chimeras revealed the predominant reaction mechanisms that create the DNA rearrangements. The highly branched DNA synthesized in MDA can assume many alternative secondary structures. DNA strands extended on an initial template can be displaced becoming available to prime on a second template creating the chimeras. Evidence supports a model in which branch migration can displace 3'-ends freeing them to prime on the new templates. More than 85% of the resulting DNA rearrangements were inverted sequences with intervening deletions that the model predicts. Intramolecular rearrangements were favored, with displaced 3'-ends reannealing to single stranded 5'-strands contained within the same branched DNA molecule. In over 70% of the chimeric junctions, the 3' termini had initiated priming at complimentary sequences of 2-21 nucleotides (nts) in the new templates. Formation of chimeras is an important limitation to the MDA method, particularly for whole genome sequencing. Identification of the mechanism for chimera formation provides new insight into the MDA reaction and suggests methods to reduce chimeras. The 454 sequencing approach used here will provide a rapid method to assess the utility of reaction modifications.

Human Respiratory Syncytial Virus Nucleoprotein and Inclusion Bodies Antagonize the Innate Immune Response Mediated by MDA5 and MAVS

PubMed Central

Lifland, Aaron W.; Jung, Jeenah; Alonas, Eric; Zurla, Chiara; Crowe, James E.

2012-01-01

Currently, the spatial distribution of human respiratory syncytial virus (hRSV) proteins and RNAs in infected cells is still under investigation, with many unanswered questions regarding the interaction of virus-induced structures and the innate immune system. Very few studies of hRSV have used subcellular imaging as a means to explore the changes in localization of retinoic-acid-inducible gene-I (RIG-I)-like receptors or the mitochondrial antiviral signaling (MAVS) protein, in response to the infection and formation of viral structures. In this investigation, we found that both RIG-I and melanoma differentiation-associated gene 5 (MDA5) colocalized with viral genomic RNA and the nucleoprotein (N) as early as 6 h postinfection (hpi). By 12 hpi, MDA5 and MAVS were observed within large viral inclusion bodies (IB). We used a proximity ligation assay (PLA) and determined that the N protein was in close proximity to MDA5 and MAVS in IBs throughout the course of the infection. Similar results were found with the transient coexpression of N and the phosphoprotein (P). Additionally, we demonstrated that the localization of MDA5 and MAVS in IBs inhibited the expression of interferon β mRNA 27-fold following Newcastle disease virus infection. From these data, we concluded that the N likely interacts with MDA5, is in close proximity to MAVS, and localizes these molecules within IBs in order to attenuate the interferon response. To our knowledge, this is the first report of a specific function for hRSV IBs and of the hRSV N protein as a modulator of the innate immune response. PMID:22623778

Human respiratory syncytial virus nucleoprotein and inclusion bodies antagonize the innate immune response mediated by MDA5 and MAVS.

PubMed

Lifland, Aaron W; Jung, Jeenah; Alonas, Eric; Zurla, Chiara; Crowe, James E; Santangelo, Philip J

2012-08-01

Currently, the spatial distribution of human respiratory syncytial virus (hRSV) proteins and RNAs in infected cells is still under investigation, with many unanswered questions regarding the interaction of virus-induced structures and the innate immune system. Very few studies of hRSV have used subcellular imaging as a means to explore the changes in localization of retinoic-acid-inducible gene-I (RIG-I)-like receptors or the mitochondrial antiviral signaling (MAVS) protein, in response to the infection and formation of viral structures. In this investigation, we found that both RIG-I and melanoma differentiation-associated gene 5 (MDA5) colocalized with viral genomic RNA and the nucleoprotein (N) as early as 6 h postinfection (hpi). By 12 hpi, MDA5 and MAVS were observed within large viral inclusion bodies (IB). We used a proximity ligation assay (PLA) and determined that the N protein was in close proximity to MDA5 and MAVS in IBs throughout the course of the infection. Similar results were found with the transient coexpression of N and the phosphoprotein (P). Additionally, we demonstrated that the localization of MDA5 and MAVS in IBs inhibited the expression of interferon β mRNA 27-fold following Newcastle disease virus infection. From these data, we concluded that the N likely interacts with MDA5, is in close proximity to MAVS, and localizes these molecules within IBs in order to attenuate the interferon response. To our knowledge, this is the first report of a specific function for hRSV IBs and of the hRSV N protein as a modulator of the innate immune response.

Responses of Reactive Oxygen Scavenging Enzymes, Proline and Malondialdehyde to Water Deficits among Six Secondary Successional Seral Species in Loess Plateau

PubMed Central

Du, Feng; Shi, Huijun; Zhang, Xingchang; Xu, Xuexuan

2014-01-01

Drought can impact local vegetation dynamics in a long term. In order to predict the possible successional pathway of local community under drought, the responses of some drought resistance indices of six successional seral species in the semi-arid Loss Hilly Region of China were illustrated and compared on three levels of soil water deficits along three growing months (7, 8 and 9). The results showed that: 1) the six species had significant differences in SOD, POD activities and MDA content. The rank correlations between SOD, POD activities and the successional niche positions of the six species were positive, and the correlation between MDA content and the niche positions was negative; 2) activities of SOD, CAT and POD, and content of proline and MDA had significant differences among the three months; 3) there existed significant interactions of SOD, CAT, POD activities and MDA content between months and species. With an exception, no interaction of proline was found. Proline in leaves had a general decline in reproductive month; 4) SOD, CAT, POD activities and proline content had negative correlations with MDA content. Among which, the correlation between SOD activity and MDA content was significant. The results implied that, in arid or semiarid region, the species at later successional stage tend to have strong drought resistance than those at early stage. Anti-drought indices can partially interpret the pathway of community succession in the drought impacted area. SOD activity is more distinct and important on the scope of protecting membrane damage through the scavenging of ROS on exposure to drought. PMID:24914928

Low-dose carbon ion irradiation effects on DNA damage and oxidative stress in the mouse testis

NASA Astrophysics Data System (ADS)

Liu, Yang; Long, Jing; Zhang, Luwei; Zhang, Hong; Liu, Bin; Zhao, Weiping; Wu, Zhehua

2011-01-01

To investigate the effects of low-dose carbon ion irradiation on reproductive system of mice, the testes of outbred Kunming strain mice were whole-body irradiated with 0, 0.05, 0.1, 0.5 and 1 Gy, respectively. We measured DNA double-strand breaks (DNA DSBs) and oxidative stress parameters including malondialdehyde (MDA) content, superoxide dismutase (SOD) activity, and testis weight and sperm count at 12 h, 21 d and 35 d after irradiation in mouse testis. At 12 h postirradiation, a significant increase in DNA DSB level but no pronounced alterations in MDA content or SOD activity were observed in 0.5 and 1 Gy groups compared with the control group. At 21 d postirradiation, there was a significant reduction in sperm count and distinct enhancements of DSB level and MDA content in 0.5 and 1 Gy groups in comparison with control. At 35 d postirradiation, the levels of DNA DSBs and MDA, and SOD activity returned to the baseline except for the MDA content in 1 Gy (P < 0.05), while extreme falls of sperm count were still observed in 0.5 (P < 0.01) and 1 Gy (P < 0.01) groups. For the 0.05 or 0.1 Gy group, no differences were found in DNA DSB level and MDA content between control and at 12 h, 21 d and 35 d after irradiation, indicating that lower doses of carbon ion irradiation have no significant influence on spermatogenesis processes. In this study, male germ cells irradiated with over 0.5 Gy of carbon ions are difficult to repair completely marked by the sperm count. Furthermore, these data suggest that the deleterious effects may be chronic or delayed in reproductive system after whole-body exposure to acute high-dose carbon ions.

The cellular and molecular effects of the androgen receptor agonist, Cl-4AS-1, on breast cancer cells.

PubMed

Ahram, Mamoun; Mustafa, Ebtihal; Abu Hammad, Shatha; Alhudhud, Mariam; Bawadi, Randa; Tahtamouni, Lubna; Khatib, Faisal; Zihlif, Malek

2018-03-26

The androgen receptor (AR) has attracted attention in the treatment of breast cancer. Due to the undesirable side effects of AR agonists, attempts have been undertaken to develop selective AR modulators. One of these compounds is Cl-4AS-1. This study examined this compound more closely at the cellular and molecular levels. Three different breast cancer cell lines were utilized, namely the luminal MCF-7 cells, the molecular apocrine MDA-MB-453 cells, and the triple negative, basal MDA-MB-231 cells. High and significant concordance between dihydrotestosterone (DHT) and Cl-4AS-1 in regulation of gene expression in MDA-MB-453 cells was found. However, some differences were noted including the expression of AR, which was upregulated by DHT, but not Cl-4AS-1. In addition, both DHT and Cl-4AS-1 caused a similar morphological change and reorganization of the actin structure of MDA-MB-453 cells into a mesenchymal phenotype. Treatment of cells with DHT resulted in induction of proliferation of MCF-7 and MDA-MB-453 cells, but no effect was observed on the growth of MDA-MB-231 cells. On the other hand, increasing doses of Cl-4AS-1 resulted in a dose-dependent inhibition on the growth of the three cell lines. This inhibition was a result of induction of apoptosis whereby Cl-4AS-1 caused a block in entry of cells into the S-phase followed by DNA degradation. These results indicate that although Cl-4AS-1 has characteristics of classical AR agonist, it has dissimilar properties that may make it useful in treating breast cancer.

Mechanism of chimera formation during the Multiple Displacement Amplification reaction

PubMed Central

Lasken, Roger S; Stockwell, Timothy B

2007-01-01

Background Multiple Displacement Amplification (MDA) is a method used for amplifying limiting DNA sources. The high molecular weight amplified DNA is ideal for DNA library construction. While this has enabled genomic sequencing from one or a few cells of unculturable microorganisms, the process is complicated by the tendency of MDA to generate chimeric DNA rearrangements in the amplified DNA. Determining the source of the DNA rearrangements would be an important step towards reducing or eliminating them. Results Here, we characterize the major types of chimeras formed by carrying out an MDA whole genome amplification from a single E. coli cell and sequencing by the 454 Life Sciences method. Analysis of 475 chimeras revealed the predominant reaction mechanisms that create the DNA rearrangements. The highly branched DNA synthesized in MDA can assume many alternative secondary structures. DNA strands extended on an initial template can be displaced becoming available to prime on a second template creating the chimeras. Evidence supports a model in which branch migration can displace 3'-ends freeing them to prime on the new templates. More than 85% of the resulting DNA rearrangements were inverted sequences with intervening deletions that the model predicts. Intramolecular rearrangements were favored, with displaced 3'-ends reannealing to single stranded 5'-strands contained within the same branched DNA molecule. In over 70% of the chimeric junctions, the 3' termini had initiated priming at complimentary sequences of 2–21 nucleotides (nts) in the new templates. Conclusion Formation of chimeras is an important limitation to the MDA method, particularly for whole genome sequencing. Identification of the mechanism for chimera formation provides new insight into the MDA reaction and suggests methods to reduce chimeras. The 454 sequencing approach used here will provide a rapid method to assess the utility of reaction modifications. PMID:17430586

Protection against canine parvovirus type 2 infection in puppies by colostrum-derived antibodies.

PubMed

Mila, Hanna; Grellet, Aurélien; Desario, Costantina; Feugier, Alexandre; Decaro, Nicola; Buonavoglia, Canio; Chastant-Maillard, Sylvie

2014-01-01

During the first weeks of life puppies remain protected against canine parvovirus type 2 (CPV2) infection thanks to maternally derived antibodies (MDA) absorbed with colostrum after birth. The objective of the present study was to present the variability in CPV2-specific passive immune transfer and its consequences in puppies naturally exposed to the parvovirus. Seventy-nine puppies from one breeding kennel were included in the study at birth and followed until 56 d of age. Once per week the MDA titre for CPV2 specific antibodies was determined in blood. Viral excretion was also evaluated on a rectal swab by CPV2 PCR assay and puppies were weighed to determine growth rate. At 2 d of age, thirty-four out of seventy-nine puppies (43 %) had MDA ≤1:160 (designed group A) and forty-five puppies (57 %) had greater MDA titres (designed group B). The level of absorbed maternal antibodies was shown to be associated with breed size and growth rate during the first 48 h of life. The MDA level declined with age in all cases; however, the proportion of puppies with the antibody level considered as protective against CPV2 infection was significantly higher in group B compared with A from day 2 until 42. Among all puppies surviving until 56 d of age, sixty-seven out of seventy (95·7 %) underwent CPV2 infection. However, puppies from group A excreted CPV2 significantly earlier than puppies from group B. The present study demonstrates the link between passive immune transfer, in terms of level of specific MDA absorbed, and length of the protection period against parvovirus infection in weaning puppies.

Comparing Apoptosis and Necrosis Effects of Arctium Lappa Root Extract and Doxorubicin on MCF7 and MDA-MB-231 Cell Lines

PubMed Central

Ghafari, Fereshteh; Rajabi, Mohammad Reza; Mazoochi, Tahereh; Taghizadeh, Mohsen; Nikzad, Hossein; Atlasi, Mohammad Ali; Taherian, Aliakbar

2017-01-01

Objective: Breast cancer is a heterogeneous disease and very common malignancy in women worldwide. The efficacy of chemotherapy as an important part of breast cancer treatment is limited due to its side effects. While pharmaceutical companies are looking for better chemicals, research on traditional medicines that generally have fewer side effects is quite interesting. In this study, apoptosis and necrosis effect of Arctium lappa and doxorubicin was compared in MCF7, and MDA-MB-231 cell lines. Materials and Methods: MCF7 and MDA-MB-231 cells were cultured in RPMI 1640 containing 10% FBS and 100 U/ml penicillin/streptomycin. MTT assay and an annexin V/propidium iodide (AV/PI) kit were used respectively to compare the survival rate and apoptotic effects of different concentrations of doxorubicin and Arctium lappa root extract on MDA-MB-231 and MCF7 cells. Results: Arctium lappa root extract was able to reduce cell viability of the two cell lines in a dose and time dependent manner similar to doxorubicin. Flow cytometry results showed that similar to doxorubicin, Arctium Lappa root extract had a dose and time dependent apoptosis effect on both cell lines. 10µg/mL of Arctium lappa root extract and 5 µM of doxorubicin showed the highest anti-proliferative and apoptosis effect in MCF7 and MDA231 cells. Conclusion: The MCF7 (ER/PR-) and MDA-MB-231 (ER/PR+) cell lines represent two major breast cancer subtypes. The similar anti-proliferative and apoptotic effects of Arctium lappa root extract and doxorubicin (which is a conventional chemotherapy drug) on two different breast cancer cell lines strongly suggests its anticancer effects and further studies. PMID:28441789

Comparing Apoptosis and Necrosis Effects of Arctium Lappa Root Extract and Doxorubicin on MCF7 and MDA-MB-231 Cell Lines

PubMed

Ghafari, Fereshteh; Rajabi, Mohammad Reza; Mazoochi, Tahereh; Taghizadeh, Mohsen; Nikzad, Hossein; Atlasi, Mohammad Ali; Taherian, Aliakbar

2017-03-01

Objective: Breast cancer is a heterogeneous disease and very common malignancy in women worldwide. The efficacy of chemotherapy as an important part of breast cancer treatment is limited due to its side effects. While pharmaceutical companies are looking for better chemicals, research on traditional medicines that generally have fewer side effects is quite interesting. In this study, apoptosis and necrosis effect of Arctium lappa and doxorubicin was compared in MCF7, and MDA-MB-231 cell lines. Materials and Methods: MCF7 and MDA-MB-231 cells were cultured in RPMI 1640 containing 10% FBS and 100 U/ml penicillin/streptomycin. MTT assay and an annexin V/propidium iodide (AV/PI) kit were used respectively to compare the survival rate and apoptotic effects of different concentrations of doxorubicin and Arctium lappa root extract on MDA-MB-231 and MCF7 cells. Results: Arctium lappa root extract was able to reduce cell viability of the two cell lines in a dose and time dependent manner similar to doxorubicin. Flow cytometry results showed that similar to doxorubicin, Arctium Lappa root extract had a dose and time dependent apoptosis effect on both cell lines. 10μg/mL of Arctium lappa root extract and 5 μM of doxorubicin showed the highest anti-proliferative and apoptosis effect in MCF7 and MDA231 cells. Conclusion: The MCF7 (ER/PR-) and MDA-MB-231 (ER/PR+) cell lines represent two major breast cancer subtypes. The similar anti-proliferative and apoptotic effects of Arctium lappa root extract and doxorubicin (which is a conventional chemotherapy drug) on two different breast cancer cell lines strongly suggests its anticancer effects and further studies. Creative Commons Attribution License

Supersonic Retropropulsion Flight Test Concepts

NASA Technical Reports Server (NTRS)

Post, Ethan A.; Dupzyk, Ian C.; Korzun, Ashley M.; Dyakonov, Artem A.; Tanimoto, Rebekah L.; Edquist, Karl T.

2011-01-01

NASA's Exploration Technology Development and Demonstration Program has proposed plans for a series of three sub-scale flight tests at Earth for supersonic retropropulsion, a candidate decelerator technology for future, high-mass Mars missions. The first flight test in this series is intended to be a proof-of-concept test, demonstrating successful initiation and operation of supersonic retropropulsion at conditions that replicate the relevant physics of the aerodynamic-propulsive interactions expected in flight. Five sub-scale flight test article concepts, each designed for launch on sounding rockets, have been developed in consideration of this proof-of-concept flight test. Commercial, off-the-shelf components are utilized as much as possible in each concept. The design merits of the concepts are compared along with their predicted performance for a baseline trajectory. The results of a packaging study and performance-based trade studies indicate that a sounding rocket is a viable launch platform for this proof-of-concept test of supersonic retropropulsion.

Orion Pad Abort 1 GN and C Design and Development

NASA Technical Reports Server (NTRS)

Medina, Edgar A.; Stachowiak, Susan J.

2010-01-01

The first flight test of the Orion Abort Flight Test project is scheduled to launch in Spring 2010. This flight test is known as Pad Abort 1 (PA-1) and it is intended to accomplish a series of flight test objectives, including demonstrating the capability of the Launch Abort System (LAS) to propel the Crew Module (CM) to a safe distance from a launch vehicle during a pad abort. The PA-1 Flight Test Article (FTA) is actively controlled by a guidance, navigation, and control (GN&C) system for much of its flight. The purpose of this paper is to describe the design, development, and analysis of the PA-1 GN&C system. A description of the technical solutions that were developed to meet the challenge of satisfying many competing requirements is presented. A historical perspective of how the Orion LAV compares to the Apollo Launch Escape Vehicle (LEV) design will also be included.

Spectroscopic studies and thermal analysis of mononuclear metal complexes with moxifloxacin and 2,2‧-bipyridine and their effects on acute lung injury induced by hydrochloric acid in rats

NASA Astrophysics Data System (ADS)

El-Hamid, S. M. Abd; El-Demerdash, R. S.; Arafat, H. F. H.; Sadeek, S. A.

2017-12-01

The article describes the interaction of Y(III), Zr(IV), La(III), Ce(IV) and U(VI) with moxifloxacin hydrochloride and 2,2‧-bipyridine. Characterization of complexes was made by elemental analyses, molar conductivity, magnetic moment measurements and spectral measurements e.g. IR, UV-Vis., 1H NMR and mass as well as thermal analyses (TG and DTG). The molar conductivity shows that the complexes are electrolytes nature. Spectroscopic investigation of the solid complexes studied here indicate that moxifloxacin hydrochloride and 2,2‧-bipyridine are coordinated to the metal ions in a neutral bidentate manner. After complete characterization, the chemical formulae of the complexes were established. The calculated bond length and force constant, F(Udbnd O), in the uranyl complex are 1.756 Å and 637.90 Nm-1, respectively. Kinetic and thermodynamic parameters were determined using Coats-Redfern and Horowitz-Metzger equations. Establishment of hydrochloric acid that induce acute lung injury (ALI) in rats by intratracheal administration through damaging the alveolar epithelium and activation of the neutrophil and subsequent oxidative stress by increasing malondialdehyde (MDA), tumor necrosis factor (TNF-α) and neutrophil, which were confirmed by histopathological investigation while decreasing in antioxidant enzymes and lymphocytes. Whereas treatment with mixed-ligand metal complexes significantly decrease MDA, TNF-α and neutrophils and increase antioxidant and lymphocytes.

29 CFR 1910.1050 - Methylenedianiline.

Code of Federal Regulations, 2010 CFR

2010-07-01

..., transportation, distribution or sale of MDA in intact containers sealed in such a manner as to contain the MDA.... Container means any barrel, bottle, can, cylinder, drum, reaction vessel, storage tank, commercial packaging... containers, or failure of control equipment which results in an unexpected and potentially hazardous release...

Oxidative stress equilibrium during obstetric event in normal pregnancy.

PubMed

Salas-Pacheco, Jose Manuel; Lourenco-Jaramillo, Diana Lelidett; Mendez-Hernandez, Edna Madai; Sandoval-Carrillo, Ada Agustina; Hernandez Rayon, Yessica Ivonne; Llave-Leon, Osmel La; Aguilar-Duran, Marisela; Lopez-Terrones, Marcos Alonso; Barraza-Salas, Marcelo; Vazquez-Alaniz, Fernando

2017-08-01

The aim of this study was to determine malondialdehyde (MDA) concentration as an oxidative stress marker and total antioxidant capacity (TAC) in pregnancy before and after perinatal event. This study was performed on 200 healthy full-term pregnant women admitted to pregnancy resolution in Maternal-Child Hospital of Durango, Mexico. Oxidative stress and TAC were assessed through detection of lipid peroxidation by quantitation of thiobarbituric acid-reactive substances (TBARS) and TAC through ferric reducing ability of the plasma (FRAP). Our results showed increased levels of MDA after vaginal delivery (VD). TAC was also increased after obstetric event, but it did not differ between VD and caesarean section. We demonstrated that MDA concentrations are increased two hours after obstetric event, and this increase correlates with VD. The TAC was increased as a compensatory mechanism during obstetric event. Another important finding is that women receiving analgesia administration in VD, as well as dexamethasone administration in caesarean section, experienced a protector effect that decreased MDA levels.

The effect of a health communication campaign on compliance with mass drug administration for schistosomiasis control in western Kenya--the SCORE project.

PubMed

Omedo, Martin; Ogutu, Michael; Awiti, Alphonce; Musuva, Rosemary; Muchiri, Geoffrey; Montgomery, Susan P; Secor, W Evan; Mwinzi, Pauline

2014-11-01

Compliance with mass drug administration (MDA) can be affected by rumors and mistrust about the drug. Communication campaigns are an effective way to influence attitudes and health behaviors in diverse public health contexts, but there is very little documentation about experiences using health communications in schistosomiasis control programs. A qualitative study was conducted with community health workers (CHWs) as informants to explore the effect of a health communication campaign on their experiences during subsequent praziquantel MDA for schistosomiasis. Discussions were audio-recorded, transcribed verbatim, translated into English where applicable, and analyzed thematically using ATLAS.ti software. According to the CHWs, exposure to mass media messages improved awareness of the MDA, which in turn, led to better treatment compliance. Our findings suggest that communication campaigns influence health behaviors and create awareness of schistosomiasis control interventions, which may ultimately improve praziquantel MDA. © The American Society of Tropical Medicine and Hygiene.

miR-429 mediates δ-tocotrienol-induced apoptosis in triple-negative breast cancer cells by targeting XIAP

PubMed Central

Wang, Chen; Ju, Hong; Shen, Chunyan; Tong, Zhongsheng

2015-01-01

Vitamin E δ-tocotrienol has been reported to possess anticancer activity both in vitro and in vivo. However, the underlying molecular mechanisms of δ-tocotrienol induced apoptosis in triple-negative breast cancer are not fully understood. Here, we reported that microRNA-429 (miR-429) is up-regulated in two TNBC cell lines (MDA-MB-231 and MDA-MB-468), treated with δ-tocotrienol. Inhibition of miR-429 may partially rescue the apoptosis induced by δ-tocotrienol in MDA-MB-231 cells. We also showed that the forced expression of miR-429 was sufficient to lead to apoptosis in MDA-MB-231 cells. Furthermore, we identified X-linked inhibitor of apoptosis protein (XIAP) as one of miR-429’s target genes. These results suggest that the activation of miR-429 by δ-tocotrienol may be an effective approach for the prevention and treatment of triple-negative breast cancer. PMID:26629059

Mutagenic screening of diamine monomers

NASA Technical Reports Server (NTRS)

Ross, W. D.; Noble, J. E.; Gridley, J. A.; Fullenkamp, J. M.; Wininger, M. T.; Graham, J. A.

1983-01-01

The effects of phenyl ring coupling moieties, of isomeric amine positions relative to the coupling groups, and of insertion of other coupling groups on the mutagenic response of a series of dianilines were investigated using the Ames Salmonella assay. Generally, S-9 metabolic activation from Aroclor-induced rat liver was required for mutagenic expression. The range of mutagenicity of steric isomers of several dianiline series was also investigated. No mutagenicity was found for purified samples of o,o' and m,p' isomers of methylene dianiline (MDA) and diaminobenzophenone, while varying degrees of mutagenicity were found for other isomers. The mutagenicity of "benzylogs" of MDA decreased as the degree of linear separation of the m,m' anilino groups by aromatic rings increased. Methylation and two-year storage increased mutagenic response in certain isomers of MDA. However, high performance liquid chromatography indicated there was no discernible change in m,p'-MDA samples aged under varied conditions over four months. Likewise, no change in mutagenicity was found.

Plasma lipophilic antioxidants and malondialdehyde in congestive heart failure patients: relationship to disease severity.

PubMed

Polidori, Maria Cristina; Savino, Ketty; Alunni, Gianfranco; Freddio, Michela; Senin, Umberto; Sies, Helmut; Stahl, Wilhelm; Mecocci, Patrizia

2002-01-15

Plasma levels of malondialdehyde (MDA), vitamin A, and of antioxidant micronutrients including vitamin E, lutein, zeaxanthin, beta-cryptoxanthin, lycopene, and alpha- and beta-carotene were measured in 30 patients with class II and III congestive heart failure (CHF) according to the New York Heart Association (NYHA) classification and in 55 controls. Ejection fraction was evaluated by echocardiography in all patients as a measure of the emptying capacity of the heart. Plasma levels of all measured compounds were significantly lower and MDA significantly higher in patients compared to controls (p <.001). Class II NYHA patients showed significantly lower MDA levels and significantly higher levels of vitamin A, vitamin E, lutein, and lycopene than class III patients. Ejection fraction was inversely correlated with MDA levels and directly correlated with vitamin A, vitamin E, lutein, and lycopene levels in patients. The present study supports the concept that an increased consumption of vitamin-rich fruits and vegetables might help in achieving cardiovascular health.

Something from (almost) nothing: the impact of multiple displacement amplification on microbial ecology.

PubMed

Binga, Erik K; Lasken, Roger S; Neufeld, Josh D

2008-03-01

Microbial ecology is a field that applies molecular techniques to analyze genes and communities associated with a plethora of unique environments on this planet. In the past, low biomass and the predominance of a few abundant community members have impeded the application of techniques such as PCR, microarray analysis and metagenomics to complex microbial populations. In the absence of suitable cultivation methods, it was not possible to obtain DNA samples from individual microorganisms. Recently, a method called multiple displacement amplification (MDA) has been used to circumvent these limitations by amplifying DNA from microbial communities in low-biomass environments, individual cells from uncultivated microbial species and active organisms obtained through stable isotope probing incubations. This review describes the development and applications of MDA, discusses its strengths and limitations and highlights the impact of MDA on the field of microbial ecology. Whole genome amplification via MDA has increased access to the genomic DNA of uncultivated microorganisms and low-biomass environments and represents a 'power tool' in the molecular toolbox of microbial ecologists.

ECSIT bridges RIG-I-like receptors to VISA in signaling events of innate antiviral responses.

PubMed

Lei, Cao-Qi; Zhang, Yu; Li, Mi; Jiang, Li-Qun; Zhong, Bo; Kim, Yong Ho; Shu, Hong-Bing

2015-01-01

Upon binding to RNA structures from invading viruses, RIG-I and MDA5 are recruited to mitochondria to interact with VISA and initiate antiviral type I interferon (IFN) responses. How this process is mediated is less understood. In this report, we demonstrate that ECSIT is an essential scaffolding protein that mediates the association of VISA and RIG-I or MDA5. Overexpression of ECSIT potentiated virus-triggered activation of IFN-regulatory factor 3 (IRF3) and expression of IFNB1, whereas knockdown of ECSIT impaired viral infection-induced activation of IRF3 and expression of IFNB1 as well as cellular antiviral responses. Mechanistically, ECSIT was associated with VISA on mitochondria and important for bridging RIG-I and MDA5 to VISA. Our findings suggest that ECSIT mediates virus-triggered type I IFN induction by bridging RIG-I and MDA5 to the VISA complex, and provide new insights into the molecular events of innate antiviral immune responses. © 2014 S. Karger AG, Basel.

Total oxidant/antioxidant status in jaundiced newborns before and after phototherapy.

PubMed

Aycicek, Ali; Erel, Ozcan

2007-01-01

To assess the effect of phototherapy on serum oxidant and antioxidant status in hyperbilirubinemic full-term newborns. Thirty-four full-term infants from 3 to 10 days of age exposed to phototherapy were studied. The serum antioxidant status was assessed by measuring the total antioxidant capacity (TAC) and individual antioxidant components: vitamin C, uric acid, albumin, thiol contents and total bilirubin. The oxidant status was assessed by determining the total oxidant status (TOS), oxidative stress index (OSI) and individual oxidant components: malondialdehyde (MDA), and lipid hydroperoxide levels. Vitamin C, uric acid, total bilirubin and MDA concentration were significantly lower, whereas serum TOS, lipid hydroperoxide and OSI levels were significantly higher after phototherapy (p < 0.05). There were significant positive correlations between serum total bilirubin and MDA (r = 0.434, p = 0.001). Although the MDA level was reduced after phototherapy, phototherapy has a negative impact on numerous parts of the oxidant/antioxidant defense system in jaundiced full-term newborns, exposing them to potential oxidative stress.

Obesity And Laboratory Diets Affects Tissue Malondialdehyde (MDA) Levels In Obese Rats

NASA Astrophysics Data System (ADS)

Chowdhury, Parimal; Scott, Joseph; Holley, Andy; Hakkak, Reza

2010-04-01

This study was conducted to investigate the interaction of obesity and laboratory diets on tissue malondialdehyde levels in rats. Female Zucker obese and lean rats were maintained on either regular grain-based diet or purified casein diet for two weeks, orally gavaged at day 50 with 65 mg/kg DMBA and sacrificed 24 hrs later. Malondialdehyde (MDA) levels were measured in blood and harvested tissues. Data were recorded as mean ± SEM and analyzed statistically. Results show that the obese group on purified casein diet had reduction of MDA levels in the brain, duodenum, liver, lung and kidney tissues as compared to lean group, p <0.05. Obese group on grain-based diet showed significant increase in MDA levels only in the duodenum, p <0.05. We conclude that dietary intervention differentially affects the oxidative markers in obese rats. It appears that purified casein diets were more effective than grain-based diet in reduction of oxidative stress in obese rats.

A Prospective Study of Bone Tumor Response Assessment in Metastatic Breast Cancer

PubMed Central

Hayashi, Naoki; Costelloe, Colleen M.; Hamaoka, Tsuyoshi; Wei, Caimiao; Niikura, Naoki; Theriault, Richard L.; Hortobagyi, Gabriel N.; Madewell, John E.; Ueno, Naoto T.

2013-01-01

In this pilot study, we prospectively compared the response of bone metastasis assessed by our MD Anderson (MDA) bone tumor response criteria (computed tomography [CT], plain radiography [XR], and skeletal scintigraphy [SS]) with the response assessed by the World Health Organization (WHO) criteria (XR and SS). Both MDA and WHO criteria predicted progression-free survival (PFS) of patients at 6 months but not at an earlier time point. Background In our previous study, new MD Anderson (MDA) bone tumor response criteria (based on computed tomography [CT], plain radiography [XR], and skeletal scintigraphy [SS]) predicted progression-free survival (PFS) better than did World Health Organization (WHO) bone tumor response criteria (plain radiography [XR] and SS) among patients with breast cancer and bone-only metastases. In this pilot study, we tested whether MDA criteria could reveal bone metastasis response earlier than WHO criteria in patients with newly diagnosed breast cancer with osseous and measurable nonosseous metastases. Methods We prospectively analyzed bone metastasis response using each imaging modality and set of bone response criteria to distinguish progressive disease (PD) from non-PD and their association with PFS and overall survival (OS). We also compared the response of osseous metastases assessed by both criteria with the response of nonosseous measurable lesions. Results The median follow-up period was 26.7 months (range, 6.1–53.3 months) in 29 patients. PFS rates differed at 6 months based on the classification of PD or non-PD using either set of criteria (MDA, P = .002; WHO, P = .014), but these rates, as well as OS, did not differ at 3 months. Response in osseous metastases by either set of criteria did not correlate with the response in nonosseous metastases. Conclusion MDA and WHO criteria predicted PFS of patients with osseous metastases at 6 months but not at an earlier time point. We plan a well-powered study to determine the role of MDA criteria in predicting bone tumor response by incorporating 18-fluorodeoxyglucose (18F) positron emission tomography (FDG-PET)/CT to see if findings using this modality are earlier than those with WHO criteria. PMID:23098575

The diverse roles of glutathione-associated cell resistance against hypericin photodynamic therapy.

PubMed

Theodossiou, Theodossis A; Olsen, Cathrine E; Jonsson, Marte; Kubin, Andreas; Hothersall, John S; Berg, Kristian

2017-08-01

The diverse responses of different cancers to treatments such as photodynamic therapy of cancer (PDT) have fueled a growing need for reliable predictive markers for treatment outcome. In the present work we have studied the differential response of two phenotypically and genotypically different breast adenocarcinoma cell lines, MCF7 and MDA-MB-231, to hypericin PDT (HYP-PDT). MDA-MB-231 cells were 70% more sensitive to HYP PDT than MCF7 cells at LD 50 . MCF7 were found to express a substantially higher level of glutathione peroxidase (GPX4) than MDA-MB-231, while MDA-MB-231 differentially expressed glutathione-S-transferase (GSTP1), mainly used for xenobiotic detoxification. Eighty % reduction of intracellular glutathione (GSH) by buthionine sulfoximine (BSO), largely enhanced the sensitivity of the GSTP1 expressing MDA-MB-231 cells to HYP-PDT, but not in MCF7 cells. Further inhibition of the GSH reduction however by carmustine (BCNU) resulted in an enhanced sensitivity of MCF7 to HYP-PDT. HYP loading studies suggested that HYP can be a substrate of GSTP for GSH conjugation as BSO enhanced the cellular HYP accumulation by 20% in MDA-MB-231 cells, but not in MCF7 cells. Studies in solutions showed that L-cysteine can bind the GSTP substrate CDNB in the absence of GSTP. This means that the GSTP-lacking MCF7 may use L-cysteine for xenobiotic detoxification, especially during GSH synthesis inhibition, which leads to L-cysteine build-up. This was confirmed by the lowered accumulation of HYP in both cell lines in the presence of BSO and the L-cysteine source NAC. NAC reduced the sensitivity of MCF7, but not MDA-MB-231, cells to HYP PDT which is in accordance with the antioxidant effects of L-cysteine and its potential as a GSTP substrate. As a conclusion we have herein shown that the different GSH based cell defense mechanisms can be utilized as predictive markers for the outcome of PDT and as a guide for selecting optimal combination strategies. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Tangeretin inhibits the proliferation of human breast cancer cells via CYP1A1/CYP1B1 enzyme induction and CYP1A1/CYP1B1-mediated metabolism to the product 4' hydroxy tangeretin.

PubMed

Surichan, Somchaiya; Arroo, Randolph R; Tsatsakis, Aristidis M; Androutsopoulos, Vasilis P

2018-04-04

Tangeretin is a polymethoxylated flavone with multifaceted anticancer activity. In the present study, the metabolism of tangeretin was evaluated in the CYP1 expressing human breast cancer cell lines MCF7 and MDA-MB-468 and in the normal breast cell line MCF10A. Tangeretin was converted to 4' OH tangeretin by recombinant CYP1 enzymes and by CYP1 enzymes expressed in MCF7 and MDA-MB-468 cells. This metabolite was absent in MCF10A cells that did not express CYP1 enzymes. Tangeretin exhibited submicromolar IC50 (0.25 ± 0.15 μM) in MDA-MB-468 cells, whereas it was less active in MCF7 cells (39.3 ± 1.5 μM) and completely inactive in MCF10A cells (>100 μM). In MDA-MB-468 cells that were coincubated with the CYP1 inhibitor acacetin, an approximately 70-fold increase was noted in the IC50 (18 ± 1.6 μM) of tangeretin. In the presence of the CYP1 inhibitor acacetin, the conversion of tangeretin to 4' OH tangeretin was significantly reduced in MDA-MB-468 cells (2.55 ± 0.19 μM vs. 6.33 ± 0.12 μM). The mechanism of antiproliferative action involved cell cycle arrest at the G1 phase for MCF7 and MDA-MB-468 cells. Tangeretin was further shown to induce CYP1 enzyme activity and CYP1A1/CYP1B1 protein expression in MCF7 and MDA-MB-468 cells. These results suggest that tangeretin inhibits the proliferation of breast cancer cells via CYP1A1/CYP1B1-mediated metabolism to the product 4' hydroxy tangeretin. Copyright © 2018 Elsevier Ltd. All rights reserved.

Phaleria macrocarpa (Boerl.) fruit induce G0/G1 and G2/M cell cycle arrest and apoptosis through mitochondria-mediated pathway in MDA-MB-231 human breast cancer cell.

PubMed

Kavitha, Nowroji; Ein Oon, Chern; Chen, Yeng; Kanwar, Jagat R; Sasidharan, Sreenivasan

2017-04-06

Phaleria macrocarpa (Scheff) Boerl, is a well-known folk medicinal plant in Indonesia. Traditionally, P. macrocarpa has been used to control cancer, impotency, hemorrhoids, diabetes mellitus, allergies, liver and hearth disease, kidney disorders, blood diseases, acne, stroke, migraine, and various skin diseases. The purpose of this study was to determine the in situ cytotoxicity effect P. macrocarpa fruit ethyl acetate fraction (PMEAF) and the underlying molecular mechanism of cell death. MDA-MB-231 cells were incubated with PMEAF for 24h. Cell cycle and viability were examined using flow cytometry analysis. Apoptosis was determined using the Annexin V assay and also by fluorescence microscopy. Apoptosis protein profiling was detected by RayBio® Human Apoptosis Array. The AO/PI staining and flow cytometric analysis of MDA-MB-231 cells treated with PMEAF were showed apoptotic cell death. The cell cycle analysis by flow cytometry analysis revealed that the accumulation of PMEAF treated MDA-MB-231 cells in G 0 /G 1 and G 2 /M-phase of the cell cycle. Moreover, the PMEAF exert cytotoxicity by increased the ROS production in MDA-MB-231 cells consistently stimulated the loss of mitochondrial membrane potential (∆ Ψm ) and induced apoptosis cell death by activation of numerous signalling proteins. The results from apoptosis protein profiling array evidenced that PMEAF stimulated the expression of 9 pro-apoptotic proteins (Bax, Bid, caspase 3, caspase 8, cytochrome c, p21, p27, p53 and SMAC) and suppressed the 4 anti-apoptotic proteins (Bcl-2, Bcl-w, XIAP and survivin) in MDA-MB-231 cells. The results indicated that PMEAF treatment induced apoptosis in MDA-MB-231 cells through intrinsic mitochondrial related pathway with the participation of pro and anti-apoptotic proteins, caspases, G 0 /G 1 and G 2 /M-phases cell cycle arrest by p53-mediated mechanism. Copyright © 2017 Elsevier Ireland Ltd. All rights reserved.

Experiences and perspectives of community health workers from implementing treatment for schistosomiasis using the community directed intervention strategy in an informal settlement in Kisumu City, western Kenya.

PubMed

Odhiambo, Gladys O; Musuva, Rosemary M; Odiere, Maurice R; Mwinzi, Pauline N

2016-09-15

The Community Directed Intervention (CDI) strategy has been used to conduct various health interventions in Africa, including control of Neglected Tropical Diseases (NTDs). Although the CDI approach has shown good results in the control of onchocerciasis and lymphatic filariasis with respect to treatment coverage using community drug distributors, its utility in the control of schistosomiasis among urban poor is yet to be established. Using a longitudinal qualitative study, we explored the experiences, opportunities, challenges as well as recommendations of Community Health Workers (CHWs) after participation in annual mass drug administration (MDA) activities for schistosomiasis using the CDI approach in an urban setting. Unstructured open-ended group discussions were conducted with CHWs after completion of annual MDA activities. Narratives were obtained from CHWs using a digital audio recorder during the group discussions, transcribed verbatim and translated into English where applicable. Thematic decomposition of data was done using ATLAS.ti. software, and themes explored using the principle of interpretative phenomenological analysis (IPA). From the perspective of the CHWs, opportunities for implementing CDI in urban settings, included the presence of CHWs, their supervisory structures and their knowledge of intervention areas, and opportunity to integrate MDA with other health interventions. Several challenges were mentioned with regards to implementing MDA using the CDI strategy among them lack of incentives, fear of side effects, misconceptions regarding treatment and mistrust, difficulties working in unsanitary environmental conditions, insecurity, and insufficient time. A key recommendation in promoting more effective MDA using the CDI approach was allocation of more time to the exercise. Findings from this study support the feasibility of using CDI for implementing MDA for schistosomiasis in informal settlements of urban areas. Extensive community sensitization and provision of incentives may help address the aforementioned challenges associated with implementing MDA using the CDI strategy. Opportunities highlighted in this study may be of value to other programmes that may be considering the adoption of the CDI strategy for rolling out interventions in the urban setting.

Interferon-Inducible Oligoadenylate Synthetase-Like Protein Acts as an Antiviral Effector against Classical Swine Fever Virus via the MDA5-Mediated Type I Interferon-Signaling Pathway.

PubMed

Li, Lian-Feng; Yu, Jiahui; Zhang, Yuexiu; Yang, Qian; Li, Yongfeng; Zhang, Lingkai; Wang, Jinghan; Li, Su; Luo, Yuzi; Sun, Yuan; Qiu, Hua-Ji

2017-06-01

Classical swine fever virus (CSFV) is the causative agent of classical swine fever (CSF), which poses a serious threat to the global pig industry. Interferons (IFNs) and IFN-stimulated genes (ISGs) play a key role in host antiviral defense. We have previously screened the porcine 2'-5'-oligoadenylate synthetase-like protein (pOASL) as a potential anti-CSFV ISG using a reporter CSFV. This study aimed to clarify the underlying antiviral mechanism of pOASL against CSFV. We confirmed that CSFV replication was significantly suppressed in lentivirus-delivered, pOASL-overexpressing PK-15 cells, whereas silencing the expression of endogenous pOASL by small interfering RNAs markedly enhanced CSFV growth. In addition, the transcriptional level of pOASL was upregulated both in vitro and in vivo upon CSFV infection. Interestingly, the anti-CSFV effects of pOASL are independent of the canonical RNase L pathway but depend on the activation of the type I IFN response. Glutathione S -transferase pulldown and coimmunoprecipitation assays revealed that pOASL interacts with MDA5, a double-stranded RNA sensor, and further enhances MDA5-mediated type I IFN signaling. Moreover, we showed that pOASL exerts anti-CSFV effects in an MDA5-dependent manner. In conclusion, pOASL suppresses CSFV replication via the MDA5-mediated type I IFN-signaling pathway. IMPORTANCE The host innate immune response plays an important role in mounting the initial resistance to viral infection. Here, we identify the porcine 2'-5'-oligoadenylate synthetase-like protein (pOASL) as an interferon (IFN)-stimulated gene (ISG) against classical swine fever virus (CSFV). We demonstrate that the anti-CSFV effects of pOASL depend on the activation of type I IFN response. In addition, we show that pOASL, as an MDA5-interacting protein, is a coactivator of MDA5-mediated IFN induction to exert anti-CSFV actions. This work will be beneficial to the development of novel anti-CSFV strategies by targeting pOASL. Copyright © 2017 Li et al.

Maternal diets with low healthy eating index or Mediterranean diet adherence scores are associated with high cord-blood insulin levels and insulin resistance markers at birth.

PubMed

Gesteiro, E; Rodríguez Bernal, B; Bastida, S; Sánchez-Muniz, F J

2012-09-01

Few studies have used healthy eating index (HEI) and mediterranean diet adherence (MDA) scores to evaluate the diet quality during pregnancy. To determine the relationship between first trimester diet quality and insulin sensitivity/resistance biomarkers at birth. Cord-blood insulin sensitivity/resistance biomarkers of the offspring of 35 women whose diets were 'adequate' or 'inadequate' according to their HEI score (>70 or ≤ 70, respectively) and their 13-point MDA score (≥ 7 or <7, respectively). Low HEI-score diets contained less (g/1000 kcal) carbohydrates (CHO; P=0.027) and fibre (P=0.011), and more fats (P<0.001) and cholesterol (P<0.001), and contributed (percentage contribution to total energy (%En)) fewer CHO (P=0.005), more fats (P=<0.001) and saturated fatty acid (SFA; P=0.002) than their high HEI-score counterparts. Low MDA-score diets contained less (g/1000 kcal) fibre (P<0.001) and more cholesterol (P=0.05), had lower polyunsaturated fatty acids+monounsaturated fatty acid/SFA (PUFA+MUFA/SFA; P=0.05) and higher SFA/CHO (P=0.021) and ω-6/ω-3 PUFA ratios (P=0.044) than their respective counterparts. Women consuming the low HEI- or low MDA-score diets had low-fasting glycaemia (P=0.016 or P=0.025, respectively) but delivered infants with high insulinaemia (P=0.048 or P=0.017, respectively), homeostatic model assessment for insulin resistance (HOMA-IR; P=0.031 or P=0.049, respectively) and glycaemia (P=0.018 or P=0.048, respectively). The relative risk (RR) of high-neonatal glycaemia and insulinaemia were 7.6 (P=0.008) and 6.7 (P=0.017) for low vs high HEI-score groups. High HOMA-IR and high glucose RR were, respectively, 3.4 (P=0.043) and 3.9 (P=0.016) in neonates from the <7 MDA- vs ≥ 7 MDA-score group. These RRs were not affected by potential confounders. Maternal diets with low HEI- or MDA-scores during the first trimester of pregnancy negatively affect insulin resistance markers at birth.

Effects of RNA interference-mediated silencing of toll-like receptor 4 gene on proliferation and apoptosis of human breast cancer MCF-7 and MDA-MB-231 cells: An in vitro study.

PubMed

Gao, Xiao-Ling; Yang, Jiao-Jiao; Wang, Shu-Juan; Chen, Yan; Wang, Bei; Cheng, Er-Jing; Gong, Jian-Nan; Dong, Yan-Ting; Liu, Dai; Wang, Xiang-Li; Huang, Ya-Qiong; An, Dong-Dong

2018-06-22

Breast cancer is known as the most prevalent cancer in women worldwide, and has an undeniable negative impact on public health, both physically, and mentally. This study aims to investigate the effects of toll-like receptor 4 (TLR4) gene silencing on proliferation and apoptosis of human breast cancer cells to explore for a new theoretical basis for its treatment. TLR4 small interference RNA (siRNA) fragment recombinant plasmids were constructed, including TLR4 siRNA-1, TLR4 siRNA-2, and TLR4 siRNA-3. Human breast cancer MCF-7 and MDA-MB-231 cells were assigned into blank, negative control (NC), TLR4 siRNA-1, TLR4 siRNA-2, and TLR4 siRNA-3 groups. MCF-7 and MDA-MB-231 cell growth was detected by MTT assay. Apoptosis and cell cycle were determined by flow cytometry. Reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis were conducted to determine the expression of TLR4, CDK4, cyclin D1, Livin, Bcl-2, p53, c-FLIP, and caspase-3. In comparison with the NC and blank groups, the TLR4 siRNA-1, TLR4 siRNA-2, and TLR4 siRNA-3 groups showed decreased the expression of TLR4, inhibited proliferation of MCF-7 and MDA-MB-231 cells and promoted MCF-7 and MDA-MB-231 cell apoptosis, and the cells were blocked in G1 phase. In comparison with the NC and blank groups, in the TLR4 siRNA-1, TLR4 siRNA-2, and TLR4 siRNA-3 groups, siRNA-TLR4 significantly increased expression of p53 and caspase-3 in MCF-7 and MDA-MB-231 cells, while it decreased the expressions of CDK4, cyclinD1, Livin, Bal-2, and c-FLIP. The study demonstrates that TLR4 gene silencing inhibits proliferation and induces apoptosis of MCF-7 and MDA-MB-231 cells. © 2018 Wiley Periodicals, Inc.

Impact of body weight on the achievement of minimal disease activity in patients with rheumatic diseases: a systematic review and meta-analysis.

PubMed

Lupoli, Roberta; Pizzicato, Paolo; Scalera, Antonella; Ambrosino, Pasquale; Amato, Manuela; Peluso, Rosario; Di Minno, Matteo Nicola Dario

2016-12-13

In this study, we evaluated the impact of obesity and/or overweight on the achievement of minimal disease activity (MDA) in patients with psoriatic arthritis (PsA) and patients with rheumatoid arthritis (RA) receiving an anti-rheumatic treatment. Obesity can be considered a low-grade, chronic systemic inflammatory disease and some studies suggested that obese patients with rheumatic diseases exhibit a lower rate of low disease activity achievement during treatment with anti-rheumatic drugs. A systematic search was performed in major electronic databases (PubMed, Web of Science, Scopus, Embase) to identify studies reporting MDA achievement in obese and/or overweight patients with RA or PsA and in normal-weight RA or PsA control subjects. Results were expressed as Odds Ratios (ORs) with pertinent 95% Confidence Intervals (95%CIs). We included 17 studies (10 on RA and 7 on PsA) comprising a total of 6693 patients (1562 with PsA and 5131 with RA) in the analysis. The MDA achievement rate was significantly lower in obese patients than in normal-weight subjects (OR 0.447, 95% CI 0.346-0.577, p < 0.001, I 2  = 62.6%, p < 0.001). Similarly, overweight patients showed a significantly lower prevalence of MDA achievement than normal-weight subjects (OR 0.867, 95% CI 0.757-0.994, p = 0.041, I 2  = 64%, p = 0.007). Interestingly, the effect of obesity on MDA was confirmed when we separately analyzed data on patients with RA and patients with PsA. In contrast, when we evaluated the effect of overweight, our results were confirmed for PsA but not for RA. A meta-regression analysis showed that follow-up duration, age, male sex, and treatment duration are covariates significantly affecting the effect of obesity/overweight on MDA achievement. The results of our meta-analysis suggest that obesity and overweight reduce the chances to achieve MDA in patients with rheumatic diseases receiving treatment with traditional or biologic disease-modifying antirheumatic drugs.

Long-Lasting Insecticidal Nets Are Synergistic with Mass Drug Administration for Interruption of Lymphatic Filariasis Transmission in Nigeria

PubMed Central

Eigege, Abel; Miri, Emmanuel; Sallau, Adamu; Umaru, John; Mafuyai, Hayward; Chuwang, Yohanna S.; Danjuma, Goshit; Danboyi, Jacob; Adelamo, Solomon E.; Mancha, Bulus S.; Okoeguale, Bridget; Patterson, Amy E.; Rakers, Lindsay; Richards, Frank O.

2013-01-01

In central Nigeria Anopheles mosquitoes transmit malaria and lymphatic filariasis (LF). The strategy used for interrupting LF transmission in this area is annual mass drug administration (MDA) with albendazole and ivermectin, but after 8 years of MDA, entomological evaluations in sentinel villages showed continued low-grade mosquito infection rates of 0.32%. After long-lasting insecticidal net (LLIN) distribution by the national malaria program in late 2010, however, we were no longer able to detect infected vectors over a 24-month period. This is evidence that LLINs are synergistic with MDA in interrupting LF transmission. PMID:24205421

Determination of MDMA, MDEA and MDA in urine by high performance liquid chromatography with fluorescence detection.

PubMed

da Costa, José Luiz; da Matta Chasin, Alice Aparecida

2004-11-05

This paper describes the development and validation of analytical methodology for the determination of the use of MDMA, MDEA and MDA in urine. After a simple liquid extraction, the analyses were carried out on a high performance liquid chromatography (HPLC) in an octadecyl column, with fluorescence detection. The mobile phase using a sodium dodecyl sulfate ion-pairing reagent allows good separation and efficiency. The method showed good linearity and precision. Recovery was between 85 and 102% and detection limits were 10, 15 and 20 ng/ml for MDA, MDMA and MDEA, respectively. No interfering substances were detected with fluorescence detection.

Radiological and Pathological Correlation in Anti-MDA5 Antibody-positive Interstitial Lung Disease: Rapidly Progressive Perilobular Opacities and Diffuse Alveolar Damage.

PubMed

Chino, Haruka; Sekine, Akimasa; Baba, Tomohisa; Iwasawa, Tae; Okudela, Koji; Takemura, Tamiko; Itoh, Harumi; Sato, Shinji; Suzuki, Yasuo; Ogura, Takashi

2016-01-01

We herein present the first case of rapidly progressive interstitial lung disease (RP-ILD) with anti-melanoma differentiation-associated protein 5 (MDA5) antibody evaluated by surgical lung biopsy (SLB). High-resolution CT scan revealed perilobular opacities, which rapidly became thicker and formed consolidation, resulting in remarkable loss of lung volume. Specimens taken from SLB revealed membranous organization with alveolar occlusion, dilation of alveolar ducts, and sacs with collapsed alveoli, which are typical features of diffuse alveolar damage (DAD). Rapidly progressive perilobular opacities may be characteristic of RP-ILD with anti-MDA5 antibody and DAD.

Working memory span in mild cognitive impairment. Influence of processing speed and cognitive reserve.

PubMed

Facal, David; Juncos-Rabadán, Onésimo; Pereiro, Arturo X; Lojo-Seoane, Cristina

2014-04-01

Mild cognitive impairment (MCI) often includes episodic memory impairment, but can also involve other types of cognitive decline. Although previous studies have shown poorer performance of MCI patients in working memory (WM) span tasks, different MCI subgroups were not studied. In the present exploratory study, 145 participants underwent extensive cognitive evaluation, which included three different WM span tasks, and were classified into the following groups: multiple-domain amnestic MCI (mda-MCI), single-domain amnestic MCI (sda-MCI), and controls. General linear model was conducted by considering the WM span tasks as the within-subject factor; the group (mda-MCI, sda-MCI, and controls) as the inter-subject factor; and processing speed, vocabulary and age as covariates. Multiple linear regression models were also used to test the influence of processing speed, vocabulary, and other cognitive reserve (CR) proxies. Results indicate different levels of impairment of WM, with more severe impairment in mda-MCI patients. The differences were still present when processing resources and CR were controlled. Between-group differences can be understood as a manifestation of the greater severity and widespread memory impairment in mda-MCI patients and may contribute to a better understanding of continuum from normal controls to mda-MCI patients. Processing speed and CR have a limited influence on WM scores, reducing but not removing differences between groups.

Role of oxidative stress in epithelial ovarian cancer in Egyptian patients.

PubMed

Ramadan, Asmaa; Hemida, Reda; Nowara, Ahmed; Eissa, Laila A; El-Gayar, Amal M

2017-05-01

Ovarian cancer has the highest mortality rate amongst all gynecologic malignancies. 90% of the cases are epithelial ovarian cancer (EOC). Ovarian cancer associated with reduction in the serum level of antioxidants super oxide dismutase (SOD) and glutathione peroxidase (GPX) and increasing in the serum level of Malondialdehyde (MDA). To find correlation between oxidative stress and epithelial ovarian cancer. In this cross-sectional study fifty-six female patients with EOC, twenty four female patients with benign ovarian tumors and ten healthy females were included in the current research study where serum level of SOD, GPX and MDA were measured. Levels of SOD and GPX were found to be significantly higher in benign group when compared with malignant group (P1<0.05). There was a significant negative association between malignancy and each of SOD and GPX (p<0.05). While there was a significant positive association between malignancy and MDA (p<0.05). There was a significant negative correlation between tumor stage and level of SOD and GPX (p<0.05). Moreover, there was a significance positive correlation between tumor stage and MDA (p< 0.05). Patients with epithelial ovarian cancer has decreased preoperative serum level of SOD and GPX antioxidants and increased level of MDA. These findings were associated with advanced tumor stage. The study confirmed the role of oxidative stress in development of epithelial ovarian cancer.

PMCA2 silencing potentiates MDA-MB-231 breast cancer cell death initiated with the Bcl-2 inhibitor ABT-263.

PubMed

Curry, Merril; Roberts-Thomson, Sarah J; Monteith, Gregory R

2016-09-30

PMCA2 overexpression in some breast cancers suggests that this calcium pump isoform may play a role in breast pathophysiology. To investigate PMCA2 as a potential drug target for breast cancer therapy, we assessed the functional consequence of PMCA2 silencing on cell death pathways and calcium signals in the basal-like MDA-MB-231 breast cancer cell line. Silencing PMCA2 expression alone has no effect on MDA-MB-231 cell viability, however, PMCA2 silencing promotes calcium-induced cell death initiated with the calcium ionophore ionomycin. Assessment of cytoplasmic calcium responses generated with various agents including ionomycin demonstrates that in MDA-MB-231 cells, PMCA2 does not play a major role in shaping global calcium signals. We also examined the ability of PMCA2 silencing to modulate caspase-dependent cell death triggered by a Bcl-2 inhibitor that is in clinical development for the treatment of various cancers, ABT-263 (Navitoclax). Despite the lack of effect on global calcium responses, PMCA2 silencing augmented Bcl-2 inhibitor (ABT-263)-mediated MDA-MB-231 breast cancer cell death. These studies provide evidence that PMCA2 inhibitors could sensitize PMCA2-positive breast cancers to cell death initiators that work through mechanisms involving the Bcl-2 survival pathway. Copyright © 2016 Elsevier Inc. All rights reserved.

Monitoring of tumor growth and metastasis potential in MDA-MB-435s/ tk-luc human breast cancer xenografts

NASA Astrophysics Data System (ADS)

Chang, Ya-Fang; Lin, Yi-Yu; Wang, Hsin-Ell; Liu, Ren-Shen; Pang, Fei; Hwang, Jeng-Jong

2007-02-01

Molecular imaging of reporter gene expression provides a rapid, sensitive and non-invasive monitoring of tumor behaviors. In this study, we reported the establishment of a novel animal model for longitudinal examination of tumor growth kinetics and metastatic spreading in vivo. The highly metastatic human breast carcinoma MDA-MB-435s cell line was engineered to stably express herpes simplex virus type 1 thymidine kinase (HSV-1- tk) and luciferase ( luc). Both 131I-FIAU and D-luciferin were used as reporter probes. For orthotopic tumor formation, MDA-MB-435s/ tk-luc cells were implanted into the first nipple of 6-week-old female NOD/SCID mice. For metastatic study, cells were injected via the lateral tail vein. Mice-bearing MDA-MB-435s/ tk-luc tumors were scanned for tumor growth and metastatsis using Xenogen IVIS50 system. Gamma scintigraphy and whole-body autoradiography were also applied to confirm the tumor localization. The results of bioluminescence imaging as well as histopathological finding showed that tumors could be detected in femur, spine, ovary, lungs, kidney, adrenal gland, lymph nodes and muscle at 16 weeks post i.v. injection, and correlated photons could be quantified. This MDA-MB-435s/ tk-luc human breast carcinoma-bearing mouse model combined with multimodalities of molecular imaging may facilitate studies on the molecular mechanisms of cancer invasion and metastasis.

Evaluation of the Level of Zinc and Malondialdehyde in Basal Cell Carcinoma.

PubMed

Majidi, Ziba; Djalali, Mahmoud; Javanbakht, Mohammad Hasan; Fathi, Mojtaba; Zarei, Mahnaz; Foladsaz, Koorosh

2017-08-01

Basal Cell Carcinoma (BCC) is one of the most common skin cancers in the world and that use to lifestyle, increasing chemical pollutions, environmental factors and poor nutrition. The most important cause of this cancer is oxidative stress and free radicals so antioxidant activities for the body are so important. The aim of this study was to determine the variation of zinc and (Malondialdehyde) MDA in BCC patients. This study has been performed on case and control patients from 2013 to 2014. The samples were collected from cell carcinoma patients at Razi Hospital in Tehran, Iran. We evaluated the level of zinc with the use of Atomic Absorption Spectroscopy (AAS) method. Besides, we evaluated MDA with colorimetric assay. The concentration of MDA was significantly higher in case group in comparison to control group ( P =0.001). In addition, case group had lower concentration of zinc than the control group ( P =0.000). There was no correlation between MDA and body mass index (BMI) and between zinc and BMI. All the patients with BCC showed a significant MDA serum in comparison with control group. However, significant decrease in zinc serum of the patients was seen that is because of consuming zinc during oxidative stress process so topical use of zinc in the form of 2+ ions could be effective on antioxidant protection against the sun UV radiation.

Inhibitory effects of sea buckthorn procyanidins on fatty acid synthase and MDA-MB-231 cells.

PubMed

Wang, Yi; Nie, Fangyuan; Ouyang, Jian; Wang, Xiaoyan; Ma, Xiaofeng

2014-10-01

Fatty acid synthase (FAS) is overexpressed in many human cancers including breast cancer and is considered to be a promising target for therapy. Sea buckthorn has long been used to treat a variety of maladies. Here, we investigated the inhibitory effect of sea buckthorn procyanidins (SBPs) isolated from the seeds of sea buckthorn on FAS and FAS overexpressed human breast cancer MDA-MB-231 cells. The FAS activity and FAS inhibition were measured by a spectrophotometer at 340 nm of nicotinamide adenine dinucleotide phosphate (NADPH) absorption. We found that SBP potently inhibited the activity of FAS with a half-inhibitory concentration (IC50) value of 0.087 μg/ml. 3-4,5-Dimethylthiazol-2-yl-2,3-diphenyl tetrazolium bromide (MTT) assay was used to test the cell viability. SBP reduced MDA-MB-231 cell viability with an IC50 value of 37.5 μg/ml. Hoechst 33258/propidium iodide dual staining and flow cytometric analysis showed that SBP induced MDA-MB-231 cell apoptosis. SBP inhibited intracellular FAS activity with a dose-dependent manner. In addition, sodium palmitate could rescue the cell apoptosis induced by SBP. These results showed that SBP was a promising FAS inhibitor which could induce the apoptosis of MDA-MB-231 cells via inhibiting FAS. These findings suggested that SBP might be useful for preventing or treating breast cancer.

Systematic evaluation of bias in microbial community profiles induced by whole genome amplification.

PubMed

Direito, Susana O L; Zaura, Egija; Little, Miranda; Ehrenfreund, Pascale; Röling, Wilfred F M

2014-03-01

Whole genome amplification methods facilitate the detection and characterization of microbial communities in low biomass environments. We examined the extent to which the actual community structure is reliably revealed and factors contributing to bias. One widely used [multiple displacement amplification (MDA)] and one new primer-free method [primase-based whole genome amplification (pWGA)] were compared using a polymerase chain reaction (PCR)-based method as control. Pyrosequencing of an environmental sample and principal component analysis revealed that MDA impacted community profiles more strongly than pWGA and indicated that this related to species GC content, although an influence of DNA integrity could not be excluded. Subsequently, biases by species GC content, DNA integrity and fragment size were separately analysed using defined mixtures of DNA from various species. We found significantly less amplification of species with the highest GC content for MDA-based templates and, to a lesser extent, for pWGA. DNA fragmentation also interfered severely: species with more fragmented DNA were less amplified with MDA and pWGA. pWGA was unable to amplify low molecular weight DNA (< 1.5 kb), whereas MDA was inefficient. We conclude that pWGA is the most promising method for characterization of microbial communities in low-biomass environments and for currently planned astrobiological missions to Mars. © 2013 Society for Applied Microbiology and John Wiley & Sons Ltd.

Major triterpenoids in Chinese hawthorn "Crataegus pinnatifida" and their effects on cell proliferation and apoptosis induction in MDA-MB-231 cancer cells.

PubMed

Wen, Lingrong; Guo, Ruixue; You, Lijun; Abbasi, Arshad Mehmood; Li, Tong; Fu, Xiong; Liu, Rui Hai

2017-02-01

The cytotoxicity and antiproliferative effect of phytochemicals presenting in the fruits of Chinese hawthorn (Crataegus pinnatifida) were evaluated. Shanlihong (Crataegus pinnatifida Bge. var. major N.E.Br.) variety possessed significant levels of flavonoids and triterpenoids, and showed potent antiproliferative effect against HepG 2 , MCF-7 and MDA-MB- 231 human cancer cells lines. Triterpenoids-enriched fraction (S9) prepared by Semi-preparative HPLC, and its predominant ingredient ursolic acid (UA) demonstrated remarkably antiproliferative activities for all the tested cancer cell lines. DNA flow cytometric analysis showed that S9 fraction and UA significantly induced G1 arrest in MDA-MB-231 cells in a dose-dependent manner. Western blotting analysis revealed that S9 fraction and UA significantly induced PCNA, CDK4, and Cyclin D1 downregulation in MDA-MB-231 cells, followed by p21 Waf1/Cip1 up-regulation. Additionally, flow cytometer and DNA ladder assays indicated that S9 fraction and UA significantly induced MDA-MB-231 cells apoptosis. Mitochondrial death pathway was involved in this apoptosis as significantly induced caspase-9 and caspase-3 activation. These results suggested that triterpenoids-enriched fraction and UA exhibited antiproliferative activity through the cell cycle arrest and apoptosis induction, and was majorly responsible for the potent anticancer activity of Chinese hawthorn. Copyright © 2016 Elsevier Ltd. All rights reserved.

Feasibility of Biological Effective Monitoring of Chrome Electroplaters to Chromium through Analysis of Serum Malondialdehyde.

PubMed

Mozafari, P; Rezazadeh Azari, M; Shokoohi, Y; Sayadi, M

2016-10-01

Great concern about occupational exposure to chromium (Cr [VI]) has been reported due to escalated risk of lung cancer in exposed workers. Consequences of occupational exposure to Cr (VI) have been reported as oxidative stress and lung tissue damage. To investigate the feasibility of biological effect monitoring of chrome electroplaters through analysis of serum malondialdehyde (MDA). 90 workers directly involved in chrome electroplating---categorized into three equal groups based on their job as near bath workers, degreaser, and washers---and 30 workers without exposure to Cr (VI), served as the control group, were studied. Personal samples were collected and analyzed according to NIOSH method 7600. Serum MDA level was measured by HPLC using a UV detector. Median Cr (VI) exposure level was 0.38 mg/m(3) in near bath workers, 0.20 mg/m(3) in degreasers, and 0.05 mg/m(3) in washers. The median serum MDA level of three exposed groups (2.76 μmol/L) was significantly (p<0.001) higher than that in the control group (2.00 μmol/L). There was a positive correlation between electroplaters' level of exposure to Cr (VI) and their serum MDA level (Spearman's ρ 0.806, p<0.001). Serum MDA level is a good biomarker for the level of occupational exposure to Cr (VI) in electroplaters.

The Impact of Two Semiannual Treatments with Albendazole Alone on Lymphatic Filariasis and Soil-Transmitted Helminth Infections: A Community-Based Study in the Republic of Congo

PubMed Central

Pion, Sébastien D. S.; Chesnais, Cédric B.; Bopda, Jean; Louya, Frédéric; Fischer, Peter U.; Majewski, Andrew C.; Weil, Gary J.; Boussinesq, Michel; Missamou, François

2015-01-01

Implementation of mass drug administration (MDA) with ivermectin plus albendazole (ALB) for lymphatic filariasis (LF) has been delayed in central Africa because of the risk of serious adverse events in subjects with high Loa loa microfilaremia. We conducted a community trial to assess the impact of semiannual MDA with ALB (400 mg) alone on LF and soil-transmitted helminth (STH) infections in the Republic of Congo. Evaluation at 12 months showed that ALB MDA had not significantly reduced Wuchereria bancrofti antigenemia or microfilaria (mf) rates in the community (from 17.3% to 16.6% and from 5.3% to 4.2%, respectively). However, the geometric mean mf count in mf-positive subjects was reduced from 202.2 to 80.9 mf/mL (60% reduction, P = 0.01). The effect of ALB was impressive in 38 subjects who were mf-positive at baseline and retested at 12 months: 37% had total mf clearance, and individual mf densities were reduced by 73.0%. MDA also dramatically reduced the hookworm infection rate in the community from 6.5% to 0.6% (91% reduction), with less impressive effects on Ascaris and Trichuris. These preliminary results suggest that semiannual community MDA with ALB is a promising strategy for controlling LF and STH in areas with coendemic loiasis. PMID:25758650

[Development of POCT and medical digital assistant for primary medical healthcare].

PubMed

Shi, Jun; Yan, Zhuang-Zhi; Pan, Zhi-Hao

2008-01-01

In this paper, we discuss the meaning, advantages and methods of applying the point of care testing (POCT) and medical digital assistant (MDA) to primary healthcare services. We also introduce the development of the POCT and MDA based on the electronic health record(EHR) system.

Regulation of Metastatic Breast Cancer Dormancy

DTIC Science & Technology

2015-09-01

individual cell motility to disseminate and eventually extravasate into common metastatic niches such as the brain, bone and liver. Once attaining the...Engineer tagged MCF7 cells with shRNA against E-cadherin and engineer tagged MDA-MB-361 and MDA- MB-231 cells to express or prevent expression of E

Physiological Factors Analysis in Unpressurized Aircraft Cabins

NASA Astrophysics Data System (ADS)

Patrao, Luis; Zorro, Sara; Silva, Jorge

2016-11-01

Amateur and sports flight is an activity with growing numbers worldwide. However, the main cause of flight incidents and accidents is increasingly pilot error, for a number of reasons. Fatigue, sleep issues and hypoxia, among many others, are some that can be avoided, or, at least, mitigated. This article describes the analysis of psychological and physiological parameters during flight in unpressurized aircraft cabins. It relates cerebral oximetry and heart rate with altitude, as well as with flight phase. The study of those parameters might give clues on which variations represent a warning sign to the pilot, thus preventing incidents and accidents due to human factors. Results show that both cerebral oximetry and heart rate change along the flight and altitude in the alert pilot. The impaired pilot might not reveal these variations and, if this is detected, he can be warned in time.

Effect of Surface Imperfections and Excrescences on the Crossflow Instability

NASA Astrophysics Data System (ADS)

Tufts, Matthew; Duncan, Glen, Jr.; Crawford, Brian; Reed, Helen; Saric, William

2012-11-01

Presented is analysis of the planned SWIFTER experiment to be flown on Texas A&M University's O-2A aircraft. Simultaneous control of the crossflow and streamwise boundary-layer instabilities is a challenge for laminar flow control on swept wings. Solving this problem is an active area of research, with a specific need to quantify the effect of surface imperfections and outer mold line excrescences on crossflow instabilities. The SWIFTER test article is a modification of a prior-tested flight model, with the additional capability of creating controlled excrescences in flight. Using a finite-element Navier-Stokes solution and a spectrally accurate boundary-layer solver, coupled with linear and nonlinear stability analyses, we show that the flow field over the test article is well suited to this study. Results are compared with flight data. The work is supported by the Air Force Research Laboratory through General Dynamics Information Technology, Inc. under sub Agreement No USAF-3446-11-50-SC-01 and the Texas A&M Supercomputing Facility.

Remotely piloted vehicles. Citations from the International Aerospace abstracts data base

NASA Technical Reports Server (NTRS)

Mauk, S. C.

1980-01-01

These citations from the international literature cover various aspects of remotely piloted vehicles. Included are articles concerning aircraft design, flight tests, aircraft control, cost effectiveness, automatic flight control, automatic pilots, and data links. Civil aviation applications are included, although military uses of remotely piloted vehicles are stressed. This updated bibliography contains 224 citations, 43 of which are new additions to the previous edition.

Calcium and bone metabolism during space flight

NASA Technical Reports Server (NTRS)

Smith, Scott M.; Heer, Martina

2002-01-01

Weightlessness induces bone loss. Understanding the nature of this loss and developing means to counteract it are significant challenges to potential human exploration missions. This article reviews the existing information from studies of bone and calcium metabolism conducted during space flight. It also highlights areas where nutrition may play a specific role in this bone loss, and where countermeasures may be developed to mitigate that loss.

HIFIRE Flight 2 Overview and Status Update 2011

NASA Technical Reports Server (NTRS)

Jackson, Kevin R.; Gruber, Mark R.; Buccellato, Salvatore

2011-01-01

A collaborative international effort, the Hypersonic International Flight Research Experimentation (HIFiRE) Program aims to study basic hypersonic phenomena through flight experimentation. HIFiRE Flight 2 teams the United States Air Force Research Lab (AFRL), NASA, and the Australian Defence Science and Technology Organisation (DSTO). Flight 2 will develop an alternative test technique for acquiring high enthalpy scramjet flight test data, allowing exploration of accelerating hydrocarbon-fueled scramjet performance and dual-to-scram mode transition up to and beyond Mach 8 flight. The generic scramjet flowpath is research quality and the test fuel is a simple surrogate for an endothermically cracked liquid hydrocarbon fuel. HIFiRE Flight 2 will be a first of its kind in contribution to scramjets. The HIFiRE program builds upon the HyShot and HYCAUSE programs and aims to leverage the low-cost flight test technique developed in those programs. It will explore suppressed trajectories of a sounding rocket propelled test article and their utility in studying ramjet-scramjet mode transition and flame extinction limits research. This paper describes the overall scramjet flight test experiment mission goals and objectives, flight test approach and strategy, ground test and analysis summary, development status and project schedule. A successful launch and operation will present to the scramjet community valuable flight test data in addition to a new tool, and vehicle, with which to explore high enthalpy scramjet technologies.

SLS Engine Section Test Article Moves From NASA Barge Pegasus To Test Stand at NASA’s Marshall Space Flight Center

NASA Image and Video Library

2017-05-18

The NASA barge Pegasus made its first trip to NASA’s Marshall Space Flight Center in Huntsville, Alabama on May 15. It arrived carrying the first piece of Space Launch System hardware built at NASA's Michoud Assembly Facility in New Orleans. The barge left Michoud on April 28 with the core stage engine section test article, traveling 1,240 miles by river to Marshall. The rocket's engine section is the bottom of the core stage and houses the four RS-25 engines. The engine section test article was moved from the barge to Marshall’s Building 4619 where it will be tested. The bottom part of the test article is structurally the same as the engine section that will be flown as part of the SLS core stage. The shiny metal top part simulates the rocket's liquid hydrogen tank, which is the fuel tank that joins to the engine section. The test article will endure tests that pull, push, and bend it, subjecting it to millions of pounds of force. This ensures the structure can withstand the incredible stresses produced by the 8.8 million pounds of thrust during launch and ascent.

Laminar flow control leading edge glove flight test article development

NASA Technical Reports Server (NTRS)

Pearce, W. E.; Mcnay, D. E.; Thelander, J. A.

1984-01-01

A laminar flow control (LFC) flight test article was designed and fabricated to fit into the right leading edge of a JetStar aircraft. The article was designed to attach to the front spar and fill in approx. 70 inches of the leading edge that are normally occupied by the large slipper fuel tank. The outer contour of the test article was constrained to align with an external fairing aft of the front spar which provided a surface pressure distribution over the test region representative of an LFC airfoil. LFC is achieved by applying suction through a finely perforated surface, which removes a small fraction of the boundary layer. The LFC test article has a retractable high lift shield to protect the laminar surface from contamination by airborne debris during takeoff and low altitude operation. The shield is designed to intercept insects and other particles that could otherwise impact the leading edge. Because the shield will intercept freezing rain and ice, a oozing glycol ice protection system is installed on the shield leading edge. In addition to the shield, a liquid freezing point depressant can be sprayed on the back of the shield.

Single-cell genomic sequencing using Multiple Displacement Amplification.

PubMed

Lasken, Roger S

2007-10-01

Single microbial cells can now be sequenced using DNA amplified by the Multiple Displacement Amplification (MDA) reaction. The few femtograms of DNA in a bacterium are amplified into micrograms of high molecular weight DNA suitable for DNA library construction and Sanger sequencing. The MDA-generated DNA also performs well when used directly as template for pyrosequencing by the 454 Life Sciences method. While MDA from single cells loses some of the genomic sequence, this approach will greatly accelerate the pace of sequencing from uncultured microbes. The genetically linked sequences from single cells are also a powerful tool to be used in guiding genomic assembly of shotgun sequences of multiple organisms from environmental DNA extracts (metagenomic sequences).

Adaptive integral dynamic surface control of a hypersonic flight vehicle

NASA Astrophysics Data System (ADS)

Aslam Butt, Waseem; Yan, Lin; Amezquita S., Kendrick

2015-07-01

In this article, non-linear adaptive dynamic surface air speed and flight path angle control designs are presented for the longitudinal dynamics of a flexible hypersonic flight vehicle. The tracking performance of the control design is enhanced by introducing a novel integral term that caters to avoiding a large initial control signal. To ensure feasibility, the design scheme incorporates magnitude and rate constraints on the actuator commands. The uncertain non-linear functions are approximated by an efficient use of the neural networks to reduce the computational load. A detailed stability analysis shows that all closed-loop signals are uniformly ultimately bounded and the ? tracking performance is guaranteed. The robustness of the design scheme is verified through numerical simulations of the flexible flight vehicle model.

Full-scale Transport Controlled Impact Demonstration Program

NASA Technical Reports Server (NTRS)

1987-01-01

The Federal Aviation Administration (FAA) and NASA conducted a full-scale air-to-surface impact-survivable impact demonstration with a remotely piloted transport aircraft on 1 December 1984, at Edwards Air Force Base, California. The test article consisted of experiments, special equipment, and supporting systems, such as antimisting kerosene (AMK), crashworthiness structural/restraint, analytical modeling, cabin fire safety, flight data recorders, post-impact investigation, instrumentation/data acquisition systems, remotely piloted vehicle/flight control systems, range and flight safety provisions, etc. This report describes the aircraft, experiments, systems, activities, and events which lead up to the Controlled Impact Demonstration (CID). An overview of the final unmanned remote control flight and sequence of impact events are delineated. Preliminary post CID observations are presented.

Report on research and technology-FY 1981

NASA Technical Reports Server (NTRS)

1981-01-01

More than 65 technical reports, papers, and articles published by personnel and contractors at the Dryden Flight Research Center are listed. Activities performed for the Offices of Aeronautics and Space Technology, Space and Terrestrial Applications, Space Transportation Systems, and Space Tracking and Data Systems are summarized. Preliminary stability and control derivatives were determined for the shuttle orbiter at hypersonic speeds from the data obtained at reentry. The shuttle tile tests, spin research vehicle nose shapes flight investigations, envelope expansion flights for the Ames tilt rotor research aircraft, and the AD-1 oblique wing programs were completed as well as the KC-135 winglet program.

Simulated airline service experience with laminar-flow control leading-edge systems

NASA Technical Reports Server (NTRS)

Maddalon, Dal V.; Fisher, David F.; Jennett, Lisa A.; Fischer, Michael C.

1987-01-01

The first JetStar leading edge flight test was made November 30, 1983. The JetStar was flown for more than 3 years. The titanium leading edge test articles today remain in virtually the same condition as they were in on that first flight. No degradation of laminar flow performance has occurred as a result of service. The JetStar simulated airline service flights have demonstrated that effective, practical leading edge systems are available for future commercial transports. Specific conclusions based on the results of the simulated airline service test program are summarized.

Flight of the dragonflies and damselflies.

PubMed

Bomphrey, Richard J; Nakata, Toshiyuki; Henningsson, Per; Lin, Huai-Ti

2016-09-26

This work is a synthesis of our current understanding of the mechanics, aerodynamics and visually mediated control of dragonfly and damselfly flight, with the addition of new experimental and computational data in several key areas. These are: the diversity of dragonfly wing morphologies, the aerodynamics of gliding flight, force generation in flapping flight, aerodynamic efficiency, comparative flight performance and pursuit strategies during predatory and territorial flights. New data are set in context by brief reviews covering anatomy at several scales, insect aerodynamics, neuromechanics and behaviour. We achieve a new perspective by means of a diverse range of techniques, including laser-line mapping of wing topographies, computational fluid dynamics simulations of finely detailed wing geometries, quantitative imaging using particle image velocimetry of on-wing and wake flow patterns, classical aerodynamic theory, photography in the field, infrared motion capture and multi-camera optical tracking of free flight trajectories in laboratory environments. Our comprehensive approach enables a novel synthesis of datasets and subfields that integrates many aspects of flight from the neurobiology of the compound eye, through the aeromechanical interface with the surrounding fluid, to flight performance under cruising and higher-energy behavioural modes.This article is part of the themed issue 'Moving in a moving medium: new perspectives on flight'. © 2016 The Authors.

78 FR 6350 - The Standard on 4,4′-Methylenedianiline for General Industry; Extension of the Office of...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-30

... employers must perform initial, periodic, and additional exposure monitoring; notify each worker in writing of their results as soon as possible but no longer than 5 days after receiving exposure monitoring... products containing MDA, including containers used to store MDA-contaminated protective clothing and...

A well-refined in vitro model derived from human embryonic stem cell for screening phytochemicals with midbrain dopaminergic differentiation-boosting potential for improving Parkinson's disease.

PubMed

Hsieh, Wen-Ting; Chiang, Been-Huang

2014-07-09

Stimulation of endogenous neurogenesis is a potential approach to compensate for loss of dopaminergic neurons of substantia nigra compacta nigra (SNpc) in patients with Parkinson's disease (PD). This objective was to establish an in vitro model by differentiating pluripotent human embryonic stem cells (hESCs) into midbrain dopaminergic (mDA) neurons for screening phytochemicals with mDA neurogenesis-boosting potentials. Consequently, a five-stage differentiation process was developed. The derived cells expressed many mDA markers including tyrosine hydroxylase (TH), β-III tubulin, and dopamine transporter (DAT). The voltage-gated ion channels and dopamine release were also examined for verifying neuron function, and the dopamine receptor agonists bromocriptine and 7-hydroxy-2-(dipropylamino)tetralin (7-OH-DPAT) were used to validate our model. Then, several potential phytochemicals including green tea catechins and ginsenosides were tested using the model. Finally, ginsenoside Rb1 was identified as the most potent phytochemical which is capable of upregulating neurotrophin expression and inducing mDA differentiation.

Serum telomerase levels in smokers and smokeless tobacco users as Maras powder.

PubMed

Bozkuş, Fulsen; Atilla, Nurhan; Şimşek, Seçil; Kurutaş, Ergül; Samur, Anıl; Arpağ, Hüseyin; Kahraman, Hasan

2017-09-01

To the best of our knowledge, no previous study regarding the serum telomerase levels in Maras powder users (MPUs) has been founded. The aim of the current study was to investigate serum telomerase levels in smokers and MPUs. The study was carried out with 98 patients (36 MPUs, 32 smokers and 30 non-smokers). Blood samples were collected, and after having measured the serum telomerase and malondialdehyde (MDA) levels of the patients, comparison were made between the groups. It has been observed that the serum telomerase and MDA levels of smokers (p< 0.001) and MPUs (p< 0.001) were significantly higher compared to those of the non-smoker control subjects. In addition, the levels of serum telomerase and MDA were observed to be higher in the MPU group compared to those of the smoker group (p< 0.001). The levels of serum telomerase and MDA were observed to be higher among MPUs and smokers. In this context, it may be useful to further measure and assess telomerase activity in such patients in order to better determine the harmful effects associated with these habits.

Protective mechanisms against oxidative stress and angiopathy in young patients with diabetes type 1 (DM1).

PubMed

Koutroumani, Nikolitsa; Partsalaki, Ioanna; Lamari, Fotini; Dettoraki, Athina; Gil, Andrea Paola Rojas; Karvela, Alexia; Kostopoulou, Eirini; Spiliotis, Bessie E

2013-01-01

Advanced glycation end-products (AGEs) via their receptor, RAGE, are involved in diabetic angiopathy. Soluble RAGE, an inhibitor of this axis, is formed by enzymatic catalysis (sRAGE) or alternative splicing (esRAGE). Malondialdehyde (MDA) is an oxidative stress marker, and ferric reducing ability of plasma (FRAP) is an anti-oxidant capacity marker. In isolated mononuclear blood cells from 110 DM1-patients (P) and 124 controls (C) (4-29 years) RAGE mRNA (g) and protein expression (pe) were measured by RT-PCR and Western immunoblotting, respectively. Plasma levels of CML (AGEs) and sRAGE were measured by ELISA, MDA by flurometry and FRAP according to 'Benzie and Strain'. P showed: (i) higher g of RAGE, especially in p>13 years of age and >5 years DM1, (ii) increased pe of esRAGE in DM1>5 years and (iii) increased FRAP and MDA. The increased esRAGE and FRAP with increased levels of CML and MDA possibly reflects a protective response against the formation of diabetic complications in these young diabetic patients.

Effects of Cu(2+) and Zn(2+) on growth and physiological characteristics of green algae, Cladophora.

PubMed

Cao, De-ju; Xie, Pan-pan; Deng, Juan-wei; Zhang, Hui-min; Ma, Ru-xiao; Liu, Cheng; Liu, Ren-jing; Liang, Yue-gan; Li, Hao; Shi, Xiao-dong

2015-11-01

Effects of various concentrations of Cu(2+) and Zn(2+) (0.0, 0.1, 0.25, 0.5, or 1.0 mg/L) on the growth, malondialdehyde (MDA), the intracellular calcium, and physiological characteristics of green algae, Cladophora, were investigated. Low Zn(2+) concentrations accelerated the growth of Cladophora, whereas Zn(2+) concentration increases to 0.25 mg/L inhibited its growth. Cu(2+) greatly influences Cladophora growth. The photosynthesis of Cladophora decreased under Zn(2+) and Cu(2+) stress. Cu(2+) and Zn(2+) treatment affected the content of total soluble sugar in Cladophora and has small increases in its protein content. Zn(2+) induced the intracellular calcium release, and copper induced the intracellular calcium increases in Cladophora. Exposure to Cu(2+) and Zn(2+) induces MDA in Cladophora. The stress concent of Cu(2+) was strictly correlated with the total soluble sugar content, Chla+Chlb, and MDA in Cladophora, and the stress concent of Zn(2+) was strictly correlated with the relative growth rate (RGR) and MDA of Cladophora.

[CONTENT OF OXIDATIVE STRESS MARKERS IN BLOOD PLASMA UNDER THE ACTION OF EXTRACTS OF GRATIOLA OFFICINALIS L., HELICHRYSUM ARENARIUM (L.) MOENCH, AND ANTHOCYANIN FORMS OF ZEA MAYS L].

PubMed

Durnova, N A; Afanas'eva, G A; Kurchatova, M N; Zaraeva, N V; Golikov, A G; Bucharskaya, A B; Golikov, A G; Bucharskaya, A B; Plastun, V O; Andreeva, N V

2015-01-01

The effect of aqueous solutions of dry ethanol extracts of Gratiola officinalis L., Helichrysum arenarium (L.) Moench, and anthocyanin forms of Zea mays L. on the dioxidin-induced lipid peroxidation in blood has been studied on rats. It is established that all these extracts are capable of reducing the amount of avera- ge-mass (AM) molecules and malonic dialdehyde (MDA) in rat blood plasma. The extract of Gratiola officinalis L. reduces the concentration of AM and MDA moleules by 43%. The extract of Helichrysum arenarium (L.) Moench reduces the concentration of AM molecules on the average by 18.66% (within 9.22 -34.81%) and MDA by 49.36% (within 34.12-79.75%). The Extract of anthocyanin forms of Zea mays L. does not reduce the concentration of AM mo- lecules, but reduces the amount of MDA in the blood of rats on average by 27.88% (within 21.58-37.82%) (p < 0.01).