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Sample records for demonstrated reduced activation

  1. Demonstration of Active Combustion Control

    Science.gov (United States)

    Lovett, Jeffrey A.; Teerlinck, Karen A.; Cohen, Jeffrey M.

    2008-01-01

    The primary objective of this effort was to demonstrate active control of combustion instabilities in a direct-injection gas turbine combustor that accurately simulates engine operating conditions and reproduces an engine-type instability. This report documents the second phase of a two-phase effort. The first phase involved the analysis of an instability observed in a developmental aeroengine and the design of a single-nozzle test rig to replicate that phenomenon. This was successfully completed in 2001 and is documented in the Phase I report. This second phase was directed toward demonstration of active control strategies to mitigate this instability and thereby demonstrate the viability of active control for aircraft engine combustors. This involved development of high-speed actuator technology, testing and analysis of how the actuation system was integrated with the combustion system, control algorithm development, and demonstration testing in the single-nozzle test rig. A 30 percent reduction in the amplitude of the high-frequency (570 Hz) instability was achieved using actuation systems and control algorithms developed within this effort. Even larger reductions were shown with a low-frequency (270 Hz) instability. This represents a unique achievement in the development and practical demonstration of active combustion control systems for gas turbine applications.

  2. Studying the effectiveness of activated carbon R95 respirators in reducing the inhalation of combustion by-products in Hanoi, Vietnam: a demonstration study

    Directory of Open Access Journals (Sweden)

    Wertheim Heiman FL

    2012-09-01

    Full Text Available Abstract Background Urban air pollution is an increasing health problem, particularly in Asia, where the combustion of fossil fuels has increased rapidly as a result of industrialization and socio-economic development. The adverse health impacts of urban air pollution are well established, but less is known about effective intervention strategies. In this demonstration study we set out to establish methods to assess whether wearing an R95 activated carbon respirator could reduce intake of polycyclic aromatic hydrocarbons (PAH in street workers in Hanoi, Vietnam. Methods In this demonstration study we performed a cross-over study in which non-smoking participants that worked at least 4 hours per day on the street in Hanoi were randomly allocated to specific respirator wearing sequences for a duration of 2 weeks. Urines were collected after each period, i.e. twice per week, at the end of the working day to measure hydroxy PAHs (OH-PAH using gas chromatography/high resolution mass spectrometry. The primary endpoint was the urinary concentration of 1-hydroxypyrene (1-OHP. Results Forty-four participants (54.5% male, median age 40 years were enrolled with the majority being motorbike taxi drivers (38.6% or street vendors (34.1%. The baseline creatinine corrected urinary level for 1-OHP was much higher than other international comparisons: 1020 ng/g creatinine (IQR: 604–1551. Wearing a R95 mask had no significant effect on 1-OHP levels: estimated multiplicative effect 1.0 (95% CI: 0.92-1.09 or other OH-PAHs, except 1-hydroxynaphthalene (1-OHN: 0.86 (95% CI: 0.11-0.96. Conclusions High levels of urine OH-PAHs were found in Hanoi street workers. No effect was seen on urine OH-PAH levels by wearing R95 particulate respirators in an area of high urban air pollution, except for 1-OHN. A lack of effect may be de to gaseous phase PAHs that were not filtered efficiently by the respirator. The high levels of urinary OH-PAHs found, urges for effective

  3. Field tests demonstrating reduced activity of ivermectin and moxidectin against small strongyles in horses on 14 farms in Central Kentucky in 2007-2009.

    Science.gov (United States)

    Lyons, Eugene T; Tolliver, Sharon C; Collins, Sandra S; Ionita, Mariana; Kuzmina, Tetiana A; Rossano, Mary

    2011-02-01

    Efficacy of ivermectin (IVM) and moxidectin (MOX) against small strongyles was evaluated in horses (n=363) in field tests on 14 farms in Central Kentucky between 2007 and 2009. Most of the horses were yearlings but a few were weanlings and mares. The number of horses treated with IVM was 255 and those treated with MOX was 108. Horses on six farms were allotted into two groups. One group was treated with each of the two drugs, whereas horses on the other eight farms were treated with only one of the two drugs--IVM on six farms and MOX on two farms. Strongyle eggs per gram of feces (EPGs) compared to initial use of IVM and MOX returned almost twice as quickly after treatment of horses on all of the farms. IVM has been used much more extensively in this geographical area than MOX. Reduced activity of MOX was evident even on farms with rare or no apparent previous use of MOX but with probable extensive use of IVM.

  4. Making Waves: Seismic Waves Activities and Demonstrations

    Science.gov (United States)

    Braile, S. J.; Braile, L. W.

    2011-12-01

    The nature and propagation of seismic waves are fundamental concepts necessary for understanding the exploration of Earth's interior structure and properties, plate tectonics, earthquakes, and seismic hazards. Investigating seismic waves is also an engaging approach to learning basic principles of the physics of waves and wave propagation. Several effective educational activities and demonstrations are available for teaching about seismic waves, including the stretching of a spring to demonstrate elasticity; slinky wave propagation activities for compressional, shear, Rayleigh and Love waves; the human wave activity to demonstrate P- and S- waves in solids and liquids; waves in water in a simple wave tank; seismic wave computer animations; simple shake table demonstrations of model building responses to seismic waves to illustrate earthquake damage to structures; processing and analysis of seismograms using free and easy to use software; and seismic wave simulation software for viewing wave propagation in a spherical Earth. The use of multiple methods for teaching about seismic waves is useful because it provides reinforcement of the fundamental concepts, is adaptable to variable classroom situations and diverse learning styles, and allows one or more methods to be used for authentic assessment. The methods described here have been used effectively with a broad range of audiences, including K-12 students and teachers, undergraduate students in introductory geosciences courses, and geosciences majors.

  5. Guidance manual for conducting technology demonstration activities

    Energy Technology Data Exchange (ETDEWEB)

    Jolley, Robert L.; Morris, Michael I.; Singh, Suman P.N.

    1991-12-01

    This demonstration guidance manual has been prepared to assist Martin Marietta Energy Systems, Inc. (Energy Systems), staff in conducting demonstrations. It is prepared in checklist style to facilitate its use and assumes that Energy Systems personnel have project management responsibility. In addition to a detailed step-by-step listing of procedural considerations, a general checklist, logic flow diagram, and several examples of necessary plans are included to assist the user in developing an understanding of the many complex activities required to manage technology demonstrations. Demonstrations are pilot-scale applications of often innovative technologies to determine the commercial viability of the technologies to perform their designed function. Demonstrations are generally conducted on well-defined problems for which existing technologies or processes are less than satisfactory in terms of effectiveness, cost, and/or regulatory compliance. Critically important issues in demonstration management include, but are not limited to, such factors as communications with line and matrix management and with the US Department of Energy (DOE) and Energy Systems staff responsible for management oversight, budgetary and schedule requirements, regulatory compliance, and safety.

  6. An Undergraduate Laboratory Activity Demonstrating Bacteriophage Specificity

    Directory of Open Access Journals (Sweden)

    Mary E. Allen

    2013-02-01

    Full Text Available Bacteriophage are among the most diverse and numerous microbes inhabiting our planet. Yet many laboratory activities fail to engage students in meaningful exploration of their diversity, unique characteristics, and abundance. In this curriculum activity students use a standard plaque assay to enumerate bacteriophage particles from a natural sample and use the scientific method to address questions about host specificity and diversity. A raw primary sewage sample is enriched for bacteriophage using hosts in the family Enterobacteriaceae. Students hypothesize about host specificity and use quantitative data (serial dilution and plaque assay to test their hypotheses. Combined class data also help them answer questions about phage diversity. The exercise was field tested with a class of 47 students using pre- and posttests. For all learning outcomes posttest scores were higher than pretest scores at or below p = 0.01. Average individualized learning gain (G was also calculated for each learning outcome. Students’ use of scientific language in reference to bacteriophage and host interaction significantly improved (p = 0.002; G = 0.50. Improved means of expression helped students construct better hypotheses on phage host specificity (G = 0.31, p = 0.01 and to explain the plaque assay method (G = 0.33, p = 0.002. At the end of the exercise students also demonstrated improved knowledge and understanding of phage specificity as related to phage therapy in humans (p < 0.001; G = 51.

  7. Simple Activity Demonstrates Wind Energy Principles

    Science.gov (United States)

    Roman, Harry T.

    2012-01-01

    Wind energy is an exciting and clean energy option often described as the fastest-growing energy system on the planet. With some simple materials, teachers can easily demonstrate its key principles in their classroom. (Contains 1 figure and 2 tables.)

  8. Experimental active control results from the SPICES smart structure demonstrations

    Science.gov (United States)

    Flamm, David S.; Toth, G. K.; Chou, Kenneth C.; Heck, Larry P.; Nowlin, William C.; Titterton, Paul J., Sr.

    1996-05-01

    The final demonstrations of the ARPA SPICES (Synthesis and Processing of Intelligent Cost Effective Structures) program test the control of two active vibration mounts manufactured from composites with embedded actuators and sensors. Both mount demonstrations address wide band control problems for real disturbances, one at low frequency and the other at high frequency. The control systems for both are two-level hierarchies, with an inner active damping augmentation loop and an outer vibration control loop. We first review the control design requirements for the demonstration and summarize our control design approach. Then we focus on presenting the experimental results of the final demonstrations. For the low frequency demonstration, two alternative control approaches were demonstrated, one involving finite impulse response modeling and the other state space modeling. For the high frequency demonstration only the finite impulse response modeling approach was used because of computational limitations due to the complex system dynamics.

  9. Promoter proximal polyadenylation sites reduce transcription activity

    DEFF Research Database (Denmark)

    Andersen, Pia Kjølhede; Lykke-Andersen, Søren; Jensen, Torben Heick

    2012-01-01

    Gene expression relies on the functional communication between mRNA processing and transcription. We previously described the negative impact of a point-mutated splice donor (SD) site on transcription. Here we demonstrate that this mutation activates an upstream cryptic polyadenylation (CpA) site...... RNA polymerase II-transcribed genes use specialized termination mechanisms to maintain high transcription levels.......Gene expression relies on the functional communication between mRNA processing and transcription. We previously described the negative impact of a point-mutated splice donor (SD) site on transcription. Here we demonstrate that this mutation activates an upstream cryptic polyadenylation (CpA) site......, which in turn causes reduced transcription. Functional depletion of U1 snRNP in the context of the wild-type SD triggers the same CpA event accompanied by decreased RNA levels. Thus, in accordance with recent findings, U1 snRNP can shield premature pA sites. The negative impact of unshielded pA sites...

  10. Characterization of Streptococcus oligofermentans sucrose metabolism demonstrates reduced pyruvic and lactic acid production

    Institute of Scientific and Technical Information of China (English)

    BAO Xu-dong; YUE Lin; GAO Xue-jun

    2011-01-01

    Background Streptococcus (S.) oligofermentans is a newly identified bacteria with a yet to be defined mechanism of sucrose metabolism that results in acid production.This study aimed to investigate the biochemical mechanisms of S.oligoferm-entans glucose metaolism.Methods The S.oligofermentans LMG21532,Lactobacillus (L.) fermentum 38 and the S.S.mutans UA140 were used to characterize sucrose metabolism by measuring lactate dehydrogenase (LDH) activity and lactic acid production.Continuous dynamics and high performance capillary electrophoresis were used to determine LDH activity and lactic acid production,respectively,from bacteria collected at 0,10 and 30 minutes after cultured in 10% sucrose.Results These analyses demonstrated that LDH activity of the three bacterial strains examined remained stable but significantly different throughout the sucrose fermentation process.The S.o/igofermentans LDH activity ((0.61±0.05) U/mg) was significantly lower than that of L.fermentum ((52.91+8.97) U/mg).In addition,the S.oligofermentans total lactate production ((0.048±0.021) mmol/L) was also significantly lower than that of L.fermentum ((0.958±0.201) mmol/L).Although the S.oligofermentans LDH production was almost double of that produced by S.mutans ((0.32±0.07) U/mg),lactic acid production was approximately one sixth that of S.mutans ((0.296±0.058) mmol/L).Additional tests examining pyruvic acid production (the LDH substrate) demonstrated that lactic acid concentrations correlated with pyruvic acid production.That is,pyruvic acid production by S.oligofermentans was undetectable following sucrose incubation,however,(0.074±t0.024) and (0.175±0.098) mmol/L pyruvic acid were produced by S.mutans and L.fermentum,respectively.Conclusion S.oligofermentans is incapable of fermenting carbohydrates to produce enough pyruvic acid,which results in reduced lactic acid production.

  11. 76 FR 10038 - Determination That a Demonstration Needle Exchange Program Would be Effective in Reducing Drug...

    Science.gov (United States)

    2011-02-23

    ... HUMAN SERVICES Determination That a Demonstration Needle Exchange Program Would be Effective in Reducing... agent for acquired immune deficiency syndrome. This determination reflects the scientific evidence supporting the important public health benefit of SSPs, and is necessary to meet the statutory...

  12. Active structures to reduce torsional vibrations

    Science.gov (United States)

    Matthias, M.; Schlote, D.; Atzrodt, H.

    2013-03-01

    This paper describes the development of different active measures to reduce torsional vibrations in power trains. The measures are based on concepts developed for active mounts to reduce the transmission of structure-borne sound. To show the potential of these active measures and investigate their mode of operation to influence torsional vibrations, numerical simulations of powertrains with different active measures were done. First experimental results from tests on an experimental (reduced size) power train were used to align the numerical models. The work was done within the project 'LOEWE-Zentrum AdRIA: Adaptronik - Research, Innovation, Application' funded by the German federal state of Hessen, and the Project AKTos: 'Active control of torsional vibrations by coupling elements' placed in the research Framework program 'Navigation and Maritime Technology for the 21st Century' funded by the German Federal Ministry of Economics and Technology.

  13. Sarcoidosis Th17 Cells are ESAT-6 Antigen Specific but Demonstrate Reduced IFN-γ Expression

    Science.gov (United States)

    Richmond, Bradley W.; Ploetze, Kristen; Isom, Joan; Chambers-Harris, Isfahan; Braun, Nicole A.; Taylor, Thyneice; Abraham, Susamma; Mageto, Yolanda; Culver, Dan A.; Oswald-Richter, Kyra A.; Drake, Wonder P.

    2013-01-01

    Rationale Sarcoidosis is a granulomatous disease of unknown etiology. Many patients with sarcoidosis demonstrate antigen-specific immunity to mycobacterial virulence factors. Th-17 cells are crucial to the immune response in granulomatous inflammation, and have recently been shown to be present in greater numbers in the peripheral blood and bronchoalveolar lavage (BAL) fluid (BALF) of sarcoidosis patients than healthy controls. It is unclear whether Th-17 cells in sarcoidosis are specific for mycobacterial antigens, or whether they have similar functionality to control Th-17 cells. Methods Flow cytometry was used to determine the numbers of Th-17 cells present in the peripheral blood and BALF of patients with sarcoidosis, the percentage of Th-17 cells that were specific to the mycobacterial virulence factor ESAT-6, and as well as to assess IFN-γ expression in Th-17 cells following polyclonal stimulation. Results Patients with sarcoidosis had greater numbers of Th-17 cells in the peripheral blood and BALF than controls and produced significantly more extracellular IL-17A (p=0.03 and p=0.02, respectively). ESAT-6 specific Th-17 cells were present in both peripheral blood and BALF of sarcoidosis patients (psarcoidosis patients produced less IFN-γ than healthy controls. Conclusions Patients with sarcoidosis have mycobacterial antigen-specific Th-17 cells peripherally and in sites of active sarcoidosis involvement. Despite the Th1 immunophenotype of sarcoidosis immunology, the Th-17 cells have reduced IFN-γ expression, compared to healthy controls. This reduction in immunity may contribute to sarcoidosis pathogenesis. PMID:23073617

  14. Demonstration of Hadoop-GIS: A Spatial Data Warehousing System Over MapReduce.

    Science.gov (United States)

    Aji, Ablimit; Sun, Xiling; Vo, Hoang; Liu, Qioaling; Lee, Rubao; Zhang, Xiaodong; Saltz, Joel; Wang, Fusheng

    2013-11-01

    The proliferation of GPS-enabled devices, and the rapid improvement of scientific instruments have resulted in massive amounts of spatial data in the last decade. Support of high performance spatial queries on large volumes data has become increasingly important in numerous fields, which requires a scalable and efficient spatial data warehousing solution as existing approaches exhibit scalability limitations and efficiency bottlenecks for large scale spatial applications. In this demonstration, we present Hadoop-GIS - a scalable and high performance spatial query system over MapReduce. Hadoop-GIS provides an efficient spatial query engine to process spatial queries, data and space based partitioning, and query pipelines that parallelize queries implicitly on MapReduce. Hadoop-GIS also provides an expressive, SQL-like spatial query language for workload specification. We will demonstrate how spatial queries are expressed in spatially extended SQL queries, and submitted through a command line/web interface for execution. Parallel to our system demonstration, we explain the system architecture and details on how queries are translated to MapReduce operators, optimized, and executed on Hadoop. In addition, we will showcase how the system can be used to support two representative real world use cases: large scale pathology analytical imaging, and geo-spatial data warehousing.

  15. Sertraline demonstrates fungicidal activity in vitro for Coccidioides immitis

    Directory of Open Access Journals (Sweden)

    Simon Paul

    2016-07-01

    Full Text Available Coccidioidomycosis causes substantial morbidity in endemic areas. Disseminated coccidioidomycosis is an AIDS defining condition and treatment often requires lifelong antifungal therapy. Sertraline, a widely used serotonin-reuptake inhibitor anti-depressant, has demonstrated activity against Candida and Cryptococcus sp. both in vitro and in vivo. To evaluate if sertraline has activity against Coccidioides, the minimal inhibitory concentration (MIC and minimal fungicidal concentration (MFC of sertraline for four clinical isolates of C. immitis were determined. Sertraline was observed to have an MIC range of 4–8 µg/ml and MFC also of 4–8 µg/ml for Coccidioides. These MIC and MFC results for C. immitis are similar to those reported for Cryptococcus sp. suggesting sertraline may potentially have utility for the treatment of coccidioidomycosis.

  16. Can persuasive and demonstrative messages to visitors reduce littering in river beaches?

    Science.gov (United States)

    Cingolani, Ana M; Barberá, Iván; Renison, Daniel; Barri, Fernando R

    2016-12-01

    Littering of public areas is a significant problem worldwide. Here we evaluate the success of persuasive and demonstrative messages at reducing littering in highly visited river beaches in Argentina. We made an intervention at the beaches which consisted of a personalized verbal request asking visitors to take their litter to the waste cans (persuasive message) while they were exposed to the example of picking up the litter already left on the beach (demonstrative message). We conducted 102 observations distributed over 29 dates, two years and four beaches. Each observation consisted of three or four rounds: before the presence of visitors we cleaned the beaches, during the stay of visitors we made the intervention (once or twice) in two out of the four beaches, and early next morning we estimated the amount of litter left per beach. Litter weight ranged from 0 to 53gvisitor(-1)day(-1). Littering per visitor was reduced an average of 35% due to the intervention (p=0.049). We also found differences among beaches (p=0.001), and an increase in littering with crowding (p=0.005). We show for the first time that the personalized request combined with the example of picking up litter is effective in reducing littering in a Latin American country. Copyright © 2016. Published by Elsevier Ltd.

  17. Reducing Skin Picking via Competing Activities

    Science.gov (United States)

    Lane, Kathleen Lynne; Thompson, Ada; Reske, Cara L.; Gable, Lauren M.; Barton-Arwood, Sally

    2006-01-01

    This study examined the outcomes of a competing activities intervention to decrease skin picking exhibited by a 9-year-old student with comorbid diagnoses. Results of an ABCBAB design revealed that the use of student-selected manipulatives resulted in reduced skin picking. (Contains 1 figure.)

  18. Four experimental demonstrations of active vibration control for flexible structures

    Science.gov (United States)

    Phillips, Doug; Collins, Emmanuel G., Jr.

    1990-01-01

    Laboratory experiments designed to test prototype active-vibration-control systems under development for future flexible space structures are described, summarizing previously reported results. The control-synthesis technique employed for all four experiments was the maximum-entropy optimal-projection (MEOP) method (Bernstein and Hyland, 1988). Consideration is given to: (1) a pendulum experiment on large-amplitude LF dynamics; (2) a plate experiment on broadband vibration suppression in a two-dimensional structure; (3) a multiple-hexagon experiment combining the factors studied in (1) and (2) to simulate the complexity of a large space structure; and (4) the NASA Marshall ACES experiment on a lightweight deployable 45-foot beam. Extensive diagrams, drawings, graphs, and photographs are included. The results are shown to validate the MEOP design approach, demonstrating that good performance is achievable using relatively simple low-order decentralized controllers.

  19. Experimental demonstration of active vibration control for flexible structures

    Science.gov (United States)

    Phillips, Douglas J.; Hyland, David C.; Collins, Emmanuel G., Jr.

    1990-01-01

    Active vibration control of flexible structures for future space missions is addressed. Three experiments that successfully demonstrate control of flexible structures are described. The first is the pendulum experiment. The structure is a 5-m compound pendulum and was designed as an end-to-end test bed for a linear proof mass actuator and its supporting electronics. Experimental results are shown for a maximum-entropy/optimal-projection controller designed to achieve 5 percent damping in the first two pendulum modes. The second experiment was based upon the Harris Multi-Hex prototype experiment (MHPE) apparatus. This is a large optical reflector structure comprising a seven-panel array and supporting truss which typifies a number of generic characteristics of large space systems. The third experiment involved control design and implementation for the ACES structure at NASA Marshall Space Flight Center. The authors conclude with some remarks on the lessons learned from conducting these experiments.

  20. GIP-overexpressing mice demonstrate reduced diet-induced obesity and steatosis, and improved glucose homeostasis.

    Directory of Open Access Journals (Sweden)

    Su-Jin Kim

    Full Text Available Glucose-dependent insulinotropic polypeptide (GIP is a gastrointestinal hormone that potentiates glucose-stimulated insulin secretion during a meal. Since GIP has also been shown to exert β-cell prosurvival and adipocyte lipogenic effects in rodents, both GIP receptor agonists and antagonists have been considered as potential therapeutics in type 2 diabetes (T2DM. In the present study, we tested the hypothesis that chronically elevating GIP levels in a transgenic (Tg mouse model would increase adipose tissue expansion and exert beneficial effects on glucose homeostasis. In contrast, although GIP Tg mice demonstrated enhanced β-cell function, resulting in improved glucose tolerance and insulin sensitivity, they exhibited reduced diet-induced obesity. Adipose tissue macrophage infiltration and hepatic steatosis were both greatly reduced, and a number of genes involved in lipid metabolism/inflammatory signaling pathways were found to be down-regulated. Reduced adiposity in GIP Tg mice was associated with decreased energy intake, involving overexpression of hypothalamic GIP. Together, these studies suggest that, in the context of over-nutrition, transgenic GIP overexpression has the potential to improve hepatic and adipocyte function as well as glucose homeostasis.

  1. An Anesthetic Drug Demonstration and an Introductory Antioxidant Activity Experiment with "Eugene, the Sleepy Fish"

    Science.gov (United States)

    Barcena, Homar; Chen, Peishan

    2016-01-01

    Students are introduced to spectrophotometry in comparing the antioxidant activity of pure eugenol and oil of cloves from a commercial source using a modified ferric reducing antioxidant power (FRAP) assay. The extraction of the essential oil from dried cloves is demonstrated to facilitate discussions on green chemistry. The anesthetic properties…

  2. ACTIVITY ATTACK ON REDUCED VARIANTS OF RIJNDAEL

    Institute of Scientific and Technical Information of China (English)

    Wei Baodian; Liu Dongsu; Wang Xinmei

    2004-01-01

    The famous Square attacks against the Rijndael algorithm have taken advantage of the change of the balance of some bytes. Further study shows that the change of activity always happens before the change of balance, which builds the foundation for a new activity attack presented in this paper. In the activity attack, the round in which the activity changes is executed in an equivalent form to avoid the obstructive restriction of the subkeys of that round.The existence of the birthday paradox guarantees much fewer plaintexts necessary for activity attacks comparing with that for corresponding Square attacks. But no benefit may result from the new attacks performed independently because the activity attacks guess four instead of one key byte once. Only when both the balance property and the activity property are exploited at the same time can much better performance be obtained. The better performance in the simulation shows that the consuming time and chosen plaintexts necessary are both reduced to one tenth of those of the corresponding Square attacks. So the activity attacks could be viewed as an efficient supplement to the Square attacks.

  3. Activity of Reducing Steel Slag of EAF

    Institute of Scientific and Technical Information of China (English)

    GUO Chinhsiang; HWANG Chaolung; LIN Tingyi

    2011-01-01

    Reducing steel slag (RSS) was mainly acquired from five electric-arc furnace (EAF)steelmaking plants (among them, the products of two plants were carbon steel and those of other plants were stainless steel) for research tests. The chemical properties, compound compositions, activities and contents of main expansive compounds were tested. The results showed that the field sampled RSS had a very high crystallinity and hydraulicity with main chemical compositions close to those of Portland cement. It can be known from the study that in case of C/S ratio higher than 2.0, the main compound compositions are C2S, C3S, C2F and f-CaO. However, after the RSS was stored for six months, an obvious variation occurred with potential pre-hydration in RSS, where the SO3 content was slightly reduced and the compressive activity index was obviously higher than that at the 28th day.

  4. Technology demonstration for reducing mercury emissions from small-scale gold refining facilities.

    Energy Technology Data Exchange (ETDEWEB)

    Habegger, L. J.; Fernandez, L. E.; Engle, M.; Bailey, J. L.; Peterson, D. P.; MacDonell, M. M.; U.S. Environmental Protection Agency

    2008-06-30

    coagulation and collection of the mercury aerosols in exhaust ducts, which is dependent on the hood and collector configuration, was also evaluated. Prototype demonstration tests verified the theoretical basis for mercury aerosol capture that can be used to optimize the baffle plate design, flow rates, and hood exhaust ducts and plenum to achieve 80% or higher removal efficiencies. Results indicated that installation configuration significantly influences a system's capture efficiency. Configurations that retained existing inlet ducts resulted in system efficiencies of more than 80%, whereas installation configurations without inlet ducts significantly reduced capture efficiency. As an alternative to increasing the volume of inlet ducts, the number of baffle plates in the system baffle assembly could be doubled to increase efficiency. Recommended installation and operation procedures were developed on the basis of these results. A water-based mercury capture system developed in Indonesia for installation in smaller shops was also tested and shown to be effective for certain applications. The cost of construction and installation of the baffle plate prototype was approximately US$400. These costs were reported as acceptable by local gold shop owners and government regulators, and were significantly lower than the cost of an alternate charcoal/copper mesh mercury filter available in the region, which costs about US$10,000. A sampling procedure that consists of a particle filter combined with a vapor analyzer was demonstrated as an effective procedure for analyzing both the aerosol and vapor components of the mercury concentrations. Two key findings for enhancing higher mercury collection were identified. First, the aerosol/vapor mercury emissions must be given sufficient time for the mercury particles to coagulate to a size that can be readily captured by the baffle plates. An interval of at least 6 seconds of transit time between the point of evaporation and contact with

  5. Technology demonstration for reducing mercury emissions from small-scale gold refining facilities.

    Energy Technology Data Exchange (ETDEWEB)

    Habegger, L. J.; Fernandez, L. E.; Engle, M.; Bailey, J. L.; Peterson, D. P.; MacDonell, M. M.; U.S. Environmental Protection Agency

    2008-06-30

    coagulation and collection of the mercury aerosols in exhaust ducts, which is dependent on the hood and collector configuration, was also evaluated. Prototype demonstration tests verified the theoretical basis for mercury aerosol capture that can be used to optimize the baffle plate design, flow rates, and hood exhaust ducts and plenum to achieve 80% or higher removal efficiencies. Results indicated that installation configuration significantly influences a system's capture efficiency. Configurations that retained existing inlet ducts resulted in system efficiencies of more than 80%, whereas installation configurations without inlet ducts significantly reduced capture efficiency. As an alternative to increasing the volume of inlet ducts, the number of baffle plates in the system baffle assembly could be doubled to increase efficiency. Recommended installation and operation procedures were developed on the basis of these results. A water-based mercury capture system developed in Indonesia for installation in smaller shops was also tested and shown to be effective for certain applications. The cost of construction and installation of the baffle plate prototype was approximately US$400. These costs were reported as acceptable by local gold shop owners and government regulators, and were significantly lower than the cost of an alternate charcoal/copper mesh mercury filter available in the region, which costs about US$10,000. A sampling procedure that consists of a particle filter combined with a vapor analyzer was demonstrated as an effective procedure for analyzing both the aerosol and vapor components of the mercury concentrations. Two key findings for enhancing higher mercury collection were identified. First, the aerosol/vapor mercury emissions must be given sufficient time for the mercury particles to coagulate to a size that can be readily captured by the baffle plates. An interval of at least 6 seconds of transit time between the point of evaporation and contact with

  6. Terpenes from Copaifera demonstrated in vitro antiparasitic and synergic activity.

    Science.gov (United States)

    Izumi, Erika; Ueda-Nakamura, Tânia; Veiga, Valdir F; Pinto, Angelo C; Nakamura, Celso Vataru

    2012-04-12

    To discover new possible therapies for Chagas' disease, we evaluated against all Trypanosoma cruzi life stages the in vitro trypanocidal and synergistic activity of terpenes isolated from Copaifera oleoresins collected in the Amazon and investigated their possible mechanism of action. Seven acid diterpenes and one sesquiterpene were tested. Terpenes promoted changes in oxidative metabolism followed by autophagic processes in the parasite cell leading to selective death. Furthermore, they were more effective against replicative forms, in particular amastigotes. A synergistic effect occurred. Cytotoxicity to erythrocytes and nucleated cells was moderate. This is the first study showing synergic activity between two terpenes against T. cruzi. Combinations of natural compounds can show high activity and may lead to new alternative treatments in the future.

  7. An Experiential Learning Activity Demonstrating Normal and Phobic Anxiety

    Science.gov (United States)

    Canu, Will H.

    2008-01-01

    This article describes an activity for an undergraduate abnormal psychology course that used student-generated data to illustrate normal versus clinically significant anxiety responses related to specific phobias. Students (N = 37) viewed 14 images of low- or high-anxiety valence and rated their subjective response to each. Discussion in a…

  8. Reducing Plug Loads in Office Spaces: Hawaii and Guam Energy Improvement Technology Demonstration Project

    Energy Technology Data Exchange (ETDEWEB)

    Sheppy, M.; Metzger, I.; Cutler, D.; Holland, G.; Hanada, A.

    2014-01-01

    As part of its overall strategy to meet its energy goals, the Naval Facilities Engineering Command (NAVFAC) partnered with the Department of Energy's National Renewable Energy Laboratory (NREL) to rapidly demonstrate and deploy cost-effective renewable energy and energy efficiency technologies. This project was one of several demonstrations of new or underutilized commercial energy technologies. The common goal was to demonstrate and measure the performance and economic benefit of the system while monitoring any ancillary impacts to related standards of service and operation and maintenance (O&M) practices. In short, demonstrations at naval facilities simultaneously evaluate the benefits and compatibility of the technology with the U.S. Department of Defense (DOD) mission, and with NAVFAC's design, construction, operations, and maintenance practices, in particular. This project demonstrated the performance of commercially available advanced power strips (APSs) for plug load energy reductions in building A4 at Joint Base Pearl Harbor-Hickam (JBPHH), Hawaii.

  9. Bigelow Expandable Activity Module (BEAM) - ISS Inflatable Module Technology Demonstration

    Science.gov (United States)

    Dasgupta, Rajib; Munday, Steve; Valle, Gerard D.

    2014-01-01

    INNOVATION: BEAM is a pathway project demonstrating the design, fabrication, test, certification, integration, operation, on-orbit performance, and disposal of the first ever man-rated space inflatable structure. The groundwork laid through the BEAM project will support developing and launching a larger inflatable space structure with even greater mass per volume (M/V) advantages need for longer space missions. OVERVIEW: Inflatable structures have been shown to have much lower mass per volume ratios (M/V) when compared with conventional space structures. BEAM is an expandable structure, launched in a packed state, and then expanded once on orbit. It is a temporary experimental module to be used for gathering structural, thermal, and radiation data while on orbit. BEAM will be launched on Space X-8, be extracted from the dragon trunk, and will attach to ISS at Node 3- Aft. BEAM performance will be monitored over a two-year period and then BEAM will be jettison using the SSRMS.

  10. MULTIPLE IMAGING TECHNIQUES DEMONSTRATE THE MANIPULATION OF SURFACES TO REDUCE BACTERIAL CONTAMINATION

    Science.gov (United States)

    Surface imaging techniques were combined to determine appropriate manipulation of technologically important surfaces for commercial applications. Stainless steel surfaces were engineered to reduce bacterial contamination, biofilm formation, and corrosion during product processing...

  11. Demonstration and Validation of a High-Performance Floor-Sealant System to Reduce Concrete Degradation

    Science.gov (United States)

    2015-05-01

    System to Reduce Concrete Degradation Final Report on Project F10-AR02 Co ns tr uc tio n En gi ne er in g R es ea rc h La bo ra to ry Clint...of a High-Performance Floor-Sealant System to Reduce Concrete Degradation Final Report on Project F10-AR02 Clint A. Wilson and Susan A. Drozdz...Under Project F10-AR02, “Application of an Innovative, High Performance Concrete Floor Sealant at Hunter Army Airfield, Georgia” ERDC/CERL TR-15-9 ii

  12. Striatal trophic activity is reduced in the aged rat brain.

    Science.gov (United States)

    Ling, Z D; Collier, T J; Sortwell, C E; Lipton, J W; Vu, T Q; Robie, H C; Carvey, P M

    2000-02-21

    Our previous studies demonstrated that the survival of a mesencephalic graft was reduced in aged animals suggesting an age-related decline in target-derived neurotrophic activity. We tested this hypothesis by examining dopamine (DA) and trophic activities from the striatum of intact or unilateral 6-hydroxydopamine (6-OHDA) lesioned rats of increasing age. Fisher 344 rats were 4, 12, 18, and 23 months old (m.o.) at sacrifice. Half the animals had received unilateral 6-OHDA lesions of the mesostriatal DA pathway 8 weeks earlier. Striatal tissue punches were analyzed for DA, homovanillic acid (HVA), and DA activity (HVA/DA) using HPLC. The remainder of the striatal tissue was homogenized to generate tissue extracts which were added to E14.5 ventral mesencephalic cultures to test trophic activity. In the non-lesioned animals, striatal DA was reduced and striatal DA activity was increased in the 18 and 23 m.o. animals relative to the 4 and 12 m.o. animals. Striatal trophic activity was inversely related to age. In the lesioned animals, striatal DA ipsilateral to 6-OHDA infusion was below detection limits while the contralateral striatum exhibited age-related changes in DA similar to those seen in the non-lesioned animals. In 4 m.o. lesioned rats, striatal trophic activity ipsilateral to 6-OHDA infusion was elevated by 26% relative to the contralateral side. The ipsi/contra-lateral differences in striatal trophic activity were reduced in 12 m.o. animals and absent in the 18 and 23 m.o. groups. These data suggest that advancing age is associated with a reduction in striatal DA as well as trophic activity. Moreover, the aged striatum loses its ability to biochemically and trophically compensate for DA reduction and therefore may represent a more challenging environment for the survival, growth, and function of a fetal graft.

  13. Demonstration of an Environmentally Benign and Reduced Corrosion Runway Deicing Fluid

    Science.gov (United States)

    2011-01-01

    petroleum consumption; conserve water; reduce waste; support sustainable communities; and leverage Federal purchasing power to promote environmentally...environmentally-sound operation of DoD airports. Wetlands and aquatic life can be adversely affected by exposure to seemingly low toxicity chemicals...Mountain Home AFB 3,450 Misawa, Japan 81,996 Hill AFB, UT 56,013 Osan, S. Korea 12,000 Elmendorf AFB, AK 105,000 Kunsan, S. Korea 24,000 (a) Obtained

  14. Neutron activation analysis for the demonstration of amphibolite rock-weathering activity of a yeast.

    Science.gov (United States)

    Rades-Rohkohl, E; Hirsch, P; Fränzle, O

    1979-12-01

    Neutron activation analysis was employed in a survey of weathering abilities of rock surface microorganisms. A yeast isolated from an amphibolite of a megalithic grave was found actively to concentrate, in media and in or on cells, iron and other elements when grown in the presence of ground rock. This was demonstrated by comparing a spectrum of neutron-activated amphibolite powder (particle size, 50 to 100 mum) with the spectra of neutron-activated, lyophilized yeast cells which had grown with or without amphibolite powder added to different media. The most active yeast (IFAM 1171) did not only solubilize Fe from the rock powder, but significant amounts of Co, Eu, Yb, Ca, Ba, Sc, Lu, Cr, Th, and U were also mobilized. The latter two elements occurred as natural radioactive isotopes in this amphibolite. When the yeast cells were grown with neutron-activated amphibolite, the cells contained the same elements. Furthermore, the growth medium contained Fe, Co, and Eu which had been solubilized from the amphibolite. This indicates the presence, in this yeast strain, of active rockweathering abilities as well as of uptake mechanisms for solubilized rock components.

  15. Brown fat activation reduces hypercholesterolaemia and protects from atherosclerosis development.

    Science.gov (United States)

    Berbée, Jimmy F P; Boon, Mariëtte R; Khedoe, P Padmini S J; Bartelt, Alexander; Schlein, Christian; Worthmann, Anna; Kooijman, Sander; Hoeke, Geerte; Mol, Isabel M; John, Clara; Jung, Caroline; Vazirpanah, Nadia; Brouwers, Linda P J; Gordts, Philip L S M; Esko, Jeffrey D; Hiemstra, Pieter S; Havekes, Louis M; Scheja, Ludger; Heeren, Joerg; Rensen, Patrick C N

    2015-03-10

    Brown adipose tissue (BAT) combusts high amounts of fatty acids, thereby lowering plasma triglyceride levels and reducing obesity. However, the precise role of BAT in plasma cholesterol metabolism and atherosclerosis development remains unclear. Here we show that BAT activation by β3-adrenergic receptor stimulation protects from atherosclerosis in hyperlipidemic APOE*3-Leiden.CETP mice, a well-established model for human-like lipoprotein metabolism that unlike hyperlipidemic Apoe(-/-) and Ldlr(-/-) mice expresses functional apoE and LDLR. BAT activation increases energy expenditure and decreases plasma triglyceride and cholesterol levels. Mechanistically, we demonstrate that BAT activation enhances the selective uptake of fatty acids from triglyceride-rich lipoproteins into BAT, subsequently accelerating the hepatic clearance of the cholesterol-enriched remnants. These effects depend on a functional hepatic apoE-LDLR clearance pathway as BAT activation in Apoe(-/-) and Ldlr(-/-) mice does not attenuate hypercholesterolaemia and atherosclerosis. We conclude that activation of BAT is a powerful therapeutic avenue to ameliorate hyperlipidaemia and protect from atherosclerosis.

  16. Expanded Hematopoietic Progenitor Cells Reselected for High Aldehyde Dehydrogenase Activity Demonstrate Islet Regenerative Functions.

    Science.gov (United States)

    Seneviratne, Ayesh K; Bell, Gillian I; Sherman, Stephen E; Cooper, Tyler T; Putman, David M; Hess, David A

    2016-04-01

    Human umbilical cord blood (UCB) hematopoietic progenitor cells (HPC) purified for high aldehyde dehydrogenase activity (ALDH(hi) ) stimulate islet regeneration after transplantation into mice with streptozotocin-induced β cell deletion. However, ALDH(hi) cells represent a rare progenitor subset and widespread use of UCB ALDH(hi) cells to stimulate islet regeneration will require progenitor cell expansion without loss of islet regenerative functions. Here we demonstrate that prospectively purified UCB ALDH(hi) cells expand efficiently under serum-free, xeno-free conditions with minimal growth factor supplementation. Consistent with the concept that ALDH-activity is decreased as progenitor cells differentiate, kinetic analyses over 9 days revealed the frequency of ALDH(hi) cells diminished as culture time progressed such that total ALDH(hi) cell number was maximal (increased 3-fold) at day 6. Subsequently, day 6 expanded cells (bulk cells) were sorted after culture to reselect differentiated progeny with low ALDH-activity (ALDH(lo) subset) from less differentiated progeny with high ALDH-activity (ALDH(hi) subset). The ALDH(hi) subset retained primitive cell surface marker coexpression (32.0% ± 7.0% CD34(+) /CD38(-) cells, 37.0% ± 6.9% CD34(+) /CD133(+) cells), and demonstrated increased hematopoietic colony forming cell function compared with the ALDH(lo) subset. Notably, bulk cells or ALDH(lo) cells did not possess the functional capacity to lower hyperglycemia after transplantation into streptozotocin-treated NOD/SCID mice. However, transplantation of the repurified ALDH(hi) subset significantly reduced hyperglycemia, improved glucose tolerance, and increased islet-associated cell proliferation and capillary formation. Thus, expansion and delivery of reselected UCB cells that retain high ALDH-activity after short-term culture represents an improved strategy for the development of cellular therapies to enhance islet regeneration in situ.

  17. Reduced-gravity Environment Hardware Demonstrations of a Prototype Miniaturized Flow Cytometer and Companion Microfluidic Mixing Technology

    Science.gov (United States)

    Bae, Candice; Sharpe, Julia Z.; Bishara, Andrew M.; Nelson, Emily S.; Weaver, Aaron S.; Brown, Daniel; McKay, Terri L.; Griffin, DeVon; Chan, Eugene Y.

    2014-01-01

    Until recently, astronaut blood samples were collected in-flight, transported to earth on the Space Shuttle, and analyzed in terrestrial laboratories. If humans are to travel beyond low Earth orbit, a transition towards space-ready, point-of-care (POC) testing is required. Such testing needs to be comprehensive, easy to perform in a reduced-gravity environment, and unaffected by the stresses of launch and spaceflight. Countless POC devices have been developed to mimic laboratory scale counterparts, but most have narrow applications and few have demonstrable use in an in-flight, reduced-gravity environment. In fact, demonstrations of biomedical diagnostics in reduced gravity are limited altogether, making component choice and certain logistical challenges difficult to approach when seeking to test new technology. To help fill the void, we are presenting a modular method for the construction and operation of a prototype blood diagnostic device and its associated parabolic flight test rig that meet the standards for flight-testing onboard a parabolic flight, reduced-gravity aircraft. The method first focuses on rig assembly for in-flight, reduced-gravity testing of a flow cytometer and a companion microfluidic mixing chip. Components are adaptable to other designs and some custom components, such as a microvolume sample loader and the micromixer may be of particular interest. The method then shifts focus to flight preparation, by offering guidelines and suggestions to prepare for a successful flight test with regard to user training, development of a standard operating procedure (SOP), and other issues. Finally, in-flight experimental procedures specific to our demonstrations are described. PMID:25490614

  18. Reduced-gravity environment hardware demonstrations of a prototype miniaturized flow cytometer and companion microfluidic mixing technology.

    Science.gov (United States)

    Phipps, William S; Yin, Zhizhong; Bae, Candice; Sharpe, Julia Z; Bishara, Andrew M; Nelson, Emily S; Weaver, Aaron S; Brown, Daniel; McKay, Terri L; Griffin, DeVon; Chan, Eugene Y

    2014-11-13

    Until recently, astronaut blood samples were collected in-flight, transported to earth on the Space Shuttle, and analyzed in terrestrial laboratories. If humans are to travel beyond low Earth orbit, a transition towards space-ready, point-of-care (POC) testing is required. Such testing needs to be comprehensive, easy to perform in a reduced-gravity environment, and unaffected by the stresses of launch and spaceflight. Countless POC devices have been developed to mimic laboratory scale counterparts, but most have narrow applications and few have demonstrable use in an in-flight, reduced-gravity environment. In fact, demonstrations of biomedical diagnostics in reduced gravity are limited altogether, making component choice and certain logistical challenges difficult to approach when seeking to test new technology. To help fill the void, we are presenting a modular method for the construction and operation of a prototype blood diagnostic device and its associated parabolic flight test rig that meet the standards for flight-testing onboard a parabolic flight, reduced-gravity aircraft. The method first focuses on rig assembly for in-flight, reduced-gravity testing of a flow cytometer and a companion microfluidic mixing chip. Components are adaptable to other designs and some custom components, such as a microvolume sample loader and the micromixer may be of particular interest. The method then shifts focus to flight preparation, by offering guidelines and suggestions to prepare for a successful flight test with regard to user training, development of a standard operating procedure (SOP), and other issues. Finally, in-flight experimental procedures specific to our demonstrations are described.

  19. Reduced Arylsulfatase B Activity in Leukocytes from Cystic Fibrosis Patients

    Science.gov (United States)

    Sharma, Girish; Burke, Jenifer; Bhattacharyya, Sumit; Sharma, Neha; Katyal, Shivani; Park, R. Lucy; Tobacman, Joanne

    2013-01-01

    Summary The enzyme Arylsulfatase B (ARSB; N-acetylgalactosamine-4-sulfatase) removes 4-sulfate groups from chondroitin-4-sulfate and dermatan sulfate and is required for the degradation of these sulfated glycosaminoglycans (GAGs). Since these GAGs accumulate in patients with Cystic Fibrosis (CF), we investigated the activity of ARSB in leukocytes of patients with CF, to consider if reduced activity of ARSB might contribute to the pathophysiology of CF. Previous cell-based experiments had demonstrated that when the deficiency of the cystic fibrosis transmembrane regulator (CFTR) was corrected in bronchial epithelial cells, the ARSB activity increased significantly. De-identified, citrated blood samples were collected from 16 children with cystic fibrosis and 31 control subjects, seen in the Pediatric Clinic at Rush University Medical Center. Polymorphonuclear (PMN) and mononuclear cell (MC) populations were separated by density gradient, and blinded determinations of ARSB activity were performed using the exogenous substrate 4-methylumbilliferyl sulfate. Interleukin-6 was measured in the plasma samples by ELISA. ARSB activity was significantly less in the PMN and MC from the CF patients than controls (p<0.0001, unpaired t-test, two-tailed). Interleukin-6 levels in plasma were significantly greater in the CF population (p<0.001). Mean age, age range, and male:female ratio of CF patients and controls were similar, and no association of ARSB activity with age, gender, or CFTR genotype was evident. Since recombinant human ARSB is used successfully for replacement therapy in Mucopolysaccharidosis VI, it may be useful to restore ARSB activity to normal levels and increase degradation of sulfated GAGs in CF patients. PMID:22550062

  20. INVERSE ELECTRON TRANSFER IN PEROXYOXALATE CHEMIEXCITATION USING EASILY REDUCIBLE ACTIVATORS

    NARCIS (Netherlands)

    Bartoloni, Fernando Heering; Monteiro Leite Ciscato, Luiz Francisco; Augusto, Felipe Alberto; Baader, Wilhelm Josef

    2010-01-01

    INVERSE ELECTRON TRANSFER IN PEROXYOXALATE CHEMIEXCITATION USING EASILY REDUCIBLE ACTIVATORS. Chemiluminescence properties of the peroxyoxalate reaction in the presence of activators bearing electron withdrawing substituents were studied, to evaluate the possible occurrence of an inverse electron tr

  1. INVERSE ELECTRON TRANSFER IN PEROXYOXALATE CHEMIEXCITATION USING EASILY REDUCIBLE ACTIVATORS

    NARCIS (Netherlands)

    Bartoloni, Fernando Heering; Monteiro Leite Ciscato, Luiz Francisco; Augusto, Felipe Alberto; Baader, Wilhelm Josef

    2010-01-01

    INVERSE ELECTRON TRANSFER IN PEROXYOXALATE CHEMIEXCITATION USING EASILY REDUCIBLE ACTIVATORS. Chemiluminescence properties of the peroxyoxalate reaction in the presence of activators bearing electron withdrawing substituents were studied, to evaluate the possible occurrence of an inverse electron tr

  2. INVERSE ELECTRON TRANSFER IN PEROXYOXALATE CHEMIEXCITATION USING EASILY REDUCIBLE ACTIVATORS

    NARCIS (Netherlands)

    Bartoloni, Fernando Heering; Monteiro Leite Ciscato, Luiz Francisco; Augusto, Felipe Alberto; Baader, Wilhelm Josef

    2010-01-01

    INVERSE ELECTRON TRANSFER IN PEROXYOXALATE CHEMIEXCITATION USING EASILY REDUCIBLE ACTIVATORS. Chemiluminescence properties of the peroxyoxalate reaction in the presence of activators bearing electron withdrawing substituents were studied, to evaluate the possible occurrence of an inverse electron

  3. Reduced-activation steels: Future development for improved creep strength

    Science.gov (United States)

    Klueh, R. L.

    2008-08-01

    Reduced-activation steels for fusion applications were developed in the 1980s to replace the elevated-temperature commercial steels first considered. The new steels were patterned after the commercial steels, with the objective that the new steels have yield stress and ultimate tensile strength and impact toughness in a Charpy test comparable to or better than the steels they replaced. That objective was achieved in reduced-activation steels developed in Japan, Europe, and the United States. Although tensile and impact toughness of the reduced-activation steels exceed those of the commercial steels they were patterned after, their creep-rupture properties are inferior to some commercial steels they replaced. They are even more inferior to commercial steels developed since the 1980s. In this paper, compositional differences between reduced-activation steels and new commercial steels are examined, and compositions are proposed for development of new-and-improved reduced-activation steels.

  4. Direct conscious telemetry recordings demonstrate increased renal sympathetic nerve activity in rats with chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Ibrahim M Salman

    2015-08-01

    Full Text Available Chronic kidney disease (CKD is associated with sympathetic hyperactivity and impaired blood pressure control reflex responses, yet direct evidence demonstrating these features of autonomic dysfunction in conscious animals is still lacking. Here we measured renal sympathetic nerve activity (RSNA and mean arterial pressure (MAP using telemetry-based recordings in a rat model of CKD, the Lewis Polycystic Kidney (LPK rat, and assessed responses to chemoreflex activation and acute stress. Male LPK and Lewis control animals (total n=16 were instrumented for telemetric recording of RSNA and MAP. At 12–13 weeks-of-age, resting RSNA and MAP, sympathetic and haemodynamic responses to both peripheral (hypoxia: 10% O2 and central chemoreflex (hypercapnia: 7% CO2 activation and acute stress (open-field exposure, were measured. As indicators of renal function, urinary protein (UPro and creatinine (Ucr levels were assessed. LPK rats had higher resting RSNA (1.2±0.1 vs. 0.6±0.1 µV, p<0.05 and MAP (151±8 vs. 97±2 mmHg, p<0.05 compared to Lewis. MAP was negatively correlated with Ucr (r=-0.80, p=0.002 and positively correlated with RSNA (r=0.66, p=0.014, with multiple linear regression modeling indicating the strongest correlation was with Ucr. RSNA and MAP responses to activation of the central chemoreflex and open-field stress were reduced in the LPK relative to the Lewis (all p<0.05. This is the first description of dual conscious telemetry recording of RSNA and MAP in a genetic rodent model of CKD. Elevated RSNA is likely a key contributor to the marked hypertension in this model, while attenuated RSNA and MAP responses to central chemoreflex activation and acute stress in the LPK indicate possible deficits in the neural processing of autonomic outflows evoked by these sympathoexcitatory pathways.

  5. Activated Sludge Ozonation to Reduce Sludge Production in MBR

    Institute of Scientific and Technical Information of China (English)

    HE Sheng-bing; XUE Gang; WANG Bao-zhen

    2005-01-01

    The total experimental period was divided into two stages.At the first stage, a series of batch studies were carried out to get an understanding of the effect of ozonation on sludge properties. At the following stages, three MBRs with different amounts of activated sludge to be ozonated were run in parallel for a long period to evaluate the influence of sludge ozonation on sludge yield and permeate quality.Through batch study, it was found that ozone could disrupt the cell walls and caused the release of plasm from the cells,then the amounts of soluble organics in the solution increased with ozonation time. With the rise of soluble organics, the amount of soluble organics to be mineralized increased as well, which wonld reduce the soluble organics content. For the counteraction between these two aspects, a pseudo-balance could be achieved, and soluble organics would vary in a limited range. Sludge ozonation also increased the contents of nitrogen and phosphorus in the solution. In addition, ozonation was effective in improving sludge settling property. On the basis of batch study, a suitable ozone dosage of 0.16 kgO3/kgMLSS wasdetermined. Three systems were run in parallel for a total period of 39 days, it was demonstrated that a part of activated sludge ozonation could reduce sludge production significantly, and biological performance of mineralization and nitrification would not be inhibited due to sludge ozonation. Experimental results proved that the combination of ozonation unit with MBR unit could achieve an excellent quality of permeate as well as a small quantity of sludge production, and economic analysis indicated that an additional ozonation operating cost for treatment of both wastewater and sludge was only 0.096Yuan (US $0.011,5)/m3 wastewater.

  6. Nitrate reducing activity pervades surface waters during upwelling.

    Digital Repository Service at National Institute of Oceanography (India)

    Fernandes, S.O.; Halarnekar, R.; Malik, A.; Vijayan, V.; Varik, S.; RituKumari; Jineesh V.K.; Gauns, M.U.; Nair, S.; LokaBharathi, P.A.

    Nitrate reducing activity (NRA) is known to be mediated by microaerophilic to anaerobic bacteria and generally occurs in the sub-surface waters. However, we hypothesize that NRA could become prominent in the surface waters during upwelling. Hence...

  7. Reduced ceramide synthase 2 activity causes progressive myoclonic epilepsy

    DEFF Research Database (Denmark)

    Mosbech, Mai-Britt; Olsen, Anne S B; Neess, Ditte;

    2014-01-01

    with progressive myoclonic epilepsy (PME). Mass spectrometry and fluorescence microscopy were used to examine the effects of reduced CERS2 activity on cellular lipid composition and plasma membrane functions. RESULTS: We identify a novel 27 kb heterozygous deletion including the CERS2 gene in a proband diagnosed...... with PME. Compared to parental controls, levels of CERS2 mRNA, protein, and activity were reduced by ˜50% in fibroblasts isolated from this proband, resulting in significantly reduced levels of ceramides and sphingomyelins containing the very long-chain fatty acids C24:0 and C26:0. The change in SL...... to development of PME....

  8. Teaching with Movement: Using the Health Privilege Activity to Physically Demonstrate Disparities in Society

    Science.gov (United States)

    Irby-Shasanmi, Amy; Oberlin, Kathleen C.; Saunders, Tiffani N.

    2012-01-01

    This article describes and evaluates an activity designed to demonstrate how biological factors (e.g., genetics), individual-level behaviors (e.g., smoking), and social factors (e.g., socioeconomic status) shape health status and access to health care. Active learning techniques were utilized to introduce the sociological imagination as it…

  9. Materials design data for reduced activation martensitic steel type EUROFER

    Science.gov (United States)

    Tavassoli, A.-A. F.; Alamo, A.; Bedel, L.; Forest, L.; Gentzbittel, J.-M.; Rensman, J.-W.; Diegele, E.; Lindau, R.; Schirra, M.; Schmitt, R.; Schneider, H. C.; Petersen, C.; Lancha, A.-M.; Fernandez, P.; Filacchioni, G.; Maday, M. F.; Mergia, K.; Boukos, N.; Baluc; Spätig, P.; Alves, E.; Lucon, E.

    2004-08-01

    Materials design limits derived so far from the data generated in Europe for the reduced activation ferritic/martensitic (RAFM) steel type Eurofer are presented. These data address the short-term needs of the ITER Test Blanket Modules and a DEMOnstration fusion reactor. Products tested include plates, bars, tubes, TIG and EB welds, as well as powder consolidated blocks and solid-solid HIP joints. Effects of thermal ageing and low dose neutron irradiation are also included. Results are sorted and screened according to design code requirements before being introduced in reference databases. From the physical properties databases, variations of magnetic properties, modulus of elasticity, density, thermal conductivity, thermal diffusivity, specific heat, mean and instantaneous linear coefficients of thermal expansion versus temperature are derived. From the tensile and creep properties databases design allowable stresses are derived. From the instrumented Charpy impact and fracture toughness databases, ductile to brittle transition temperature, toughness and behavior of materials in different fracture modes are evaluated. From the fatigue database, total strain range versus number of cycles to failure curves are plotted and used to derive fatigue design curves. Cyclic curves are also derived and compared with monotonic hardening curves. Finally, irradiated and aged materials data are compared to ensure that the safety margins incorporated in unirradiated design limits are not exceeded.

  10. Sox11 Reduces Caspase-6 Cleavage and Activity.

    Directory of Open Access Journals (Sweden)

    Elaine Waldron-Roby

    Full Text Available The apoptotic cascade is an orchestrated event, whose final stages are mediated by effector caspases. Regulatory binding proteins have been identified for caspases such as caspase-3, -7, -8, and -9. Many of these proteins belong to the inhibitor of apoptosis (IAP family. By contrast, caspase-6 is not believed to be influenced by IAPs, and little is known about its regulation. We therefore performed a yeast-two-hybrid screen using a constitutively inactive form of caspase-6 for bait in order to identify novel regulators of caspase-6 activity. Sox11 was identified as a potential caspase-6 interacting protein. Sox11 was capable of dramatically reducing caspase-6 activity, as well as preventing caspase-6 self- cleavage. Several regions, including amino acids 117-214 and 362-395 within sox11 as well as a nuclear localization signal (NLS all contributed to the reduction in caspase-6 activity. Furthermore, sox11 was also capable of decreasing other effector caspase activity but not initiator caspases -8 and -9. The ability of sox11 to reduce effector caspase activity was also reflected in its capacity to reduce cell death following toxic insult. Interestingly, other sox proteins also had the ability to reduce caspase-6 activity but to a lesser extent than sox11.

  11. Structural Basis for Reduced FGFR2 Activity in LADD Syndrome: Implications for FGFR Autoinhibition and Activation

    Energy Technology Data Exchange (ETDEWEB)

    Lew,E.; Bae, J.; Rohmann, E.; Wollnik, B.; Schlessinger, J.

    2007-01-01

    Mutations in fibroblast growth factor receptor 2 (FGFR2) and its ligand, FGF10, are known to cause lacrimo-auriculo-dento-digital (LADD) syndrome. Multiple gain-of-function mutations in FGF receptors have been implicated in a variety of severe skeletal disorders and in many cancers. We aimed to elucidate the mechanism by which a missense mutation in the tyrosine kinase domain of FGFR2, described in the sporadic case of LADD syndrome, leads to reduced tyrosine kinase activity. In this report, we describe the crystal structure of a FGFR2 A628T LADD mutant in complex with a nucleotide analog. We demonstrate that the A628T LADD mutation alters the configuration of key residues in the catalytic pocket that are essential for substrate coordination, resulting in reduced tyrosine kinase activity. Further comparison of the structures of WT FGFR2 and WT FGFR1 kinases revealed that FGFR2 uses a less stringent mode of autoinhibition than FGFR1, which was also manifested in faster in vitro autophosphorylation kinetics. Moreover, the nearly identical conformation of WT FGFR2 kinase and the A628T LADD mutant to either the phosphorylated FGFR2 or FGFR2 harboring pathological activating mutations in the kinase hinge region suggests that FGFR autoinhibition and activation are better explained by changes in the conformational dynamics of the kinase rather than by static crystallographic snapshots of minor structural variations.

  12. Authentic Active Learning Activities Demonstrating the Use of Serial Dilutions and Plate Counts

    Directory of Open Access Journals (Sweden)

    Jordon K. March

    2011-09-01

    Full Text Available Serial dilution and plate counting is often taught in courses for both microbiology and allied health students. Lecture examples and examination questions addressing how the method is used can sometimes be contrived: artificial data sets may have little or no meaning other than to have students perform a calculation. Here we provide a set of activities employing data sets acquired from the primary literature. Our objective was to have the students think critically about a real scenario in which serial dilution and plate count was used. Each activity requires students to read a paragraph describing the study, predict the results, perform the appropriate calculations, and then evaluate the results in light of their predictions. To test the efficacy of these activities, a pretest quiz was given to approximately 100 students in an allied health/general microbiology course. After a lecture on how microbes are enumerated, students were given a different quiz. The class was then divided randomly into groups of three or four students and assigned one of the activities. A postactivity quiz was also administered. Approximately two weeks later, a serial dilution/plate count question was used on an examination and served as a final posttest. Standardized learning gains were calculated for the quiz administered after each learning activity. Even though learning gains were significantly higher after the lecture, there was also a significant improvement between the lecture and the activity. Using an exercise based on an authentic set of data significantly improved student learning gains, and is a useful practice for teaching microbiology.

  13. RemoveDebris – Mission Analysis for a Low Cost Active Debris Removal Demonstration in 2016

    OpenAIRE

    Joffre, E; Forshaw, J.; Secretin, T; Reynaud, S.; Salmon, T; Aurelien, P; Aglietti, G.

    2015-01-01

    Contracted by the European Commission in the frame of the EU’s Seventh Framework Programme for Research (FP7), a wide European consortium has been working since 2013 towards the design of a low cost in-orbit demonstration called RemoveDEBRIS. With a targeted launch date in the second quarter of 2016, the RemoveDEBRIS mission aims at demonstrating key Active Debris Removal (ADR) technologies, including capture means (net and harpoon firing on a distant target), relative navigation techniques (...

  14. Early Site Permit Demonstration Program: Recommendations for communication activities and public participation in the Early Site Permit Demonstration Program

    Energy Technology Data Exchange (ETDEWEB)

    1993-01-27

    On October 24, 1992, President Bush signed into law the National Energy Policy Act of 1992. The bill is a sweeping, comprehensive overhaul of the Nation`s energy laws, the first in more than a decade. Among other provisions, the National Energy Policy Act reforms the licensing process for new nuclear power plants by adopting a new approach developed by the US Nuclear Regulatory Commission (NRC) in 1989, and upheld in court in 1992. The NRC 10 CFR Part 52 rule is a three-step process that guarantees public participation at each step. The steps are: early site permit approval; standard design certifications; and, combined construction/operating licenses for nuclear power reactors. Licensing reform increases an organization`s ability to respond to future baseload electricity generation needs with less financial risk for ratepayers and the organization. Costly delays can be avoided because design, safety and siting issues will be resolved before a company starts to build a plant. Specifically, early site permit approval allows for site suitability and acceptability issues to be addressed prior to an organization`s commitment to build a plant. Responsibility for site-specific activities, including communications and public participation, rests with those organizations selected to try out early site approval. This plan has been prepared to assist those companies (referred to as sponsoring organizations) in planning their communications and public involvement programs. It provides research findings, information and recommendations to be used by organizations as a resource and starting point in developing their own plans.

  15. Selective IRAK4 Inhibition Attenuates Disease in Murine Lupus Models and Demonstrates Steroid Sparing Activity.

    Science.gov (United States)

    Dudhgaonkar, Shailesh; Ranade, Sourabh; Nagar, Jignesh; Subramani, Siva; Prasad, Durga Shiv; Karunanithi, Preethi; Srivastava, Ratika; Venkatesh, Kamala; Selvam, Sabariya; Krishnamurthy, Prasad; Mariappan, T Thanga; Saxena, Ajay; Fan, Li; Stetsko, Dawn K; Holloway, Deborah A; Li, Xin; Zhu, Jun; Yang, Wen-Pin; Ruepp, Stefan; Nair, Satheesh; Santella, Joseph; Duncia, John; Hynes, John; McIntyre, Kim W; Carman, Julie A

    2017-02-01

    The serine/threonine kinase IL-1R-associated kinase (IRAK)4 is a critical regulator of innate immunity. We have identified BMS-986126, a potent, highly selective inhibitor of IRAK4 kinase activity that demonstrates equipotent activity against multiple MyD88-dependent responses both in vitro and in vivo. BMS-986126 failed to inhibit assays downstream of MyD88-independent receptors, including the TNF receptor and TLR3. Very little activity was seen downstream of TLR4, which can also activate an MyD88-independent pathway. In mice, the compound inhibited cytokine production induced by injection of several different TLR agonists, including those for TLR2, TLR7, and TLR9. The compound also significantly suppressed skin inflammation induced by topical administration of the TLR7 agonist imiquimod. BMS-986126 demonstrated robust activity in the MRL/lpr and NZB/NZW models of lupus, inhibiting multiple pathogenic responses. In the MRL/lpr model, robust activity was observed with the combination of suboptimal doses of BMS-986126 and prednisolone, suggesting the potential for steroid sparing activity. BMS-986126 also demonstrated synergy with prednisolone in assays of TLR7- and TLR9-induced IFN target gene expression using human PBMCs. Lastly, BMS-986126 inhibited TLR7- and TLR9-dependent responses using cells derived from lupus patients, suggesting that inhibition of IRAK4 has the potential for therapeutic benefit in treating lupus. Copyright © 2017 by The American Association of Immunologists, Inc.

  16. Test, Evaluation, and Demonstration of Practical Devices/Systems to Reduce Aerodynamic Drag of Tractor/Semitrailer Combination Unit Trucks

    Energy Technology Data Exchange (ETDEWEB)

    Scott Smith; Karla Younessi; Matt Markstaller; Dan Schlesinger; Bhaskar Bhatnagar; Donald Smith; Bruno Banceu; Ron Schoon; V.K. Sharma; Mark Kachmarsky; Srikant Ghantae; Michael Sorrels; Conal Deedy; Justin Clark; Skip Yeakel; Michael D. Laughlin; Charlotte Seigler; Sidney Diamond

    2007-04-30

    effect on fuel economy was determined, either through on-road testing or full-size wind tunnel testing. All of the manufacturers worked with devices and systems that offer practical solutions to reduce aerodynamic drag, accounting for functionality, durability, cost effectiveness, reliability, and maintainability. The project team members and their roles and responsibilities are shown in Figure 2-1. Figure 2-2 shows the Phase I and II project schedules for all four projects and associated management activities.

  17. Deactivation of the inferior colliculus by cooling demonstrates intercollicular modulation of neuronal activity

    Directory of Open Access Journals (Sweden)

    Llwyd David Orton

    2012-12-01

    Full Text Available The auditory pathways coursing through the brainstem are organised bilaterally in mirror image about the midline and at several levels the two sides are interconnected. One of the most prominent points of interconnection is the commissure of the inferior colliculus (CoIC. Anatomical studies have revealed that these fibres make reciprocal connections which follow the tonotopic organisation of the inferior colliculus (IC, and that the commissure contains both excitatory and, albeit fewer, inhibitory fibres. The role of these connections in sound processing is largely unknown. Here we describe a method to address this question in the anaesthetised guinea pig. We used a cryoloop placed on one IC to produce reversible deactivation while recording electrophysiological responses to sounds in both ICs. We recorded single units, multi-unit clusters and local field potentials (LFPs before, during and after cooling. The degree and spread of cooling was measured with a thermocouple placed in the IC and other auditory structures. Cooling sufficient to eliminate firing was restricted to the IC contacted by the cryoloop. The temperature of other auditory brainstem structures, including the contralateral IC and the cochlea were minimally affected. Cooling below 20 °C reduced or eliminated the firing of action potentials in frequency laminae at depths corresponding to characteristic frequencies up to ~8 kHz. Modulation of neural activity also occurred in the un-cooled IC with changes in single unit firing and LFPs. Components of LFPs signalling lemniscal afferent input to the IC showed little change in amplitude or latency with cooling, whereas the later components, which likely reflect inter- and intra-collicular processing, showed marked changes in form and amplitude. We conclude that the cryoloop is an effective method of selectively deactivating one IC in guinea pig, and demonstrate that auditory processing in the IC is strongly influenced by the other.

  18. Demonstration of active vibration control on a stirling-cycle cryocooler testbed

    Science.gov (United States)

    Johnson, Bruce G.; Flynn, Frederick J.; Gaffney, Monique S.; Johnson, Dean L.; Ross, Ronald G., Jr.

    1992-01-01

    SatCon Technology Corporation has demonstrated excellent vibration reduction performance using active control on the JPL Stirling-cycle cryocooler testbed. The authors address the use of classical narrowband feedback control to meet the cryocooler vibration specifications using one cryocooler in a self-cancellation configuration. Similar vibration reduction performance was obtained using a cryocooler back-to-back configuration by actively controlling a reaction mass actuator that was used to mimic the second cooler.

  19. Direct conscious telemetry recordings demonstrate increased renal sympathetic nerve activity in rats with chronic kidney disease

    OpenAIRE

    Ibrahim M. Salman; Divya Sarma Kandukuri; Joanne Lesley Harrison; Cara Margaret Hildreth; Jacqueline Kathleen Phillips

    2015-01-01

    Chronic kidney disease (CKD) is associated with sympathetic hyperactivity and impaired blood pressure control reflex responses, yet direct evidence demonstrating these features of autonomic dysfunction in conscious animals is still lacking. Here we measured renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) using telemetry-based recordings in a rat model of CKD, the Lewis Polycystic Kidney (LPK) rat, and assessed responses to chemoreflex activation and acute stress. Male...

  20. A Classroom Activity to Demonstrate Self-Other Agreement in Personality Judgments

    Science.gov (United States)

    Kaplan, Seth A.; Stachowski, Alicia A.; Bradley-Geist, Jill C.

    2012-01-01

    This article describes a classroom activity to demonstrate (dis)agreement in personality judgments, using an exercise derived from Watson's research on the accuracy of rating strangers' personalities. On the first day of class, undergraduate students in psychology courses rated their own personality and the personality of a classmate, using items…

  1. Can Graduated Compressive Stockings Reduce Muscle Activity during Running?

    Science.gov (United States)

    Lucas-Cuevas, Ángel Gabriel; Priego Quesada, José Ignacio; Giménez, José Vicente; Aparicio, Inmaculada; Cortell-Tormo, Juan Manuel; Pérez-Soriano, Pedro

    2017-01-01

    Purpose: Graduated compressive stockings (GCS) have been suggested to influence performance by reducing muscle oscillations and improving muscle function and efficiency. However, no study to date has analyzed the influence of GCS on muscle activity during running. The objective of the study was to analyze the influence of GCS on the perception of…

  2. Reduced autonomic activity during stepwise exposure to high altitude

    NARCIS (Netherlands)

    Sevre, K; Bendz, B; Hanko, E; Nakstad, AR; Hauge, A; Kasin, JI; Lefrandt, JD; Smit, AJ; Eide, [No Value; Rostrup, M

    2001-01-01

    Several studies have shown increased sympathetic activity during acute exposure to hypobaric hypoxia. In a recent field study we found reduced plasma catecholamines during the first days after a stepwise ascent to high altitude. In the present study 14 subjects were exposed to a simulated ascent in

  3. Brown fat activation reduces hypercholesterolaemia and protects from atherosclerosis development

    NARCIS (Netherlands)

    Berbeé, J.F.P.; Boon, M.R.; Khedoe, P.P.S.J.; Bartelt, A.; Schlein, C.; Worthmann, A.; Kooijman, S.; Hoeke, G.; Mol, I.M.; John, C.; Jung, C.; Vazirpanah, N.; Brouwers, L.P.J.; Gordts, P.L.S.M.; Esko, J.D.; Hiemstra, P.S.; Havekes, L.M.; Scheja, L.; Heeren, J.; Rensen, P.C.N.

    2015-01-01

    Brown adipose tissue (BAT) combusts high amounts of fatty acids, thereby lowering plasma triglyceride levels and reducing obesity. However, the precise role of BAT in plasma cholesterol metabolism and atherosclerosis development remains unclear. Here we show that BAT activation by b3-adrenergic rece

  4. Low level laser therapy reduces inflammation in activated Achilles tendinitis

    Science.gov (United States)

    Bjordal, Jan M.; Iversen, Vegard; Lopes-Martins, Rodrigo Alvaro B.

    2006-02-01

    Objective: Low level laser therapy (LLLT) has been forwarded as therapy for osteoarthritis and tendinopathy. Results in animal and cell studies suggest that LLLT may act through a biological mechanism of inflammatory modulation. The current study was designed to investigate if LLLT has an anti-inflammatory effect on activated tendinitis of the Achilles tendon. Methods: Seven patients with bilateral Achilles tendonitis (14 tendons) who had aggravated symptoms by pain-inducing activity immediately prior to the study. LLLT (1.8 Joules for each of three points along the Achilles tendon with 904nm infrared laser) and placebo LLLT were administered to either Achilles tendons in a random order to which patients and therapist were blinded. Inflammation was examined by 1) mini-invasive microdialysis for measuring the concentration of inflammatory marker PGE II in the peritendinous tissue, 2) ultrasound with Doppler measurement of peri- and intratendinous blood flow, 3) pressure pain algometry and 4) single hop test. Results: PGE 2- levels were significantly reduced at 75, 90 and 105 minutes after active LLLT compared both to pre-treatment levels (p=0.026) and to placebo LLLT (p=0.009). Changes in pressure pain threshold (PPT) were significantly different (P=0.012) between groups. PPT increased by a mean value of 0.19 kg/cm2 [95%CI:0.04 to 0.34] after treatment in the active LLLT group, while pressure pain threshold was reduced by -0.20 kg/cm2 [95%CI:-0.45 to 0.05] after placebo LLLT. Conclusion: LLLT can be used to reduce inflammatory musculskeletal pain as it reduces inflammation and increases pressure pain threshold levels in activity-induced pain episodes of Achilles tendinopathy.

  5. In Situ Sediment Treatment Using Activated Carbon: A Demonstrated Sediment Cleanup Technology

    Science.gov (United States)

    Patmont, Clayton R; Ghosh, Upal; LaRosa, Paul; Menzie, Charles A; Luthy, Richard G; Greenberg, Marc S; Cornelissen, Gerard; Eek, Espen; Collins, John; Hull, John; Hjartland, Tore; Glaza, Edward; Bleiler, John; Quadrini, James

    2015-01-01

    This paper reviews general approaches for applying activated carbon (AC) amendments as an in situ sediment treatment remedy. In situ sediment treatment involves targeted placement of amendments using installation options that fall into two general approaches: 1) directly applying a thin layer of amendments (which potentially incorporates weighting or binding materials) to surface sediment, with or without initial mixing; and 2) incorporating amendments into a premixed, blended cover material of clean sand or sediment, which is also applied to the sediment surface. Over the past decade, pilot- or full-scale field sediment treatment projects using AC—globally recognized as one of the most effective sorbents for organic contaminants—were completed or were underway at more than 25 field sites in the United States, Norway, and the Netherlands. Collectively, these field projects (along with numerous laboratory experiments) have demonstrated the efficacy of AC for in situ treatment in a range of contaminated sediment conditions. Results from experimental studies and field applications indicate that in situ sequestration and immobilization treatment of hydrophobic organic compounds using either installation approach can reduce porewater concentrations and biouptake significantly, often becoming more effective over time due to progressive mass transfer. Certain conditions, such as use in unstable sediment environments, should be taken into account to maximize AC effectiveness over long time periods. In situ treatment is generally less disruptive and less expensive than traditional sediment cleanup technologies such as dredging or isolation capping. Proper site-specific balancing of the potential benefits, risks, ecological effects, and costs of in situ treatment technologies (in this case, AC) relative to other sediment cleanup technologies is important to successful full-scale field application. Extensive experimental studies and field trials have shown that when

  6. In Vitro and in Vivo Demonstration of Photodynamic Activity and Cytoplasm Imaging through TPE Nanoparticles.

    Science.gov (United States)

    Jayaram, Dhanya T; Ramos-Romero, Sara; Shankar, Balaraman H; Garrido, Cristina; Rubio, Nuria; Sanchez-Cid, Lourdes; Gómez, Salvador Borros; Blanco, Jeronimo; Ramaiah, Danaboyina

    2016-01-15

    We synthesized novel tetraphenylethene (TPE) conjugates, which undergo unique self-assembly to form spherical nanoparticles that exhibited aggregation induced emission (AIE) in the near-infrared region. These nanoparticles showed significant singlet oxygen generation efficiency, negligible dark toxicity, rapid cellular uptake, efficient localization in cytoplasm, and high in vitro photocytotoxicity as well as in vivo photodynamic activity against a human prostate tumor animal model. This study demonstrates, for the first time, the power of the self-assembled AIE active tetraphenylethene conjugates in aqueous media as a nanoplatform for future therapeutic applications.

  7. Comparative metagenomics demonstrating different degradative capacity of activated biomass treating hydrocarbon contaminated wastewater.

    Science.gov (United States)

    Yadav, Trilok Chandra; Pal, Rajesh Ramavadh; Shastri, Sunita; Jadeja, Niti B; Kapley, Atya

    2015-01-01

    This study demonstrates the diverse degradative capacity of activated biomass, when exposed to different levels of total dissolved solids (TDS) using a comparative metagenomics approach. The biomass was collected at two time points to examine seasonal variations. Four metagenomes were sequenced on Illumina Miseq platform and analysed using MG-RAST. STAMP tool was used to analyse statistically significant differences amongst different attributes of metagenomes. Metabolic pathways related to degradation of aromatics via the central and peripheral pathways were found to be dominant in low TDS metagenome, while pathways corresponding to central carbohydrate metabolism, nitrogen, organic acids were predominant in high TDS sample. Seasonal variation was seen to affect catabolic gene abundance as well as diversity of the microbial community. Degradation of model compounds using activated sludge demonstrated efficient utilisation of single aromatic ring compounds in both samples but cyclic compounds were not efficiently utilised by biomass exposed to high TDS.

  8. Expression of feline recombinant interferon-gamma in baculovirus and demonstration of biological activity.

    Science.gov (United States)

    Argyle, D J; Harris, M; Lawrence, C; McBride, K; Barron, R; McGillivray, C; Onions, D E

    1998-07-08

    We have previously reported the cloning of the coding sequence for feline-specific interferon-gamma. Here, we describe the expression of this sequence in a baculovirus system and demonstrate the biological activity of the recombinant protein. The coding sequence for feline interferon was directionally cloned into the baculovirus transfer vector pAcCL29-1. Transfer vector and linearized wild-type AcMNPV (BacPAK6) were used to co-transfect Sf9 cells by calcium phosphate coprecipitation. Subsequently, wild-type and recombinant viruses were separated by plaque assay. Recombinant plaques were expanded and a master stock of virus is produced. Production of biologically active interferon-gamma from infected Sf9 cells was demonstrated using a standard cytopathic effect reduction assay, utilising vesicular stomatitis virus (VSV), and an MHC class II induction assay.

  9. Novel active noise-reducing headset using earshell vibration control.

    Science.gov (United States)

    Rafaely, Boaz; Carrilho, Joao; Gardonio, Paolo

    2002-10-01

    Active noise-reducing (ANR) headsets are available commercially in applications varying from aviation communication to consumer audio. Current ANR systems use passive attenuation at high frequencies and loudspeaker-based active noise control at low frequencies to achieve broadband noise reduction. This paper presents a novel ANR headset in which the external noise transmitted to the user's ear via earshell vibration is reduced by controlling the vibration of the earshell using force actuators acting against an inertial mass or the earshell headband. Model-based theoretical analysis using velocity feedback control showed that current piezoelectric actuators provide sufficient force but require lower stiffness for improved low-frequency performance. Control simulations based on experimental data from a laboratory headset showed that good performance can potentially be achieved in practice by a robust feedback controller, while a single-frequency real-time control experiment verified that noise reduction can be achieved using earshell vibration control.

  10. Mutagenic activation reduces carcinogenic activity of ortho-aminoazotoluene for mouse liver.

    Science.gov (United States)

    Ovchinnikova, L P; Bogdanova, L A; Kaledin, V I

    2013-03-01

    Pentachlorophenol (aromatic amine and azo stain metabolic stimulation inhibitor) reduced the hepatocarcinogenic activity of 4-aminoazobenzene and reduced that of ortho-aminoazotoluene in suckling mice. Both 4-aminoazobenzene and ortho-aminoazotoluene exhibited mutagenic activity in Ames' test in vitro on S. typhimurium TA 98 strain with activation with liver enzymes; this mutagenic activity was similarly suppressed by adding pentachlorophenol into activation medium. Induction of xenobiotic metabolism enzymes, stimulating the mutagenic activity of ortho-aminoazotoluene, suppressed its carcinogenic effect on mouse liver. Hence, ortho-aminotoluene (the initial compound), but not its mutagenic metabolites, was the direct active hepatocarcinogen for mice.

  11. Demonstration of Motor Imagery- and Phantom-Movement Related Neuronal Activity in Human Thalamus

    OpenAIRE

    Anderson, William S.; Weiss, Nirit; Lawson, Herman Christopher; Ohara, Shinji; Rowland, Lance; Lenz, Frederick A.

    2011-01-01

    Functional imaging studies demonstrate that motor imagery activates multiple structures in the human forebrain. We now show that phantom movements in an amputee and imagined movements in intact subjects elicit responses from neurons in several human thalamic nuclei. These include the somatic sensory nucleus receiving input from the periphery (ventral caudal – Vc), and the motor nuclei receiving input from the cerebellum (ventral intermediate -Vim) and the basal ganglia (ventral oral posterior...

  12. Novel bacterial metabolite merochlorin A demonstrates in vitro activity against multi-drug resistant methicillin-resistant Staphylococcus aureus.

    Directory of Open Access Journals (Sweden)

    George Sakoulas

    Full Text Available BACKGROUND: We evaluated the in vitro activity of a merochlorin A, a novel compound with a unique carbon skeleton, against a spectrum of clinically relevant bacterial pathogens and against previously characterized clinical and laboratory Staphylococcus aureus isolates with resistance to numerous antibiotics. METHODS: Merochlorin A was isolated and purified from a marine-derived actinomycete strain CNH189. Susceptibility testing for merochlorin A was performed against previously characterized human pathogens using broth microdilution and agar dilution methods. Cytotoxicity was assayed in tissue culture assays at 24 and 72 hours against human HeLa and mouse sarcoma L929 cell lines. RESULTS: The structure of as new antibiotic, merochlorin A, was assigned by comprehensive spectroscopic analysis. Merochlorin A demonstrated in vitro activity against Gram-positive bacteria, including Clostridium dificile, but not against Gram negative bacteria. In S. aureus, susceptibility was not affected by ribosomal mutations conferring linezolid resistance, mutations in dlt or mprF conferring resistance to daptomycin, accessory gene regulator knockout mutations, or the development of the vancomycin-intermediate resistant phenotype. Merochlorin A demonstrated rapid bactericidal activity against MRSA. Activity was lost in the presence of 20% serum. CONCLUSIONS: The unique meroterpenoid, merochlorin A demonstrated excellent in vitro activity against S. aureus and C. dificile and did not show cross-resistance to contemporary antibiotics against Gram positive organisms. The activity was, however, markedly reduced in 20% human serum. Future directions for this compound may include evaluation for topical use, coating biomedical devices, or the pursuit of chemically modified derivatives of this compound that retain activity in the presence of serum.

  13. Reduced PKC α Activity Induces Senescent Phenotype in Erythrocytes

    Directory of Open Access Journals (Sweden)

    Rukmini B. Govekar

    2012-01-01

    Full Text Available The molecular mechanism mediating expression of senescent cell antigen-aggregated or cleaved band 3 and externalized phosphatidylserine (PS on the surface of aged erythrocytes and their premature expression in certain anemias is not completely elucidated. The erythrocytes with these surface modifications undergo macrophage-mediated phagocytosis. In this study, the role of protein kinase C (PKC isoforms in the expression of these surface modifications was investigated. Inhibition of PKC α by 30 μM rottlerin (R30 and 2.3 nM Gö 6976 caused expression of both the senescent cell marker-externalized PS measured by FACS analysis and aggregated band 3 detected by western blotting. In contrast to this observation, but in keeping with literature, PKC activation by phorbol-12-myristate-13-acetate (PMA also led to the expression of senescence markers. We explain this antithesis by demonstrating that PMA-treated cells show reduction in the activity of PKC α, thereby simulating inhibition. The reduction in PKC α activity may be attributed to the known downregulation of PMA-activated PKC α, caused by its membrane translocation and proteolysis. We demonstrate membrane translocation of PKC α in PMA-treated cells to substantiate this inference. Thus loss of PKC α activity either by inhibition or downregulation can cause surface modifications which can trigger erythrophagocytosis.

  14. Innovative Adaptive Control Method Demonstrated for Active Suppression of Instabilities in Engine Combustors

    Science.gov (United States)

    Kopasakis, George

    2005-01-01

    This year, an improved adaptive-feedback control method was demonstrated that suppresses thermoacoustic instabilities in a liquid-fueled combustor of a type used in aircraft engines. Extensive research has been done to develop lean-burning (low fuel-to-air ratio) combustors that can reduce emissions throughout the mission cycle to reduce the environmental impact of aerospace propulsion systems. However, these lean-burning combustors are susceptible to thermoacoustic instabilities (high-frequency pressure waves), which can fatigue combustor components and even downstream turbine blades. This can significantly decrease the safe operating life of the combustor and turbine. Thus, suppressing the thermoacoustic combustor instabilities is an enabling technology for meeting the low-emission goals of the NASA Ultra-Efficient Engine Technology (UEET) Project.

  15. Demonstration of alternative and classical complement pathway activity in colostrum from buffalo (Bubalus bubalis).

    Science.gov (United States)

    Matheswaran, K; Dhinakar Raj, G; Nachimuthu, K

    2003-09-01

    Buffalo colostrum caused lysis of unsensitized red blood cells (RBC) from sheep, goats, rabbits and chickens. RBC from cattle and buffalo were resistant to lysis. That lysis was due to the presence of natural antibodies to these RBC was ruled out since there was no reduction in haemolytic titres even after adsorption with the respective RBC. The addition of EGTA to the diluent had no effect on the haemolytic activity. These findings indicate the presence of alternative complement pathway (ACP) activity in buffalo colostrum. The haemolytic activity of buffalo complement for unsensitized rabbit RBC was reduced to very low levels by heating at 50 degrees C for 45 min. Treatment with zymosan also inhibited the haemolytic activity, while inulin had no effect. The maximum activity of ACP occurred in the presence of 4 mmol/L Mg(2+) in the diluent. The range of ACP activities in colostrum from buffaloes varied from 4.06 to 8.48 CH50 units/ml. Using a standard system for titrating the classical complement pathway and rabbit red blood cells sensitized with goat haemolysin, the range of complement activity in buffalo colostrum was 4.81-6.77 CH50/ml.

  16. Low-chromium reduced-activation ferritic steels for fusion

    Energy Technology Data Exchange (ETDEWEB)

    Klueh, R.L.; Alexander, D.J.; Kenik, E.A. [Oak Ridge National Laboratory, TN (United States)

    1996-04-01

    Development of reduced-activation ferritic steels has concentrated on high-chromium (8-10 wt% Cr) steels. However, there are advantages for a low-chromium steel, and initial ORNL studies on reduced-activation steels were on compositions with 2.25 to 12% Cr. Those studies showed an Fe-2.25Cr-2W-0.25V-0.1C (2 1/4Cr-2WV) steel to have the highest strenglth of the steels studied. Although this steel had the best strength, Charpy impact properties were inferior to those of an Fe-9Cr-2W-0.25V-0.07Ta-0.1C (9Cr-2WVTa) and an Fe-2.25Cr-2W-0.1C (2 1/4Cr-2W) steel. Therefore, further development of the low-chromium Cr-W steels was required. These results indicate that it is possible to develop low-chromium reduced-activation ferritic steels that have tensile and impact properties as good or better than those of high-chromium (7-9% Cr) steels. Further improvement of properties should be possible by optimizing the composition.

  17. Active vibration control testing of the SPICES program: final demonstration article

    Science.gov (United States)

    Dunne, James P.; Jacobs, Jack H.

    1996-05-01

    The Synthesis and Processing of Intelligent Cost Effective Structures (SPICES) Program is a partnership program sponsored by the Advanced Research Projects Agency. The mission of the program is to develop cost effective material processing and synthesis technologies to enable new products employing active vibration suppression and control devices to be brought to market. The two year program came to fruition in 1995 through the fabrication of the final smart components and testing of an active plate combined with two trapezoidal rails, forming an active mount. Testing of the SPICES combined active mount took place at McDonnell Douglas facilities in St. Louis, MO, in October-December 1995. Approximately 15 dB reduction in overall response of a motor mounted on the active structure was achieved. Further details and results of the SPICES combined active mount demonstration testing are outlined. Results of numerous damping and control strategies that were developed and employed in the testing are presented, as well as aspects of the design and fabrication of the SPICES active mount components.

  18. The Second-Generation Exportin-1 Inhibitor KPT-8602 Demonstrates Potent Activity against Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Vercruysse, Thomas; De Bie, Jolien; Neggers, Jasper E; Jacquemyn, Maarten; Vanstreels, Els; Schmid-Burgk, Jonathan L; Hornung, Veit; Baloglu, Erkan; Landesman, Yosef; Senapedis, William; Shacham, Sharon; Dagklis, Antonis; Cools, Jan; Daelemans, Dirk

    2016-10-25

    Purpose: Human exportin-1 (XPO1) is the key nuclear-cytoplasmic transport protein that exports different cargo proteins out of the nucleus. Inducing nuclear accumulation of these proteins by inhibiting XPO1 causes cancer cell death. First clinical validation of pharmacological inhibition of XPO1 was obtained with the Selective Inhibitor of Nuclear Export (SINE) compound selinexor (KPT-330) demonstrating activity in phase-II/IIb clinical trials when dosed 1 to 3 times weekly. The second-generation SINE compound KPT-8602 shows improved tolerability and can be dosed daily. Here, we investigate and validate the drug-target interaction of KPT-8602 and explore its activity against acute lymphoblastic leukemia (ALL).Experimental Design: We examined the effect of KPT-8602 on XPO1 function and XPO1-cargo as well as on a panel of leukemia cell lines. Mutant XPO1 leukemia cells were designed to validate KPT-8602's drug-target interaction. In vivo, anti-ALL activity was measured in a mouse ALL model and patient-derived ALL xenograft models.Results: KPT-8602 induced caspase-dependent apoptosis in a panel of leukemic cell lines in vitro Using CRISPR/Cas9 genome editing, we demonstrated the specificity of KPT-8602 for cysteine 528 in the cargo-binding groove of XPO1 and validated the drug target interaction. In vivo, KPT-8602 showed potent anti-leukemia activity in a mouse ALL model as well as in patient-derived T- and B-ALL xenograft models without affecting normal hematopoiesis.Conclusions: KPT-8602 is highly specific for XPO1 inhibition and demonstrates potent anti-leukemic activity supporting clinical application of the second-generation SINE compound for the treatment of ALL. Clin Cancer Res; 1-14. ©2016 AACR.

  19. The Lytic SA Phage Demonstrate Bactericidal Activity against Mastitis Causing Staphylococcus aureus

    Directory of Open Access Journals (Sweden)

    Hamza Ameer

    2016-01-01

    Full Text Available Staphylococcus aureus is the major causative agent of mastitis among dairy animals as it causes intramammary gland infection. Due to antibiotic resistance and contamination of antibiotics in the milk of diseased animals; alternative therapeutic agents are required to cure mastitis. Lytic bacteriophages and their gene products can be potential therapeutic agents against bacteria as they are host specific and less harmful than antibiotics. In this study, Staphylococcus aureus were isolated from milk samples of the infected animals and identified biochemically. SA phage was isolated from sewage water showing lytic activity against Staphylococcus aureus isolates. The highest lytic activity of bacteriophages was observed at 37°C and pH 7, and the most suitable storage condition was at 4°C. SA phage efficiently reduced bacterial growth in the bacterial reduction assay. The characterization and bacterial growth reduction activity of the bacteriophages against Staphylococcus aureus signifies their underlying potential of phage therapy against mastitis.

  20. In vivo characterization of estrogen receptor modulators with reduced genomic versus nongenomic activity in vitro.

    Science.gov (United States)

    Otto, Christiane; Fuchs, Iris; Altmann, Helga; Klewer, Mario; Schwarz, Gilda; Bohlmann, Rolf; Nguyen, Duy; Zorn, Ludwig; Vonk, Richardus; Prelle, Katja; Osterman, Thua; Malmström, Chira; Fritzemeier, Karl-Heinrich

    2008-07-01

    Estrogen receptor (ER) ligands that are able to prevent postmenopausal bone loss, but have reduced activity in the uterus and the mammary gland might be of great value for hormone therapy. It is well established that the classical ER can activate genomic as well as nongenomic signal transduction pathways. In this study, we analyse the in vivo behaviour of ER ligands that stimulate nongenomic ER effects to the same extent as estradiol, but show clearly reduced activation of genomic ER effects in vitro. Using different readout parameters such as morphological changes, cellular proliferation, and target gene induction, we are able to demonstrate that ER ligands with reduced genomic activity in vitro show a better dissociation of bone versus uterine and mammary gland effects than estradiol that stimulates genomic and nongenomic effects to the same extent. We conclude that pathway-selective ER ligands may represent an interesting option for hormone therapy.

  1. Feasibility of Actively Cooled Silicon Nitride Airfoil for Turbine Applications Demonstrated

    Science.gov (United States)

    Bhatt, Ramakrishna T.

    2001-01-01

    Nickel-base superalloys currently limit gas turbine engine performance. Active cooling has extended the temperature range of service of nickel-base superalloys in current gas turbine engines, but the margin for further improvement appears modest. Therefore, significant advancements in materials technology are needed to raise turbine inlet temperatures above 2400 F to increase engine specific thrust and operating efficiency. Because of their low density and high-temperature strength and thermal conductivity, in situ toughened silicon nitride ceramics have received a great deal of attention for cooled structures. However, the high processing costs and low impact resistance of silicon nitride ceramics have proven to be major obstacles for widespread applications. Advanced rapid prototyping technology in combination with conventional gel casting and sintering can reduce high processing costs and may offer an affordable manufacturing approach. Researchers at the NASA Glenn Research Center, in cooperation with a local university and an aerospace company, are developing actively cooled and functionally graded ceramic structures. The objective of this program is to develop cost-effective manufacturing technology and experimental and analytical capabilities for environmentally stable, aerodynamically efficient, foreign-object-damage-resistant, in situ toughened silicon nitride turbine nozzle vanes, and to test these vanes under simulated engine conditions. Starting with computer aided design (CAD) files of an airfoil and a flat plate with internal cooling passages, the permanent and removable mold components for gel casting ceramic slips were made by stereolithography and Sanders machines, respectively. The gel-cast part was dried and sintered to final shape. Several in situ toughened silicon nitride generic airfoils with internal cooling passages have been fabricated. The uncoated and thermal barrier coated airfoils and flat plates were burner rig tested for 30 min without

  2. Blockade of mast cell activation reduces cutaneous scar formation.

    Science.gov (United States)

    Chen, Lin; Schrementi, Megan E; Ranzer, Matthew J; Wilgus, Traci A; DiPietro, Luisa A

    2014-01-01

    Damage to the skin initiates a cascade of well-orchestrated events that ultimately leads to repair of the wound. The inflammatory response is key to wound healing both through preventing infection and stimulating proliferation and remodeling of the skin. Mast cells within the tissue are one of the first immune cells to respond to trauma, and upon activation they release pro-inflammatory molecules to initiate recruitment of leukocytes and promote a vascular response in the tissue. Additionally, mast cells stimulate collagen synthesis by dermal fibroblasts, suggesting they may also influence scar formation. To examine the contribution of mast cells in tissue repair, we determined the effects the mast cell inhibitor, disodium cromoglycate (DSCG), on several parameters of dermal repair including, inflammation, re-epithelialization, collagen fiber organization, collagen ultrastructure, scar width and wound breaking strength. Mice treated with DSCG had significantly reduced levels of the inflammatory cytokines IL-1α, IL-1β, and CXCL1. Although DSCG treatment reduced the production of inflammatory mediators, the rate of re-epithelialization was not affected. Compared to control, inhibition of mast cell activity caused a significant decrease in scar width along with accelerated collagen re-organization. Despite the reduced scar width, DSCG treatment did not affect the breaking strength of the healed tissue. Tryptase β1 exclusively produced by mast cells was found to increase significantly in the course of wound healing. However, DSCG treatment did not change its level in the wounds. These results indicate that blockade of mast cell activation reduces scar formation and inflammation without further weakening the healed wound.

  3. Blockade of mast cell activation reduces cutaneous scar formation.

    Directory of Open Access Journals (Sweden)

    Lin Chen

    Full Text Available Damage to the skin initiates a cascade of well-orchestrated events that ultimately leads to repair of the wound. The inflammatory response is key to wound healing both through preventing infection and stimulating proliferation and remodeling of the skin. Mast cells within the tissue are one of the first immune cells to respond to trauma, and upon activation they release pro-inflammatory molecules to initiate recruitment of leukocytes and promote a vascular response in the tissue. Additionally, mast cells stimulate collagen synthesis by dermal fibroblasts, suggesting they may also influence scar formation. To examine the contribution of mast cells in tissue repair, we determined the effects the mast cell inhibitor, disodium cromoglycate (DSCG, on several parameters of dermal repair including, inflammation, re-epithelialization, collagen fiber organization, collagen ultrastructure, scar width and wound breaking strength. Mice treated with DSCG had significantly reduced levels of the inflammatory cytokines IL-1α, IL-1β, and CXCL1. Although DSCG treatment reduced the production of inflammatory mediators, the rate of re-epithelialization was not affected. Compared to control, inhibition of mast cell activity caused a significant decrease in scar width along with accelerated collagen re-organization. Despite the reduced scar width, DSCG treatment did not affect the breaking strength of the healed tissue. Tryptase β1 exclusively produced by mast cells was found to increase significantly in the course of wound healing. However, DSCG treatment did not change its level in the wounds. These results indicate that blockade of mast cell activation reduces scar formation and inflammation without further weakening the healed wound.

  4. A Demonstration Project on Driving with Reduced Visual Acuity and a Bioptic Telescope System in the Netherlands

    NARCIS (Netherlands)

    Melis-Dankers, Bart J.M.; Kooijman, Aart C.; Brouwer, Wiebo H.; Busscher, Rens B.; Bredewoud, Ruud A.; Derksen, Peter H.; Amersfoort, Anoeska; IJsseldijk, Martin A.M.; Delden, Geert W. van; Grotenhuis, Thea H.P.A.; Witvliet, M.D.

    2008-01-01

    Background: In Europe, driving a passenger car is prohibited if binocular best corrected visual acuity (BCVA) is below 0.5 (20/40). Some US states allow people with reduced visual acuity to use a bioptic telescope system when driving. The aim of our study is to introduce a bioptic telescope system

  5. Laboratory demonstration of a primary active mirror for space with the LATT: large aperture telescope technology

    Science.gov (United States)

    Briguglio, Runa; Biasi, Roberto; Gallieni, Daniele; Vettore, Christian; d'Amato, Francesco; Xompero, Marco; Arcidiacono, Carmelo; Lisi, Franco; Riccardi, Armando; Patauner, Christian; Lazzarini, Paolo; Tintori, Matteo; Duò, Fabrizio; Pucci, Mauro; Zuccaro Marchi, Alessandro; Maresi, Luca

    2016-07-01

    The LATT project is an ESA contract under TRP programme to demonstrate the scalability of the technology from ground-based adaptive mirrors to space active primary mirrors. A prototype spherical mirror based on a 40 cm diameter 1 mm thin glass shell with 19 contactless, voice-coil actuators and co-located position sensors have been manufactured and integrated into a final unit with an areal density lower than 20 kg/m2. Laboratory tests demonstrated the controllability with very low power budget and the survival of the fragile glass shell exposed to launch accelerations, thanks to an electrostatic locking mechanism; such achievements pushes the technology readiness level toward 5. With this prototype, the LATT project explored the feasibility of using an active and lightweight primary for space telescopes. The concept is attractive for large segmented telescopes, with surface active control to shape and co-phase them once in flight. In this paper we will describe the findings of the technological advances and the results of the environmental and optical tests.

  6. Radioactive Demonstrations Of Fluidized Bed Steam Reforming (FBSR) With Hanford Low Activity Wastes

    Energy Technology Data Exchange (ETDEWEB)

    Jantzen, C. M.; Crawford, C. L.; Burket, P. R.; Bannochie, C. J.; Daniel, W. G.; Nash, C. A.; Cozzi, A. D.; Herman, C. C.

    2012-10-22

    Several supplemental technologies for treating and immobilizing Hanford low activity waste (LAW) are being evaluated. One immobilization technology being considered is Fluidized Bed Steam Reforming (FBSR) which offers a low temperature (700-750?C) continuous method by which wastes high in organics, nitrates, sulfates/sulfides, or other aqueous components may be processed into a crystalline ceramic (mineral) waste form. The granular waste form produced by co-processing the waste with kaolin clay has been shown to be as durable as LAW glass. The FBSR granular product will be monolithed into a final waste form. The granular component is composed of insoluble sodium aluminosilicate (NAS) feldspathoid minerals such as sodalite. Production of the FBSR mineral product has been demonstrated both at the industrial, engineering, pilot, and laboratory scales on simulants. Radioactive testing at SRNL commenced in late 2010 to demonstrate the technology on radioactive LAW streams which is the focus of this study.

  7. RemoveDEBRIS: An in-orbit active debris removal demonstration mission

    Science.gov (United States)

    Forshaw, Jason L.; Aglietti, Guglielmo S.; Navarathinam, Nimal; Kadhem, Haval; Salmon, Thierry; Pisseloup, Aurélien; Joffre, Eric; Chabot, Thomas; Retat, Ingo; Axthelm, Robert; Barraclough, Simon; Ratcliffe, Andrew; Bernal, Cesar; Chaumette, François; Pollini, Alexandre; Steyn, Willem H.

    2016-10-01

    Since the beginning of the space era, a significant amount of debris has progressively been generated. Most of the objects launched into space are still orbiting the Earth and today these objects represent a threat as the presence of space debris incurs risk of collision and damage to operational satellites. A credible solution has emerged over the recent years: actively removing debris objects by capturing them and disposing of them. This paper provides an update to the mission baseline and concept of operations of the EC FP7 RemoveDEBRIS mission drawing on the expertise of some of Europe's most prominent space institutions in order to demonstrate key active debris remove (ADR) technologies in a low-cost ambitious manner. The mission will consist of a microsatellite platform (chaser) that ejects 2 CubeSats (targets). These targets will assist with a range of strategically important ADR technology demonstrations including net capture, harpoon capture and vision-based navigation using a standard camera and LiDAR. The chaser will also host a drag sail for orbital lifetime reduction. The mission baseline has been revised to take into account feedback from international and national space policy providers in terms of risk and compliance and a suitable launch option is selected. A launch in 2017 is targeted. The RemoveDEBRIS mission aims to be one of the world's first in-orbit demonstrations of key technologies for active debris removal and is a vital prerequisite to achieving the ultimate goal of a cleaner Earth orbital environment.

  8. Demonstration of a 4-Sensor Folded Sangac Sensor Array with Active Phase Biasing Scheme

    Institute of Scientific and Technical Information of China (English)

    Zhang-Qi Song; Ming-Ye Yang; Xue-Liang Zhang; Yong-Ming Hu

    2008-01-01

    A 4-sensor folded Sagnae sensor array with an active phase biasing scheme is presented. The overlapping of the signal and noise pulse is avoided through a time division multiplexing scheme and the noise pulses is eliminated almost completely. The scheme can address 16 sensors when the repeat frequency of input pulse is at 68.3 kHz. The alternative phase bias technique is demonstrated, which can provide sensors with stable phase bias. The future benefit of this technique is that the 1/f noise in the circuit can be suppressed.

  9. Direct conscious telemetry recordings demonstrate increased renal sympathetic nerve activity in rats with chronic kidney disease.

    Science.gov (United States)

    Salman, Ibrahim M; Sarma Kandukuri, Divya; Harrison, Joanne L; Hildreth, Cara M; Phillips, Jacqueline K

    2015-01-01

    Chronic kidney disease (CKD) is associated with sympathetic hyperactivity and impaired blood pressure control reflex responses, yet direct evidence demonstrating these features of autonomic dysfunction in conscious animals is still lacking. Here we measured renal sympathetic nerve activity (RSNA) and mean arterial pressure (MAP) using telemetry-based recordings in a rat model of CKD, the Lewis Polycystic Kidney (LPK) rat, and assessed responses to chemoreflex activation and acute stress. Male LPK and Lewis control animals (total n = 16) were instrumented for telemetric recording of RSNA and MAP. At 12-13 weeks-of-age, resting RSNA and MAP, sympathetic and haemodynamic responses to both peripheral (hypoxia: 10% O2) and central chemoreflex (hypercapnia: 7% CO2) activation and acute stress (open-field exposure), were measured. As indicators of renal function, urinary protein (UPro) and creatinine (UCr) levels were assessed. LPK rats had higher resting RSNA (1.2 ± 0.1 vs. 0.6 ± 0.1 μV, p dual conscious telemetry recording of RSNA and MAP in a genetic rodent model of CKD. Elevated RSNA is likely a key contributor to the marked hypertension in this model, while attenuated RSNA and MAP responses to central chemoreflex activation and acute stress in the LPK indicate possible deficits in the neural processing of autonomic outflows evoked by these sympathoexcitatory pathways.

  10. Complementary effects of antioxidants and sunscreens in reducing UV-induced skin damage as demonstrated by skin biomarker expression.

    Science.gov (United States)

    Oresajo, Christian; Yatskayer, Margarita; Galdi, Angelike; Foltis, Peter; Pillai, Sreekumar

    2010-06-01

    UV-exposure of the skin causes oxidative stress, leading to inflammatory reactions and premature skin aging. Sunscreens protect by absorbing or reflecting UV on the skin surface. Antioxidants provide protection by quenching UV-induced reactive oxygen species inside skin. To evaluate the complementary photoprotective benefits of formulas containing either an antioxidant complex of Cassia alata leaf extract or a combination of the antioxidant complex and sunscreens on normal healthy volunteers using biomarkers of skin damage. Each formula and a placebo control were applied separately to selected areas on the lower back of 10 individuals for 4 consecutive days. On Day 4, the control and three test sites were exposed to 5 x MED (minimal erythemal dose) of solar-simulated UV-irradiation (UVR). On Day 5, 4-mm punch biopsies were collected from the four exposed sites and a control site (untreated, unexposed) for immunohistochemistry. Exposure to 5 x MED demonstrated significant damage as assessed by thymine dimer formation, MMP-9 and p53 protein expression on untreated exposed skin. The formula containing sunscreens + the antioxidant complex was the most protective, followed by the formula with the antioxidant alone. The study demonstrated that a combination of antioxidants and sunscreens complement each other, resulting in superior photoprotection.

  11. The impact of initiation: Early onset marijuana smokers demonstrate altered Stroop performance and brain activation

    Directory of Open Access Journals (Sweden)

    K.A. Sagar

    2015-12-01

    Full Text Available Marijuana (MJ use is on the rise, particularly among teens and emerging adults. This poses serious public health concern, given the potential deleterious effects of MJ on the developing brain. We examined 50 chronic MJ smokers divided into early onset (regular MJ use prior to age 16; n = 24 and late onset (age 16 or later; n = 26, and 34 healthy control participants (HCs. All completed a modified Stroop Color Word Test during fMRI. Results demonstrated that MJ smokers exhibited significantly poorer performance on the Interference subtest of the Stroop, as well as altered patterns of activation in the cingulate cortex relative to HCs. Further, early onset MJ smokers exhibited significantly poorer performance relative to both HCs and late onset smokers. Additionally, earlier age of MJ onset as well as increased frequency and magnitude (grams/week of MJ use were predictive of poorer Stroop performance. fMRI results revealed that while late onset smokers demonstrated a more similar pattern of activation to the control group, a different pattern was evident in the early onset group. These findings underscore the importance of assessing age of onset and patterns of MJ use and support the need for widespread education and intervention efforts among youth.

  12. Meditation leads to reduced default mode network activity beyond an active task.

    Science.gov (United States)

    Garrison, Kathleen A; Zeffiro, Thomas A; Scheinost, Dustin; Constable, R Todd; Brewer, Judson A

    2015-09-01

    Meditation has been associated with relatively reduced activity in the default mode network, a brain network implicated in self-related thinking and mind wandering. However, previous imaging studies have typically compared meditation to rest, despite other studies having reported differences in brain activation patterns between meditators and controls at rest. Moreover, rest is associated with a range of brain activation patterns across individuals that has only recently begun to be better characterized. Therefore, in this study we compared meditation to another active cognitive task, both to replicate the findings that meditation is associated with relatively reduced default mode network activity and to extend these findings by testing whether default mode activity was reduced during meditation, beyond the typical reductions observed during effortful tasks. In addition, prior studies had used small groups, whereas in the present study we tested these hypotheses in a larger group. The results indicated that meditation is associated with reduced activations in the default mode network, relative to an active task, for meditators as compared to controls. Regions of the default mode network showing a Group × Task interaction included the posterior cingulate/precuneus and anterior cingulate cortex. These findings replicate and extend prior work indicating that the suppression of default mode processing may represent a central neural process in long-term meditation, and they suggest that meditation leads to relatively reduced default mode processing beyond that observed during another active cognitive task.

  13. Levetiracetam reduces abnormal network activations in temporal lobe epilepsy

    Science.gov (United States)

    Wandschneider, Britta; Stretton, Jason; Sidhu, Meneka; Centeno, Maria; Kozák, Lajos R.; Symms, Mark; Thompson, Pamela J.; Duncan, John S.

    2014-01-01

    Objective: We used functional MRI (fMRI) and a left-lateralizing verbal and a right-lateralizing visual-spatial working memory (WM) paradigm to investigate the effects of levetiracetam (LEV) on cognitive network activations in patients with drug-resistant temporal lobe epilepsy (TLE). Methods: In a retrospective study, we compared task-related fMRI activations and deactivations in 53 patients with left and 54 patients with right TLE treated with (59) or without (48) LEV. In patients on LEV, activation patterns were correlated with the daily LEV dose. Results: We isolated task- and syndrome-specific effects. Patients on LEV showed normalization of functional network deactivations in the right temporal lobe in right TLE during the right-lateralizing visual-spatial task and in the left temporal lobe in left TLE during the verbal task. In a post hoc analysis, a significant dose-dependent effect was demonstrated in right TLE during the visual-spatial WM task: the lower the LEV dose, the greater the abnormal right hippocampal activation. At a less stringent threshold (p < 0.05, uncorrected for multiple comparisons), a similar dose effect was observed in left TLE during the verbal task: both hippocampi were more abnormally activated in patients with lower doses, but more prominently on the left. Conclusions: Our findings suggest that LEV is associated with restoration of normal activation patterns. Longitudinal studies are necessary to establish whether the neural patterns translate to drug response. Classification of evidence: This study provides Class III evidence that in patients with drug-resistant TLE, levetiracetam has a dose-dependent facilitation of deactivation of mesial temporal structures. PMID:25253743

  14. Comparative Demonstration of Active and Semi-Passive In Situ Bioremediation Approaches for Perchlorate Impacted Groundwater: Active In Situ Bioremediation Demonstration (Aerojet Facility)

    Science.gov (United States)

    2012-12-01

    which was passed through a cylinder of sodium chlorite (NaClO Biofouling Control 2) within the unit housing, generating 8% chlorine dioxide gas...Soluble electron donors such as sodium lactate, citric acid, or ethanol have been used in field applications, and it may be possible to use mobile...serves as an electron acceptor, and is reduced via chlorate to chlorite . Chlorite then undergoes a biologically-mediated dismutation reaction

  15. Comparative Demonstration of Active and Semi-Passive In Situ Bioremediation Approaches for Perchlorate Impacted Groundwater: Active In Situ Bioremediation Demonstration

    Science.gov (United States)

    2013-04-01

    4% chlorine), which was passed through a cylinder of sodium chlorite (NaClO2) within the unit housing, generating 8% chlorine dioxide gas (ClO2...mediated redox reactions, whereby perchlorate serves as an electron acceptor, and is reduced via chlorate to chlorite . Chlorite then undergoes a...injection and extraction wells to achieve the desired electron donor coverage. Soluble electron donors such as sodium lactate, citric acid, or

  16. Dynamic Susceptibility Contrast Perfusion Magnetic Resonance Imaging Demonstrates Reduced Periventricular Cerebral Blood Flow in Dogs with Ventriculomegaly

    Directory of Open Access Journals (Sweden)

    Martin J. Schmidt

    2017-08-01

    Full Text Available The nature of ventriculomegaly in dogs is still a matter of debate. Signs of increased intraventricular pressure and atrophy of the cerebral white matter have been found in dogs with ventriculomegaly, which would imply increased intraventricular pressure and, therefore, a pathological condition, i.e., to some extent. Reduced periventricular blood flow was found in people with high elevated intraventricular pressure. The aim of this study was to compare periventricular brain perfusion in dogs with and without ventriculomegaly using perfusion weighted-magnetic-resonance-imaging to clarify as to whether ventriculomegaly might be associated with an increase in intraventricular pressure. Perfusion was measured in 32 Cavalier King Charles spaniels (CKCS with ventriculomegaly, 10 CKCSs were examined as a control group. Cerebral blood flow (CBF was measured using free-hand regions of interest (ROI in five brain regions: periventricular white matter, caudate nucleus, parietal cortex, hippocampus, and thalamus. CBF was significantly lower in the periventricular white matter of the dogs with ventriculomegaly (p = 0.0029 but not in the other ROIs. Reduction of periventricular CBF might imply increase of intraventricular pressure in ventriculomegaly.

  17. Cold pressor test demonstrates residual sympathetic cardiovascular activation in familial dysautonomia.

    Science.gov (United States)

    Hilz, M J; Axelrod, F B; Braeske, K; Stemper, B

    2002-04-15

    In familial dysautonomia (FD), i.e. Riley-Day-syndrome, sympathetic cardiovascular function, as well as afferent temperature and pain mediating neurons, are significantly reduced. Thus, it was questioned if cold pressor test (CPT), which normally enhances sympathetic outflow and induces peripheral vasoconstriction by the activation of thermo- and nociceptive system activation, could be used to assess sympathetic function in FD. To evaluate whether CPT can be used to assess sympathetic activation in FD, we performed CPT in 15 FD patients and 18 controls. After a 35-min resting period, participants immersed their right hand and arm up to the elbow into 0-1 degrees C cold water while we monitored heart rate (HR), respiration, beat-to-beat radial artery blood pressure (BP), and laser Doppler skin blood flow (SBF) at the right index finger pulp. From these measurements, heart rate variability parameters were calculated: root mean square of successive differences (RMSSD), coefficient of variation (CV), low and high frequency (LF, HF) power spectra of the electrocardiogram (ECG). All participants perceived cold stimulation and indicated discomfort. In controls, SBF decreased and HR and BP increased rapidly upon CPT. After 60 s, SBF indicated secondary vasodilatation in six controls, BP rise attenuated and HR returned to baseline in all controls. In the patients, SBF remained unchanged, HR and BP increased significantly, but after 50-60 s of CPT and changes were lower than in controls (p<0.05). RMSSD and CV decreased and LF increased significantly only in the controls. We conclude that CPT activates sympathetic HR and BP modulation despite impaired pain and temperature perception in FD patients. BP increase in the presence of almost unchanged SBF might be due to HR increase and to nociceptive arousal and emotionally induced catecholamine release as seen in emotional crises of FD patients. CPT assesses sympathetic cardiovascular responses independently from baroreflex

  18. Chitosan-propolis nanoparticle formulation demonstrates anti-bacterial activity against Enterococcus faecalis biofilms.

    Science.gov (United States)

    Ong, Teik Hwa; Chitra, Ebenezer; Ramamurthy, Srinivasan; Siddalingam, Rajinikanth Paruvathanahalli; Yuen, Kah Hay; Ambu, Stephen Periathamby; Davamani, Fabian

    2017-01-01

    Propolis obtained from bee hives is a natural substance with antimicrobial properties. It is limited by its insolubility in aqueous solutions; hence ethanol and ethyl acetate extracts of Malaysian propolis were prepared. Both the extracts displayed antimicrobial and anti-biofilm properties against Enterococcus faecalis, a common bacterium associated with hospital-acquired infections. High performance liquid chromatography (HPLC) analysis of propolis revealed the presence of flavonoids like kaempferol and pinocembrin. This study investigated the role of propolis developed into nanoparticles with chitosan for its antimicrobial and anti-biofilm properties against E. faecalis. Bacteria that grow in a slimy layer of biofilm are resistant to penetration by antibacterial agents. The use of nanoparticles in medicine has received attention recently due to better bioavailability, enhanced penetrative capacity and improved efficacy. A chitosan-propolis nanoformulation was chosen based on ideal physicochemical properties such as particle size, zeta potential, polydispersity index, encapsulation efficiency and the rate of release of the active ingredients. This formulation inhibited E. faecalis biofilm formation and reduced the number of bacteria in the biofilm by ~90% at 200 μg/ml concentration. When tested on pre-formed biofilms, the formulation reduced bacterial number in the biofilm by ~40% and ~75% at 200 and 300 μg/ml, respectively. The formulation not only reduced bacterial numbers, but also physically disrupted the biofilm structure as observed by scanning electron microscopy. Treatment of biofilms with chitosan-propolis nanoparticles altered the expression of biofilm-associated genes in E. faecalis. The results of this study revealed that chitosan-propolis nanoformulation can be deemed as a potential anti-biofilm agent in resisting infections involving biofilm formation like chronic wounds and surgical site infections.

  19. Chitosan-propolis nanoparticle formulation demonstrates anti-bacterial activity against Enterococcus faecalis biofilms

    Science.gov (United States)

    Ong, Teik Hwa; Chitra, Ebenezer; Ramamurthy, Srinivasan; Siddalingam, Rajinikanth Paruvathanahalli; Yuen, Kah Hay; Ambu, Stephen Periathamby

    2017-01-01

    Propolis obtained from bee hives is a natural substance with antimicrobial properties. It is limited by its insolubility in aqueous solutions; hence ethanol and ethyl acetate extracts of Malaysian propolis were prepared. Both the extracts displayed antimicrobial and anti-biofilm properties against Enterococcus faecalis, a common bacterium associated with hospital-acquired infections. High performance liquid chromatography (HPLC) analysis of propolis revealed the presence of flavonoids like kaempferol and pinocembrin. This study investigated the role of propolis developed into nanoparticles with chitosan for its antimicrobial and anti-biofilm properties against E. faecalis. Bacteria that grow in a slimy layer of biofilm are resistant to penetration by antibacterial agents. The use of nanoparticles in medicine has received attention recently due to better bioavailability, enhanced penetrative capacity and improved efficacy. A chitosan-propolis nanoformulation was chosen based on ideal physicochemical properties such as particle size, zeta potential, polydispersity index, encapsulation efficiency and the rate of release of the active ingredients. This formulation inhibited E. faecalis biofilm formation and reduced the number of bacteria in the biofilm by ~90% at 200 μg/ml concentration. When tested on pre-formed biofilms, the formulation reduced bacterial number in the biofilm by ~40% and ~75% at 200 and 300 μg/ml, respectively. The formulation not only reduced bacterial numbers, but also physically disrupted the biofilm structure as observed by scanning electron microscopy. Treatment of biofilms with chitosan-propolis nanoparticles altered the expression of biofilm-associated genes in E. faecalis. The results of this study revealed that chitosan-propolis nanoformulation can be deemed as a potential anti-biofilm agent in resisting infections involving biofilm formation like chronic wounds and surgical site infections. PMID:28362873

  20. A chitosan based, laser activated thin film surgical adhesive, 'SurgiLux': preparation and demonstration.

    Science.gov (United States)

    Foster, L John R; Karsten, Elizabeth

    2012-10-23

    Sutures are a 4,000 year old technology that remain the 'gold-standard' for wound closure by virtue of their repair strength (~100 KPa). However, sutures can act as a nidus for infection and in many procedures are unable to effect wound repair or interfere with functional tissue regeneration.(1) Surgical glues and adhesives, such as those based on fibrin and cyanoacrylates, have been developed as alternatives to sutures for the repair of such wounds. However, current commercial adhesives also have significant disadvantages, ranging from viral and prion transfer and a lack of repair strength as with the fibrin glues, to tissue toxicity and a lack of biocompatibility for the cyanoacrylate based adhesives. Furthermore, currently available surgical adhesives tend to be gel-based and can have extended curing times which limit their application.(2) Similarly, the use of UV lasers to facilitate cross-linking mechanisms in protein-based or albumin 'solders' can lead to DNA damage while laser tissue welding (LTW) predisposes thermal damage to tissues.(3) Despite their disadvantages, adhesives and LTW have captured approximately 30% of the wound closure market reported to be in excess of US $5 billion per annum, a significant testament to the need for sutureless technology.(4) In the pursuit of sutureless technology we have utilized chitosan as a biomaterial for the development of a flexible, thin film, laser-activated surgical adhesive termed 'SurgiLux'. This novel bioadhesive uses a unique combination of biomaterials and photonics that are FDA approved and successfully used in a variety of biomedical applications and products. SurgiLux overcomes all the disadvantages associated with sutures and current surgical adhesives (see Table 1). In this presentation we report the relatively simple protocol for the fabrication of SurgiLux and demonstrate its laser activation and tissue weld strength. SurgiLux films adhere to collagenous tissue without chemical modification such as

  1. An investigation of the influence of reconceptualization of demonstrative experimental activities of optics in high school

    Directory of Open Access Journals (Sweden)

    Jair Lúcio Prados Ribeiro

    2013-08-01

    Full Text Available In this work, we analyze the influence that the use of demonstrative experiments can bring to the learning of optics. It is assumed that the development of experimental activities, when reconceptualized according to Hodson proposal, tends to contribute to the generation of cognitive conflicts when compared to traditional didactic experience. Justifications are given for an analysis of changes under a Piagetian bias, reconciled with Hodson proposal. The methodology used to structure the topics presentations was quasi-experimental, contrasting an experimental group with a control group. The measuring of the effectiveness of the suggested working method was made from a quantitative analysis, which identified some of the topics discussed had better results in learning, being more tied to the experiments carried out.

  2. High-frequency TRNS reduces BOLD activity during visuomotor learning.

    Directory of Open Access Journals (Sweden)

    Catarina Saiote

    Full Text Available Transcranial direct current stimulation (tDCS and transcranial random noise stimulation (tRNS consist in the application of electrical current of small intensity through the scalp, able to modulate perceptual and motor learning, probably by changing brain excitability. We investigated the effects of these transcranial electrical stimulation techniques in the early and later stages of visuomotor learning, as well as associated brain activity changes using functional magnetic resonance imaging (fMRI. We applied anodal and cathodal tDCS, low-frequency and high-frequency tRNS (lf-tRNS, 0.1-100 Hz; hf-tRNS 101-640 Hz, respectively and sham stimulation over the primary motor cortex (M1 during the first 10 minutes of a visuomotor learning paradigm and measured performance changes for 20 minutes after stimulation ceased. Functional imaging scans were acquired throughout the whole experiment. Cathodal tDCS and hf-tRNS showed a tendency to improve and lf-tRNS to hinder early learning during stimulation, an effect that remained for 20 minutes after cessation of stimulation in the late learning phase. Motor learning-related activity decreased in several regions as reported previously, however, there was no significant modulation of brain activity by tDCS. In opposition to this, hf-tRNS was associated with reduced motor task-related-activity bilaterally in the frontal cortex and precuneous, probably due to interaction with ongoing neuronal oscillations. This result highlights the potential of lf-tRNS and hf-tRNS to differentially modulate visuomotor learning and advances our knowledge on neuroplasticity induction approaches combined with functional imaging methods.

  3. KTN0158, a Humanized Anti-KIT Monoclonal Antibody, Demonstrates Biologic Activity against both Normal and Malignant Canine Mast Cells.

    Science.gov (United States)

    London, Cheryl A; Gardner, Heather L; Rippy, Sarah; Post, Gerald; La Perle, Krista; Crew, Linda; Lopresti-Morrow, Lori; Garton, Andrew J; McMahon, Gerald; LaVallee, Theresa M; Gedrich, Richard

    2016-11-04

    Purpose: KTN0158 is a novel anti-KIT antibody that potently inhibits wild-type and mutant KIT. This study evaluated the safety, biologic activity, and pharmacokinetic/pharmacodynamics profile of KTN0158 in dogs with spontaneous mast cell tumors (MCT) as a prelude to human clinical applications.Experimental Design: Cell proliferation, KIT phosphorylation, and mast cell degranulation were evaluated in vitro KTN0158 was administered to 4 research dogs to assess clinical effects and cutaneous mast cell numbers. Thirteen dogs with spontaneous MCT were enrolled into a prospective phase I dose-escalating open-label clinical study of KTN0158 evaluating 3 dose levels and 2 schedules and with weekly assessments for response and clinical toxicities.Results: KTN0158 was a potent inhibitor of human and dog KIT activation and blocked mast cell degranulation in vitro In dogs, KTN0158 was well tolerated and reduced cutaneous mast cell numbers in a dose-dependent manner. Clinical benefit of KTN0158 administration in dogs with MCT (n = 5 partial response; n = 7 stable disease) was observed regardless of KIT mutation status, and decreased KIT phosphorylation was demonstrated in tumor samples. Histopathology after study completion demonstrated an absence of neoplastic cells in the primary tumors and/or metastatic lymph nodes from 4 dogs. Reversible hematologic and biochemical adverse events were observed at doses of 10 and 30 mg/kg. The MTD was established as 10 mg/kg.Conclusions: KTN0158 inhibits KIT phosphorylation, demonstrates an acceptable safety profile in dogs, and provides objective responses in canine MCT patients with and without activating KIT mutations, supporting future clinical evaluation of KTN0158 in people. Clin Cancer Res; 1-10. ©2016 AACR.

  4. Nitride-strengthened reduced activation ferritic/martensitic steels

    Energy Technology Data Exchange (ETDEWEB)

    Hu Ping [Institute of Metal Research, Chinese Academy of Sciences, No. 72, Wenhua Road, Shenhe District, Shenyang, Liaoning 110016 (China); Graduate School of Chinese Academy of Sciences, Beijing 100049 (China); Yan Wei, E-mail: weiyan@imr.ac.cn [Institute of Metal Research, Chinese Academy of Sciences, No. 72, Wenhua Road, Shenhe District, Shenyang, Liaoning 110016 (China); Deng Lifen [Institute of Metal Research, Chinese Academy of Sciences, No. 72, Wenhua Road, Shenhe District, Shenyang, Liaoning 110016 (China); Graduate School of Chinese Academy of Sciences, Beijing 100049 (China); Sha Wei [School of Planning, Architecture and Civil Engineering, Queen' s University of Belfast, Belfast BT9 5AG (United Kingdom); Shan Yiyin; Yang Ke [Institute of Metal Research, Chinese Academy of Sciences, No. 72, Wenhua Road, Shenhe District, Shenyang, Liaoning 110016 (China)

    2010-12-15

    Two nitride-strengthened reduced activation ferritic/martensitic (RAFM) steels with different Mn contents were investigated. The experimental steels were designed based on the chemical composition of Eurofer 97 steel but the C content was reduced to an extremely low level. Microstructure observation and hardness tests showed that the steel with low Mn content (0.47 wt.%) could not obtain a full martensitic microstructure due to the inevitable {delta}-ferrite independent of cooling rate after soaking. This steel showed similar room temperature strength and higher strength at 600 deg. C, but lower impact toughness, compared with Eurofer 97 steel. Fractography of the Charpy impact specimen revealed that the low room temperature toughness should be related to the Ta-rich inclusions initiating the cleavage fracture. The larger amount of V-rich nitrides and more dissolved Cr in the matrix could be responsible for the strength being similar to Eurofer 97 steel. In the second steel developed from the first steel by increasing the Mn content from 0.47 wt.% to 3.73 wt.%, a microstructure of full martensite could be obtained.

  5. Baicalein reduces the invasion of glioma cells via reducing the activity of p38 signaling pathway.

    Directory of Open Access Journals (Sweden)

    Zhenni Zhang

    Full Text Available Baicalein, one of the major flavonids in Scutellaria baicalensis, has historically been used in anti-inflammatory and anti-cancer therapies. However, the anti-metastatic effect and related mechanism(s in glioma are still unclear. In this study, we thus utilized glioma cell lines U87MG and U251MG to explore the effect of baicalein. We found that administration of baicalein significantly inhibited migration and invasion of glioma cells. In addition, after treating with baicalein for 24 h, there was a decrease in the levels of matrix metalloproteinase-2 (MMP-2 and MMP-9 expression as well as proteinase activity in glioma cells. Conversely, the expression of tissue inhibitor of metalloproteinase-1 (TIMP-1 and TIMP-2 was increased in a dose-dependent manner. Moreover, baicalein treatment significantly decreased the phosphorylated level of p38, but not ERK1/2, JNK1/2 and PI3K/Akt. Combined treatment with a p38 inhibitor (SB203580 and baicalein resulted in the synergistic reduction of MMP-2 and MMP-9 expression and then increase of TIMP-1 and TIMP-2 expression; and the invasive capabilities of U87MG cells were also inhibited. However, p38 chemical activator (anisomycin could block these effects produced by baicalein, suggesting baicalein directly downregulate the p38 signaling pathway. In conclusion, baicalein inhibits glioma cells invasion and metastasis by reducing cell motility and migration via suppression of p38 signaling pathway, suggesting that baicalein is a potential therapeutic agent for glioma.

  6. Rectification of SEMG as a tool to demonstrate synchronous motor unit activity during vibration.

    Science.gov (United States)

    Sebik, Oguz; Karacan, Ilhan; Cidem, Muharrem; Türker, Kemal S

    2013-04-01

    The use of surface electromyography (SEMG) in vibration studies is problematic since motion artifacts occupy the same frequency band with the SEMG signal containing information on synchronous motor unit activity. We hypothesize that using a harsher, 80-500 Hz band-pass filter and using rectification can help eliminate motion artifacts and provide a way to observe synchronous motor unit activity that is phase locked to vibration using SEMG recordings only. Multi Motor Unit (MMU) action potentials using intramuscular electrodes along with SEMG were recorded from the gastrocnemius medialis (GM) of six healthy male volunteers. Data were collected during whole body vibration, using vibration frequencies of 30 Hz, 35 Hz, 40 Hz or 50 Hz. A computer simulation was used to investigate the efficacy of filtering under different scenarios: with or without artifacts and/or motor unit synchronization. Our findings indicate that motor unit synchronization took place during WBV as verified by MMU recordings. A harsh filtering regimen along with rectification proved successful in demonstrating motor unit synchronization in SEMG recordings. Our findings were further supported by the results from the computer simulation, which indicated that filtering and rectification was efficient in discriminating motion artifacts from motor unit synchronization. We suggest that the proposed signal processing technique may provide a new methodology to evaluate the effects of vibration treatments using only SEMG. This is a major advantage, as this non-intrusive method is able to overcome movement artifacts and also indicate the synchronization of underlying motor units.

  7. Long terminal repeat sequences from virulent and attenuated equine infectious anemia virus demonstrate distinct promoter activities.

    Science.gov (United States)

    Zhou, Tao; Yuan, Xiu-Fang; Hou, Shao-Hua; Tu, Ya-Bin; Peng, Jin-Mei; Wen, Jian-Xin; Qiu, Hua-Ji; Wu, Dong-Lai; Chen, Huan-Chun; Wang, Xiao-Jun; Tong, Guang-Zhi

    2007-09-01

    In the early 1970s, the Chinese Equine Infectious Anemia Virus (EIAV) vaccine, EIAV(DLA), was developed through successive passages of a wild-type virulent virus (EIAV(L)) in donkeys in vivo and then in donkey macrophages in vitro. EIAV attenuation and cell tropism adaptation are associated with changes in both envelope and long terminal repeat (LTR). However, specific LTR changes during Chinese EIAV attenuation have not been demonstrated. In this study, we compared LTR sequences from both virulent and attenuated EIAV strains and documented the diversities of LTR sequence from in vivo and in vitro infections. We found that EIAV LTRs of virulent strains were homologous, while EIAV vaccine have variable LTRs. Interestingly, experimental inoculation of EIAV(DLA) into a horse resulted in a restriction of the LTR variation. Furthermore, LTRs from EIAV(DLA) showed higher Tat transactivated activity than LTRs from virulent strains. By using chimeric clones of wild-type LTR and vaccine LTR, the main difference of activity was mapped to the changes of R region, rather than U3 region.

  8. Reducing RBM20 activity improves diastolic dysfunction and cardiac atrophy.

    Science.gov (United States)

    Hinze, Florian; Dieterich, Christoph; Radke, Michael H; Granzier, Henk; Gotthardt, Michael

    2016-12-01

    Impaired diastolic filling is a main contributor to heart failure with preserved ejection fraction (HFpEF), a syndrome with increasing prevalence and no treatment. Both collagen and the giant sarcomeric protein titin determine diastolic function. Since titin's elastic properties can be adjusted physiologically, we evaluated titin-based stiffness as a therapeutic target. We adjusted RBM20-dependent cardiac isoform expression in the titin N2B knockout mouse with increased ventricular stiffness. A ~50 % reduction of RBM20 activity does not only maintain cardiac filling in diastole but also ameliorates cardiac atrophy and thus improves cardiac function in the N2B-deficient heart. Reduced RBM20 activity partially normalized gene expression related to muscle development and fatty acid metabolism. The adaptation of cardiac growth was related to hypertrophy signaling via four-and-a-half lim-domain proteins (FHLs) that translate mechanical input into hypertrophy signals. We provide a novel link between cardiac isoform expression and trophic signaling via FHLs and suggest cardiac splicing as a therapeutic target in diastolic dysfunction. Increasing the length of titin isoforms improves ventricular filling in heart disease. FHL proteins are regulated via RBM20 and adapt cardiac growth. RBM20 is a therapeutic target in diastolic dysfunction.

  9. Defect-induced enhanced photocatalytic activities of reduced α-Fe2O3 nanoblades

    Science.gov (United States)

    Feng, Honglei; Wang, Yiqian; Wang, Chao; Diao, Feiyu; Zhu, Wenhui; Mu, Peng; Yuan, Lu; Zhou, Guangwen; Rosei, Federico

    2016-07-01

    Bicrystalline α-Fe2O3 nanoblades (NBs) synthesized by thermal oxidation of iron foils were reduced in vacuum, to study the effect of reduction treatment on microstructural changes and photocatalytic properties. After the vacuum reduction, most bicrystalline α-Fe2O3 NBs transform into single-layered NBs, which contain more defects such as oxygen vacancies, perfect dislocations and dense pores. By comparing the photodegradation capability of non-reduced and reduced α-Fe2O3 NBs over model dye rhodamine B (RhB) in the presence of hydrogen peroxide, we find that vacuum-reduction induced microstructural defects can significantly enhance the photocatalytic efficiency. Even after 10 cycles, the reduced α-Fe2O3 NBs still show a very high photocatalytic activity. Our results demonstrate that defect engineering is a powerful tool to enhance the photocatalytic performance of nanomaterials.

  10. Active member vibration control experiment in a KC-135 reduced gravity environment

    Science.gov (United States)

    Lawrence, C. R.; Lurie, B. J.; Chen, G.-S.; Swanson, A. D.

    1991-01-01

    An active member vibration control experiment in a KC-135 reduced gravity environment was carried out by the Air Force Flight Dynamics Laboratory and the Jet Propulsion Laboratory. Two active members, consisting of piezoelectric actuators, displacement sensors, and load cells, were incorporated into a 12-meter, 104 kg box-type test structure. The active member control design involved the use of bridge (compound) feedback concept, in which the collocated force and velocity signals are feedback locally. An impact-type test was designed to accommodate the extremely short duration of the reduced gravity testing window in each parabolic flight. The moving block analysis technique was used to estimate the modal frequencies and dampings from the free-decay responses. A broadband damping performance was demonstrated up to the ninth mode of 40 Hz. The best damping performance achieved in the flight test was about 5 percent in the fourth mode of the test structure.

  11. U.S. Department of Energy -- Advanced Vehicle Testing Activity: Plug-in Hybrid Electric Vehicle Testing and Demonstration Activities

    Energy Technology Data Exchange (ETDEWEB)

    James E. Francfort; Donald Karner; John G. Smart

    2009-05-01

    The U.S. Department of Energy’s (DOE) Advanced Vehicle Testing Activity (AVTA) tests plug-in hybrid electric vehicles (PHEV) in closed track, dynamometer and onroad testing environments. The onroad testing includes the use of dedicated drivers on repeated urban and highway driving cycles that range from 10 to 200 miles, with recharging between each loop. Fleet demonstrations with onboard data collectors are also ongoing with PHEVs operating in several dozen states and Canadian Provinces, during which trips- and miles-per-charge, charging demand and energy profiles, and miles-per-gallon and miles-per-kilowatt-hour fuel use results are all documented, allowing an understanding of fuel use when vehicles are operated in charge depleting, charge sustaining, and mixed charge modes. The intent of the PHEV testing includes documenting the petroleum reduction potential of the PHEV concept, the infrastructure requirements, and operator recharging influences and profiles. As of May 2008, the AVTA has conducted track and dynamometer testing on six PHEV conversion models and fleet testing on 70 PHEVs representing nine PHEV conversion models. A total of 150 PHEVs will be in fleet testing by the end of 2008, all with onboard data loggers. The onroad testing to date has demonstrated 100+ miles per gallon results in mostly urban applications for approximately the first 40 miles of PHEV operations. The primary goal of the AVTA is to provide advanced technology vehicle performance benchmark data for technology modelers, research and development programs, and technology goal setters. The AVTA testing results also assist fleet managers in making informed vehicle purchase, deployment and operating decisions. The AVTA is part of DOE’s Vehicle Technologies Program. These AVTA testing activities are conducted by the Idaho National Laboratory and Electric Transportation Engineering Corporation, with Argonne National Laboratory providing dynamometer testing support. The proposed paper

  12. Nitrate and sulfate reducers-retrievable number of bacteria and their activities in Indian waters

    Digital Repository Service at National Institute of Oceanography (India)

    LokaBharathi, P.A.; Nair, S.; Chandramohan, D.

    Culturable heterotrophic, nitrate reducing and sulfate reducing bacteria (HB, NRB and SRB) were enumerated from 25, 50, 100 and 200 m depths at 15 stations and their potential activities viz. Nitrate reducing (NRA) and Sulfate reducing (SRA) were...

  13. Immune activation reduces sperm quality in the great tit.

    Directory of Open Access Journals (Sweden)

    Sylvain Losdat

    Full Text Available Mounting an immune response against pathogens incurs costs to organisms by its effects on important life-history traits, such as reproductive investment and survival. As shown recently, immune activation produces large amounts of reactive species and is suggested to induce oxidative stress. Sperm are highly susceptible to oxidative stress, which can negatively impact sperm function and ultimately male fertilizing efficiency. Here we address the question as to whether mounting an immune response affects sperm quality through the damaging effects of oxidative stress. It has been demonstrated recently in birds that carotenoid-based ornaments can be reliable signals of a male's ability to protect sperm from oxidative damage. In a full-factorial design, we immune-challenged great tit males while simultaneously increasing their vitamin E availability, and assessed the effect on sperm quality and oxidative damage. We conducted this experiment in a natural population and tested the males' response to the experimental treatment in relation to their carotenoid-based breast coloration, a condition-dependent trait. Immune activation induced a steeper decline in sperm swimming velocity, thus highlighting the potential costs of an induced immune response on sperm competitive ability and fertilizing efficiency. We found sperm oxidative damage to be negatively correlated with sperm swimming velocity. However, blood resistance to a free-radical attack (a measure of somatic antioxidant capacity as well as plasma and sperm levels of oxidative damage (lipid peroxidation remained unaffected, thus suggesting that the observed effect did not arise through oxidative stress. Towards the end of their breeding cycle, swimming velocity of sperm of more intensely colored males was higher, which has important implications for the evolution of mate choice and multiple mating in females because females may accrue both direct and indirect benefits by mating with males having

  14. Demonstration of sulfur solubility determinations in high waste loading, low-activity waste glasses

    Energy Technology Data Exchange (ETDEWEB)

    Fox, K. M. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL)

    2016-04-25

    A method recommended by Pacific Northwest National Laboratory (PNNL) for sulfate solubility determinations in simulated low-activity waste glasses was demonstrated using three compositions from a recent Hanford high waste loading glass study. Sodium and sulfate concentrations in the glasses increased after each re-melting step. Visual observations of the glasses during the re-melting process reflected the changes in composition. The measured compositions showed that the glasses met the targeted values. The amount of SO3 retained in the glasses after washing was relatively high, ranging from 1.6 to 2.6 weight percent (wt %). Measured SnO2 concentrations were notably low in all of the study glasses. The composition of the wash solutions should be measured in future work to determine whether SnO2 is present with the excess sulfate washed from the glass. Increases in batch size and the amount of sodium sulfate added did not have a measureable impact on the amount of sulfate retained in the glass, although this was tested for only a single glass composition. A batch size of 250 g and a sodium sulfate addition targeting 7 wt %, as recommended by PNNL, will be used in future experiments.

  15. Deformation behavior of reduced activation ferritic steel during tensile test

    Energy Technology Data Exchange (ETDEWEB)

    Shiba, Kiyoyuki [Department of Material Science and Engineering, Japan Atomic Energy Research Institute, Tokai-mura, Naka-gun, Ibakaki 319-1195 (Japan)]. E-mail: shiba@realab01.tokai.jaeri.go.jp; Hirose, Takanori [Department of Fusion Engineering Research, Japan Atomic Energy Research Institute, 801-1 Mukouyama, Naka, Ibaraki 311-0193 (Japan)

    2006-02-15

    Deformation behavior of reduced activation martensitic steel F82H during tensile tests were studied. True stress-true strain diagrams were calculated with minimum diameter determined from the specimen profile obtained by laser micro-gauge scanning the diameter along the longitudinal direction during tensile test. Cylindrical specimens of F82H were used for the measurement and test temperatures were room temperature (RT), 300, 400, 500 and 600 deg. C. Tensile tests were carried out with 1 x 10{sup -4} s{sup -1} of strain rate. Other strain rates (1 x 10{sup -3} and 1 x 10{sup -5} s{sup -1}) were applied for the tests at RT. Although uniform elongation of F82H is relatively small at elevated temperature, true stress increases to fracture after necking starts. True stress decreases temporarily after yielding at 600 deg. C, but it increases again to fracture like the specimens tested at lower temperatures. Influence of strain rate to true stress-true strain relationship at room temperature was small, but unstable deformation occurred in narrower area at higher strain rate.

  16. Curcumin inhibits srebp-2 expression in activated hepatic stellate cells in vitro by reducing the activity of specificity protein-1.

    Science.gov (United States)

    Kang, Qiaohua; Chen, Anping

    2009-12-01

    Elevated levels of cholesterol/low-density lipoprotein (LDL) are a risk factor for the development of nonalcoholic steatohepatitis and its associated hepatic fibrosis. However, underlying mechanisms remain elusive. We previously reported that curcumin induced gene expression of peroxisome proliferator-activated receptor (PPAR)-gamma and stimulated its activity, leading to the inhibition of the activation of hepatic stellate cells (HSCs), the major effector cells during hepatic fibrogenesis. We recently showed that curcumin suppressed gene expression of LDL receptor in activated HSCs in vitro by repressing gene expression of the transcription factor sterol regulatory element binding protein-2 (SREBP-2), leading to the reduction in the level of intracellular cholesterol in HSCs and to the attenuation of the stimulatory effects of LDL on HSCs activation. The current study aimed at exploring molecular mechanisms by which curcumin inhibits srebp-2 expression in HSCs. Promoter deletion assays, mutagenesis assays, and EMSAs localize a specificity protein-1 (SP-1) binding GC-box in the srebp-2 promoter, which is responsible for enhancing the promoter activity and responding to curcumin in HSCs. Curcumin suppresses gene expression of SP-1 and reduces its trans-activation activity, which are mediated by the activation of PPARgamma. The inhibitory effect of curcumin on SP-1 binding to the GC-box is confirmed by chromatin immuno-precipitation. In summary, our results demonstrate that curcumin inhibits srebp-2 expression in cultured HSCs by activating PPARgamma and reducing the SP-1 activity, leading to the repression of ldlr expression. These results provide novel insights into molecular mechanisms by which curcumin inhibits LDL-induced HSC activation.

  17. Reduced mitochondria cytochrome oxidase activity in adult children of mothers with Alzheimer's disease.

    Science.gov (United States)

    Mosconi, Lisa; de Leon, Mony; Murray, John; E, Lezi; Lu, Jianghua; Javier, Elizabeth; McHugh, Pauline; Swerdlow, Russell H

    2011-01-01

    Biomarker studies demonstrate inheritance of glucose hypometabolism and increased amyloid-β deposition in adult offspring of mothers, but not fathers, affected by late-onset Alzheimer's disease (LOAD). The underlying genetic mechanisms are unknown. We investigated whether cognitively normal (NL) individuals with a maternal history of LOAD (MH) have reduced platelet mitochondrial cytochrome oxidase activity (COX, electron transport chain complex IV) compared to those with paternal (PH) or negative family history (NH). Thirty-six consecutive NL individuals (age 55 ± 15 y, range 27-71 y, 56% female, CDR = 0, MMSE ≥28, 28% APOE-4 carriers), including 12 NH, 12 PH, and 12 MH, received a blood draw to measure platelet mitochondrial COX activity. Citrate synthase activity (CS) was measured as a reference. Groups were comparable for clinical and neuropsychological measures. We found that after correcting for CS, COX activity was reduced by 29% in MH compared to NH, and by 30% in MH compared to PH (p ≤ 0.006). Results remained significant controlling for age, gender, education, and APOE. No differences were found between PH and NH. COX measures discriminated MH from the other groups with accuracy ≥75%, and relative risk ≥3 (p ≤ 0.005). Among NL with LOAD-parents, only those with MH showed reduced COX activity in platelet mitochondria compared to PH and NH. The association between maternal history of LOAD and systemic COX reductions suggests transmission via mitochondrial DNA, which is exclusively maternally inherited in humans.

  18. Raft disorganization leads to reduced plasmin activity in Alzheimer's disease brains.

    Science.gov (United States)

    Ledesma, Maria Dolores; Abad-Rodriguez, José; Galvan, Cristian; Biondi, Elisa; Navarro, Pilar; Delacourte, Andre; Dingwall, Colin; Dotti, Carlos G

    2003-12-01

    The serine protease plasmin can efficiently degrade amyloid peptide in vitro, and is found at low levels in the hippocampus of patients with Alzheimer's disease (AD). The cause of such paucity remains unknown. We show here that the levels of total brain plasminogen and plasminogen-binding molecules are normal in these brain samples, yet plasminogen membrane binding is greatly reduced. Biochemical analysis reveals that the membranes of these brains have a mild, still significant, cholesterol reduction compared to age-matched controls, and anomalous raft microdomains. This was reflected by the loss of raft-enriched proteins, including plasminogen-binding and -activating molecules. Using hippocampal neurons in culture, we demonstrate that removal of a similar amount of membrane cholesterol is sufficient to induce raft disorganization, leading to reduced plasminogen membrane binding and low plasmin activity. These results suggest that brain raft alterations may contribute to AD by rendering the plasminogen system inefficient.

  19. AMPK up-activation reduces motility and regulates other functions of boar spermatozoa.

    Science.gov (United States)

    Hurtado de Llera, A; Martin-Hidalgo, D; Gil, M C; Garcia-Marin, L J; Bragado, M J

    2015-01-01

    We recently demonstrated that AMPK inhibition in spermatozoa regulates motility, plasma membrane organization, acrosome integrity and mitochondrial membrane potential. As AMPK activity varies in different energy conditions induced by sperm environment, this work investigates the functional effects of AMPK activation in boar spermatozoa. Spermatozoa were incubated under non-stimulating (TBM) or Ca(2+) and [Formula: see text]-stimulating (TCM) media in the presence/absence of AMPK activator, A769662, for different times. AMPK activity, evaluated as Thr(172) phosphorylation by western blot, is effectively increased by A769662 in spermatozoa. AMPK activation significantly reduces the percentage of motile spermatozoa under Ca(2+) and/or [Formula: see text]-stimulating conditions. Moreover, AMPK activation in spermatozoa incubated in TBM or TCM significantly reduces curvilinear VCL, straight-line VSL and average VAP velocities, which subsequently lead to a significant decrease in the percentage of rapid spermatozoa (VAP > 80 μm/s). The effect of AMPK activation on motility is intensified by the absence of BSA in the incubation medium. AMPK activation for a short time prevents the decline in cell viability and in the sperm population displaying high mitochondrial membrane potential which is induced by Ca(2+) and [Formula: see text]. Sustained (24 h) AMPK activation under TBM or TCM significantly increases both lipid disorganization and phosphatidylserine externalization in the sperm plasma membrane, and diminishes the acrosome membrane integrity. In summary, AMPK activation modifies essential sperm processes such as motility, viability, mitochondrial membrane potential, acrosome membrane integrity, and organization and fluidity of plasma membrane. As these spermatozoa processes are required under different environmental conditions when transiting through the female reproductive tract to achieve fertilization, we conclude that balanced levels of AMPK activity are

  20. Do school-based physical activity interventions increase or reduce inequalities in health?

    Science.gov (United States)

    Vander Ploeg, Kerry A; Maximova, Katerina; McGavock, Jonathan; Davis, Wendy; Veugelers, Paul

    2014-07-01

    Little is known about the effectiveness of school-based health promotion on physical activity inequalities among children from low-income areas. This study compared the two-year change in physical activity among 10-11 year-old children attending schools with and without health promotion programs by activity level, body weight status, and socioeconomic backgrounds to assess whether health promotion programs reduce or exacerbate health inequalities. This was a quasi-experimental trial of a Comprehensive School Health (CSH) program implemented in schools located in socioeconomically disadvantaged neighbourhoods in Edmonton, Alberta, Canada. In the spring of 2009 and 2011, pedometer (7 full days) and demographic data were collected from cross-sectional samples of grade five children from 10 intervention and 20 comparison schools. Socioeconomic status was determined from parent self-report. Low-active, active, and high-active children were defined according to step-count tertiles. Multilevel linear regression methods adjusted for potential confounders were used to assess the relative inequity in physical activity and were compared between groups and over-time. In 2009, a greater proportion of students in the intervention schools were overweight (38% vs. 31% p = 0.03) and were less active (10,827 vs. 12,265 steps/day p active students, from -13.4% to 0% among active students, and from -15.1% to -2.7% among high-active students. The relative difference between intervention and comparison schools reduced from -11.1% to -1.6% among normal weight students, from -16.8% to -1.4% among overweight students, and was balanced across socioeconomic subgroups. These findings demonstrate that CSH programs implemented in socioeconomically disadvantaged neighbourhoods reduced inequalities in physical activity. Investments in school-based health promotion are a viable, promising, and important approach to improve physical activity and prevent childhood obesity, and may also

  1. Catastrophic NAD+ depletion in activated T lymphocytes through Nampt inhibition reduces demyelination and disability in EAE.

    Science.gov (United States)

    Bruzzone, Santina; Fruscione, Floriana; Morando, Sara; Ferrando, Tiziana; Poggi, Alessandro; Garuti, Anna; D'Urso, Agustina; Selmo, Martina; Benvenuto, Federica; Cea, Michele; Zoppoli, Gabriele; Moran, Eva; Soncini, Debora; Ballestrero, Alberto; Sordat, Bernard; Patrone, Franco; Mostoslavsky, Raul; Uccelli, Antonio; Nencioni, Alessio

    2009-11-19

    Nicotinamide phosphoribosyltransferase (Nampt) inhibitors such as FK866 are potent inhibitors of NAD(+) synthesis that show promise for the treatment of different forms of cancer. Based on Nampt upregulation in activated T lymphocytes and on preliminary reports of lymphopenia in FK866 treated patients, we have investigated FK866 for its capacity to interfere with T lymphocyte function and survival. Intracellular pyridine nucleotides, ATP, mitochondrial function, viability, proliferation, activation markers and cytokine secretion were assessed in resting and in activated human T lymphocytes. In addition, we used experimental autoimmune encephalomyelitis (EAE) as a model of T-cell mediated autoimmune disease to assess FK866 efficacy in vivo. We show that activated, but not resting, T lymphocytes undergo massive NAD(+) depletion upon FK866-mediated Nampt inhibition. As a consequence, impaired proliferation, reduced IFN-gamma and TNF-alpha production, and finally autophagic cell demise result. We demonstrate that upregulation of the NAD(+)-degrading enzyme poly-(ADP-ribose)-polymerase (PARP) by activated T cells enhances their susceptibility to NAD(+) depletion. In addition, we relate defective IFN-gamma and TNF-alpha production in response to FK866 to impaired Sirt6 activity. Finally, we show that FK866 strikingly reduces the neurological damage and the clinical manifestations of EAE. In conclusion, Nampt inhibitors (and possibly Sirt6 inhibitors) could be used to modulate T cell-mediated immune responses and thereby be beneficial in immune-mediated disorders.

  2. Catastrophic NAD+ Depletion in Activated T Lymphocytes through Nampt Inhibition Reduces Demyelination and Disability in EAE

    Science.gov (United States)

    Ferrando, Tiziana; Poggi, Alessandro; Garuti, Anna; D'Urso, Agustina; Selmo, Martina; Benvenuto, Federica; Cea, Michele; Zoppoli, Gabriele; Moran, Eva; Soncini, Debora; Ballestrero, Alberto; Sordat, Bernard; Patrone, Franco; Mostoslavsky, Raul; Uccelli, Antonio; Nencioni, Alessio

    2009-01-01

    Nicotinamide phosphoribosyltransferase (Nampt) inhibitors such as FK866 are potent inhibitors of NAD+ synthesis that show promise for the treatment of different forms of cancer. Based on Nampt upregulation in activated T lymphocytes and on preliminary reports of lymphopenia in FK866 treated patients, we have investigated FK866 for its capacity to interfere with T lymphocyte function and survival. Intracellular pyridine nucleotides, ATP, mitochondrial function, viability, proliferation, activation markers and cytokine secretion were assessed in resting and in activated human T lymphocytes. In addition, we used experimental autoimmune encephalomyelitis (EAE) as a model of T-cell mediated autoimmune disease to assess FK866 efficacy in vivo. We show that activated, but not resting, T lymphocytes undergo massive NAD+ depletion upon FK866-mediated Nampt inhibition. As a consequence, impaired proliferation, reduced IFN-γ and TNF-α production, and finally autophagic cell demise result. We demonstrate that upregulation of the NAD+-degrading enzyme poly-(ADP-ribose)-polymerase (PARP) by activated T cells enhances their susceptibility to NAD+ depletion. In addition, we relate defective IFN-γ and TNF-α production in response to FK866 to impaired Sirt6 activity. Finally, we show that FK866 strikingly reduces the neurological damage and the clinical manifestations of EAE. In conclusion, Nampt inhibitors (and possibly Sirt6 inhibitors) could be used to modulate T cell-mediated immune responses and thereby be beneficial in immune-mediated disorders. PMID:19936064

  3. Catastrophic NAD+ depletion in activated T lymphocytes through Nampt inhibition reduces demyelination and disability in EAE.

    Directory of Open Access Journals (Sweden)

    Santina Bruzzone

    Full Text Available Nicotinamide phosphoribosyltransferase (Nampt inhibitors such as FK866 are potent inhibitors of NAD(+ synthesis that show promise for the treatment of different forms of cancer. Based on Nampt upregulation in activated T lymphocytes and on preliminary reports of lymphopenia in FK866 treated patients, we have investigated FK866 for its capacity to interfere with T lymphocyte function and survival. Intracellular pyridine nucleotides, ATP, mitochondrial function, viability, proliferation, activation markers and cytokine secretion were assessed in resting and in activated human T lymphocytes. In addition, we used experimental autoimmune encephalomyelitis (EAE as a model of T-cell mediated autoimmune disease to assess FK866 efficacy in vivo. We show that activated, but not resting, T lymphocytes undergo massive NAD(+ depletion upon FK866-mediated Nampt inhibition. As a consequence, impaired proliferation, reduced IFN-gamma and TNF-alpha production, and finally autophagic cell demise result. We demonstrate that upregulation of the NAD(+-degrading enzyme poly-(ADP-ribose-polymerase (PARP by activated T cells enhances their susceptibility to NAD(+ depletion. In addition, we relate defective IFN-gamma and TNF-alpha production in response to FK866 to impaired Sirt6 activity. Finally, we show that FK866 strikingly reduces the neurological damage and the clinical manifestations of EAE. In conclusion, Nampt inhibitors (and possibly Sirt6 inhibitors could be used to modulate T cell-mediated immune responses and thereby be beneficial in immune-mediated disorders.

  4. Heparins with reduced anti-coagulant activity reduce myocardial reperfusion injury.

    Science.gov (United States)

    Barry, William H; Kennedy, Thomas P

    2011-05-01

    Heparin which is desulfated at the 2-O and 3-O positions (ODSH) has reduced anti-coagulant properties, and reduced interaction with heparin antibodies. Because of the reduced anti-coagulant effect, ODSH can be safely administered to animals and humans intravenously at doses up to 20 mg/kg, resulting in a serum concentration of up to 250µg/ml. Administration of ODSH causes a 35% reduction in infarct size in dogs and pigs subjected to coronary artery occlusion and reperfusion when given 5 min before reperfusion. ODSH has anti-inflamatory effects, manifest as a decrease in neutrophil infiltration into ischemic tissue at high doses, but this effect does not entirely account for the reduction in infarct size. ODSH decreases Na(+) and Ca(2+) loading in isolated cardiac myocytes subjected to simulated ischemia. This effect appears due to an ODSH-induced reduction in an enhanced Na(+) influx via the Na channel in the membrane of cardiac myocyes caused by oxygen radicals generated during ischemia and reperfusion. Reduction in Na(+) influx decreases Ca(2+) loading by reducing Ca2(+) influx via Na/Ca exchange, thus reducing Ca(2+) - dependent reperfusion injury. ODSH does not appear to interact with antibodies to the heparin/platelet factor 4 complex, and does not cause heparin-induced thrombocytopenia. Because of these therapeutic and safety considerations, ODSH would appear to be a promising heparin derivative for prevention of reperfusion injury in humans undergoing thrombolytic or catheter-based reperfusion for acute myocardial infarction. The review article discussed the use of heparin and the discussion of some of the important patents, including: US6489311; US7478358; PCTUS2008070836 and PCTUS2009037836.

  5. Impaired endothelial progenitor cell activity is associated with reduced arterial elasticity in patients with essential hypertension.

    Science.gov (United States)

    Yang, Zhen; Chen, Long; Su, Chen; Xia, Wen-Hao; Wang, Yan; Wang, Jie-Mei; Chen, Fei; Zhang, Yuan-Yuan; Wu, Fang; Xu, Shi-Yue; Zhang, Xiao-Lin; Tao, Jun

    2010-01-01

    Endothelial dysfunction is related to reduced arterial elasticity in patients with essential hypertension. Circulating endothelial progenitor cells (EPCs), an important endogenous repair approach for endothelial injury, is altered in hypertensive patients. However, the association between alteration in circulating EPCs and hypertension-related reduced arterial elasticity has not been reported. The purpose of this study is to investigate the association between alteration in circulating EPCs and hypertension-related reduced arterial elasticity. We measured the artery elasticity profiles including brachial-ankle PWV (baPWV) and C1 large and C2 small artery elasticity indices in patients with essential hypertension (n = 20) and age-matched normotensive subjects (n = 21). The number and activity of circulating EPCs isolated from peripheral blood were determined. Compared to normotensive subjects, the patients with hypertension exhibited decreased C1 large and C2 small artery elasticity indices, as well as increased baPWV. The number of circulating EPCs did not differ between the two groups. The migratory and proliferative activities of circulating EPCs in hypertensive patients were lower than those in normotensive subjects. Both proliferatory and migratory activities of circulating EPCs closely correlated with arterial elasticity profiles, including baPWV and C1 large and C2 small artery elasticity indices. Multivariate analysis identified both proliferative and migratory activities of circulating EPCs as independent predictors of the artery elasticity profiles. The present study demonstrates for the first time that impaired activity of circulating EPCs is associated with reduced arterial elasticity in patients with hypertension. The fall in endogenous repair capacity of vascular endothelium may be involved in the pathogenesis of hypertension-related vascular injury.

  6. Acycloguanosyl 5'-thymidyltriphosphate, a thymidine analogue prodrug activated by telomerase, reduces pancreatic tumor growth in mice.

    Science.gov (United States)

    Polvani, Simone; Calamante, Massimo; Foresta, Valeria; Ceni, Elisabetta; Mordini, Alessandro; Quattrone, Alessandro; D'Amico, Massimo; Luchinat, Claudio; Bertini, Ivano; Galli, Andrea

    2011-02-01

    Gemcitabine is the standard of care for metastatic and nonresectable pancreatic tumors. Phase II and III trials have not demonstrated efficacy of recently developed reagents, compared with gemcitabine alone; new chemotherapic agents are needed. Ninety percent of pancreatic tumors have telomerase activity, and expression correlates with tumor stage. We developed a thymidine analogue prodrug, acycloguanosyl 5'-thymidyltriphosphate (ACV-TP-T), that is metabolized by telomerase and releases the active form of acyclovir. We investigated the antitumor efficacy of ACV-TP-T in vitro and in vivo. We evaluated proliferation and apoptosis of human pancreatic cancer cells (PANC-1, MiaPaca2, BxPc3, PL45, and Su.86.86) incubated with ACV-TP-T. The presence of ACV-TP-T and its metabolite inside the cells were analyzed by mass spectrometry. In vivo efficacy was evaluated in nude mice carrying PANC-1 or MiaPaca2 pancreatic xenograft tumors. The prodrug of ACV-TP-T was actively metabolized inside pancreatic cancer cells into the activated form of acyclovir; proliferation was reduced, apoptosis was increased, and the cell cycle was altered in pancreatic cancer incubated with ACV-TP-T, compared with controls. Administration of ACV-TP-T to mice reduced growth, increased apoptosis, and reduced proliferation and vascularization of pancreatic xenograft tumors. ACV-TP-T, a thymidine analogue that is metabolized by telomerase and releases the active form of acyclovir, reduces proliferation and induces apoptosis of human pancreatic cancer cell lines in vitro and pancreatic xenograft tumors in mice. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

  7. Short term exposure to elevated levels of leptin reduces proximal tubule cell metabolic activity.

    Science.gov (United States)

    Briffa, Jessica F; Grinfeld, Esther; McAinch, Andrew J; Poronnik, Philip; Hryciw, Deanne H

    2014-01-25

    Leptin plays a pathophysiological role in the kidney, however, its acute effects on the proximal tubule cells (PTCs) are unknown. In opossum kidney (OK) cells in vitro, Western blot analysis identified that exposure to leptin increases the phosphorylation of the mitogen-activated protein kinase (MAPK) p44/42 and the mammalian target of rapamycin (mTOR). Importantly leptin (0.05, 0.10, 0.25 and 0.50 μg/ml) significantly reduced the metabolic activity of PTCs, and significantly decreased protein content per cell. Investigation of the role of p44/42 and mTOR on metabolic activity and protein content per cell, demonstrated that in the presence of MAPK inhibitor U0126 and mTOR inhibitor Ku-63794, that the mTOR pathway is responsible for the reduction in PTC metabolic activity in response to leptin. However, p44/42 and mTOR play no role the reduced protein content per cell in OKs exposed to leptin. Therefore, leptin modulates metabolic activity in PTCs via an mTOR regulated pathway.

  8. An Interactive Classroom Activity Demonstrating Reaction Mechanisms and Rate-Determining Steps

    Science.gov (United States)

    Jennings, Laura D.; Keller, Steven W.

    2005-01-01

    An interactive classroom activity that includes two-step reaction of unwrapping and eating chocolate candies is described which brings not only the reaction intermediate, but also the reactants and products into macroscopic view. The qualitative activation barriers of both steps can be adjusted independently.

  9. Demonstration of bacteriocin activity in bovine and bison strains of Pasteurella multocida. [UV radiation

    Energy Technology Data Exchange (ETDEWEB)

    Chengappa, M.M.; Carter, G.R.

    1977-08-01

    Of 33 strains of Pasteurella multocida examined, 14 showed bacteriocin activity and 17 were susceptible to bacteriocin. The activity was increased by about twofold if the cultures were induced with ultraviolet radiation; however, no increase in bacteriocin activity was observed if the potential producer strains were induced with mitomycin C. The bacteriocin activity of potential producer strains was increased if CaCl/sub 2/ was incorporated in the medium. The patterns of bacteriocin susceptibility indicate that these substances may ultimately contribute to a typing scheme for the species. An extra-chromosomal genetic element was not detected when a potential producer strain was not detected when a potential producer strain was tested by the dye-buoyant density gradient method. This fact suggests that the genetic material responsible for bacteriocin activity in P multocida is located on the host chromosome proper.

  10. Piano Playing Reduces Stress More than Other Creative Art Activities

    Science.gov (United States)

    Toyoshima, Kumiko; Fukui, Hajime; Kuda, Kiyoto

    2011-01-01

    Few studies have been conducted on the physiological effects of creative art activities. In this study, the effects of creative art activities on human stress were investigated, and their effects were compared in 57 healthy college students (27 males and 30 females). Subjects were divided into four groups, each of which participated in 30-minute…

  11. Piano Playing Reduces Stress More than Other Creative Art Activities

    Science.gov (United States)

    Toyoshima, Kumiko; Fukui, Hajime; Kuda, Kiyoto

    2011-01-01

    Few studies have been conducted on the physiological effects of creative art activities. In this study, the effects of creative art activities on human stress were investigated, and their effects were compared in 57 healthy college students (27 males and 30 females). Subjects were divided into four groups, each of which participated in 30-minute…

  12. Demonstrations of LSS active vibration control technology on representative ground-based testbeds

    Science.gov (United States)

    Hyland, David C.; Phillips, Douglas J.; Collins, Emmanuel G., Jr.

    1991-01-01

    This paper describes two experiments which successfully demonstrate control of flexible structures. The first experiment involved control design and implementation for the ACES structure at NASA Marshall Space Flight Center, while the second experiment was conducted using the Multi-Hex Prototype structure. The paper concludes with some remarks on the lessons learned from conducting these experiments.

  13. Sulphate reducing activity detected in soil samples from Antarctica, Ecology Glacier Forefield, King George Island.

    Science.gov (United States)

    Wolicka, Dorota; Zdanowski, Marek K; Żmuda-Baranowska, Magdalena J; Poszytek, Anna; Grzesiak, Jakub

    2014-01-01

    We determined sulphate-reducing activities in media inoculated with soils and with kettle lake sediments in order to investigate their potential in geomicrobiological processes in low-temperature, terrestrial maritime Antarctic habitats. Soil and sediment samples were collected in a glacier valley abandoned by Ecology Glacier during the last 30 years: from a new formed kettle lake sediment and forefield soil derived from ground moraine. Inoculated with these samples, liquid Postgate C and minimal media supplemented with various carbon sources as electron donors were incubated for 8 weeks at 4°C. High rates of sulphate reduction were observed only in media inoculated with soil. No sulphate reduction was detected in media inoculated with kettle lake sediments. In soil samples culture media calcite and elemental sulphur deposits were observed, demonstrating that sulphate-reducing activity is associated with a potential to mineral formation in cold environments. Cells observed on scanning microscopy (SEM) micrographs of post-culture-soil deposits could be responsible for sulphate-reducing activity.

  14. Cycloartane-3,24,25-triol inhibits MRCKα kinase and demonstrates promising anti prostate cancer activity in vitro

    Directory of Open Access Journals (Sweden)

    Lowe Henry I C

    2012-11-01

    Full Text Available Abstract Background Given the high occurrence of prostate cancer worldwide and one of the major sources of the discovery of new lead molecules being medicinal plants, this research undertook to investigate the possible anti-cancer activity of two natural cycloartanes; cycloartane-3,24,25-diol (extracted in our lab from Tillandsia recurvata and cycloartane-3,24,25-triol (purchased. The inhibition of MRCKα kinase has emerged as a potential solution to restoring the tight regulation of normal cellular growth, the loss of which leads to cancer cell formation. Methods Kinase inhibition was investigated using competition binding (to the ATP sites assays which have been previously established and authenticated and cell proliferation was measured using the WST-1 assay. Results Cycloartane-3,24,25-triol demonstrated strong selectivity towards the MRCKα kinase with a Kd50 of 0.26 μM from a total of 451 kinases investigated. Cycloartane-3,24,25-triol reduced the viability of PC-3 and DU145 cell lines with IC50 values of 2.226 ± 0.28 μM and 1.67 ± 0.18 μM respectively. Conclusions These results will prove useful in drug discovery as Cycloartane-3,24,25-triol has shown potential for development as an anti-cancer agent against prostate cancer.

  15. Reduced ceramide synthase 2 activity causes progressive myoclonic epilepsy

    DEFF Research Database (Denmark)

    Mosbech, Mai-Britt; Olsen, Anne S B; Neess, Ditte

    2014-01-01

    composition was also reflected in a reduction in cholera toxin B immunofluorescence, indicating that membrane composition and function are altered. INTERPRETATION: We propose that reduced levels of CERS2, and consequently diminished levels of ceramides and SLs containing very long-chain fatty acids, lead...

  16. Active Supervision: An Intervention to Reduce High School Tardiness

    Science.gov (United States)

    Johnson-Gros, Kristin N.; Lyons, Elizabeth A.; Griffin, Jennifer R.

    2008-01-01

    One proactive approach to aid in reducing disciplinary problems in schools is implementing Positive Behavior Support (PBS) strategies. To successfully implement PBS school-wide, Sugai and Horner (2002a) emphasize a multisystems perspective, which focuses on school-wide discipline, classroom management, non-classroom settings, and individual…

  17. Studies on the oxidizing system in Holt's medium for histochemical demonstration of esterase activity

    DEFF Research Database (Denmark)

    Kirkeby, S; Blecher, S R

    1978-01-01

    cells contain an esterase activity which is not inhibited by conventional SH blocking agents, nor by high concentrations of FFC. From these results it appears that the mode of action of FFC in Holt's medium is as follows. At low concentrations FFC appears to act primarily as a catalytic agent......Esterase activity in guinea-pig thyroid and mouse epididymis epithelial cells has been studied using 5-bromoindoxyl acetate as substrate. The pattern of esterase activity in the thyroid of the guinea-pig is constant, irrespective of whether ferri-ferrocyanide (FFC) or certain copper compounds...... are used as oxidizing agents in the incubation medium. The intensity of the coloured reaction product is increased when cobalt or manganese are added to the incubation medium. Activity is depressed by high concentrations of FFC when resent in incubation medium or preincubational buffer only. Epididymis...

  18. Reduced oxide soldering activation (ROSA) PWB solderability testing

    Energy Technology Data Exchange (ETDEWEB)

    Hernandez, C.L.; Hosking, F.M. [Sandia National Labs., Albuquerque, NM (United States). Physical and Joining Metallurgy Dept.; Reed, J. [Texas Instruments, Austin, TX (United States); Tench, D.M.; White, J. [Rockwell Science Center, Thousand Oaks, CA (United States)

    1996-02-01

    The effect of ROSA pretreatment on the solderability of environmentally stressed PWB test coupons was investigated. The PWB surface finish was an electroplated, reflowed solder. Test results demonstrated the ability to recover plated-through-hole fill of steam aged samples with solder after ROSA processing. ROSA offers an alternative method for restoring the solderability of aged PWB surfaces.

  19. Impaired cognitive control and reduced cingulate activity during mental fatigue

    NARCIS (Netherlands)

    Lorist, MM; Boksem, MAS; Ridderinkhof, KR

    2005-01-01

    Neurocognitive mechanisms underlying the effects of mental fatigue are poorly understood. Here, we examined whether error-related brain activity, indexing performance monitoring by the anterior cingulate cortex (ACC), and strategic behavioural adjustments were modulated by mental fatigue, as induced

  20. Recovery of autonomic nervous activity after myocardial infarction demonstrated by short-term measurements of SDNN

    DEFF Research Database (Denmark)

    Vaage-Nilsen, M; Rasmussen, Verner; Jensen, Gorm Boje;

    2001-01-01

    , and determine the role of these as independent risk factors compared to clinical, arrhythmic, ischemic and anamnestic variables. Measurements from a normal healthy middle-aged male population were used as reference (n = 63). METHODS: SDNN from a five-minute period during day and night-time, respectively......, was examined in 103 patients 1 week (n = 54), 1 month (n = 72) and 12-16 months (n = 54) after infarction. RESULTS: Day SDNN did not change during one-and-a-half years after AMI, and was significantly reduced compared with healthy males. Night SDNN, low after 1 week, with recovery 1 month after AMI......, was significantly reduced compared with healthy males early, but not late after AMI. Thus, the study indicated during day-time a continuous abnormal sympathetic preponderance in the course of 16 months after AMI, and during night-time a gradual recovery of parasympathetic preponderance beginning early after AMI...

  1. Cardiopulmonary bypass reduces peripheral microvascular contractile function by inhibition of mitogen-activated protein kinase activity.

    Science.gov (United States)

    Khan, Tanveer A; Bianchi, Cesario; Araujo, Eugenio G; Ruel, Marc; Voisine, Pierre; Li, Jianyi; Liddicoat, John R; Sellke, Frank W

    2003-08-01

    Mitogen-activated protein kinases (MAPK) have been implicated in pathophysiologic responses to cardiopulmonary bypass (CPB). MAPK are deactivated by phosphatases, such as MAPK phosphatase-1 (MKP-1). We hypothesized that MAPK mediate peripheral microvascular contractile dysfunction caused by CPB in humans. Skeletal muscle was harvested before and after CPB. Protein levels of MKP-1 and activated extracellular signal-regulated kinase 1/2 (ERK1/2) and p38 were measured. MKP-1 gene expression was measured. Peripheral microvessel responses to vasopressors were studied by videomicroscopy. Contractile function also was measured after MAPK inhibition with PD98059 (ERK1/2) and SB203580 (p38). ERK1/2, p38, and MKP-1 were localized by immunohistochemistry and in situ hybridization. ERK1/2 and p38 activity was decreased in peripheral tissue after CPB. MKP-1 was increased after CPB. Contractile responses of peripheral arterioles to phenylephrine and vasopressin were decreased after CPB. Microvessel reactivity also was reduced after treatment with PD98059 and SB203580. ERK1/2, p38, and MKP-1 localized to peripheral arterioles in tissue sections. CPB reduces ERK1/2 and p38 activity in peripheral tissue, potentially by MKP-1. Contractile responses of peripheral arterioles to phenylephrine and vasopressin are dependent on ERK1/2 and p38 and are decreased after CPB. These results suggest that alterations in MAPK pathways in part regulate peripheral microvascular dysfunction after CPB in humans.

  2. The 28-day exposure to fenpropathrin decreases locomotor activity and reduces activity of antioxidant enzymes in mice brains.

    Science.gov (United States)

    Nieradko-Iwanicka, Barbara; Borzęcki, Andrzej

    2016-04-01

    Fenpropathrin (Fen) is a pyrethroid (Pyr) insecticide. Pyrs are used in veterinary medicine, in agriculture and for domestic purposes. As their use increases, new questions about their side effects and mode of action in non-target organisms arise. The objective of this work was to characterize dose-response relationship for in vivo motor function and memory in mice exposed to Fen for 28 days and to assess its influence on activity of antioxidant enzymes in mice brains. The experiment was performed using 64 female mice. Fen at the dose of 11.9mg/kg of body mass, 5.95mg/kg or 2.38mg/kg was administered ip to the mice for 28 consecutive days. Motor function and spatial working memory were tested on days 7, 14 and 28. On day 29, the animals were sacrificed and brains were used to determine activities of superoxide dismutase (SOD) and glutathione peroxidase (GPx). Fen significantly decreased locomotor activity in mice receiving the highest dose at every stage of the experiment. Lower doses reduced locomotion on days 7 and 14. Fen did not produce memory impairment. A decrease in activities of SOD and GPx was recorded in mice brains. The decrease of SOD activity in mice brains results from direct inhibition of the enzyme by Fen and/or increased utilization due to excessive free radical formation in conditions of Fen-induced oxidative stress. The reduction in GPx activity is probably due to limited glutathione availability. The reduced locomotor activity is a behavioral demonstration of Fen-induced damage in the dopaminergic system. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  3. Histochemical demonstration of activity of acid phosphatase and beta-glucuronidase in bovine incisor tooth germs

    DEFF Research Database (Denmark)

    Kirkeby, S; Salling, E; Moe, D

    1983-01-01

    Activity of acid phosphatase and beta-glucuronidase was shown in bovine preodontoblasts and preameloblasts prior to the onset of secretion. In the preameloblasts the rather weak reaction consisted of small discrete granules dispersed in the cytoplasm apical, lateral, and proximal to the nucleus....... After initiation of enamel formation, a change in localization and intensity of the colored reaction product was observed in the ameloblasts. The activity appeared stronger and was restricted to a narrow zone just apical to the nucleus. It is proposed that the acid hydrolases in the tooth forming cells...... are located to the Golgi complex. The differences in activity of acid hydrolases between bone and tooth forming cells are expounded....

  4. Salvia leriifolia Benth (Lamiaceae) extract demonstrates in vitro antioxidant properties and cholinesterase inhibitory activity.

    Science.gov (United States)

    Loizzo, Monica R; Tundis, Rosa; Conforti, Filomena; Menichini, Federica; Bonesi, Marco; Nadjafi, Farsad; Frega, Natale Giuseppe; Menichini, Francesco

    2010-12-01

    The object of the present study was to investigate the in vitro antioxidant properties and cholinesterase inhibitory activity of Salvia leriifolia Benth extracts and fractions. The functional role of herbs and spices and their constituents is a hot topic in food-related plant research. Salvia species have been used since ancient times in folk medicine for cognitive brain function and have been subjected to extensive research. Thus, we hypothesize that S leriifolia, because of its functional properties, would be a good candidate to use as a nutraceutical product for improving memory in the elderly or patients affected by Alzheimer disease (ad). To test this hypothesis, we examined the cholinesterase inhibitory activity using the modified colorimetric Ellman's method against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The n-hexane exhibited the highest activity, with inhibitory concentration 50% (IC(50)) values of 0.59 and 0.21 mg/mL, for AChE and BChE, respectively. This extract was fractionated, and 9 of these fractions (A-I) were obtained and tested. Fraction G, characterized by the presence of sesquiterpenes as major components, was the most active against AChE (IC(50) = 0.05 mg/mL). Because oxidative stress is a critical event in the pathogenesis of AD, we decided to screen the antioxidant activity (AA) using 2,2-diphenyl-1-picrylhydrazyl test, β-carotene bleaching test, and bovine brain peroxidation (thiobarbituric acid) assay. The ethyl acetate extract showed the highest activity, with IC(50) values of 2 and 33 μg/mL on β-carotene bleaching test and thiobarbituric acid test, respectively. These results suggest potential health benefits of S leriifolia extracts. However, this finding requires additional investigation in vivo.

  5. Sensory stimuli reduce the dimensionality of cortical activity

    Science.gov (United States)

    Mazzucato, Luca; Fontanini, Alfredo; La Camera, Giancarlo

    Neural ensembles in alert animals generate complex patterns of activity. Although cortical activity unfolds in a space whose dimension is equal to the number of neurons, it is often restricted to a lower dimensional subspace. Dimensionality is the minimal number of dimensions that accurately capture neural dynamics, and may be related to the computational tasks supported by the neural circuit. Here, we investigate the dimensionality of neural ensembles from the insular cortex of alert rats during periods of `ongoing' (spontaneous) and stimulus-evoked activity. We find that the dimensionality grows with ensemble size, and does so significantly faster during ongoing compared to evoked activity. We explain both results using a recurrent spiking network with clustered architecture, and obtain analytical results on the dependence of dimensionality on ensemble size, number of clusters, and pair-wise noise correlations. The theory predicts a characteristic scaling with ensemble size and the existence of an upper bound on dimensionality, which grows with the number of clusters and decreases with the amount of noise correlations. To our knowledge, this is the first mechanistic model of neural dimensionality in cortex during both spontaneous and evoked activity.

  6. Metformin reduces airway inflammation and remodeling via activation of AMP-activated protein kinase.

    Science.gov (United States)

    Park, Chan Sun; Bang, Bo-Ram; Kwon, Hyouk-Soo; Moon, Keun-Ai; Kim, Tae-Bum; Lee, Ki-Young; Moon, Hee-Bom; Cho, You Sook

    2012-12-15

    Recent reports have suggested that metformin has anti-inflammatory and anti-tissue remodeling properties. We investigated the potential effect of metformin on airway inflammation and remodeling in asthma. The effect of metformin treatment on airway inflammation and pivotal characteristics of airway remodeling were examined in a murine model of chronic asthma generated by repetitive challenges with ovalbumin and fungal-associated allergenic protease. To investigate the underlying mechanism of metformin, oxidative stress levels and AMP-activated protein kinase (AMPK) activation were assessed. To further elucidate the role of AMPK, we examined the effect of 5-aminoimidazole-4-carboxamide-1-β-4-ribofuranoside (AICAR) as a specific activator of AMPK and employed AMPKα1-deficient mice as an asthma model. The role of metformin and AMPK in tissue fibrosis was evaluated using a bleomycin-induced acute lung injury model and in vitro experiments with cultured fibroblasts. Metformin suppressed eosinophilic inflammation and significantly reduced peribronchial fibrosis, smooth muscle layer thickness, and mucin secretion. Enhanced AMPK activation and decreased oxidative stress in lungs was found in metformin-treated asthmatic mice. Similar results were observed in the AICAR-treated group. In addition, the enhanced airway inflammation and fibrosis in heterozygous AMPKα1-deficient mice were induced by both allergen and bleomycin challenges. Fibronectin and collagen expression was diminished by metformin through AMPKα1 activation in cultured fibroblasts. Therefore metformin reduced both airway inflammation and remodeling at least partially through the induction of AMPK activation and decreased oxidative stress. These data provide insight into the beneficial role of metformin as a novel therapeutic drug for chronic asthma.

  7. The effect of science demonstrations as a community service activity on pre-service science teachers' teaching practices

    Science.gov (United States)

    Gurel, Derya Kaltakci

    2016-03-01

    In the scope of this study, pre-service science teachers (PSST) developed and carried out science demonstrations with everyday materials for elementary school students as a community service activity. 17 PSST enrolled in the community services practices course at Kocaeli University comprised the sample of the present study. Community service practices aim to develop consciousness of social responsibility and professional skills, as well as to gain awareness of social and community problems and find solutions for pre-service teachers. With this aim, each PSST developed five science demonstration activities and their brochures during a semester. At the end of the semester, a total of 85 demonstrations were carried out at public elementary schools, which are especially located in socioeconomically poor districts of Kocaeli, Turkey. In the present case study, the effect of developing and carrying out science demonstrations for elementary school students on six of the PSST' teaching practices on density and buoyancy concept was investigated. 30-minute interviews conducted with each PSST, videos recorded during their demonstration performances, brochures they prepared for their demonstration activities, and reflection papers were used as data collection tools of the study. The results showed that community service practices with science demonstrations had positive effects on PSST' science content knowledge and pedagogical content knowledge.

  8. Burnout Is Associated with Reduced Parasympathetic Activity and Reduced HPA Axis Responsiveness, Predominantly in Males

    Directory of Open Access Journals (Sweden)

    Wieke de Vente

    2015-01-01

    Full Text Available There is mounting evidence that burnout is a risk factor for cardiovascular disease (CVD. Stress-related dysregulation of the sympathetic and parasympathetic system and the hypothalamic pituitary adrenal (HPA axis may explain the enhanced risk for CVD. To test this hypothesis, 55 patients (34 males and 21 females with burnout on sickness absence and 40 healthy participants (16 males and 24 females were exposed to a psychosocial stressor consisting of mental arithmetic and public speech. Physiological variables (i.e., blood pressure, heart rate, cardiac output, vascular resistance, cortisol, and alpha-amylase were measured. Basal levels, reactivity, and recovery were compared between groups. In male patients, baseline systolic blood pressure was higher, whereas basal alpha-amylase and cortisol reactivity were lower than in healthy males. In female patients, a tendency for lower basal cortisol was found as compared to healthy females. Furthermore, reduced basal heart rate variability and a trend for elevated basal cardiac output were observed in both male and female patients. Burnout is characterised by dysregulation of the sympathetic and parasympathetic system and the HPA axis, which was more pronounced in males than in females. This study further supports burnout as being a risk factor for CVD through dysregulation of the sympathetic and parasympathetic system and the HPA axis.

  9. Of Heart & Kidneys: Hands-On Activities for Demonstrating Organ Function & Repair

    Science.gov (United States)

    Kao, Robert M.

    2014-01-01

    A major challenge in teaching organ development and disease is deconstructing a complex choreography of molecular and cellular changes over time into a linear stepwise process for students. As an entry toward learning developmental concepts, I propose two inexpensive hands-on activities to help facilitate learning of (1) how to identify defects in…

  10. Of Heart & Kidneys: Hands-On Activities for Demonstrating Organ Function & Repair

    Science.gov (United States)

    Kao, Robert M.

    2014-01-01

    A major challenge in teaching organ development and disease is deconstructing a complex choreography of molecular and cellular changes over time into a linear stepwise process for students. As an entry toward learning developmental concepts, I propose two inexpensive hands-on activities to help facilitate learning of (1) how to identify defects in…

  11. Demonstration in human plasma of a lectin activity analogous to that of bovine conglutinin

    DEFF Research Database (Denmark)

    Baatrup, G; Thiel, S; Isager, H

    1987-01-01

    Evidence of the existence in human plasma of an activity analogous to that of bovine conglutinin is presented. The human plasma component was characterized antigenically and functionally. Human plasma was shown to agglutinate complement-coated erythrocytes in the presence of Ca2+, and this conglu...

  12. An Activity To Demonstrate the Concept of Sampling Error for the Introductory Biology Classroom.

    Science.gov (United States)

    Rutledge, Michael L.

    2001-01-01

    This activity makes students a part of an investigation that determines the frequency of a particular plant variety in a simulated population. Provides an opportunity for students to observe the inherent variability of estimates, observe the relationship between sample size and sampling error, and consider aspects of research design. (Author/SAH)

  13. Studies on the oxidizing system in Holt's medium for histochemical demonstration of esterase activity

    DEFF Research Database (Denmark)

    Kirkeby, S; Blecher, S R

    1978-01-01

    are used as oxidizing agents in the incubation medium. The intensity of the coloured reaction product is increased when cobalt or manganese are added to the incubation medium. Activity is depressed by high concentrations of FFC when resent in incubation medium or preincubational buffer only. Epididymis...

  14. Abnormal activation of the motor cortical network in idiopathic scoliosis demonstrated by functional MRI.

    Science.gov (United States)

    Domenech, Julio; García-Martí, G; Martí-Bonmatí, L; Barrios, C; Tormos, J M; Pascual-Leone, A

    2011-07-01

    The aetiology of idiopathic scoliosis (IS) remains unknown, but there is growing support for the possibility of an underlying neurological disorder. Functional magnetic resonance imaging (fMRI) can characterize the abnormal activation of the sensorimotor brain network in movement disorders and could provide further insights into the neuropathogenesis of IS. Twenty subjects were included in the study; 10 adolescents with IS (mean age of 15.2, 8 girls and 2 boys) and 10 age-matched healthy controls. The average Cobb angle of the primary curve in the IS patients was 35° (range 27°-55°). All participants underwent a block-design fMRI experiment in a 1.5-Tesla MRI scanner to explore cortical activation following a simple motor task. Rest periods alternated with activation periods during which participants were required to open and close their hand at an internally paced rate of approximately 1 Hz. Data were analyzed with Statistical Parametric Mapping (SPM5) including age, sex and laterality as nuisance variables to minimise the presence of bias in the results. Compared to controls, IS patients showed significant increases in blood oxygenation level dependent (BOLD) activity in contralateral supplementary motor area when performing the motor task with either hand. No significant differences were observed when testing between groups in the functional activation in the primary motor cortex, premotor cortex and somatosensory cortex. Additionally, the IS group showed a greater interhemispheric asymmetry index than the control group (0.30 vs. 0.13, p motor areas during movement execution in patients with IS. These findings support the hypothesis that a sensorimotor integration disorder underlies the pathogenesis of IS.

  15. Antipollution skin protection – a new paradigm and its demonstration on two active compounds

    Directory of Open Access Journals (Sweden)

    Portugal-Cohen M

    2017-05-01

    Full Text Available Meital Portugal-Cohen,1,2 Miriam Oron,1,2 Dror Cohen,1–3 Zeevi Ma’or1,2 1AHAVA Dead Sea Laboratories, Lod, Israel; 2The Dead Sea Laboratory for Skin Biochemistry and Biotechnology, Dead Sea and Arava Science Center, Masada, Israel; 3The Institute for Drug Research, The Hebrew University of Jerusalem, Jerusalem, Israel Background: Urban pollution is a major source of concern for human health and is a complex of many environmental factors. The topical exposure to pollution activates cutaneous stress.Objective: In this study, we tested the antipollution protection of two active components: Dead Sea minerals (Dead Sea mineral-rich water [DSW] and anionic polysaccharide (PolluStop® [PS].Materials and methods: Two representative pollution models were studied using reconstructed epidermis: 1 mixture of pollutants (MOP containing heavy metals and atmospheric particulate matter and 2 ozone exposure. DSW and PS were topically applied alone or in combination, and their protection against pollution was assessed by testing the levels of the inflammation markers interleukin 1α (IL-1α and prostaglandin E2 (PGE2.Results: MOP exposure induced IL-1α release, which was attenuated following pre-application with DSW and PS alone or in combination. Ozone exposure induced IL-1α and PGE2 release. Pre-application with DSW or PS alone did not inhibit IL-1α and PGE2 overproduction. Only when DSW and PS were mixed together, inhibition of these inflammatory markers was observed.Conclusion: The observations reveal the potential use of active agents in combination for a selective mode of protection from urban pollution. This is because many active materials cannot solely provide a broad protection against different types of pollutants. This strategy might be beneficial for future antipollution regimen formulated in both pharmaceutical and cosmetic products. Keywords: urban pollution, dermal exposure, inflammation, oxidation, alternative skin models, antipollution

  16. DENSE PHASE REBURN COMBUSTION SYSTEM (DPRCS) DEMONSTRATION ON A 154 MWE TANGENTIAL FURNACE: ADDITIONAL AREA OF INTEREST-TO DEVELOP AND DEMONSTRATE AN IN-FURNACE MULTI-POLLUTANT REDUCTION TECHNOLOGY TO REDUCE NOx, SO2 & Hg

    Energy Technology Data Exchange (ETDEWEB)

    Allen C. Wiley; Steven Castagnero; Geoff Green; Kevin Davis; David White

    2004-03-01

    Semi-dense phase pneumatic delivery and injection of calcium and sodium sorbents, and microfine powdered coal, at various sidewall elevations of an online operating coal-fired power plant, was investigated for the express purpose of developing an in-furnace, economic multi-pollutant reduction methodology for NO{sub x}, SO{sub 2} & Hg. The 154 MWe tangentially-fired furnace that was selected for a full-scale demonstration, was recently retrofitted for NO{sub x} reduction with a high velocity rotating-opposed over-fire air system. The ROFA system, a Mobotec USA technology, has a proven track record of breaking up laminar flow along furnace walls, thereby enhancing the mix of all constituents of combustion. The knowledge gained from injecting sorbents and micronized coal into well mixed combustion gases with significant improvement in particulate retention time, should serve well the goals of an in-furnace multi-pollutant reduction technology; that of reducing back-end cleanup costs on a wide variety of pollutants, on a cost per ton basis, by first accomplishing significant in-furnace reductions of all pollutants.

  17. Reduced Frontal Activation with Increasing 2nd Language Proficiency

    Science.gov (United States)

    Stein, Maria; Federspiel, Andrea; Koenig, Thomas; Wirth, Miranka; Lehmann, Christoph; Wiest, Roland; Strik, Werner; Brandeis, Daniel; Dierks, Thomas

    2009-01-01

    The factors influencing the degree of separation or overlap in the neuronal networks responsible for the processing of first and second language are still subject to investigation. This longitudinal study investigates how increasing second language proficiency influences activation differences during lexico-semantic processing of first and second…

  18. IL-19 Reduces Ligation-Mediated Neointimal Hyperplasia by Reducing Vascular Smooth Muscle Cell Activation

    Science.gov (United States)

    Ellison, Stephen; Gabunia, Khatuna; Richards, James M.; Kelemen, Sheri E.; England, Ross N.; Rudic, Dan; Azuma, Yasu-Taka; Munroy, M. Alexandra; Eguchi, Satoru; Autieri, Michael V.

    2015-01-01

    We tested the hypothesis that IL-19, a putative member of the type 2 helper T-cell family of anti-inflammatory interleukins, can attenuate intimal hyperplasia and modulate the vascular smooth muscle cell (VSMC) response to injury. Ligated carotid artery of IL-19 knockout (KO) mice demonstrated a significantly higher neointima/intima ratio compared with wild-type (WT) mice (P = 0.04). More important, the increased neointima/intima ratio in the KO could be reversed by injection of 10 ng/g per day recombinant IL-19 into the KO mouse (P = 0.04). VSMCs explanted from IL-19 KO mice proliferated significantly more rapidly than WT. This could be inhibited by addition of IL-19 to KO VSMCs (P = 0.04 and P < 0.01). IL-19 KO VSMCs migrated more rapidly compared with WT (P < 0.01). Interestingly, there was no type 1 helper T-cell polarization in the KO mouse, but there was significantly greater leukocyte infiltrate in the ligated artery in these mice compared with WT. IL-19 KO VSMCs expressed significantly greater levels of inflammatory mRNA, including IL-1β, tumor necrosis factor α, and monocyte chemoattractant protein-1 in response to tumor necrosis factor α stimulation (P < 0.01 for all). KO VSMCs expressed greater adhesion molecule expression and adherence to monocytes. Together, these data indicate that IL-19 is a previously unrecognized counterregulatory factor for VSMCs, and its expression is an important protective mechanism in regulation of vascular restenosis. PMID:24814101

  19. Demonstration of intuitive thinking in conditions of competitive activity depending on athletes' psychophysiological state.

    Directory of Open Access Journals (Sweden)

    Korobeynikov G.V.

    2012-07-01

    Full Text Available One investigated application of intuitive thinking, depending on the physiological status of skilled fighters in their competitive activity. In research members of the team of Ukraine in Greco-Roman wrestling participated. 29 effective throws were analysed reverse a capture from position orchestra. One analyzed the effectiveness of intuitive thinking in athletes of different weight categories and the distribution coefficients of correlation of psychophysiological functions of athletes directly in competition during championships of Ukraine, World and Europe. One found that expression of intuitive thinking is associated with weight category of skilled fighters. It is shown that the effectiveness of intuitive thinking in terms of competitive activity is related to physiological state, and, above all qualified wrestlers' neurodynamic functions.

  20. Toxoplasma gondii: demonstration of intrinsic peroxidase activity during lacto-peroxidase mediated radioiodination of tachyzoites

    Energy Technology Data Exchange (ETDEWEB)

    Gallois, Y.; Tricaud, A.; Foussard, F.; Hodbert, J.; Girault, A.; Mauras, G.; Dubremetz, J.F.

    1986-01-01

    Tachyzoites of Toxoplasma gondii have been radioiodinated under various conditions with or without lactoperoxidase, with glucose oxidase being used to generate hydrogen peroxide. Erythrocytes were iodinated simultaneously as a control. In our conditions, tachyzoites were more intensely labelled in the absence of lactoperoxidase. This result can be explained by the existence of an intrinsic peroxidase activity which interfere with the exogenously added enzyme during surface radioiodination.

  1. Active vibration-based SHM system: demonstration on an operating Vestas V27 wind turbine

    DEFF Research Database (Denmark)

    Tcherniak, Dmitri; Mølgaard, Lasse Lohilahti

    2016-01-01

    with the system and a 3.5 month monitoring campaign was conducted while the turbine was operating normally. During the campaign, a defect – a trailing edge opening – was artificially introduced into the blade and its size was gradually increased from the original 15 cm to 45 cm. Using an unsupervised learning......This study presents a system that is able to detect defects like cracks, leading/trailing edge opening or delamination of at least 15 cm size, remotely, without stopping the wind turbine. The system is vibration-based: mechanical energy is artificially introduced by means of an electromechanical......-to-noise ratio. At the same time, the corresponding wavelength is short enough to deliver required damage detection resolution and long enough to be able to propagate the entire blade length. The paper demonstrates the system on a 225 kW Vesta s V27 wind turbine. One blade of the wind turbine was equipped...

  2. Cover Your Cough! A Short and Simple Activity to Demonstrate the Antimicrobial Effect of Desiccation

    Directory of Open Access Journals (Sweden)

    Jennifer Cook Easterwood

    2013-08-01

    Full Text Available Many undergraduate microbiology laboratory manuals include exercises demonstrating the antimicrobial effects of physical agents, such as UV light and heat, and chemical agents, such as disinfectants and antibiotics (3, 4. There is, however, a lack of exercises examining the effects of desiccation on bacterial growth and survival. This particular form of antimicrobial control is especially relevant today with an increased emphasis on coughing and sneezing into one’s sleeve or a tissue, where microbes will not contaminate hands and will eventually desiccate and die (2. Desiccation can have bacteriostatic or bactericidal effects depending on the species, the material on which the organism has desiccated, and the length of time. The absence of water can damage many cellular components, including enzymes, nucleic acids, and cell membranes (1. However, many prokaryotes have some degree of resistance to desiccation, with Escherichia coli surviving around 24 hours and Bacillus species surviving upwards of 300 years, though these numbers can vary due to a number of confounding factors (5. Some of these factors include the method by which desiccation occurred, whether desiccation occurred in a natural or laboratory situation, and the species itself (5. To address the effects of desiccation on bacterial growth and survival, a short, simple exercise was developed. By inoculating various materials with bacterial cultures and allowing them to air-dry for 24 hours, students can visualize the effects of desiccation by analyzing the growth, or lack thereof, when organisms are transferred to nutrient agar plates. This exercise has been used in a health professions microbiology course as well as a microbiology course for biology and biochemistry majors. It is short enough to be conducted during a standard lecture period or during a longer laboratory period in conjunction with other experiments demonstrating the effectiveness of physical agents on microbial

  3. Functionally Selective AT(1) Receptor Activation Reduces Ischemia Reperfusion Injury

    DEFF Research Database (Denmark)

    Hostrup, Anders; Christensen, Gitte Lund; Bentzen, Bo Hjort;

    2012-01-01

    of the physiological functions of AngII. The AT(1)R mediates its effects through both G protein-dependent and independent signaling, which can be separated by functionally selective agonists. In the present study we investigate the effect of AngII and the ß-arrestin biased agonist [SII]AngII on ischemia......-reperfusion injury in rat hearts. Isolated hearts mounted in a Langendorff perfused rat heart preparations showed that preconditioning with [SII]AngII reduced the infarct size induced by global ischemia from 46±8.4% to 22±3.4%. In contrast, neither preconditioning with AngII nor postconditioning with AngII or [SII...

  4. Recent progress of R and D activities on reduced activation ferritic/martensitic steels

    Energy Technology Data Exchange (ETDEWEB)

    Huang, Q., E-mail: qunying.huang@fds.org.cn [Institute of Nuclear Energy Safety Technology, Chinese Academy of Sciences, P.O. Box 1135, Hefei, Anhui 230031 (China); Baluc, N. [CRPP-EPFL, ODGA C110 5232 Villigen PSI (Switzerland); Dai, Y. [LNM, PSI, 5232 Villigen PSI (Switzerland); Jitsukawa, S. [JAEA, 2-4 Shirakata, Tokai-Mura, Ibaraki-Ken 319-1195 (Japan); Kimura, A. [IAE, Kyoto University, Gokasho, Uji, Kyoto 611-0011 (Japan); Konys, J. [KIT, P.O. Box 3640, 76021 Karlsruhe (Germany); Kurtz, R.J. [PNNL, Richland, WA 99352 (United States); Lindau, R. [KIT, P.O. Box 3640, 76021 Karlsruhe (Germany); Muroga, T. [NIFS, Oroshi, Toki, Gifu 509-5292 (Japan); Odette, G.R. [UCSB, Santa Barbara, CA (United States); Raj, B. [IGCAR, Kalpakkam 603 102 (India); Stoller, R.E.; Tan, L. [ORNL, P.O. Box 2008, Oak Ridge, TN 37831 (United States); Tanigawa, H. [JAEA, Naka, Ibaraki 311-0193 (Japan); Tavassoli, A.-A.F. [DMN/Dir, DEN, CEA Saclay, 91191 Gif-sur-Yvette cedex (France); Yamamoto, T. [UCSB, Santa Barbara, CA (United States); Wan, F. [DMPC, USTB, Beijing 100083 (China); Wu, Y. [Institute of Nuclear Energy Safety Technology, Chinese Academy of Sciences, P.O. Box 1135, Hefei, Anhui 230031 (China)

    2013-11-15

    Several types of reduced activation ferritic/martensitic (RAFM) steel have been developed over the past 30 years in China, Europe, India, Japan, Russia and the USA for application in ITER test blanket modules (TBMs) and future fusion DEMO and power reactors. The progress has been particularly important during the past few years with evaluation of mechanical properties of these steels before and after irradiation and in contact with different cooling media. This paper presents recent RAFM steel results obtained in ITER partner countries in relation to different TBM and DEMO options.

  5. First demonstration that brain CYP2D-mediated opiate metabolic activation alters analgesia in vivo

    Science.gov (United States)

    Zhou, Kaidi; Khokhar, Jibran Y.; Zhao, Bin; Tyndale, Rachel F.

    2013-01-01

    The response to centrally-acting drugs is highly variable between individuals and does not always correlate with plasma drug levels. Drug-metabolizing CYP enzymes in the brain may contribute to this variability by affecting local drug and metabolite concentrations. CYP2D metabolizes codeine to the active morphine metabolite. We investigate the effect of inhibiting brain, and not liver, CYP2D activity on codeine-induced analgesia. Rats received intracerebroventricular injections of CYP2D inhibitors (20 μg propranolol or 40 μg propafenone) or vehicle controls. Compared to vehicle-pretreated rats, inhibitor-pretreated rats had: a) lower analgesia in the tail-flick test (p0.6 and p>0.7, respectively), tested at 30 min after 30 mg/kg subcutaneous codeine, and c) lower morphine formation from codeine ex vivo by brain membranes (p0.9). Analgesia trended toward a correlation with brain morphine concentrations (p=0.07) and correlated with brain morphine to codeine ratios (p0.8) or plasma morphine to codeine ratios (p>0.8). Our findings suggest that brain CYP2D affects brain morphine levels after peripheral codeine administration, and may thereby alter codeine's therapeutic efficacy, side-effect profile and abuse liability. Brain CYPs are highly variable due to genetics, environmental factors and age, and may therefore contribute to interindividual variation in the response to centrally-acting drugs. PMID:23623752

  6. Antiproliferative activity of Eremanthus crotonoides extracts and centratherin demonstrated in brain tumor cell lines

    Directory of Open Access Journals (Sweden)

    Jonathas F. R. Lobo

    2012-12-01

    Full Text Available The genus Eremanthus is recognized by the predominance of sesquiterpene lactones from the furanoheliangolide type, a class of substances extensively tested against cancer cell lines. Thus, the species E. crotonoides (DC. Sch. Bip., Asteraceae, obtained on "restinga" vegetation was evaluated against U251 and U87-MG glioma cell lines using the MTT colorimetric assay. Dichloromethane fraction was cytotoxic to both glioblastoma multiforme cell lines. We then conducted UPLC-PDA-ESI-MS/MS analysis of the dichloromethane fraction, which allowed the identification of the sesquiterpene lactones centratherin and goyazensolide. The isolation of centratherin was performed using chromatographic techniques and the identification of this substance was confirmed according to NMR data. Cytotoxic activity of centratherin alone was also evaluated against both U251 and U87-MG cells, which showed IC50 values comparable with those obtained for the commercial anticancer drug doxorubicin. All the tested samples showed cytotoxic activity against glioblastoma multiforme cells which suggests that E. crotonoides extracts may be important sources of antiproliferative substances and that the centratherin may serve as prototype for developing new antiglioblastoma drugs.

  7. Barriers associated with reduced physical activity in COPD patients

    Directory of Open Access Journals (Sweden)

    Priscila Batista Amorim

    2014-10-01

    Full Text Available OBJECTIVE: To evaluate the ability of COPD patients to perform activities of daily living (ADL; to identify barriers that prevent these individuals from performing ADL; and to correlate those barriers with dyspnea severity, six-minute walk test (6MWT, and an ADL limitation score. METHODS: In COPD patients and healthy, age-matched controls, the number of steps, the distance walked, and walking time were recorded with a triaxial accelerometer, for seven consecutive days. A questionnaire regarding perceived barriers and the London Chest Activity of Daily Living (LCADL scale were used in order to identify the factors that prevent the performance of ADL. The severity of dyspnea was assessed with two scales, whereas submaximal exercise capacity was determined on the basis of the 6MWT. RESULTS: We evaluated 40 COPD patients and 40 controls. In comparison with the control values, the mean walk time was significantly shorter for COPD patients (68.5 ± 25.8 min/day vs. 105.2 ± 49.4 min/day; p < 0.001, as was the distance walked (3.9 ± 1.9 km/day vs. 6.4 ± 3.2 km/day; p < 0.001. The COPD patients also walked fewer steps/day. The most common self-reported barriers to performing ADL were lack of infrastructure, social influences, and lack of willpower. The 6MWT distance correlated with the results obtained with the accelerometer but not with the LCADL scale results. CONCLUSIONS: Patients with COPD are less active than are healthy adults of a comparable age. Physical inactivity and the barriers to performing ADL have immediate implications for clinical practice, calling for early intervention measures.

  8. Copper sulphate reduces the metabolic activity of Gammarus fossarum in laboratory and field experiments

    Energy Technology Data Exchange (ETDEWEB)

    Schmidlin, Lara, E-mail: lara.schmidlin@unibas.ch; Fumetti, Stefanie von; Nagel, Peter

    2015-04-15

    Highlights: • Copper-contaminated food significantly reduces the ETS activity of G. fossarum. • The ETS and feeding activity of G. fossarum were significantly higher in the lab. • A combination of test chamber experiments in the laboratory and field is optimal. - Abstract: The specialised fauna of freshwater springs is affected by contamination of the water with xenobiotics from human activities in the surrounding landscape. We assessed the effects of exposure to toxins in laboratory and field experiments by using copper sulphate as a model substance and Gammarus fossarum Koch, 1836, as the model organism. This amphipod is a common representative of the European spring fauna and copper is a widespread contaminant, mainly from agricultural practice. The experiments were conducted in test chambers placed in flow channels and directly in a spring. The gammarids were fed with conditioned beech leaf discs, which had been exposed to a 0.8 mg Cu/L solution for 96 h. The feeding activity of the amphipods was quantified on the level of the organism; and the respiratory electron transport system (ETS) assay was conducted in order to determine changes on the cellular level in the test organisms. The results show that the feeding activity, when the leaf discs were contaminated with copper, was not significantly different from the control. The ETS activity of the gammarids, which had been feeding on the copper contaminated leaf discs was however significantly reduced. The results followed the same pattern for gammarids from both the laboratory and the spring. By conducting the experiments not only in a laboratory but also directly in a spring in the field, we took a crucial step towards a more realistic approach when examining environmental pollutants on an organism. Our findings demonstrate the importance of conducting experiments out in the field, in natural conditions, as well as in the laboratory.

  9. Transcriptome sequencing demonstrates that human papillomavirus is not active in cutaneous squamous cell carcinoma.

    Science.gov (United States)

    Arron, Sarah T; Ruby, J Graham; Dybbro, Eric; Ganem, Don; Derisi, Joseph L

    2011-08-01

    β-Human papillomavirus (β-HPV) DNA is present in some cutaneous squamous cell carcinomas (cuSCCs), but no mechanism of carcinogenesis has been determined. We used ultra-high-throughput sequencing of the cancer transcriptome to assess whether papillomavirus transcripts are present in these cancers. In all, 67 cuSCC samples were assayed for β-HPV DNA by PCR, and viral loads were measured with type-specific quantitative PCR. A total of 31 SCCs were selected for whole transcriptome sequencing. Transcriptome libraries were prepared in parallel from the HPV18-positive HeLa cervical cancer cell line and HPV16-positive primary cervical and periungual SCCs. Of the tumors, 30% (20/67) were positive for β-HPV DNA, but there was no difference in β-HPV viral load between tumor and normal tissue (P=0.310). Immunosuppression and age were significantly associated with higher viral load (P=0.016 for immunosuppression; P=0.0004 for age). Transcriptome sequencing failed to identify papillomavirus expression in any of the skin tumors. In contrast, HPV16 and HPV18 mRNA transcripts were readily identified in primary cervical and periungual cancers and HeLa cells. These data demonstrate that papillomavirus mRNA expression is not a factor in the maintenance of cuSCCs.

  10. Using Wavelet Entropy to Demonstrate how Mindfulness Practice Increases Coordination between Irregular Cerebral and Cardiac Activities.

    Science.gov (United States)

    Sik, Hin Hung; Gao, Junling; Fan, Jicong; Wu, Bonnie Wai Yan; Leung, Hang Kin; Hung, Yeung Sam

    2017-05-10

    In both the East and West, traditional teachings say that the mind and heart are somehow closely correlated, especially during spiritual practice. One difficulty in proving this objectively is that the natures of brain and heart activities are quite different. In this paper, we propose a methodology that uses wavelet entropy to measure the chaotic levels of both electroencephalogram (EEG) and electrocardiogram (ECG) data and show how this may be used to explore the potential coordination between the mind and heart under different experimental conditions. Furthermore, Statistical Parametric Mapping (SPM) was used to identify the brain regions in which the EEG wavelet entropy was the most affected by the experimental conditions. As an illustration, the EEG and ECG were recorded under two different conditions (normal rest and mindful breathing) at the beginning of an 8-week standard Mindfulness-based Stress Reduction (MBSR) training course (pretest) and after the course (posttest). Using the proposed method, the results consistently showed that the wavelet entropy of the brain EEG decreased during the MBSR mindful breathing state as compared to that during the closed-eye resting state. Similarly, a lower wavelet entropy of heartrate was found during MBSR mindful breathing. However, no difference in wavelet entropy during MBSR mindful breathing was found between the pretest and posttest. No correlation was observed between the entropy of brain waves and the entropy of heartrate during normal rest in all participants, whereas a significant correlation was observed during MBSR mindful breathing. Additionally, the most well-correlated brain regions were located in the central areas of the brain. This study provides a methodology for the establishment of evidence that mindfulness practice (i.e., mindful breathing) may increase the coordination between mind and heart activities.

  11. Nandrolone reduces activation of Notch signaling in denervated muscle associated with increased Numb expression

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Xin-Hua [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Yao, Shen; Qiao, Rui-Fang; Levine, Alice C. [Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Kirschenbaum, Alexander [Department of Urology, Mount Sinai School of Medicine, New York, NY 10029 (United States); Pan, Jiangping; Wu, Yong [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Qin, Weiping [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Bauman, William A. [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Rehabilitation Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Cardozo, Christopher P., E-mail: chris.cardozo@mssm.edu [Center of Excellence for the Medical Consequences of Spinal Cord Injury, James J. Peter VA Medical Center, Bronx, NY 10468 (United States); Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States); Rehabilitation Medicine, Mount Sinai School of Medicine, New York, NY 10029 (United States)

    2011-10-14

    Highlights: {yields} Nerve transection increased Notch signaling in paralyzed muscle. {yields} Nandrolone prevented denervation-induced Notch signaling. {yields} Nandrolone induced the expression of an inhibitor of the Notch signaling, Numb. {yields} Reduction of denervation-induced Notch signaling by nandrolone is likely through upregulation of Numb. -- Abstract: Nandrolone, an anabolic steroid, slows denervation-atrophy in rat muscle. The molecular mechanisms responsible for this effect are not well understood. Androgens and anabolic steroids activate Notch signaling in animal models of aging and thereby mitigate sarcopenia. To explore the molecular mechanisms by which nandrolone prevents denervation-atrophy, we investigated the effects of nandrolone on Notch signaling in denervated rat gastrocnemius muscle. Denervation significantly increased Notch activity reflected by elevated levels of nuclear Notch intracellular domain (NICD) and expression of Hey1 (a Notch target gene). Activation was greatest at 7 and 35 days after denervation but remained present at 56 days after denervation. Activation of Notch in denervated muscle was prevented by nandrolone associated with upregulated expression of Numb mRNA and protein. These data demonstrate that denervation activates Notch signaling, and that nandrolone abrogates this response associated with increased expression of Numb, suggesting a potential mechanism by which nandrolone reduces denervation-atrophy.

  12. Hydrogen sulfide reduces serum triglyceride by activating liver autophagy via the AMPK-mTOR pathway.

    Science.gov (United States)

    Sun, Li; Zhang, Song; Yu, Chengyuan; Pan, Zhenwei; Liu, Yang; Zhao, Jing; Wang, Xiaoyu; Yun, Fengxiang; Zhao, Hongwei; Yan, Sen; Yuan, Yue; Wang, Dingyu; Ding, Xue; Liu, Guangzhong; Li, Wenpeng; Zhao, Xuezhu; Liu, Zhaorui; Li, Yue

    2015-12-01

    Autophagy plays an important role in liver triglyceride (TG) metabolism. Inhibition of autophagy could reduce the clearance of TG in the liver. Hydrogen sulfide (H2S) is a potent stimulator of autophagic flux. Recent studies showed H2S is protective against hypertriglyceridemia (HTG) and noalcoholic fatty liver disease (NAFLD), while the mechanism remains to be explored. Here, we tested the hypothesis that H2S reduces serum TG level and ameliorates NAFLD by stimulating liver autophagic flux by the AMPK-mTOR pathway. The level of serum H2S in patients with HTG was lower than that of control subjects. Sodium hydrosulfide (NaHS, H2S donor) markedly reduced serum TG levels of male C57BL/6 mice fed a high-fat diet (HFD), which was abolished by coadministration of chloroquine (CQ), an inhibitor of autophagic flux. In HFD mice, administration of NaSH increased the LC3BII-to-LC3BI ratio and decreased the p62 protein level. Meanwhile, NaSH increased the phosphorylation of AMPK and thus reduced the phosphorylation of mTOR in a Western blot study. In cultured LO2 cells, high-fat treatment reduced the ratio of LC3BII to LC3BI and the phosphorylation of AMPK, which were reversed by the coadministration of NaSH. Knockdown of AMPK by siRNA in LO2 cells blocked the autophagic enhancing effects of NaSH. The same qualitative effect was observed in AMPKα2(-/-) mice. These results for the first time demonstrated that H2S could reduce serum TG level and ameliorate NAFLD by activating liver autophagy via the AMPK-mTOR pathway.

  13. Direct evidence of swimming demonstrates active dispersal in the sea turtle "lost years".

    Science.gov (United States)

    Putman, Nathan F; Mansfield, Katherine L

    2015-05-04

    Although oceanic dispersal in larval and juvenile marine animals is widely studied, the relative contributions of swimming behavior and ocean currents to movements and distribution are poorly understood [1-4]. The sea turtle "lost years" [5] (often referred to as the surface-pelagic [6] or oceanic [7] stage) are a classic example. Upon hatching, young turtles migrate offshore and are rarely observed until they return to coastal waters as larger juveniles [5]. Sightings of small turtles downcurrent of nesting beaches and in association with drifting organisms (e.g., Sargassum algae) led to this stage being described as a "passive migration" during which turtles' movements are dictated by ocean currents [5-10]. However, laboratory and modeling studies suggest that dispersal trajectories might also be shaped by oriented swimming [11-15]. Here, we use an experimental approach designed to directly test the passive-migration hypothesis by deploying pairs of surface drifters alongside small green (Chelonia mydas) and Kemp's ridley (Lepidochelys kempii) wild-caught turtles, tracking their movements via satellite telemetry. We conclusively demonstrate that these turtles do not behave as passive drifters. In nearly all cases, drifter trajectories were uncharacteristic of turtle trajectories. Species-specific and location-dependent oriented swimming behavior, inferred by subtracting track velocity from modeled ocean velocity, contributed substantially to individual movement and distribution. These findings highlight the importance of in situ observations for depicting the dispersal of weakly swimming animals. Such observations, paired with information on the mechanisms of orientation, will likely allow for more accurate predictions of the ecological and evolutionary processes shaped by animal movement.

  14. Point-of-care platelet function assays demonstrate reduced responsiveness to clopidogrel, but not aspirin, in patients with Drug-Eluting Stent Thrombosis whilst on dual antiplatelet therapy

    Directory of Open Access Journals (Sweden)

    Dawkins Keith D

    2008-02-01

    Full Text Available Abstract Background To test the hypothesis that point-of-care assays of platelet reactivity would demonstrate reduced response to antiplatelet therapy in patients who experienced Drug Eluting Stent (DES ST whilst on dual antiplatelet therapy compared to matched DES controls. Whilst the aetiology of stent thrombosis (ST is multifactorial there is increasing evidence from laboratory-based assays that hyporesponsiveness to antiplatelet therapy is a factor in some cases. Methods From 3004 PCI patients, seven survivors of DES ST whilst on dual antiplatelet therapy were identified and each matched with two patients without ST. Analysis was performed using (a short Thrombelastogram PlateletMapping™ (TEG and (b VerifyNow Aspirin and P2Y12 assays. TEG analysis was performed using the Area Under the Curve at 15 minutes (AUC15 as previously described. Results There were no differences in responses to aspirin. There was significantly greater platelet reactivity on clopidogrel in the ST group using the Accumetrics P2Y12 assay (183 ± 51 vs. 108 ± 31, p = 0.02 and a trend towards greater reactivity using TEG AUC15 (910 ± 328 vs. 618 ± 129, p = 0.07. 57% of the ST group by TEG and 43% of the ST cases by Accumetrics PRU had results > two standard deviations above the expected mean in the control group. Conclusion This study demonstrates reduced platelet response to clopidogrel in some patients with DES ST compared to matched controls. The availability of point-of-care assays that can detect these responses raises the possibility of prospectively identifying DES patients at risk of ST and manipulating their subsequent risk.

  15. BMI1 attenuates etoposide-induced G2/M checkpoints via reducing ATM activation.

    Science.gov (United States)

    Wei, F; Ojo, D; Lin, X; Wong, N; He, L; Yan, J; Xu, S; Major, P; Tang, D

    2015-06-04

    The BMI1 protein contributes to stem cell pluripotency and oncogenesis via multiple functions, including its newly identified role in DNA damage response (DDR). Although evidence clearly demonstrates that BMI1 facilitates the repair of double-stranded breaks via homologous recombination (HR), it remains unclear how BMI1 regulates checkpoint activation during DDR. We report here that BMI1 has a role in G2/M checkpoint activation in response to etoposide (ETOP) treatment. Ectopic expression of BMI1 in MCF7 breast cancer and DU145 prostate cancer cells significantly reduced ETOP-induced G2/M arrest. Conversely, knockdown of BMI1 in both lines enhanced the arrest. Consistent with ETOP-induced activation of the G2/M checkpoints via the ATM pathway, overexpression and knockdown of BMI1, respectively, reduced and enhanced ETOP-induced phosphorylation of ATM at serine 1981 (ATM pS1981). Furthermore, the phosphorylation of ATM targets, including γH2AX, threonine 68 (T68) on CHK2 (CHK2 pT68) and serine 15 (S15) on p53 were decreased in overexpression and increased in knockdown BMI1 cells in response to ETOP. In line with the requirement of NBS1 in ATM activation, we were able to show that BMI1 associates with NBS1 and that this interaction altered the binding of NBS1 with ATM. BMI1 consists of a ring finger (RF), helix-turn-helix-turn-helix-turn (HT), proline/serine (PS) domain and two nuclear localization signals (NLS). Although deletion of either RF or HT did not affect the association of BMI1 with NBS1, the individual deletions of PS and one NLS (KRMK) robustly reduced the interaction. Stable expression of these BMI1 mutants decreased ETOP-induced ATM pS1981 and CHK2 pT68, but not ETOP-elicited γH2AX in MCF7 cells. Furthermore, ectopic expression of BMI1 in non-transformed breast epithelial MCF10A cells also compromised ETOP-initiated ATM pS1981 and γH2AX. Taken together, we provide compelling evidence that BMI1 decreases ETOP-induced G2/M checkpoint activation via

  16. Method of demonstrating calcium in human foot by neutron activation of (. cap alpha. , N)-sources

    Energy Technology Data Exchange (ETDEWEB)

    Zaychik, V.E.; Kondrashov, A.E.; Morukov, B.V.

    Bone demineralization during long-term exposure to weightlessness and hypokinesia is presently a universally recognized fact. A method is described which employs neutron activation analysis for a direct quantitative in vivo assay of calcium in the human foot. When the foot is exposed to neutrons, the stable nuclide Ca/sup 46/ is converted into the radionuclide Ca/sup 49/. The gamma radiation emitted by Ca/sup 49/ is then measured spectrometrically. A special device, developed for the delivery of neutrons to the foot, consists of a stainless steel tank filled with water, surrounded on the side by lithium-containing screens. A cassette with neutron sources is at the bottom of the tank and can be delivered to the desired position in channel-driver carriers. A special footrest provides support during irradiation. The spectrometry unit, consisting of 4 scintillation counters, also is equipped with a specially designed footrest. The maximum relative error of a single measurement did not exceed 4.82%. The mean equivalent dose in the foot was about 1 rem, a dose low enough to permit examinations three times a year, if necessary.

  17. Tocotrienol-Rich Fraction from Rice Bran Demonstrates Potent Radiation Protection Activity

    Directory of Open Access Journals (Sweden)

    Kimberly J. Krager

    2015-01-01

    Full Text Available The vitamin E analogs δ-tocotrienol (DT3 and γ-tocotrienol (GT3 have significant protective and mitigative capacity against the detrimental effects of ionizing radiation (IR. However, the expense of purification limits their potential use. This study examined the tocotrienol-rich fraction of rice bran (TRFRB isolated from rice bran deodorizer distillate, a rice oil refinement waste product, to determine its protective effects against IR induced oxidative damage and H2O2. Several cell lines were treated with tocotrienols or TRFRB prior to or following exposure to H2O2 or IR. To determine the radioprotective capacity cells were analyzed for morphology, mitochondrial bioenergetics, clonogenic survival, glutathione oxidation, cell cycle, and migration rate. TRFRB displayed similar antioxidant activity compared to pure tocotrienols. Cells pretreated with TRFRB or DT3 exhibited preserved cell morphology and mitochondrial respiration when exposed to H2O2. Oxidized glutathione was decreased in TRFRB treated cells exposed to IR. TRFRB reversed mitochondrial uncoupling and protected cells migration rates following IR exposure. The protective antioxidant capacity of TRFRB treated cells against oxidative injury was similar to that of purified DT3. TRFRB effectively protects normal cells against IR induced injury suggesting that rice bran distillate may be an inexpensive and abundant alternate source.

  18. An Active Learning Mammalian Skeletal Muscle Lab Demonstrating Contractile and Kinetic Properties of Fast- and Slow-Twitch Muscle

    Science.gov (United States)

    Head, S. I.; Arber, M. B.

    2013-01-01

    The fact that humans possess fast and slow-twitch muscle in the ratio of approximately 50% has profound implications for designing exercise training strategies for power and endurance activities. With the growth of exercise and sport science courses, we have seen the need to develop an undergraduate student laboratory that demonstrates the basic…

  19. An Active Learning Mammalian Skeletal Muscle Lab Demonstrating Contractile and Kinetic Properties of Fast- and Slow-Twitch Muscle

    Science.gov (United States)

    Head, S. I.; Arber, M. B.

    2013-01-01

    The fact that humans possess fast and slow-twitch muscle in the ratio of approximately 50% has profound implications for designing exercise training strategies for power and endurance activities. With the growth of exercise and sport science courses, we have seen the need to develop an undergraduate student laboratory that demonstrates the basic…

  20. Metastases suppressor NME2 associates with telomere ends and telomerase and reduces telomerase activity within cells.

    Science.gov (United States)

    Kar, Anirban; Saha, Dhurjhoti; Purohit, Gunjan; Singh, Ankita; Kumar, Parveen; Yadav, Vinod Kumar; Kumar, Pankaj; Thakur, Ram Krishna; Chowdhury, Shantanu

    2012-03-01

    Analysis of chromatin-immunoprecipitation followed by sequencing (ChIP-seq) usually disregards sequence reads that do not map within binding positions (peaks). Using an unbiased approach, we analysed all reads, both that mapped and ones that were not included as part of peaks. ChIP-seq experiments were performed in human lung adenocarcinoma and fibrosarcoma cells for the metastasis suppressor non-metastatic 2 (NME2). Surprisingly, we identified sequence reads that uniquely represented human telomere ends in both cases. In vivo presence of NME2 at telomere ends was validated using independent methods and as further evidence we found intranuclear association of NME2 and the telomere repeat binding factor 2. Most remarkably, results demonstrate that NME2 associates with telomerase and reduces telomerase activity in vitro and in vivo, and sustained NME2 expression resulted in reduced telomere length in aggressive human cancer cells. Anti-metastatic function of NME2 has been demonstrated in human cancers, however, mechanisms are poorly understood. Together, findings reported here suggest a novel role for NME2 as a telomere binding protein that can alter telomerase function and telomere length. This presents an opportunity to investigate telomere-related interactions in metastasis suppression.

  1. Microbiological analysis of common preservatives used in food items and demonstration of their in vitro anti-bacterial activity

    Directory of Open Access Journals (Sweden)

    Tohora Sultana

    2014-12-01

    Full Text Available Objective: To quantify the microorganisms contaminating the common preservatives used in food as well as to detect their in vitro anti-bacterial traits. Methods: A total of 9 preservatives were subjected to conventional cultural and biochemical methods for microbial enumeration. Anti-bacterial activities were demonstrated through the agar well diffusion method. Results: All samples were found to be contaminated with bacteria up to 105 CFU/g and with the fungal flora within a range of 1 01-1 02 CFU/g. Escherichia coli, Pseudomonas spp. and Staphylococcus spp. were demonstrated in most of the samples. Sodium sulfite and citric acid possessed the strongest anti-bacterial trait against all of the test bacteria. Acetic acid exhibited activity against 6 out of 8 test bacteria while vinegar exhibited the activity against 4 bacteria. Activity of salt was demonstrated only against Listeria spp. and Bacillus spp., while activity of sugar and honey was found only against Escherichia coli and Klebsiella spp., respectively. Conclusions: According to the current investigation, sodium sulfite and citric acid samples were found to be satisfactory preservatives both in terms of microbiological criteria and their antibacterial traits.

  2. Epithermal neutron activation analysis of Cr(VI)-reducer basalt-inhabiting bacteria.

    Science.gov (United States)

    Tsibakhashvili, Nelly Yasonovna; Frontasyeva, Marina Vladimirovna; Kirkesali, Elena Ivanovna; Aksenova, Nadezhda Gennadievna; Kalabegishvili, Tamaz Levanovich; Murusidze, Ivana Georgievich; Mosulishvili, Ligury Mikhailovich; Holman, Hoi-Ying N

    2006-09-15

    Epithermal neutron activation analysis (ENAA) has been applied to study elemental composition of Cr(VI)-reducer bacteria isolated from polluted basalts from the Republic of Georgia. Cr(VI)-reducing ability of the bacteria was examined by electron spin resonance, demonstrating that the bacteria differ in their rates of Cr(VI) reduction. A well-pronounced correlation between the ability of the bacteria to accumulate Cr(V) and their ability to reduce Cr(V) to Cr(III) observed in our experiments is discussed. Elemental analysis of these bacteria also revealed that basalt-inhabiting bacteria are distinguished by relative contents of essential elements such as K, Na, Mg, Fe, Mn, Zn, and Co. A high rate of Cr(III) formation correlates with a high concentration of Co in the bacterium. ENAA detected some similarity in the elemental composition of the bacteria. The relatively high contents of Fe detected in the bacteria (140-340 microg/g of dry weight) indicate bacterial adaptation to the environmental conditions typical of the basalts. The concentrations of at least 12-19 different elements were determined in each type of bacteria simultaneously starting with the major to ultratrace elements. The range of concentrations spans over 8 orders of magnitude.

  3. Epithermal Neutron Activation Analysis (ENAA) of Cr(VI)-reducer Basalt-inhabiting Bacteria

    CERN Document Server

    Tsibakhashvili, N Ya; Kirkesali, E I; Aksenova, N G; Kalabegishvili, T L; Murusidze, I G; Mosulishvili, L M; Holman, H Y N

    2005-01-01

    Epithermal neutron activation analysis (ENAA) has been applied to studying elemental composition of Cr(VI)-reducer bacteria isolated from polluted basalts from the Republic of Georgia. Cr(VI)-reducing ability of the bacteria was examined by electron spin resonance (ESR) demonstrating that the bacteria differ in the rates of Cr(VI) reduction. A well-pronounced correlation between the ability of the bacteria to accumulate Cr(V) and their ability to reduce Cr(V) to Cr(III) observed in our experiments is discussed. Elemental analysis of these bacteria also revealed that basalt-inhabiting bacteria are distinguished by relative contents of essential elements such as K, Na, Mg, Fe, Mn, Zn, and Co. A high rate of Cr(III) formation correlates with a high concentration of Co in the bacterium. ENAA detected some similarity in the elemental composition of the bacteria. The relatively high contents of Fe detected in the bacteria (140-340 $\\mu $g/g of dry weight) indicate bacterial adaptation to the environmental condition...

  4. Development of Reduced Activation Ferritic-Martensitic Steels and fabrication technologies for Indian test blanket module

    Energy Technology Data Exchange (ETDEWEB)

    Raj, Baldev [Indira Gandhi Centre for Atomic Research, Kalpakkam 603 102 (India); Jayakumar, T., E-mail: tjk@igcar.gov.in [Indira Gandhi Centre for Atomic Research, Kalpakkam 603 102 (India)

    2011-10-01

    For the development of Reduced Activation Ferritic-Martensitic Steel (RAFMS), for the Indian Test Blanket Module for ITER, a 3-phase programme has been adopted. The first phase consists of melting and detailed characterization of a laboratory scale heat conforming to Eurofer 97 composition, to demonstrate the capability of the Indian industry for producing fusion grade steel. In the second phase which is currently in progress, the chemical composition will be optimized with respect to tungsten and tantalum for better combination of mechanical properties. Characterization of the optimized commercial scale India-specific RAFM steel will be carried out in the third phase. The first phase of the programme has been successfully completed and the tensile, impact and creep properties are comparable with Eurofer 97. Laser and electron beam welding parameters have been optimized and welding consumables were developed for Narrow Gap - Gas Tungsten Arc welding and for laser-hybrid welding.

  5. Connexin26 (GJB2) deficiency reduces active cochlear amplification leading to late-onset hearing loss.

    Science.gov (United States)

    Zhu, Y; Chen, J; Liang, C; Zong, L; Chen, J; Jones, R O; Zhao, H-B

    2015-01-22

    Connexin26 (Cx26, GJB2) mutations account for >50% of nonsyndromic hearing loss. The deafness is not always congenital. A large group of these patients (∼30%) demonstrate a late-onset hearing loss, starting in childhood. They have normal hearing early in life and are therefore good candidates for applying protective and therapeutic interventions. However, the underlying deafness mechanism is unclear. In this study, we used a time-controlled, inducible gene knockout technique to knockout Cx26 expression in the cochlea after birth. We found that deletion of Cx26 after postnatal day 5 (P5) in mice could lead to late-onset hearing loss. Similar to clinical observations, the mice demonstrated progressive, mild to moderate hearing loss. The hearing loss initiated at high frequencies and then extended to the middle- and low-frequency range. The cochlea showed normal development and had no apparent hair cell loss. However, distortion product otoacoustic emission (DPOAE) was reduced. The reduction was also progressive and large at high-frequencies. Consistent with DPOAE reduction, we found that outer hair cell electromotility-associated nonlinear capacitance was shifted to the right and the slope of voltage dependence was reduced. The endocochlear potential was reduced in Cx26 conditional knockout (cKO) mice but the reduction was not associated with progressive hearing loss. These data suggest that Cx26 deficiency may impair active cochlear amplification leading to late-onset hearing loss. Our study also helps develop newer protective and therapeutic interventions to this common nonsyndromic hearing loss.

  6. Reduced osteoblast activity in the mice lacking TR4 nuclear receptor leads to osteoporosis

    Directory of Open Access Journals (Sweden)

    Lin Shin-Jen

    2012-06-01

    Full Text Available Abstract Background Early studies suggested that TR4 nuclear receptor might play important roles in the skeletal development, yet its detailed mechanism remains unclear. Methods We generated TR4 knockout mice and compared skeletal development with their wild type littermates. Primary bone marrow cells were cultured and we assayed bone differentiation by alkaline phosphatase and alizarin red staining. Primary calvaria were cultured and osteoblastic marker genes were detected by quantitative PCR. Luciferase reporter assays, chromatin immunoprecipitation (ChIP assays, and electrophoretic mobility shift assays (EMSA were performed to demonstrate TR4 can directly regulate bone differentiation marker osteocalcin. Results We first found mice lacking TR4 might develop osteoporosis. We then found that osteoblast progenitor cells isolated from bone marrow of TR4 knockout mice displayed reduced osteoblast differentiation capacity and calcification. Osteoblast primary cultures from TR4 knockout mice calvaria also showed higher proliferation rates indicating lower osteoblast differentiation ability in mice after loss of TR4. Mechanism dissection found the expression of osteoblast markers genes, such as ALP, type I collagen alpha 1, osteocalcin, PTH, and PTHR was dramatically reduced in osteoblasts from TR4 knockout mice as compared to those from TR4 wild type mice. In vitro cell line studies with luciferase reporter assay, ChIP assay, and EMSA further demonstrated TR4 could bind directly to the promoter region of osteocalcin gene and induce its gene expression at the transcriptional level in a dose dependent manner. Conclusions Together, these results demonstrate TR4 may function as a novel transcriptional factor to play pathophysiological roles in maintaining normal osteoblast activity during the bone development and remodeling, and disruption of TR4 function may result in multiple skeletal abnormalities.

  7. Experimental demonstration of low-complexity fiber chromatic dispersion mitigation for reduced guard-interval OFDM coherent optical communication systems based on digital spectrum sub-band multiplexing.

    Science.gov (United States)

    Malekiha, Mahdi; Tselniker, Igor; Nazarathy, Moshe; Tolmachev, Alex; Plant, David V

    2015-10-05

    We experimentally demonstrate a novel digital signal processing (DSP) structure for reduced guard-interval (RGI) OFDM coherent optical systems. The proposed concept is based on digitally slicing optical channel bandwidth into multiple spectrally disjoint sub-bands which are then processed in parallel. Each low bandwidth sub-band has a smaller delay-spread compared to a full-band signal. This enables compensation of both chromatic dispersion (CD) and polarization mode dispersion using a simple timing and one-tap-per-symbol frequency domain equalizer with a small cyclic prefix overhead. In terms of the DSP architecture, this allows for a highly efficient parallelization of DSP tasks performed over the received signal samples by deploying multiple processors running at a lower clock rate. It should be noted that this parallelization is performed in the frequency domain and it allows for flexible optical transceiver schemes. In addition, the resulting optical receiver is simplified due to the removal of the CD compensation equalizer compared to conventional RGI-OFDM systems. In this paper we experimentally demonstrate digital sub-banding of optical bandwidth. We test the system performance for different modulation formats (QPSK, 16QAM and 32QAM) over various transmission distances and optical launch powers using a 1.5% CP overhead in all scenarios. We also compare the proposed RGI-OFDM architecture performance against common single carrier modulation formats. At the same total data rate and signal bandwidth both systems have similar performance and transmission reach whereas the proposed method allows for a significant reduction of computational complexity due to removal of CD pre/post compensation equalizer.

  8. Activation of PPAR-γ reduces HPA axis activity in diabetic rats by up-regulating PI3K expression.

    Science.gov (United States)

    Torres, Rafael Carvalho; Magalhães, Nathalia Santos; E Silva, Patrícia M R; Martins, Marco A; Carvalho, Vinicius F

    2016-10-01

    Increased hypothalamus-pituitary-adrenal axis (HPA) activity in diabetes is strongly associated with several morbidities noted in patients with the disease. We previously demonstrated that hyperactivity of HPA axis under diabetic conditions is associated with up-regulation of adrenocorticotrophic hormone (ACTH) receptors (MC2R) in adrenal and down-regulation of glucocorticoid receptors (GR and MR) in pituitary. This study investigates the role of peroxisome proliferator-activated receptor (PPAR)-γ in HPA axis hyperactivity in diabetic rats. Diabetes was induced by intravenous injection of alloxan into fasted rats. The PPAR-γ agonist rosiglitazone and/or PI3K inhibitor wortmannin were administered daily for 18 consecutive days, starting 3days after diabetes induction. Plasma ACTH and corticosterone were evaluated by radioimmunoassay, while intensities of MC2R, proopiomelanocortin (POMC), GR, MR, PI3K p110α and PPAR-γ were assessed using immunohistochemistry. Rosiglitazone treatment inhibited adrenal hypertrophy and hypercorticoidism observed in diabetic rats. Rosiglitazone also significantly reversed the diabetes-induced increase in the MC2R expression in adrenal cortex. We noted that rosiglitazone reduced the number of corticotroph cells and inhibited both anterior pituitary POMC expression and plasma ACTH levels. Furthermore, rosiglitazone treatment was unable to restore the reduced expression of GR and MR in the anterior pituitary of diabetic rats. Rosiglitazone increased the number of PPAR-γ(+) cells and expression of PI3K p110α in both anterior pituitary and adrenal cortex of diabetic rats. In addition, wortmannin blocked the ability of rosiglitazone to restore corticotroph cell numbers, adrenal hypertrophy and plasma corticosterone levels in diabetic rats. In conclusion, our findings revealed that rosiglitazone down-regulates HPA axis hyperactivity in diabetic rats via a mechanism dependent on PI3K activation in pituitary and adrenal glands.

  9. Highly Ordered Graphene Oxide and Reduced Graphene Oxide Based Polymer Nanocomposites: Promise and Limits for Dynamic Impacts Demonstrated in Model Organic Coatings.

    Science.gov (United States)

    Schmelter, Dirk; Hintze-Bruening, Horst

    2016-06-29

    Graphene oxide (GO) dispersed in water has been combined with a mixture of aqueous polymer dispersions and melamine formaldehyde resin (MF). Stable low viscous fluids with no obvious signs of mesoscale ordering at 0.3 wt % yield transparent films with GO loadings up to one weight percent in the form of homogeneously aligned double strands, each comprising few individual layers of the carbon allotrope. While baking of the films at 160 °C results in minor thermal reduction of GO, in situ reduction with excess hydroxylamine (HA) in the presence of the polymer colloids yields stable dispersions in which amphiphilic graphene like flakes temporarily encapsulate gaseous reaction products. Depending on the parameters in the time-temperature domain, the hollow spheres may be transferred into solid material or disassemble during film formation, the latter case providing black, smooth, and transparent films with up to eight magnitudes increased electrical conductivity and an oxygen permeability 30-fold higher compared to the neat polymer matrix. In contrast, GO reduces oxygen permeability by that factor, while water permeability stays unchanged. Thermo-mechanical measurements reveal matrix stiffening by the platelets as well as by HA, the latter via modifying the MF reactivity. Excellent stone chip resistance and ballistic impact tests demonstrate efficient energy dissipation and crack deflection provided by the laminate like morphology of GO based composite. On the contrary, the same material only provides moderate substrate protection in rain erosion tests.

  10. Reducing conditions are the key for efficient production of active ribonuclease inhibitor in Escherichia coli

    Directory of Open Access Journals (Sweden)

    Neubauer Peter

    2011-05-01

    Full Text Available Abstract Background The eukaryotic RNase ribonuclease/angiogenin inhibitors (RI are a protein group distinguished by a unique structure - they are composed of hydrophobic leucine-rich repeat motifs (LRR and contain a high amount of reduced cysteine residues. The members of this group are difficult to produce in E. coli and other recombinant hosts due to their high aggregation tendency. Results In this work dithiothreitol (DTT was successfully applied for improving the yield of correctly folded ribonuclease/angiogenin inhibitor in E. coli K12 periplasmic and cytoplasmic compartments. The feasibility of the in vivo folding concepts for cytoplasmic and periplasmic production were demonstrated at batch and fed-batch cultivation modes in shake flasks and at the bioreactor scale. Firstly, the best secretion conditions of RI in the periplasmic space were evaluated by using a high throughput multifactorial screening approach of a vector library, directly with the Enbase fed-batch production mode in 96-well plates. Secondly, the effect of the redox environment was evaluated in isogenic dsbA+ and dsbA- strains at the various cultivation conditions with reducing agents in the cultivation medium. Despite the fusion to the signal peptide, highest activities were found in the cytoplasmic fraction. Thus by removing the signal peptide the positive effect of the reducing agent DTT was clearly proven also for the cytoplasmic compartment. Finally, optimal periplasmic and cytoplasmic RI fed-batch production processes involving externally added DTT were developed in shake flasks and scaled up to the bioreactor scale. Conclusions DTT highly improved both, periplasmic and cytoplasmic accumulation and activity of RI at low synthesis rate, i.e. in constructs harbouring weak recombinant synthesis rate stipulating genetic elements together with cultivation at low temperature. In a stirred bioreactor environment RI folding was strongly improved by repeated pulse addition

  11. Active Lubrication for Reducing Wear and Vibration: A combination of Fluid Power Control and Tribology

    DEFF Research Database (Denmark)

    Nicoletti, Rodrigo; Santos, Ilmar

    2002-01-01

    The use of fluid power to reduce and control rotor vibration in rotating machines is investigated. An active hybrid bearing is studied, whose main objective is to reduce wear and vibration between rotating and stationary machinery parts. By injecting pressurised oil into the oil film, through...... with experiment, and simulations show the feasibility of controlling shaft vibration through this active device....

  12. The effects of natural antioxidants on oxidative processes and metmyoglobin reducing activity in beef patties

    NARCIS (Netherlands)

    Bekhit, A.E.D.; Geesink, G.H.; Ilian, M.A.; Morton, J.D.; Bickerstaffe, R.

    2003-01-01

    The effects of antioxidants on oxidative processes and metmyoglobin-reducing activity in beef patties were investigated in two experiments. In the first experiment colour, colour stability, TBA values and MetMb-reducing activity were measured during storage, at 2 oC, of raw beef patties treated with

  13. The effects of natural antioxidants on oxidative processes and metmyoglobin reducing activity in beef patties

    NARCIS (Netherlands)

    Bekhit, A.E.D.; Geesink, G.H.; Ilian, M.A.; Morton, J.D.; Bickerstaffe, R.

    2003-01-01

    The effects of antioxidants on oxidative processes and metmyoglobin-reducing activity in beef patties were investigated in two experiments. In the first experiment colour, colour stability, TBA values and MetMb-reducing activity were measured during storage, at 2 oC, of raw beef patties treated with

  14. Ampicillin in Combination with Ceftaroline, Cefepime, or Ceftriaxone Demonstrates Equivalent Activities in a High-Inoculum Enterococcus faecalis Infection Model.

    Science.gov (United States)

    Luther, Megan K; Rice, Louis B; LaPlante, Kerry L

    2016-05-01

    Ampicillin-ceftriaxone combination therapy has become a predominant treatment for serious Enterococcus faecalis infections, such as endocarditis. Unfortunately, ceftriaxone use is associated with future vancomycin-resistant enterococcus colonization. We evaluated E. faecalis in an in vitro pharmacodynamic model against simulated human concentration-time profiles of ampicillin plus ceftaroline, cefepime, ceftriaxone, or gentamicin. Ampicillin-cefepime and ampicillin-ceftaroline demonstrated activities similar to those of ampicillin-ceftriaxone against E. faecalis.

  15. Methods for demonstration of enzyme activity in muscle fibres at the muscle/bone interface in demineralized tissue

    DEFF Research Database (Denmark)

    Kirkeby, S; Vilmann, H

    1981-01-01

    A method for demonstration of activity for ATPase and various oxidative enzymes (succinic dehydrogenase, alpha-glycerophosphate dehydrogenase, and lactic dehydrogenase) in muscle/bone sections of fixed and demineralized tissue has been developed. It was found that it is possible to preserve...... with the aid of a mapping of presence of phosphomonoesterases on bone surfaces, the method may be used to study possible biochemical interactions between bone and muscle tissue at the muscle/bone interface....

  16. [Biochemical demonstration of HCO3--und Cl--dependent ATPase activities in the rectum of larval dragonflies and inhibition of rectal chloride uptake by thiocyanate (author's transl)].

    Science.gov (United States)

    Komnick, H; Schmitz, M; Hinssen, H

    1980-02-01

    Hydrogencarbonate and chloride activated, ouabain-insensitive ATPase activities are demonstrated in the salt-absorbing rectum of larval dragonflies. Maximal activation is achieved at approx. 30 mM HCO3- and 20 mM Cl-, respectively. The stimulation of each anion obeys Michaelis-Menten kinetics Km values are 4.65 mM for HCO3-- and 10.25 mM for Cl--activation. The activating anion of one type of ATPase simultaneously exerts an inhibitory effect on the other. Cl--activation is also reduced by Mg.ATP in concentrations above 0.5 mM and by Tris-Hepes buffer exceeding 2.5 mM. Both anion-dependent ATPase activities are found enriched in subcellular membraneous fractions of the rectum. Thiocyanate inhibits both activities and causes a significant decrease in rectal uptake of radioactive chloride from hypo-osmotic external solution. In the case of HCO3- dependent ATPase a competitive inhibition as SCN- was found with an inhibitor constant of Ki=0.5 mM.

  17. Status and key issues of reduced activation ferritic/martensitic steels as the structural material for a DEMO blanket

    Science.gov (United States)

    Tanigawa, H.; Shiba, K.; Möslang, A.; Stoller, R. E.; Lindau, R.; Sokolov, M. A.; Odette, G. R.; Kurtz, R. J.; Jitsukawa, S.

    2011-10-01

    The status and key issues of reduced activation ferritic/martensitic (RAFM) steels R&D are reviewed as the primary candidate structural material for fusion energy demonstration reactor blankets. This includes manufacturing technology, the as-fabricated and irradiates material database and joining technologies. The review indicated that the manufacturing technology, joining technology and database accumulation including irradiation data are ready for initial design activity, and also identifies various issues that remain to be solved for engineering design activity and qualification of the material for international fusion material irradiation facility (IFMIF) irradiation experiments that will validate the data base.

  18. Status and key issues of reduced activation ferritic/martensitic steels as the structural material for a DEMO blanket

    Energy Technology Data Exchange (ETDEWEB)

    Tanigawa, Hiroyasu [ORNL; Stoller, Roger E [ORNL; Sokolov, Mikhail A [ORNL; Odette, G.R. [University of California, Santa Barbara; Jitsukawa, Shiro [Japan Atomic Energy Agency (JAEA); Shiba, K. [Japan Atomic Energy Agency (JAEA); Kurtz, Richard [Pacific Northwest National Laboratory (PNNL); Moeslang, A. [Forschungszentrum Karlsruhe, Karlsruhe, Germany; Lindau, R. [Forschungszentrum Karlsruhe, Karlsruhe, Germany

    2011-01-01

    The status and key issues of reduced activation ferritic/martensitic (RAFM) steels R&D are reviewed as the primary candidate structural material for fusion energy demonstration reactor blankets. This includes manufacturing technology, the as-fabricated and irradiates material database and joining technologies. The review indicated that the manufacturing technology, joining technology and database accumulation including irradiation data are ready for initial design activity, and also identifies various issues that remain to be solved for engineering design activity and qualification of the material for international fusion material irradiation facility (IFMIF) irradiation experiments that will validate the data base.

  19. Sleep- and wake-dependent changes in neuronal activity and reactivity demonstrated in fly neurons using in vivo calcium imaging.

    Science.gov (United States)

    Bushey, Daniel; Tononi, Giulio; Cirelli, Chiara

    2015-04-14

    Sleep in Drosophila shares many features with mammalian sleep, but it remains unknown whether spontaneous and evoked activity of individual neurons change with the sleep/wake cycle in flies as they do in mammals. Here we used calcium imaging to assess how the Kenyon cells in the fly mushroom bodies change their activity and reactivity to stimuli during sleep, wake, and after short or long sleep deprivation. As before, sleep was defined as a period of immobility of >5 min associated with a reduced behavioral response to a stimulus. We found that calcium levels in Kenyon cells decline when flies fall asleep and increase when they wake up. Moreover, calcium transients in response to two different stimuli are larger in awake flies than in sleeping flies. The activity of Kenyon cells is also affected by sleep/wake history: in awake flies, more cells are spontaneously active and responding to stimuli if the last several hours (5-8 h) before imaging were spent awake rather than asleep. By contrast, long wake (≥29 h) reduces both baseline and evoked neural activity and decreases the ability of neurons to respond consistently to the same repeated stimulus. The latter finding may underlie some of the negative effects of sleep deprivation on cognitive performance and is consistent with the occurrence of local sleep during wake as described in behaving rats. Thus, calcium imaging uncovers new similarities between fly and mammalian sleep: fly neurons are more active and reactive in wake than in sleep, and their activity tracks sleep/wake history.

  20. Activation of self-knowledge reduces conflict during occupational choice: an ERP study.

    Science.gov (United States)

    Nakao, Takashi; Takezawa, Tomohiro; Shiraishi, Maiko; Miyatani, Makoto

    2009-01-01

    We investigated whether the activation of self-knowledge reduces conflict during occupational choice, which can elicit many correct answers. Conflict was measured via event-related brain potentials (ERPs). Results of this study showed that activation of self-knowledge reduces conflict during occupational choice. Our results suggest that, in a situation in which two or more possible correct answers exist, people use self-knowledge as a benchmark to reduce conflict by biasing either choice of behavior.

  1. Parasympathetic activation is involved in reducing epileptiform discharges when listening to Mozart music.

    Science.gov (United States)

    Lin, Lung-Chang; Chiang, Ching-Tai; Lee, Mei-Wen; Mok, Hin-Kiu; Yang, Yi-Hsin; Wu, Hui-Chuan; Tsai, Chin-Lin; Yang, Rei-Cheng

    2013-08-01

    Listening to Mozart K.448 has been demonstrated to improve spatial task scores, leading to what is known as the Mozart effect. Our previous work revealed the positive effects of Mozart K.448 in reducing epileptiform discharges in children with epilepsy. However, the mechanism remains unclear. parasympathetic activation has been shown to help seizure control in many studies. In this study, we investigated the effect of Mozart music on epileptiform discharges and autonomic activity. Sixty-four epileptic children with epileptiform discharges were included. They all received electroencephalogram and electrocardiogram examinations simultaneously before, during, and after listening to Mozart K.448 or K.545. The total number of epileptiform discharges during each session (before, during, and after music) were divided by the duration (in minutes) of the session and then compared. Heart rate variability including time and frequency domain analysis was used to represent the autonomic function. The results showed that epileptiform discharges were significantly reduced during and right after listening to Mozart music (33.3 ± 31.1% reduction, pMozart K.448 and 38.6 ± 43.3% reduction, pMozart K.545) (28.1 ± 43.2% reduction, pMozart K.448 and 46.0 ± 40.5% reduction, pMozart K.545). No significant difference was noticed between the two pieces of music. The reduction was greatest in patients with generalized seizures and discharges. Significant increases in high-frequency (HF), the square root of the mean squared differences of successive RR intervals (RMSSD), the standard deviation of differences between adjacent RR intervals (SDSD), and a decrease in mean beats per minute (bpm) were found during listening to Mozart music. Most of the patients with reduced epileptiform discharges also showed a decreased LF/HF ratio, low-frequency normalized units (LF nu), mean bpm, and an increased high-frequency normalized units (HF nu). Listening to Mozart music decreased epileptiform

  2. An investigation of an active landing gear system to reduce aircraft vibrations caused by landing impacts and runway excitations

    Science.gov (United States)

    Wang, Haitao; Xing, J. T.; Price, W. G.; Li, Weiji

    2008-10-01

    A mathematical model is developed to control aircraft vibrations caused by runway excitation using an active landing gear system. Equations are derived to describe the integrated aircraft-active system. The nonlinear characteristics of the system are modelled and it is actively controlled using a Proportional Integral Derivative (PID) strategy. The performance of this system and its corresponding passive system are compared using numerical simulations. It is demonstrated that the impact loads and the vertical displacement of the aircraft's centre of gravity caused by landing and runway excitations are greatly reduced using the active system, which result in improvements to the performance of the landing gear system, benefits the aircraft's fatigue life, taxiing performance, crew/passenger comfort and reduces requirements on the unevenness of runways.

  3. CX3CL1 reduces neurotoxicity and microglial activation in a rat model of Parkinson's disease

    Directory of Open Access Journals (Sweden)

    Hudson Charles E

    2011-01-01

    Full Text Available Abstract Background Parkinson's disease is characterized by a progressive loss of dopaminergic neurons in the substantia nigra. The cause of the neurodegeneration is unknown. Neuroinflammation has been clearly shown in Parkinson's disease and may be involved in the progressive nature of the disease. Microglia are capable of producing neuronal damage through the production of bioactive molecules such as cytokines, as well as reactive oxygen species (ROS, and nitric oxide (NO. The inflammatory response in the brain is tightly regulated at multiple levels. One form of immune regulation occurs via neurons. Fractalkine (CX3CL1, produced by neurons, suppresses the activation of microglia. CX3CL1 is constitutively expressed. It is not known if addition of exogenous CX3CL1 beyond otherwise physiologically normal levels could decrease microglia activation and thereby minimize the secondary neurodegeration following a neurotoxic insult. Methods The intrastriatal 6-hydroxydopamine (6-OHDA rat model of Parkinson disease, was used to test the hypothesis that exogenous CX3CL1 could be neuroprotective. Treatment with recombinant CX3CL1 was delivered to the striatum by an osmotic minipump for 28 days beginning 7 days after the initial insult. Unbiased stereological methods were used to quantify the lesion size in the striatum, the amount of neuronal loss in the substantia nigra, and the amount of microglia activation. Results As hypothesized, CX3CL1 was able to suppress this microglia activation. The reduced microglia activation was found to be neuroprotective as the CX3CL1 treated rats had a smaller lesion volume in the striatum and importantly significantly fewer neurons were lost in the CX3CL1 treated rats. Conclusion These findings demonstrated that CX3CL1 plays a neuroprotective role in 6-OHDA-induced dopaminergic lesion and it might be an effective therapeutic target for many neurodegenerative diseases, including Parkinson disease and Alzheimer disease

  4. Nitrite reductase activity of sulphate-reducing bacteria prevents their inhibition by nitrate-reducing, sulphide-oxidizing bacteria.

    Science.gov (United States)

    Greene, E A; Hubert, C; Nemati, M; Jenneman, G E; Voordouw, G

    2003-07-01

    Sulphate-reducing bacteria (SRB) can be inhibited by nitrate-reducing, sulphide-oxidizing bacteria (NR-SOB), despite the fact that these two groups are interdependent in many anaerobic environments. Practical applications of this inhibition include the reduction of sulphide concentrations in oil fields by nitrate injection. The NR-SOB Thiomicrospira sp. strain CVO was found to oxidize up to 15 mM sulphide, considerably more than three other NR-SOB strains that were tested. Sulphide oxidation increased the environmental redox potential (Eh) from -400 to +100 mV and gave 0.6 nitrite per nitrate reduced. Within the genus Desulfovibrio, strains Lac3 and Lac6 were inhibited by strain CVO and nitrate for the duration of the experiment, whereas inhibition of strains Lac15 and D. vulgaris Hildenborough was transient. The latter had very high nitrite reductase (Nrf) activity. Southern blotting with D. vulgaris nrf genes as a probe indicated the absence of homologous nrf genes from strains Lac3 and Lac6 and their presence in strain Lac15. With respect to SRB from other genera, inhibition of the known nitrite reducer Desulfobulbus propionicus by strain CVO and nitrate was transient, whereas inhibition of Desulfobacterium autotrophicum and Desulfobacter postgatei was long-lasting. The results indicate that inhibition of SRB by NR-SOB is caused by nitrite production. Nrf-containing SRB can overcome this inhibition by further reducing nitrite to ammonia, preventing a stalling of the favourable metabolic interactions between these two bacterial groups. Nrf, which is widely distributed in SRB, can thus be regarded as a resistance factor that prevents the inhibition of dissimilatory sulphate reduction by nitrite.

  5. Matrine reduces the proliferation and invasion of colorectal cancer cells via reducing the activity of p38 signaling pathway.

    Science.gov (United States)

    Ren, Hongtao; Zhang, Shuqun; Ma, Hongbing; Wang, Yali; Liu, Di; Wang, Xijing; Wang, Zhongwei

    2014-12-01

    Matrine has been used in anti-inflammatory and anti-cancer therapies for a long time. However, the anti-metastatic effect and related mechanism(s) in colorectal cancer (CRC) are still unclear. In this study, we investigated whether the administration of matrine could inhibit the proliferation, motility, and invasion of human CRC cells via regulating p38 signaling pathway. Results showed that matrine inhibited migration and invasion of CRC cells in vitro and in vivo. Additionally, after being treated with matrine for 24 h, the expression levels of matrix metalloproteinase-2 (MMP-2) and MMP-9 as well as proteinase activity in CRC cells were reduced in a dose-dependent manner. Moreover, matrine reduced the phosphorylation level of p38 obviously. Combined treatment with p38 inhibitor (SB203580) and matrine resulted in a synergistic reduction of invasion as well as MMP-2/-9 expression in CRC cells. It was also found that matrine inhibited the proliferation and metastasis of CRC tumor in vivo. In conclusion, p38 signaling pathway may involve in matrine's inhibitory effects on migration and invasion of CRC cells by reducing the expression of MMP-2/-9, suggesting that matrine may be a potential therapeutic agent for CRC.

  6. Allopurinol reduces antigen-specific and polyclonal activation of human T cells

    Directory of Open Access Journals (Sweden)

    Damián ePérez-Mazliah

    2012-09-01

    Full Text Available Allopurinol is the most popular commercially available xanthine oxidase inhibitor and it is widely used for treatment of symptomatic hyperuricaemia, or gout. Although, several anti-inflammatory actions of allopurinol have been demonstrated in vivo and in vitro, there have been few studies on the action of allopurinol on T cells. In the current study, we have assessed the effect of allopurinol on antigen-specific and mitogen-driven activation and cytokine production in human T cells. Allopurinol markedly decreased the frequency of IFN-γ and IL-2-producing T cells, either after polyclonal or antigen-specific stimulation with Herpes Simplex virus 1, Influenza virus, tetanus toxoid and Trypanosoma cruzi-derived antigens. Allopurinol attenuated CD69 upregulation after CD3 and CD28 engagement and significantly reduced the levels of spontaneous and mitogen-induced intracellular reactive oxygen species in T cells. The diminished T cell activation and cytokine production in the presence of allopurinol support a direct action of allopurinol on human T cells, offering a potential pharmacological tool for the management of cell-mediated inflammatory diseases.

  7. Can an incentive-based intervention increase physical activity and reduce sitting among adults? the ACHIEVE (Active Choices IncEntiVE) feasibility study.

    Science.gov (United States)

    Ball, Kylie; Hunter, Ruth F; Maple, Jaimie-Lee; Moodie, Marj; Salmon, Jo; Ong, Kok-Leong; Stephens, Lena D; Jackson, Michelle; Crawford, David

    2017-03-21

    Despite recent interest in the potential of incentivisation as a strategy for motivating healthier behaviors, little remains known about the effectiveness of incentives in promoting physical activity and reducing sedentary behavior, and improving associated health outcomes. This pre-post-test design study investigated the feasibility, appeal and effects of providing non-financial incentives for promoting increased physical activity, reduced sedentary time, and reduced body mass index (BMI) and blood pressure among inactive middle-aged adults. Inactive men (n = 36) and women (n = 46) aged 40-65 years were recruited via a not-for-profit insurance fund and participated in a 4 month pre-post design intervention. Baseline and post-intervention data were collected on self-reported physical activity and sitting time (IPAQ-Long), BMI and blood pressure. Participants were encouraged to increase physical activity to 150 mins/week and reduce sedentary behavior by 150 mins/week in progressive increments. Incentives included clothing, recipe books, store gift vouchers, and a chance to win one of four Apple iPad Mini devices. The incentive component of the intervention was supported by an initial motivational interview and text messaging to encourage participants and provide strategies to increase physical activity and reduce sedentary behaviors. Only two participants withdrew during the program, demonstrating the feasibility of recruiting and retaining inactive middle-aged participants. While two-thirds of the sample qualified for the easiest physical activity incentive (by demonstrating 100 mins physical activity/week or 100 mins reduced sitting time/week), only one third qualified for the most challenging incentive. Goals to reduce sitting appeared more challenging, with 43% of participants qualifying for the first incentive, but only 20% for the last incentive. More men than women qualified for most incentives. Mean leisure-time physical activity increased by 252

  8. Wound healing and antibacterial activities of chondroitin sulfate- and acharan sulfate-reduced silver nanoparticles

    Science.gov (United States)

    Im, A.-Rang; Kim, Jee Young; Kim, Hyun-Seok; Cho, Seonho; Park, Youmie; Kim, Yeong Shik

    2013-10-01

    For topical applications in wound healing, silver nanoparticles (AgNPs) have attracted much attention as antibacterial agents. Herein, we describe a green-synthetic route for the production of biocompatible and crystalline AgNPs using two glycosaminoglycans, chondroitin sulfate (CS) and acharan sulfate (AS), as reducing agents. The synthetic approach avoids the use of toxic chemicals, and the yield of AgNPs formation is found to be 98.1% and 91.1% for the chondroitin sulfate-reduced silver nanoparticles (CS-AgNPs) and the acharan sulfate-reduced silver nanoparticles (AS-AgNPs), respectively. Nanoparticles with mostly spherical and amorphous shapes were observed, with an average diameter of 6.16 ± 2.26 nm for CS-AgNPs and 5.79 ± 3.10 nm for AS-AgNPs. Images of the CS-AgNPs obtained from atomic force microscopy revealed the self-assembled structure of CS was similar to a densely packed woven mat with AgNPs sprinkled on the CS. These nanoparticles were stable under cell culture conditions without any noticeable aggregation. An approximately 128-fold enhancement of the antibacterial activities of the AgNPs was observed against Enterobacter cloacae and Escherichia coli when compared to CS and AS alone. In addition, an in vivo animal model of wound healing activity was tested using mice that were subjected to deep incision wounds. In comparison to the controls, the ointments containing CS-AgNPs and AS-AgNPs stimulated wound closure under histological examination and accelerated the deposition of granulation tissue and collagen in the wound area. The wound healing activity of the ointments containing CS-AgNPs and AS-AgNPs are comparable to that of a commercial formulation of silver sulfadiazine even though the newly prepared ointments contain a lower silver concentration. Therefore, the newly prepared AgNPs demonstrate potential for use as an attractive biocompatible nanocomposite for topical applications in the treatment of wounds.

  9. Methods for demonstration of enzyme activity in muscle fibres at the muscle/bone interface in demineralized tissue

    DEFF Research Database (Denmark)

    Kirkeby, S; Vilmann, H

    1981-01-01

    A method for demonstration of activity for ATPase and various oxidative enzymes (succinic dehydrogenase, alpha-glycerophosphate dehydrogenase, and lactic dehydrogenase) in muscle/bone sections of fixed and demineralized tissue has been developed. It was found that it is possible to preserve...... considerable amounts of the above mentioned enzymes in the muscle fibres at the muscle/bone interfaces. The best results were obtained after 20 min fixation, and 2-3 weeks of storage in MgNa2EDTA containing media. As the same technique previously has been used to describe patterns of resorption and deposition...

  10. A model for the training effects in swimming demonstrates a strong relationship between parasympathetic activity, performance and index of fatigue.

    Directory of Open Access Journals (Sweden)

    Sébastien Chalencon

    Full Text Available Competitive swimming as a physical activity results in changes to the activity level of the autonomic nervous system (ANS. However, the precise relationship between ANS activity, fatigue and sports performance remains contentious. To address this problem and build a model to support a consistent relationship, data were gathered from national and regional swimmers during two 30 consecutive-week training periods. Nocturnal ANS activity was measured weekly and quantified through wavelet transform analysis of the recorded heart rate variability. Performance was then measured through a subsequent morning 400 meters freestyle time-trial. A model was proposed where indices of fatigue were computed using Banister's two antagonistic component model of fatigue and adaptation applied to both the ANS activity and the performance. This demonstrated that a logarithmic relationship existed between performance and ANS activity for each subject. There was a high degree of model fit between the measured and calculated performance (R(2=0.84±0.14,p<0.01 and the measured and calculated High Frequency (HF power of the ANS activity (R(2=0.79±0.07, p<0.01. During the taper periods, improvements in measured performance and measured HF were strongly related. In the model, variations in performance were related to significant reductions in the level of 'Negative Influences' rather than increases in 'Positive Influences'. Furthermore, the delay needed to return to the initial performance level was highly correlated to the delay required to return to the initial HF power level (p<0.01. The delay required to reach peak performance was highly correlated to the delay required to reach the maximal level of HF power (p=0.02. Building the ANS/performance identity of a subject, including the time to peak HF, may help predict the maximal performance that could be obtained at a given time.

  11. Demonstration of elevated levels of active cathepsin S in dextran sulfate sodium colitis using a new activatable probe.

    Science.gov (United States)

    Barlow, N; Nasser, Y; Zhao, P; Sharma, N; Guerrero-Alba, R; Edgington-Mitchell, L E; Lieu, T; Veldhuis, N A; Poole, D P; Conner, J W; Lindström, E; Craig, A W; Graham, B; Vanner, S J; Bunnett, N W

    2015-11-01

    Proteases play a major role in inflammatory diseases of the gastrointestinal tract. Activatable probes are a major technological advance, enabling sensitive detection of active proteases in tissue samples. Our aim was to synthesize an activatable probe for cathepsin S and validate its use in a mouse model of colitis. We designed and synthesized a new fluorescent activatable probe, NB200, for the detection of active cathepsin S. Colitis was induced in C57BL/6 mice by the administration of 3% dextran sulfate sodium (DSS). Homogenized mouse colons, with or without the addition of the specific cathepsin S inhibitor MV026031, were incubated with NB200 in a fluorescent plate reader. NB200 selectively detected purified cathepsin S and not other common inflammatory proteases. Homogenates of colon from mice with DSS colitis induced a significant fluorescent increase when compared to control animals (control vs DSS: p < 0.05 at 200 min and p < 0.01 at 220-240 min), indicating cathepsin S activation. The cathepsin S inhibitor abolished this increase in fluorescence (DSS vs DSS + MV026031: p < 0.05 at 140 min, p < 0.01 at 180 min, p < 0.001 at 200-240 min), which confirms cathepsin S activation. Cathepsin S activity correlated with the disease activity index (Spearman r = 0.77, p = 0.017). Our investigation has demonstrated the utility of activatable probes for detecting protease activity in intestinal inflammation. Panels of such probes may allow 'signature' protease profiles to be established for a range of inflammatory diseases and disorders. © 2015 John Wiley & Sons Ltd.

  12. Impurity content of reduced-activation ferritic steels and a vanadium alloy

    Energy Technology Data Exchange (ETDEWEB)

    Klueh, R.L.; Grossbeck, M.L.; Bloom, E.E. [Oak Ridge National Lab., TN (United States)

    1997-04-01

    Inductively coupled plasma mass spectrometry was used to analyze a reduced-activation ferritic/martensitic steel and a vanadium alloy for low-level impurities that would compromise the reduced-activation characteristics of these materials. The ferritic steel was from the 5-ton IEA heat of modified F82H, and the vanadium alloy was from a 500-kg heat of V-4Cr-4Ti. To compare techniques for analysis of low concentrations of impurities, the vanadium alloy was also examined by glow discharge mass spectrometry. Two other reduced-activation steels and two commercial ferritic steels were also analyzed to determine the difference in the level of the detrimental impurities in the IEA heat and steels for which no extra effort was made to restrict some of the tramp impurities. Silver, cobalt, molybdenum, and niobium proved to be the tramp impurities of most importance. The levels observed in these two materials produced with present technology exceeded the limits for low activation for either shallow land burial or recycling. The chemical analyses provide a benchmark for the improvement in production technology required to achieve reduced activation; they also provide a set of concentrations for calculating decay characteristics for reduced-activation materials. The results indicate the progress that has been made and give an indication of what must still be done before the reduced-activation criteria can be achieved.

  13. Novel method demonstrates differential ligand activation and phosphatase-mediated deactivation of insulin receptor tyrosine-specific phosphorylation.

    Science.gov (United States)

    Cieniewicz, Anne M; Cooper, Philip R; McGehee, Jennifer; Lingham, Russell B; Kihm, Anthony J

    2016-08-01

    Insulin receptor signaling is a complex cascade leading to a multitude of intracellular functional responses. Three natural ligands, insulin, IGF1 and IGF2, are each capable of binding with different affinities to the insulin receptor, and result in variable biological responses. However, it is likely these affinity differences alone cannot completely explain the myriad of diverse cellular outcomes. Ligand binding initiates activation of a signaling cascade resulting in phosphorylation of the IR itself and other intracellular proteins. The direct catalytic activity along with the temporally coordinated assembly of signaling proteins is critical for insulin receptor signaling. We hypothesized that determining differential phosphorylation among individual tyrosine sites activated by ligand binding or dephosphorylation by phosphatases could provide valuable insight into insulin receptor signaling. Here, we present a sensitive, novel immunoassay adapted from Meso Scale Discovery technology to quantitatively measure changes in site-specific phosphorylation levels on endogenous insulin receptors from HuH7 cells. We identified insulin receptor phosphorylation patterns generated upon differential ligand activation and phosphatase-mediated deactivation. The data demonstrate that insulin, IGF1 and IGF2 elicit different insulin receptor phosphorylation kinetics and potencies that translate to downstream signaling. Furthermore, we show that insulin receptor deactivation, regulated by tyrosine phosphatases, occurs distinctively across specific tyrosine residues. In summary, we present a novel, quantitative and high-throughput assay that has uncovered differential ligand activation and site-specific deactivation of the insulin receptor. These results may help elucidate some of the insulin signaling mechanisms, discriminate ligand activity and contribute to a better understanding of insulin receptor signaling. We propose this methodology as a powerful approach to characterize

  14. Trying To Reduce Your Technostress?: Helpful Activities for Teachers and Library Media Specialists.

    Science.gov (United States)

    McKenzie, Barbara K.; And Others

    1997-01-01

    As pressure increases to integrate technology into instruction, many teachers and library media specialists are having difficulty coping with "technostress." Presents suggestions and activities for teachers and library media specialists designed to reduce "technostress." (PEN)

  15. Fetoscopic laser coagulation of intertwin anastomoses reduces discordant placental autophagic activities in discordant twin growth

    Directory of Open Access Journals (Sweden)

    Yao-Lung Chang

    2015-10-01

    Conclusion: The discordance of placenta autophagic activity in the monochorionic twin with sIUGR was reduced after laser coagulation of the intertwin anastomoses, which may result from the effect of correction of the discordant intertwin placenta perfusion.

  16. Pleomorphism and acetylene-reducing activity of free-living rhizobia.

    OpenAIRE

    Kaneshiro, T; Baker, F.L.; Johnson, D.E.

    1983-01-01

    Cowpea-type Rhizobium sp. strain 32H1 and Rhizobium japonicum USDA 26 and 110 grown on a glutamate-mannitol-gluconate agar medium showed increases in the number of pleomorphic cells coincident with their acetylene-reducing activity. Pleomorphs appeared to be inhibited in growth nonuniformly, because acetylene-reducing cultures were mixtures of rod, branched (V, Y, and T), and other irregularly shaped cells. In contrast, strain USDA 10 consistently failed to reduce acetylene, even though it al...

  17. Active Lubrication for Reducing Wear and Vibration: A combination of Fluid Power Control and Tribology

    DEFF Research Database (Denmark)

    Nicoletti, Rodrigo; Santos, Ilmar

    2002-01-01

    The use of fluid power to reduce and control rotor vibration in rotating machines is investigated. An active hybrid bearing is studied, whose main objective is to reduce wear and vibration between rotating and stationary machinery parts. By injecting pressurised oil into the oil film, through ori...

  18. Crocetin Reduces Activation of Hepatic Apoptotic Pathways and Improves Survival in Experimental Hemorrhagic Shock

    Science.gov (United States)

    Yang, Rongjie; Vernon, Kathy; Thomas, Ann; Morrison, David; Qureshi, Nilofer; Van Way, Charles W

    2014-01-01

    Background Hemorrhagic shock results in cellular damage and cell death. A primary mechanism is cellular apoptosis from mitochondrial damage. This study demonstrated that administration of crocetin to experimental animals during resuscitation from shock significantly improved postshock survival and reduced apoptosis. Crocetin is a component of saffron and has long been used in traditional medicine in Asia. Methods Male Sprague-Dawley rats (350 ± 30g) were randomly assigned to 1 of 4 groups of 8 animals. Hemorrhagic shock was induced by withdrawing blood until the mean arterial pressure was 35–40 mm Hg, and blood pressure was maintained at that level for 60 minutes with further withdrawals as needed. Resuscitation was carried out by administration of 21 mL/kg lactated Ringer’s solution and return of shed blood, with or without concurrent administration of crocetin (2 mg/kg). Control animals were sham-treated with surgical preparation, without shock or resuscitation, and with and without crocetin. Rats were sacrificed 24 hours after completion of resuscitation. The extent of activation of hepatic apoptosis was established by measuring levels of hepatic cytosolic cytochrome c, caspase-3, and bcl-2. A separate group of 53 animals treated identically was used to assess survival. Results Crocetin administration during resuscitation resulted in less extensive activation of hepatic apoptosis and significantly increased survival relative to controls. Conclusions Crocetin administration to experimental animals during resuscitation post hemorrhage increased survival, at least in part by protecting the liver from activation of apoptotic cell death. This agent continues to show promise as a potential treatment strategy for hemorrhagic shock. PMID:21224437

  19. Periowave demonstrates bactericidal activity against periopathogens and leads to improved clinical outcomes in the treatment of adult periodontitis

    Science.gov (United States)

    Street, Cale N.; Andersen, Roger; Loebel, Nicolas G.

    2009-02-01

    Periodontitis affects half of the U.S. population over 50, and is the leading cause of tooth loss after 35. It is believed to be caused by growth of complex bacterial biofilms on the tooth surface below the gumline. Photodynamic therapy, a technology used commonly in antitumor applications, has more recently been shown to exhibit antimicrobial efficacy. We have demonstrated eradication of the periopathogens Porphyromonas gingivalis, Fusobacterium nucleatum, and Aggregatibacter actinomycetemcomitans in vitro using PeriowaveTM; a commercial photodisinfection system. In addition, several clinical studies have now demonstrated the efficacy of this treatment. A pilot study in the U.S. showed that 68% of patients treated with PeriowaveTM adjunctively to scaling and root planing (SRP) showed clinical attachment level increase of >1 mm, as opposed to 30% with SRP alone. In a subsequent larger study, a second PeriowaveTM treatment 6 weeks after initial treatment led to pocket depth improvements of >1.5 mm in 89% of patients. Finally, in the most recent multicenter, randomized, examiner-blinded study conducted on 121 subjects in Canada, PeriowaveTM treatment produced highly significant gains in attachment level (0.88 mm vs. 0.57 mm; p=0.003) and pocket depth (0.87 mm vs. 0.63 mm; p=0.01) as compared to SRP alone. In summary, PeriowaveTM demonstrated strong bactericidal activity against known periopathogens, and treatment of periodontitis using this system produced significantly better clinical outcomes than SRP alone. This, along with the absence of any adverse events in patients treated to date demonstrates that PDT is a safe and effective treatment for adult chronic periodontitis.

  20. Leptospira interrogans activation of peripheral blood monocyte glycolipoprotein demonstrated in whole blood by the release of IL-6

    Directory of Open Access Journals (Sweden)

    F. Dorigatti

    2005-06-01

    Full Text Available Glycolipoprotein (GLP from pathogenic serovars of Leptospira has been implicated in the pathogenesis of leptospirosis by its presence in tissues of experimental animals with leptospirosis, the inhibition of the Na,K-ATPase pump activity, and induced production of cytokines. The aims of the present study were to investigate the induction of IL-6 by GLP in peripheral blood mononuclear cells (PBMC and to demonstrate monocyte stimulation at the cellular level in whole blood from healthy volunteers. PBMC were stimulated with increasing concentrations (5 to 2500 ng/ml of GLP extracted from the pathogenic L. interrogans serovar Copenhageni, lipopolysaccharide (positive control or medium (negative control, and supernatants were collected after 6, 20/24, and 48 h, and kept at -80ºC until use. Whole blood was diluted 1:1 in RPMI medium and cultivated for 6 h, with medium, GLP and lipopolysaccharide as described above. Monensin was added after the first hour of culture. Supernatant cytokine levels from PBMC were measured by ELISA and intracellular IL-6 was detected in monocytes in whole blood cultures by flow-cytometry. Monocytes were identified in whole blood on the basis of forward versus side scatter parameters and positive reactions with CD45 and CD14 antibodies. GLP ( > or = 50 ng/ml-induced IL-6 levels in supernatants were detected after 6-h incubation, reaching a peak after 20/24 h. The percentage of monocytes staining for IL-6 increased with increasing GLP concentration. Thus, our findings show a GLP-induced cellular activation by demonstrating the ability of GLP to induce IL-6 and the occurrence of monocyte activation in whole blood at the cellular level.

  1. Olanzapine reduces physical activity in rats exposed to activity-based anorexia : possible implications for treatment of anorexia nervosa?

    NARCIS (Netherlands)

    Hillebrand, Jacquelien J G; van Elburg, Annemarie A; Kas, Martien J H; van Engeland, Herman; Adan, Roger A H

    2005-01-01

    BACKGROUND: Anorexia nervosa (AN) patients often show extreme hypophagia and excessive physical activity. Activity-based anorexia (ABA) is considered an animal model of AN and mimics food restriction and hyperactivity in rats. This study investigated whether treatment with olanzapine (Zyprexa) reduc

  2. Olanzapine reduces physical activity in rats exposed to activity-based anorexia : possible implications for treatment of anorexia nervosa?

    NARCIS (Netherlands)

    Hillebrand, Jacquelien J G; van Elburg, Annemarie A; Kas, Martien J H; van Engeland, Herman; Adan, Roger A H

    2005-01-01

    BACKGROUND: Anorexia nervosa (AN) patients often show extreme hypophagia and excessive physical activity. Activity-based anorexia (ABA) is considered an animal model of AN and mimics food restriction and hyperactivity in rats. This study investigated whether treatment with olanzapine (Zyprexa) reduc

  3. Reduced glutathione as a physiological co-activator in the activation of peptidylarginine deiminase

    DEFF Research Database (Denmark)

    Damgaard, Dres; Bjørn, Mads Emil; Steffensen, Maria A

    2016-01-01

    BACKGROUND: Citrullination catalysed by peptidylarginine deiminases (PADs) plays an important pathogenic role in anti-citrullinated protein antibody (ACPA)-positive rheumatoid arthritis (RA) and, possibly, several other inflammatory diseases. Non-physiological reducing agents such as dithiothreit...

  4. Eff ects of natural antioxidants on colour stability, lipid oxidation and metmyoglobin reducing activity in raw beef patties

    Directory of Open Access Journals (Sweden)

    Fang Liu

    2015-03-01

    Full Text Available Background. Minced meats undergo oxidative changes and develop rancidity more quickly than intact muscle since grinding exposes more of the muscle surface to air and microbial contamination. Due to concerns about toxicological safety of synthetic antioxidants, recent studies have put more focus on natural antioxidant compounds derived from food components. Material and methods. The effects of four natural antioxidants (vitamin E, carnosine, grape seed extract and tea catechins on oxidative processes and metmyoglobin reducing activity in raw beef patties during refrigerated (4°C storage were investigated and the results were compared with butylated hydroxyanisole treatment patties. The correlation of lipid oxidation, colour and metmyoglobin reducing activity of beef patties were also studied. Results. Samples treated with carnosine had the highest redness values on the eighth day. Tea catechins, vitamin E and grape seed extract showed higher protective effect against lipid oxidation than carnosine. Metmyoglobin reducing activity increased greatly in all samples during the storage. Signifi cant correlation between redness value and lipid oxidation was demonstrated, while a weak correlation between metmyoglobin reducing activity and any other parameters was shown.

  5. PPAR-γ agonist stabilizes KLF4 protein via activating Akt signaling and reducing KLF4 ubiquitination

    Energy Technology Data Exchange (ETDEWEB)

    Sun, Yan; Zheng, Bin; Zhang, Xin-hua; He, Ming; Guo, Zong-wei; Wen, Jin-kun, E-mail: wjk@hebmu.edu.cn

    2014-01-10

    Highlights: •PPAR-γ increases KLF4 protein level but does not influence KLF4 gene transcription. •The increase of KLF4 protein levels induced by pioglitazone is PPAR-γ-dependent. •Pioglitazone stabilizes KLF4 protein via activating Akt signaling and reducing KLF4 ubiquitination. -- Abstract: Peroxisome proliferator activated receptor γ (PPAR-γ) plays important roles in cell cycle regulation, differentiation and apoptosis. Krüppel-like factor 4 (KLF4) modulates vascular smooth muscle cell (VSMC) phenotype. Both KLF4 and PPAR-γ are involved in VSMC proliferation and differentiation. However, the actual relationship between KLF4 and PPAR-γ in VSMCs is not clear. In this study, we found that PPAR-γ agonist pioglitazone increases KLF4 protein levels but does not influence KLF4 gene transcription. PPAR-γ overexpression increases, while PPAR-γ knockdown reduces KLF4 expression, suggesting that the increase in KLF4 protein levels induced by pioglitazone is PPAR-γ-dependent. Further study showed that pioglitazone enhances KLF4 protein stability through reducing KLF4 ubiquitination. Furthermore, we demonstrated that stabilization of KLF4 by pioglitazone was related to the activation of Akt signaling pathway. Taken together, we revealed that PPAR-γ agonist pioglitazone stabilizes KLF4 protein via activating Akt signaling and reducing KLF4 ubiquitination, providing further insights into PPAR-γ and KLF4 in regulating each other’s expression in VSMCs.

  6. Bovine CCL28 Mediates Chemotaxis via CCR10 and Demonstrates Direct Antimicrobial Activity against Mastitis Causing Bacteria.

    Science.gov (United States)

    Pallister, Kyler B; Mason, Sara; Nygaard, Tyler K; Liu, Bin; Griffith, Shannon; Jones, Jennifer; Linderman, Susanne; Hughes, Melissa; Erickson, David; Voyich, Jovanka M; Davis, Mary F; Wilson, Eric

    2015-01-01

    In addition to the well characterized function of chemokines in mediating the homing and accumulation of leukocytes to tissues, some chemokines also exhibit potent antimicrobial activity. Little is known of the potential role of chemokines in bovine mammary gland health and disease. The chemokine CCL28 has previously been shown to play a key role in the homing and accumulation of IgA antibody secreting cells to the lactating murine mammary gland. CCL28 has also been shown to act as an antimicrobial peptide with activity demonstrated against a wide range of pathogens including bacteria, fungi and protozoans. Here we describe the cloning and function of bovine CCL28 and document the concentration of this chemokine in bovine milk. Bovine CCL28 was shown to mediate cellular chemotaxis via the CCR10 chemokine receptor and exhibited antimicrobial activity against a variety of bovine mastitis causing organisms. The concentration of bovine CCL28 in milk was found to be highly correlated with the lactation cycle. Highest concentrations of CCL28 were observed soon after parturition, with levels decreasing over time. These results suggest a potential role for CCL28 in the prevention/resolution of bovine mastitis.

  7. Bovine CCL28 Mediates Chemotaxis via CCR10 and Demonstrates Direct Antimicrobial Activity against Mastitis Causing Bacteria.

    Directory of Open Access Journals (Sweden)

    Kyler B Pallister

    Full Text Available In addition to the well characterized function of chemokines in mediating the homing and accumulation of leukocytes to tissues, some chemokines also exhibit potent antimicrobial activity. Little is known of the potential role of chemokines in bovine mammary gland health and disease. The chemokine CCL28 has previously been shown to play a key role in the homing and accumulation of IgA antibody secreting cells to the lactating murine mammary gland. CCL28 has also been shown to act as an antimicrobial peptide with activity demonstrated against a wide range of pathogens including bacteria, fungi and protozoans. Here we describe the cloning and function of bovine CCL28 and document the concentration of this chemokine in bovine milk. Bovine CCL28 was shown to mediate cellular chemotaxis via the CCR10 chemokine receptor and exhibited antimicrobial activity against a variety of bovine mastitis causing organisms. The concentration of bovine CCL28 in milk was found to be highly correlated with the lactation cycle. Highest concentrations of CCL28 were observed soon after parturition, with levels decreasing over time. These results suggest a potential role for CCL28 in the prevention/resolution of bovine mastitis.

  8. Sulfate reducing bacteria and their activities in oil sands process-affected water biofilm

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Hong; Yu, Tong, E-mail: tong.yu@ualberta.ca; Liu, Yang, E-mail: yang.liu@ualberta.ca

    2015-12-01

    Biofilm reactors were constructed to grow stratified multispecies biofilm in oil sands process-affected water (OSPW) supplemented with growth medium. The development of sulfate reducing bacteria (SRB) within the biofilm and the biofilm treatment of OSPW were evaluated. The community structure and potential activity of SRB in the biofilm were investigated with H{sub 2}S microsensor measurements, dsrB gene-based denaturing gradient gel electrophoresis (DGGE), and the real time quantitative polymerase chain reaction (qPCR). Multispecies biofilm with a thickness of 1000 μm was successfully developed on engineered biocarriers. H{sub 2}S production was observed in the deeper anoxic zone of the biofilm from around 750 μm to 1000 μm below the bulk water-biofilm interface, revealing sulfate reduction in the deeper zone of the stratified biofilm. The biofilm removed chemical oxygen demand (COD), sulfate, and nitrogen. The study expands current knowledge of biofilm treatment of OSPW and the function of anaerobic SRB in OSPW biofilm, and thus provides information for future bioreactor development in the reclamation of OSPW. - Graphical abstract: The development of sulfate reducing bacteria (SRB) within Oil Sands Process-affected Water (OSPW) biofilm and the biofilm treatment of OSPW were evaluated by Liu and coworkers. Combined microsensor and molecular biology techniques were utilized in this study. Their results demonstrated that multispecies biofilm with a thickness of 1000 μm was successfully developed on engineered biocarriers. H{sub 2}S production was observed in the deeper anoxic zone of the biofilm from around 750 μm to 1000 μm below the bulk water-biofilm interface, revealing sulfate reduction in the deeper zone of the biofilm. The biofilm removed chemical oxygen demand (COD), sulfate, and nitrogen. - Highlights: • Biofilm in oil sands wastewater was developed on engineered biocarriers. • Bacterial community and in situ activity of SRB were studied in the

  9. Enhanced antifungal activity by disinfected titanium dioxide nanotubes via reduced nano-adhesion bonds.

    Science.gov (United States)

    Beltrán-Partida, Ernesto; Valdez-Salas, Benjamín; Curiel-Álvarez, Mario; Castillo-Uribe, Sandra; Escamilla, Alan; Nedev, Nicola

    2017-07-01

    We have provided evidence that the beneficial effect of super-oxidized water (SOW) disinfected Ti6Al4V-TiO2 nanotubes (NTs) can reduce bacterial adhesion and biofilm formation. However, the need of antifungal nanostructured surfaces with osteoactive capabilities is an important goal that has been arising for dental implants (DI) applications. Thus, in the present study we isolated and tested the effects of Candida albicans (C. albicans) on disinfected, wetter and nanoroughness NTs compared to a non-modified control. Moreover, we elucidated part of the fungal adhesion mechanism by studying and relating the mycotic adhesion kinetics and the formation of fungal nanoadhesion bonds among the experimental materials, to gain new insight of the fungal-material-interface. Similarly, the initial behavior of human alveolar bone osteoblasts (HAOb) was microscopically evaluated. NTs significantly reduced the yeasts adhesion and viability with non-outcomes of biofilm than the non-modified surface. Cross-sectioning of the fungal cells revealed promoted nano-contact bonds with superior fungal spread on the control alloy interface; meanwhile NTs evidenced decreased tendency along time; suggesting, down-regulation by the nanostructured morphology and the SOW treatment. Importantly, the initial performance of HAOb demonstrated strikingly promoted anchorage with effects of filopodia formation and increased vital cell on NTs with SOW. The present study proposes SOW treatment as an active protocol for synthesis and disinfection of NTs with potent antifungal capability, acting in part by the reduction of nano-adhesion bonds at the surface-fungal interface; opening up a novel route for the investigation of mycotic-adhesion processes at the nanoscale for bone implants applications. Copyright © 2017 Elsevier B.V. All rights reserved.

  10. Instructions, Feedback, and Reinforcement in Reducing Activity Levels in the Classroom.

    Science.gov (United States)

    Schulman, Jerome L.; And Others

    1979-01-01

    Results indicated that the intervention package--including instructions, feedback from an electronic device that measures motor activity, and contingent reinforcement--was successful in reducing activity in the classroom for 8 of the 11 emotionally disturbed Ss (ages 9 to 13 years). (Author/DLS)

  11. Solid Waste Educational Resources and Activities: Let's Reduce, Reuse, and Recycle. [CD-ROM].

    Science.gov (United States)

    Environmental Protection Agency, Washington, DC. Solid Waste and Emergency Response.

    This contains games, activities, publications, and resources for students and teachers on how to reduce, reuse, recycle, and properly manage waste. It also contains a screen saver featuring runners-up from the Earth Day 2000 art contest. Activities and games include titles such as "Planet Protectors,""Recycle City,""Trash…

  12. Lysosomal Acid Lipase Activity Is Reduced Both in Cryptogenic Cirrhosis and in Cirrhosis of Known Etiology.

    Directory of Open Access Journals (Sweden)

    Umberto Vespasiani-Gentilucci

    Full Text Available Liver cirrhosis is characterized by a severe acquired reduction of LAL-activity, the precise causes and consequences of which need to be further addressed. DBS-determined lysosomal enzyme activities seem to be affected by white blood cell and platelet counts, and the specificity of these tests can be reduced when applied to determined populations, such as cirrhotics.

  13. Exceptionally strong sorption of infochemicals to activated carbon reduces their bioavailability to fish

    NARCIS (Netherlands)

    Jonker, Michiel T O; van Mourik, Louise

    2014-01-01

    The addition of activated carbon (AC) to sediments is a relatively new approach to remediate contaminated sites. Activated carbon strongly sorbs hydrophobic organic contaminants, thereby reducing their bioavailability and uptake in organisms. Because of its high sorption capacity, AC might, however,

  14. Activated charcoal filter effectively reduces p-benzosemiquinone from the mainstream cigarette smoke and prevents emphysema

    Indian Academy of Sciences (India)

    Neekkan Dey; Archita Das; Arunava Ghosh; Indu B Chatterjee

    2010-06-01

    In this paper, we have made a comparative evaluation of the cytotoxicity and pathophysiological effects of mainstream smoke from cellulose acetate (CA)-filtered cigarettes with that of charcoal-filtered cigarettes developed in our laboratory. Previously, we had demonstrated that the mainstream smoke from an Indian CA-filtered commercial cigarette contains p-benzosemiquinone (p-BSQ), a major, highly toxic, long-lived water-soluble radical. Here, we have examined 16 brands of different CA-filtered cigarettes including Kentucky research cigarettes, and observed that mainstream smoke from all the cigarettes contains substantial amounts of p-BSQ (100–200 g/cigarette). We also show that when the CA filter is replaced by a charcoal filter, the amount of p-BSQ in the mainstream smoke is reduced by 73–80%, which is accompanied by a reduction of carbonyl formation in bovine serum albumin to the extent of 70–90%. The charcoal filter also prevented cytotoxicity in A549 cells as evidenced by MTT assay, apoptosis as evidenced by FACS analysis, TUNEL assay, overexpression of Bax, activation of p53 and caspase 3, as well as emphysematous lung damage in a guinea pig model as seen by histology and morphometric analysis. The results indicate that the charcoal filter developed in our laboratory may protect smokers from cigarette smoke-induced cytotoxity, protein modification, apoptosis and emphysema.

  15. Reduced sulfotransferase SULT2A1 activity in patients with Alzheimer's disease.

    Science.gov (United States)

    Vaňková, M; Hill, M; Velíková, M; Včelák, J; Vacínová, G; Lukášová, P; Vejražková, D; Dvořáková, K; Rusina, R; Holmerová, I; Jarolímová, E; Vaňková, H; Bendlová, B

    2015-01-01

    Steroids are important components in the pathophysiology of Alzheimer's disease (AD). Although their role has been studied, the corresponding metabolomic data is limited. In the present study we evaluate the role of steroid sulfotransferase SULT2A1 in the pathophysiology of AD on the basis of circulating steroids (measured by GC-MS), in which the sulfation catalyzed by SULT2A1 dominates over glucuronidation (pregnenolone/sulfate, DHEA/sulfate, androstenediol/sulfate and 5alpha-reduced pregnane and androstane catabolites). To estimate a general trend of SUL2A1 activity in AD patients we compared the ratios of steroid conjugates to their unconjugated counterparts (C/U) in controls (11 men and 22 women) and AD patients (18 men and 16 women) for individual circulating steroids after adjustment for age and BMI using ANCOVA model including the factors AD status and gender. Decreased C/U ratio for the C19 steroids demonstrate an association between attenuated sulfation of C19 steroids in adrenal zona reticularis and the pathophysiology of AD.

  16. Development of new generation reduced activation ferritic-martensitic steels for advanced fusion reactors

    Science.gov (United States)

    Tan, L.; Snead, L. L.; Katoh, Y.

    2016-09-01

    International development of reduced activation ferritic-martensitic (RAFM) steels has focused on 9 wt percentage Cr, which primarily contain M23C6 (M = Cr-rich) and small amounts of MX (M = Ta/V, X = C/N) precipitates, not adequate to maintain strength and creep resistance above ∼500 °C. To enable applications at higher temperatures for better thermal efficiency of fusion reactors, computational alloy thermodynamics coupled with strength modeling have been employed to explore a new generation RAFM steels. The new alloys are designed to significantly increase the amount of MX nanoprecipitates, which are manufacturable through standard and scalable industrial steelmaking methods. Preliminary experimental results of the developed new alloys demonstrated noticeably increased amount of MX, favoring significantly improved strength, creep resistance, and Charpy impact toughness as compared to current RAFM steels. The strength and creep resistance were comparable or approaching to the lower bound of, but impact toughness was noticeably superior to 9-20Cr oxide dispersion-strengthened ferritic alloys.

  17. Demonstration of Active Power Controls by Utility-Scale PV Power Plant in an Island Grid: Preprint

    Energy Technology Data Exchange (ETDEWEB)

    Gevorgian, Vahan; O' Neill, Barbara

    2017-02-01

    The National Renewable Energy Laboratory (NREL), AES, and the Puerto Rico Electric Power Authority conducted a demonstration project on a utility-scale photovoltaic (PV) plant to test the viability of providing important ancillary services from this facility. As solar generation increases globally, there is a need for innovation and increased operational flexibility. A typical PV power plant consists of multiple power electronic inverters and can contribute to grid stability and reliability through sophisticated 'grid-friendly' controls. In this way, it may mitigate the impact of its variability on the grid and contribute to important system requirements more like traditional generators. In 2015, testing was completed on a 20-MW AES plant in Puerto Rico, and a large amount of test data was produced and analyzed that demonstrates the ability of PV power plants to provide various types of new grid-friendly controls. This data showed how active power controls can leverage PV's value from being simply an intermittent energy resource to providing additional ancillary services for an isolated island grid. Specifically, the tests conducted included PV plant participation in automatic generation control, provision of droop response, and fast frequency response.

  18. Promoting physical activity and reducing climate change : Opportunities to replace short car trips with active transportation

    NARCIS (Netherlands)

    Maibach, E.; Steg, L.; Anable, J.

    2009-01-01

    Automobile use is a significant contributor to climate change, local air pollution, pedestrian injuries and deaths, declines in physical activity and obesity. A significant proportion of car use is for short trips that can relatively easily be taken with active transportation options - walking or

  19. Activated charcoal and baking soda to reduce odor associated with extensive blistering disorders

    Directory of Open Access Journals (Sweden)

    Chakravarthi Arun

    2008-01-01

    Full Text Available Background: Skin disease leading to extensive blistering and loss of skin is associated with a characteristic smell. Odor can cause physiologic disturbances such as increase in heart rate and respiratory rate. It can also cause nausea and vomiting and is disturbing to bystanders. Aims: To test odor reducing capability of activated charcoal. Methods: In this blinded experimental study we used putrefied amniotic membrane to produce odor and studied the effectiveness of activated charcoal and soda-bi-carbonate to reduce odor. Results: Statistical analysis with Kruskal Wall′s Chi Square Test and Man Whitney U test showed significant reduction of odor using activated charcoal by itself or along with soda-bi-carbonate. Conclusion: We recommend the usage of activated charcoal with/without soda bicarbonate as an inexpensive practical measure to reduce foul odor associated with extensive skin loss.

  20. Tested Demonstrations.

    Science.gov (United States)

    Sands, Robert; And Others

    1982-01-01

    Procedures for two demonstrations are provided. The solubility of ammonia gas in water is demonstrated by introducing water into a closed can filled with the gas, collapsing the can. The second demonstration relates scale of standard reduction potentials to observed behavior of metals in reactions with hydrogen to produce hydrogen gas. (Author/JN)

  1. Eupatilin exerts neuroprotective effects in mice with transient focal cerebral ischemia by reducing microglial activation

    Science.gov (United States)

    Cho, Kyu Suk; Jeon, Se Jin; Kwon, Oh Wook; Jang, Dae Sik; Kim, Sun Yeou; Ryu, Jong Hoon; Choi, Ji Woong

    2017-01-01

    Microglial activation and its-driven neuroinflammation are characteristic pathogenetic features of neurodiseases, including focal cerebral ischemia. The Artemisia asiatica (Asteraceae) extract and its active component, eupatilin, are well-known to reduce inflammatory responses. But the therapeutic potential of eupatilin against focal cerebral ischemia is not known, along with its anti-inflammatory activities on activated microglia. In this study, we investigated the neuroprotective effect of eupatilin on focal cerebral ischemia through its anti-inflammation, particularly on activated microglia, employing a transient middle cerebral artery occlusion/reperfusion (tMCAO), combined with lipopolysaccharide-stimulated BV2 microglia. Eupatilin exerted anti-inflammatory responses in activated BV2 microglia, in which it reduced secretion of well-known inflammatory markers, including nitrite, IL-6, TNF-α, and PGE2, in a concentration-dependent manner. These observed in vitro effects of eupatilin led to in vivo neuroprotection against focal cerebral ischemia. Oral administration of eupatilin (10 mg/kg) in a therapeutic paradigm significantly reduced brain infarction and improved neurological functions in tMCAO-challenged mice. The same benefit was also observed when eupatilin was given even within 5 hours after MCAO induction. In addition, the neuroprotective effects of a single administration of eupatilin (10 mg/kg) immediately after tMCAO challenge persisted up to 3 days after tMCAO. Eupatilin administration reduced the number of Iba1-immunopositive cells across ischemic brain and induced their morphological changes from amoeboid into ramified in the ischemic core, which was accompanied with reduced microglial proliferation in ischemic brain. Eupatilin suppressed NF-κB signaling activities in ischemic brain by reducing IKKα/β phosphorylation, IκBα phosphorylation, and IκBα degradation. Overall, these data indicate that eupatilin is a neuroprotective agent against

  2. SIRT1 Activating Compounds Reduce Oxidative Stress and Prevent Cell Death in Neuronal Cells

    Directory of Open Access Journals (Sweden)

    Reas S Khan

    2012-12-01

    Full Text Available Activation of SIRT1, an NAD+-dependent deacetylase, prevents retinal ganglion cell (RGC loss in optic neuritis, an inflammatory demyelinating optic nerve disease. While SIRT1 deacetylates numerous protein targets, downstream mechanisms of SIRT1 activation mediating this neuroprotective effect are unknown. SIRT1 increases mitochondrial function and reduces oxidative stress in muscle and other cells, and oxidative stress occurs in neuronal degeneration. We examined whether SIRT1 activators reduce oxidative stress and promote mitochondrial function in neuronal cells. Oxidative stress, marked by reactive oxygen species (ROS accumulation, was induced in RGC-5 cells by serum deprivation, or addition of doxorubicin or hydrogen peroxide, and resulted in significant cell loss. SIRT1 activators resveratrol and SRTAW04 reduced ROS levels, and promoted cell survival in RGC-5 cells as well as primary RGC cultures. Effects were blocked by SIRT1 siRNA. SIRT1 activators also increased expression of succinate dehydrogenase, a mitochondrial enzyme, and promoted deacetylation of PGC-1α, a co-enzyme involved in mitochondrial function. Results show SIRT1 activators prevent cell loss by reducing oxidative stress and promoting mitochondrial function in a neuronal cell line. Results suggest SIRT1 activators can mediate neuroprotective effects during optic neuritis by these mechanisms, and they have the potential to preserve neurons in other neurodegenerative diseases that involve oxidative stress.

  3. Intermittent peripheral tissue ischemia during coronary ischemia reduces myocardial infarction through a KATP-dependent mechanism: first demonstration of remote ischemic perconditioning

    DEFF Research Database (Denmark)

    Schmidt, Michael Rahbek; Smerup, M; Konstantinov, I E

    2006-01-01

    . Intermittent limb ischemia during myocardial ischemia reduces MI, preserves global systolic and diastolic function, and protects against arrhythmia during the reperfusion phase through a K(ATP) channel-dependent mechanism. Understanding this process may have important therapeutic implications for a range...

  4. Exploratory Characterization of Phenolic Compounds with Demonstrated Anti-Diabetic Activity in Guava Leaves at Different Oxidation States

    Science.gov (United States)

    Díaz-de-Cerio, Elixabet; Verardo, Vito; Gómez-Caravaca, Ana María; Fernández-Gutiérrez, Alberto; Segura-Carretero, Antonio

    2016-01-01

    Psidium guajava L. is widely used like food and in folk medicine all around the world. Many studies have demonstrated that guava leaves have anti-hyperglycemic and anti-hyperlipidemic activities, among others, and that these activities belong mainly to phenolic compounds, although it is known that phenolic composition in guava tree varies throughout seasonal changes. Andalusia is one of the regions in Europe where guava is grown, thus, the aim of this work was to study the phenolic compounds present in Andalusian guava leaves at different oxidation states (low, medium, and high). The phenolic compounds in guava leaves were determined by HPLC-DAD-ESI-QTOF-MS. The results obtained by chromatographic analysis reported that guava leaves with low degree of oxidation had a higher content of flavonols, gallic, and ellagic derivatives compared to the other two guava leaf samples. Contrary, high oxidation state guava leaves reported the highest content of cyanidin-glucoside that was 2.6 and 15 times higher than guava leaves with medium and low oxidation state, respectively. The QTOF platform permitted the determination of several phenolic compounds with anti-diabetic properties and provided new information about guava leaf phenolic composition that could be useful for nutraceutical production. PMID:27187352

  5. Exploratory Characterization of Phenolic Compounds with Demonstrated Anti-Diabetic Activity in Guava Leaves at Different Oxidation States.

    Science.gov (United States)

    Díaz-de-Cerio, Elixabet; Verardo, Vito; Gómez-Caravaca, Ana María; Fernández-Gutiérrez, Alberto; Segura-Carretero, Antonio

    2016-05-11

    Psidium guajava L. is widely used like food and in folk medicine all around the world. Many studies have demonstrated that guava leaves have anti-hyperglycemic and anti-hyperlipidemic activities, among others, and that these activities belong mainly to phenolic compounds, although it is known that phenolic composition in guava tree varies throughout seasonal changes. Andalusia is one of the regions in Europe where guava is grown, thus, the aim of this work was to study the phenolic compounds present in Andalusian guava leaves at different oxidation states (low, medium, and high). The phenolic compounds in guava leaves were determined by HPLC-DAD-ESI-QTOF-MS. The results obtained by chromatographic analysis reported that guava leaves with low degree of oxidation had a higher content of flavonols, gallic, and ellagic derivatives compared to the other two guava leaf samples. Contrary, high oxidation state guava leaves reported the highest content of cyanidin-glucoside that was 2.6 and 15 times higher than guava leaves with medium and low oxidation state, respectively. The QTOF platform permitted the determination of several phenolic compounds with anti-diabetic properties and provided new information about guava leaf phenolic composition that could be useful for nutraceutical production.

  6. Exploratory Characterization of Phenolic Compounds with Demonstrated Anti-Diabetic Activity in Guava Leaves at Different Oxidation States

    Directory of Open Access Journals (Sweden)

    Elixabet Díaz-de-Cerio

    2016-05-01

    Full Text Available Psidium guajava L. is widely used like food and in folk medicine all around the world. Many studies have demonstrated that guava leaves have anti-hyperglycemic and anti-hyperlipidemic activities, among others, and that these activities belong mainly to phenolic compounds, although it is known that phenolic composition in guava tree varies throughout seasonal changes. Andalusia is one of the regions in Europe where guava is grown, thus, the aim of this work was to study the phenolic compounds present in Andalusian guava leaves at different oxidation states (low, medium, and high. The phenolic compounds in guava leaves were determined by HPLC-DAD-ESI-QTOF-MS. The results obtained by chromatographic analysis reported that guava leaves with low degree of oxidation had a higher content of flavonols, gallic, and ellagic derivatives compared to the other two guava leaf samples. Contrary, high oxidation state guava leaves reported the highest content of cyanidin-glucoside that was 2.6 and 15 times higher than guava leaves with medium and low oxidation state, respectively. The QTOF platform permitted the determination of several phenolic compounds with anti-diabetic properties and provided new information about guava leaf phenolic composition that could be useful for nutraceutical production.

  7. Intrinsic unfoldase/foldase activity of the chaperonin GroEL directly demonstrated using multinuclear relaxation-based NMR

    Science.gov (United States)

    Libich, David S.; Tugarinov, Vitali; Clore, G. Marius

    2015-01-01

    The prototypical chaperonin GroEL assists protein folding through an ATP-dependent encapsulation mechanism. The details of how GroEL folds proteins remain elusive, particularly because encapsulation is not an absolute requirement for successful re/folding. Here we make use of a metastable model protein substrate, comprising a triple mutant of Fyn SH3, to directly demonstrate, by simultaneous analysis of three complementary NMR-based relaxation experiments (lifetime line broadening, dark state exchange saturation transfer, and Carr–Purcell–Meinboom–Gill relaxation dispersion), that apo GroEL accelerates the overall interconversion rate between the native state and a well-defined folding intermediate by about 20-fold, under conditions where the “invisible” GroEL-bound states have occupancies below 1%. This is largely achieved through a 500-fold acceleration in the folded-to-intermediate transition of the protein substrate. Catalysis is modulated by a kinetic deuterium isotope effect that reduces the overall interconversion rate between the GroEL-bound species by about 3-fold, indicative of a significant hydrophobic contribution. The location of the GroEL binding site on the folding intermediate, mapped from 15N, 1HN, and 13Cmethyl relaxation dispersion experiments, is composed of a prominent, surface-exposed hydrophobic patch. PMID:26124125

  8. The facial massage reduced anxiety and negative mood status, and increased sympathetic nervous activity.

    Science.gov (United States)

    Hatayama, Tomoko; Kitamura, Shingo; Tamura, Chihiro; Nagano, Mayumi; Ohnuki, Koichiro

    2008-12-01

    The aim of this study was to clarify the effects of 45 min of facial massage on the activity of autonomic nervous system, anxiety and mood in 32 healthy women. Autonomic nervous activity was assessed by heart rate variability (HRV) with spectral analysis. In the spectral analysis of HRV, we evaluated the high-frequency components (HF) and the low- to high-frequency ratio (LF/HF ratio), reflecting parasympathetic nervous activity and sympathetic nervous activity, respectively. The State Trait Anxiety Inventory (STAI) and the Profile of Mood Status (POMS) were administered to evaluate psychological status. The score of STAI and negative scale of POMS were significantly reduced following the massage, and only the LF/HF ratio was significantly enhanced after the massage. It was concluded that the facial massage might refresh the subjects by reducing their psychological distress and activating the sympathetic nervous system.

  9. Chlorination and ozonation differentially reduced the microcystin content and tumour promoting activity of a complex cyanobacterial extract

    Directory of Open Access Journals (Sweden)

    Iva Sovadinova

    2017-05-01

    Full Text Available Despite intensive research and management efforts in the past decades, cyanobacterial blooms and their toxins, such as microcystins (MCs, continue to represent a major ecological and health problem in fresh waters throughout the world. Our objective was to compare the efficacy of two commonly used drinking water treatment technologies, chlorination and ozonation, in removing MCs and in reducing tumour promotion-related effects of cyanobacteria, such as inhibition of gap junctional intercellular communication (GJIC and activation of mitogen activated protein kinases (MAPKs in a rat liver epithelial stem-like cell line (WB-F344. This combined chemical and bioassay approach demonstrated that ozone effectively removed all MCs from an extract of a globally important bloom-forming cyanobacterium, Microcystis sp. Ozone also significantly reduced the overall tumour promotional potency of the cyanobacterial extract, as indicated by a substantial reduction in the ability of the extract to inhibit GJIC and activate extracellular receptor kinase 1/2 (ERK1/2. Although comparable reduction of total organic carbon was achieved by ozone and chlorine treatment, chlorination was much less effective in removing MCs and reducing the effects on GJIC. Chlorination had a biphasic effect with an observed decrease of extract-induced activation of ERK1/2 at the lower chlorine doses; whereas at high doses of chlorine the by-products of chlorination actually induced the activation of ERK1/2. The extracts induced p38 activation, and chlorination was not effective in reversing this effect, while ozone did reverse this effect, albeit not as much as the activation of ERK1/2. Thus, ozone was effective in reducing the toxicity of cyanobacterial extracts while chlorination was not only lacking efficacy, but at high doses of chlorination further produced by-products that were equally toxic as the untreated samples. Our study indicates the value of using an effect-based approach to

  10. Energy activity guide : simple steps to reduce your household energy use

    Energy Technology Data Exchange (ETDEWEB)

    Byckalo-Khan, F.; Wallace, C.L. (ed.)

    2003-07-01

    This guide presents 13 practical activities that can help households reduce energy consumption in order to create a more sustainable lifestyle and to help meet Canada's Kyoto commitment to reduce greenhouse gas emissions. Most energy sources create pollution that harms both human health and the Earth. The burning of fossil fuels creates greenhouse gas emissions that contribute to climate change, smog, pollution and adverse health effects. This guide offers suggestions on how households can reduce the impact on the environment while saving money. Some of the initiatives include lowering the thermostat, replacing incandescent light bulbs with compact fluorescent light bulbs, turning off appliances when not in use, weatherising building envelopes, using a clothes line to dry clothes instead of a dryer, laundering clothes with cold water, and proper maintenance of heating equipment. An energy use chart is included with this guide to help track activities and to estimate how much time and money is required by each activity. refs., figs.

  11. Cross-person activity recognition using reduced kernel extreme learning machine.

    Science.gov (United States)

    Deng, Wan-Yu; Zheng, Qing-Hua; Wang, Zhong-Min

    2014-05-01

    Activity recognition based on mobile embedded accelerometer is very important for developing human-centric pervasive applications such as healthcare, personalized recommendation and so on. However, the distribution of accelerometer data is heavily affected by varying users. The performance will degrade when the model trained on one person is used to others. To solve this problem, we propose a fast and accurate cross-person activity recognition model, known as TransRKELM (Transfer learning Reduced Kernel Extreme Learning Machine) which uses RKELM (Reduced Kernel Extreme Learning Machine) to realize initial activity recognition model. In the online phase OS-RKELM (Online Sequential Reduced Kernel Extreme Learning Machine) is applied to update the initial model and adapt the recognition model to new device users based on recognition results with high confidence level efficiently. Experimental results show that, the proposed model can adapt the classifier to new device users quickly and obtain good recognition performance.

  12. Characterization of esterase activity in the Bianchetta trevigiana grape variety under reducing conditions

    Directory of Open Access Journals (Sweden)

    Lomolino G

    2012-10-01

    Full Text Available Giovanna Lomolino, Anna LanteDepartment of Agronomy Food Natural Resources Animals and Environment, Agripolis, Università di Padova Viale dell'Università, Padova, ItalyBackground and methods: While extensive research has been carried out on the enzymes responsible for ester synthesis and hydrolysis by wine strains of Saccharomyces cerevisiae, grape esterase activity is limited. In this study, the autochthonous grape variety, Bianchetta trevigiana, widespread in the Prosecco wine production area of Treviso, Conegliano, and Asolo, Italy, was characterized according to its esterase activity. Because grape skin is very rich in compounds which impart qualitative characteristics to wine, the study of esterase was carried out on this part of the fruit.Results: During enzyme extraction from grape skin, the presence of the reducing agent, β-mercaptoethanol, allowed a better protein yield but reduced esterase activity. Further addition of increasing doses of reducing agents to grape skin protein extract, such as of K2S2O5 (used in winemaking and DTT, reduced or inhibited esterase activity. Even though the zymographic profiles of the extracts obtained with and without β-mercaptoethanol were qualitatively equal, the intensity of enzymatic bands, measured by densitometry, was different.Conclusion: The presence of reducing agents affected the activity of grape skin esterase, and given that this enzyme is involved in the hydrolysis and synthesis of esters, which are important compounds responsible for the flavor of wine, addition of reducing agents could affect the aromatic profile of wine.Keywords: esterase, grape, reducing agent, wine

  13. Use of Metallopeptide Based Mimics Demonstrates That the Metalloprotein Nitrile Hydratase Requires Two Oxidized Cysteinates for Catalytic Activity

    Energy Technology Data Exchange (ETDEWEB)

    Shearer, J.; Callan, P; Amie, J

    2010-01-01

    Nitrile hydratases (NHases) are non-heme Fe{sup III} or non-corrin Co{sup III} containing metalloenzymes that possess an N{sub 2}S{sub 3} ligand environment with nitrogen donors derived from amidates and sulfur donors derived from cysteinates. A closely related enzyme is thiocyanate hydrolase (SCNase), which possesses a nearly identical active-site coordination environment as CoNHase. These enzymes are redox inactive and perform hydrolytic reactions; SCNase hydrolyzes thiocyanate anions while NHase converts nitriles into amides. Herein an active CoNHase metallopeptide mimic, [Co{sup III}NHase-m1] (NHase-m1 = AcNH-CCDLP-CGVYD-PA-COOH), that contains Co{sup III} in a similar N{sub 2}S{sub 3} coordination environment as CoNHase is reported. [Co{sup III}NHase-m1] was characterized by electrospray ionization-mass spectrometry (ESI-MS), gel-permeation chromatography (GPC), Co K-edge X-ray absorption spectroscopy (Co-S: 2.21 {angstrom}; Co-N: 1.93 {angstrom}), vibrational, and optical spectroscopies. We find that [Co{sup III}NHase-m1] will perform the catalytic conversion of acrylonitrile into acrylamide with up to 58 turnovers observed after 18 h at 25 C (pH 8.0). FTIR data used in concert with calculated vibrational data (mPWPW91/aug-cc-TZVPP) demonstrates that the active form of [Co{sup III}NHase-m1] has a ligated SO{sub 2} (? = 1091 cm{sup -1}) moiety and a ligated protonated SO(H) (? = 928 cm{sup -1}) moiety; when only one oxygenated cysteinate ligand (i.e., a mono-SO{sub 2} coordination motif) or the bis-SO{sub 2} coordination motif are found within [Co{sup III}NHase-m1] no catalytic activity is observed. Calculations of the thermodynamics of ligand exchange (B3LYP/aug-cc-TZVPP) suggest that the reason for this is that the SO{sub 2}/SO(H) equatorial ligand motif promotes both water dissociation from the Co{sup III}-center and nitrile coordination to the Co{sup III}-center. In contrast, the under- or overoxidized motifs will either strongly favor a five coordinate Co

  14. Leishmania infantum-chagasi activates SHP-1 and reduces NFAT5/TonEBP activity in the mouse kidney inner medulla.

    Science.gov (United States)

    Zhou, Xiaoming; Wang, Hong; Koles, Nancy L; Zhang, Aihong; Aronson, Naomi E

    2014-09-01

    Visceral leishmaniasis patients have been reported to have a urine concentration defect. Concentration of urine by the renal inner medulla is essentially dependent on a transcription factor, NFAT5/TonEBP, because it activates expression of osmoprotective genes betaine/glycine transporter 1 (BGT1) and sodium/myo-inositol transporter (SMIT), and water channel aquaporin-2, all of which are imperative for concentrating urine. Leishmania parasites evade macrophage immune defenses by activating protein tyrosine phosphatases, among which SHP-1 is critical. We previously demonstrated that SHP-1 inhibits tonicity-dependent activation of NFAT5/TonEBP in HEK293 cells through screening a genome-wide small interfering (si) RNA library against phosphatases (Zhou X, Gallazzini M, Burg MB, Ferraris JD. Proc Natl Acad Sci USA 107: 7072-7077, 2010). We sought to examine whether Leishmania can activate SHP-1 and inhibit NFAT5/TonEBP activity in the renal inner medulla in a murine model of visceral leishmaniasis by injection of female BALB/c mice with a single intravenous dose of 5 × 10(5) L. chagasi metacyclic promastigotes. We found that SHP-1 is expressed in the kidney inner medulla. L. chagasi activates SHP-1 with an increase in stimulatory phosphorylation of SHP-1-Y536 in the region. L. chagasi reduces expression of NFAT5/TonEBP mRNA and protein as well as expression of its targeted genes: BGT1, SMIT, and aquaporin-2. The culture supernatant from L. chagasi metacyclic promastigotes increases SHP-1 protein abundance and potently inhibits NFAT5 transcriptional activity in mIMCD3 cells. However, L. chagasi in our animal model has no significant effect on urinary concentration. We conclude that L. chagasi, most likely through its secreted virulence factors, activates SHP-1 and reduces NFAT5/TonEBP gene expression, which leads to reduced NFAT5/TonEBP transcriptional activity in the kidney inner medulla.

  15. Focal Adhesion Kinase Inhibitors in Combination with Erlotinib Demonstrate Enhanced Anti-Tumor Activity in Non-Small Cell Lung Cancer.

    Directory of Open Access Journals (Sweden)

    Grant A Howe

    Full Text Available Blockade of epidermal growth factor receptor (EGFR activity has been a primary therapeutic target for non-small cell lung cancers (NSCLC. As patients with wild-type EGFR have demonstrated only modest benefit from EGFR tyrosine kinase inhibitors (TKIs, there is a need for additional therapeutic approaches in patients with wild-type EGFR. As a key component of downstream integrin signalling and known receptor cross-talk with EGFR, we hypothesized that targeting focal adhesion kinase (FAK activity, which has also been shown to correlate with aggressive stage in NSCLC, would lead to enhanced activity of EGFR TKIs. As such, EGFR TKI-resistant NSCLC cells (A549, H1299, H1975 were treated with the EGFR TKI erlotinib and FAK inhibitors (PF-573,228 or PF-562,271 both as single agents and in combination. We determined cell viability, apoptosis and 3-dimensional growth in vitro and assessed tumor growth in vivo. Treatment of EGFR TKI-resistant NSCLC cells with FAK inhibitor alone effectively inhibited cell viability in all cell lines tested; however, its use in combination with the EGFR TKI erlotinib was more effective at reducing cell viability than either treatment alone when tested in both 2- and 3-dimensional assays in vitro, with enhanced benefit seen in A549 cells. This increased efficacy may be due in part to the observed inhibition of Akt phosphorylation when the drugs were used in combination, where again A549 cells demonstrated the most inhibition following treatment with the drug combination. Combining erlotinib with FAK inhibitor was also potent in vivo as evidenced by reduced tumor growth in the A549 mouse xenograft model. We further ascertained that the enhanced sensitivity was irrespective of the LKB1 mutational status. In summary, we demonstrate the effectiveness of combining erlotinib and FAK inhibitors for use in known EGFR wild-type, EGFR TKI resistant cells, with the potential that a subset of cell types, which includes A549, could be

  16. Active optics and modified-Rumsey wide-field telescopes: MINITRUST demonstrators with vase- and tulip-form mirrors

    Science.gov (United States)

    Lemaître, Gérard R.; Montiel, Pierre; Joulié, Patrice; Dohlen, Kjetil; Lanzoni, Patrick

    2005-12-01

    Wide-field astronomy requires the development of larger aperture telescopes. The optical properties of a three-mirror modified-Rumsey design provide significant advantages when compared to other telescope designs: (i) at any wavelength, the design has a flat field and is anastigmatic; (ii) the system is extremely compact, i.e., it is almost four times shorter than a Schmidt. Compared to the equally compact flat-field Ritchey-Chrétien with a doublet-lens corrector, as developed for the Sloan digital sky survey - and which requires the polishing of six optical surfaces - the proposed modified-Rumsey design requires only a two-surface polishing and provides a better imaging quality. All the mirrors are spheroids of the hyperboloid type. Starting from the classical Rumsey design, it is shown that the use of all eight available free parameters allows the simultaneous aspherization of the primary and tertiary mirrors by active optics methods from a single deformable substrate. The continuity conditions between the primary and the tertiary hyperbolizations are achieved by an intermediate narrow ring of constant thickness that is not optically used. After the polishing of a double vase form in a spherical shape, the primary-tertiary hyperbolizations are achieved by in situ stressing. The tulip-form secondary is hyperbolized by stress polishing. Other active optics alternatives are possible for a space telescope. The modified-Rumsey design is of interest for developing large space- and ground-based survey telescopes in UV, visible, or IR ranges, such as currently demonstrated with the construction of identical telescopes MINITRUST-1 and -2, f/5 - 2° field of view. Double-pass optical tests show diffraction-limited images.

  17. Removal of visual feedback alters muscle activity and reduces force variability during constant isometric contractions.

    Science.gov (United States)

    Baweja, Harsimran S; Patel, Bhavini K; Martinkewiz, Julie D; Vu, Julie; Christou, Evangelos A

    2009-07-01

    The purpose of this study was to compare force accuracy, force variability and muscle activity during constant isometric contractions at different force levels with and without visual feedback and at different feedback gains. In experiment 1, subjects were instructed to accurately match the target force at 2, 15, 30, 50, and 70% of their maximal isometric force with abduction of the index finger and maintain their force even in the absence of visual feedback. Each trial lasted 22 s and visual feedback was removed from 8-12 to 16-20 s. Each subject performed 6 trials at each target force, half with visual gain of 51.2 pixels/N and the rest with a visual gain of 12.8 pixels/N. Force error was calculated as the root mean square error of the force trace from the target line. Force variability was quantified as the standard deviation and coefficient of variation (CVF) of the force trace. The EMG activity of the agonist (first dorsal interosseus; FDI) was measured with bipolar surface electrodes placed distal to the innervation zone. Independent of visual gain and force level, subjects exhibited lower force error with the visual feedback condition (2.53 +/- 2.95 vs. 2.71 +/- 2.97 N; P feedback was removed (CVF: 4.06 +/- 3.11 vs. 4.47 +/- 3.14, P feedback condition and this difference increased especially at higher force levels (70%: 370 +/- 149 vs. 350 +/- 143 microV, P feedback. Subjects performed constant isometric contractions with the abduction of the index finger at an absolute force of 2 N, with two distinct feedback gains of 15 and 3,000 pixels/N. In agreement with the findings of experiment 1, subjects exhibited lower force error in the presence of visual feedback especially when the feedback gain was high (0.057 +/- 0.03 vs. 0.095 +/- 0.05 N). However, force variability was not affected by the vastly distinct feedback gains at this force, which supported and extended the findings from experiment 1. Our findings demonstrate that although removal of visual

  18. Tested Demonstrations.

    Science.gov (United States)

    Gilbert, George L., Ed.

    1983-01-01

    Free radical chlorination of methane is used in organic chemistry to introduce free radical/chain reactions. In spite of its common occurrence, demonstrations of the reaction are uncommon. Therefore, such a demonstration is provided, including background information, preparation of reactants/reaction vessel, introduction of reactants, irradiation,…

  19. Tested Demonstrations.

    Science.gov (United States)

    Gilbert, George L., Ed.

    1983-01-01

    Discusses a supplement to the "water to rose" demonstration in which a pink color is produced. Also discusses blood buffer demonstrations, including hydrolysis of sodium bicarbonate, simulated blood buffer, metabolic acidosis, natural compensation of metabolic acidosis, metabolic alkalosis, acidosis treatment, and alkalosis treatment. Procedures…

  20. Complete Demonstration.

    Science.gov (United States)

    Yelon, Stephen; Maddocks, Peg

    1986-01-01

    Describes four-step approach to educational demonstration: tell learners they will have to perform; what they should notice; describe each step before doing it; and require memorization of steps. Examples illustrate use of this process to demonstrate a general mental strategy, and industrial design, supervisory, fine motor, and specific…

  1. Tested Demonstrations.

    Science.gov (United States)

    Gilbert, George L., Ed.

    1987-01-01

    Describes two laboratory demonstrations in chemistry. One uses dry ice, freon, and freezer bags to demonstrate volume changes, vapor-liquid equilibrium, a simulation of a rain forest, and vaporization. The other uses the clock reaction technique to illustrate fast reactions and kinetic problems in releasing carbon dioxide during respiration. (TW)

  2. Tested Demonstrations.

    Science.gov (United States)

    Gilbert, George L., Ed.

    1986-01-01

    Outlines a simple, inexpensive way of demonstrating electroplating using the reaction between nickel ions and copper metal. Explains how to conduct a demonstration of the electrolysis of water by using a colored Na2SO4 solution as the electrolyte so that students can observe the pH changes. (TW)

  3. Reduced ventilation-perfusion (V/Q) mismatch following endobronchial valve insertion demonstrated by Gallium-68 V/Q photon emission tomography/computed tomography.

    Science.gov (United States)

    Leong, Paul; Le Roux, Pierre-Yves; Callahan, Jason; Siva, Shankar; Hofman, Michael S; Steinfort, Daniel P

    2017-09-01

    Endobronchial valves (EBVs) are increasingly deployed in the management of severe emphysema. Initial studies focussed on volume reduction as the mechanism, with subsequent improvement in forced expiratory volume in 1 s (FEV1). More recent studies have emphasized importance of perfusion on predicting outcomes, though findings have been inconsistent. Gallium-68 ventilation-perfusion (V/Q) photon emission tomography (PET)/computed tomography (CT) is a novel imaging modality with advantages in spatial resolution, quantitation, and speed over conventional V/Q scintigraphy. We report a pilot case in which V/Q-PET/CT demonstrated discordant findings compared with quantitative CT analysis, and directed left lower lobe EBV placement. The patient experienced a significant improvement in 6-min walk distance (6MWD) without change in spirometry. Post-EBV V/Q-PET/CT demonstrated a marked decrease in unmatched (detrimental) V/Q areas and improvement in overall V/Q matching on post-EBV V/Q-PET/CT. These preliminary novel findings suggest that EBVs improve V/Q matching and may explain the observed functional improvements.

  4. Aldehyde dehydrogenase 2 activation in aged heart improves the autophagy by reducing the carbonyl modification on SIRT1.

    Science.gov (United States)

    Wu, Bing; Yu, Lu; Wang, Yishi; Wang, Hongtao; Li, Chen; Yin, Yue; Yang, Jingrun; Wang, Zhifa; Zheng, Qiangsun; Ma, Heng

    2016-01-19

    Cardiac aging is characterized by accumulation of damaged proteins and decline of autophagic efficiency. Here, by forestalling SIRT1 carbonylated inactivation in aged heart, we determined the benefits of activation of aldehyde dehydrogenase 2 (ALDH2) on the autophagy. In this study, the ALDH2 KO mice progressively developed age-related heart dysfunction and showed reduction in the life span, which strongly suggests that ALDH2 ablation leads to cardiac aging. What's more, aged hearts displayed a significant decrease ALDH2 activity, resulting in accumulation of 4-HNE-protein adducts and protein carbonyls, impairment in the autophagy flux, and, consequently, deteriorated cardiac function after starvation. Sustained Alda-1 (selective ALDH2 activator) treatment increased cardiac ALDH2 activity and abrogated these effects. Using SIRT1 deficient heterozygous (Sirt1+/-) mice, we found that SIRT1 was necessary for ALDH2 activation-induced autophagy. We further demonstrated that ALDH2 activation attenuated SIRT1 carbonylation and improved SIRT1 activity, thereby increasing the deacetylation of nuclear LC3 and FoxO1. Sequentially, ALDH2 enhanced SIRT1 regulates LC3-Atg7 interaction and FoxO1 increased Rab7 expression, which were both necessary and sufficient for restoring autophagy flux. These results highlight that both accumulation of proteotoxic carbonyl stress linkage with autophagy decline contribute to heart senescence. ALDH2 activation is adequate to improve the autophagy flux by reducing the carbonyl modification on SIRT1, which in turn plays an important role in maintaining cardiac health during aging.

  5. Preclinical demonstration of synergistic Active Nutrients/Drug (AND combination as a potential treatment for malignant pleural mesothelioma.

    Directory of Open Access Journals (Sweden)

    Viviana Volta

    Full Text Available Malignant pleural mesothelioma (MPM is a poor prognosis disease lacking adequate therapy. We have previously shown that ascorbic acid administration is toxic to MPM cells. Here we evaluated a new combined therapy consisting of ascorbate/epigallocatechin-3-gallate/gemcitabine mixture (called AND, for Active Nutrients/Drug. In vitro effects of AND therapy on various MPM cell lines revealed a synergistic cytotoxic mechanism. In vivo experiments on a xenograft mouse model for MPM, obtained by REN cells injection in immunocompromised mice, showed that AND strongly reduced the size of primary tumor as well as the number and size of metastases, and prevented abdominal hemorrhage. Kaplan Meier curves and the log-rank test indicated a marked increase in the survival of AND-treated animals. Histochemical analysis of dissected tumors showed that AND induced a shift from cell proliferation to apoptosis in cancer cells. Lysates of tumors from AND-treated mice, analyzed with an antibody array, revealed decreased TIMP-1 and -2 expressions and no effects on angiogenesis regulating factors. Multiplex analysis for signaling protein phosphorylation exhibited inactivation of cell proliferation pathways. The complex of data showed that the AND treatment is synergistic in vitro on MPM cells, and blocks in vivo tumor progression and metastasization in REN-based xenografts. Hence, the AND combination is proposed as a new treatment for MPM.

  6. Evaluation of in vitro urease and lipoxygenase inhibition activity of weight reducing tablets.

    Science.gov (United States)

    Jaffary, Syed Rashid Ali; Ahmed, Syed Waseemuddin; Shakeel, Sadia; Asif, Hafiz Muhammad; Usmanghani, Khan

    2016-07-01

    Enzyme inhibition is a significant part of research in pharmaceutical field in view of the fact that these studies have directed to the innovations of drugs having remarkable performance in diverse physiological conditions. The present study was aimed to assess urease and lipoxygenase inhibitory activity of weight reducing tablets. For evaluating the urease activity indophenol method was employed using Thiourea as the model urease inhibitor. The lipoxygenase inhibition was evaluated by measuring the hydroperoxides produced in lipoxygenation reaction using a purified lipoxygenase with lionoleic acid as substrate. When formulation of the weight reducing tablets was compared at various concentrations (50, 100 and 500µg/ml). The antiurease activity and lipoxygenase inhibition activity increased in a dose dependent manner. The formulations under test have an excellent antiurease and lipoxygenase inhibition potential and prospective to be used in the cure of a variety of complications associated with the production of urease and lipoxygenase enzymes.

  7. Zileuton prevents the activation of the leukotriene pathway and reduces sebaceous lipogenesis.

    Science.gov (United States)

    Zouboulis, Christos C; Seltmann, Holger; Alestas, Theodosios

    2010-02-01

    Arachidonic acid (AA) activates the 5-lipoxygenase, induces leukotriene-B(4) (LTB(4)) synthesis, enhances interleukin-6 (IL-6) release and increases intracellular neutral lipids in human sebocytes. Moreover, the enzymes of LTB(4) biosynthesis are activated in acne-involved sebaceous glands. Zileuton a 5-lipoxygenase inhibitor, reduces the number of inflammatory acne lesions and lipogenesis in patients with acne. In this study, we investigated the activity of zileuton on LTB(4) generation, lipid content and IL-6 and -8 release from human SZ95 sebocytes in vitro. Pretreatment with zileuton partially prevented the AA-induced LTB(4) and IL-6 release and increased neutral lipid content. IL-6 release and neutral lipid content were also reduced under long-term zileuton treatment. In conclusion, zileuton prevents the activation of the leukotriene pathway and enhancement of lipogenesis by AA in human sebocytes in vitro.

  8. Construction and Characterization of Novel Staphylokinase Variants with Antiplatelet Aggregation Activity and Reduced Immunogenecity

    Institute of Scientific and Technical Information of China (English)

    Hua-Bo SU; Yu-Gao ZHANG; Jin-Tian HE; Wei MO; Yan-Ling ZHANG; Xian-Mei TAO; Hou-Yan SONG

    2004-01-01

    To develop target thrombolytic agents with fibrinolytic activity, antiplatelet aggregation activity and reduced immunogenicity, two staphylokinase variants containing Arg-Gly-Asp (RGD) motif were constructed. Gene expression was induced in E. coli JF1125 and the variants, designated DGR and RL1, were purified with gel filtration and ion-exchange chromatography and the purity was over 95%. The fibrinolytic activity and kinetic constants of the two variants were comparable to those of recombinant wild-type staphylokinase. Both the variants can inhibit the platelet aggregation at a final concentration of 2 μM. Thetiters of antibodies against variants were much lower than those against recombinant staphylokinase in guineapigs, which indicated that the immunogenicity of the variants was greatly reduced. These results confirm thatit is possible to design and produce a bifunctional protein that possesses fibrinolytic and antiplatelet aggregation activities.

  9. Lead reduces tension development and the myosin ATPase activity of the rat right ventricular myocardium

    Directory of Open Access Journals (Sweden)

    D.V. Vassallo

    2008-09-01

    Full Text Available Lead (Pb2+ poisoning causes hypertension, but little is known regarding its acute effects on cardiac contractility. To evaluate these effects, force was measured in right ventricular strips that were contracting isometrically in 45 male Wistar rats (250-300 g before and after the addition of increasing concentrations of lead acetate (3, 7, 10, 30, 70, 100, and 300 µM to the bath. Changes in rate of stimulation (0.1-1.5 Hz, relative potentiation after pauses of 15, 30, and 60 s, effect of Ca2+ concentration (0.62, 1.25, and 2.5 mM, and the effect of isoproterenol (20 ng/mL were determined before and after the addition of 100 µM Pb2+. Effects on contractile proteins were evaluated after caffeine treatment using tetanic stimulation (10 Hz and measuring the activity of the myosin ATPase. Pb2+ produced concentration-dependent force reduction, significant at concentrations greater than 30 µM. The force developed in response to increasing rates of stimulation became smaller at 0.5 and 0.8 Hz. Relative potentiation increased after 100 µM Pb2+ treatment. Extracellular Ca2+ increment and isoproterenol administration increased force development but after 100 µM Pb2+ treatment the force was significantly reduced suggesting an effect of the metal on the sarcolemmal Ca2+ influx. Concentration of 100 µM Pb2+ also reduced the peak and plateau force of tetanic contractions and reduced the activity of the myosin ATPase. Results showed that acute Pb2+ administration, although not affecting the sarcoplasmic reticulum activity, produces a concentration-dependent negative inotropic effect and reduces myosin ATPase activity. Results suggest that acute lead administration reduced myocardial contractility by reducing sarcolemmal calcium influx and the myosin ATPase activity. These results also suggest that lead exposure is hazardous and has toxicological consequences affecting cardiac muscle.

  10. Reducing Display Bottle Cooler Energy Consumption Using PCM As Active Thermal Storage

    OpenAIRE

    Beek, Marcel van; de Jong, Hans

    2014-01-01

    The final results of an analytical and experimental study in reducing the energy consumption of a display bottle cooler using Phase Change Material (PCM) as an active thermal storage are presented. The objective of the study was to design and built a 350 dm3 glass door bottle cooler having an appliance energy consumption reduction of over 75% compared to state of the art bottle coolers (2010 figures). Calculation results show that active thermal storage using PCM can be effectively applied to...

  11. Intermittent hypoxia in rats reduces activation of Ca2+ sparks in mesenteric arteries.

    Science.gov (United States)

    Jackson-Weaver, Olan; Osmond, Jessica M; Naik, Jay S; Gonzalez Bosc, Laura V; Walker, Benjimen R; Kanagy, Nancy L

    2015-12-01

    Ca(+) sparks are vascular smooth muscle cell (VSMC) Ca(2+)-release events that are mediated by ryanodine receptors (RyR) and promote vasodilation by activating large-conductance Ca(2+)-activated potassium channels and inhibiting myogenic tone. We have previously reported that exposing rats to intermittent hypoxia (IH) to simulate sleep apnea augments myogenic tone in mesenteric arteries through loss of hydrogen sulfide (H2S)-induced dilation. Because we also observed that H2S can increase Ca(2+) spark activity, we hypothesized that loss of H2S after IH exposure reduces Ca(2+) spark activity and that blocking Ca(2+) spark generation reduces H2S-induced dilation. Ca(2+) spark activity was lower in VSMC of arteries from IH compared with sham-exposed rats. Furthermore, depolarizing VSMC by increasing luminal pressure (from 20 to 100 mmHg) or by elevating extracellular [K(+)] increased spark activity in VSMC of arteries from sham rats but had no effect in arteries from IH rats. Inhibiting endogenous H2S production in sham arteries prevented these increases. NaHS or phosphodiesterase inhibition increased spark activity to the same extent in sham and IH arteries. Depolarization-induced increases in Ca(2+) spark activity were due to increased sparks per site, whereas H2S increases in spark activity were due to increased spark sites per cell. Finally, inhibiting Ca(2+) spark activity with ryanodine (10 μM) enhanced myogenic tone in arteries from sham but not IH rats and blocked dilation to exogenous H2S in arteries from both sham and IH rats. Our results suggest that H2S regulates RyR activation and that H2S-induced dilation requires Ca(2+) spark activation. IH exposure decreases endogenous H2S-dependent Ca(2+) spark activation to cause membrane depolarization and enhance myogenic tone in mesenteric arteries.

  12. A biological/chemical process for reduced waste and energy consumption, Caprolactam production: Phase 1, Select microorganisms and demonstrate feasibility. Final report

    Energy Technology Data Exchange (ETDEWEB)

    St.Martin, E.J.

    1995-08-01

    A novel biological/chemical process for converting cyclohexane into caprolactam was investigated. Microorganisms in a bioreactor would be used to convert cyclohexane into caprolactone followed by chemical synthesis of caprolactam using ammonia. The proposed bioprocess would be more energy efficient and reduce byproducts and wastes that are generated by the current chemical process. We have been successful in isolating from natural soil and water samples two microorganisms that can utilize cyclohexane as a sole source of carbon and energy for growth. These microorganisms were shown to have the correct metabolic intermediates and enzymes to convert cyclohexane into cyclohexanol, cyclohexanone and caprolactone. Genetic techniques to create and select for caprolactone hydrolase negative-mutants are being developed. These blocked-mutants will be used to convert cyclohexane into caprolactone but, because of the block, be unable to metabolize the caprolactone further and excrete it as a final end product.

  13. Assessment of xylanase activity in dry storage as a potential method of reducing feedstock cost.

    Science.gov (United States)

    Smith, William A; Thompson, David N; Thompson, Vicki S; Radtke, Corey W; Carter, Brady

    2009-05-01

    Enzymatic preprocessing of lignocellulosic biomass in dry storage systems has the potential to improve feedstock characteristics and lower ethanol production costs. To assess the potential for endoxylanase activity at low water contents, endoxylanase activity was tested using a refined wheat arabinoxylan substrate and three commercial endoxylanases over the water activity range 0.21-1.0, corresponding to water contents of 5% to >60% (dry basis). Homogeneously mixed dry samples were prepared at a fixed enzyme to substrate ratio and incubated in chambers at a variety of fixed water activities. Replicates were sacrificed periodically, and endoxylanase activity was quantified as an increase in reducing sugar relative to desiccant-stored controls. Endoxylanase activity was observed at water activities over 0.91 in all enzyme preparations in less than 4 days and at a water activity of 0.59 in less than 1 week in two preparations. Endoxylanase activity after storage was confirmed for selected desiccant-stored controls by incubation at 100% relative humidity. Water content to water activity relationships were determined for three lignocellulosic substrates, and results indicate that two endoxylanase preparations retained limited activity as low as 7% to 13% water content (dry basis), which is well within the range of water contents representative of dry biomass storage. Future work will examine the effects of endoxylanase activity toward substrates such as corn stover, wheat straw, and switchgrass in low water content environments.

  14. Survival and virulence of Salmonella enterica serovar enteritidis filaments induced by reduced water activity.

    Science.gov (United States)

    Stackhouse, Robert R; Faith, Nancy G; Kaspar, Charles W; Czuprynski, Charles J; Wong, Amy C Lee

    2012-04-01

    Salmonella enterica serovar Enteritidis strain E40 filaments were developed under conditions of a reduced water activity (a(w)) of 0.95 in tryptic soy broth (TSB) or tryptic soy agar (TSA) supplemented with 8% or 7% NaCl, respectively. Filament formation was accompanied by an increase of biomass without an increase in CFU and was affected by incubation temperature and the physical milieu. The greatest amount of filaments was recovered from TSA with 7% NaCl and incubation at 30°C. Within 2 h of transfer to fresh TSB, filaments started to septate into normal-sized cells, resulting in a rapid increase in CFU. S. Enteritidis E40 filaments were not more tolerant of low- or high-temperature stresses than nonfilamented control cells. However, there was greater survival of filaments in 10% bile salts after 24 to 48 h of incubation, during pH 2.0 acid challenge for 10 min, and under desiccation on stainless steel surfaces at 25°C and 75.5% relative humidity for 7 days. S. Enteritidis E40 filaments invaded and multiplied within Caco-2 human intestinal epithelial cells to a similar degree as control cells when a comparable CFU of filaments and control cells was used. S. Enteritidis E40 filaments established a successful infection in mice via intragastric inoculation. The filaments colonized the gastrointestinal tract and disseminated to the spleen and liver at levels comparable to those attained by control cells, even when animals were inoculated with 10- to 100-fold fewer CFU. To our knowledge this is the first demonstration of virulence of stress-induced Salmonella filaments in vitro and in vivo. Formation of filaments by Salmonella in food products and food processing environments is significant to food safety, because detection and quantitation of the pathogen may be compromised. The finding that these filaments are virulent further enhances their potential public health impact.

  15. High salt reduces the activation of IL-4- and IL-13-stimulated macrophages.

    Science.gov (United States)

    Binger, Katrina J; Gebhardt, Matthias; Heinig, Matthias; Rintisch, Carola; Schroeder, Agnes; Neuhofer, Wolfgang; Hilgers, Karl; Manzel, Arndt; Schwartz, Christian; Kleinewietfeld, Markus; Voelkl, Jakob; Schatz, Valentin; Linker, Ralf A; Lang, Florian; Voehringer, David; Wright, Mark D; Hubner, Norbert; Dechend, Ralf; Jantsch, Jonathan; Titze, Jens; Müller, Dominik N

    2015-11-01

    A high intake of dietary salt (NaCl) has been implicated in the development of hypertension, chronic inflammation, and autoimmune diseases. We have recently shown that salt has a proinflammatory effect and boosts the activation of Th17 cells and the activation of classical, LPS-induced macrophages (M1). Here, we examined how the activation of alternative (M2) macrophages is affected by salt. In stark contrast to Th17 cells and M1 macrophages, high salt blunted the alternative activation of BM-derived mouse macrophages stimulated with IL-4 and IL-13, M(IL-4+IL-13) macrophages. Salt-induced reduction of M(IL-4+IL-13) activation was not associated with increased polarization toward a proinflammatory M1 phenotype. In vitro, high salt decreased the ability of M(IL-4+IL-13) macrophages to suppress effector T cell proliferation. Moreover, mice fed a high salt diet exhibited reduced M2 activation following chitin injection and delayed wound healing compared with control animals. We further identified a high salt-induced reduction in glycolysis and mitochondrial metabolic output, coupled with blunted AKT and mTOR signaling, which indicates a mechanism by which NaCl inhibits full M2 macrophage activation. Collectively, this study provides evidence that high salt reduces noninflammatory innate immune cell activation and may thus lead to an overall imbalance in immune homeostasis.

  16. Altered Biomarkers of Mucosal Immunity and Reduced Vaginal Lactobacillus Concentrations in Sexually Active Female Adolescents

    Science.gov (United States)

    Madan, Rebecca Pellett; Carpenter, Colleen; Fiedler, Tina; Kalyoussef, Sabah; McAndrew, Thomas C.; Viswanathan, Shankar; Kim, Mimi; Keller, Marla J.; Fredricks, David N.; Herold, Betsy C.

    2012-01-01

    Background Genital secretions collected from adult women exhibit in vitro activity against herpes simplex virus (HSV) and Escherichia coli (E. coli), but prior studies have not investigated this endogenous antimicrobial activity or its mediators in adolescent females. Methodology/Principal Findings Anti-HSV and anti-E.coli activity were quantified from cervicovaginal lavage (CVL) specimens collected from 20 sexually active adolescent females (15–18 years). Soluble immune mediators that may influence this activity were measured in CVL, and concentrations of Lactobacillus jensenii and crispatus were quantified by PCR from vaginal swabs. Results for adolescents were compared to those obtained from 54 healthy, premenopausal adult women. Relative to specimens collected from adults, CVL collected from adolescent subjects had significantly reduced activity against E. coli and diminished concentrations of protein, IgG, and IgA but significantly increased anti-HSV activity and concentrations of interleukin (IL)-1α, IL-6 and IL-1 receptor antagonist. Vaginal swabs collected from adolescent subjects had comparable concentrations of L. crispatus but significantly reduced concentrations of L. jensenii, relative to adult swabs. Conclusions/Significance Biomarkers of genital mucosal innate immunity may differ substantially between sexually active adolescents and adult women. These findings warrant further study and may have significant implications for prevention of sexually transmitted infections in adolescent females. PMID:22808157

  17. Tested Demonstrations.

    Science.gov (United States)

    Gilbert, George L.

    1990-01-01

    Included are three demonstrations that include the phase change of ice when under pressure, viscoelasticity and colloid systems, and flame tests for metal ions. The materials, procedures, probable results, and applications to real life situations are included. (KR)

  18. Tested Demonstrations.

    Science.gov (United States)

    Gilbert, George L., Ed.

    1980-01-01

    Presented is a Corridor Demonstration which can be set up in readily accessible areas such as hallways or lobbies. Equipment is listed for a display of three cells (solar cells, fuel cells, and storage cells) which develop electrical energy. (CS)

  19. Tested Demonstrations.

    Science.gov (United States)

    Gilbert, George L., Ed.

    1987-01-01

    Presents three demonstrations suitable for undergraduate chemistry classes. Focuses on experiments with calcium carbide, the induction by iron of the oxidation of iodide by dichromate, and the classical iodine clock reaction. (ML)

  20. Ovulation efficiency is reduced in mice that lack plasminogen activator gene function: functional redundancy among physiological plasminogen activators.

    Science.gov (United States)

    Leonardsson, G; Peng, X R; Liu, K; Nordström, L; Carmeliet, P; Mulligan, R; Collen, D; Ny, T

    1995-01-01

    Several lines of indirect evidence suggest that plasminogen activation plays a crucial role in degradation of the follicular wall during ovulation. However, single-deficient mice lacking tissue-type plasminogen activator (tPA), urokinase-type plasminogen activator (uPA), or PA inhibitor type 1(PAI-1) gene function were recently found to have normal reproduction, although mice with a combined deficiency of tPA and uPA were significantly less fertile. To investigate whether the reduced fertility of mice lacking PA gene function is due to a reduced ovulation mechanism, we have determined the ovulation efficiency in 25-day-old mice during gonadotropin-induced ovulation. Our results reveal that ovulation efficiency is normal in mice with a single deficiency of tPA or uPA but reduced by 26% in mice lacking both physiological PAs. This result suggests that plasminogen activation plays a role in ovulatory response, although neither tPA nor uPA individually or in combination is obligatory for ovulation. The loss of an individual PA seems to be functionally complemented by the remaining PA but this compensation does not appear to involve any compensatory up-regulation. Our data imply that a functionally redundant mechanism for plasmin formation operates during gonadotropin-induced ovulation and that PAs together with other proteases generate the proteolytic activity required for follicular wall degradation. Images Fig. 3 Fig. 4 PMID:8618918

  1. Tensile and impact behaviour of BATMAN II steels, Ti-bearing reduced activation martensitic alloys

    Science.gov (United States)

    Filacchioni, G.; Casagrande, E.; De Angelis, U.; De Santis, G.; Ferrara, D.; Pilloni, L.

    Two series of Reduced Activation Ferrous alloys (RAF) have been produced and studied by Casaccia's Laboratories. These martensitic alloys are named BATMAN steels. They are among the few presently developed RAF materials to exploit Ti as a carbide forming and grain size stabilizing element instead of Ta. In this work their mechanical properties are illustrated.

  2. Green synthesis and nanotopography of heparin-reduced gold nanoparticles with enhanced anticoagulant activity.

    Science.gov (United States)

    Kim, Hyun-Seok; Jun, Sang Hui; Koo, Yean Kyoung; Cho, Seonho; Park, Youmie

    2013-03-01

    This paper reports on the green synthesis of heparin-reduced gold nanoparticles and their nanotopography as studied with atomic force microscopy. The study also evaluated the anticoagulant activity of the newly prepared gold nanoparticles. The heparin-reduced gold nanoparticles were homogeneous, showing characteristic surface plasmon resonance bands of approximately 523-527 nm, and their shapes were mostly spherical and amorphous. The average diameter of the nanoparticles measured from atomic force microscopic images was either 20.26 +/- 3.35 nm or 40.85 +/- 8.95 nm depending on the different precursor salts and heparin concentrations. Atomic force microscopic images revealed that the topography of the heparin polymer aggregated when deposited onto mica, resembling a chain of mountains. This characteristic nanotopography of the heparin disappeared after the synthesis of the gold nanoparticles was performed. Interestingly, prolonged prothrombin time, thrombin time, and activated partial thromboplastin time were observed in the heparin-reduced gold nanoparticles when compared to a control heparin, suggesting the enhancement of anticoagulant activity in heparin-reduced gold nanoparticles. Hence, the green synthesis of gold nanoparticles with heparin using a simple reaction step could be a viable procedure for enhancing heparin's anticoagulant activity.

  3. High Resolution Ultrasound Imaging Using Adaptive Beamforming with Reduced Number of Active Elements

    DEFF Research Database (Denmark)

    Holfort, Iben Kraglund; Gran, Fredrik; Jensen, Jørgen Arendt

    2009-01-01

    is proposed. By reducing the number of active sensor elements, an increased resolution can be obtained with the MV beamformer. This observation is directly opposite the well-known relation between the spatial extent of the aperture and the achievable resolution. The investigations are based on Field II...

  4. Reducing GBA2 activity ameliorates neuropathology in niemann-pick type C mice

    NARCIS (Netherlands)

    A.R.A. Marques (André); J. Aten (Jan); R. Ottenhoff (Roelof); C.P.A.A. van Roomen (Cindy); D. Herrera Moro (Daniela); N. Claessen (Nike); M.F. Vinueza Veloz (Maria); K. Zhou (Kuikui); Z. Lin (Zhanmin); M. Mirzaian (Mina); R.G. Boot (Rolf); C.I. de Zeeuw (Chris); H.S. Overkleeft (Herman); Y. Yildiz (Yildiz); J.M.F.G. Aerts (Johannes)

    2015-01-01

    textabstractThe enzyme glucocerebrosidase (GBA) hydrolyses glucosylceramide (GlcCer) in lysosomes. Markedly reduced GBA activity is associated with severe manifestations of Gaucher disease including neurological involvement. Mutations in the GBA gene have recently also been identified as major genet

  5. Reducing GBA2 Activity Ameliorates Neuropathology in Niemann-Pick Type C Mice

    NARCIS (Netherlands)

    Marques, André R A; Aten, Jan; Ottenhoff, Roelof; van Roomen, Cindy P A A; Herrera Moro, Daniela; Claessen, Nike; Vinueza Veloz, María Fernanda; Zhou, Kuikui; Lin, Zhanmin; Mirzaian, Mina; Boot, Rolf G; De Zeeuw, Chris I; Overkleeft, Herman S; Yildiz, Yildiz; Aerts, Johannes M F G

    2015-01-01

    The enzyme glucocerebrosidase (GBA) hydrolyses glucosylceramide (GlcCer) in lysosomes. Markedly reduced GBA activity is associated with severe manifestations of Gaucher disease including neurological involvement. Mutations in the GBA gene have recently also been identified as major genetic risk fact

  6. Initial Evaluation of Active Minds: A Student Organization Dedicated to Reducing the Stigma of Mental Illness

    Science.gov (United States)

    McKinney, Kathleen G.

    2009-01-01

    This study examined whether a new student organization, Active Minds, aimed at increasing awareness of "mental illness" and reducing stigma had an impact on students' stigma and willingness to seek psychological help. Three classes were recruited to become involved in the organization. In a pretest/posttest design, stigma and willingness to seek…

  7. A multi coding technique to reduce transition activity in VLSI circuits

    Science.gov (United States)

    Vithyalakshmi, N.; Rajaram, M.

    2014-02-01

    Advances in VLSI technology have enabled the implementation of complex digital circuits in a single chip, reducing system size and power consumption. In deep submicron low power CMOS VLSI design, the main cause of energy dissipation is charging and discharging of internal node capacitances due to transition activity. Transition activity is one of the major factors that also affect the dynamic power dissipation. This paper proposes power reduction analyzed through algorithm and logic circuit levels. In algorithm level the key aspect of reducing power dissipation is by minimizing transition activity and is achieved by introducing a data coding technique. So a novel multi coding technique is introduced to improve the efficiency of transition activity up to 52.3% on the bus lines, which will automatically reduce the dynamic power dissipation. In addition, 1 bit full adders are introduced in the Hamming distance estimator block, which reduces the device count. This coding method is implemented using Verilog HDL. The overall performance is analyzed by using Modelsim and Xilinx Tools. In total 38.2% power saving capability is achieved compared to other existing methods.

  8. Initial Evaluation of Active Minds: A Student Organization Dedicated to Reducing the Stigma of Mental Illness

    Science.gov (United States)

    McKinney, Kathleen G.

    2009-01-01

    This study examined whether a new student organization, Active Minds, aimed at increasing awareness of "mental illness" and reducing stigma had an impact on students' stigma and willingness to seek psychological help. Three classes were recruited to become involved in the organization. In a pretest/posttest design, stigma and willingness to seek…

  9. Dietary fiber stabilizes blood glucose and insulin levels and reduces physical activity in sows (Sus scrofa)

    NARCIS (Netherlands)

    Leeuw, de J.A.; Jongbloed, A.W.; Verstegen, M.W.A.

    2004-01-01

    The aim of this study was to test whether a diet with a high level of fermentable dietary fiber can stabilize interprandial blood glucose and insulin levels, prevent declines below basal levels, and reduce physical activity in limited-fed breeding sows. Stable levels of glucose and insulin may preve

  10. Voluntary access to a warm plate reduces hyperactivity in activity-based anorexia

    NARCIS (Netherlands)

    Hillebrand, Jacquelien J G; de Rijke, Corine E; Brakkee, Jan H; Kas, Martien J H; Adan, Roger A H

    2005-01-01

    Activity-based anorexia (ABA) is considered an animal model of anorexia nervosa. In ABA, scheduled feeding in combination with voluntary wheel running leads to hyperactivity, reduced food intake, severe body weight loss and hypothermia. In this study it was investigated whether hyperactivity in ABA

  11. Dietary fiber stabilizes blood glucose and insulin levels and reduces physical activity in sows (Sus scrofa)

    NARCIS (Netherlands)

    Leeuw, de J.A.; Jongbloed, A.W.; Verstegen, M.W.A.

    2004-01-01

    The aim of this study was to test whether a diet with a high level of fermentable dietary fiber can stabilize interprandial blood glucose and insulin levels, prevent declines below basal levels, and reduce physical activity in limited-fed breeding sows. Stable levels of glucose and insulin may preve

  12. Active Lubrication: Feasibility and Limitations on Reducing Vibration in Rotating Machinery

    DEFF Research Database (Denmark)

    Nicoletti, Rodrigo; Santos, Ilmar

    2003-01-01

    In the present work, experimental results show the feasibility of reducing the amplitude of resonance peaks in rotor-bearing test rig, in the frequency domain, by using active lubricated bearings. The most important consequence of this vibration reduction in rotating machines is the feasibility o...

  13. Active Lubrication: Feasibility and Limitations on Reducing Vibration in Rotating Machinery

    DEFF Research Database (Denmark)

    Nicoletti, Rodrigo; Santos, Ilmar

    2004-01-01

    In the present work, experimental results show the feasibility of reducing the amplitude of resonance peaks in rotor-bearing test rig, in the frequency domain, by using active lubricated bearings. The most important consequence of this vibration reduction in rotating machines is the feasibility o...

  14. Reduced ADAMTS13 activity is associated with thrombotic risk in systemic lupus erythematosus.

    Science.gov (United States)

    Martin-Rodriguez, S; Reverter, J C; Tàssies, D; Espinosa, G; Heras, M; Pino, M; Escolar, G; Diaz-Ricart, M

    2015-10-01

    Severe deficiency of ADAMTS13 activity leads to von Willebrand factor (VWF) ultralarge multimers with high affinity for platelets, causing thrombotic thrombocytopenic purpura. Other pathological conditions with moderate ADAMTS13 activity exhibit a thrombotic risk. We examined the ADAMTS13 activity in systemic lupus erythematosus (SLE) and its value as a thrombotic biomarker. ADAMTS13 activity, VWF antigen and multimeric structure, and vascular cell adhesion molecule 1 (VCAM-1) were measured in plasma samples from 50 SLE patients and 50 healthy donors. Disease activity (systemic lupus erythematosus disease activity index; SLEDAI) and organ damage (systemic lupus international collaborating clinics) scores, thrombotic events, antiphospholipid syndrome (APS) and antiphospholipid antibodies (aPLs) were registered. SLE patients showed decreased ADAMTS13 activity and high VWF levels compared with controls (66 ± 27% vs. 101 ± 8%, P 60%, 60-40% and <40%), comparative analysis showed significant association between ADAMTS13 activity and SLEDAI (P < 0.05), presence of aPLs (P < 0.001), APS (P < 0.01) and thrombotic events (P < 0.01). Reduced ADAMTS13 activity together with increased VWF levels were especially notable in patients with active disease and with aPLs. ADAMTS13 activity, in combination with other laboratory parameters, could constitute a potential prognostic biomarker of thrombotic risk in SLE. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  15. Contribution of chlorogenic acids to the iron-reducing activity of coffee beverages.

    Science.gov (United States)

    Moreira, Daniel P; Monteiro, Mariana C; Ribeiro-Alves, Mirna; Donangelo, Carmen M; Trugo, Luiz C

    2005-03-09

    The iron-reducing activity of coffee beverages was determined by the ferric reducing antioxidant power (FRAP) assay. The influence on FRAP due to the degree of roasting (light, medium, and dark), species (Coffea arabica and Coffea robusta), and caffeine content (regular and decaffeinated) was investigated using ground and soluble coffee samples. The concentration of specific chlorogenic acids and caffeine in the beverages was determined by high-performance liquid chromatography and related to FRAP using Pearson correlation coefficients. All measurements were expressed per unit of soluble solids. Beverages prepared with ground coffee had, on average, 27% higher FRAP values than those prepared with soluble coffee (p 0.91) was found between FRAP and the total content of chlorogenic acids, particularly that of the caffeoylquinic acid isomers. The iron-reducing activity of coffee beverages was not influenced by caffeine.

  16. Placental Vesicles Carry Active Endothelial Nitric Oxide Synthase and Their Activity is Reduced in Preeclampsia.

    Science.gov (United States)

    Motta-Mejia, Carolina; Kandzija, Neva; Zhang, Wei; Mhlomi, Vuyane; Cerdeira, Ana Sofia; Burdujan, Alexandra; Tannetta, Dionne; Dragovic, Rebecca; Sargent, Ian L; Redman, Christopher W; Kishore, Uday; Vatish, Manu

    2017-08-01

    Preeclampsia, a multisystem hypertensive disorder of pregnancy, is associated with increased systemic vascular resistance. Placentae from patients with preeclampsia have reduced levels of endothelial nitric oxide synthase (eNOS) and, thus, less nitric oxide (NO). Syncytiotrophoblast extracellular vesicles (STBEV), comprising microvesicles (STBMV) and exosomes, carry signals from the syncytiotrophoblast to the mother. We hypothesized that STBEV-bound eNOS (STBEV-eNOS), capable of producing NO, are released into the maternal circulation. Dual-lobe ex vivo placental perfusion and differential centrifugation was used to isolate STBEV from preeclampsia (n=8) and normal pregnancies (NP; n=11). Plasma samples of gestational age-matched preeclampsia and NP (n=6) were used to isolate circulating STBMV. STBEV expressed placental alkaline phosphatase, confirming placental origin. STBEV coexpressed eNOS, but not inducible nitric oxide synthase, confirmed using Western blot, flow cytometry, and immunodepletion. STBEV-eNOS produced NO, which was significantly inhibited by N  (G)-nitro-l-arginine methyl ester (eNOS inhibitor; Ppreeclampsia-perfused placentae had lower levels of STBEV-eNOS (STBMV; Ppreeclampsia women had lower STBEV-eNOS expression compared with that from NP women (Ppreeclampsia placentae, as well as in plasma. The lower STBEV-eNOS NO production seen in preeclampsia may contribute to the decreased NO bioavailability in this disease. © 2017 The Authors.

  17. Reduced Specificity of Hippocampal and Posterior Ventrolateral Prefrontal Activity during Relational Retrieval in Normal Aging

    Science.gov (United States)

    Giovanello, Kelly S.; Schacter, Daniel L.

    2012-01-01

    Neuroimaging studies of episodic memory in young adults demonstrate greater functional neural activity in ventrolateral pFC and hippocampus during retrieval of relational information as compared with item information. We tested the hypothesis that healthy older adults--individuals who exhibit behavioral declines in relational memory--would show…

  18. Pilot-scale treatability testing -- Recycle, reuse, and disposal of materials from decontamination and decommissioning activities: Soda blasting demonstration

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    1995-08-01

    The US Department of Energy (DOE) is in the process of defining the nature and magnitude of decontamination and decommissioning (D and D) obligations at its sites. With disposal costs rising and available storage facilities decreasing, DOE is exploring and implementing new waste minimizing D and D techniques. Technology demonstrations are being conducted by LMES at a DOE gaseous diffusion processing plant, the K-25 Site, in Oak Ridge, Tennessee. The gaseous diffusion process employed at Oak Ridge separated uranium-235 from uranium ore for use in atomic weapons and commercial reactors. These activities contaminated concrete and other surfaces within the plant with uranium, technetium, and other constituents. The objective of current K-25 D and D research is to make available cost-effective and energy-efficient techniques to advance remediation and waste management methods at the K-25 Site and other DOE sites. To support this objective, O`Brien and Gere tested a decontamination system on K-25 Site concrete and steel surfaces contaminated with radioactive and hazardous waste. A scouring system has been developed that removes fixed hazardous and radioactive surface contamination and minimizes residual waste. This system utilizes an abrasive sodium bicarbonate medium that is projected at contaminated surfaces. It mechanically removes surface contamination while leaving the surface intact. Blasting residuals are captured and dissolved in water and treated using physical/chemical processes. Pilot-scale testing of this soda blasting system and bench and pilot-scale treatment of the generated residuals were conducted from December 1993 to September 1994.

  19. RADIOACTIVE DEMONSTRATIONS OF FLUIDIZED BED STEAM REFORMING WITH ACUTAL HANFORD LOW ACTIVITY WASTES VERIFYING FBSR AS A SUPPLEMENTARY TREATMENT

    Energy Technology Data Exchange (ETDEWEB)

    Jantzen, C.; Crawford, C.; Burket, P.; Bannochie, C.; Daniel, G.; Nash, C.; Cozzi, A.; Herman, C.

    2012-01-12

    The U.S. Department of Energy's Office of River Protection is responsible for the retrieval, treatment, immobilization, and disposal of Hanford's tank waste. Currently there are approximately 56 million gallons of highly radioactive mixed wastes awaiting treatment. A key aspect of the River Protection Project cleanup mission is to construct and operate the Waste Treatment and Immobilization Plant (WTP). The WTP will separate the tank waste into high-level waste (HLW) and low-activity waste (LAW) fractions, both of which will subsequently be vitrified. The projected throughput capacity of the WTP LAW Vitrification Facility is insufficient to complete the cleanup mission in the time frame required by the Hanford Federal Facility Agreement and Consent Order, also known as the Tri-Party Agreement (TPA). Therefore, Supplemental Treatment is required both to meet the TPA treatment requirements as well as to more cost effectively complete the tank waste treatment mission. Fluidized Bed Steam Reforming (FBSR) is one of the supplementary treatments being considered. FBSR offers a moderate temperature (700-750 C) continuous method by which LAW and other secondary wastes can be processed irrespective of whether they contain organics, nitrates/nitrites, sulfates/sulfides, chlorides, fluorides, and/or radio-nuclides like I-129 and Tc-99. Radioactive testing of Savannah River LAW (Tank 50) shimmed to resemble Hanford LAW and actual Hanford LAW (SX-105 and AN-103) have produced a ceramic (mineral) waste form which is the same as the non-radioactive waste simulants tested at the engineering scale. The radioactive testing demonstrated that the FBSR process can retain the volatile radioactive components that cannot be contained at vitrification temperatures. The radioactive and nonradioactive mineral waste forms that were produced by co-processing waste with kaolin clay in an FBSR process are shown to be as durable as LAW glass.

  20. Cyclic instability of martensite laths in reduced activation ferritic/martensitic steels

    Energy Technology Data Exchange (ETDEWEB)

    Armas, A.F.; Petersen, C. E-mail: claus.petersen@imf.fzk.de; Schmitt, R.; Avalos, M.; Alvarez, I

    2004-08-01

    Low cycle fatigue tests were performed in the temperature range between room temperature and 550 deg. C in low activation quenched and tempered steels. After the first few cycles a pronounced cyclic softening that continues up to failure is observed for all these steels. Although this softening is coincident with similar behaviour observed in commercial martensitic alloys, reduced activation steels present some remarkable different features. Almost all cyclic curves never reach a saturation stress and after few cycles, dependent on the total strain range, they converge in a common softening stage independent of the strain range. The mechanism governing this softening stage is almost independent of temperatures below 450 deg. C. The cyclic softening observed in the reduced activation steels is more pronounced than for MANET II and commercial martensitic steels. This fact is related to the difference in the Martensite Start temperature.

  1. An Active Learning Classifier for Further Reducing Diabetic Retinopathy Screening System Cost

    Directory of Open Access Journals (Sweden)

    Yinan Zhang

    2016-01-01

    Full Text Available Diabetic retinopathy (DR screening system raises a financial problem. For further reducing DR screening cost, an active learning classifier is proposed in this paper. Our approach identifies retinal images based on features extracted by anatomical part recognition and lesion detection algorithms. Kernel extreme learning machine (KELM is a rapid classifier for solving classification problems in high dimensional space. Both active learning and ensemble technique elevate performance of KELM when using small training dataset. The committee only proposes necessary manual work to doctor for saving cost. On the publicly available Messidor database, our classifier is trained with 20%–35% of labeled retinal images and comparative classifiers are trained with 80% of labeled retinal images. Results show that our classifier can achieve better classification accuracy than Classification and Regression Tree, radial basis function SVM, Multilayer Perceptron SVM, Linear SVM, and K Nearest Neighbor. Empirical experiments suggest that our active learning classifier is efficient for further reducing DR screening cost.

  2. Arctigenin Inhibits Adipogenesis by Inducing AMPK Activation and Reduces Weight Gain in High-Fat Diet-Induced Obese Mice.

    Science.gov (United States)

    Han, Yo-Han; Kee, Ji-Ye; Park, Jinbong; Kim, Hye-Lin; Jeong, Mi-Young; Kim, Dae-Seung; Jeon, Yong-Deok; Jung, Yunu; Youn, Dong-Hyun; Kang, JongWook; So, Hong-Seob; Park, Raekil; Lee, Jong-Hyun; Shin, Soyoung; Kim, Su-Jin; Um, Jae-Young; Hong, Seung-Heon

    2016-09-01

    Although arctigenin (ARC) has been reported to have some pharmacological effects such as anti-inflammation, anti-cancer, and antioxidant, there have been no reports on the anti-obesity effect of ARC. The aim of this study is to investigate whether ARC has an anti-obesity effect and mediates the AMP-activated protein kinase (AMPK) pathway. We investigated the anti-adipogenic effect of ARC using 3T3-L1 pre-adipocytes and human adipose tissue-derived mesenchymal stem cells (hAMSCs). In high-fat diet (HFD)-induced obese mice, whether ARC can inhibit weight gain was investigated. We found that ARC reduced weight gain, fat pad weight, and triglycerides in HFD-induced obese mice. ARC also inhibited the expression of peroxisome proliferator-activated receptor gamma (PPARγ) and CCAAT/enhancer-binding protein alpha (C/EBPα) in in vitro and in vivo. Furthermore, ARC induced the AMPK activation resulting in down-modulation of adipogenesis-related factors including PPARγ, C/EBPα, fatty acid synthase, adipocyte fatty acid-binding protein, and lipoprotein lipase. This study demonstrates that ARC can reduce key adipogenic factors by activating the AMPK in vitro and in vivo and suggests a therapeutic implication of ARC for obesity treatment. J. Cell. Biochem. 117: 2067-2077, 2016. © 2016 Wiley Periodicals, Inc.

  3. α-Solanine inhibits human melanoma cell migration and invasion by reducing matrix metalloproteinase-2/9 activities.

    Science.gov (United States)

    Lu, Ming-Kun; Shih, Yuan-Wei; Chang Chien, Tzu-Tsung; Fang, Li-Heng; Huang, Hsiang-Ching; Chen, Pin-Shern

    2010-01-01

    α-Solanine, a naturally occurring steroidal glycoalkaloid in potato sprouts, was found to possess anti-carcinogenic properties, such as inhibiting proliferation and inducing apoptosis of tumor cells. However, the effect of α-solanine on cancer metastasis remains unclear. In the present study, we examined the effect of α-solanine on metastasis in vitro. Data demonstrated that α-solanine inhibited proliferation of human melanoma cell line A2058 in a dose-dependent manner. When treated with non-toxic doses of α-solanine, cell migration and invasion were markedly suppressed. Furthermore, α-solanine reduced the activity of matrix metalloproteinase-2 (MMP-2) and MMP-9, which are involved in the migration and invasion of cancer cells. Our biochemical assays indicated that α-solanine potently suppressed the phosphorylation of c-Jun N-terminal kinase (JNK), phosphatidylinositide-3 kinase (PI3K) and Akt, while it did not affect phosphorylation of extracellular signal regulating kinase (ERK). In addition, α-solanine significantly decreased the nuclear level of nuclear factor kappa B (NF-κB), suggesting that α-solanine inhibited NF-κB activity. Taken together, the results suggested that α-solanine inhibited migration and invasion of A2058 cells by reducing MMP-2/9 activities. It also inhibited JNK and PI3K/Akt signaling pathways as well as NF-κB activity. These findings reveal new therapeutic potential for α-solanine in anti-metastatic therapy.

  4. Free radical scavenging activity and reducing power of Acacia nilotica wood lignin.

    Science.gov (United States)

    Aadil, Keshaw Ram; Barapatre, Anand; Sahu, Sudha; Jha, Harit; Tiwary, Bhupendra Nath

    2014-06-01

    Nine different fractions of lignin extracted by alkali, hot water and organosolv methods from Acacia wood powder were assessed for antioxidants activity. Results indicated that methanolic lignin fraction had highest polyphenol content of 393.30±9.2μg/ml (GAE). The oraganosolv lignin with total phenols and phenolic hydroxyl group content exhibited significant antioxidant activity as compared to other lignin fractions. Antioxidant properties of acetone fractions revealed a high antiradical scavenging activity (extraction methods on functional groups of lignin fractions was confirmed by analytical methods and Fourier transform infrared spectroscopy (FTIR) analysis. Whereas the phenolic content showed strong correlation with reducing capacity, the antiradical activity was moderately correlated with phenolic content. A high phenolic hydroxyl groups content of organosolv lignin fractions provides evidence for the presence of active therapeutic antioxidant compounds for their testing as potential value added products for cosmetics and pharmaceutical industries. Copyright © 2014 Elsevier B.V. All rights reserved.

  5. Tested Demonstrations.

    Science.gov (United States)

    Gilbert, George L., Ed.

    1987-01-01

    Describes two demonstrations to illustrate characteristics of substances. Outlines a method to detect the changes in pH levels during the electrolysis of water. Uses water pistols, one filled with methane gas and the other filled with water, to illustrate the differences in these two substances. (TW)

  6. ICT Demonstration

    DEFF Research Database (Denmark)

    Jensen, Tine Wirenfeldt; Bay, Gina

    In this demonstration we present and discuss two interrelated on-line learning resources aimed at supporting international students at Danish universities in building study skills (the Study Metro) and avoiding plagiarism (Stopplagiarism). We emphasize the necessity of designing online learning r...

  7. Mesenchymal Stem/Multipotent Stromal Cells from Human Decidua Basalis Reduce Endothelial Cell Activation.

    Science.gov (United States)

    Alshabibi, Manal A; Al Huqail, Al Joharah; Khatlani, Tanvir; Abomaray, Fawaz M; Alaskar, Ahmed S; Alawad, Abdullah O; Kalionis, Bill; Abumaree, Mohamed Hassan

    2017-09-15

    Recently, we reported the isolation and characterization of mesenchymal stem cells from the decidua basalis of human placenta (DBMSCs). These cells express a unique combination of molecules involved in many important cellular functions, which make them good candidates for cell-based therapies. The endothelium is a highly specialized, metabolically active interface between blood and the underlying tissues. Inflammatory factors stimulate the endothelium to undergo a change to a proinflammatory and procoagulant state (ie, endothelial cell activation). An initial response to endothelial cell activation is monocyte adhesion. Activation typically involves increased proliferation and enhanced expression of adhesion and inflammatory markers by endothelial cells. Sustained endothelial cell activation leads to a type of damage to the body associated with inflammatory diseases, such as atherosclerosis. In this study, we examined the ability of DBMSCs to protect endothelial cells from activation through monocyte adhesion, by modulating endothelial proliferation, migration, adhesion, and inflammatory marker expression. Endothelial cells were cocultured with DBMSCs, monocytes, monocyte-pretreated with DBMSCs and DBMSC-pretreated with monocytes were also evaluated. Monocyte adhesion to endothelial cells was examined following treatment with DBMSCs. Expression of endothelial cell adhesion and inflammatory markers was also analyzed. The interaction between DBMSCs and monocytes reduced endothelial cell proliferation and monocyte adhesion to endothelial cells. In contrast, endothelial cell migration increased in response to DBMSCs and monocytes. Endothelial cell expression of adhesion and inflammatory molecules was reduced by DBMSCs and DBMSC-pretreated with monocytes. The mechanism of reduced endothelial proliferation involved enhanced phosphorylation of the tumor suppressor protein p53. Our study shows for the first time that DBMSCs protect endothelial cells from activation by

  8. Toll-Like Receptor 4 Reduces Oxidative Injury via Glutathione Activity in Sheep

    Directory of Open Access Journals (Sweden)

    Shoulong Deng

    2016-01-01

    Full Text Available Toll-like receptor 4 (TLR4 is an important sensor of Gram-negative bacteria and can trigger activation of the innate immune system. Increased activation of TLR4 can lead to the induction of oxidative stress. Herein, the pathway whereby TLR4 affects antioxidant activity was studied. In TLR4-overexpressing sheep, TLR4 expression was found to be related to the integration copy number when monocytes were challenged with lipopolysaccharide (LPS. Consequently, production of malondialdehyde (MDA was increased, which could increase the activation of prooxidative stress enzymes. Meanwhile, activation of an antioxidative enzyme, glutathione peroxidase (GSH-Px, was increased. Real-time PCR showed that expression of activating protein-1 (AP-1 and the antioxidative-related genes was increased. By contrast, the expression levels of superoxide dismutase 1 (SOD1 and catalase (CAT were reduced. In transgenic sheep, glutathione (GSH levels were dramatically reduced. Furthermore, transgenic sheep were intradermally injected with LPS in each ear. The amounts of inflammatory infiltrates were correlated with the number of TLR4 copies that were integrated in the genome. Additionally, the translation of γ-glutamylcysteine synthetase (γ-GCS was increased. Our findings indicated that overexpression of TLR4 in sheep could ameliorate oxidative injury through GSH secretion that was induced by LPS stimulation. Furthermore, TLR4 promoted γ-GCS translation through the AP-1 pathway, which was essential for GSH synthesis.

  9. Field Demonstration of Active Desiccant Modules Designed to Integrate with Standard Unitary Rooftop Package Equipment - Final Report: Phase 3

    Energy Technology Data Exchange (ETDEWEB)

    Fischer, J

    2004-03-15

    This report summarizes the investigation of two active desiccant module (ADM) pilot site installations initiated in 2001. Both pilot installations were retrofits at existing facilities served by conventional heating, ventilating, and air-conditioning (HVAC) systems that had encountered frequent humidity control, indoor air quality (IAQ), and other operational problems. Each installation involved combining a SEMCO, Inc., ADM (as described in Fischer and Sand 2002) with a standard packaged rooftop unit built by the Trane Company. A direct digital control (DDC) system integral to the ADM performed the dual function of controlling the ADM/rooftop combination and facilitating data collection, trending, and remote performance monitoring. The first installation involved providing preconditioned outdoor air to replace air exhausted from the large kitchen hood and bathrooms of a Hooters restaurant located in Rome, Georgia. This facility had previously added an additional rooftop unit in an attempt to achieve occupant comfort without success. The second involved conditioning the outdoor air delivered to each room of a wing of the Mountain Creek Inn at the Callaway Gardens resort. This hotel, designed in the ''motor lodge'' format with each room opening to the outdoors, is located in southwest Georgia. Controlling the space humidity always presented a serious challenge. Uncomfortable conditions and musty odors had caused many guests to request to move to other areas within the resort. This is the first field demonstration performed by Oak Ridge National Laboratory where significant energy savings, operating cost savings, and dramatically improved indoor environmental conditions can all be claimed as the results of a retrofit desiccant equipment field installation. The ADM/rooftop combination installed at the restaurant resulted in a reduction of about 34% in the electricity used by the building's air-conditioning system. This represents a reduction of

  10. Reduced muscle activation during exercise related to brain oxygenation and metabolism in humans

    DEFF Research Database (Denmark)

    Rasmussen, P; Nielsen, J; Overgaard, M

    2010-01-01

    to the ability to generate a maximal voluntary contraction and to the transcranial magnetic stimulated force generation. To determine the role of a reduced OCI and in central fatigue, 16 males performed low intensity, maximal intensity and hypoxic cycling exercise. Exercise fatigue was evaluated by ratings...... of perceived exertion (RPE), arm maximal voluntary force (MVC), and voluntary activation of elbow flexor muscles assessed with transcranial magnetic stimulation. Low intensity exercise did not produce any indication of central fatigue or marked cerebral metabolic deviations. Exercise in hypoxia (0.10) reduced...

  11. Low Amount of Salinomycin Greatly Increases Akt Activation, but Reduces Activated p70S6K Levels

    Directory of Open Access Journals (Sweden)

    Sungpil Yoon

    2013-08-01

    Full Text Available The present study identified a novel salinomycin (Sal-sensitization mechanism in cancer cells. We analyzed the signal proteins Akt, Jnk, p38, Jak, and Erk1/2 in cancer cell lines that had arrested growth following low amounts of Sal treatment. We also tested the signal molecules PI3K, PDK1, GSK3β, p70S6K, mTOR, and PTEN to analyze the PI3K/Akt/mTOR pathway. The results showed that Sal sensitization positively correlates with large reductions in p70S6K activation. Interestingly, Akt was the only signal protein to be significantly activated by Sal treatment. The Akt activation appeared to require the PI3K pathway as its activation was abolished by the PI3K inhibitors LY294002 and wortmannin. The Akt activation by Sal was conserved in the other cell lines analyzed, which originated from other organs. Both Akt activation and C-PARP production were proportionally increased with increased doses of Sal. In addition, the increased levels of pAkt were not reduced over the time course of the experiment. Co-treatment with Akt inhibitors sensitized the Sal-treated cancer cells. The results thereby suggest that Akt activation is increased in cells that survive Sal treatment and resist the cytotoxic effect of Sal. Taken together; these results indicate that Akt activation may promote the resistance of cancer cells to Sal.

  12. [Physical activity programmes to reduce overweight and obesity in children and adolescents; a systematic review].

    Science.gov (United States)

    Aguilar Cordero, M J; Ortegón Piñero, A; Mur Vilar, N; Sánchez García, J C; García Verazaluce, J J; García García, I; Sánchez López, A M

    2014-10-01

    Obesity treatment has been the subject of much controversy; various authors have recommended the application of a comprehensive treatment programme, and in the light of this previous research, we consider the question of what is the most effective programme of physical activity to reduce overweight and obesity in children and adolescents. To analyse major studies on the effectiveness of physical activity in reducing overweight and obesity in children and adolescents. Systematic review of the results of physical activity programmes, published in scientific articles, to reduce overweight and obesity. Using an automated database search in PubMed and Google Scholar, conducted from October 2013 to March 2014, we identified 85 valid items. In selecting the items, the criteria applied included the usefulness and relevance of the subject matter and the credibility or experience of the research study authors. The internal and external validity of each of the articles reviewed was taken into account. This review confirmed the effectiveness of physical activity in reducing overweight and obesity in children and adolescents. The most effective programmes were those combining aerobic and anaerobic exercises. It is generally accepted that at least 180 minutes per week should be dedicated to exercise, in the form of three 60-minute sessions of moderate intensity. Such programmes could be sufficient for persons with overweight or obesity. Researchers in this field agree that when a diet based on an appropriate distribution of meals is combined with regular physical activity, they reinforce each other, and thus optimum results are obtained. Weight reduction programmes that take account of family involvement are more effective than nutrition education itself or other routine interventions that fail to consider family involvement. The role of pa rents and of the persons around the child or adolescent is essential to reinforce positive behaviour toward lifestyle change. Copyright AULA

  13. Turbulent Pumping of Magnetic Flux Reduces Solar Cycle Memory and thus Impacts Predictability of the Sun's Activity

    CERN Document Server

    Karak, Bidya Binay

    2012-01-01

    Prediction of the Sun's magnetic activity is important because of its effect on space environmental conditions and climate. However, recent efforts to predict the amplitude of the solar cycle have resulted in diverging forecasts with no consensus. It is understood that the dynamical memory of the solar dynamo mechanism governs predictability and this memory is different for advection- and diffusion-dominated solar convection zones. By utilizing stochastically forced, kinematic dynamo simulations, we demonstrate that the inclusion of downward turbulent pumping of magnetic flux reduces the memory of both advection- and diffusion-dominated solar dynamos to only one cycle; stronger pumping degrades this memory further. We conclude that reliable predictions for the maximum of solar activity can be made only at the preceding minimum and for more accurate predictions, sequential data assimilation would be necessary in forecasting models to account for the Sun's short memory.

  14. Thiocoraline activates the Notch pathway in carcinoids and reduces tumor progression in vivo.

    Science.gov (United States)

    Wyche, T P; Dammalapati, A; Cho, H; Harrison, A D; Kwon, G S; Chen, H; Bugni, T S; Jaskula-Sztul, R

    2014-12-01

    Carcinoids are slow-growing neuroendocrine tumors (NETs) that are characterized by hormone overproduction; surgery is currently the only option for treatment. Activation of the Notch pathway has previously been shown to have a role in tumor suppression in NETs. The marine-derived thiodepsipeptide thiocoraline was investigated in vitro in two carcinoid cell lines (BON and H727). Carcinoid cells treated with nanomolar concentrations of thiocoraline resulted in a decrease in cell proliferation and an alteration of malignant phenotype evidenced by decrease of NET markers, achaete-scute complex like-1, chromogranin A and neurospecific enolase. Western blotting analysis demonstrated the activation of Notch1 on the protein level in BON cells. Additionally, thiocoraline activated downstream Notch targets HES1, HES5 and HEY2. Thiocoraline effectively suppressed carcinoid cell growth by promoting cell cycle arrest in BON and H727 cells. An in vivo study demonstrated that thiocoraline, formulated with polymeric micelles, slowed carcinoid tumor progression. Thus the therapeutic potential of thiocoraline, which induced activation of the Notch pathway, in carcinoid tumors was demonstrated.

  15. Polarized Light Corridor Demonstrations.

    Science.gov (United States)

    Davies, G. R.

    1990-01-01

    Eleven demonstrations of light polarization are presented. Each includes a brief description of the apparatus and the effect demonstrated. Illustrated are strain patterns, reflection, scattering, the Faraday Effect, interference, double refraction, the polarizing microscope, and optical activity. (CW)

  16. Reduced salience and default mode network activity in women with anorexia nervosa

    Science.gov (United States)

    McFadden, Kristina L.; Tregellas, Jason R.; Shott, Megan E.; Frank, Guido K.W.

    2014-01-01

    Background The neurobiology of anorexia nervosa is poorly understood. Neuronal networks contributing to action selection, self-regulation and interoception could contribute to pathologic eating and body perception in people with anorexia nervosa. We tested the hypothesis that the salience network (SN) and default mode network (DMN) would show decreased intrinsic activity in women with anorexia nervosa and those who had recovered from the disease compared to controls. The basal ganglia (BGN) and sensorimotor networks (SMN) were also investigated. Methods Between January 2008 and January 2012, women with restricting-type anorexia nervosa, women who recovered from the disease and healthy control women completed functional magnetic resonance imaging during a conditioned stimulus task. Network activity was studied using independent component analysis. Results We studied 20 women with anorexia nervosa, 24 recovered women and 24 controls. Salience network activity in the anterior cingulate cortex was reduced in women with anorexia nervosa (p = 0.030; all results false-discovery rate–corrected) and recovered women (p = 0.039) compared to controls. Default mode network activity in the precuneus was reduced in women with anorexia compared to controls (p = 0.023). Sensorimotor network activity in the supplementary motor area (SMA; p = 0.008), and the left (p = 0.028) and right (p = 0.002) postcentral gyrus was reduced in women with anorexia compared to controls; SMN activity in the SMA (p = 0.019) and the right postcentral gyrus (p = 0.008) was reduced in women with anorexia compared to recovered women. There were no group differences in the BGN. Limitations Differences between patient and control populations (e.g., depression, anxiety, medication) are potential confounds, but were included as covariates. Conclusion Reduced SN activity in women with anorexia nervosa and recovered women could be a trait-related biomarker or illness remnant, altering the drive to approach

  17. Enhanced Catalytic Activity of Pt Supported on Nitrogen-Doped Reduced Graphene Oxide Electrodes for Fuel Cells.

    Science.gov (United States)

    Sun, Qizhong; Park, Soo-Jin; Kim, Seok

    2015-11-01

    We report an efficient method for the synthesis of nitrogen-doped reduced graphene oxide supported Pt nanocatalysts (Pt/N-RGO). Nitrogen-doped reduced graphene oxide (N-RGO) was prepared by pyrolysis of graphene oxide with cyanamide as a nitrogen source. Then, the Pt nanoparticles were deposited over N-RGO by one-step chemical polyol reduction process. The morphology and structure of as-prepared catalysts were characterized by transmission electron microscopy (TEM), and X-ray diffraction (XRD). Subsequently, electrocatalytic activities of the catalysts were evaluated by cyclic voltammetry (CV). As a result, the Pt/N-RGO catalysts exhibit the superior electrochemical activity toward methanol oxidation in compared with that of Pt loaded on undoped reduced graphene oxide (Pt/RGO) and Pt/carbon blacks (Pt/C). This was mainly attributed to the better distribution of Pt nanoparticles as well as the synergistic electrochemical effects of the nitrogen doped supports. These results demonstrate that N-RGO could be a promising candidate as a high performance catalyst support for a fuel cell application.

  18. Paricalcitol reduces peritoneal fibrosis in mice through the activation of regulatory T cells and reduction in IL-17 production.

    Directory of Open Access Journals (Sweden)

    Guadalupe T González-Mateo

    Full Text Available Fibrosis is a significant health problem associated with a chronic inflammatory reaction. The precise mechanisms involved in the fibrotic process are still poorly understood. However, given that inflammation is a major causative factor, immunomodulation is a possible therapeutic approach to reduce fibrosis. The vitamin D receptor (VDR that is present in all hematopoietic cells has been associated with immunomodulation. We investigated whether the intraperitoneal administration of paricalcitol, a specific activator of the VDR, modulates peritoneal dialysis fluid (PDF-induced peritoneal fibrosis. We characterized the inflammatory process in the peritoneal cavity of mice treated or not treated with paricalcitol and analyzed the ensuing fibrosis. The treatment reduced peritoneal IL-17 levels, which strongly correlated with a significantly lower peritoneal fibrotic response. In vitro studies demonstrate that both CD4+ and CD8+ regulatory T cells appear to impact the regulation of IL-17. Paricalcitol treatment resulted in a significantly increased frequency of CD8+ T cells showing a regulatory phenotype. The frequency of CD4+ Tregs tends to be increased, but it did not achieve statistical significance. However, paricalcitol treatment increased the number of CD4+ and CD8+ Treg cells in vivo. In conclusion, the activation of immunological regulatory mechanisms by VDR signaling could prevent or reduce fibrosis, as shown in peritoneal fibrosis induced by PDF exposure in mice.

  19. Pomegranate-Derived Polyphenols Reduce Reactive Oxygen Species Production via SIRT3-Mediated SOD2 Activation

    Science.gov (United States)

    Zhao, Chong; Sakaguchi, Takenori; Fujita, Kosuke; Ito, Hideyuki; Nishida, Norihisa; Nagatomo, Akifumi; Tanaka-Azuma, Yukimasa

    2016-01-01

    Pomegranate-derived polyphenols are expected to prevent life-style related diseases. In this study, we evaluated the ability of 8 pomegranate-derived polyphenols, along with other polyphenols, to augment SIRT3, a mammalian SIR2 homolog localized in mitochondria. We established a system for screening foods/food ingredients that augment the SIRT3 promoter in Caco-2 cells and identified 3 SIRT3-augmenting pomegranate-derived polyphenols (eucalbanin B, pomegraniin A, and eucarpanin T1). Among them, pomegraniin A activated superoxide dismutase 2 (SOD2) through SIRT3-mediated deacetylation, thereby reducing intracellular reactive oxygen species. The other SIRT3-augmenting polyphenols tested also activated SOD2, suggesting antioxidant activity. Our findings clarify the underlying mechanisms involved in the antioxidant activity of pomegraniin A. PMID:27840668

  20. Instructions, feedback, and reinforcement in reducing activity levels in the classroom.

    Science.gov (United States)

    Schulman, J L; Suran, B G; Stevens, T M; Kupst, M J

    1979-01-01

    The biomotometer, an electronic device which simultaneously measures motor activity and provides auditory feedback, was used in combination with material reinforcers in an experiment to reduce children's activity level in a classroom setting. Subjects were nine boys and two girls, aged 9--13, from a day hospital program for emotionally disturbed children. After five baseline trials, each child had five contingent reinforcement trials in which he/she received feedback "beeps" from the biomotometer and was given toy or candy rewards after each trial in which activity fell at least 20% below mean baseline level. Then five noncontingent reinforcement trials were run in which children received rewards for wearing the apparatus without the feedback attachment. Results indicated that the intervention "package," including instructions, feedback, and contingent reinforcement, was successful in all five trials for 8 of 11 children. Activity levels increased during the final noncontingent phase.

  1. Development and demonstration of a method to monitor the effects of measures to reduce VOC emissions in the EU. LIFE 95/NL/A11/NL/365/ZHL [1996-1998] (Final Report )

    NARCIS (Netherlands)

    Keuken, M.P.; Oss, R.F. van

    1998-01-01

    In 1996, TNO was granted by the European Commission to carry out in the framework of the LIFE programme a project entitled "Development and dem-onstration of a method to monitor the effects of measures to reduce VOC emis-sions in the EU". An additional grant was supplied by the Dutch Ministry for Ho

  2. Inhibition of gamma-secretase activity reduces Abeta production, reduces oxidative stress, increases mitochondrial activity and leads to reduced vulnerability to apoptosis: Implications for the treatment of Alzheimer's disease.

    Science.gov (United States)

    Sheng, Baiyang; Gong, Kai; Niu, Ying; Liu, Lingling; Yan, Yufang; Lu, Guangyuan; Zhang, Lihai; Hu, Min; Zhao, Nanming; Zhang, Xiufang; Tang, Peifu; Gong, Yandao

    2009-05-15

    It has been argued that gamma-secretase should be considered as a pharmacological target, as there are few mechanism-based experimental and clinical studies on gamma-secretase treatment. In this study, we found that N2a cells bearing APP695 or its Swedish mutant exhibited increased basal levels of ROS, nitric oxide (NO), protein carbonyls, MDA and intracellular calcium, as well as reduced level of the mitochondrial membrane potential and ATP. When the activity of gamma-secretase was inhibited by expression of the D385A PS1 variant, cells (N2a/Swe.D385A) showed reduced basal levels of ROS, nitric oxide (NO), protein carbonyls, MDA and intracellular calcium, as well as increased mitochondrial membrane potential and ATP level. In addition, N2a/Swe.D385A cells showed reduced vulnerability to H(2)O(2)-induced apoptosis. The Bcl-2 and JNK/ERK pathways were proven to be involved in the change of vulnerability to H(2)O(2)-induced apoptosis. Moreover, we discovered that inhibition of gamma-secretase by DAPT would lead to a reduction of ROS levels and stabilization of mitochondrial function in APP (N2a/APP695) and APP Swedish mutant (N2a/APPswe) transfected cells. At last, it was shown that Abeta antibody and antiserum prevented increase of ROS and reduction of mitochondrial membrane potential in N2a/Swe.DeltaE9 cells but not in N2a/Swe.D385A cells, which indicated that reduced formation of Abeta was the reason for reduction of ROS formation and increase of mitochondrial membrane potential when PS-1 activity was impaired in N2a/Swe.D385A cells. We concluded that neurotoxicity was positively correlated with the activity of gamma-secretase, which suggested inhibition of gamma-secretase is a rational pharmacological target for Alzheimer's disease treatment.

  3. Application of Feedforward Adaptive Active-Noise Control for Reducing Blade Passing Noise in Centrifugal Fans

    Science.gov (United States)

    WU, J.-D.; BAI, M. R.

    2001-02-01

    This paper describes two configurations of feedforward adaptive active-noise control (ANC) technique for reducing blade passing noise in centrifugal fans. In one configuration, the control speaker is installed at the cut-off region of the fan, while in the other configuration at the exit duct. The proposed ANC system is based on the filtered-x least-mean-squares (FXLMS) algorithm with multi-sine synthesized reference signal and frequency counting and is implemented by using a digital signal processor (DSP). Experiments are carried out to evaluate the proposed system for reducing the noise at the blade passing frequency (BPF) and its harmonics at various flow speeds. The results of the experiment indicated that the ANC technique is effective in reducing the blade passing noise for two configurations by using the feedforward adaptive control.

  4. Back-stepping active disturbance rejection control design for integrated missile guidance and control system via reduced-order ESO.

    Science.gov (United States)

    Xingling, Shao; Honglun, Wang

    2015-07-01

    This paper proposes a novel composite integrated guidance and control (IGC) law for missile intercepting against unknown maneuvering target with multiple uncertainties and control constraint. First, by using back-stepping technique, the proposed IGC law design is separated into guidance loop and control loop. The unknown target maneuvers and variations of aerodynamics parameters in guidance and control loop are viewed as uncertainties, which are estimated and compensated by designed model-assisted reduced-order extended state observer (ESO). Second, based on the principle of active disturbance rejection control (ADRC), enhanced feedback linearization (FL) based control law is implemented for the IGC model using the estimates generated by reduced-order ESO. In addition, performance analysis and comparisons between ESO and reduced-order ESO are examined. Nonlinear tracking differentiator is employed to construct the derivative of virtual control command in the control loop. Third, the closed-loop stability for the considered system is established. Finally, the effectiveness of the proposed IGC law in enhanced interception performance such as smooth interception course, improved robustness against multiple uncertainties as well as reduced control consumption during initial phase are demonstrated through simulations.

  5. Melatonin Reduces Inflammatory Injury Through Inhibiting NF-κB Activation in Rats With Colitis

    Directory of Open Access Journals (Sweden)

    Jun-Hua Li

    2005-01-01

    Full Text Available Proinflammatory mediators are important in the pathogenesis of IBD, which are regulated by activation of NF-κB. The aim of this study was to investigate whether melatonin reduces inflammatory injury and inhibits proinflammatory molecule and NF-κB in rats with colitis. Rat colitis model was established by TNBS enema. NF-κB p65, TNF-α, ICAM-1, and IκBα in colon tissue were examined by immunohistochemistry, EMSA, RT-PCR, and Western blot analysis. Expression of proinflammatory molecule and activation of NF-κB were upregulated and IκB level decreased in rats with colitis. Melatonin reduces colonic inflammatory injury through downregulating proinflammatory molecule mediated by NF-κB inhibition and blockade of IκBα degradation.

  6. Blocking Surgically Induced Lysyl Oxidase Activity Reduces the Risk of Lung Metastases

    Directory of Open Access Journals (Sweden)

    Chen Rachman-Tzemah

    2017-04-01

    Full Text Available Surgery remains the most successful curative treatment for cancer. However, some patients with early-stage disease who undergo surgery eventually succumb to distant metastasis. Here, we show that in response to surgery, the lungs become more vulnerable to metastasis due to extracellular matrix remodeling. Mice that undergo surgery or that are preconditioned with plasma from donor mice that underwent surgery succumb to lung metastases earlier than controls. Increased lysyl oxidase (LOX activity and expression, fibrillary collagen crosslinking, and focal adhesion signaling contribute to this effect, with the hypoxic surgical site serving as the source of LOX. Furthermore, the lungs of recipient mice injected with plasma from post-surgical colorectal cancer patients are more prone to metastatic seeding than mice injected with baseline plasma. Downregulation of LOX activity or levels reduces lung metastasis after surgery and increases survival, highlighting the potential of LOX inhibition in reducing the risk of metastasis following surgery.

  7. Niflumic acid reduces the hyperpolarization-activated current (I(h)) in rod photoreceptor cells.

    Science.gov (United States)

    Satoh, T O; Yamada, M

    2001-08-01

    We examined the effects of niflumic acid (NFA), a chloride channel blocker, on the hyperpolarization-activated current (I(h)) in newt rod photoreceptors. At 100 microM, NFA delayed the activation of I(h) induced by hyperpolarizing voltage pulses to -83 mV from a holding potential of -43 mV, and reduced the steady-state current. However, reduction by NFA was weakened when I(h) was activated by hyperpolarizing steps to -123 mV, suggesting that these effects were voltage-dependent. The suppressive effects of NFA on I(h) were accompanied by a negative shift in activation voltage. NFA also delayed the relaxation of I(h) tail currents, showing that this drug also inhibited deactivation of the current. The reversal potential and the fully activated conductance were not affected. These observations suggest that NFA reduces I(h) by modifying the gating kinetics of the underlying channels. The suppressive actions of NFA remained when intracellular Ca2+ was strongly chelated, and the failure of suppression by NFA in inside-out patches suggests that the agent may act on the I(h) channel from the extracellular side. These results, obtained in rod photoreceptors, are consistent with similar effects of NFA on I(f) in cardiac myocytes, suggesting that both currents share similar pharmacological properties.

  8. Structural and mechanical properties of welded joints of reduced activation martensitic steels

    Energy Technology Data Exchange (ETDEWEB)

    Filacchioni, G. E-mail: gianni.filacchioni@casaccia.enea.it; Montanari, R.; Tata, M.E.; Pilloni, L

    2002-12-01

    Gas tungsten arc welding and electron beam welding methods were used to realise welding pools on plates of reduced activation martensitic steels. Structural and mechanical features of these simulated joints have been investigated in as-welded and post-welding heat-treated conditions. The research allowed to assess how each welding technique affects the original mechanical properties of materials and to find suitable post-welding heat treatments. This paper reports results from experimental activities on BATMAN II and F82H mod. steels carried out in the frame of the European Blanket Project - Structural Materials Program.

  9. Thermophysical and mechanical properties of Fe-(8-9)%Cr reduced activation steels

    Energy Technology Data Exchange (ETDEWEB)

    Zinkle, S.J.; Robertson, J.P.; Klueh, R.L. [Oak Ridge National Lab., TN (United States)

    1998-09-01

    The key thermophysical and mechanical properties for 8--9%Cr reduced activation ferritic/martensitic steels are summarized, including temperature-dependent tensile properties in the unirradiated and irradiated conditions, stress-rupture behavior, elastic constants, thermal conductivity, thermal expansion, specific heat, and ductile-to-brittle transition temperature. The estimated lower and upper temperatures limits for structural applications are 250 and 550 C due to radiation hardening/embrittlement and thermal creep considerations, respectively.

  10. Antiretroviral treatment effect on immune activation reduces cerebrospinal fluid HIV-1 infection.

    Science.gov (United States)

    Sinclair, Elizabeth; Ronquillo, Rollie; Lollo, Nicole; Deeks, Steven G; Hunt, Peter; Yiannoutsos, Constantin T; Spudich, Serena; Price, Richard W

    2008-04-15

    To define the effect of antiretroviral therapy (ART) on activation of T cells in cerebrospinal fluid (CSF) and blood, and interactions of this activation with CSF HIV-1 RNA concentrations. Cross-sectional analysis of 14 HIV-negative subjects and 123 neuroasymptomatic HIV-1-infected subjects divided into 3 groups: not on ART (termed "offs"), on ART with plasma HIV-1 RNA >500 copies/mL ("failures"), and on ART with plasma HIV-1 RNA activation was measured by coexpression of CD38 and human leukocyte antigen DR (HLA-DR). Other measurements included CSF neopterin and white blood cell (WBC) counts. CD8 T-cell activation in CSF and blood was highly correlated across all subjects and was highest in the offs, lower in the failures, and lower still in the successes. While CD8 activation was reduced in failures compared to offs across the range of plasma HIV-1, it maintained a coincident relation to CSF HIV-1 in both viremic groups. In addition to correlation with CSF HIV-1 concentrations, CD8 activation in blood and CSF correlated with CSF WBCs and CSF neopterin. Multivariate analysis confirmed the association of blood CD8 T-cell activation, along with plasma HIV-1 RNA and CSF neopterin, with CSF HIV-1 RNA levels. The similarity of CD8 T-cell activation in blood and CSF suggests these cells move from blood to CSF with only minor changes in CD38/HLA-DR expression. Differences in the relation of CD8 activation to HIV-1 concentrations in the blood and CSF in the 2 viremic groups suggest that changes in immune activation not only modulate CSF HIV-1 replication but also contribute to CSF treatment effects. The magnitude of systemic HIV-1 infection and intrathecal macrophage activation are also important determinants of CSF HIV-1 RNA levels.

  11. Alcohol Synthesis over Pre-Reduced Activated Carbon-Supported Molybdenum-Based Catalysts

    Directory of Open Access Journals (Sweden)

    Edwin L. Kugler

    2003-01-01

    Full Text Available Activated carbon (AC-supported molybdenum catalysts, either with or without a potassium promoter, were prepared by the incipient wetness impregnation method. The materials were characterized using differential thermal analysis (DTA and temperature programmed reduction (TPR, and were used for mixed alcohol synthesis from syngas (CO+H2. DTA results showed that a new phase, related to the interaction between Mo species and the AC support, is formed during the calcination of the Mo/AC catalyst, and the introduction of a K promoter has noticeable effect on the interaction. TPR results indicated that the Mo is more difficult to reduce after being placed onto the AC support, and the addition of a K promoter greatly promotes the formation of Mo species reducible at relatively low temperatures, while it retards the generation of Mo species that are reducible only at higher temperatures. These differences in the reduction behavior of the catalysts are atributed to the interaction between the active components (Mo and K and the support. Potassium-doping significantly promotes the formation of alcohols at the expense of CO conversion, especially to hydrocarbons. It is postulated that Mo species with intermediate valence values (averaged around +3.5 are more likely to be the active phase(s for alcohol synthesis from CO hydrogenation, while those with lower Mo valences are probably responsible for the production of hydrocarbons.

  12. PGE2 reduces MMP-14 and increases plasminogen activator inhibitor-1 in cardiac fibroblasts.

    Science.gov (United States)

    Kassem, Kamal M; Clevenger, Margarette H; Szandzik, David L; Peterson, Edward; Harding, Pamela

    2014-10-01

    Prostaglandin E2 (PGE2) is elevated during cardiac injury and we have previously shown that mice lacking the PGE2 EP4 receptor display dilated cardiomyopathy (DCM) with increased expression of the membrane type matrix metalloproteinase, MMP-14. We thus hypothesized that PGE2 regulates expression of MMP-14 and also affects fibroblast migration. Primary cultures of neonatal rat ventricular fibroblasts (NVFs) were used to test the effects of PGE2. Gene and protein expression was assessed by real time RT-PCR and Western blot, MMP activity was determined by zymography and migration of NVF was assessed by motility in a transwell system. PGE2 reduced expression of MMP-14 and these effects were antagonized by an EP4 antagonist. An EP4 agonist mimicked the effect of PGE2. PGE2 also increased mRNA and protein levels of plasminogen activator inhibitor-1 (PAI-1), an inhibitor of MMP activation. However, PGE2-stimulation of PAI-1 was mediated by the EP1/EP3 receptor and not EP4. Migration of NVF was assessed by motility in a transwell system. Treatment of NVFs with PGE2 reduced the number of cells migrating toward 10% FCS. Treatment with the EP2 agonist also reduced migration but did not affect MMP-14 expression or PAI-1. Our results suggest that PGE2 utilizes different receptors and mechanisms to ultimately decrease MMP expression and NVF migration. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. The role of gamma-band activity in the representation of faces: reduced activity in the fusiform face area in congenital prosopagnosia.

    Directory of Open Access Journals (Sweden)

    Christian Dobel

    Full Text Available BACKGROUND: Congenital prosopagnosia (CP describes an impairment in face processing that is presumably present from birth. The neuronal correlates of this dysfunction are still under debate. In the current paper, we investigate high-frequent oscillatory activity in response to faces in persons with CP. Such neuronal activity is thought to reflect higher-level representations for faces. METHODOLOGY: Source localization of induced Gamma-Band Responses (iGBR measured by magnetoencephalography (MEG was used to establish the origin of oscillatory activity in response to famous and unknown faces which were presented in upright and inverted orientation. Persons suffering from congenital prosopagnosia (CP were compared to matched controls. PRINCIPAL FINDINGS: Corroborating earlier research, both groups revealed amplified iGBR in response to upright compared to inverted faces predominately in a time interval between 170 and 330 ms and in a frequency range from 50-100 Hz. Oscillatory activity upon known faces was smaller in comparison to unknown faces, suggesting a "sharpening" effect reflecting more efficient processing for familiar stimuli. These effects were seen in a wide cortical network encompassing temporal and parietal areas involved in the disambiguation of homogenous stimuli such as faces, and in the retrieval of semantic information. Importantly, participants suffering from CP displayed a strongly reduced iGBR in the left fusiform area compared to control participants. CONCLUSIONS: In sum, these data stress the crucial role of oscillatory activity for face representation and demonstrate the involvement of a distributed occipito-temporo-parietal network in generating iGBR. This study also provides the first evidence that persons suffering from an agnosia actually display reduced gamma band activity. Finally, the results argue strongly against the view that oscillatory activity is a mere epiphenomenon brought fourth by rapid eye-movements (micro

  14. Tropical cyclone activity enhanced by Sahara greening and reduced dust emissions during the African Humid Period

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    Pausata, Francesco S. R.; Emanuel, Kerry A.; Chiacchio, Marc; Diro, Gulilat T.; Zhang, Qiong; Sushama, Laxmi; Stager, J. Curt; Donnelly, Jeffrey P.

    2017-06-01

    Tropical cyclones (TCs) can have devastating socioeconomic impacts. Understanding the nature and causes of their variability is of paramount importance for society. However, historical records of TCs are too short to fully characterize such changes and paleo-sediment archives of Holocene TC activity are temporally and geographically sparse. Thus, it is of interest to apply physical modeling to understanding TC variability under different climate conditions. Here we investigate global TC activity during a warm climate state (mid-Holocene, 6,000 yBP) characterized by increased boreal summer insolation, a vegetated Sahara, and reduced dust emissions. We analyze a set of sensitivity experiments in which not only solar insolation changes are varied but also vegetation and dust concentrations. Our results show that the greening of the Sahara and reduced dust loadings lead to more favorable conditions for tropical cyclone development compared with the orbital forcing alone. In particular, the strengthening of the West African Monsoon induced by the Sahara greening triggers a change in atmospheric circulation that affects the entire tropics. Furthermore, whereas previous studies suggest lower TC activity despite stronger summer insolation and warmer sea surface temperature in the Northern Hemisphere, accounting for the Sahara greening and reduced dust concentrations leads instead to an increase of TC activity in both hemispheres, particularly over the Caribbean basin and East Coast of North America. Our study highlights the importance of regional changes in land cover and dust concentrations in affecting the potential intensity and genesis of past TCs and suggests that both factors may have appreciable influence on TC activity in a future warmer climate.

  15. The nitric oxide donor pentaerythritol tetranitrate reduces platelet activation in congestive heart failure.

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    Ulrike Flierl

    Full Text Available Platelet activation associated with endothelial dysfunction and impaired endogenous platelet inhibition is part of the cardiovascular phenotype of congestive heart failure (CHF and contributes to the increased risk for thromboembolic complications. Pentaerythritol tetranitrate (PETN has been shown to release nitric oxide without development of nitrate tolerance. We investigated the effect of chronic PETN treatment on platelet activation and aggregation in an experimental CHF model.Chronic ischemic heart failure was induced in male Wistar rats by coronary artery ligation. Starting 7 days thereafter, rats were randomised to placebo or PETN (80 mg/kg twice daily. After 9 weeks, activation of circulating platelets was determined measuring platelet bound fibrinogen, which requires activated glycoprotein IIb/IIIa on the platelet surface. Binding was quantified by flow-cytometry using a FITC-labelled anti-fibrinogen antibody. Platelet-bound fibrinogen was significantly increased in CHF-Placebo (mean fluorescence intensity: Sham 88±4, CHF-Placebo 104±6, p<0.05 and reduced following treatment with PETN (89±7, p<0.05 vs. CHF-Placebo. Maximal and final ADP-induced aggregation was significantly enhanced in CHF-Placebo vs. Sham-operated animals and normalized / decreased following chronic PETN treatment. Moreover, platelet adhesion was significantly reduced (number of adherent platelets: control: 85.6±5.5, PETN: 40±3.3; p<0.001 and VASP phosphorylation significantly enhanced following in vitro PETN treatment.Chronic NO supplementation using PETN reduces platelet activation in CHF rats. Thus, PETN may constitute a useful approach to prevent thromboembolic complications in CHF.

  16. Constitutive activation of BMP signalling abrogates experimental metastasis of OVCA429 cells via reduced cell adhesion

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    Shepherd Trevor G

    2010-02-01

    Full Text Available Abstract Background Activation of bone morphogenetic protein (BMP4 signalling in human ovarian cancer cells induces a number of phenotypic changes in vitro, including altered cell morphology, adhesion, motility and invasion, relative to normal human ovarian surface epithelial cells. From these in vitro analyses, we had hypothesized that active BMP signalling promotes the metastatic potential of ovarian cancer. Methods To test this directly, we engineered OVCA429 human ovarian cancer cells possessing doxycycline-inducible expression of a constitutively-active mutant BMP receptor, ALK3QD, and administered these cells to immunocompromised mice. Further characterization was performed in vitro to address the role of activated BMP signalling on the EOC phenotype, with particular emphasis on epithelial-mesenchymal transition (EMT and cell adhesion. Results Unexpectedly, doxycycline-induced ALK3QD expression in OVCA429 cells reduced tumour implantation on peritoneal surfaces and ascites formation when xenografted into immunocompromised mice by intraperitoneal injection. To determine the potential mechanisms controlling this in vivo observation, we followed with several cell culture experiments. Doxycycline-induced ALK3QD expression enhanced the refractile, spindle-shaped morphology of cultured OVCA429 cells eliciting an EMT-like response. Using in vitro wound healing assays, we observed that ALK3QD-expressing cells migrated with long, cytoplasmic projections extending into the wound space. The phenotypic alterations of ALK3QD-expressing cells correlated with changes in specific gene expression patterns of EMT, including increased Snail and Slug and reduced E-cadherin mRNA expression. In addition, ALK3QD signalling reduced β1- and β3-integrin expression, critical molecules involved in ovarian cancer cell adhesion. The combination of reduced E-cadherin and β-integrin expression correlates directly with the reduced EOC cell cohesion in spheroids and

  17. Ligand binding reduces SUMOylation of the peroxisome proliferator-activated receptor γ (PPARγ activation function 1 (AF1 domain.

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    Rolf Diezko

    Full Text Available Peroxisome proliferator-activated receptor gamma (PPARγ is a ligand-activated nuclear receptor regulating adipogenesis, glucose homeostasis and inflammatory responses. The activity of PPARγ is controlled by post-translational modifications including SUMOylation and phosphorylation that affects its biological and molecular functions. Several important aspects of PPARγ SUMOylation including SUMO isoform-specificity and the impact of ligand binding on SUMOylation remain unresolved or contradictory. Here, we present a comprehensive study of PPARγ1 SUMOylation. We show that PPARγ1 can be modified by SUMO1 and SUMO2. Mutational analyses revealed that SUMOylation occurs exclusively within the N-terminal activation function 1 (AF1 domain predominantly at lysines 33 and 77. Ligand binding to the C-terminal ligand-binding domain (LBD of PPARγ1 reduces SUMOylation of lysine 33 but not of lysine 77. SUMOylation of lysine 33 and lysine 77 represses basal and ligand-induced activation by PPARγ1. We further show that lysine 365 within the LBD is not a target for SUMOylation as suggested in a previous report, but it is essential for full LBD activity. Our results suggest that PPARγ ligands negatively affect SUMOylation by interdomain communication between the C-terminal LBD and the N-terminal AF1 domain. The ability of the LBD to regulate the AF1 domain may have important implications for the evaluation and mechanism of action of therapeutic ligands that bind PPARγ.

  18. Rifampicin reduces advanced glycation end products and activates DAF-16 to increase lifespan in Caenorhabditis elegans.

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    Golegaonkar, Sandeep; Tabrez, Syed S; Pandit, Awadhesh; Sethurathinam, Shalini; Jagadeeshaprasad, Mashanipalya G; Bansode, Sneha; Sampathkumar, Srinivasa-Gopalan; Kulkarni, Mahesh J; Mukhopadhyay, Arnab

    2015-06-01

    Advanced glycation end products (AGEs) are formed when glucose reacts nonenzymatically with proteins; these modifications are implicated in aging and pathogenesis of many age-related diseases including type II diabetes, atherosclerosis, and neurodegenerative disorders. Thus, pharmaceutical interventions that can reduce AGEs may delay age-onset diseases and extend lifespan. Using LC-MS(E), we show that rifampicin (RIF) reduces glycation of important cellular proteins in vivo and consequently increases lifespan in Caenorhabditis elegans by up to 60%. RIF analog rifamycin SV (RSV) possesses similar properties, while rifaximin (RMN) lacks antiglycation activity and therefore fails to affect lifespan positively. The efficacy of RIF and RSV as potent antiglycating agents may be attributed to the presence of a p-dihydroxyl moiety that can potentially undergo spontaneous oxidation to yield highly reactive p-quinone structures, a feature absent in RMN. We also show that supplementing rifampicin late in adulthood is sufficient to increase lifespan. For its effect on longevity, rifampicin requires DAF-18 (nematode PTEN) as well as JNK-1 and activates DAF-16, the FOXO homolog. Interestingly, the drug treatment modulates transcription of a different subset of DAF-16 target genes, those not controlled by the conserved Insulin-IGF-1-like signaling pathway. RIF failed to increase the lifespan of daf-16 null mutant despite reducing glycation, showing thereby that DAF-16 may not directly affect AGE formation. Together, our data suggest that the dual ability to reduce glycation in vivo and activate prolongevity processes through DAF-16 makes RIF and RSV effective lifespan-extending interventions.

  19. Greater positive schizotypy relates to reduced N100 activity during rejection scenes.

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    Premkumar, Preethi; Onwumere, Juliana; Wilson, Daniel; Sumich, Alexander; Castro, Antonio; Kumari, Veena; Kuipers, Elizabeth

    2014-08-01

    Social anxiety due to rejection sensitivity (RS) exacerbates psychosis-like experiences in the general population. While reduced dorsal anterior cingulate cortex (dACC) activity during social rejection in high schizotypy has suggested self-distancing from rejection, earlier stages of mental processing such as feature encoding could also contribute to psychosis-like experiences. This study aimed to determine the stage of mental processing of social rejection that relates to positive schizotypy. Forty-one healthy participants were assessed for schizotypy and RS. Event-related potential amplitudes (ERPs) were measured at frontal, temporal and parieto-occipital sites and their cortical sources (dACC, temporal pole and lingual gyrus) at early (N100) and late (P300 and late slow wave, LSW) timeframes during rejection, acceptance and neutral scenes. ERPs were compared between social interaction types. Correlations were performed between positive schizotypy (defined as the presence of perceptual aberrations, hallucinatory experiences and magical thinking), RS and ERPs during rejection. Amplitude was greater during rejection than acceptance or neutral conditions at the dACC-P300, parieto-occipital-P300, dACC-LSW and frontal-LSW. RS correlated positively with positive schizotypy. Reduced dACC N100 activity during rejection correlated with greater positive schizotypy and RS. Reduced dACC N100 activity and greater RS independently predicted positive schizotypy. An N100 deficit that indicates reduced feature encoding of rejection scenes increases with greater positive schizotypy and RS. Higher RS shows that a greater tendency to misattribute ambiguous social situations as rejecting also increases with positive schizotypy. These two processes, namely primary bottom-up sensory processing and secondary misattribution of rejection, combine to increase psychosis-like experiences. Copyright © 2014 Elsevier Ltd. All rights reserved.

  20. Oxidative stress-mediated antibacterial activity of graphene oxide and reduced graphene oxide in Pseudomonas aeruginosa

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    Gurunathan S

    2012-11-01

    Full Text Available Sangiliyandi Gurunathan, Jae Woong Han, Ahmed Abdal Dayem, Vasuki Eppakayala, Jin-Hoi KimDepartment of Animal Biotechnology, Konkuk University, Seoul, South KoreaBackground: Graphene holds great promise for potential use in next-generation electronic and photonic devices due to its unique high carrier mobility, good optical transparency, large surface area, and biocompatibility. The aim of this study was to investigate the antibacterial effects of graphene oxide (GO and reduced graphene oxide (rGO in Pseudomonas aeruginosa. In this work, we used a novel reducing agent, betamercaptoethanol (BME, for synthesis of graphene to avoid the use of toxic materials. To uncover the impacts of GO and rGO on human health, the antibacterial activity of two types of graphene-based material toward a bacterial model P. aeruginosa was studied and compared.Methods: The synthesized GO and rGO was characterized by ultraviolet-visible absorption spectroscopy, particle-size analyzer, X-ray diffraction, scanning electron microscopy and Raman spectroscopy. Further, to explain the antimicrobial activity of graphene oxide and reduced graphene oxide, we employed various assays, such as cell growth, cell viability, reactive oxygen species generation, and DNA fragmentation.Results: Ultraviolet-visible spectra of the samples confirmed the transition of GO into graphene. Dynamic light-scattering analyses showed the average size among the two types of graphene materials. X-ray diffraction data validated the structure of graphene sheets, and high-resolution scanning electron microscopy was employed to investigate the morphologies of prepared graphene. Raman spectroscopy data indicated the removal of oxygen-containing functional groups from the surface of GO and the formation of graphene. The exposure of cells to GO and rGO induced the production of superoxide radical anion and loss of cell viability. Results suggest that the antibacterial activities are contributed to by loss of

  1. Pedophilia is linked to reduced activation in hypothalamus and lateral prefrontal cortex during visual erotic stimulation.

    Science.gov (United States)

    Walter, Martin; Witzel, Joachim; Wiebking, Christine; Gubka, Udo; Rotte, Michael; Schiltz, Kolja; Bermpohl, Felix; Tempelmann, Claus; Bogerts, Bernhard; Heinze, Hans Jochen; Northoff, Georg

    2007-09-15

    Although pedophilia is of high public concern, little is known about underlying neural mechanisms. Although pedophilic patients are sexually attracted to prepubescent children, they show no sexual interest toward adults. This study aimed to investigate the neural correlates of deficits of sexual and emotional arousal in pedophiles. Thirteen pedophilic patients and 14 healthy control subjects were tested for differential neural activity during visual stimulation with emotional and erotic pictures with functional magnetic resonance imaging. Regions showing differential activations during the erotic condition comprised the hypothalamus, the periaqueductal gray, and dorsolateral prefrontal cortex, the latter correlating with a clinical measure. Alterations of emotional processing concerned the amygdala-hippocampus and dorsomedial prefrontal cortex. Hypothesized regions relevant for processing of erotic stimuli in healthy individuals showed reduced activations during visual erotic stimulation in pedophilic patients. This suggests an impaired recruitment of key structures that might contribute to an altered sexual interest of these patients toward adults.

  2. Reduced graphene oxide is not a universal promoter for photocatalytic activities of TiO2

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    Hui Ling Tan

    2017-03-01

    Full Text Available Addition of reduced graphene oxide (RGO to P25 TiO2 was made and its impacts on photocatalytic oxidation of various organic substances were studied. Although the presence of RGO in TiO2 can enhance certain TiO2-based photocatalytic reactions, it is not a universal observation that can be expected in all types of organic substances. The factor of photocatalytic activity enhancement is strongly affected by the various functional groups appeared in the organic substances. In this work, it is realised that the length of alkyl chain in alcohols and carboxylic acids have the minimum influence on the overall activity while the number of hydroxyl groups can promote the further activity enhancement in the presence of RGO.

  3. Entecavir Exhibits Inhibitory Activity against Human Immunodeficiency Virus under Conditions of Reduced Viral Challenge▿

    Science.gov (United States)

    Lin, Pin-Fang; Nowicka-Sans, Beata; Terry, Brian; Zhang, Sharon; Wang, Chunfu; Fan, Li; Dicker, Ira; Gali, Volodymyr; Higley, Helen; Parkin, Neil; Tenney, Daniel; Krystal, Mark; Colonno, Richard

    2008-01-01

    Entecavir (ETV) was developed for the treatment of chronic hepatitis B virus (HBV) infection and is globally approved for that indication. Initial preclinical studies indicated that ETV had no significant activity against human immunodeficiency virus type 1 (HIV-1) in cultured cell lines at physiologically relevant ETV concentrations, using traditional anti-HIV assays. In response to recent clinical observations of anti-HIV activity of ETV in HIV/HBV-coinfected patients not receiving highly active antiretroviral therapy (HAART), additional investigative studies were conducted to expand upon earlier results. An extended panel of HIV-1 laboratory and clinical strains and cell types was tested against ETV, along with a comparison of assay methodologies and resistance profiling. These latest studies confirmed that ETV has only weak activity against HIV, using established assay systems. However, a >100-fold enhancement of antiviral activity (equivalent to the antiviral activity of lamivudine) could be obtained when assay conditions were modified to reduce the initial viral challenge. Also, the selection of a M184I virus variant during the passage of HIV-1 at high concentrations of ETV confirmed that ETV can exert inhibitory pressure on the virus. These findings may have a significant impact on how future assays are performed with compounds to be used in patients infected with HIV. These results support the recommendation that ETV therapy should be administered in concert with HAART for HIV/HBV-coinfected patients. PMID:18316521

  4. Morphological analysis of activity-reduced adult-born neurons in the mouse olfactory bulb

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    Jeffrey E Dahlen

    2011-05-01

    Full Text Available Adult born neurons are added to the olfactory bulb (OB throughout life in rodents. While many factors have been identified as regulating the survival and integration of adult-born neurons (ABNs into existing circuitry, the understanding of how these factors affect ABN morphology and connectivity is limited. Here we compare how cell intrinsic (siRNA knock down of voltage gated sodium channels NaV1.1-1.3 and circuit level (naris occlusion reductions in activity affect ABN morphology during integration into the OB. We found that both manipulations reduce the number of dendritic spines (and thus likely the number of reciprocal synaptic connections formed with the surrounding circuitry and inhibited dendritic ramification of ABNs. Further, we identified regions of ABN apical dendrites where the largest and most significant decreases occur following siRNA knock down or naris occlusion. In siRNA knock down cells, reduction of spines is observed in proximal regions of the apical dendrite. This suggests that distal regions of the dendrite may remain active independent of NaV1.1-1.3 channel expression, perhaps facilitated by activation of T-type calcium channels and NMDA receptors. By contrast, circuit level reduction of activity by naris occlusion resulted in a global depression of spine number. Together, these results indicate that ABNs retain the ability to develop their typical overall morphological features regardless of experienced activity, and activity modulates the number and location of formed connections.

  5. Exogenous cholecystokinin-8 reduces vagal efferent nerve activity in rats through CCKA receptors

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    Bucinskaite, Violeta; Kurosawa, Mieko; Lundeberg, Thomas

    2000-01-01

    It has been proposed that the vagus nerve plays a role in mediating cholecystokinin-8 (CCK-8) effect on such gastric functions as motility, emptying and gastric acid secretion. To examine the contribution of the efferent pathways in realizing these effects, efferent mass activity in the ventral gastric vagal nerve in Sprague-Dawley rats was recorded.Intravenous infusion of CCK-8 (0.1–1 nmol) suppressed the efferent activity. The effect of CCK-8 was significantly reduced in animals with total subdiaphragmatic vagotomy in comparison to those with partial vagotomy.Intravenous infusion of CCKA receptor antagonist L-364,718 (1–100×10−6 g) blocked the response of vagal efferent activity to 0.1 nmol CCK-8, but the CCKB receptor antagonist L-365,260 (1–100×10−6 g) did not in the conditions of either partial or total vagotomy.Intracisternal infusion of L-364,718 (1×10−6 g) blocked the response of vagal efferent activity to 0.1 nmol CCK-8 i.v.Infusion of exogenous CCK-8 did not affect the activity of supradiaphragmatic vagal afferents.The results suggest that the effect of systemically administered CCK-8 on vagal efferent activity is mediated by both peripherally (subdiaphragmatically) and centrally localized CCKA receptors. PMID:10780970

  6. Reduced fructosamine-3-kinase activity and its mRNA in human distal colorectal carcinoma.

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    Notarnicola, M; Caruso, Maria G; Tutino, V; Guerra, V; Frisullo, S; Altomare, D F; Misciagna, G

    2010-09-01

    Fructosamine-3-Kinase (FN3K) is an enzyme phosphorilating fructoselysine (FL) residues on glycated proteins, resulting in the production of protein-bound FL-3-phosphate. The pathological role of the non-enzymatic modification of proteins by reducing sugars has become increasingly evident in various types of disorders, including the cancer. In this study, our aim was to study FN3K enzyme activity, as well as its mRNA in human colorectal cancer (CRC). Thirty consecutive CRC patients undergoing surgery of the colon were enrolled in the study. FN3K enzymatic activity and gene expression were analyzed using a radiometric assay and quantitative RT-PCR, respectively. FN3K is a functionally active enzyme in human colon tissue, without significant differences between normal mucosa and cancer. The mean level of FN3K mRNA was significantly lower in cancer than in the corresponding normal colorectal mucosa The colorectal tumors located on the left side showed lower levels of both enzymatic activity and mRNA FN3K than tumors located in the right side of colon. This paper is the first studying FN3K enzyme activity in human CRC, showing a significant relationship between enzymatic activity, its mRNA and tumor side.

  7. Relationship satisfaction predicts sexual activity following risk-reducing salpingo-oophorectomy.

    Science.gov (United States)

    Lorenz, Tierney; McGregor, Bonnie; Swisher, Elizabeth

    2014-06-01

    Changes in sexual function are a common outcome following risk-reducing salpingo-oophorectomy (RRSO), a prophylactic surgery for women at high risk of ovarian and other gynecologic cancers. Despite the known importance of sexuality in patients' quality of life and satisfaction with surgery, little is known about what predicts sexual activity following RRSO. The present study examined how mental and physical health variables predicted sexual activity before and after RRSO. We conducted a secondary analysis of quality of life measures collected in 85 women at high risk for ovarian cancer. Participants completed validated measures of mental, physical, and relationship health 1-2 weeks before surgery, and 2, 6 and 12 months following surgery. Across analyses, relationship satisfaction emerged as the most significant predictor of change in sexual activity: women with high relationship satisfaction were more likely to continue to have regular sexual activity following RRSO, even in the presence of vaginal menopausal symptoms. The effect of depression, anxiety and overall physical health on sexual activity was non-significant when controlling for relationship satisfaction. When counseling women about RRSO and its impact on sexual activity, clinicians should discuss the effect of the patient's relationship health on this outcome.

  8. Simulated microgravity alters multipotential differentiation of rat mesenchymal stem cells in association with reduced telomerase activity

    Science.gov (United States)

    Sun, Lianwen; Gan, Bo; Fan, Yubo; Xie, Tian; Hu, Qinghua; Zhuang, Fengyuan

    Microgravity is one of the most important characteristics in space flight. Exposure to microgravity results in extensive physiological changes in humans. Bone loss is one of the changes with serious consequences; however, the mechanism retains unclear. As the origin of osteoprogenitors, mesenchymal stem cells (MSCs) may play an important role in it. After cultured under simulated microgravity (in a rotary cell culture system, RCCS), MSCs were stained using oil red O to identify adipocytes. The mRNA level of bone morphogenetic protein (BMP)-2 and peroxisome proliferators-activated receptor (PPAR) γ2 was determined by RT-PCR. Otherwise, MSCs were induced to osteogenic differentiation after microgravity culture, and then the activity of alkaline phosphatase (ALP) was determined by PNPP and the content of osteocalcin (OC) by ELISA. Furthermore, the telomerase activity in MSCs was measured by TRAP. The results showed that simulated microgravity inhibited osteoblastic differentiation and induced adipogenic differentiation accompanied by the change of gene expression of BMP-2 and PPARγ2 in MSCs. Meanwhile, the telomerase activity decreased significantly in MSCs under simulated microgravity. The reduced bone formation in space flight may partly be due to the altered potential differentiation of MSCs associated with telomerase activity which plays a key role in regulating the lifespan of cell proliferation and differentiation. Therefore, telomerase activation/replacement may act as a potential countermeasure for microgravity-induced bone loss.

  9. Task-Driven Activity Reduces the Cortical Activity Space of the Brain: Experiment and Whole-Brain Modeling.

    Science.gov (United States)

    Ponce-Alvarez, Adrián; He, Biyu J; Hagmann, Patric; Deco, Gustavo

    2015-08-01

    How a stimulus or a task alters the spontaneous dynamics of the brain remains a fundamental open question in neuroscience. One of the most robust hallmarks of task/stimulus-driven brain dynamics is the decrease of variability with respect to the spontaneous level, an effect seen across multiple experimental conditions and in brain signals observed at different spatiotemporal scales. Recently, it was observed that the trial-to-trial variability and temporal variance of functional magnetic resonance imaging (fMRI) signals decrease in the task-driven activity. Here we examined the dynamics of a large-scale model of the human cortex to provide a mechanistic understanding of these observations. The model allows computing the statistics of synaptic activity in the spontaneous condition and in putative tasks determined by external inputs to a given subset of brain regions. We demonstrated that external inputs decrease the variance, increase the covariances, and decrease the autocovariance of synaptic activity as a consequence of single node and large-scale network dynamics. Altogether, these changes in network statistics imply a reduction of entropy, meaning that the spontaneous synaptic activity outlines a larger multidimensional activity space than does the task-driven activity. We tested this model's prediction on fMRI signals from healthy humans acquired during rest and task conditions and found a significant decrease of entropy in the stimulus-driven activity. Altogether, our study proposes a mechanism for increasing the information capacity of brain networks by enlarging the volume of possible activity configurations at rest and reliably settling into a confined stimulus-driven state to allow better transmission of stimulus-related information.

  10. Task-Driven Activity Reduces the Cortical Activity Space of the Brain: Experiment and Whole-Brain Modeling.

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    Adrián Ponce-Alvarez

    2015-08-01

    Full Text Available How a stimulus or a task alters the spontaneous dynamics of the brain remains a fundamental open question in neuroscience. One of the most robust hallmarks of task/stimulus-driven brain dynamics is the decrease of variability with respect to the spontaneous level, an effect seen across multiple experimental conditions and in brain signals observed at different spatiotemporal scales. Recently, it was observed that the trial-to-trial variability and temporal variance of functional magnetic resonance imaging (fMRI signals decrease in the task-driven activity. Here we examined the dynamics of a large-scale model of the human cortex to provide a mechanistic understanding of these observations. The model allows computing the statistics of synaptic activity in the spontaneous condition and in putative tasks determined by external inputs to a given subset of brain regions. We demonstrated that external inputs decrease the variance, increase the covariances, and decrease the autocovariance of synaptic activity as a consequence of single node and large-scale network dynamics. Altogether, these changes in network statistics imply a reduction of entropy, meaning that the spontaneous synaptic activity outlines a larger multidimensional activity space than does the task-driven activity. We tested this model's prediction on fMRI signals from healthy humans acquired during rest and task conditions and found a significant decrease of entropy in the stimulus-driven activity. Altogether, our study proposes a mechanism for increasing the information capacity of brain networks by enlarging the volume of possible activity configurations at rest and reliably settling into a confined stimulus-driven state to allow better transmission of stimulus-related information.

  11. Mechanism of Epac activation: structural and functional analyses of Epac2 hinge mutants with constitutive and reduced activities.

    Science.gov (United States)

    Tsalkova, Tamara; Blumenthal, Donald K; Mei, Fang C; White, Mark A; Cheng, Xiaodong

    2009-08-28

    Epac2 is a member of the family of exchange proteins directly activated by cAMP (Epac). Our previous studies suggest a model of Epac activation in which cAMP binding to the enzyme induces a localized "hinge" motion that reorients the regulatory lobe relative to the catalytic lobe without inducing large conformational changes within individual lobes. In this study, we identified the location of the major hinge in Epac2 by normal mode motion correlation and structural alignment analyses. Targeted mutagenesis was then performed to test the functional importance of hinge bending for Epac activation. We show that substitution of the conserved residue phenylalanine 435 with glycine (F435G) facilitates the hinge bending and leads to a constitutively active Epac2 capable of stimulating nucleotide exchange in the absence of cAMP. In contrast, substitution of the same residue with a bulkier side chain, tryptophan (F435W), impedes the hinge motion and results in a dramatic decrease in Epac2 catalytic activity. Structural parameters determined by small angle x-ray scattering further reveal that whereas the F435G mutant assumes a more extended conformation in the absence of cAMP, the F435W mutant is incapable of adopting the fully extended and active conformation in the presence of cAMP. These findings demonstrate the importance of hinge motion in Epac activation. Our study also suggests that phenylalanine at position 435 is the optimal size side chain to keep Epac closed and inactive in the absence of cAMP while still allowing the proper hinge motion for full Epac extension and activation in the presence of cAMP.

  12. Reduced influenza viral neutralizing activity of natural human trimers of surfactant protein D

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    Sorensen Grith L

    2007-02-01

    Full Text Available Abstract Background Surfactant protein D (SP-D plays important roles in innate host defense against influenza A virus (IAV infection. Common human polymorphisms of SP-D have been found in many human populations and associated with increased risk of certain infections. We recently reported that the Thr/Thr 11 form of SP-D is associated with low serum levels and assembles predominantly as trimers as opposed to the more common multimeric forms of SP-D. Methods Preliminary experiments were done to establish the effects of different monoclonal antibodies against SP-D on ability of SP-D to bind to or neutralize the virus. We then purified natural human trimeric and multimeric forms of SP-D from amniotic fluid and tested ability of these preparations to bind to IAV, to inhibit infectivity and hemagglutination activity of IAV in vitro. Results In initial experiments mAbs directed against different areas on the CRD of SP-D were found to have differing effects on antiviral activity. Using an mAb that did not interfere with antiviral activity of SP-D, we confirm that natural SP-D trimers had reduced ability to bind to IAV. In addition, the trimers had reduced ability to neutralize IAV as compared to natural human SP-D multimers as well as reduced hemagglutination inhibiting activity against several strains of IAV. Natural SP-D trimers also had different interactions with human neutrophil peptide defensins (HNPs in viral neutralization assays as compared to multimeric SP-D. Conclusion These studies indicate that a common human polymorphic form of SP-D may modulate host defense against IAV and give impetus to clinical studies correlating this genotype with risk for IAV infection in susceptible groups. We also show that mAbs directed against different areas on the carbohydrate recognition domain of SP-D can be useful for dissecting out different functional properties of the protein.

  13. The HR96 activator, atrazine, reduces sensitivity of D. magna to triclosan and DHA.

    Science.gov (United States)

    Sengupta, Namrata; Litoff, Elizabeth J; Baldwin, William S

    2015-06-01

    HR96 is a CAR/PXR/VDR ortholog in invertebrates, and a promiscuous endo- and xenobiotic nuclear receptor involved in acclimation to toxicants. Daphnia HR96 is activated by chemicals such as atrazine and linoleic acid (LA) (n-6 fatty acid), and inhibited by triclosan and docosahexaenoic acid (DHA) (n-3 fatty acid). We hypothesized that inhibitors of HR96 may block the protective responses of HR96 based on previously performed luciferase assays. Therefore, we performed acute toxicity tests with two-chemical mixtures containing a HR96 inhibitor (DHA or triclosan) and a HR96 activator (LA or atrazine). Surprisingly, results demonstrate that triclosan and DHA are less toxic when co-treated with 20-80 μM atrazine. Atrazine provides concentration-dependent protection as lower concentrations have no effect and higher concentrations cause toxicity. LA, a weaker HR96 activator, did not provide protection from triclosan or DHA. Atrazine's protective effects are presumably due to its ability to activate HR96 or other toxicologically relevant transcription factors and induce protective enzymes. Atrazine did not significantly induce glucosyltransferase, a crucial enzyme in triclosan detoxification. However, atrazine did increase antioxidant activities, crucial pathways in triclosan's toxicity, as measured through GST activity and the TROLOX equivalence assay. The increase in antioxidant capacity is consistent with atrazine providing protection from a wide range of toxicants that induce ROS, including triclosan and unsaturated fatty acids predisposed to lipid peroxidation.

  14. Demonstration of interleukin 1 activity in apparently homogeneous specimens of the pI 5 form of rabbit endogenous pyrogen.

    Science.gov (United States)

    Hanson, D F; Murphy, P A

    1984-08-01

    Rabbit mononuclear cells from oil-induced peritoneal exudates were purified by centrifugation on Percoll gradients, suspended in tissue culture medium, and stimulated with opsonized Staphylococcus epidermidis. The supernatants from these macrophages caused fever when injected intravenously into rabbits (endogenous pyrogen [EP] activity). The EP activity was contained in two protein fractions, with pIs of 7.3 and ca. 5.0. The same fractions caused mouse thymocytes to incorporate tritiated thymidine when incubated in vitro with small quantities of phytohemagglutinin (interleukin 1 [IL-1] activity). The pI 5.0 form of EP was purified to apparent homogeneity by sequential use of ammonium sulfate precipitation, gel filtration, ion-exchange chromatography, hydrophobic chromatography, and high-resolution isoelectric focusing. EP and IL-1 activities were not separable by any of these procedures. Active fractions from isoelectric focusing were analyzed by polyacrylamide gel electrophoresis in the presence of sodium dodecyl sulfate. Only one band was visible as judged by a silver staining method, and IL-1 activity could be recovered by renaturing eluates from the same region of sodium dodecyl sulfate gels run in parallel. An estimate of specific activity was made by comparing the intensity of stained bands of EP with the intensity of bands containing known quantities of lysozyme or RNase. By this criterion, the specific activity of purified pI 5 EP was between 17,000 and 58,000 degrees C U/mg of protein, and the specific activity in terms of IL-1 was between 59 million and 360 million U per mg of protein. These observations suggest that both EP and IL-1 activities can be expressed by a single molecular species. The implications of this coincidence are discussed. It was also shown that highly purified pI 5 EP obtained from macrophages stimulated in the presence of 14C-labeled amino acids contained significant 14C radioactivity. This suggests that the pI 5.0 EP, like the pI 7

  15. Multitaxon activity profiling reveals differential microbial response to reduced seawater pH and oil pollution.

    Science.gov (United States)

    Coelho, Francisco J R C; Cleary, Daniel F R; Costa, Rodrigo; Ferreira, Marina; Polónia, Ana R M; Silva, Artur M S; Simões, Mário M Q; Oliveira, Vanessa; Gomes, Newton C M

    2016-09-01

    There is growing concern that predicted changes to global ocean chemistry will interact with anthropogenic pollution to significantly alter marine microbial composition and function. However, knowledge of the compounding effects of climate change stressors and anthropogenic pollution is limited. Here, we used 16S and 18S rRNA (cDNA)-based activity profiling to investigate the differential responses of selected microbial taxa to ocean acidification and oil hydrocarbon contamination under controlled laboratory conditions. Our results revealed that a lower relative abundance of sulphate-reducing bacteria (Desulfosarcina/Desulfococcus clade) due to an adverse effect of seawater acidification and oil hydrocarbon contamination (reduced pH-oil treatment) may be coupled to changes in sediment archaeal communities. In particular, we observed a pronounced compositional shift and marked reduction in the prevalence of otherwise abundant operational taxonomic units (OTUs) belonging to the archaeal Marine Benthic Group B and Marine Hydrothermal Vent Group (MHVG) in the reduced pH-oil treatment. Conversely, the abundance of several putative hydrocarbonoclastic fungal OTUs was higher in the reduced pH-oil treatment. Sediment hydrocarbon profiling, furthermore, revealed higher concentrations of several alkanes in the reduced pH-oil treatment, corroborating the functional implications of the structural changes to microbial community composition. Collectively, our results advance the understanding of the response of a complex microbial community to the interaction between reduced pH and anthropogenic pollution. In future acidified marine environments, oil hydrocarbon contamination may alter the typical mixotrophic and k-/r-strategist composition of surface sediment microbiomes towards a more heterotrophic state with lower doubling rates, thereby impairing the ability of the ecosystem to recover from acute oil contamination events.

  16. GASIS demonstration

    Energy Technology Data Exchange (ETDEWEB)

    Vidas, E.H. [Energy and Environmental Analysis, Inc., Arlington, VA (United States)

    1995-04-01

    A prototype of the GASIS database and retrieval software has been developed and is the subject of this poster session and computer demonstration. The prototype consists of test or preliminary versions of the GASIS Reservoir Data System and Source Directory datasets and the software for query and retrieval. The prototype reservoir database covers the Rocky Mountain region and contains the full GASIS data matrix (all GASIS data elements) that will eventually be included on the CD-ROM. It is populated for development purposes primarily by the information included in the Rocky Mountain Gas Atlas. The software has been developed specifically for GASIS using Foxpro for Windows. The application is an executable file that does not require Foxpro to run. The reservoir database software includes query and retrieval, screen display, report generation, and data export functions. Basic queries by state, basin, or field name will be assisted by scrolling selection lists. A detailed query screen will allow record selection on the basis of any data field, such as depth, cumulative production, or geological age. Logical operators can be applied to any-numeric data element or combination of elements. Screen display includes a {open_quotes}browse{close_quotes} display with one record per row and a detailed single record display. Datasets can be exported in standard formats for manipulation with other software packages. The Source Directory software will allow record retrieval by database type or subject area.

  17. Mitogen-activated protein kinase inhibition and cardioplegia-cardiopulmonary bypass reduce coronary myogenic tone.

    Science.gov (United States)

    Khan, Tanveer A; Bianchi, Cesario; Ruel, Marc; Voisine, Pierre; Li, Jianyi; Liddicoat, John R; Sellke, Frank W

    2003-09-09

    Cardioplegia-cardiopulmonary bypass (C/CPB) is associated with coronary microcirculatory dysfunction. Regulation of the microcirculation includes myogenic tone. Mitogen-activated protein kinases (MAPK) have been implicated in coronary vasomotor function. We hypothesized that vasomotor dysfunction of the coronary microcirculation is mediated in part by alterations in extracellular signal regulated kinase 1/2 (ERK1/2) activity following C/CPB in humans. Atrial myocardium was harvested from patients (n=15) before and after blood cardioplegia and short-term reperfusion under conditions of CPB. Myogenic tone of coronary arterioles was measured by videomicroscopy. Microvessel tone was determined post-C/CPB and after PD98059, a MAPK/ERK kinase 1/2 (MEK1/2) inhibitor. MAPK phosphatase-1 (MKP-1) and activated ERK1/2 were measured by Western blot. MKP-1 gene expression was determined by Northern blot. In situ hybridization and immunohistochemistry were used to localize myocardial MKP-1 and activated ERK1/2, respectively. Myogenic tone was reduced in coronary arterioles post-C/CPB (-10.5+/-0.9%, P<0.01 versus control/pre-C/CPB, n=5). Myogenic tone was decreased in coronary microvessels after 30 micromol/L (n=5) and 50 micromol/L (n=5) PD98059 treatment (-11.0+/-0.8% and -14.6+/-2.0%, respectively, both P<0.01 versus control/pre-C/CPB). Myocardial levels of activated ERK1/2 were reduced post-C/CPB (0.6+/-0.1, post/pre-C/CPB ratio, P<0.05, n=5) while MKP-1 levels increased (4.2+/-0.6, post/pre-C/CPB ratio, P<0.05, n=5). Myocardial MKP-1 gene expression increased post-C/CPB (3.0+/-0.8, post/pre-C/CPB ratio, P<0.05, n=5). MKP-1 and activated ERK1/2 localized to coronary arterioles in myocardial sections. Coronary myogenic tone is dependent on ERK1/2 and decreased after C/CPB. C/CPB reduces levels of activated ERK1/2, potentially by increased levels of MKP-1. The ERK1/2 signal transduction pathway in part mediates coronary microvascular dysfunction after C/CPB in humans.

  18. Polyenylpyrrole derivatives inhibit NLRP3 inflammasome activation and inflammatory mediator expression by reducing reactive oxygen species production and mitogen-activated protein kinase activation.

    Directory of Open Access Journals (Sweden)

    Kuo-Feng Hua

    Full Text Available Two polyenylpyrroles from a soil ascomycete Gymnoascus reessii were previously identified as hit compounds in screening for cytotoxicity against lung cancer cells. These compounds and various analogs, which have been previously synthesized and tested for anti-lung cancer cell activity, were tested for anti-inflammatory activity. After preliminary screening for cytotoxicity for RAW 264.7 murine macrophage cells, the non-toxic compounds were tested for anti-inflammatory activity using lipopolysaccharide (LPS-activated RAW 264.7 cells. Compounds 1h, 1i, and 1n reduced LPS-induced nitric oxide (NO production, with respective ED50 values of 15 ± 2, 16 ± 2, and 17 ± 2 µM. They also reduced expression of inducible NO synthase and interleukin-6 (IL-6 without affecting cyclooxygenase-2 expression. Compound 1h also reduced secretion of IL-6 and tumor necrosis factor-α by LPS-activated J774A.1 murine macrophage cells, primary mice peritoneal macrophages, and JAWSII murine bone marrow-derived dendritic cells and reduced NLRP3 inflammasome-mediated interleukin-1β (IL-1β secretion by LPS + adenosine triphosphate-activated J774A.1 and JAWSII cells. The underlying mechanisms for the anti-inflammatory activity of compound 1h were found to be a decrease in LPS-induced reactive oxygen species (ROS production, mitogen-activated protein kinase phosphorylation, and NF-κB activation and a decrease in ATP-induced ROS production and PKC-α phosphorylation. These results provide promising insights into the anti-inflammatory activity of these conjugated polyenes and a molecular rationale for future therapeutic intervention in inflammation-related diseases. They also show how compound 1h regulates inflammation and suggest it may be a new source for the development of anti-inflammatory agents to ameliorate inflammation- and NLRP3 inflammasome-related diseases.

  19. Observing Exoplanets with High-dispersion Coronagraphy. II. Demonstration of an Active Single-mode Fiber Injection Unit

    Science.gov (United States)

    Mawet, D.; Ruane, G.; Xuan, W.; Echeverri, D.; Klimovich, N.; Randolph, M.; Fucik, J.; Wallace, J. K.; Wang, J.; Vasisht, G.; Dekany, R.; Mennesson, B.; Choquet, E.; Delorme, J.-R.; Serabyn, E.

    2017-04-01

    High-dispersion coronagraphy (HDC) optimally combines high-contrast imaging techniques such as adaptive optics/wavefront control plus coronagraphy to high spectral resolution spectroscopy. HDC is a critical pathway toward fully characterizing exoplanet atmospheres across a broad range of masses from giant gaseous planets down to Earth-like planets. In addition to determining the molecular composition of exoplanet atmospheres, HDC also enables Doppler mapping of atmosphere inhomogeneities (temperature, clouds, wind), as well as precise measurements of exoplanet rotational velocities. Here, we demonstrate an innovative concept for injecting the directly imaged planet light into a single-mode fiber, linking a high-contrast adaptively corrected coronagraph to a high-resolution spectrograph (diffraction-limited or not). Our laboratory demonstration includes three key milestones: close-to-theoretical injection efficiency, accurate pointing and tracking, and on-fiber coherent modulation and speckle nulling of spurious starlight signal coupling into the fiber. Using the extreme modal selectivity of single-mode fibers, we also demonstrated speckle suppression gains that outperform conventional image-based speckle nulling by at least two orders of magnitude.

  20. Partial ozonation of activated sludge to reduce excess sludge, improve denitrification and control scumming and bulking

    Energy Technology Data Exchange (ETDEWEB)

    Boehler, Marc; Siegrist, Hansruedi

    2003-07-01

    Disposal of sewage sludge is forbidden and agricultural use of stabilized sludge will be banned in 2005 in Switzerland. The sludge has to be dewatered, dried, Incinerated and the ashes disposed in landfills. These processes are cost intensive and lead also to the loss of valuable phosphate resources incorporated in the sludge ash. The implementation of processes that could reduce excess sludge production and recycle phosphate is therefore recommended. Partial ozonation of the return sludge of an activated sludge system reduces significantly excess sludge production, improves settling properties of the sludge and reduces bulking and scumming. The solubilized COD will also improve denitrification if the treated sludge is recycled to the anoxic zone. But ozonation will partly inhibit and kill nitrifiers and might therefore lead to a decrease of the effective solid retention time of the nitrifier, which reduces the safety of the nitrification. This paper discusses the effect of ozonation on sludge reduction, the operation stability of nitrification, improvement of denitrification and gives also an energy and cost evaluation. (author)

  1. Synthetic pheromones as a management technique - dispensers reduce Linepithema humile activity in a commercial vineyard.

    Science.gov (United States)

    Westermann, Fabian L; Bell, Vaughn A; Suckling, David M; Lester, Philip J

    2016-04-01

    Invasive ants, such as the Argentine ant, have often been reported to facilitate honeydew-producing hemipteran pests such as mealybugs, which can be vectors of plant pathogens. Synthetic pheromones may offer a target-specific method to control such ants and consequently lower the abundance of honeydew-producing pests. Here we report the results of a trial to suppress Argentine ants in grapevines using ant pheromone dispensers. Compared with untreated controls, we observed a significant drop in Argentine ant activity on the ground, irrespective of whether pheromone dispensers were placed at ground level, within the canopy or in both locations. Ant counts in the canopy confirmed that Argentine ant abundance was reduced under the influence of the pheromone dispenser placed at ground level compared with untreated controls. However, placing dispensers only in the canopy did not reduce the numbers of ants within the canopy compared with untreated controls. Our results showed that pheromone dispensers can significantly reduce Argentine ant foraging in grapevines if they are positioned appropriately. This technique could potentially reduce the abundance of associated mealybugs and potentially attendant virus vectoring areawide. © 2015 Society of Chemical Industry.

  2. Reduced expression of dermcidin, a peptide active against propionibacterium acnes, in sweat of patients with acne vulgaris.

    Science.gov (United States)

    Nakano, Toshiaki; Yoshino, Takashi; Fujimura, Takao; Arai, Satoru; Mukuno, Akira; Sato, Naoya; Katsuoka, Kensei

    2015-09-01

    Dermcidin (DCD), an antimicrobial peptide with a broad spectrum of activity against bacteria such as Propionibacterum acnes, is expressed constitutively in sweat in the absence of stimulation due to injury or inflammation. The aim of this study was to determine the relationship between DCD expression and acne vulgaris associated with P. acnes. The antimicrobial activity of recombinant full-length DCD (50 μg/ml) was 97% against Escherichia coli and 100% against Staphylococcus aureus. Antimicrobial activity against P. acnes ranged from 68% at 50 μg/ml DCD to 83% at 270 μg/ml DCD. DCD concentration in sweat from patients with acne vulgaris (median 9.8 μg/ml, range 6.9-95.3 μg/ml) was significantly lower than in healthy subjects (median 136.7 μg/ml, range 45.4-201.6 μg/ml) (p = 0.001). DCD demonstrated concentration-dependent, but partial, microbicidal activity against P. acnes. These results suggest that reduced DCD concentration in sweat in patients with inflammatory acne may permit proliferation of P. acnes in pilosebaceous units, resulting in progression of inflammatory acne.

  3. Combined approach to demonstrate acetylcholinesterase activity changes in the rat brain following tabun intoxication and its treatment.

    Science.gov (United States)

    Bajgar, Jiri; Hajek, Petr; Kassa, Jiri; Slizova, Dasa; Krs, Otakar; Karasova, Jana Zdarova; Fusek, Josef; Capek, Lukas; Voicu, Victor A

    2012-01-01

    Reactivation effects of K203 and currently available oximes (obidoxime, HI-6) in combination with atropine on acetylcholinesterase activities in the brain parts of rats poisoned with tabun were studied. The activity was determined by quantitative histochemical and biochemical methods correlating between them very well. The tabun-induced changes in acetylcholinsterase activity as well as in reactivation potency of reactivators used were different in various parts of the brain. Pontomedullar area seems to be important for observed changes following tabun intoxication and its treatment. From the oximes studied, the reactivation effect of K203 was comparable with obidoxime; HI-6 was ineffective. Combination of bio- and histochemical methods allow fine differentiation among the action of different oximes following tabun poisoning.

  4. Niclosamide, an old antihelminthic agent, demonstrates antitumor activity by blocking multiple signaling pathways of cancer stem cells

    Institute of Scientific and Technical Information of China (English)

    Jing-Xuan Pan; Ke Ding; Cheng-Yan Wang

    2012-01-01

    Niclosamide,an oral antihelminthic drug,has been used to treat tapeworm infection for about 50 years.Niclosamide is also used as a molluscicide for water treatment in schistosomiasis control programs.Recently,several groups have independently discovered that niclosamide is also active against cancer cells,but its precise mechanism of antitumor action is not fully understood.Evidence supports that niclosamide targets multiple signaling pathways (NF-κB,Wnt/β-catenin,Notch,ROS,mTORC1,and Stat3),most of which are closely involved with cancer stem cells.The exciting advances in elucidating the antitumor activity and the molecular targets of this drug will be discussed.A method for synthesizing a phosphate pro-drug of niclosamide is provided.Given its potential antitumor activity,clinical trials for niclosamide and its derivatives are warranted for cancer treatment.

  5. Objective measurements of activity patterns in people with newly diagnosed Type 2 diabetes demonstrate a sedentary lifestyle.

    Science.gov (United States)

    Cichosz, S L; Fleischer, J; Hoeyem, P; Laugesen, E; Poulsen, P L; Christiansen, J S; Ejskjær, N; Hansen, T K

    2013-09-01

    To evaluate physical activity in people with newly diagnosed Type 2 diabetes using objective measures. We analysed data from a study aimed at assessing carotid femoral pulse wave velocity in which a piezoelectric accelerometer was worn by 100 people with newly diagnosed Type 2 diabetes and by 100 age- and sex-matched control subjects. Differences in physical activity patterns were investigated. Compared with the control group, the people with Type 2 diabetes spent significantly more time engaged in sedentary or lower level activities during the day, with a mean (sd) time of 926 (44) vs 898 (70) min, P sedentary lifestyle compared with well-matched controls. © 2013 The Authors. Diabetic Medicine © 2013 Diabetes UK.

  6. TLR4 mutation reduces microglial activation, increases Aβ deposits and exacerbates cognitive deficits in a mouse model of Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Song Min

    2011-08-01

    Full Text Available Abstract Background Amyloid plaques, a pathological hallmark of Alzheimer's disease (AD, are accompanied by activated microglia. The role of activated microglia in the pathogenesis of AD remains controversial: either clearing Aβ deposits by phagocytosis or releasing proinflammatory cytokines and cytotoxic substances. Microglia can be activated via toll-like receptors (TLRs, a class of pattern-recognition receptors in the innate immune system. We previously demonstrated that an AD mouse model homozygous for a loss-of-function mutation of TLR4 had increases in Aβ deposits and buffer-soluble Aβ in the brain as compared with a TLR4 wild-type AD mouse model at 14-16 months of age. However, it is unknown if TLR4 signaling is involved in initiation of Aβ deposition as well as activation and recruitment of microglia at the early stage of AD. Here, we investigated the role of TLR4 signaling and microglial activation in early stages using 5-month-old AD mouse models when Aβ deposits start. Methods Microglial activation and amyloid deposition in the brain were determined by immunohistochemistry in the AD models. Levels of cerebral soluble Aβ were determined by ELISA. mRNA levels of cytokines and chemokines in the brain and Aβ-stimulated monocytes were quantified by real-time PCR. Cognitive functions were assessed by the Morris water maze. Results While no difference was found in cerebral Aβ load between AD mouse models at 5 months with and without TLR4 mutation, microglial activation in a TLR4 mutant AD model (TLR4M Tg was less than that in a TLR4 wild-type AD model (TLR4W Tg. At 9 months, TLR4M Tg mice had increased Aβ deposition and soluble Aβ42 in the brain, which were associated with decrements in cognitive functions and expression levels of IL-1β, CCL3, and CCL4 in the hippocampus compared to TLR4W Tg mice. TLR4 mutation diminished Aβ-induced IL-1β, CCL3, and CCL4 expression in monocytes. Conclusion This is the first demonstration of TLR4

  7. Reduced 11beta-hydroxysteroid dehydrogenase activity in patients with the nephrotic syndrome.

    Science.gov (United States)

    Vogt, B; Dick, B; N'Gankam, V; Frey, F J; Frey, B M

    1999-02-01

    Patients with the nephrotic syndrome (NS) exhibit abnormal renal sodium retention which cannot completely explained by a secondary hyperaldosteronism due to reduced renal perfusion. As an alternative mechanism to explain this phenomenon we postulate a cortisol-mediated mineralocorticoid effect as a consequence of a reduced activity of 11beta-hydroxysteroid dehydrogenase (11beta-HSD). A down-regulation of 11beta-HSD, i.e. of the shuttle of active to inactive glucocorticosteroids, has been shown to cause mineralocorticoid effects. Therefore we investigated the activity of 11beta-HSD by measuring the urinary ratio of (tetrahydrocortisol + 5alpha-tetrahydrocortisol)/tetrahydrocortisone [(THF+5alpha-THF)/THE] by gas-chromatography in 29 NS patients with biopsy-proven glomerulonephritis and 29 healthy control subjects. The ratio of (THF+5alpha-THF)/THE was higher in NS patients (median 1.49, range 0.45-4.07) than in the control subjects (0.98, 0.60-1.36; pnew mechanism contributing to the exaggerated sodium retention in patients with the NS.

  8. Obesity and insulin resistance are associated with reduced activity in core memory regions of the brain.

    Science.gov (United States)

    Cheke, Lucy G; Bonnici, Heidi M; Clayton, Nicola S; Simons, Jon S

    2017-02-01

    Increasing research in animals and humans suggests that obesity may be associated with learning and memory deficits, and in particular with reductions in episodic memory. Rodent models have implicated the hippocampus in obesity-related memory impairments, but the neural mechanisms underlying episodic memory deficits in obese humans remain undetermined. In the present study, lean and obese human participants were scanned using fMRI while completing a What-Where-When episodic memory test (the "Treasure-Hunt Task") that assessed the ability to remember integrated item, spatial, and temporal details of previously encoded complex events. In lean participants, the Treasure-Hunt task elicited significant activity in regions of the brain known to be important for recollecting episodic memories, such as the hippocampus, angular gyrus, and dorsolateral prefrontal cortex. Both obesity and insulin resistance were associated with significantly reduced functional activity throughout the core recollection network. These findings indicate that obesity is associated with reduced functional activity in core brain areas supporting episodic memory and that insulin resistance may be a key player in this association. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

  9. Bacteriophages of wastewater foaming-associated filamentous Gordonia reduce host levels in raw activated sludge

    Science.gov (United States)

    Liu, Mei; Gill, Jason J.; Young, Ry; Summer, Elizabeth J.

    2015-01-01

    Filamentous bacteria are a normal and necessary component of the activated sludge wastewater treatment process, but the overgrowth of filamentous bacteria results in foaming and bulking associated disruptions. Bacteriophages, or phages, were investigated for their potential to reduce the titer of foaming bacteria in a mixed-microbial activated sludge matrix. Foaming-associated filamentous bacteria were isolated from activated sludge of a commercial wastewater treatment plan and identified as Gordonia species by 16S rDNA sequencing. Four representative phages were isolated that target G. malaquae and two un-named Gordonia species isolates. Electron microscopy revealed the phages to be siphophages with long tails. Three of the phages - GordTnk2, Gmala1, and GordDuk1 - had very similar ~76 kb genomes, with >93% DNA identity. These genomes shared limited synteny with Rhodococcus equi phage ReqiDocB7 and Gordonia phage GTE7. In contrast, the genome of phage Gsput1 was smaller (43 kb) and was not similar enough to any known phage to be placed within an established phage type. Application of these four phages at MOIs of 5–15 significantly reduced Gordonia host levels in a wastewater sludge model by approximately 10-fold as compared to non-phage treated reactors. Phage control was observed for nine days after treatment. PMID:26349678

  10. Reduced amygdala and ventral striatal activity to happy faces in PTSD is associated with emotional numbing.

    Directory of Open Access Journals (Sweden)

    Kim L Felmingham

    Full Text Available There has been a growing recognition of the importance of reward processing in PTSD, yet little is known of the underlying neural networks. This study tested the predictions that (1 individuals with PTSD would display reduced responses to happy facial expressions in ventral striatal reward networks, and (2 that this reduction would be associated with emotional numbing symptoms. 23 treatment-seeking patients with Posttraumatic Stress Disorder were recruited from the treatment clinic at the Centre for Traumatic Stress Studies, Westmead Hospital, and 20 trauma-exposed controls were recruited from a community sample. We examined functional magnetic resonance imaging responses during the presentation of happy and neutral facial expressions in a passive viewing task. PTSD participants rated happy facial expression as less intense than trauma-exposed controls. Relative to controls, PTSD participants revealed lower activation to happy (-neutral faces in ventral striatum and and a trend for reduced activation in left amygdala. A significant negative correlation was found between emotional numbing symptoms in PTSD and right ventral striatal regions after controlling for depression, anxiety and PTSD severity. This study provides initial evidence that individuals with PTSD have lower reactivity to happy facial expressions, and that lower activation in ventral striatal-limbic reward networks may be associated with symptoms of emotional numbing.

  11. Micro-structuring of polycarbonate-urethane surfaces in order to reduce platelet activation and adhesion.

    Science.gov (United States)

    Clauser, Johanna; Gester, Kathrin; Roggenkamp, Jan; Mager, Ilona; Maas, Judith; Jansen, Sebastian V; Steinseifer, Ulrich

    2014-01-01

    In the development of new hemocompatible biomaterials, surface modification appears to be a suitable method in order to reduce the thrombogenetic potential of such materials. In this study, polycarbonate-urethane (PCU) tubes with different surface microstructures to be used for aortic heart valve models were investigated with regard to the thrombogenicity. The surface structures were produced by using a centrifugal casting process for manufacturing PCU tubes with defined casting mold surfaces which are conferred to the PCU surface during the process. Tubes with different structures defined by altering groove widths were cut into films and investigated under dynamic flow conditions in contact with porcine blood. The analysis was carried out by laser scanning microscopy which allowed for counting various morphological types of platelets with regard to the grade of activation. The comparison between plain and shaped PCU samples showed that the surface topography led to a decline of the activation of the coagulation cascade and thus to the reduction of the fibrin synthesis. Comparing different types of structures revealed that smooth structures with a small groove width (d ~ 3 μm) showed less platelet activation as well as less adhesion in contrast to a distinct wave structure (d ~ 90 μm). These results prove surface modification of polymer biomaterials to be a suitable method for reducing thrombogenicity and hence give reason for further alterations and improvements.

  12. Bacteriophages of wastewater foaming-associated filamentous Gordonia reduce host levels in raw activated sludge.

    Science.gov (United States)

    Liu, Mei; Gill, Jason J; Young, Ry; Summer, Elizabeth J

    2015-09-09

    Filamentous bacteria are a normal and necessary component of the activated sludge wastewater treatment process, but the overgrowth of filamentous bacteria results in foaming and bulking associated disruptions. Bacteriophages, or phages, were investigated for their potential to reduce the titer of foaming bacteria in a mixed-microbial activated sludge matrix. Foaming-associated filamentous bacteria were isolated from activated sludge of a commercial wastewater treatment plan and identified as Gordonia species by 16S rDNA sequencing. Four representative phages were isolated that target G. malaquae and two un-named Gordonia species isolates. Electron microscopy revealed the phages to be siphophages with long tails. Three of the phages--GordTnk2, Gmala1, and GordDuk1--had very similar ~76 kb genomes, with >93% DNA identity. These genomes shared limited synteny with Rhodococcus equi phage ReqiDocB7 and Gordonia phage GTE7. In contrast, the genome of phage Gsput1 was smaller (43 kb) and was not similar enough to any known phage to be placed within an established phage type. Application of these four phages at MOIs of 5-15 significantly reduced Gordonia host levels in a wastewater sludge model by approximately 10-fold as compared to non-phage treated reactors. Phage control was observed for nine days after treatment.

  13. Quetiapine treatment reverses depressive-like behavior and reduces DNA methyltransferase activity induced by maternal deprivation.

    Science.gov (United States)

    Ignácio, Zuleide M; Réus, Gislaine Z; Abelaira, Helena M; Maciel, Amanda L; de Moura, Airam B; Matos, Danyela; Demo, Júlia P; da Silva, Júlia B I; Gava, Fernanda F; Valvassori, Samira S; Carvalho, André F; Quevedo, João

    2017-03-01

    Stress in early life has been appointed as an important phenomenon in the onset of depression and poor response to treatment with classical antidepressants. Furthermore, childhood trauma triggers epigenetic changes, which are associated with the pathophysiology of major depressive disorder (MDD). Treatment with atypical antipsychotics such as quetiapine, exerts therapeutic effect for MDD patients and induces epigenetic changes. This study aimed to analyze the effect of chronic treatment with quetiapine (20mg/kg) on depressive-like behavior of rats submitted to maternal deprivation (MD), as well as the activity of histone acetylation by the enzymes histone acetyl transferases (HAT) and deacetylases (HDAC) and DNA methylation, through DNA methyltransferase enzyme (DNMT) in the prefrontal cortex (PFC), nucleus accumbens (NAc) and hippocampus. Maternally deprived rats had a depressive-like behavior in the forced swimming test and an increase in the HDAC and DNMT activities in the hippocampus and NAc. Treatment with quetiapine reversed depressive-like behavior and reduced the DNMT activity in the hippocampus. This is the first study to show the antidepressant-like effect of quetiapine in animals subjected to MD and a protective effect by quetiapine in reducing epigenetic changes induced by stress in early life. These results reinforce an important role of quetiapine as therapy for MDD. Copyright © 2016 Elsevier B.V. All rights reserved.

  14. Acutely decreased thermoregulatory energy expenditure or decreased activity energy expenditure both acutely reduce food intake in mice.

    Directory of Open Access Journals (Sweden)

    Karl J Kaiyala

    Full Text Available Despite the suggestion that reduced energy expenditure may be a key contributor to the obesity pandemic, few studies have tested whether acutely reduced energy expenditure is associated with a compensatory reduction in food intake. The homeostatic mechanisms that control food intake and energy expenditure remain controversial and are thought to act over days to weeks. We evaluated food intake in mice using two models of acutely decreased energy expenditure: 1 increasing ambient temperature to thermoneutrality in mice acclimated to standard laboratory temperature or 2 exercise cessation in mice accustomed to wheel running. Increasing ambient temperature (from 21 °C to 28 °C rapidly decreased energy expenditure, demonstrating that thermoregulatory energy expenditure contributes to both light cycle (40 ± 1% and dark cycle energy expenditure (15 ± 3% at normal ambient temperature (21 °C. Reducing thermoregulatory energy expenditure acutely decreased food intake primarily during the light cycle (65 ± 7%, thus conflicting with the delayed compensation model, but did not alter spontaneous activity. Acute exercise cessation decreased energy expenditure only during the dark cycle (14 ± 2% at 21 °C; 21 ± 4% at 28 °C, while food intake was reduced during the dark cycle (0.9 ± 0.1 g in mice housed at 28 °C, but during the light cycle (0.3 ± 0.1 g in mice housed at 21 °C. Cumulatively, there was a strong correlation between the change in daily energy expenditure and the change in daily food intake (R(2 = 0.51, p<0.01. We conclude that acutely decreased energy expenditure decreases food intake suggesting that energy intake is regulated by metabolic signals that respond rapidly and accurately to reduced energy expenditure.

  15. The Associative Memory Deficit in Aging Is Related to Reduced Selectivity of Brain Activity during Encoding.

    Science.gov (United States)

    Saverino, Cristina; Fatima, Zainab; Sarraf, Saman; Oder, Anita; Strother, Stephen C; Grady, Cheryl L

    2016-09-01

    Human aging is characterized by reductions in the ability to remember associations between items, despite intact memory for single items. Older adults also show less selectivity in task-related brain activity, such that patterns of activation become less distinct across multiple experimental tasks. This reduced selectivity or dedifferentiation has been found for episodic memory, which is often reduced in older adults, but not for semantic memory, which is maintained with age. We used fMRI to investigate whether there is a specific reduction in selectivity of brain activity during associative encoding in older adults, but not during item encoding, and whether this reduction predicts associative memory performance. Healthy young and older adults were scanned while performing an incidental encoding task for pictures of objects and houses under item or associative instructions. An old/new recognition test was administered outside the scanner. We used agnostic canonical variates analysis and split-half resampling to detect whole-brain patterns of activation that predicted item versus associative encoding for stimuli that were later correctly recognized. Older adults had poorer memory for associations than did younger adults, whereas item memory was comparable across groups. Associative encoding trials, but not item encoding trials, were predicted less successfully in older compared with young adults, indicating less distinct patterns of associative-related activity in the older group. Importantly, higher probability of predicting associative encoding trials was related to better associative memory after accounting for age and performance on a battery of neuropsychological tests. These results provide evidence that neural distinctiveness at encoding supports associative memory and that a specific reduction of selectivity in neural recruitment underlies age differences in associative memory.

  16. Reducing friction-induced vibration using intelligent active force control (AFC) with piezoelectric actuators

    Indian Academy of Sciences (India)

    S M Hashemi-Dehkordi; A R Abu-Bakar; M Mailah

    2012-12-01

    In this paper, a novel approach to reduce the effect of mode coupling that causes friction induced vibration (FIV) is proposed by applying an intelligent active force control (AFC)-based strategy employing piezoelectric actuators with hysteresis effect to a simplified two degree-of-freedom mathematical model of a friction-induced vibration system. At first, the model is simulated and analysed using a closed loop pure Proportional-Integral-Derivative (PID) controller. Later, it is integrated with the intelligent AFC with fuzzy logic (FL) estimator and simulated under similar operating condition. After running several tests with different sets of operating and loading conditions, the results both in time and frequency domains show that the PID controller with the intelligent AFC is much more effective in reducing the vibration, compared to the pure PID controller alone.

  17. Application of an active controller for reducing small-amplitude vertical vibration in a vehicle seat

    Science.gov (United States)

    Wu, Jian-Da; Chen, Rong-Jun

    2004-07-01

    This report describes the principle and application of active vibration control (AVC) for reducing undesired small-amplitude vertical vibration in the driver's seat of a vehicle. Three different control algorithms are implemented and compared in the experimental investigation. Apart from adaptive control and robust control, a hybrid control algorithm consisting of a combination of an adaptive controller with a filtered-x least mean squares (FXLMS) algorithm and a feedback structure with a robust synthesis theory for obtaining fast convergence and robust performance are proposed. A frequency domain technique is used for achieving the control plant identification and controller design. All of the proposed AVC controllers are implemented in a digital signal processor (DSP) platform, using a finite impulse response (FIR) filter for real-time control. A characteristic analysis and experimental comparison of three control algorithms for reducing the small amplitude vertical vibration in a vehicle seat are also presented in this paper.

  18. Reduced lymphocyte activation in space - Role of cell-substratum interactions

    Science.gov (United States)

    Gmuender, F. K.; Kiess, M.; Lee, J.; Cogoli, A.; Sonnenfeld, G.

    1992-01-01

    The effect of substratum adhesiveness on lymphocyte responsiveness was investigated by reducing and blocking cell adhesion with poly-HEMA in a simple on ground system. Cells grown on medium thick and thick poly-HEMA films were rounded in shape and displayed no signs of spreading. By contrast, on tissue culture plastic and very thin poly-HEMA films, they showed clear signs of spreading. The mitogenic response of lymphocytes grown on thick poly-HEMA films was reduced by up to 68 percent of the control (tissue culture plastic). Interferon gamma production was virtually nil when the cells were grown on the least adhesive substratum. These results show that activated lymphocytes need to anchor and spread prior to achieving an optimal proliferation response. It is concluded that decreased lymphocyte adhesion could contribute to the depressed in vitro lymphocyte responsiveness found in the microgravity conditions of space flight.

  19. Tryptophan-Assisted Synthesis Reduces Bimetallic Gold/Silver Nanoparticle Cytotoxicity and Improves Biological Activity

    Directory of Open Access Journals (Sweden)

    Igor O. Shmarakov

    2014-10-01

    Full Text Available Aiming to reduce the potential in vivo hepato-and nephrotoxicity of Ag/Au bimetallic nanoparticles (NPs stabilized by sodium dodecyl sulphate (SDS, an approach involving a simultaneous reduction of silver nitrate and tetrachlorauratic acid using tryptophan (Trp as a reducing/stabilizing agent was applied during NP synthesis. The obtained Ag/Au/Trp NPs (5–15 nm sized were able to form stable aggregates with an average size of 370–450 nm and were potentially less toxic than Ag/Au/SDS in relation to a mouse model system based on clinical biochemical parameters and oxidative damage product estimation. Ag/Au/Trp NPs were shown to exhibit anticancer activity in relation to a Lewis lung carcinoma model. The data generated from the present study support the fact that the use of tryptophan in NP synthesis is effective in attenuating the potential hepatotoxicity and nephrotoxicity of NPs during their in vivo application.

  20. Activation of Spinal α2-Adrenoceptors Using Diluted Bee Venom Stimulation Reduces Cold Allodynia in Neuropathic Pain Rats

    Directory of Open Access Journals (Sweden)

    Suk-Yun Kang

    2012-01-01

    Full Text Available Cold allodynia is an important distinctive feature of neuropathic pain. The present study examined whether single or repetitive treatment of diluted bee venom (DBV reduced cold allodynia in sciatic nerve chronic constriction injury (CCI rats and whether these effects were mediated by spinal adrenergic receptors. Single injection of DBV (0.25 or 2.5 mg/kg was performed into Zusanli acupoint 2 weeks post CCI, and repetitive DBV (0.25 mg/kg was injected for 2 weeks beginning on day 15 after CCI surgery. Single treatment of DBV at a low dose (0.25 mg/kg did not produce any anticold allodynic effect, while a high dose of DBV (2.5 mg/kg significantly reduced cold allodynia. Moreover, this effect of high-dose DBV was completely blocked by intrathecal pretreatment of idazoxan (α2-adrenoceptor antagonist, but not prazosin (α1-adrenoceptor antagonist or propranolol (nonselective β-adrenoceptor antagonist. In addition, coadministration of low-dose DBV (0.25 mg/kg and intrathecal clonidine (α2-adrenoceptor agonist synergically reduced cold allodynia. On the other hand, repetitive treatments of low-dose DBV showing no motor deficit remarkably suppressed cold allodynia from 7 days after DBV treatment. This effect was also reversed by intrathecal idazoxan injection. These findings demonstrated that single or repetitive stimulation of DBV could alleviate CCI-induced cold allodynia via activation of spinal α2-adrenoceptor.

  1. Activated expression of an Arabidopsis HD-START protein confers drought tolerance with improved root system and reduced stomatal density.

    Science.gov (United States)

    Yu, Hong; Chen, Xi; Hong, Yuan-Yuan; Wang, Yao; Xu, Ping; Ke, Sheng-Dong; Liu, Hai-Yan; Zhu, Jian-Kang; Oliver, David J; Xiang, Cheng-Bin

    2008-04-01

    Drought is one of the most important environmental constraints limiting plant growth and agricultural productivity. To understand the underlying mechanism of drought tolerance and to identify genes for improving this important trait, we conducted a gain-of-function genetic screen for improved drought tolerance in Arabidopsis thaliana. One mutant with improved drought tolerance was isolated and designated as enhanced drought tolerance1. The mutant has a more extensive root system than the wild type, with deeper roots and more lateral roots, and shows a reduced leaf stomatal density. The mutant had higher levels of abscisic acid and Pro than the wild type and demonstrated an increased resistance to oxidative stress and high levels of superoxide dismutase. Molecular genetic analysis and recapitulation experiments showed that the enhanced drought tolerance is caused by the activated expression of a T-DNA tagged gene that encodes a putative homeodomain-START transcription factor. Moreover, overexpressing the cDNA of the transcription factor in transgenic tobacco also conferred drought tolerance associated with improved root architecture and reduced leaf stomatal density. Therefore, we have revealed functions of the homeodomain-START factor that were gained upon altering its expression pattern by activation tagging and provide a key regulator that may be used to improve drought tolerance in plants.

  2. Sol–gel synthesis of palladium nanoparticles supported on reduced graphene oxide: an active electrocatalyst for hydrogen evolution reaction

    Indian Academy of Sciences (India)

    Fereshteh Chekin

    2015-08-01

    In this work, the synthesis and characterization of palladium nanoparticle-reduced graphene oxide hybrid (Pd–rGO) material is reported. Techniques of X-ray diffraction, transmission electron microscope (TEM), energy-dispersive X-ray, FT-IR spectroscopy, thermogravimetric analysis and cyclic voltammetry were used to characterize the structure and properties of the Pd–rGO. Results demonstrate the effect of Pd on the reduced GO. The average particle size of the Pd nanoparticles supported on rGO obtained from TEM is about 12–18 nm. Moreover, glassy carbon electrode (GCE) modified with palladium nanoparticle–graphene oxide hybrid (Pd–rGO/GCE) was prepared by casting of the Pd–rGO solution on GCE. The electrochemical and catalytic activity of the Pd–rGO/GCE was studied in 0.1 M H2SO4 solution. The Pd–rGO/GCE electrode exhibited remarkable electrocatalytic activity for the hydrogen evolution reaction (HER). At potential more negative than −0.4 V vs. Ag|AgCl|KCl3M, the current is mainly due to hydrogen evolution reaction. Finally, the kinetic parameters of hydrogen evolution reaction are also discussed on the Pd–rGO/GCE.

  3. alpha-MSH tripeptide analogs activate the melanocortin 1 receptor and reduce UV-induced DNA damage in human melanocytes.

    Science.gov (United States)

    Abdel-Malek, Zalfa A; Ruwe, Andrew; Kavanagh-Starner, Renny; Kadekaro, Ana Luisa; Swope, Viki; Haskell-Luevano, Carrie; Koikov, Leonid; Knittel, James J

    2009-10-01

    One skin cancer prevention strategy that we are developing is based on synthesizing and testing melanocortin analogs that reduce and repair DNA damage resulting from exposure to solar ultraviolet (UV) radiation, in addition to stimulating pigmentation. Previously, we reported the effects of tetrapeptide analogs of alpha-melanocortin (alpha-MSH) that were more potent and stable than the physiological alpha-MSH, and mimicked its photoprotective effects against UV-induced DNA damage in human melanocytes. Here, we report on a panel of tripeptide analogs consisting of a modified alpha-MSH core His(6)-d-Phe(7)-Arg(8), which contained different N-capping groups, C-terminal modifications, or arginine mimics. The most potent tripeptides in activating cAMP formation and tyrosinase of human melanocytes were three analogs with C-terminal modifications. The most effective C-terminal tripeptide mimicked alpha-MSH in reducing hydrogen peroxide generation and enhancing nucleotide excision repair following UV irradiation. The effects of these three analogs required functional MC1R, as they were absent in human melanocytes that expressed non-functional receptor. These results demonstrate activation of the MC1R by tripeptide melanocortin analogs. Designing small analogs for topical delivery should prove practical and efficacious for skin cancer prevention.

  4. Recent status and improvement of reduced-activation ferritic-martensitic steels for high-temperature service

    Science.gov (United States)

    Tan, L.; Katoh, Y.; Tavassoli, A.-A. F.; Henry, J.; Rieth, M.; Sakasegawa, H.; Tanigawa, H.; Huang, Q.

    2016-10-01

    Reduced-activation ferritic-martensitic (RAFM) steels, candidate structural materials for fusion reactors, have achieved technological maturity after about three decades of research and development. The recent status of a few developmental aspects of current RAFM steels, such as aging resistance, plate thickness effects, fracture toughness, and fatigue, is updated in this paper, together with ongoing efforts to develop next-generation RAFM steels for superior high-temperature performance. In addition to thermomechanical treatments, including nonstandard heat treatment, alloy chemistry refinements and modifications have demonstrated some improvements in high-temperature performance. Castable nanostructured alloys (CNAs) were developed by significantly increasing the amount of nanoscale MX (M = V/Ta/Ti, X = C/N) precipitates and reducing coarse M23C6 (M = Cr). Preliminary results showed promising improvement in creep resistance and Charpy impact toughness. Limited low-dose neutron irradiation results for one of the CNAs and China low activation martensitic are presented and compared with data for F82H and Eurofer97 irradiated up to ∼70 displacements per atom at ∼300-325 °C.

  5. In vitro reactivity to implant metals demonstrates a person-dependent association with both T-cell and B-cell activation.

    Science.gov (United States)

    Hallab, Nadim James; Caicedo, Marco; Epstein, Rachel; McAllister, Kyron; Jacobs, Joshua J

    2010-02-01

    Hypersensitivity to metallic implants remains relatively unpredictable and poorly understood. We initially hypothesized that metal-induced lymphocyte proliferation responses to soluble metal challenge (ions) are mediated exclusively by early T-cell activation (not B-cells), typical of a delayed-type-hypersensitivity response. We tested this by comparing proliferation (6 days) of primary lymphocytes with early T-cell and B-cell activation (48 h) in three groups of subjects likely to demonstrate elevated metal reactivity: group 1 (n = 12) history of metal sensitivity with no implant; group 2a (n = 6) well performing metal-on-metal THRs, and group 2b (n = 20) subjects with poorly performing metal-on-polymer total joint arthroplasties (TJA). Group 1 showed 100% (12/12) metal reactivity (stimulation index > 2) to Ni. Groups 2a and 2b were 83% (5/6) and 75% (15/22) metal reactive (to Co, Cr, or Ni), respectively. Of the n = 32 metal-reactive subjects to Co, Cr, or Ni (SI > 2), n = 22/32 demonstrated >2-fold elevations in % of T-cell or B-cell activation (CD25+, CD69+) to metal challenge when compared with untreated control. 18/22 metal-activated subjects demonstrated an exclusively T-cell or B-cell activation response to metal challenge, where 6/18 demonstrated exclusively B-cell activation and 12/18 demonstrated a T-cell only response, as measured by surface activation markers CD25+ and CD69+. However, there was no direct correlation (R(2) metal reactivity than did subject-dependent results of flow-cytometry analysis of T-cell or B-cell activation. The high incidence of lymphocyte reactivity and activation indicate that more complex than initially hypothesized immune responses may contribute to the etiology of debris-induced osteolysis in metal-sensitive individuals.

  6. Goal striving strategies and effort mobilization: When implementation intentions reduce effort-related cardiac activity during task performance.

    Science.gov (United States)

    Freydefont, Laure; Gollwitzer, Peter M; Oettingen, Gabriele

    2016-09-01

    Two experiments investigate the influence of goal and implementation intentions on effort mobilization during task performance. Although numerous studies have demonstrated the beneficial effects of setting goals and making plans on performance, the effects of goals and plans on effort-related cardiac activity and especially the cardiac preejection period (PEP) during goal striving have not yet been addressed. According to the Motivational Intensity Theory, participants should increase effort mobilization proportionally to task difficulty as long as success is possible and justified. Forming goals and making plans should allow for reduced effort mobilization when participants perform an easy task. However, when the task is difficult, goals and plans should differ in their effect on effort mobilization. Participants who set goals should disengage, whereas participants who made if-then plans should stay in the field showing high effort mobilization during task performance. As expected, using an easy task in Experiment 1, we observed a lower cardiac PEP in both the implementation intention and the goal intention condition than in the control condition. In Experiment 2, we varied task difficulty and demonstrated that while participants with a mere goal intention disengaged from difficult tasks, participants with an implementation intention increased effort mobilization proportionally with task difficulty. These findings demonstrate the influence of goal striving strategies (i.e., mere goals vs. if-then plans) on effort mobilization during task performance.

  7. IL-6 Inhibition Reduces STAT3 Activation and Enhances the Antitumor Effect of Carboplatin

    Science.gov (United States)

    Wang, Zhi-Yong; Zhang, Jun-Ai; Wu, Xian-Jin; Liang, Yan-Fang; Lu, Yuan-Bin; Gao, Yu-Chi; Dai, You-Chao; Yu, Shi-Yan; Jia, Yan; Fu, Xiao-Xia; Rao, Xiaoquan; Xu, Jun-Fa

    2016-01-01

    Recent studies suggest that tumor-associated macrophage-produced IL-6 is an important mediator within the tumor microenvironment that promotes tumor growth. The activation of IL-6/STAT3 axis has been associated with chemoresistance and poor prognosis of a variety of cancers including colorectal carcinoma and thus serves as a potential immunotherapeutic target for cancer treatment. However, it is not fully understood whether anticytokine therapy could reverse chemosensitivity and enhance the suppressive effect of chemotherapy on tumor growth. In this study, we aimed to investigate the effect of IL-6 inhibition therapy on the antitumor effect of carboplatin. Enhanced expression of IL-6 and activation of STAT3 were observed in human colorectal carcinoma samples compared to normal colorectal tissue, with higher levels of IL-6/STAT3 in low grade carcinomas. Treatment of carboplatin (CBP) dose-dependently increased IL-6 production and STAT3 activation in human colorectal LoVo cells. Blockade of IL-6 with neutralizing antibody enhanced chemosensitivity of LoVo cells to carboplatin as evidenced by increased cell apoptosis. IL-6 blockade abolished carboplatin-induced STAT3 activation. IL-6 blockade and carboplatin synergistically reduced cyclin D1 expression and enhanced caspase-3 activity in LoVo cells. Our results suggest that inhibition of IL-6 may enhance chemosensitivity of colon cancers with overactive STAT3 to platinum agents. PMID:27006530

  8. Light pollution reduces activity, food consumption and growth rates in a sandy beach invertebrate.

    Science.gov (United States)

    Luarte, T; Bonta, C C; Silva-Rodriguez, E A; Quijón, P A; Miranda, C; Farias, A A; Duarte, C

    2016-11-01

    The continued growth of human activity and infrastructure has translated into a widespread increase in light pollution. Natural daylight and moonlight cycles play a fundamental role for many organisms and ecological processes, so an increase in light pollution may have profound effects on communities and ecosystem services. Studies assessing ecological light pollution (ELP) effects on sandy beach organisms have lagged behind the study of other sources of disturbance. Hence, we assessed the influence of this stressor on locomotor activity, foraging behavior, absorption efficiency and growth rate of adults of the talitrid amphipod Orchestoidea tuberculata. In the field, an artificial light system was assembled to assess the local influence of artificial light conditions on the amphipod's locomotor activity and use of food patches in comparison to natural (ambient) conditions. Meanwhile in the laboratory, two experimental chambers were set to assess amphipod locomotor activity, consumption rates, absorption efficiency and growth under artificial light in comparison to natural light-dark cycles. Our results indicate that artificial light have significantly adverse effects on the activity patterns and foraging behavior of the amphipods, resulting on reduced consumption and growth rates. Given the steady increase in artificial light pollution here and elsewhere, sandy beach communities could be negatively affected, with unexpected consequences for the whole ecosystem. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. Carbamazepine reduces memory induced activation of mesial temporal lobe structures: a pharmacological fMRI-study

    Directory of Open Access Journals (Sweden)

    Okujava Michael

    2001-11-01

    Full Text Available Abstract Background and Purpose It is not known whether carbamazepine (CBZ; a drug widely used in neurology and psychiatry influences the blood oxygenation level dependent (BOLD contrast changes induced by neuronal activation and measured by functional MRI (fMRI. We aimed to investigate the influence of CBZ on memory induced activation of the mesial temporal lobes in patients with symptomatic temporal lobe epilepsy (TLE. Material and Methods Twenty-one individual patients with refractory symptomatic TLE with different CBZ serum levels and 20 healthy controls were studied using BOLD fMRI. Mesial temporal lobe (MTL activation was induced by a task that is based on the retrieval of individually familiar visuo-spatial knowledge. The extent of significant MTL fMRI activation was measured and correlated with the CBZ serum level. Results In TLE patients, the extent of significant fMRI activation over both MTL was negatively correlated to the CBZ serum level (Spearman r = -0.654, P Conclusions In TLE patients, carbamazepine reduces the fMRI-detectable changes within the mesial temporal lobes as induced by effortful memory retrieval. FMRI appears to be suitable to study the effects of chronic drug treatment in patients with epilepsy.

  10. IL-6 Inhibition Reduces STAT3 Activation and Enhances the Antitumor Effect of Carboplatin

    Directory of Open Access Journals (Sweden)

    Zhi-Yong Wang

    2016-01-01

    Full Text Available Recent studies suggest that tumor-associated macrophage-produced IL-6 is an important mediator within the tumor microenvironment that promotes tumor growth. The activation of IL-6/STAT3 axis has been associated with chemoresistance and poor prognosis of a variety of cancers including colorectal carcinoma and thus serves as a potential immunotherapeutic target for cancer treatment. However, it is not fully understood whether anticytokine therapy could reverse chemosensitivity and enhance the suppressive effect of chemotherapy on tumor growth. In this study, we aimed to investigate the effect of IL-6 inhibition therapy on the antitumor effect of carboplatin. Enhanced expression of IL-6 and activation of STAT3 were observed in human colorectal carcinoma samples compared to normal colorectal tissue, with higher levels of IL-6/STAT3 in low grade carcinomas. Treatment of carboplatin (CBP dose-dependently increased IL-6 production and STAT3 activation in human colorectal LoVo cells. Blockade of IL-6 with neutralizing antibody enhanced chemosensitivity of LoVo cells to carboplatin as evidenced by increased cell apoptosis. IL-6 blockade abolished carboplatin-induced STAT3 activation. IL-6 blockade and carboplatin synergistically reduced cyclin D1 expression and enhanced caspase-3 activity in LoVo cells. Our results suggest that inhibition of IL-6 may enhance chemosensitivity of colon cancers with overactive STAT3 to platinum agents.

  11. Constitutively active RAS signaling reduces 1,25 dihydroxyvitamin D-mediated gene transcription in intestinal epithelial cells by reducing vitamin D receptor expression.

    Science.gov (United States)

    DeSmet, Marsha L; Fleet, James C

    2017-10-01

    High vitamin D status is associated with reduced colon cancer risk but these studies ignore the diversity in the molecular etiology of colon cancer. RAS activating mutations are common in colon cancer and they activate pro-proliferative signaling pathways. We examined the impact of RAS activating mutations on 1,25 dihydroxyvitamin D (1,25(OH)2D)-mediated gene expression in cultured colon and intestinal cell lines. Transient transfection of Caco-2 cells with a constitutively active mutant K-RAS (G12 V) significantly reduced 1,25(OH)2D-induced activity of both a human 25-hydroxyvitamin D, 24 hydroxyase (CYP24A1) promoter-luciferase and an artificial 3X vitamin D response element (VDRE) promoter-luciferase reporter gene. Young Adult Mouse Colon (YAMC) and Rat Intestinal Epithelial (RIE) cell lines with stable expression of mutant H-RAS had suppressed 1,25(OH)2D-mediated induction of CYP24A1 mRNA. The RAS effects were associated with lower Vitamin D receptor (VDR) mRNA and protein levels in YAMC and RIE cells and they could be partially reversed by VDR overexpression. RAS-mediated suppression of VDR levels was not due to either reduced VDR mRNA stability or increased VDR gene methylation. However, chromatin accessibility to the VDR gene at the proximal promoter (-300bp), an enhancer region at -6kb, and an enhancer region located in exon 3 was significantly reduced in RAS transformed YAMC cells (YAMC-RAS). These data show that constitutively active RAS signaling suppresses 1,25(OH)2D-mediated gene transcription in colon epithelial cells by reducing VDR gene transcription but the mechanism for this suppression is not yet known. These data suggest that cancers with RAS-activating mutations may be less responsive to vitamin D mediated treatment or chemoprevention. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. 34 CFR 380.4 - What activities may the Secretary fund under Statewide supported employment demonstration projects?

    Science.gov (United States)

    2010-07-01

    ... WITH THE MOST SEVERE DISABILITIES AND TECHNICAL ASSISTANCE PROJECTS General § 380.4 What activities may... organizations and employers. (2) Staff training. (3) Program evaluation. (4) Reorganization, expansion, or, if... the job; (ii) Ongoing supervision of individuals with the most severe disabilities on the job; (iii...

  13. Catalytic diesel particulate filters reduce the in vitro estrogenic activity of diesel exhaust.

    Science.gov (United States)

    Wenger, Daniela; Gerecke, Andreas C; Heeb, Norbert V; Naegeli, Hanspeter; Zenobi, Renato

    2008-04-01

    An in vitro reporter gene assay based on human breast cancer T47D cells (ER-CALUX) was applied to examine the ability of diesel exhaust to induce or inhibit estrogen receptor (ER)-mediated gene expression. Exhaust from a heavy-duty diesel engine was either treated by iron- or copper/iron-catalyzed diesel particulate filters (DPFs) or studied as unfiltered exhaust. Collected samples included particle-bound and semivolatile constituents of diesel exhaust. Our findings show that all of the samples contained compounds that were able to induce ER-mediated gene expression as well as compounds that suppressed the activity of the endogenous hormone 17beta-estradiol (E2). Estrogenic activity prevailed over antiestrogenic activity. We found an overall ER-mediated activity of 1.63 +/- 0.31 ng E2 CALUX equivalents (E2-CEQs) per m(3) of unfiltered exhaust. In filtered exhaust, we measured 0.74 +/- 0.07 (iron-catalyzed DPF) and 0.55 +/- 0.09 ng E2-CEQ m(-3) (copper/iron-catalyzed DPF), corresponding to reductions in estrogenic activity of 55 and 66%, respectively. Our study demonstrates that both catalytic DPFs lowered the ER-mediated endocrine-disrupting potential of diesel exhaust.

  14. Catalytic diesel particulate filters reduce the in vitro estrogenic activity of diesel exhaust

    Energy Technology Data Exchange (ETDEWEB)

    Wenger, Daniela; Gerecke, Andreas C.; Heeb, Norbert V. [Laboratory for Analytical Chemistry, Empa, Swiss Federal Laboratories for Materials Testing and Research, Duebendorf (Switzerland); Naegeli, Hanspeter [University of Zurich-Vetsuisse, Institute of Pharmacology and Toxicology, Zurich (Switzerland); Zenobi, Renato [ETH Zurich, Department of Chemistry and Applied Biosciences, Zurich (Switzerland)

    2008-04-15

    An in vitro reporter gene assay based on human breast cancer T47D cells (ER-CALUX {sup registered}) was applied to examine the ability of diesel exhaust to induce or inhibit estrogen receptor (ER)-mediated gene expression. Exhaust from a heavy-duty diesel engine was either treated by iron- or copper/iron-catalyzed diesel particulate filters (DPFs) or studied as unfiltered exhaust. Collected samples included particle-bound and semivolatile constituents of diesel exhaust. Our findings show that all of the samples contained compounds that were able to induce ER-mediated gene expression as well as compounds that suppressed the activity of the endogenous hormone 17{beta}-estradiol (E2). Estrogenic activity prevailed over antiestrogenic activity. We found an overall ER-mediated activity of 1.63 {+-} 0.31 ng E2 CALUX equivalents (E2-CEQs) per m{sup 3} of unfiltered exhaust. In filtered exhaust, we measured 0.74 {+-} 0.07 (iron-catalyzed DPF) and 0.55 {+-} 0.09 ng E2-CEQ m{sup -3} (copper/iron-catalyzed DPF), corresponding to reductions in estrogenic activity of 55 and 66%, respectively. Our study demonstrates that both catalytic DPFs lowered the ER-mediated endocrine-disrupting potential of diesel exhaust. (orig.)

  15. Joining techniques for a reduced activation 12Cr steel for inertial fusion energy

    Energy Technology Data Exchange (ETDEWEB)

    Hunt, R.M., E-mail: hunt52@llnl.gov; El-Dasher, B., E-mail: eldasher2@llnl.gov; Choi, B.W., E-mail: choi3@llnl.gov; Torres, S.G., E-mail: torres4@llnl.gov

    2014-10-15

    Highlights: • We characterized joining techniques for a candidate material for inertial confinement fusion: reduced activation ferritic martensitic 12% chromium steel. • E-beam, TIG, and laser welds were completed with good quality without significant cracking or porosity. • A heat treatment of 950 °C for 1 h normalized the weld fusion zone and heat-affected zone to the base metal microstructure. • Diffusion bonding at 950 °C or greater for 2 h produced an interface with over 600 MPa tensile strength. - Abstract: At Lawrence Livermore National Laboratory, we are developing a reduced activation ferritic martensitic steel that is based on the ferritic martensitic steel HT-9. As a part of the development of this steel, we tested a series of welding processes for characterization, including conventional welds (electron beam, tungsten inert gas, and laser) as well as solid-state welds (hot isostatic pressing). We also heat treated the joints at various temperatures between 750 °C and 1050 °C to find a suitable normalization scheme. The modified HT-9 reduced activation ferritic martensitic steel appears highly suitable to welding and diffusion bonding. All welds showed good quality fusion zones with insignificant cracking or porosity. Additionally, a heat treatment schedule of 950 °C for one hour caused minimal grain growth while still converging the hardness of the base metal with that of the fusion and heat-affected zones. Also, modified HT-9 diffusion bonds that were created at temperatures of at least 950 °C for two hours at 103 MPa had interface tensile strengths of greater than 600 MPa. The diffusion bonds showed no evidence of increased hardness nor void formation at the diffusion bonded interface.

  16. Reducing the decline in physical activity during pregnancy: a systematic review of behaviour change interventions.

    Directory of Open Access Journals (Sweden)

    Sinead Currie

    Full Text Available PURPOSE: Physical activity (PA typically declines throughout pregnancy. Low levels of PA are associated with excessive weight gain and subsequently increase risk of pre-eclampsia, gestational diabetes mellitus, hypertension disorders, delivery by caesarean section and stillbirth. Systematic reviews on PA during pregnancy have not explored the efficacy of behaviour change techniques or related theory in altering PA behaviour. This systematic review evaluated the content of PA interventions to reduce the decline of PA in pregnant women with a specific emphasis on the behaviour change techniques employed to elicit this change. SEARCH AND REVIEW METHODOLOGY: Literature searches were conducted in eight databases. Strict inclusion and exclusion criteria were employed. Two reviewers independently evaluated each intervention using the behaviour change techniques (BCT taxonomy to identify the specific behaviour change techniques employed. Two reviewers independently assessed the risk of bias using the guidelines from the Cochrane Collaboration. Overall quality was determined using the GRADE approach. FINDINGS: A total of 1140 potentially eligible papers were identified from which 14 studies were selected for inclusion. Interventions included counselling (n = 6, structured exercise (n = 6 and education (n = 2. Common behaviour change techniques employed in these studies were goal setting and planning, feedback, repetition and substitution, shaping knowledge and comparison of behaviours. Regular face-to-face meetings were also commonly employed. PA change over time in intervention groups ranged from increases of 28% to decreases of 25%. In 8 out of 10 studies, which provided adequate data, participants in the intervention group were more physically active post intervention than controls. CONCLUSIONS AND IMPLICATIONS: Physical activity interventions incorporating behaviour change techniques help reduce the decline in PA throughout pregnancy

  17. Posttraumatic tibia valga: a case demonstrating asymmetric activity at the proximal growth plate on technetium bone scan

    Energy Technology Data Exchange (ETDEWEB)

    Zionts, L.E.; Harcke, H.T.; Brooks, K.M.; MacEwen, G.D.

    1987-07-01

    Posttraumatic tibia valga is a well-recognized complication following fracture of the upper tibial metaphysis in young children. We present a case of a child who developed a valgus deformity following fracture of the proximal tibia and fibula in which quantitative bone scintigraphy at 5 months after injury demonstrated increased uptake at the proximal tibial growth plate with proportionally greater uptake on the medial side. This finding suggests that the valgus deformity in this patient was due to a relative increase in vascularity and consequent overgrowth of the medial portion of the proximal tibial physis.

  18. Effect of W and Ta on creep–fatigue interaction behavior of reduced activation ferritic–martensitic (RAFM) steels

    Energy Technology Data Exchange (ETDEWEB)

    Shankar, Vani, E-mail: vani@igcar.gov.in [Metallurgy and Materials Group, Indira Gandhi Centre for Atomic Research, Kalpakkam 603102 (India); Institute for Plasma Research, Ahmedabad 382428 (India); Mariappan, K.; Sandhya, R.; Laha, K.; Jayakumar, T.; Kumar, E. Rajendra [Metallurgy and Materials Group, Indira Gandhi Centre for Atomic Research, Kalpakkam 603102 (India); Institute for Plasma Research, Ahmedabad 382428 (India)

    2015-11-15

    Highlights: • SR correlated with deformation under CFI in RAFM steels. • Stress relaxation directly related to plastic strain accumulated, inversely to CFI life. • Optimum combination of W and Ta best for CFI life. • RAFM steels demonstrated compressive dwell sensitivity. • SR tends toward constant value at long hold. - Abstract: The aim of this work is to understand the effect of varying tungsten and tantalum contents on creep–fatigue interaction (CFI) behavior of reduced activation ferritic–martensitic (RAFM) steels. Increase in W improved CFI life. Effect of changing Ta and W upon the resultant CFI life seems to be interrelated and an optimum combination of both W and Ta works out to be the best for CFI life. Stress relaxation obtained during application of hold can be a useful parameter to relate deformation and damage in the RAFM steels.

  19. Effect of TaC Particles Dissolution on Grain Coarsening in Reduced Activation Steels

    Institute of Scientific and Technical Information of China (English)

    XIA Zhi-xin; ZHANG Chi; HUANG Qun-ying; LIU Shao-jun; LI Zhao-dong; YANG Zhi-gang

    2011-01-01

    The effect of TaC on grains and packets coarsening in the reduced activation ferritic/martensitic (RAFM) steels was investigated. It was found that the combined effect of the austenitizing temperature and heating rate resulted in the heterogeneous austenite grain growth. When the austenitizing temperature was raised above 1 423 K, the TaC particles disappeared, and the homogenous grains abruptly increased. The thermodynamic model for dissolution of TaC particles during austenitizing was applied to interpret the results.

  20. Reduced influenza viral neutralizing activity of natural human trimers of surfactant protein D

    DEFF Research Database (Denmark)

    Hartshorn, Kevan L; White, Mitchell R; Tecle, Tesfaldet

    2007-01-01

    BACKGROUND: Surfactant protein D (SP-D) plays important roles in innate host defense against influenza A virus (IAV) infection. Common human polymorphisms of SP-D have been found in many human populations and associated with increased risk of certain infections. We recently reported that the Thr...... human SP-D multimers as well as reduced hemagglutination inhibiting activity against several strains of IAV. Natural SP-D trimers also had different interactions with human neutrophil peptide defensins (HNPs) in viral neutralization assays as compared to multimeric SP-D. CONCLUSION: These studies......-D can be useful for dissecting out different functional properties of the protein....

  1. Report of IEA workshop on reduced activation ferritic/martensitic steels

    Energy Technology Data Exchange (ETDEWEB)

    NONE

    2001-03-01

    IEA Workshop on Reduced Activation Ferritic/Martensitic Steels under implementing agreement for program of research and development on fusion materials was held at Tokyo Yayoi Kaikan and JAERI headquarter on November 2-3, 2000. The objective of this workshop was a review of the fusion material development programs, the progress of the collaboration and the irradiation effects studies on RAF/M steels in the collaborating parties (Europe, Russia the United States, and Japan). Moreover, the development of plans for future collaboration was discussed. The present report contains viewgraphs presented at the workshop. (author)

  2. Addition of selenium nanoparticles to electrospun silk scaffolds improves mammalian cell activity while reducing bacterial growth

    Directory of Open Access Journals (Sweden)

    Stanley Chung

    2016-07-01

    Full Text Available Silk possesses many beneficial wound healing properties, and electrospun scaffolds are especially applicable for skin applications, due to their smaller interstices and higher surface areas compared to non-electrospun equivalents. However, purified silk promotes microbial growth. In contrast, selenium nanoparticles have excellent antibacterial properties and are a novel antimicrobial chemistry. Here, electrospun silk scaffolds were doped with selenium nanoparticles to impart antibacterial properties to the silk scaffolds. Results showed significantly improved bacterial inhibition and improvement in human dermal fibroblast metabolic activity. These results suggest that the addition of selenium nanoparticles to electrospun silk is a promising approach to improve wound healing with reduced infection, without relying on antibiotics.

  3. Synthesis and antispasmodic activity of lidocaine derivatives endowed with reduced local anesthetic action.

    Science.gov (United States)

    Costa, Jorge C S; Neves, Josiane S; de Souza, Marcus V N; Siqueira, Rodrigo A; Romeiro, Nelilma C; Boechat, Nubia; e Silva, Patrícia M R; Martins, Marco A

    2008-02-01

    The present structure-activity relationship (SAR) study focused on chemical modifications of the structure of the local anesthetic lidocaine, and indicated analogues having reduced anesthetic potency, but with superior potency relative to the prototype in preventing anaphylactic or histamine-evoked ileum contraction. From the SAR analysis, 2-(diethylamino)-N-(trifluoromethyl-phenyl) and 2-(diethylamino)-N-(dimethyl-phenyl) acetamides were selected as the most promising compounds. New insights into the applicability of non-anesthetic lidocaine derivatives as templates in drug discovery for allergic syndromes are provided.

  4. Reduced order generalized integrators with phase compensation for three-phase active power filter

    DEFF Research Database (Denmark)

    Xie, Chuan; Li, Kai; Zhao, Xin

    2017-01-01

    Current regulation is a critical issue for the stable operation of three-phase active power filters (APF). The challenge of the current controller lies in how to track the high slew rate reference with zero steady-state error in a fast and accurate way. Conventionally, multiple paralleled second-order...... generalized integrators (SOGIs) are utilized to achieve those objectives. However, it will increase the computational burden due to calculation of the multiple paralleled SOGIs. To overcome this issue, phase compensated reduced order generalized integrator (ROGI) is proposed in this paper. Compared...

  5. Reduced activity without hyperphagia contributes to obesity in Tubby mutant mice

    OpenAIRE

    Coyle, Christopher A.; Strand, Sarah C.; Deborah J Good

    2008-01-01

    The Tub gene was originally identified as a spontaneous mutation in C57Bl/6J mice, and associated with adult-onset obesity (Tub MUT mice). Although the original Tub MUT mouse was identified over 15 years ago, there have been few reports on the animal’s food intake, body fat percentage or energy expenditure. In this study, we report food intake, body weight from 5–20 weeks, body fat, body temperature and three different measures of physical activity behavior. Tub MUT mice display reduced food ...

  6. Evidence for reduced charge recombination in carbon nanotube/perovskite-based active layers

    Science.gov (United States)

    Bag, Monojit; Renna, Lawrence A.; Jeong, Seung Pyo; Han, Xu; Cutting, Christie L.; Maroudas, Dimitrios; Venkataraman, D.

    2016-10-01

    Using impedance spectroscopy and computation, we show that incorporation of multi-walled carbon nanotubes (MWCNTs) in the bulk of the active layer of perovskite-based solar cells reduces charge recombination and increases the open circuit voltage. An ∼87% reduction in recombination was achieved when MWCNTs were introduced in the planar-heterostructure perovskite solar cell containing mixed counterions. The open circuit voltage (Voc) of perovskite/MWCNTs devices was increased by 70 mV, while the short circuit current density (Jsc) and fill factor (FF) remained unchanged.

  7. Restricted mobility of specific functional groups reduces anti-cancer drug activity in healthy cells

    DEFF Research Database (Denmark)

    Longo Martins, Murillo; Ignazzi, Rosanna; Eckert, Juergen;

    2016-01-01

    The most common cancer treatments currently available are radio- and chemo-therapy. These therapies have, however, drawbacks, such as, the reduction in quality of life and the low efficiency of radiotherapy in cases of multiple metastases. To lessen these effects, we have encapsulated an anti...... with reduced clearance rate and toxicity. X-rays and neutrons were used to investigate the carrier structure, as well as to assess the drug mobility within the bio-nanocomposite. From these unique data we show that partial mobility restriction of active groups of the drug molecule suggests why this carrier...

  8. Subjective word-finding difficulty reduces engagement in social leisure activities in Alzheimer's disease.

    Science.gov (United States)

    Farrell, Meagan T; Zahodne, Laura B; Stern, Yaakov; Dorrejo, Jhedy; Yeung, Philip; Cosentino, Stephanie

    2014-06-01

    To assess the influence of subjective word-finding difficulty on degree of engagement in social leisure activities among individuals with Alzheimer's disease (AD). Analysis of data collected from the second cohort of the Multicenter Study of Predictors of Disease Course in Alzheimer's disease. Four study sites in the United States and France. Individuals diagnosed with mild to moderate AD (N = 236). On separate questionnaires, participants were asked to 1) report whether they had trouble finding the right word when speaking (subjective word-finding difficulty) and 2) rate their frequency and enjoyment of social and nonsocial leisure activities. Objective language measures included object naming and verbal fluency. Measures of dependence, depression, cognitive status, age, sex, and education were also included as covariates in regression analyses. Fifty-two percent of the sample reported word-finding difficulty, and subjective complaints were correlated with poorer verbal fluency scores. Subjective word-finding difficulty was selectively related to social but not nonsocial activity measures. Endorsers of word-finding difficulty reported less frequency and enjoyment of social leisure activities, controlling for effects of covariates and objective word-finding ability. In contrast, lower engagement in nonsocial activities was associated with older age and higher depression scores but not with word-finding complaints. Caregivers' reports of study participants' activities corroborated these results. Individuals with AD who are aware of increasing word-finding failures are less likely to participate in and enjoy socially oriented leisure activities. This finding may have significant implications for clinical and health outcomes in AD. Failure to evaluate subjective language complaints could result in social withdrawal symptoms, threatening the individual's quality of life and increasing caregiver burden. Reduced social interaction may ultimately exacerbate language

  9. A high-fat diet rich in corn oil reduces spontaneous locomotor activity and induces insulin resistance in mice.

    Science.gov (United States)

    Wong, Chi Kin; Botta, Amy; Pither, Jason; Dai, Chuanbin; Gibson, William T; Ghosh, Sanjoy

    2015-04-01

    Over the last few decades, polyunsaturated fatty acid (PUFA), especially n-6 PUFA, and monounsaturated fatty acid content in 'Western diets' has increased manyfold. Such a dietary shift also parallels rising sedentary behavior and diabetes in the Western world. We queried if a shift in dietary fats could be linked to physical inactivity and insulin insensitivity in mice. Eight-week old female C57/Bl6 mice were fed either high-fat (HF) diets [40% energy corn oil (CO) or isocaloric olive oil (OO) diets] or chow (n=10/group) for 6 weeks, followed by estimation of spontaneous locomotor activity, body composition and in vivo metabolic outcomes. Although lean mass and resting energy expenditure stayed similar in both OO- and CO-fed mice, only CO-fed mice demonstrated reduced spontaneous locomotor activity. Such depressed activity in CO-fed mice was accompanied by a lower respiratory ratio, hyperinsulinemia and impaired glucose disposal following intraperitoneal glucose tolerance and insulin tolerance tests compared to OO-fed mice. Unlike the liver, where both HF diets increased expression of fat oxidation genes like PPARs, the skeletal muscle of CO-fed mice failed to up-regulate such genes, thereby supporting the metabolic insufficiencies observed in these mice. In summary, this study demonstrates a specific contribution of n-6 PUFA-rich oils like CO to the loss of spontaneous physical activity and insulin sensitivity in mice. If these data hold true for humans, this study could provide a novel link between recent increases in dietary n-6 PUFA to sedentary behavior and the development of insulin resistance in the Western world.

  10. On the Procedures for the Demonstration of the RF Safety of Active and Passive Implants in MRI Environments

    Institute of Scientific and Technical Information of China (English)

    Eugenia CABOT; Maria CABANES-SEMPERE; Niels KUSTER

    2016-01-01

    As a diagnostic method, magnetic resonance imaging (MRI) is not allowed to be used in patients with medical implants, including both active implants (such as cardiac deifbrillators or deep brain stimulators) and passive implants (such as orthopedics implants and support). MRI imaging scanning can produce magnetic ifelds, which will produce concentrated electromagnetic induction on metal edges of the implants, such as electrodes. The magnetic ifeld can also signiifcantly increase the temperature of surrounding tissues. Besides, the currents and voltage produced by active implants when exposed to MRI scanning can lead to damage and malfunction of pulse generators. Therefore, patients with medical implants cannot receive MRI as a diagnostic method. This safety protocol prevents a large group of patients from receiving MRI diagnosis. This leads to the conclusion that the safety evaluation of implants under MRI environment requires the combination of accurate data analysis and experimental techniques so as to establish the standard testing program.

  11. Degenerative disc disease in the lumbar spine: Another cause for focally reduced activity on marrow scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Cooper, M. (Addenbrookes Hospital, Cambridge (United Kingdom). Dept. of Radiology); Miles, K.A. (Addenbrookes Hospital, Cambridge (United Kingdom). Dept. of Radiology Addenbrookes Hospital, Cambridge (United Kingdom). Dept. of Nuclear Medicine); Wraight, E.P. (Addenbrookes Hospital, Cambridge (United Kingdom). Dept. of Nuclear Medicine); Dixon, A.K. (Addenbrookes Hospital, Cambridge (United Kingdom). Dept. of Radiology Cambridge Univ. (United Kingdom))

    1992-05-01

    A patient is presented in whom a focal reduction in marrow activity in the lumbar spine on both leucocyte and nanocolloid marrow scintigraphy was subsequently shown to be due to fatty infiltration of marrow in association with disc degeneration. Degenerative disease in the lumbar spine has not been previously described as a cause of abnormal bone marrow distribution by such means and needs to be distinguished from a more serious pathology, such as malignant infiltration and vertebral infection, which it may mimic. In a retrospective review of 33 nanocolloid bone marrow and 117 leucocyte scintigrams, 8 showed a degree of reduced marrow activity in the lumbar spine consistent with that caused by degenerative changes. (orig.).

  12. Gardening as a potential activity to reduce falls in older adults.

    Science.gov (United States)

    Chen, Tuo-Yu; Janke, Megan C

    2012-01-01

    This study examines whether participation in gardening predicts reduced fall risk and performance on balance and gait-speed measures in older adults. Data on adults age 65 and older (N = 3,237) from the Health and Retirement Study and Consumption and Activities Mail Survey were analyzed. Participants who spent 1 hr or more gardening in the past week were defined as gardeners, resulting in a total of 1,585 gardeners and 1,652 nongardeners. Independent t tests, chi square, and regression analyses were conducted to examine the relationship between gardening and health outcomes. Findings indicate that gardeners reported significantly better balance and gait speed and had fewer chronic conditions and functional limitations than nongardeners. Significantly fewer gardeners than nongardeners reported a fall in the past 2 yr. The findings suggest that gardening may be a potential activity to incorporate into future fall-prevention programs.

  13. Reduced activation martensitic steels as a structural material for ITER test blanket

    Energy Technology Data Exchange (ETDEWEB)

    Shiba, K. E-mail: shiba@realab01.tokai.jaeri.go.jp; Enoeda, M.; Jitsukawa, S

    2004-08-01

    A Japanese ITER test blanket module (TBM) is planed to use reduced-activation martensitic steel F82H. Feasibility of F82H for ITER test blanket module is discussed in this paper. Several kinds of property data, including physical properties, magnetic properties, mechanical properties and neutron-irradiation data on F82H have been obtained, and these data are complied into a database to be used for the designing of the ITER TBM. Currently obtained data suggests F82H will not have serious problems for ITER TBM. Optimization of F82H improves the induced activity, toughness and HIP resistance. Furthermore, modified F82H is resistant to temperature instability during material production.

  14. Ebola Virus Disease Is Characterized by Poor Activation and Reduced Levels of Circulating CD16+ Monocytes.

    Science.gov (United States)

    Lüdtke, Anja; Ruibal, Paula; Becker-Ziaja, Beate; Rottstegge, Monika; Wozniak, David M; Cabeza-Cabrerizo, Mar; Thorenz, Anja; Weller, Romy; Kerber, Romy; Idoyaga, Juliana; Magassouba, N'Faly; Gabriel, Martin; Günther, Stephan; Oestereich, Lisa; Muñoz-Fontela, César

    2016-10-15

    A number of previous studies have identified antigen-presenting cells (APCs) as key targets of Ebola virus (EBOV), but the role of APCs in human Ebola virus disease (EVD) is not known. We have evaluated the phenotype and kinetics of monocytes, neutrophils, and dendritic cells (DCs) in peripheral blood of patients for whom EVD was diagnosed by the European Mobile Laboratory in Guinea. Acute EVD was characterized by reduced levels of circulating nonclassical CD16(+) monocytes with a poor activation profile. In survivors, CD16(+) monocytes were activated during recovery, coincident with viral clearance, suggesting an important role of this cell subset in EVD pathophysiology. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  15. A Simple Assay Demonstrating the Effect of Rehydration on the Orsellinate Depside Hydrolase Activity of Evernia prunastri.

    Science.gov (United States)

    González, A; Vicente, C; Estrella Legaz, M

    1984-09-01

    A new, simple assay of orsellinate depside hydrolase (EC. 3.1.1.40) by high performance liquid chromatography is described. Enzymatic hydrolysis of evernic acid produces equimolar amounts of both orsellinic and everninic acids. Evernia prunastri thallus has a pre-existent, partially inactive hydrolase, which is activated after rehydration of the thallus. Copyright © 1984 Gustav Fisher Verlag, Stuttgart. Published by Elsevier GmbH.. All rights reserved.

  16. Industry consequences of reduced petroleum activity; Naeringsmessige konsekvenser av redusert petroleumsaktivitet

    Energy Technology Data Exchange (ETDEWEB)

    2010-10-22

    Norwegian oil production is falling. Top of the petroleum production was reached in 2004, and in line with forecasts from the Norwegian Petroleum Directorate and Econ Poeyry (2009), we anticipate a continued decline in production towards an end around 2080. Petroleum industries accounted for about a quarter of Norwegian value creation in 2008. The industries provide strong growth impetus to the Norwegian economy through investments in new fields and operation of existing ones. The petroleum activity on the Norwegian shelf add to our estimates, the basis for about 90 000 jobs in the petroleum industry and the supplier industry. The prescribed reduction in Norwegian petroleum activities will naturally reduce petroleum-related employment. We calculate in this report the effect of a reduction in the petroleum activity with regard to employment. The calculations show a strong decline in employment in the period 2025-2080. In order to reduce the effects of the fall, the Norwegian authorities can open more areas for petroleum production. We show in this report the employment consequences of an opening of the areas off Lofoten, Vesteraalen and Senja may have for employment. To calculate the employment effects are based on an estimate of 2 billion barrels of oil equivalent (boe), and assuming that it made more commercial discoveries. This estimate lies between the updated estimate of Petroleum Directorate announced 16 April 2010 and the projection industry refers to. Our estimate of 2 billion barrels is based on continued technological advances that increase the recovery rate. Based on an estimate of 2 billion barrels, our calculations show that this can lay the basis for between 3000 and 8000 permanent jobs in the petroleum industry and supplier industry. We do not know today whether it is or how much petroleum resources in the areas concerned. If there is no commercial discoveries, employment effect will only be related to exploration activity. If however, there are more

  17. Catalytic activity of various pepsin reduced Au nanostructures towards reduction of nitroarenes and resazurin

    Energy Technology Data Exchange (ETDEWEB)

    Sharma, Bhagwati; Mandani, Sonam; Sarma, Tridib K., E-mail: tridib@iiti.ac.in [Indian Institute of Technology Indore, Discipline of Chemistry, School of Basic Sciences (India)

    2015-01-15

    Pepsin, a digestive protease enzyme, could function as a reducing as well as stabilizing agent for the synthesis of Au nanostructures of various size and shape under different reaction conditions. The simple tuning of the pH of the reaction medium led to the formation of spherical Au nanoparticles, anisotropic Au nanostructures such as triangles, hexagons, etc., as well as ultra small fluorescent Au nanoclusters. The activity of the enzyme was significantly inhibited after its participation in the formation of Au nanoparticles due to conformational changes in the native structure of the enzyme which was studied by fluorescence, circular dichroism (CD), and infra red spectroscopy. However, the Au nanoparticle-enzyme composites served as excellent catalyst for the reduction of p-nitrophenol and resazurin, with the catalytic activity varying with size and shape of the nanoparticles. The presence of pepsin as the surface stabilizer played a crucial role in the activity of the Au nanoparticles as reduction catalysts, as the approach of the reacting molecules to the nanoparticle surface was actively controlled by the stabilizing enzyme.

  18. Reducing GBA2 Activity Ameliorates Neuropathology in Niemann-Pick Type C Mice.

    Directory of Open Access Journals (Sweden)

    André R A Marques

    Full Text Available The enzyme glucocerebrosidase (GBA hydrolyses glucosylceramide (GlcCer in lysosomes. Markedly reduced GBA activity is associated with severe manifestations of Gaucher disease including neurological involvement. Mutations in the GBA gene have recently also been identified as major genetic risk factor for Parkinsonism. Disturbed metabolism of GlcCer may therefore play a role in neuropathology. Besides lysosomal GBA, cells also contain a non-lysosomal glucosylceramidase (GBA2. Given that the two β-glucosidases share substrates, we speculated that over-activity of GBA2 during severe GBA impairment might influence neuropathology. This hypothesis was studied in Niemann-Pick type C (Npc1-/- mice showing secondary deficiency in GBA in various tissues. Here we report that GBA2 activity is indeed increased in the brain of Npc1-/- mice. We found that GBA2 is particularly abundant in Purkinje cells (PCs, one of the most affected neuronal populations in NPC disease. Inhibiting GBA2 in Npc1-/- mice with a brain-permeable low nanomolar inhibitor significantly improved motor coordination and extended lifespan in the absence of correction in cholesterol and ganglioside abnormalities. This trend was recapitulated, although not to full extent, by introducing a genetic loss of GBA2 in Npc1-/- mice. Our findings point to GBA2 activity as therapeutic target in NPC.

  19. Enhancing physical activity and reducing obesity through smartcare and financial incentives: A pilot randomized trial.

    Science.gov (United States)

    Shin, Dong Wook; Yun, Jae Moon; Shin, Jung-Hyun; Kwon, Hyuktae; Min, Hye Yeon; Joh, Hee-Kyung; Chung, Won Joo; Park, Jin Ho; Jung, Kee-Taig; Cho, BeLong

    2017-02-01

    A pilot randomized trial assessed the feasibility and effectiveness of an intervention combining Smartcare (activity tracker with a smartphone application) and financial incentives. A three-arm, open-label randomized controlled trial design involving traditional education, Smartcare, and Smartcare with financial incentives was involved in this study. The latter group received financial incentives depending on the achievement of daily physical activity goals (process incentive) and weight loss targets (outcome incentive). Male university students (N = 105) with body mass index of ≥27 were enrolled. The average weight loss in the traditional education, Smartcare, and Smartcare with financial incentives groups was -0.4, -1.1, and -3.1 kg, respectively, with significantly greater weight loss in the third group (both Ps incentives groups (odds ratio for the Smartcare with financial incentive vs. Smartcare = 7.27, 95% confidence interval: 1.45-36.47). Levels of physical activity were significantly higher in this group. The addition of financial incentives to Smartcare was effective in increasing physical activity and reducing obesity. © 2017 The Obesity Society.

  20. Polyphosphate, cyclic AMP, guanosine tetraphosphate, and c-di-GMP reduce in vitro Lon activity

    Science.gov (United States)

    Osbourne, Devon O; Soo, Valerie WC; Konieczny, Igor; Wood, Thomas K

    2014-01-01

    Lon protease is conserved from bacteria to humans and regulates cellular processes by degrading different classes of proteins including antitoxins, transcriptional activators, unfolded proteins, and free ribosomal proteins. Since we found that Lon has several putative cyclic diguanylate (c-di-GMP) binding sites and since Lon binds polyphosphate (polyP) and lipid polysaccharide, we hypothesized that Lon has an affinity for phosphate-based molecules that might regulate its activity. Hence we tested the effect of polyP, cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), guanosine tetraphosphate (ppGpp), c-di-GMP, and GMP on the ability of Lon to degrade α-casein. Inhibition of in vitro Lon activity occurred for polyP, cAMP, ppGpp, and c-di-GMP. We also demonstrated by HPLC that Lon is able to bind c-di-GMP. Therefore, four cell signals were found to regulate the activity of Lon protease. PMID:24874800

  1. Polyphosphate, cyclic AMP, guanosine tetraphosphate, and c-di-GMP reduce in vitro Lon activity.

    Science.gov (United States)

    Osbourne, Devon O; Soo, Valerie W C; Konieczny, Igor; Wood, Thomas K

    2014-01-01

    Lon protease is conserved from bacteria to humans and regulates cellular processes by degrading different classes of proteins including antitoxins, transcriptional activators, unfolded proteins, and free ribosomal proteins. Since we found that Lon has several putative cyclic diguanylate (c-di-GMP) binding sites and since Lon binds polyphosphate (polyP) and lipid polysaccharide, we hypothesized that Lon has an affinity for phosphate-based molecules that might regulate its activity. Hence we tested the effect of polyP, cyclic adenosine monophosphate (cAMP), cyclic guanosine monophosphate (cGMP), guanosine tetraphosphate (ppGpp), c-di-GMP, and GMP on the ability of Lon to degrade α-casein. Inhibition of in vitro Lon activity occurred for polyP, cAMP, ppGpp, and c-di-GMP. We also demonstrated by HPLC that Lon is able to bind c-di-GMP. Therefore, four cell signals were found to regulate the activity of Lon protease.

  2. Ellagic acid, phenolic acids, and flavonoids in Malaysian honey extracts demonstrate in vitro anti-inflammatory activity.

    Science.gov (United States)

    Kassim, Mustafa; Achoui, Mouna; Mustafa, Mohd Rais; Mohd, Mustafa Ali; Yusoff, Kamaruddin Mohd

    2010-09-01

    Natural honey has been used in traditional medicine of different cultures throughout the world. This study looked into the extraction of Malaysian honey and the evaluation of the anti-inflammatory activity of these extracts. It was hypothesized that honey extracts contain varying amounts of phenolic compounds and that they possess different in vitro anti-inflammatory activities. Honey extracts were analyzed using liquid chromatography-mass spectrometry to identify and compare phenolic compounds, whereas high-performance liquid chromatography was used for their quantification. Subsequently, honey methanol extract (HME) and honey ethyl acetate extract (HEAE) were tested in vitro for their effect on nitric oxide production in stimulated macrophages. The extracts were also tested for their effects on tumor necrosis factor-α (TNF) cytotoxicity in L929 cells. The major phenolics in the extracts were ellagic, gallic, and ferulic acids; myricetin; chlorogenic acid; and caffeic acid. Other compounds found in lower concentrations were hesperetin, p-coumaric acid, chrysin, quercetin, luteolin, and kaempferol. Ellagic acid was the most abundant of the phenolic compounds recorded, with mean concentrations of 3295.83 and 626.74 μg/100 g of honey in HME and HEAE, respectively. The median maximal effective concentrations for in vitro nitric oxide inhibition by HEAE and HME were calculated to be 37.5 and 271.7 μg/mL, respectively. The median maximal effective concentrations for protection from TNF cytotoxicity by HEAE and HME were 168.1 and 235.4 μg/mL, respectively. In conclusion, HEAE exhibited greater activity in vitro, whereas HME contained a higher concentration of phenolic compounds per 100 g of honey. Copyright © 2010 Elsevier Inc. All rights reserved.

  3. Reduced E-cadherin facilitates renal cell carcinoma progression by WNT/β-catenin signaling activation.

    Science.gov (United States)

    Zhang, Xinqi; Yang, Mingxi; Shi, Hua; Hu, Jianxin; Wang, Yuanlin; Sun, Zhaolin; Xu, Shuxiong

    2017-02-15

    Reduced expression of E-cadherin was observed in renal cell carcinoma (RCC). However, its potential clinical value and correlation with WNT/β-catenin signaling in RCC progression was still unclear. Immunohistochemical staining was performed in RCC tissue microarray to examine the expression status and prognosis value of E-cadherin and β-catenin. The potential role of E-cadherin in β-catenin translocation was analyzed with immunobloting assays. A significant negative correlation was observed between E-cadherin and β-catenin expression in RCC tissues. E-cadherin inhibits β-catenin translocation from membrane to cytoplasm in RCC tissues, which was an important step for WNT/β-catenin signaling. Reduced E-cadherin expression was associated with poor prognosis. More importantly, E-cadherin-/β-catenin+ was an independent detrimental factor for survival estimation of RCC patients. Reduced E-cadherin expression in RCC promoted cancer progression via WNT/β-catenin signaling pathway activation. E-cadherin/β-catenin provides a valuable prognosis marker for RCC, which may be an effective target for RCC therapy.

  4. The statin class of HMG-CoA reductase inhibitors demonstrate differential activation of the nuclear receptors PXR, CAR and FXR, as well as their downstream target genes.

    Science.gov (United States)

    Howe, Katharine; Sanat, Faizah; Thumser, Alfred E; Coleman, Tanya; Plant, Nick

    2011-07-01

    The therapeutic class of HMG-CoA reductase inhibitors, the statins are central agents in the treatment of hypercholesterolaemia and the associated conditions of cardiovascular disease, obesity and metabolic syndrome. Although statin therapy is generally considered safe, a number of known adverse effects do occur, most commonly treatment-associated muscular pain. In vitro evidence also supports the potential for drug-drug interactions involving this class of agents, and to examine this a ligand-binding assay was used to determine the ability of six clinically used statins for their ability to directly activate the nuclear receptors pregnane X-receptor (PXR), farnesoid X-receptor (FXR) and constitutive androstane receptor (CAR), demonstrating a relative activation of PXR>FXR>CAR. Using reporter gene constructs, we demonstrated that this order of activation is mirrored at the transcriptional activation level, with PXR-mediated gene activation being pre-eminent. Finally, we described a novel regulatory loop, whereby activation of FXR by statins increases PXR reporter gene expression, potentially enhancing PXR-mediated responses. Delineating the molecular interactions of statins with nuclear receptors is an important step in understanding the full biological consequences of statin exposure. This demonstration of their ability to directly activate nuclear receptors, leading to nuclear receptor cross-talk, has important potential implications for their use within a polypharmacy paradigm.

  5. Self-assembly of a thin highly reduced graphene oxide film and its high electrocatalytic activity

    Science.gov (United States)

    Bai, Yan-Feng; Zhang, Yong-Fang; Zhou, An-Wei; Li, Hai-Wai; Zhang, Yu; Luong, John H. T.; Cui, Hui-Fang

    2014-10-01

    A thin highly reduced graphene oxide (rGO) film was self-assembled at the dimethyl formamide (DMF)-air interface through evaporation-induced water-assisted thin film formation at the pentane-DMF interface, followed by complete evaporation of pentane. The thin film was transferred onto various solid substrates for film characterization and electrochemical sensing. UV-visible spectrometry, scanning electron microscopy (SEM), atomic force microscopy (AFM) and electrochemistry techniques were used to characterize the film. An rGO film showing 82.8% of the transmittance at 550 nm corresponds to a few layers of rGO nanosheets. The rGO nanosheets cross-stack with each other, lying approximately in the plane of the film. An rGO film collected on a glassy carbon (GC) electrode exhibited improved electrical conductivity compared to GC, with the electrode charge-transfer resistance (Rct) reduced from 31 Ω to 22 Ω. The as-formed rGO/GC electrode was mechanically very stable, exhibiting significantly enhanced electrocatalytic activity to H2O2 and dopamine. Multiple layers of the rGO films on the GC electrode showed even stronger electrocatalytic activity to dopamine than that of the single rGO film layer. The controllable formation of a stable rGO film on various solid substrates has potential applications for nanoelectronics and sensors/biosensors.

  6. Underwater explosive welding of tungsten to reduced-activation ferritic steel F82H

    Energy Technology Data Exchange (ETDEWEB)

    Mori, Daichi [Institute of Advanced Energy, Kyoto University, Gokasho, Uji, Kyoto 611-0011 (Japan); Kasada, Ryuta, E-mail: r-kasada@iae.kyoto-u.ac.jp [Institute of Advanced Energy, Kyoto University, Gokasho, Uji, Kyoto 611-0011 (Japan); Konishi, Satoshi [Institute of Advanced Energy, Kyoto University, Gokasho, Uji, Kyoto 611-0011 (Japan); Morizono, Yasuhiro [Graduate School of Science and Technology, Kumamoto University, 2-39-1 Kurokami, Kumamoto 860-8555 (Japan); Hokamoto, Kazuyuki [Institute of Pulsed Power Science, Kumamoto University, 2-39-1 Kurokami, Kumamoto 860-8555 (Japan)

    2014-10-15

    Highlights: • The underwater explosive welding was successfully applied in the joining of tungsten to F82H reduced activation ferritic steel. • Microstructure of the interface showed the formation of a wave-like interface with a thin mixed layer of tungsten and F82H. • Nanoindentation hardness results exhibited a gradual change away from the welded interface without hardened layer. • Small punch tests on the welded specimens resulted in the cracking at a center of tungsten followed by the interfacial cracking. - Abstract: The present study reports the underwater explosive welding of commercially pure tungsten onto the surface of a reduced-activation ferritic steel F82H plate. Cross-sectional observation revealed the formation of a wave-like interface, consisting of a thin mixed layer of W and F82H. The results of nanoindentation hardness testing identified a gradual progressive change in the interface, with no hardened or brittle layer being observed. Small punch tests on the welded specimens resulted in cracking at the center of the tungsten, followed by crack propagation toward both the tungsten surface and the tungsten/steel interface.

  7. Helium Retention and Desorption Behaviour of Reduced Activation Ferritic/Martenstic Steel

    Science.gov (United States)

    Wang, Pinghuai; Nobuta, Yuji; Hino, Tomoaki; Yamauchi, Yuji; Chen, Jiming; Xu, Zengyu; Li, Xiongwei; Liu, Shi

    2009-04-01

    The reduced activation ferritic/martenstic steel CLF-1 prepared by the Southwestern Institute of Physics in China was irradiated by helium ions with an energy of 5 keV at room temperature using an electron cyclotron resonance (ECR) ion irradiation apparatus. After the irradiation, the helium retention and desorption were investigated using a technique of thermal desorption spectroscopy (TDS). The experiment was conducted with both the normal and welded samples. Blisters were observed after the helium ion irradiation, and the surface density of blisters in the welded samples was lower than that in the non-welded samples. Three desorption peaks were observed in both the non-welded and welded samples. These desorption peaks corresponded to those of blister ruptures and the helium release from the inner bubbles and the defects. The amount of helium retained in the welded samples was approximately the same as that in the non-welded samples, which was much less than other reduced activation materials, such as vanadium alloy and SiC/SiC composites.

  8. Characterization of microstructural and mechanical properties of a reduced activation ferritic oxide dispersion strengthened steel

    Science.gov (United States)

    Eiselt, Ch. Ch.; Klimenkov, M.; Lindau, R.; Möslang, A.

    2011-09-01

    For specific blanket and divertor applications in future fusion power reactors a replacement of presently considered Reduced Activation Ferritic Martensitic (RAFM) steels as structural material by suitable oxide dispersion strengthened (ODS) ferritic martensitic steels would allow a substantial increase of the operating temperature from ˜823 K to about 923 K. Temperatures above 973 K in the He cooled modular divertor concept necessitate the use of Reduced Activation Ferritic (RAF)-ODS-steels, which are not limited by a phase transition. The development concentrates on the ferritic ODS-steel Fe-13Cr-1W-0.3Ti-0.3Y 2O 3. The microstructures of a mechanically alloyed powder particle are observed by X-ray diffraction (XRD) and transmission electron microscopy (TEM). Ageing experiments for 1000 h and 3000 h at 1123.5 K and 1223.5 K of compacted Fe-13Cr-1W-0.3Ti-0.3Y 2O 3 were executed. The impact especially on the oxide particles in terms of segregation and decomposition effects were monitored by electron energy loss spectroscopy (EELS). Long term vacuum creep experiments have been performed with rolled Fe-13Cr-1W-0.3Ti-0.3Y 2O 3 at 923.5 K and 1023.5 K, which will be compared to reference alloys.

  9. Joining techniques for a reduced activation 12Cr steel for inertial fusion energy

    Energy Technology Data Exchange (ETDEWEB)

    Hunt, R. M. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); El-Dasher, B. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Choi, B. W. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States); Torres, S. G. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2014-10-01

    At Lawrence Livermore National Laboratory, we are developing a reduced activation ferritic martensitic steel that is based on the ferritic martensitic steel HT-9. As a part of the development of this steel, we tested a series of welding processes for characterization, including conventional welds (electron beam, tungsten inert gas, and laser) as well as solid-state welds (hot isostatic pressing). We also heat treated the joints at various temperatures between 750 °C and 1050 °C to find a suitable normalization scheme. The modified HT-9 reduced activation ferritic martensitic steel appears highly suitable to welding and diffusion bonding. All welds showed good quality fusion zones with insignificant cracking or porosity. Additionally, a heat treatment schedule of 950 °C for one hour caused minimal grain growth while still converging the hardness of the base metal with that of the fusion and heat-affected zones. Also, modified HT-9 diffusion bonds that were created at temperatures of at least 950 °C for two hours at 103 MPa had interface tensile strengths of greater than 600 MPa. The diffusion bonds showed no evidence of increased hardness nor void formation at the diffusion bonded interface.

  10. The Soul, as an Uninhibited Mental Activity, is Reduced into Consciousness by Rules of Quantum Physics.

    Science.gov (United States)

    Ceylan, Mehmet Emin; Dönmez, Aslıhan; Ünsalver, Barış Önen; Evrensel, Alper; Kaya Yertutanol, Fatma Duygu

    2017-06-09

    This paper is an effort to describe, in neuroscientific terms, one of the most ambiguous concepts of the universe-the soul. Previous efforts to understand what the soul is and where it may exist have accepted the soul as a subjective and individual entity. We will make two additions to this view: (1) The soul is a result of uninhibited mental activity and lacks spatial and temporal information; (2) The soul is an undivided whole and, to become divided, the soul has to be reduced into unconscious and conscious mental events. This reduction process parallels the maturation of the frontal cortex and GABA becoming the main inhibitory neurotransmitter. As examples of uninhibited mental activity, we will discuss the perceptual differences of a newborn, individuals undergoing dissociation, and individuals induced by psychedelic drugs. Then, we will explain the similarities between the structure of the universe and the structure of the brain, and we propose that consideration of the rules of quantum physics is necessary to understand how the soul is reduced into consciousness.

  11. Helium Retention and Desorption Behaviour of Reduced Activation Ferritic/Martenstic Steel

    Institute of Scientific and Technical Information of China (English)

    WANG Pinghuai; NOBUTA Yuji; HINO Tomoaki; YAMAUCHI Yuji; CHEN Zilning; XU Zengyu; LI Xiongwei; LIU Shi

    2009-01-01

    The reduced activation ferritic/martenstic steel CLF-1 prepared by the Southwest-ern Institute of Physics in China was irradiated by helium ions with an energy of 5 keV at room temperature using an electron cyclotron resonance (ECR) ion irradiation apparatus. After the irradiation, the helium retention and desorption were investigated using a technique of thermal desorption spectroscopy (TDS). The experiment was conducted with both the normal and welded samples. Blisters were observed after the helium ion irradiation, and the surface density of blisters in the welded samples was lower than that in the non-welded samples. Three desorption peaks were observed in both the non-welded and welded samples. These desorption peaks corresponded to those of blister ruptures and the helium release from the inner bubbles and the defects. The amount of helium retained in the welded samples was approximately the same as that in the non-welded samples, which was much less than other reduced activation materials, such as vanadium alloy and SiC/SiC composites.

  12. Embrittlement behaviour of low-activation alloys with reduced boron content after neutron irradiation

    Science.gov (United States)

    Schneider, H.-C.; Dafferner, B.; Aktaa, J.

    2003-09-01

    Ferritic/martensitic steels for fusion applications have been irradiated up to 2.4 dpa in the Petten high flux reactor (HFR); their embrittlement behaviour was investigated by instrumented Charpy-V tests with subsize specimens. The aim of this mid-dose range programme was a comparison of low-activation alloys subjected to different heat treatments and with reduced B contents (down to 2 wt ppm). In the present report, the results of different OPTIFER alloys (Ia, II, IV, V, VI), as obtained in Phases IA and IB of the HFR-irradiation programme (2.4 dpa, at 250-450 °C), are analysed and assessed in comparison to the results of the former MANITU programme. The evaluation clearly shows the eliminated embrittlement problem for the advanced European reduced-activation alloys in comparison to international reference steels. This improvement can be clearly correlated to the reduction of the boron content. Furthermore, the influence of different heat treatments on the impact properties is presented.

  13. Reduced PAK1 activity sensitizes FA/BRCA-proficient breast cancer cells to PARP inhibition.

    Science.gov (United States)

    Villamar Cruz, Olga; Prudnikova, Tatiana Y; Araiza-Olivera, Daniela; Perez-Plasencia, Carlos; Johnson, Neil; Bernhardy, Andrea J; Slifker, Michael; Renner, Catherine; Chernoff, Jonathan; Arias-Romero, Luis E

    2016-11-22

    Cells that are deficient in homologous recombination, such as those that have mutations in any of the Fanconi Anemia (FA)/BRCA genes, are hypersensitive to inhibition of poly(ADP-ribose) polymerase (PARP). However, FA/BRCA-deficient tumors represent a small fraction of breast cancers, which might restrict the therapeutic utility of PARP inhibitor monotherapy. The gene encoding the serine-threonine protein kinase p21-activated kinase 1 (PAK1) is amplified and/or overexpressed in several human cancer types including 25-30% of breast tumors. This enzyme controls many cellular processes by phosphorylating both cytoplasmic and nuclear substrates. Here, we show that depletion or pharmacological inhibition of PAK1 down-regulated the expression of genes involved in the FA/BRCA pathway and compromised the ability of cells to repair DNA by Homologous Recombination (HR), promoting apoptosis and reducing colony formation. Combined inhibition of PAK1 and PARP in PAK1 overexpressing breast cancer cells had a synergistic effect, enhancing apoptosis, suppressing colony formation, and delaying tumor growth in a xenograft setting. Because reduced PAK1 activity impaired FA/BRCA function, inhibition of this kinase in PAK1 amplified and/or overexpressing breast cancer cells represents a plausible strategy for expanding the utility of PARP inhibitors to FA/BRCA-proficient cancers.

  14. Evaluation of organic substrates to enhance the sulfate-reducing activity in phosphogypsum.

    Science.gov (United States)

    Castillo, Julio; Pérez-López, Rafael; Sarmiento, Aguasanta M; Nieto, José M

    2012-11-15

    Several experiments were conducted to evaluate the activity and growth of sulfate-reducing bacteria (SRB) in a metal-rich culture medium (approx. 250 mg/L Fe, 75 mg/L Zn and Cu, 10mg/L Cd) with phosphogypsum as bacterial inoculum. Phosphogypsum was collected from the stack covering the salt-marshes of the Tinto river (SW Spain). Three organic amendments were used as carbon sources, two low-cost wastes (horse manure and legume compost) and one sample of natural soil (vegetal cover). In the experiments, sulfate was reduced to sulfide during the growth of SRB populations, and concentrations were decreased in the solution. Metal concentrations also decreased to values below the detection limit. Metal removal took place by precipitation of newly-formed sulfides. Pyrite-S was the main sulfide component (approx. 200 μmol/g and 80% of pyritization) and occurred mainly as framboidal grains and rarely as isolated polyhedral crystals. Horse manure was the most successful organic substrate to promote SRB activity (sulfate removal of 61%), followed by vegetal cover (49%) and legume compost (31%). These findings propose the possibility of using naturally-occurring SRB in the phosphogypsum for bioremediation strategies based on natural soil covers with organic amendments.

  15. Diffusion bonding beryllium to Reduced Activation Ferritic Martensitic steel: Development of processes and techniques

    Energy Technology Data Exchange (ETDEWEB)

    Hunt, R.M., E-mail: hunt52@llnl.gov [Mechanical and Aerospace Engineering Department, UCLA, 44-128 Engineering IV, 420 Westwood Plaza, Los Angeles, CA 90025-1597 (United States); Goods, S.H., E-mail: shgoods@sandia.gov [Sandia National Laboratories (United States); Ying, A., E-mail: ying@fusion.ucla.edu [Mechanical and Aerospace Engineering Department, UCLA, 44-128 Engineering IV, 420 Westwood Plaza, Los Angeles, CA 90025-1597 (United States); Dorn, C.K., E-mail: christopher.dorn@materion.com [Materion Brush Beryllium and Composites (United States); Abdou, M., E-mail: abdou@fusion.ucla.edu [Mechanical and Aerospace Engineering Department, UCLA, 44-128 Engineering IV, 420 Westwood Plaza, Los Angeles, CA 90025-1597 (United States)

    2012-09-15

    Highlights: Black-Right-Pointing-Pointer We diffusion bonded Be to Reduced Activation Ferritic Martensitic steel. Black-Right-Pointing-Pointer Thin copper and titanium interlayers improved the bond's shear strength to 168 MPa. Black-Right-Pointing-Pointer A slow cooling scheme and intermediate hold step greatly increased bond strength. Black-Right-Pointing-Pointer Failure occurred in Be-Ti and Cu-Ti intermetallic compounds. - Abstract: Beryllium was successfully bonded to a Reduced Activation Ferritic Martensitic (RAFM) steel with a maximum strength of 150 MPa in tension and 168 MPa in shear. These strengths were achieved using Hot Isostatic Pressing (HIP), at temperatures between 700 Degree-Sign C and 750 Degree-Sign C for 2 h and under a pressure of 103 MPa. To obtain these strengths, 10 {mu}m of titanium and 20 {mu}m of copper were deposited on the beryllium substrate prior to HIP bonding. The copper film acted a bonding aid to the RAFM steel, while the titanium acted as a diffusion barrier between the copper and the beryllium, suppressing the formation of brittle intermetallics that are known to compromise mechanical performance. Slow cooling from the peak HIP temperature along with an imposed hold time at 450 Degree-Sign C further enhanced the final mechanical strength of the bond.

  16. Reduced junctional Na+/Ca2+-exchanger activity contributes to sarcoplasmic reticulum Ca2+ leak in junctophilin-2-deficient mice

    Science.gov (United States)

    Wang, Wei; Landstrom, Andrew P.; Wang, Qiongling; Munro, Michelle L.; Beavers, David; Ackerman, Michael J.; Soeller, Christian

    2014-01-01

    Expression silencing of junctophilin-2 (JPH2) in mouse heart leads to ryanodine receptor type 2 (RyR2)-mediated sarcoplasmic reticulum (SR) Ca2+ leak and rapid development of heart failure. The mechanism and physiological significance of JPH2 in regulating RyR2-mediated SR Ca2+ leak remains elusive. We sought to elucidate the role of JPH2 in regulating RyR2-mediated SR Ca2+ release in the setting of cardiac failure. Cardiac myocytes isolated from tamoxifen-inducible conditional knockdown mice of JPH2 (MCM-shJPH2) were subjected to confocal Ca2+ imaging. MCM-shJPH2 cardiomyocytes exhibited an increased spark frequency width with altered spark morphology, which caused increased SR Ca2+ leakage. Single channel studies identified an increased RyR2 open probability in MCM-shJPH2 mice. The increase in spark frequency and width was observed only in MCM-shJPH2 and not found in mice with increased RyR2 open probability with native JPH2 expression. Na+/Ca2+-exchanger (NCX) activity was reduced by 50% in MCM-shJPH2 with no detectable change in NCX expression. Additionally, 50% inhibition of NCX through Cd2+ administration alone was sufficient to increase spark width in myocytes obtained from wild-type mice. Additionally, superresolution analysis of RyR2 and NCX colocalization showed a reduced overlap between RyR2 and NCX in MCM-shJPH2 mice. In conclusion, decreased JPH2 expression causes increased SR Ca2+ leakage by directly increasing open probability of RyR2 and by indirectly reducing junctional NCX activity through increased dyadic cleft Ca2+. This demonstrates two novel and independent cellular mechanisms by which JPH2 regulates RyR2-mediated SR Ca2+ leak and heart failure development. PMID:25193470

  17. Steviol reduces MDCK Cyst formation and growth by inhibiting CFTR channel activity and promoting proteasome-mediated CFTR degradation.

    Directory of Open Access Journals (Sweden)

    Chaowalit Yuajit

    Full Text Available Cyst enlargement in polycystic kidney disease (PKD involves cAMP-activated proliferation of cyst-lining epithelial cells and transepithelial fluid secretion into the cyst lumen via cystic fibrosis transmembrane conductance regulator (CFTR chloride channel. This study aimed to investigate an inhibitory effect and detailed mechanisms of steviol and its derivatives on cyst growth using a cyst model in Madin-Darby canine kidney (MDCK cells. Among 4 steviol-related compounds tested, steviol was found to be the most potent at inhibiting MDCK cyst growth. Steviol inhibition of cyst growth was dose-dependent; steviol (100 microM reversibly inhibited cyst formation and cyst growth by 72.53.6% and 38.2±8.5%, respectively. Steviol at doses up to 200 microM had no effect on MDCK cell viability, proliferation and apoptosis. However, steviol acutely inhibited forskolin-stimulated apical chloride current in MDCK epithelia, measured with the Ussing chamber technique, in a dose-dependent manner. Prolonged treatment (24 h with steviol (100 microM also strongly inhibited forskolin-stimulated apical chloride current, in part by reducing CFTR protein expression in MDCK cells. Interestingly, proteasome inhibitor, MG-132, abolished the effect of steviol on CFTR protein expression. Immunofluorescence studies demonstrated that prolonged treatment (24 h with steviol (100 microM markedly reduced CFTR expression at the plasma membrane. Taken together, the data suggest that steviol retards MDCK cyst progression in two ways: first by directly inhibiting CFTR chloride channel activity and second by reducing CFTR expression, in part, by promoting proteasomal degradation of CFTR. Steviol and related compounds therefore represent drug candidates for treatment of polycystic kidney disease.

  18. Serotonin/dopamine interactions in a hyperactive mouse: reduced serotonin receptor 1B activity reverses effects of dopamine transporter knockout.

    Directory of Open Access Journals (Sweden)

    Frank Scott Hall

    Full Text Available Knockout (KO mice that lack the dopamine transporter (SL6A3; DAT display increased locomotion that can be attenuated, under some circumstances, by administration of drugs that normally produce psychostimulant-like effects, such as amphetamine and methylphenidate. These results have led to suggestions that DAT KO mice may model features of attention deficit hyperactivity disorder (ADHD and that these drugs may act upon serotonin (5-HT systems to produce these unusual locomotor decreasing effects. Evidence from patterns of brain expression and initial pharmacologic studies led us to use genetic and pharmacologic approaches to examine the influence of altered 5-HT1B receptor activity on hyperactivity in DAT KO mice. Heterozygous 5-HT1B KO and pharmacologic 5-HT1B antagonism both attenuated locomotor hyperactivity in DAT KO mice. Furthermore, DAT KO mice with reduced, but not eliminated, 5-HT1B receptor expression regained cocaine-stimulated locomotion, which was absent in DAT KO mice with normal levels of 5-HT1B receptor expression. Further experiments demonstrated that the degree of habituation to the testing apparatus determined whether cocaine had no effect on locomotion in DAT KO or reduced locomotion, helping to resolve differences among prior reports. These findings of complementation of the locomotor effects of DAT KO by reducing 5-HT1B receptor activity underscore roles for interactions between specific 5-HT receptors and dopamine (DA systems in basal and cocaine-stimulated locomotion and support evaluation of 5-HT1B antagonists as potential, non-stimulant ADHD therapeutics.

  19. Major depression in mothers predict reduced ventral striatum activation in adolescent female offspring with and without depression

    Science.gov (United States)

    Prior research has identified reduced reward-related brain activation as a promising endophenotype for the early identification of adolescents with major depressive disorder. However, it is unclear whether reduced reward-related brain activation constitutes a true vulnerability for major depressive ...

  20. Activation of Rap1 inhibits NADPH oxidase-dependent ROS generation in retinal pigment epithelium and reduces choroidal neovascularization

    Science.gov (United States)

    Wang, Haibo; Jiang, Yanchao; Shi, Dallas; Quilliam, Lawrence A.; Chrzanowska-Wodnicka, Magdalena; Wittchen, Erika S.; Li, Dean Y.; Hartnett, M. Elizabeth

    2014-01-01

    Activation of Rap1 GTPase can improve the integrity of the barrier of the retina pigment epithelium (RPE) and reduce choroidal neovascularization (CNV). Inhibition of NADPH oxidase activation also reduces CNV. We hypothesize that Rap1 inhibits NADPH oxidase-generated ROS and thereby reduces CNV formation. Using a murine model of laser-induced CNV, we determined that reduced Rap1 activity in RPE/choroid occurred with CNV formation and that activation of Rap1 by 2′-O-Me-cAMP (8CPT)-reduced laser-induced CNV via inhibiting NADPH oxidase-generated ROS. In RPE, inhibition of Rap1 by Rap1 GTPase-activating protein (Rap1GAP) increased ROS generation, whereas activation of Rap1 by 8CPT reduced ROS by interfering with the assembly of NADPH oxidase membrane subunit p22phox with NOX4 or cytoplasmic subunit p47phox. Activation of NADPH oxidase with Rap1GAP reduced RPE barrier integrity via cadherin phosphorylation and facilitated choroidal EC migration across the RPE monolayer. Rap1GAP-induced ROS generation was inhibited by active Rap1a, but not Rap1b, and activation of Rap1a by 8CPT in Rap1b−/− mice reduced laser-induced CNV, in correlation with decreased ROS generation in RPE/choroid. These findings provide evidence that active Rap1 reduces CNV by interfering with the assembly of NADPH oxidase subunits and increasing the integrity of the RPE barrier.—Wang, H., Jiang, Y., Shi, D., Quilliam, L. A., Chrzanowska-Wodnicka, M., Wittchen, E. S., Li, D. Y., Hartnett, M. E. Activation of Rap1 inhibits NADPH oxidase-dependent ROS generation in retinal pigment epithelium and reduces choroidal neovascularization. PMID:24043260

  1. Highly Stable Tetra-Phenolato Titanium(IV Agent Formulated into Nanoparticles Demonstrates Anti-Tumoral Activity and Selectivity

    Directory of Open Access Journals (Sweden)

    Sigalit Meker

    2015-10-01

    Full Text Available Titanium(IV complexes exhibit high potential as anti-tumor agents, particularly due to their low intrinsic toxicity and cytotoxicity toward cisplatin resistant cells. Nevertheless, Ti(IV complexes generally undergo rapid hydrolysis that previously hampered their utilization as anticancer drugs. We recently overcame this difficulty by developing a highly stable Ti(IV complex that is based on tetra-phenolato, hexadentate ligand, formulated into organic nanoparticles. Herein we investigated the activity of this complex in vitro and in vivo. Although inactive when tested directly due to poor solubility, when formulated, this complex displayed (a high cytotoxicity toward cisplatin resistant human ovarian cells, A2780-cp, with resistance factor of 1.1; (b additive behavior in combination with cisplatin toward ovarian and colon cancer cells; (c selectivity toward cancer cells as implied by its mild activity toward non-cancerous, fibroblast lung cells, MRC-5; (d high stability and durability as manifested by the ability to maintain cytotoxicity, even following one week of incubation in 100% aquatic medium solution; and (e in vivo efficacy toward solid tumors of human colon cancer cells, HT-29, in nude mice without any clinical signs of toxicity. These features support the formulated phenolato Ti(IV complex being an effective and selective anti-tumoral agent.

  2. Individuals with chronic low back pain demonstrate delayed onset of the back muscle activity during prone hip extension.

    Science.gov (United States)

    Suehiro, Tadanobu; Mizutani, Masatoshi; Ishida, Hiroshi; Kobara, Kenichi; Osaka, Hiroshi; Watanabe, Susumu

    2015-08-01

    Prone hip extension (PHE) is commonly used in the evaluation of the stability of the lumbopelvic region. There is little evidence of difference in muscle activity onset timing between healthy individuals and individuals with chronic low back pain (CLBP) during PHE. The purpose of this study was to determine if individuals with and without CLBP differ in the onset time of the trunk and hip extensor muscles activity during PHE. The participants were 20 patients with CLBP and 20 healthy individuals. Electromyography data of the erector spinae, multifidus, gluteus maximus, and semitendinosus were collected during PHE using a surface electromyograph. Relative differences in the onset times between each muscle and the prime mover (i.e., the semitendinosus) were calculated. The onsets of the bilateral multifidus and contralateral erector spinae were significantly delayed in the CLBP group compared with the healthy group (pleg movement not being significantly different between the groups. The onset times of the gluteus maximus and ipsilateral erector spinae showed no significant differences between the groups. These results suggest that individuals with CLBP use an altered, and possibly inadequate, trunk muscle recruitment pattern.

  3. Asbestos-induced endothelial cell activation and injury. Demonstration of fiber phagocytosis and oxidant-dependent toxicity.

    Science.gov (United States)

    Garcia, J G; Gray, L D; Dodson, R F; Callahan, K S

    1988-10-01

    Vascular endothelial cell injury is important in the development of a variety of chronic interstitial lung disorders. However, the involvement of such injury in the inflammatory response associated with the inhalation of asbestos fibers is unclear and the mechanism of asbestos fiber cytotoxicity remains unknown. In the present study, human umbilical vein endothelial cells were challenged with amosite asbestos and several parameters of cellular function were examined. Electron microscopic examination revealed that endothelial cell exposure to asbestos resulted in active phagocytosis of these particulates. Biochemical evidence of dose-dependent asbestos-mediated endothelial cell activation was indicated by increased metabolism of arachidonic acid. For example, amosite asbestos (500 micrograms/ml) produced a ninefold increase in prostacyclin (PGI2) levels over those levels in non-exposed cells. Incubation of human endothelial cells with asbestos fibers induced specific 51Cr release in both a dose- and time-dependent fashion indicative of cellular injury. Injury induced by amosite asbestos was not significantly attenuated by treatment of the endothelial cell monolayer with either the iron chelator deferoxamine, which prevents hydroxyl radical (.OH) formation, or by the superoxide anion (O2-) scavenger, superoxide dismutase. However, significant dose-dependent protection was observed with the hydrogen peroxide (H2O2) scavenger, catalase. Chelation of elemental iron present within amosite asbestos fibers by deferoxamine produced a 33% reduction in asbestos cytotoxicity, suggesting a potential role for hydroxyl radical-mediated injury via the iron-catalyzed Haber-Weiss reaction.(ABSTRACT TRUNCATED AT 250 WORDS)

  4. BiPO{sub 4}/reduced graphene oxide composites photocatalyst with high photocatalytic activity

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yihe, E-mail: zyh@cugb.edu.cn [National Laboratory of Mineral Materials, School of Materials Science and Technology, China University of Geosciences, Beijing 10083 (China); Shen, Bo [National Laboratory of Mineral Materials, School of Materials Science and Technology, China University of Geosciences, Beijing 10083 (China); Huang, Hongwei, E-mail: hhw@cugb.edu.cn [National Laboratory of Mineral Materials, School of Materials Science and Technology, China University of Geosciences, Beijing 10083 (China); He, Ying [National Laboratory of Mineral Materials, School of Materials Science and Technology, China University of Geosciences, Beijing 10083 (China); Fei, Bin [Institute of Textile and Clothing, The Hong Kong Polytechnic University, Kowloon, Hong Kong (China); Lv, Fengzhu [National Laboratory of Mineral Materials, School of Materials Science and Technology, China University of Geosciences, Beijing 10083 (China)

    2014-11-15

    Graphical abstract: The composite photocatalysts composed of BiPO{sub 4} and reduced graphene oxide (rGO) were synthesized by a facile hydrothermal method. The BiPO{sub 4}/rGO composites exhibit much better photocatalytic performance than pure BiPO{sub 4}. - Highlights: • BiPO{sub 4} nanoparticles are immobilized on reduced graphene oxide (rGO) as photocatalysts. • The BiPO{sub 4}/rGO composites show enhanced photocatalytic activity than the pure BiPO{sub 4} nanoparticles. • The crystallization phases of BiPO{sub 4} can be determined by the amount of graphene. - Abstract: The composite photocatalysts composed of BiPO{sub 4} and reduced graphene oxide (rGO) were synthesized by a facile hydrothermal method. Fourier transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), transmission electron spectroscopy (TEM), photoluminescence emission spectra (PL) and UV–vis diffuse reflection spectroscopy (DRS) were used to characterize the titled composites. The results showed that the BiPO{sub 4} particles can be immobilized on the surface of rGO sheets, and the crystallization phases of BiPO{sub 4} were significantly influenced by the amount of graphene. The phase transformation of BiPO{sub 4} crystal from hexagonal to monoclinic phase was observed. The introduction of rGO improved the optical properties of BiPO{sub 4} and thereby enhancing the utilization of light. Compared with pure BiPO{sub 4} under similar synthesis condition, the BiPO{sub 4}/rGO composites exhibit a much higher photodegradation activity, which was confirmed by photoluminescence (PL) spectra and photocurrent (PC) generation.

  5. Dexamethasone enhances glutamine synthetase activity and reduces N-methyl-D-aspartate neurotoxicity in mixed cultures of neurons and astrocytes

    Directory of Open Access Journals (Sweden)

    Edith Debroas

    2015-05-01

    Full Text Available Astrocytes are claimed to protect neurons against excitotoxicity by clearing glutamate from the extracellular space and rapidly converting it into glutamine. Glutamine, is then released into the extracellular medium, taken up by neurons and transformed back into glutamate which is then stored into synaptic vesicles. Glutamine synthetase (GS, the key enzyme that governs this glutamate/glutamine cycle, is known to be upregulated by glucocorticoids. In the present work we have thus studied in parallel the effects of dexamethasone on glutamine synthetase activity and NMDA-induced neuronal death in cultures derived from the brain cortex of murine embryos. We showed that dexamethasone was able to markedly enhance GS activity in cultures of astrocytes but not in near pure neuronal cultures. The pharmacological characteristics of the dexamethasone action strongly suggest that it corresponds to a typical receptor-mediated effect. We also observed that long lasting incubation (72 h of mixed astrocyte-neuron cultures in the presence of 100 nM dexamethasone significantly reduced the toxicity of NMDA treatment. Furthermore we demonstrated that methionine sulfoximine, a selective inhibitor of GS, abolished the dexamethasone-induced increase in GS activity and also markedly potentiated NMDA toxicity. Altogether these results suggest that dexamethasone may promote neuroprotection through a stimulation of astrocyte glutamine synthetase.

  6. Palpability Support Demonstrated

    DEFF Research Database (Denmark)

    Brønsted, Jeppe; Grönvall, Erik; Fors, David

    2007-01-01

    is based on the Active Surfaces concept in which therapists rehabilitate physically and mentally impaired children by means of an activity that stimulates the children both physically and cognitively. In this paper we demonstrate how palpability can be supported in a prototype of the Active Surfaces...

  7. Palmitic acid, verified by lipid profiling using secondary ion mass spectrometry, demonstrates anti-multiple myeloma activity.

    Science.gov (United States)

    Nagata, Yasuyuki; Ishizaki, Itsuko; Waki, Michihiko; Ide, Yoshimi; Hossen, Md Amir; Ohnishi, Kazunori; Miyayama, Takuya; Setou, Mitsutoshi

    2015-06-01

    Recent studies indicate that lipid metabolic changes affect the survival of multiple myeloma (MM) cells. Time-of-flight secondary ion mass spectrometry (TOF-SIMS), an imaging mass spectrometry technique, is used to visualize the subcellular distribution of biomolecules including lipids. We therefore applied this method to human clinical specimens to analyze the membrane fatty acid composition and determine candidate molecules for MM therapies. We isolated MM cells and normal plasma cells (PCs) from bone marrow aspirates of MM patients and healthy volunteers, respectively, and these separated cells were analyzed by TOF-SIMS. Multiple ions including fatty acids were detected and their ion counts were estimated. In MM cells, the mean intensity of palmitic acid was significantly lower than the mean intensity in PCs. In a cell death assay, palmitic acid reduced U266 cell viability dose-dependently at doses between 50 and 1000 μM. The percentage of apoptotic cells increased from 24h after palmitic acid administration. In contrast, palmitic acid had no effect on the viability of normal peripheral blood mononuclear cells (PBMCs). The results of this study indicated that palmitic acid is a potential candidate for novel therapeutic agents that specifically attack MM cells.

  8. Post-training glucocorticoid receptor activation during Pavlovian conditioning reduces Pavlovian-instrumental transfer in rats.

    Science.gov (United States)

    Pielock, Steffi M; Sommer, Susanne; Hauber, Wolfgang

    2013-03-01

    Considerable evidence suggests that glucocorticoid receptor activation can enhance memory consolidation in Pavlovian learning tasks. For instance, post-training injections of the synthetic glucocorticoid receptor agonist dexamethasone increased conditioned responding to reward-predictive Pavlovian stimuli. Here we explored whether post-training dexamethasone injections can enhance appetitive Pavlovian learning and amplify the ability of Pavlovian stimuli to invigorate instrumental behaviour, a phenomenon termed Pavlovian-instrumental transfer (PIT). Animals were given 8 training days with two sessions per day, an instrumental training session in the morning and a Pavlovian training session in the afternoon. Dexamethasone or vehicle injections were administered daily immediately after Pavlovian training sessions. In a subsequent transfer test, we measured the general PIT effect, i.e. the enhancement of lever pressing for expected reward during presentation of an appetitive Pavlovian stimulus predictive for the same reward. Repeated high-dose (1.2 mg/kg, i.p.) dexamethasone injections elicited pronounced body weight loss, markedly reduced instrumental performance and left Pavlovian learning unaltered, whereas repeated low-dose (3 μg/kg, i.p.) dexamethasone injections inhibited body weight gain, slightly reduced instrumental performance and left Pavlovian learning unaltered during training. Importantly, in rats subjected to high- and low-dose dexamethasone injections, the overall response rates and the PIT effect were reduced in the transfer test. Thus, dexamethasone given after Pavlovian training was not able to amplify the invigorating effects of Pavlovian stimuli on instrumental action. Considerable evidence suggests that body weight changes after repeated low- and high-dose dexamethasone treatment as observed here are associated with muscle atrophy that could impair response capabilities. However, our data suggest that impaired response capabilities are not a

  9. Magnitude of malate-aspartate reduced nicotinamide adenine dinucleotide shuttle activity in intact respiring tumor cells.

    Science.gov (United States)

    Greenhouse, W V; Lehninger, A L

    1977-11-01

    Measurements of respiration, CO2 and lactate production, and changes in the levels of various key metabolites of the glycolytic sequence and tricarboxylic acid cycle were made on five lines of rodent ascites tumor cells (two strains of Ehrlich ascites tumor cells, Krebs II carcinoma, AS-30D carcinoma, and L1210 cells) incubated aerobically in the presence of uniformly labeled D-[14C]glucose. From these data, as well as earlier evidence demonstrating that the reduced nicotinamide adenine dinucleotide (NADH) shuttle in these cells requires a transaminase step and is thus identified as the malate-aspartate shuttle (W.V.V. Greenhouse and A.L. Lehninger, Cancer Res., 36: 1392-1396, 1976), metabolic flux diagrams were constructed for the five cell lines. These diagrams show the relative rates of glycolysis, the tricarboxylic acid cycle, electron transport, and the malate-aspartate shuttle in these tumors. Large amounts of cytosolic NADH were oxidized by the mitochondrial respiratory chain via the NADH shuttle, comprising anywhere from about 20 to 80% of the total flow of reducing equivalents to oxygen in these tumors. Calculations of the sources of energy for adenosine triphosphate synthesis indicated that on the average about one-third of the respiratory adenosine triphosphate is generated by electron flow originating from cytosolic NADH via the malate-aspartate shuttle.

  10. Mutation in E1, the ubiquitin activating enzyme, reduces Drosophila lifespan and results in motor impairment.

    Science.gov (United States)

    Liu, Hsiu-Yu; Pfleger, Cathie M

    2013-01-01

    Neurodegenerative diseases cause tremendous suffering for those afflicted and their families. Many of these diseases involve accumulation of mis-folded or aggregated proteins thought to play a causal role in disease pathology. Ubiquitinated proteins are often found in these protein aggregates, and the aggregates themselves have been shown to inhibit the activity of the proteasome. These and other alterations in the Ubiquitin Pathway observed in neurodegenerative diseases have led to the question of whether impairment of the Ubiquitin Pathway on its own can increase mortality or if ongoing neurodegeneration alters Ubiquitin Pathway function as a side-effect. To address the role of the Ubiquitin Pathway in vivo, we studied loss-of-function mutations in the Drosophila Ubiquitin Activating Enzyme, Uba1 or E1, the most upstream enzyme in the Ubiquitin Pathway. Loss of only one functional copy of E1 caused a significant reduction in adult lifespan. Rare homozygous hypomorphic E1 mutants reached adulthood. These mutants exhibited further reduced lifespan and showed inappropriate Ras activation in the brain. Removing just one functional copy of Ras restored the lifespan of heterozygous E1 mutants to that of wild-type flies and increased the survival of homozygous E1 mutants. E1 homozygous mutants also showed severe motor impairment. Our findings suggest that processes that impair the Ubiquitin Pathway are sufficient to cause early mortality. Reduced lifespan and motor impairment are seen in the human disease X-linked Infantile Spinal Muscular Atrophy, which is associated with mutation in human E1 warranting further analysis of these mutants as a potential animal model for study of this disease.

  11. Identification of Anabolic Selective Androgen Receptor Modulators with Reduced Activities in Reproductive Tissues and Sebaceous Glands

    Science.gov (United States)

    Schmidt, Azriel; Harada, Shun-Ichi; Kimmel, Donald B.; Bai, Chang; Chen, Fang; Rutledge, Su Jane; Vogel, Robert L.; Scafonas, Angela; Gentile, Michael A.; Nantermet, Pascale V.; McElwee-Witmer, Sheila; Pennypacker, Brenda; Masarachia, Patricia; Sahoo, Soumya P.; Kim, Yuntae; Meissner, Robert S.; Hartman, George D.; Duggan, Mark E.; Rodan, Gideon A.; Towler, Dwight A.; Ray, William J.

    2009-01-01

    Androgen replacement therapy is a promising strategy for the treatment of frailty; however, androgens pose risks for unwanted effects including virilization and hypertrophy of reproductive organs. Selective Androgen Receptor Modulators (SARMs) retain the anabolic properties of androgens in bone and muscle while having reduced effects in other tissues. We describe two structurally similar 4-aza-steroidal androgen receptor (AR) ligands, Cl-4AS-1, a full agonist, and TFM-4AS-1, which is a SARM. TFM-4AS-1 is a potent AR ligand (IC50, 38 nm) that partially activates an AR-dependent MMTV promoter (55% of maximal response) while antagonizing the N-terminal/C-terminal interaction within AR that is required for full receptor activation. Microarray analyses of MDA-MB-453 cells show that whereas Cl-4AS-1 behaves like 5α-dihydrotestosterone (DHT), TFM-4AS-1 acts as a gene-selective agonist, inducing some genes as effectively as DHT and others to a lesser extent or not at all. This gene-selective agonism manifests as tissue-selectivity: in ovariectomized rats, Cl-4AS-1 mimics DHT while TFM-4AS-1 promotes the accrual of bone and muscle mass while having reduced effects on reproductive organs and sebaceous glands. Moreover, TFM-4AS-1 does not promote prostate growth and antagonizes DHT in seminal vesicles. To confirm that the biochemical properties of TFM-4AS-1 confer tissue selectivity, we identified a structurally unrelated compound, FTBU-1, with partial agonist activity coupled with antagonism of the N-terminal/C-terminal interaction and found that it also behaves as a SARM. TFM-4AS-1 and FTBU-1 represent two new classes of SARMs and will allow for comparative studies aimed at understanding the biophysical and physiological basis of tissue-selective effects of nuclear receptor ligands. PMID:19846549

  12. Induction of ferroxidase enzymatic activity by copper reduces MPP+-evoked neurotoxicity in rats.

    Science.gov (United States)

    Rubio-Osornio, Moisés; Montes, Sergio; Heras-Romero, Yessica; Guevara, Jorge; Rubio, Carmen; Aguilera, Penélope; Rivera-Mancia, Susana; Floriano-Sánchez, Esaú; Monroy-Noyola, Antonio; Ríos, Camilo

    2013-03-01

    Parkinson's disease (PD) is a neurodegenerative disorder characterized by decreased dopamine, intracellular inclusions (Lewy bodies) and brain iron deposits. PD has also been related with reduced ferroxidase activity, diminished antioxidant defenses and lipid peroxidation. Striatal injection of 1-methyl-4-phenylpyridinium (MPP(+)) into rodents reproduces the major biochemical characteristics of PD, including oxidative stress. Copper (Cu) plays an important role as prosthetic group of several proteins involved in iron metabolism and antioxidant responses, such as ceruloplasmin (Cp). In the present study, intraperitoneal CuSO4 injection (10μmol/kg) produced an insignificant increase of Cu content in striatum and midbrain (17.5% and 7%, respectively). After 10 and 11h, Cu induced 6- and 4-fold increase Cp mRNA in midbrain and striatum, respectively. Cu-supplement also produced a time-dependent increase ferroxidase activity in striatal tissue, reaching a maximum 16h after Cu treatment in midbrain; while, ferrous iron content diminished 18% in striatum and 8% in midbrain. In regard the PD model, we found that MPP(+) (10μg/8μL, intrastriatal), induced a significant (P<0.05) reduction of striatal ferroxidase activity; this effect was reverted by Cu pre-treatment 16h before MPP(+). Likewise, Cu-supplement prevented lipid fluorescent products formation in striatum, evaluated (P<0.01) 6h after MPP(+). In the long term, apomorphine-evoked circling behavior was evaluated 6 days after MPP(+) injury; Cu pre-treatment significantly reduced (P<0.05) the apomorphine-induced ipsilateral turns in MPP(+)-lesioned rats. These results suggest that Cu-induced expression of Cp could be an interesting scope against the deleterious effects of iron deposits in PD.

  13. Efficient degradation of trichloroethylene in water using persulfate activated by reduced graphene oxide-iron nanocomposite.

    Science.gov (United States)

    Ahmad, Ayyaz; Gu, Xiaogang; Li, Li; Lv, Shuguang; Xu, Yisheng; Guo, Xuhong

    2015-11-01

    Graphene oxide (GO) and nano-sized zero-valent iron-reduced graphene oxide (nZVI-rGO) composite were prepared. The GO and nZVI-rGO composite were characterized by transmission electron microscopy (TEM), Fourier transform infrared (FTIR), energy-dispersive spectroscopy (EDS), and Raman spectroscopy. The size of nZVI was about 6 nm as observed by TEM. The system of nZVI-rGO and persulfate (PS) was used for the degradation of trichloroethylene (TCE) in water, and showed 26.5% more efficiency as compared to nZVI/PS system. The different parameters were studied to determine the efficiency of nZVI-rGO to activate the PS system for the TCE degradation. By increasing the PS amount, TCE removal was also improved while no obvious effect was observed by varying the catalyst loading. Degradation was decreased as the TCE initial concentration was increased from 20 to 100 mg/L. Moreover, when initial solution pH was increased, efficiency deteriorated to 80%. Bicarbonate showed more negative effect on TCE removal among the solution matrix. To better understand the effects of radical species in the system, the scavenger tests were performed. The •SO4(-) and •O2(-) were predominant species responsible for TCE removal. The nZVI-rGO-activated PS process shows potential applications in remediation of highly toxic organic contaminants such as TCE present in the groundwater. Graphical abstract Persulfate activated by reduced graphene oxide and nano-sized zero-valent iron composite can be used for efficient degradation of trichloroethylene (TCE) in water.

  14. Identification of anabolic selective androgen receptor modulators with reduced activities in reproductive tissues and sebaceous glands.

    Science.gov (United States)

    Schmidt, Azriel; Harada, Shun-Ichi; Kimmel, Donald B; Bai, Chang; Chen, Fang; Rutledge, Su Jane; Vogel, Robert L; Scafonas, Angela; Gentile, Michael A; Nantermet, Pascale V; McElwee-Witmer, Sheila; Pennypacker, Brenda; Masarachia, Patricia; Sahoo, Soumya P; Kim, Yuntae; Meissner, Robert S; Hartman, George D; Duggan, Mark E; Rodan, Gideon A; Towler, Dwight A; Ray, William J

    2009-12-25

    Androgen replacement therapy is a promising strategy for the treatment of frailty; however, androgens pose risks for unwanted effects including virilization and hypertrophy of reproductive organs. Selective Androgen Receptor Modulators (SARMs) retain the anabolic properties of androgens in bone and muscle while having reduced effects in other tissues. We describe two structurally similar 4-aza-steroidal androgen receptor (AR) ligands, Cl-4AS-1, a full agonist, and TFM-4AS-1, which is a SARM. TFM-4AS-1 is a potent AR ligand (IC(50), 38 nm) that partially activates an AR-dependent MMTV promoter (55% of maximal response) while antagonizing the N-terminal/C-terminal interaction within AR that is required for full receptor activation. Microarray analyses of MDA-MB-453 cells show that whereas Cl-4AS-1 behaves like 5alpha-dihydrotestosterone (DHT), TFM-4AS-1 acts as a gene-selective agonist, inducing some genes as effectively as DHT and others to a lesser extent or not at all. This gene-selective agonism manifests as tissue-selectivity: in ovariectomized rats, Cl-4AS-1 mimics DHT while TFM-4AS-1 promotes the accrual of bone and muscle mass while having reduced effects on reproductive organs and sebaceous glands. Moreover, TFM-4AS-1 does not promote prostate growth and antagonizes DHT in seminal vesicles. To confirm that the biochemical properties of TFM-4AS-1 confer tissue selectivity, we identified a structurally unrelated compound, FTBU-1, with partial agonist activity coupled with antagonism of the N-terminal/C-terminal interaction and found that it also behaves as a SARM. TFM-4AS-1 and FTBU-1 represent two new classes of SARMs and will allow for comparative studies aimed at understanding the biophysical and physiological basis of tissue-selective effects of nuclear receptor ligands.

  15. Lysine and arginine reduce the effects of cerebral ischemic insults and inhibit glutamate-induced neuronal activity in rats

    Directory of Open Access Journals (Sweden)

    Takashi Kondoh

    2010-06-01

    Full Text Available Intravenous administration of arginine was shown to be protective against cerebral ischemic insults via nitric oxide production and possibly via additional mechanisms. The present study aimed at evaluating the neuroprotective effects of oral administration of lysine (a basic amino acid, arginine, and their combination on ischemic insults (cerebral edema and infarction and hemispheric brain swelling induced by transient middle cerebral artery occlusion/reperfusion in rats. Magnetic resonance imaging and 2,3,5-triphenyltetrazolium chloride staining were performed two days after ischemia induction. In control animals, the major edematous areas were observed in the cerebral cortex and striatum. The volumes associated with cortical edema were significantly reduced by lysine (2.0 g/kg, arginine (0.6 g/kg, or their combined administration (0.6 g/kg each. Protective effects of these amino acids on infarction were comparable to the inhibitory effects on edema formation. Interestingly, these amino acids, even at low dose (0.6 g/kg, were effective to reduce hemispheric brain swelling. Additionally, the effects of in vivo microiontophoretic (juxtaneuronal applications of these amino acids on glutamate-evoked neuronal activity in the ventromedial hypothalamus were investigated in awake rats. Glutamate-induced neuronal activity was robustly inhibited by microiontophoretic applications of lysine or arginine onto neuronal membranes. Taken together, our results demonstrate the neuroprotective effects of oral ingestion of lysine and arginine against ischemic insults (cerebral edema and infarction, especially in the cerebral cortex, and suggest that suppression of glutamate-induced neuronal activity might be the primary mechanism associated with these neuroprotective effects.

  16. Naringenin reduces oxidative stress and improves mitochondrial dysfunction via activation of the Nrf2/ARE signaling pathway in neurons.

    Science.gov (United States)

    Wang, Kaihua; Chen, Zhenzhen; Huang, Longjian; Meng, Bing; Zhou, Xinmei; Wen, Xiaodong; Ren, Ding

    2017-09-13

    Oxidative stress and mitochondrial dysfunction are considered to be major contributing factors in the development and progression of many neurodegenerative diseases. Naringenin (NAR) is an abundant flavanone in the Citrus genus and has been found to exert antioxidant, anticarcinogenic and antimutagenic effects. However, the potential underlying mechanism of its antioxidant effects remains unclear. In the present study, the authors investigated the antioxidant effect of NAR on neurons in vitro. Neurons isolated from the brains of Sprague-Dawley rats were randomly divided into a control group, model group, NAR-L group, NAR-M group and NAR-H group. The model group received hypoxia and re-oxygenation treatment, and the NAR-L, NAR-M and NAR-H groups received 20, 40 and 80 µM NAR, respectively. The levels of reactive oxygen species (ROS) in each group were detected by chloromethyl-2',7'dichlorodihydro fluorescein diacetate staining, and differences in mitochondrial dysfunction were analyzed through measurement of mitochondrial membrane potential (∆ψm), adenine nucleotide translocase transport activity and adenine nucleotide levels. MTT and flow cytometry assays were also used to analyze cell proliferation and apoptosis, and the effects of NAR on the nuclear factor erythroid 2-related factor 2 (Nrf2)/antioxidant response element (ARE) signaling pathway were investigated using small interfering RNA methods. The authors detected an increased accumulation of ROS in the model group, and high-dose NAR could significantly reduce the levels of ROS. Furthermore, NAR could improve mitochondrial dysfunction, as indicated by increased levels of high-energy phosphates, enhanced mitochondrial ANT transport activity and increased mitochondrial membrane potential. Moreover, NAR increased cell viability and decreased the rate of cell apoptosis. NAR also increased the expression of Nrf2 and its downstream target genes. These findings demonstrated that NAR could reduce oxidative

  17. Biotransformation of bisphenol AF to its major glucuronide metabolite reduces estrogenic activity.

    Directory of Open Access Journals (Sweden)

    Ming Li

    Full Text Available Bisphenol AF (BPAF, an endocrine disrupting chemical, can induce estrogenic activity through binding to estrogen receptor (ER. However, the metabolism of BPAF in vivo and the estrogenic activity of its metabolites remain unknown. In the present study, we identified four metabolites including BPAF diglucuronide, BPAF glucuronide (BPAF-G, BPAF glucuronide dehydrated and BPAF sulfate in the urine of Sprague-Dawley (SD rats. BPAF-G was further characterized by nuclear magnetic resonance (NMR. After treatment with a single dose of BPAF, BPAF was metabolized rapidly to BPAF-G, as detected in the plasma of SD rats. Biotransformation of BPAF to BPAF-G was confirmed with human liver microsomes (HLM, and Vmax of glucuronidation for HLM was 11.6 nmol/min/mg. We also found that BPAF glucuronidation could be mediated through several human recombinant UDP-glucuronosyltransferases (UGTs including UGT1A1, UGT1A3, UGT1A8, UGT1A9, UGT2B4, UGT2B7, UGT2B15 and UGT2B17, among which UGT2B7 showed the highest efficiency of glucuronidation. To explain the biological function of BPAF biotransformation, the estrogenic activities of BPAF and BPAF-G were evaluated in ER-positive breast cancer T47D and MCF7 cells. BPAF significantly stimulates ER-regulated gene expression and cell proliferation at the dose of 100 nM and 1 μM in breast cancer cells. However, BPAF-G did not show any induction of estrogenic activity at the same dosages, implying that formation of BPAF-G is a potential host defense mechanism against BPAF. Based on our study, biotransformation of BPAF to BPAF-G can eliminate BPAF-induced estrogenic activity, which is therefore considered as reducing the potential threat to human beings.

  18. Impaired dual tasking in Parkinson's disease is associated with reduced focusing of cortico-striatal activity.

    Science.gov (United States)

    Nieuwhof, Freek; Bloem, Bastiaan R; Reelick, Miriam F; Aarts, Esther; Maidan, Inbal; Mirelman, Anat; Hausdorff, Jeffrey M; Toni, Ivan; Helmich, Rick C

    2017-03-17

    Impaired dual tasking, namely the inability to concurrently perform a cognitive and a motor task (e.g. 'stops walking while talking'), is a largely unexplained and frequent symptom of Parkinson's disease. Here we consider two circuit-level accounts of how striatal dopamine depletion might lead to impaired dual tasking in patients with Parkinson's disease. First, the loss of segregation between striatal territories induced by dopamine depletion may lead to dysfunctional overlaps between the motor and cognitive processes usually implemented in parallel cortico-striatal circuits. Second, the known dorso-posterior to ventro-anterior gradient of dopamine depletion in patients with Parkinson's disease may cause a funnelling of motor and cognitive processes into the relatively spared ventro-anterior putamen, causing a neural bottleneck. Using functional magnetic resonance imaging, we measured brain activity in 19 patients with Parkinson's disease and 26 control subjects during performance of a motor task (auditory-cued ankle movements), a cognitive task (implementing a switch-stay rule), and both tasks simultaneously (dual task). The distribution of task-related activity respected the known segregation between motor and cognitive territories of the putamen in both groups, with motor-related responses in the dorso-posterior putamen and task switch-related responses in the ventro-anterior putamen. During dual task performance, patients made more motor and cognitive errors than control subjects. They recruited a striatal territory (ventro-posterior putamen) not engaged during either the cognitive or the motor task, nor used by controls. Relatively higher ventro-posterior putamen activity in controls was associated with worse dual task performance. These observations suggest that dual task impairments in Parkinson's disease are related to reduced spatial focusing of striatal activity. This pattern of striatal activity may be explained by a loss of functional segregation

  19. O-GlcNAc modification of PPAR{gamma} reduces its transcriptional activity

    Energy Technology Data Exchange (ETDEWEB)

    Ji, Suena; Park, Sang Yoon [Department of Biology, Yonsei University, Seoul 120-749 (Korea, Republic of); Roth, Juergen [Department of Integrated OMICS for Biomedical Science, Graduate School, Yonsei University, Seoul 120-749 (Korea, Republic of); Kim, Hoe Suk, E-mail: hoeskim@snu.ac.kr [Institute of Radiation Medicine, Medical Research Center, Seoul National University, Seoul 110-744 (Korea, Republic of); Cho, Jin Won, E-mail: chojw311@yonsei.ac.kr [Department of Biology, Yonsei University, Seoul 120-749 (Korea, Republic of); Department of Integrated OMICS for Biomedical Science, Graduate School, Yonsei University, Seoul 120-749 (Korea, Republic of)

    2012-01-27

    Highlights: Black-Right-Pointing-Pointer We found that PPAR{gamma} is modified by O-GlcNAc in 3T3-L1 adipocytes. Black-Right-Pointing-Pointer The Thr54 of PPAR{gamma}1 is the major O-GlcNAc site. Black-Right-Pointing-Pointer Transcriptional activity of PPAR{gamma}1 was decreased on treatment with the OGA inhibitor. -- Abstract: The peroxisome proliferator-activated receptor {gamma} (PPAR{gamma}), a member of the nuclear receptor superfamily, is a key regulator of adipogenesis and is important for the homeostasis of the adipose tissue. The {beta}-O-linked N-acetylglucosamine (O-GlcNAc) modification, a posttranslational modification on various nuclear and cytoplasmic proteins, is involved in the regulation of protein function. Here, we report that PPAR{gamma} is modified by O-GlcNAc in 3T3-L1 adipocytes. Mass spectrometric analysis and mutant studies revealed that the threonine 54 of the N-terminal AF-1 domain of PPAR{gamma} is the major O-GlcNAc site. Transcriptional activity of wild type PPAR{gamma} was decreased 30% by treatment with the specific O-GlcNAcase (OGA) inhibitor, but the T54A mutant of PPAR{gamma} did not respond to inhibitor treatment. In 3T3-L1 cells, an increase in O-GlcNAc modification by OGA inhibitor reduced PPAR{gamma} transcriptional activity and terminal adipocyte differentiation. Our results suggest that the O-GlcNAc state of PPAR{gamma} influences its transcriptional activity and is involved in adipocyte differentiation.

  20. Salidroside reduces cold-induced mucin production by inhibiting TRPM8 activation.

    Science.gov (United States)

    Li, Qi; Zhou, Xiang-Dong; Kolosov, Victor P; Perelman, Juliy M

    2013-09-01

    Salidroside is an effective component of the traditional Chinese herb, Rhodiola rosea, that is known to have the ability to protect individuals from cold attacks. In the present study, we investigated the effects of salidroside on respiratory epithelial cells exposed to cold temperatures. We wished to determine whether salidroside exerts any effect on cold-induced mucin (MUC) production and the possible mechanisms involved in this process. We incubated HBE16 cells with salidroside, exposed them to a cold stimulus (18˚C), and assayed the following endpoints: MUC production (the expression of MUC5AC), concentration intracellular of free calcium ([Ca2+]i), the activation of the transient receptor potential melastatin 8 (TRPM8) channel and the cAMP response element-binding protein (CREB). Our results revealed a significant increase in the [Ca2+]i concentration, as well as in TRPM8 and CREB expression in the cold-stimulated cells. MUC5AC expression was also increased. Treatment of the cells with salidroside at concentrations of 50 and 100 µM decreased the [Ca2+]i concentration, with a maximal effect detected in the cells treated with 100 µM salidroside. The expression of TRPM8 and TRPM8 channel conductivity were also repressed by salidroside; salidroside decreased the high levels of CREB activity and phosphorylation observed in the cold-stimulated cells. Furthermore, we transfected the cold-stimulated cells with CREB small interfering RNA (siRNA) to analyze TRPM8 gene expression in the absence of CREB activity. The results revealed that the cells treated with either CREB siRNA or salidroside expressed low levels of TRPM8 mRNA and protein. These results indicate that salidroside reduces MUC overproduction induced by cold stimuli and that salidroside exerts its protective effects by inhibiting TRPM8 activation, mainly by decreasing CREB activity.

  1. Molecular basis of reduced pyridoxine 5'-phosphate oxidase catalytic activity in neonatal epileptic encephalopathy disorder.

    Science.gov (United States)

    Musayev, Faik N; Di Salvo, Martino L; Saavedra, Mario A; Contestabile, Roberto; Ghatge, Mohini S; Haynes, Alexina; Schirch, Verne; Safo, Martin K

    2009-11-06

    Mutations in pyridoxine 5'-phosphate oxidase are known to cause neonatal epileptic encephalopathy. This disorder has no cure or effective treatment and is often fatal. Pyridoxine 5'-phosphate oxidase catalyzes the oxidation of pyridoxine 5'-phosphate to pyridoxal 5'-phosphate, the active cofactor form of vitamin B(6) required by more than 140 different catalytic activities, including enzymes involved in amino acid metabolism and biosynthesis of neurotransmitters. Our aim is to elucidate the mechanism by which a homozygous missense mutation (R229W) in the oxidase, linked to neonatal epileptic encephalopathy, leads to reduced oxidase activity. The R229W variant is approximately 850-fold less efficient than the wild-type enzyme due to an approximately 192-fold decrease in pyridoxine 5'-phosphate affinity and an approximately 4.5-fold decrease in catalytic activity. There is also an approximately 50-fold reduction in the affinity of the R229W variant for the FMN cofactor. A 2.5 A crystal structure of the R229W variant shows that the substitution of Arg-229 at the FMN binding site has led to a loss of hydrogen-bond and/or salt-bridge interactions between FMN and Arg-229 and Ser-175. Additionally, the mutation has led to an alteration of the configuration of a beta-strand-loop-beta-strand structure at the active site, resulting in loss of two critical hydrogen-bond interactions involving residues His-227 and Arg-225, which are important for substrate binding and orientation for catalysis. These results provide a molecular basis for the phenotype associated with the R229W mutation, as well as providing a foundation for understanding the pathophysiological consequences of pyridoxine 5'-phosphate oxidase mutations.

  2. Neural basis of moral elevation demonstrated through inter-subject synchronization of cortical activity during free-viewing.

    Directory of Open Access Journals (Sweden)

    Zoë A Englander

    Full Text Available BACKGROUND: Most research investigating the neural basis of social emotions has examined emotions that give rise to negative evaluations of others (e.g. anger, disgust. Emotions triggered by the virtues and excellences of others have been largely ignored. Using fMRI, we investigated the neural basis of two "other-praising" emotions--Moral Elevation (a response to witnessing acts of moral beauty, and Admiration (which we restricted to admiration for physical skill. METHODOLOGY/PRINCIPAL FINDINGS: Ten participants viewed the same nine video clips. Three clips elicited moral elevation, three elicited admiration, and three were emotionally neutral. We then performed pair-wise voxel-by-voxel correlations of the BOLD signal between individuals for each video clip and a separate resting-state run. We observed a high degree of inter-subject synchronization, regardless of stimulus type, across several brain regions during free-viewing of videos. Videos in the elevation condition evoked significant inter-subject synchronization in brain regions previously implicated in self-referential and interoceptive processes, including the medial prefrontal cortex, precuneus, and insula. The degree of synchronization was highly variable over the course of the videos, with the strongest synchrony occurring during portions of the videos that were independently rated as most emotionally arousing. Synchrony in these same brain regions was not consistently observed during the admiration videos, and was absent for the neutral videos. CONCLUSIONS/SIGNIFICANCE: Results suggest that the neural systems supporting moral elevation are remarkably consistent across subjects viewing the same emotional content. We demonstrate that model-free techniques such as inter-subject synchronization may be a useful tool for studying complex, context dependent emotions such as self-transcendent emotion.

  3. Neural Basis of Moral Elevation Demonstrated through Inter-Subject Synchronization of Cortical Activity during Free-Viewing

    Science.gov (United States)

    Englander, Zoë A.; Haidt, Jonathan; Morris, James P.

    2012-01-01

    Background Most research investigating the neural basis of social emotions has examined emotions that give rise to negative evaluations of others (e.g. anger, disgust). Emotions triggered by the virtues and excellences of others have been largely ignored. Using fMRI, we investigated the neural basis of two “other-praising" emotions – Moral Elevation (a response to witnessing acts of moral beauty), and Admiration (which we restricted to admiration for physical skill). Methodology/Principal Findings Ten participants viewed the same nine video clips. Three clips elicited moral elevation, three elicited admiration, and three were emotionally neutral. We then performed pair-wise voxel-by-voxel correlations of the BOLD signal between individuals for each video clip and a separate resting-state run. We observed a high degree of inter-subject synchronization, regardless of stimulus type, across several brain regions during free-viewing of videos. Videos in the elevation condition evoked significant inter-subject synchronization in brain regions previously implicated in self-referential and interoceptive processes, including the medial prefrontal cortex, precuneus, and insula. The degree of synchronization was highly variable over the course of the videos, with the strongest synchrony occurring during portions of the videos that were independently rated as most emotionally arousing. Synchrony in these same brain regions was not consistently observed during the admiration videos, and was absent for the neutral videos. Conclusions/Significance Results suggest that the neural systems supporting moral elevation are remarkably consistent across subjects viewing the same emotional content. We demonstrate that model-free techniques such as inter-subject synchronization may be a useful tool for studying complex, context dependent emotions such as self-transcendent emotion. PMID:22745745

  4. Reduced task-induced variations in the distribution of activity across back muscle regions in individuals with low back pain.

    Science.gov (United States)

    Falla, Deborah; Gizzi, Leonardo; Tschapek, Marika; Erlenwein, Joachim; Petzke, Frank

    2014-05-01

    This study investigated change in the distribution of lumbar erector spinae muscle activity and pressure pain sensitivity across the low back in individuals with low back pain (LBP) and healthy controls. Surface electromyographic (EMG) signals were recorded from multiple locations over the lumbar erector spinae muscle with a 13×5 grid of electrodes from 19 people with chronic nonspecific LBP and 17 control subjects as they performed a repetitive lifting task. The EMG root mean square (RMS) was computed for each location of the grid to form a map of the EMG amplitude distribution. Pressure pain thresholds (PPT) were recorded before and after the lifting task over a similar area of the back. For the control subjects, the EMG RMS progressively increased more in the caudal region of the lumbar erector spinae during the repetitive task, resulting in a shift in the distribution of muscle activity. In contrast, the distribution of muscle activity remained unaltered in the LBP group despite an overall increase in EMG amplitude. PPT was lower in the LBP group after completion of the repetitive task compared to baseline (average across all locations: pre: 268.0±165.9 kPa; post: 242.0±166.7 kPa), whereas no change in PPT over time was observed for the control group (320.1±162.1 kPa; post: 322.0±179.5 kPa). The results demonstrate that LBP alters the normal adaptation of lumbar erector spinae muscle activity to exercise, which occurs in the presence of exercise-induced hyperalgesia. Reduced variability of muscle activity may have important implications for the provocation and recurrence of LBP due to repetitive tasks. Copyright © 2014 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

  5. Prior pallidotomy reduces and modifies neuronal activity in the subthalamic nucleus of Parkinson's disease patients.

    Science.gov (United States)

    Zaidel, A; Moran, A; Marjan, G; Bergman, H; Israel, Z

    2008-01-01

    Parkinson's disease (PD) patients with prior radio-frequency lesions in the internal segment of the globus pallidus (GPi, pallidotomy), whose symptoms have deteriorated, may be candidates for further invasive treatment such as subthalamic deep brain stimulation (STN DBS). Six patients with prior pallidotomy (five unilaterally; one bilaterally) underwent bilateral STN DBS. The microelectrode recordings (MERs, used intraoperatively for STN verification), ipsilateral and contralateral to pallidotomy, and MERs from 11 matched PD patients who underwent bilateral STN DBS without prior pallidotomy were compared. For each trajectory, average, variance and mean successive difference (MSD, a measure of irregularity) of the root mean square (RMS) of the STN MER were calculated. The RMS in trajectories ipsilateral to pallidotomy showed significant reduction of the mean average and MSD of STN activity when compared with trajectories from patients without prior pallidotomy. The RMS parameters contralateral to pallidotomy tend to lie between those ipsilateral to pallidotomy and those without prior pallidotomy. The average STN power spectral density of oscillatory activity was notably lower ipsilateral to pallidotomy than contralateral, or without prior pallidotomy. The finding that pallidotomy reduces STN activity and changes firing characteristics, in conjunction with the effectiveness of STN DBS despite prior pallidotomy, calls for reappraisal and modification of the current model of the basal ganglia (BG) cortical network. It highlights the critical role of direct projections from the BG to brain-stem structures and suggests a possible GPi-STN reciprocal positive-feedback mechanism.

  6. Inhibition of nuclear factor kappa B activation reduces Coxsackievirus B3 replication in lymphoid cells.

    Science.gov (United States)

    Sobotta, Katharina; Wilsky, Steffi; Althof, Nadine; Wiesener, Nadine; Wutzler, Peter; Henke, Andreas

    2012-02-01

    Interactions between viral replication machineries and host cell metabolism display interesting information how certain viruses capitalize cellular pathways to support progeny production. Among those pathogens, Coxsackievirus B3 (CVB3) has been identified to manipulate intracellular signaling very comprehensively. Next to others, this human pathogenic virus causes acute and chronic forms of myocarditis, pancreatitis, and meningitis. Here, activation of nuclear factor kappa B (NFκB) signaling appears to be involved in successful infection. Viral replication is not restricted to solid organs but involves susceptible immune cells as well. In the present study, p65 phosphorylation as one aspect of NFκB activation and inhibition via BAY 11-7085 administration was analyzed in the context of CVB3 replication in lymphoid cells. During CVB3 infection, an up-regulation of p65 translation is detectable, which is accompanied by noticeable phosphorylation. Inhibition of NFκB signaling reduces viral replication in a dose- and time-dependent manner. Taken together, these results indicate that during CVB3 replication in human and murine lymphoid cells, NFκB signaling is activated and facilitates viral replication. Therefore, antiviral strategies to target such central cellular signaling pathways may represent potential possibilities for the development of new virostatica. Copyright © 2011 Elsevier B.V. All rights reserved.

  7. Investigation on Using SBS and Active Carbon Filler to Reduce the VOC Emission from Bituminous Materials

    Directory of Open Access Journals (Sweden)

    Peiqiang Cui

    2014-08-01

    Full Text Available Bituminous materials are playing a vital role in pavement design and the roofing industry because of outstanding properties. Unfortunately, bituminous materials will release volatile organic compounds (VOC, making them non-environmentally friendly. Therefore, technologies that can be used to decrease the VOC emission are urgently required. In this research, the VOC emission and material behaviors were analyzed and compared to investigate the possibility of adding styrene butadiene styrene (SBS and active carbon filler into bituminous materials to develop environmentally-friendly materials. Thermal gravimetric analysis-mass spectrometry (TG-MS and ultraviolet-visible spectroscopy testing (UV-Vis were employed to characterize the VOC emission process. Temperature sweep testing and frequency sweep testing were conducted to evaluate the rheological properties of bituminous materials. Research results indicated that the combined introduction of 4 wt% styrene butadiene styrene (SBS and 4 wt% active carbon filler cannot only significantly lower the VOC emission speed and amount, but also improve the deformation resistance behavior at a higher temperature. SBS and active carbon filler can be used to reduce the VOC emission form bituminous materials.

  8. Tonically Active α5GABAA Receptors Reduce Motoneuron Excitability and Decrease the Monosynaptic Reflex

    Directory of Open Access Journals (Sweden)

    Martha Canto-Bustos

    2017-09-01

    Full Text Available Motoneurons, the final common path of the Central Nervous System (CNS, are under a complex control of its excitability in order to precisely translate the interneuronal pattern of activity into skeletal muscle contraction and relaxation. To fulfill this relevant function, motoneurons are provided with a vast repertoire of receptors and channels, including the extrasynaptic GABAA receptors which have been poorly investigated. Here, we confirmed that extrasynaptic α5 subunit-containing GABAA receptors localize with choline acetyltransferase (ChAT positive cells, suggesting that these receptors are expressed in turtle motoneurons as previously reported in rodents. In these cells, α5GABAA receptors are activated by ambient GABA, producing a tonic shunt that reduces motoneurons’ membrane resistance and affects their action potential firing properties. In addition, α5GABAA receptors shunted the synaptic excitatory inputs depressing the monosynaptic reflex (MSR induced by activation of primary afferents. Therefore, our results suggest that α5GABAA receptors may play a relevant physiological role in motor control.

  9. Effectiveness of powered hospital bed movers for reducing physiological strain and back muscle activation.

    Science.gov (United States)

    Daniell, Nathan; Merrett, Simon; Paul, Gunther

    2014-07-01

    Battery powered bed movers are becoming increasingly common within the hospital setting. The use of powered bed movers is believed to result in reduced physical efforts required by health care workers, which may be associated with a decreased risk of occupation related injuries. However, little work has been conducted assessing how powered bed movers impact on levels of physiological strain and muscle activation for the user. The muscular efforts associated with moving hospital beds using three different methods; powered StaminaLift Bed Mover (PBM1), powered Gzunda Bed Mover (PBM2) and manual pushing were measured on six male subjects. Fourteen muscles were assessed moving a weighted hospital bed along a standardized route in an Australian hospital environment. Trunk inclination and upper spine acceleration were also quantified. Powered bed movers exhibited significantly lower muscle activation levels than manual pushing for the majority of muscles. When using the PBM1, users adopted a more upright posture which was maintained while performing different tasks (e.g. turning a corner, entering a lift), while trunk inclination varied considerably for manual pushing and the PBM2. The reduction in lower back muscular activation levels may result in lower incidence of lower back injury. Copyright © 2013 Elsevier Ltd and The Ergonomics Society. All rights reserved.

  10. Muscle glycogenolysis is not activated by changes in cytosolic P-metabolites: a 31P and 1H MRS demonstration.

    Science.gov (United States)

    Hsu, Alex C; Dawson, M Joan

    2003-04-01

    Skeletal muscle contraction and glycogenolysis are closely coupled. The standard explanation for this coupling, as taught in modern biochemistry textbooks, is that the metabolic products of contraction (ADP, AMP, P(i)) feed back to activate glycogenolytic enzymes, thus providing for resynthesis of ATP. However, both in vivo (31)P MRS analyses and chemical analyses of muscle extracts have provided results that are contrary to this theory, at least in its simplest form. The MRS studies suffer from ambiguous assumptions. More importantly, in (31)P MRS studies the dependent and independent variables are often confounded because the glycogenolytic rate is calculated from the same data which are used to calculate the other metabolic variables. The analysis of biopsies has been necessarily quite limited, and suffers from a different set of experimental artifacts. Thus, the problem of contraction-glycogenolysis-coupling was reassessed using a quantitatively accurate (1)H MRS method. It is confirmed that glycogenolysis and contractions are closely coupled during repetitive exercise, while glycogenolysis and P-metabolite concentrations are not. A simple metabolic feedback system cannot explain contraction-glycogenolysis-coupling.

  11. Grouping annotations on the subcellular layered interactome demonstrates enhanced autophagy activity in a recurrent experimental autoimmune uveitis T cell line.

    Directory of Open Access Journals (Sweden)

    Xiuzhi Jia

    Full Text Available Human uveitis is a type of T cell-mediated autoimmune disease that often shows relapse-remitting courses affecting multiple biological processes. As a cytoplasmic process, autophagy has been seen as an adaptive response to cell death and survival, yet the link between autophagy and T cell-mediated autoimmunity is not certain. In this study, based on the differentially expressed genes (GSE19652 between the recurrent versus monophasic T cell lines, whose adoptive transfer to susceptible animals may result in respective recurrent or monophasic uveitis, we proposed grouping annotations on a subcellular layered interactome framework to analyze the specific bioprocesses that are linked to the recurrence of T cell autoimmunity. That is, the subcellular layered interactome was established by the Cytoscape and Cerebral plugin based on differential expression, global interactome, and subcellular localization information. Then, the layered interactomes were grouping annotated by the ClueGO plugin based on Gene Ontology and Kyoto Encyclopedia of Genes and Genomes databases. The analysis showed that significant bioprocesses with autophagy were orchestrated in the cytoplasmic layered interactome and that mTOR may have a regulatory role in it. Furthermore, by setting up recurrent and monophasic uveitis in Lewis rats, we confirmed by transmission electron microscopy that, in comparison to the monophasic disease, recurrent uveitis in vivo showed significantly increased autophagy activity and extended lymphocyte infiltration to the affected retina. In summary, our framework methodology is a useful tool to disclose specific bioprocesses and molecular targets that can be attributed to a certain disease. Our results indicated that targeted inhibition of autophagy pathways may perturb the recurrence of uveitis.

  12. PARP Inhibitor Activity Correlates with SLFN11 Expression and Demonstrates Synergy with Temozolomide in Small Cell Lung Cancer.

    Science.gov (United States)

    Lok, Benjamin H; Gardner, Eric E; Schneeberger, Valentina E; Ni, Andy; Desmeules, Patrice; Rekhtman, Natasha; de Stanchina, Elisa; Teicher, Beverly A; Riaz, Nadeem; Powell, Simon N; Poirier, John T; Rudin, Charles M

    2017-01-15

    PARP inhibitors (PARPi) are a novel class of small molecule therapeutics for small cell lung cancer (SCLC). Identification of predictors of response would advance our understanding, and guide clinical application, of this therapeutic strategy. Efficacy of PARP inhibitors olaparib, rucaparib, and veliparib, as well as etoposide and cisplatin in SCLC cell lines, and gene expression correlates, was analyzed using public datasets. HRD genomic scar scores were calculated from Affymetrix SNP 6.0 arrays. In vitro talazoparib efficacy was measured by cell viability assays. For functional studies, CRISPR/Cas9 and shRNA were used for genomic editing and transcript knockdown, respectively. Protein levels were assessed by immunoblotting and immunohistochemistry (IHC). Quantitative synergy of talazoparib and temozolomide was determined in vitro In vivo efficacy of talazoparib, temozolomide, and the combination was assessed in patient-derived xenograft (PDX) models. We identified SLFN11, but not HRD genomic scars, as a consistent correlate of response to all three PARPi assessed, with loss of SLFN11 conferring resistance to PARPi. We confirmed these findings in vivo across multiple PDX and defined IHC staining for SLFN11 as a predictor of talazoparib response. As temozolomide has activity in SCLC, we investigated combination therapy with talazoparib and found marked synergy in vitro and efficacy in vivo, which did not solely depend on SLFN11 or MGMT status. SLFN11 is a relevant predictive biomarker of sensitivity to PARP inhibitor monotherapy in SCLC and we identify combinatorial therapy with TMZ as a particularly promising therapeutic strategy that warrants further clinical investigation. Clin Cancer Res; 23(2); 523-35. ©2016 AACR. ©2016 American Association for Cancer Research.

  13. Interfacial Engineering of Bimetallic Ag/Pt Nanoparticles on Reduced Graphene Oxide Matrix for Enhanced Antimicrobial Activity.

    Science.gov (United States)

    Zhang, Mei; Zhao, Yanhua; Yan, Li; Peltier, Raoul; Hui, Wenli; Yao, Xi; Cui, Yali; Chen, Xianfeng; Sun, Hongyan; Wang, Zuankai

    2016-04-06

    Environmental biofouling caused by the formation of biofilm has been one of the most urgent global concerns. Silver nanoparticles (NPs), owing to their wide-spectrum antimicrobial property, have been widely explored to combat biofilm, but their extensive use has raised growing concern because they persist in the environment. Here we report a novel hybrid nanocomposite that imparts enhanced antimicrobial activity and low cytotoxicity yet with the advantage of reduced silver loading. The nanocomposite consists of Pt/Ag bimetallic NPs (BNPs) decorated on the porous reduced graphene oxide (rGO) nanosheets. We demonstrate that the enhanced antimicrobial property against Escherichia coli is ascribed to the intricate control of the interfaces between metal compositions, rGO matrix, and bacteria, where the BNPs lead to a rapid release of silver ions, and the trapping of bacteria by the porous rGO matrix further provides high concentration silver ion sites for efficient bacteria-bactericide interaction. We envision that our facile approach significantly expands the design space for the creation of silver-based antimicrobial materials to achieve a wide spectrum of functionalities.

  14. Reduced activity of CD13/aminopeptidase N (APN) in aggressive meningiomas is associated with increased levels of SPARC.

    Science.gov (United States)

    Mawrin, Christian; Wolke, Carmen; Haase, Daniela; Krüger, Sabine; Firsching, Raimund; Keilhoff, Gerburg; Paulus, Werner; Gutmann, David H; Lal, Anita; Lendeckel, Uwe

    2010-01-01

    Meningiomas are the second most common brain tumors in adults, and meningiomas exhibit a tendency to invade adjacent structures. Compared with high-grade gliomas, little is known about the molecular changes that potentially underlie the invasive behavior of meningiomas. In this study, we examined the expression and function of the membrane alanyl-aminopeptidase [mAAP, aminopeptidase N (APN), CD13, EC3.4.11.2] zinc-dependent ectopeptidase in meningiomas and meningioma cell lines, based on its prior association with tumor invasion in colorectal and renal carcinomas. We found a significant reduction of APNmRNA and protein expression, as well as enzymatic activity, in high-grade meningiomas. While meningioma tumor cell proliferation was not affected by either pharmacologic APN inhibition or siRNA-mediated APN silencing, APN pharmacologic and siRNA knockdown significantly reduced meningioma cell invasion in vitro. Next, we employed pathway-specific cDNA microarray analyses to identify extracellular matrix and adhesion molecules regulated by APN, and found that APN-siRNA knockdown substantially increased the expression of secreted protein, acidic and rich in cysteine (SPARC)/osteonectin. Finally, we demonstrated that SPARC, which has been previously associated with meningioma invasiveness, was increased in aggressive meningiomas. Collectively, these results suggest that APN expression and enzymatic function is reduced in aggressive meningiomas, and that alterations in the balance between APN and SPARC might favor meningioma invasion.

  15. Isoliquiritigenin reduces oxidative damage and alleviates mitochondrial impairment by SIRT1 activation in experimental diabetic neuropathy.

    Science.gov (United States)

    Yerra, Veera Ganesh; Kalvala, Anil Kumar; Kumar, Ashutosh

    2017-09-01

    Sirtuin (SIRT1) inactivation underlies the pathogenesis of insulin resistance and hyperglycaemia-associated vascular complications, but its role in diabetic neuropathy (DN) has not been yet explored. We have evaluated hyperglycaemia-induced alteration of SIRT1 signalling and the effect of isoliquiritigenin (ILQ) on SIRT1-directed AMP kinase (AMPK) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) signalling in peripheral nerves of streptozotocin (STZ) (55 mg/kg, ip)-induced diabetic rats and in high glucose (30 mM)-exposed neuro2a (N2A) cells. Diabetic rats and high glucose-exposed N2A cells showed reduction in SIRT1 expression with consequent decline in mitochondrial biogenesis and autophagy. ILQ (10 & 20 mg/kg, po) administration to diabetic rats for 2 weeks and exposure to glucose-insulted N2A cells resulted in significant SIRT1 activation with concurrent increase in mitochondrial biogenesis and autophagy. ILQ administration also enhanced NAD(+)/NADH ratio in peripheral sciatic nerves which explains its possible SIRT1 modulatory effect. Functional and behavioural studies show beneficial effect of ILQ as it alleviated nerve conduction and nerve blood flow deficits in diabetic rats along with improvement in behavioural parameters (hyperalgesia and allodynia). ILQ treatment to N2A cells reduced high glucose-driven ROS production and mitochondrial membrane depolarization. Further, ILQ-mediated SIRT1 activation facilitated the Nrf2-directed antioxidant signalling. Overall, results from this study suggest that SIRT1 activation by ILQ mimic effects of calorie restriction, that is, PGC-1α-mediated mitochondrial biogenesis, FOXO3a mediated stress resistance and AMPK mediated autophagy effects to counteract the multiple manifestations in experimental DN. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Theta burst stimulation reduces disability during the activities of daily living in spatial neglect.

    Science.gov (United States)

    Cazzoli, Dario; Müri, René M; Schumacher, Rahel; von Arx, Sebastian; Chaves, Silvia; Gutbrod, Klemens; Bohlhalter, Stephan; Bauer, Daniel; Vanbellingen, Tim; Bertschi, Manuel; Kipfer, Stefan; Rosenthal, Clive R; Kennard, Christopher; Bassetti, Claudio L; Nyffeler, Thomas

    2012-11-01

    Left-sided spatial neglect is a common neurological syndrome following right-hemispheric stroke. The presence of spatial neglect is a powerful predictor of poor rehabilitation outcome. In one influential account of spatial neglect, interhemispheric inhibition is impaired and leads to a pathological hyperactivity in the contralesional hemisphere, resulting in a biased attentional allocation towards the right hemifield. Inhibitory transcranial magnetic stimulation can reduce the hyperactivity of the contralesional, intact hemisphere and thereby improve spatial neglect symptoms. However, it is not known whether this improvement is also relevant to the activities of daily living during spontaneous behaviour. The primary aim of the present study was to investigate whether the repeated application of continuous theta burst stimulation trains could ameliorate spatial neglect on a quantitative measure of the activities of daily living during spontaneous behaviour. We applied the Catherine Bergego Scale, a standardized observation questionnaire that can validly and reliably detect the presence and severity of spatial neglect during the activities of daily living. Eight trains of continuous theta burst stimulation were applied over two consecutive days on the contralesional, left posterior parietal cortex in patients suffering from subacute left spatial neglect, in a randomized, double-blind, sham-controlled design, which also included a control group of neglect patients without stimulation. The results showed a 37% improvement in the spontaneous everyday behaviour of the neglect patients after the repeated application of continuous theta burst stimulation. Remarkably, the improvement persisted for at least 3 weeks after stimulation. The amelioration of spatial neglect symptoms in the activities of daily living was also generally accompanied by significantly better performance in the neuropsychological tests. No significant amelioration in symptoms was observed after sham

  17. Active power decoupling with reduced converter stress for single-phase power conversion and interfacing

    Indian Academy of Sciences (India)

    SUJATA BHOWMICK; L UMANAND

    2017-08-01

    Single-phase DC–AC power electronic converters suffer from pulsating power at double the line frequency. The commonest practice to handle the issue is to provide a huge electrolytic capacitor for smoothening out the ripple. However, the electrolytic capacitors having short end of lifetime limit the overall lifetime of the converter. Another way of handling the ripple power is by active power decoupling (APD) using the storage devices and a set of semiconductor switches. Here, a novel topology has been proposed in implementing APD. The topology claims the benefit of (1) reduced stress on converter switches and (2) using smaller capacitance value, thus alleviating the use of electrolytic capacitor and in turn improving the lifetime of the converter. The circuit consists of a third leg, a storage capacitor and a storage inductor. The analysis and the simulation results are shown to prove the effectiveness of the topology.

  18. Joining technologies of reduced activation ferritic/martensitic steel for blanket fabrication

    Energy Technology Data Exchange (ETDEWEB)

    Hirose, T. [JAERI, Naka Fusion Establishment, 801-1 Mukouyama, Naka, Ibaraki 311-0193 (Japan)]. E-mail: hiroset@fusion.naka.jaeri.go.jp; Shiba, K. [JAERI, Naka Fusion Establishment, 801-1 Mukouyama, Naka, Ibaraki 311-0193 (Japan); Ando, M. [JAERI, Naka Fusion Establishment, 801-1 Mukouyama, Naka, Ibaraki 311-0193 (Japan); Enoeda, M. [JAERI, Naka Fusion Establishment, 801-1 Mukouyama, Naka, Ibaraki 311-0193 (Japan); Akiba, M. [JAERI, Naka Fusion Establishment, 801-1 Mukouyama, Naka, Ibaraki 311-0193 (Japan)

    2006-02-15

    Reduced activation ferritic/martensitic steel, like F82H has been developed as a structural material for in vessel components because of its superior resistance to irradiation damage. As a blanket fabrication process, hot isostatic pressing (HIP) bonding has the great merit of near-net-shaping processing. The degassing conditions and surface roughness were investigated as parameters of HIP conditions. Although the surface roughness and degassing conditions had slight effects on tensile properties, the lack of degassing caused significant degradation of impact properties. A dissimilar metal joint between sintered tungsten and F82H was fabricated by a spark plasma sintering (SPS) method. The joint had no defects in spite of the large difference in thermal expansion coefficient between tungsten and F82H. It is considered that formation of a compliant layer of the ferritic phase can lead to successful bonding for the tungsten and F82H joint even without an artificial interlayer.

  19. Measuring and Reducing Off-Target Activities of Programmable Nucleases Including CRISPR-Cas9.

    Science.gov (United States)

    Koo, Taeyoung; Lee, Jungjoon; Kim, Jin-Soo

    2015-06-01

    Programmable nucleases, which include zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and RNA-guided engineered nucleases (RGENs) repurposed from the type II clustered, regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated protein 9 (Cas9) system are now widely used for genome editing in higher eukaryotic cells and whole organisms, revolutionising almost every discipline in biological research, medicine, and biotechnology. All of these nucleases, however, induce off-target mutations at sites homologous in sequence with on-target sites, limiting their utility in many applications including gene or cell therapy. In this review, we compare methods for detecting nuclease off-target mutations. We also review methods for profiling genome-wide off-target effects and discuss how to reduce or avoid off-target mutations.

  20. Microstructural evolution of reduced-activation martensitic steel under single and sequential ion irradiations

    Energy Technology Data Exchange (ETDEWEB)

    Luo, Fengfeng [Key Laboratory of Artificial Micro- and Nano-structures of Ministry of Education, Hubei Nuclear Solid Physics Key Laboratory and School of Physics and Technology, Wuhan University, Wuhan 430072 (China); Guo, Liping, E-mail: guolp@whu.edu.cn [Key Laboratory of Artificial Micro- and Nano-structures of Ministry of Education, Hubei Nuclear Solid Physics Key Laboratory and School of Physics and Technology, Wuhan University, Wuhan 430072 (China); Jin, Shuoxue; Li, Tiecheng; Zheng, Zhongcheng [Key Laboratory of Artificial Micro- and Nano-structures of Ministry of Education, Hubei Nuclear Solid Physics Key Laboratory and School of Physics and Technology, Wuhan University, Wuhan 430072 (China); Yang, Feng; Xiong, Xuesong; Suo, Jinping [State Key Laboratory of Mould Technology, Institute of Materials Science and Engineering, Huazhong University of Science and Technology, Wuhan 430074 (China)

    2013-07-15

    Microstructural evolution of super-clean reduced-activation martensitic steels irradiated with single-beam (Fe{sup +}) and sequential-beam (Fe{sup +} plus He{sup +}) at 350 °C and 550 °C was studied. Sequential-beam irradiation induced smaller size and larger number density of precipitates compared to single-beam irradiatio