WorldWideScience

Sample records for demonstrated significant activity

  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. [Significance of the demonstration of Actinomyces in cervical cytological smears].

    Science.gov (United States)

    Dybdahl, H; Baandrup, U

    1988-10-17

    In recent years there has been well documented evidence of a connection between adnexitis and the use of IUDs. It has also been reported that Actinomyces-caused adnexitis is often a serious precursor of tubo-ovarian abscesses which require surgical attention. The investigation included a total of 17,734 routine Pap smears taken in the pathology department over a 4-month period. The smears were screened for the presence of Actinomyces and information on type of IUD and gynecological symptoms was gathered from women testing positive for Actinomyces. Comparable information was gathered from 2 age-matched control groups. 1 group consisted of women with an IUD but without Actinomyces; the other group consisted of women without an IUD and without Actinomyces. Of the 180 patients with Actinomyces, 175 were IUD users and only 5 were nonusers. The incidence of gynecological symptoms among the patients showed increased frequency for women with Actinomyces only with regard to cervical discharge. The Nova-T IUD was found to be significantly less frequently associated with Actinomyces than the other IUDs.

  3. 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.

  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. 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.)

  7. Environmental Assessment and Finding of No Significant Impact: Kalina Geothermal Demonstration Project Steamboat Springs, Nevada

    Energy Technology Data Exchange (ETDEWEB)

    N/A

    1999-02-22

    The Department of Energy (DOE) has prepared an Environmental Assessment (EA) to provide the DOE and other public agency decision makers with the environmental documentation required to take informed discretionary action on the proposed Kalina Geothermal Demonstration project. The EA assesses the potential environmental impacts and cumulative impacts, possible ways to minimize effects associated with partial funding of the proposed project, and discusses alternatives to DOE actions. The DOE will use this EA as a basis for their decision to provide financial assistance to Exergy, Inc. (Exergy), the project applicant. Based on the analysis in the EA, DOE has determined that the proposed action is not a major Federal action significantly affecting the quality of the human or physical environment, within the meaning of the National Environmental Policy Act (NEPA) of 1969. Therefore, the preparation of an environmental impact statement is not required and DOE is issuing this Finding of No Significant Impact (FONSI).

  8. Behaviorally inhibited individuals demonstrate significantly enhanced conditioned response acquisition under non-optimal learning conditions.

    Science.gov (United States)

    Holloway, J L; Allen, M T; Myers, C E; Servatius, R J

    2014-03-15

    Behavioral inhibition (BI) is an anxiety vulnerability factor associated with hypervigilance to novel stimuli, threat, and ambiguous cues. The progression from anxiety risk to a clinical disorder is unknown, although the acquisition of defensive learning and avoidance may be a critical feature. As the expression of avoidance is also central to anxiety development, the present study examined avoidance acquisition as a function of inhibited temperament using classical eyeblink conditioning. Individuals were classified as behaviorally inhibited (BI) or non-inhibited (NI) based on combined scores from the Adult and Retrospective Measures of Behavioural Inhibition (AMBI and RMBI, respectively). Acquisition was assessed using delay, omission, or yoked conditioning schedules of reinforcement. Omission training was identical to delay, except that the emission of an eyeblink conditioned response (CR) resulted in omission of the unconditioned airpuff stimulus (US) on that trial. Each subject in the yoked group was matched on total BI score to a subject in the omission group, and received the same schedule of CS and US delivery, resulting in a partial reinforcement training schedule. Delay conditioning elicited significantly more CRs compared to the omission and yoked contingencies, the latter two of which did not differ from each other. Thus, acquisition of an avoidance response was not apparent. BI individuals demonstrated enhanced acquisition overall, while partial reinforcement training significantly distinguished between BI and NI groups. Enhanced learning in BI may be a function of an increased defensive learning capacity, or sensitivity to uncertainty. Further work examining the influence of BI on learning acquisition is important for understanding individual differences in disorder etiology in anxiety vulnerable cohorts.

  9. 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.

  10. The demonstration of significant ferroelectricity in epitaxial Y-doped HfO2 film

    OpenAIRE

    Takao Shimizu; Kiliha Katayama; Takanori Kiguchi; Akihiro Akama; Konno, Toyohiko J.; Osami Sakata; Hiroshi Funakubo

    2016-01-01

    Ferroelectricity and Curie temperature are demonstrated for epitaxial Y-doped HfO2 film grown on (110) yttrium oxide-stabilized zirconium oxide (YSZ) single crystal using Sn-doped In2O3 (ITO) as bottom electrodes. The XRD measurements for epitaxial film enabled us to investigate its detailed crystal structure including orientations of the film. The ferroelectricity was confirmed by electric displacement filed – electric filed hysteresis measurement, which revealed saturated polarization of 16...

  11. Significance of coronary artery calcification demonstrated by computed tomography in detecting coronary artery stenosis

    Energy Technology Data Exchange (ETDEWEB)

    Shiraki, Teruo; Akiyama, Yoko; Kita, Masahide [Iwakuni national Hospital, Yamaguchi (Japan)] [and others

    2002-02-01

    Serial 27 patients with angina attack were enrolled in this trial. Plain computed tomography (CT) of the chest and coronary angiogram were performed simultaneously. Calcification of main branch of coronary arteies (left main trunk, left anterior desending artery, left circumflex artery, right coronary artery) was judged visually. More than 50% stenosis was defined significant by quantitative coronary angiogram. Correlation between calcified lesions detected by CT and angiographic stenoses showed high specificity and negative predictive value was also high (sensitity=58%, specificity=80%, positive predictive value=27%, negative predictive value=94%, p<0.05). There was no significant correlation between patients with calcification of corornary artery and angiographic stenosis. The present study showed the low probability of significant stenosis without calcification and the high probability with multiple calcified lesions. (author)

  12. The demonstration of significant ferroelectricity in epitaxial Y-doped HfO2 film

    Science.gov (United States)

    Shimizu, Takao; Katayama, Kiliha; Kiguchi, Takanori; Akama, Akihiro; Konno, Toyohiko J.; Sakata, Osami; Funakubo, Hiroshi

    2016-09-01

    Ferroelectricity and Curie temperature are demonstrated for epitaxial Y-doped HfO2 film grown on (110) yttrium oxide-stabilized zirconium oxide (YSZ) single crystal using Sn-doped In2O3 (ITO) as bottom electrodes. The XRD measurements for epitaxial film enabled us to investigate its detailed crystal structure including orientations of the film. The ferroelectricity was confirmed by electric displacement filed – electric filed hysteresis measurement, which revealed saturated polarization of 16 μC/cm2. Estimated spontaneous polarization based on the obtained saturation polarization and the crystal structure analysis was 45 μC/cm2. This value is the first experimental estimations of the spontaneous polarization and is in good agreement with the theoretical value from first principle calculation. Curie temperature was also estimated to be about 450 °C. This study strongly suggests that the HfO2-based materials are promising for various ferroelectric applications because of their comparable ferroelectric properties including polarization and Curie temperature to conventional ferroelectric materials together with the reported excellent scalability in thickness and compatibility with practical manufacturing processes.

  13. Point mutations in firefly luciferase C-domain demonstrate its significance in green color of bioluminescence.

    Science.gov (United States)

    Modestova, Yulia; Koksharov, Mikhail I; Ugarova, Natalia N

    2014-09-01

    Firefly luciferase is a two-domain enzyme that catalyzes the bioluminescent reaction of firefly luciferin oxidation. Color of the emitted light depends on the structure of the enzyme, yet the exact color-tuning mechanism remains unknown by now, and the role of the C-domain in it is rarely discussed, because a very few color-shifting mutations in the C-domain were described. Recently we reported a strong red-shifting mutation E457K in the C-domain; the bioluminescence spectra of this enzyme were independent of temperature or pH. In the present study we investigated the role of the residue E457 in the enzyme using the Luciola mingrelica luciferase with a thermostabilized N-domain as a parent enzyme for site-directed mutagenesis. We obtained a set of mutants and studied their catalytic properties, thermal stability and bioluminescence spectra. Experimental spectra were represented as a sum of two components (bioluminescence spectra of putative "red" and "green" emitters); λmax of these components were constant for all the mutants, but the ratio of these emitters was defined by temperature and mutations in the C-domain. We suggest that each emitter is stabilized by a specific conformation of the active site; thus, enzymes with two forms of the active site coexist in the reactive media. The rigid structure of the C-domain is crucial for maintaining the conformation corresponding to the "green" emitter. We presume that the emitters are the keto- and enol forms of oxyluciferin.

  14. Novel stable isotope analyses demonstrate significant rates of glucose cycling in mouse pancreatic islets.

    Science.gov (United States)

    Wall, Martha L; Pound, Lynley D; Trenary, Irina; O'Brien, Richard M; Young, Jamey D

    2015-06-01

    A polymorphism located in the G6PC2 gene, which encodes an islet-specific glucose-6-phosphatase catalytic subunit, is the most important common determinant of variations in fasting blood glucose (FBG) levels in humans. Studies of G6pc2 knockout (KO) mice suggest that G6pc2 represents a negative regulator of basal glucose-stimulated insulin secretion (GSIS) that acts by hydrolyzing glucose-6-phosphate (G6P), thereby reducing glycolytic flux. However, this conclusion conflicts with the very low estimates for the rate of glucose cycling in pancreatic islets, as assessed using radioisotopes. We have reassessed the rate of glucose cycling in pancreatic islets using a novel stable isotope method. The data show much higher levels of glucose cycling than previously reported. In 5 mmol/L glucose, islets from C57BL/6J chow-fed mice cycled ∼16% of net glucose uptake. The cycling rate was further increased at 11 mmol/L glucose. Similar cycling rates were observed using islets from high fat-fed mice. Importantly, glucose cycling was abolished in G6pc2 KO mouse islets, confirming that G6pc2 opposes the action of the glucose sensor glucokinase by hydrolyzing G6P. The demonstration of high rates of glucose cycling in pancreatic islets explains why G6pc2 deletion enhances GSIS and why variants in G6PC2 affect FBG in humans. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  15. 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…

  16. 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.

  17. 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.

  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. Identification of sequence motifs significantly associated with antisense activity

    Directory of Open Access Journals (Sweden)

    Peek Andrew S

    2007-06-01

    Full Text Available Abstract Background Predicting the suppression activity of antisense oligonucleotide sequences is the main goal of the rational design of nucleic acids. To create an effective predictive model, it is important to know what properties of an oligonucleotide sequence associate significantly with antisense activity. Also, for the model to be efficient we must know what properties do not associate significantly and can be omitted from the model. This paper will discuss the results of a randomization procedure to find motifs that associate significantly with either high or low antisense suppression activity, analysis of their properties, as well as the results of support vector machine modelling using these significant motifs as features. Results We discovered 155 motifs that associate significantly with high antisense suppression activity and 202 motifs that associate significantly with low suppression activity. The motifs range in length from 2 to 5 bases, contain several motifs that have been previously discovered as associating highly with antisense activity, and have thermodynamic properties consistent with previous work associating thermodynamic properties of sequences with their antisense activity. Statistical analysis revealed no correlation between a motif's position within an antisense sequence and that sequences antisense activity. Also, many significant motifs existed as subwords of other significant motifs. Support vector regression experiments indicated that the feature set of significant motifs increased correlation compared to all possible motifs as well as several subsets of the significant motifs. Conclusion The thermodynamic properties of the significantly associated motifs support existing data correlating the thermodynamic properties of the antisense oligonucleotide with antisense efficiency, reinforcing our hypothesis that antisense suppression is strongly associated with probe/target thermodynamics, as there are no enzymatic

  1. 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.

  2. Adolescents with Major Depression Demonstrate Increased Amygdala Activation

    Science.gov (United States)

    Yang, Tony T.; Simmons, Alan N.; Matthews, Scott C.; Tapert, Susan F.; Frank, Guido K.; Max, Jeffrey E.; Bischoff-Grethe, Amanda; Lansing, Amy E.; Brown, Gregory; Strigo, Irina A.; Wu, Jing; Paulus, Martin P.

    2010-01-01

    Objective: Functional neuroimaging studies have led to a significantly deeper understanding of the underlying neural correlates and the development of several mature models of depression in adults. In contrast, our current understanding of the underlying neural substrates of adolescent depression is very limited. Although numerous studies have…

  3. Adaptive management of the Great Barrier Reef: a globally significant demonstration of the benefits of networks of marine reserves.

    Science.gov (United States)

    McCook, Laurence J; Ayling, Tony; Cappo, Mike; Choat, J Howard; Evans, Richard D; De Freitas, Debora M; Heupel, Michelle; Hughes, Terry P; Jones, Geoffrey P; Mapstone, Bruce; Marsh, Helene; Mills, Morena; Molloy, Fergus J; Pitcher, C Roland; Pressey, Robert L; Russ, Garry R; Sutton, Stephen; Sweatman, Hugh; Tobin, Renae; Wachenfeld, David R; Williamson, David H

    2010-10-26

    The Great Barrier Reef (GBR) provides a globally significant demonstration of the effectiveness of large-scale networks of marine reserves in contributing to integrated, adaptive management. Comprehensive review of available evidence shows major, rapid benefits of no-take areas for targeted fish and sharks, in both reef and nonreef habitats, with potential benefits for fisheries as well as biodiversity conservation. Large, mobile species like sharks benefit less than smaller, site-attached fish. Critically, reserves also appear to benefit overall ecosystem health and resilience: outbreaks of coral-eating, crown-of-thorns starfish appear less frequent on no-take reefs, which consequently have higher abundance of coral, the very foundation of reef ecosystems. Effective marine reserves require regular review of compliance: fish abundances in no-entry zones suggest that even no-take zones may be significantly depleted due to poaching. Spatial analyses comparing zoning with seabed biodiversity or dugong distributions illustrate significant benefits from application of best-practice conservation principles in data-poor situations. Increases in the marine reserve network in 2004 affected fishers, but preliminary economic analysis suggests considerable net benefits, in terms of protecting environmental and tourism values. Relative to the revenue generated by reef tourism, current expenditure on protection is minor. Recent implementation of an Outlook Report provides regular, formal review of environmental condition and management and links to policy responses, key aspects of adaptive management. Given the major threat posed by climate change, the expanded network of marine reserves provides a critical and cost-effective contribution to enhancing the resilience of the Great Barrier Reef.

  4. 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.

  5. 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.

  6. A designer bleomycin with significantly improved DNA cleavage activity.

    Science.gov (United States)

    Huang, Sheng-Xiong; Feng, Zhiyang; Wang, Liyan; Galm, Ute; Wendt-Pienkowski, Evelyn; Yang, Dong; Tao, Meifeng; Coughlin, Jane M; Duan, Yanwen; Shen, Ben

    2012-08-15

    The bleomycins (BLMs) are used clinically in combination with a number of other agents for the treatment of several types of tumors, and the BLM, etoposide, and cisplatin treatment regimen cures 90-95% of metastatic testicular cancer patients. BLM-induced pneumonitis is the most feared, dose-limiting side effect of BLM in chemotherapy, which can progress into lung fibrosis and affect up to 46% of the total patient population. There have been continued efforts to develop new BLM analogues in the search for anticancer drugs with better clinical efficacy and lower lung toxicity. We have previously cloned and characterized the biosynthetic gene clusters for BLMs from Streptomyces verticillus ATCC15003, tallysomycins from Streptoalloteichus hindustanus E465-94 ATCC31158, and zorbamycin (ZBM) from Streptomyces flavoviridis SB9001. Comparative analysis of the three biosynthetic machineries provided the molecular basis for the formulation of hypotheses to engineer novel analogues. We now report engineered production of three new analogues, 6'-hydroxy-ZBM, BLM Z, and 6'-deoxy-BLM Z and the evaluation of their DNA cleavage activities as a measurement for their potential anticancer activity. Our findings unveiled: (i) the disaccharide moiety plays an important role in the DNA cleavage activity of BLMs and ZBMs, (ii) the ZBM disaccharide significantly enhances the potency of BLM, and (iii) 6'-deoxy-BLM Z represents the most potent BLM analogue known to date. The fact that 6'-deoxy-BLM Z can be produced in reasonable quantities by microbial fermentation should greatly facilitate follow-up mechanistic and preclinical studies to potentially advance this analogue into a clinical drug.

  7. Prognotic significance of pretreatment proliferative activity in adult acute leukemia.

    Science.gov (United States)

    Hart, J S; George, S L; Frei, E; Bodey, G P; Nickerson, R C; Freireich, E J

    1977-04-01

    A statistical analysis of the prognostic significance of eight pretreatment variables was undertaken for 71 previously untreated adult patients with acute leukemia seen at M.D. Anderson Hospital over a 5 1/2-year period. None of the patients had received any prior therapy. Nearly all of the patients (68 of the 71) were treated with 4- or 5-day courses of arabinosyl-cytosine alone or in combination with cyclophosphamide, vincristine (oncovin) and prednisone (COAP). The pretreatment variables studied were age at diagnosis, the percent labeling index of the bone marrow leukemic cells, diagnosis, the highest temperature prior to start of treatment, the marrow clot section cellularity and smear differential percent of blasts, percent absolute marrow leukemic cell infiltrate and absolute number of blasts X 10(3)/mm3 in the peripheral blood. Fifty-one patients had acute myeloblastic leukemia (AML) and 20 patients had acute lymphoblastic leukemia (ALL). Using a statistical regression model approach, the only variables found to be of significant prognostic importance with respect to the probability of complete remission for AML patients were the pretreatment percent labeling index, the age of the patient and the highest temperature prior to start of treatment. Unlike AML, the initial percent labeling index did not appear to be of prognostic significance for ALL patients. AML patients with high labeling indices (larger than or equal to 9%) and young patients in general (especially those less than 40 years old) had the best remission rates. With respect to the length of complete remission and survival for all patients, the only important variables were the pretreatment percent labeling index and the age of the patient, respectively. Once in complete remission, an initially high labeling index was an unfavorable sign with respect to length of remission, regardless of the patient's diagnosis. The results of this study are supportive of studies in experimental systems

  8. 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.

  9. 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.

  10. Orienting response elicitation by personally significant information under subliminal stimulus presentation: demonstration using the concealed information test.

    Science.gov (United States)

    Maoz, Keren; Breska, Assaf; Ben-Shakhar, Gershon

    2012-12-01

    Considerable evidence suggests that subliminal information can trigger cognitive and neural processes. Here, we examined whether elicitation of orienting response by personally significant (PS) verbal information requires conscious awareness of the input. Subjects were exposed to the Concealed Information Test (CIT), in which autonomic responses for autobiographical items are typically larger than for control items. These items were presented subliminally using two different masking protocols: single or multiple presentation of the masked item. An objective test was used to verify unawareness to the stimuli. As predicted, PS items elicited significantly stronger skin conductance responses than the control items in both exposure conditions. The results extend previous findings showing that autonomic responses can be elicited following subliminal exposure to aversive information, and also may have implications on the applied usage of the CIT.

  11. A clip-based protocol for breast boost radiotherapy provides clear target visualisation and demonstrates significant volume reduction over time

    Energy Technology Data Exchange (ETDEWEB)

    Lewis, Lorraine [Department of Radiation Oncology, Northern Sydney Cancer Centre, Royal North Shore Hospital, Sydney, New South Wales (Australia); Cox, Jennifer [Department of Radiation Oncology, Northern Sydney Cancer Centre, Royal North Shore Hospital, Sydney, New South Wales (Australia); Faculty of Health Sciences, University of Sydney, Sydney, New South Wales (Australia); Morgia, Marita [Department of Radiation Oncology, Northern Sydney Cancer Centre, Royal North Shore Hospital, Sydney, New South Wales (Australia); Atyeo, John [Faculty of Health Sciences, University of Sydney, Sydney, New South Wales (Australia); Lamoury, Gillian [Department of Radiation Oncology, Northern Sydney Cancer Centre, Royal North Shore Hospital, Sydney, New South Wales (Australia)

    2015-09-15

    The clinical target volume (CTV) for early stage breast cancer is difficult to clearly identify on planning computed tomography (CT) scans. Surgical clips inserted around the tumour bed should help to identify the CTV, particularly if the seroma has been reabsorbed, and enable tracking of CTV changes over time. A surgical clip-based CTV delineation protocol was introduced. CTV visibility and its post-operative shrinkage pattern were assessed. The subjects were 27 early stage breast cancer patients receiving post-operative radiotherapy alone and 15 receiving post-operative chemotherapy followed by radiotherapy. The radiotherapy alone (RT/alone) group received a CT scan at median 25 days post-operatively (CT1rt) and another at 40 Gy, median 68 days (CT2rt). The chemotherapy/RT group (chemo/RT) received a CT scan at median 18 days post-operatively (CT1ch), a planning CT scan at median 126 days (CT2ch), and another at 40 Gy (CT3ch). There was no significant difference (P = 0.08) between the initial mean CTV for each cohort. The RT/alone cohort showed significant CTV volume reduction of 38.4% (P = 0.01) at 40 Gy. The Chemo/RT cohort had significantly reduced volumes between CT1ch: median 54 cm{sup 3} (4–118) and CT2ch: median 16 cm{sup 3}, (2–99), (P = 0.01), but no significant volume reduction thereafter. Surgical clips enable localisation of the post-surgical seroma for radiotherapy targeting. Most seroma shrinkage occurs early, enabling CT treatment planning to take place at 7 weeks, which is within the 9 weeks recommended to limit disease recurrence.

  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. ANTICOMPLEMENTARY ACTIVITY IN HUMAN SERUM OF LUNG CANCER PATIENTS AND ITS POSSIBLE CLINICAL SIGNIFICANCE

    Institute of Scientific and Technical Information of China (English)

    Liu Huirong; Liang Feng; Zhang Weifang; Zheng Zhenqun

    1998-01-01

    Objective: To identify whether the level of anticomplementary activity in serum is different between lung cancer patients and normal subjects. Method: With a sensitive immune haemolytic assay, the anticomplementary activity in the sera of 50 normal subjects and 61lung cancer patients were demonstrated. Results: It was found that all samples contained complement-inhibition activity, although some were of low degree. Increased anticomplementary activity was found to be associated significantly with lung cancer. With the progression of cancer the anticomplementary activity in sera increased in different lung cancer patients. Conclusion: Such a higher anticomplementary activity in sera of lung cancer patients might be one of the immunosuppressive contents induced by the tumor cells.

  14. Finding Significant Correlates of Conscious Activity in Rhythmic EEG

    Directory of Open Access Journals (Sweden)

    Piotr J. Durka

    2005-11-01

    Full Text Available One of the important issues in designing an EEG-based brain-computer interface is an exact delineation of the rhythms, related to the intended or performed action. Traditionally, related bands were found by trial and error procedures seeking maximum reactivity. Even then, large values of ERD/ERS did not imply the statistical significance of the results. This paper presents complete methodology, allowing for a high-resolution presentation of the whole time-frequency picture of event-related changes in the energy density of signals, revealing the microstructure of rhythms, and determination of the time-frequency regions of energy changes, which are related to the intentions in a statistically significant way.

  15. Significance of magnetic resonance imaging for early rheumatoid arthritis activity

    Directory of Open Access Journals (Sweden)

    E Y Pogozeva

    2009-01-01

    Full Text Available Objective. To assess possibility of magnetic resonance image (MRI application for rheu- matoid arthritis (RA activity and severity assessment.Material and methods. 100 pts with RA who fulfilled the 1987 ACR criteria with disease duration less than 12 months were included. Standard clinical examination with evaluation of tender and swollen joint counts, acute phase markers, hand and foot X-ray and hand MRI with 0,2 T Artoscan apparatus (ESAOTE Biomedica, Italy were performed.Results. MRI showed hand joint synovitis in 94,5%, erosions – in 67,3% of cases. X-ray examination revealed erosions in only 20,8% of pts. Localization of erosions revealed by X-ray and MRI coincided in 36,4% of cases and in 61,8% of pts erosions were detected only by MRI. MRI confirmed clinical conclusion about presence or absence of metacarpophalangeal and wrist joint synovitis in 64,5% and 74,5% of cases respectively. In8,2% and 21,8% MRI revealed signs of synovitis in clinically intact joints. MRI synovitis score correlated with clinical and laboratory measures of disease activity – DAS 28 (r=0,37, p=0,001, CRP(r=0,30, p=0,001, ESR (r=0,42, p=0,001, HAQ (r=0,24, p=0,001. Weak correlation was revealed between ESR and presence of erosions (r=0,29, CRP, ESR and MRI signs of bone marrow edema (r=0,27, p=0,005 and r=0,29, p=0,002 respectively. Relationship between laboratory and clinical features was weaker and referred only to CRP level and swollen joint count (p=0,05.Conclusion. MRI signs may be used as additional and independent measures of inflammatory activity (particularly synovitis score and severity of RA

  16. Mode of action and functional significance of 7alpha-hydroxypregnenolone stimulating locomotor activity

    Directory of Open Access Journals (Sweden)

    Shogo eHaraguchi

    2011-08-01

    Full Text Available Previous studies over the past two decades have demonstrated that the brain and other nervous systems possess key steroidogenic enzymes and produces pregnenolone and other various neurosteroids in vertebrates in general. Recently, 7alpha-hydroxypregnenolone, a novel bioactive neurosteroid, was identified in the brain of newts and quail. Importantly, this novel neurosteroid is produced from pregnenolone through the enzymatic activity of cytochrome P4507alpha and acts on brain tissue as a neuronal modulator to stimulate locomotor activity in these vertebrates. Subsequently, the mode of action of 7alpha-hydroxypregnenolone was demonstrated. 7alpha-Hydroxypregnenolone stimulates locomotor activity through activation of the dopaminergic system. To understand the functional significance of 7alpha-hydroxypregnenolone in the regulation of locomotor activity, diurnal and seasonal changes in 7alpha-hydroxypregnenolone synthesis were further characterized. Melatonin derived from the pineal gland and eyes regulates 7alpha-hydroxypregnenolone synthesis in the brain, thus inducing diurnal locomotor changes. Prolactin, an adenohypophyseal hormone, regulates 7alpha-hydroxypregnenolone synthesis in the brain, and also induces seasonal locomotor changes. In addition, 7alpha-hydroxypregnenolone mediates corticosterone action to modulate locomotor activity under stress. This review summarizes the current knowledge regarding the mode of action and functional significance of 7alpha-hydroxypregnenolone, a newly identified bioactive neurosteroid stimulating locomotor activity.

  17. Significance of High-frequency Electrical Brain Activity.

    Science.gov (United States)

    Kobayashi, Katsuhiro; Akiyama, Tomoyuki; Agari, Takashi; Sasaki, Tatsuya; Shibata, Takashi; Hanaoka, Yoshiyuki; Akiyama, Mari; Endoh, Fumika; Oka, Makio; Date, Isao

    2017-06-01

     Electroencephalogram (EEG) data include broadband electrical brain activity ranging from infra-slow bands (frequency bands (e.g., the approx. 10 Hz alpha rhythm) to high-frequency bands of up to 500 Hz. High-frequency oscillations (HFOs) including ripple and fast ripple oscillations (80-200 Hz and>200 / 250 Hz, respectively) are particularly of note due to their very close relationship to epileptogenicity, with the possibility that they could function as a surrogate biomarker of epileptogenicity. In contrast, physiological high-frequency activity plays an important role in higher brain functions, and the differentiation between pathological / epileptic and physiological HFOs is a critical issue, especially in epilepsy surgery. HFOs were initially recorded with intracranial electrodes in patients with intractable epilepsy as part of a long-term invasive seizure monitoring study. However, fast oscillations (FOs) in the ripple and gamma bands (40-80 Hz) are now noninvasively detected by scalp EEG and magnetoencephalography, and thus the scope of studies on HFOs /FOs is rapidly expanding.

  18. 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.

  19. Recent earthquake activity in Trichonis region and its tectonic significance

    Directory of Open Access Journals (Sweden)

    N. DELIBASIS

    1977-06-01

    Full Text Available SUMMARY. - The aftershock activity associated with the central Greece
    (Trichonis Lake earthquake of |une-Dec. 1975, has been studied, with emphasis
    on the time and magnitude distribution. It has been found that the value of b,
    in Gutenberg - R i c h t e r ' s relationship was near the same for the primary as
    well as the secondary or second order aftershocks of the sequences, but depends
    upon the focal depth.
    A correlation between the calculated focal mechanisms and the associated
    stress components to the distribution pattern of meizoseismic effects as well
    as to the geological structure of the seismic region was found.
    The seismic region lies at the top of an anticline which was found moving
    downwards, apparently due to compressional stresses.
    Within the series of three earthquakes the progress of the destruction of
    the buildings was observed and reported. The interest is concentrated to modern
    buildings out of reinforced concrete and infill brick walls. The relatively unexpected
    rather bad performance of the later case of buildings was compared to that
    of the traditional small houses out of brick or stone masonry, the behaviour of
    which may be considered as better from what it was expected.

  20. Using animal models to determine the significance of complement activation in Alzheimer's disease

    Directory of Open Access Journals (Sweden)

    Loeffler David A

    2004-10-01

    Full Text Available Abstract Complement inflammation is a major inflammatory mechanism whose function is to promote the removal of microorganisms and the processing of immune complexes. Numerous studies have provided evidence for an increase in this process in areas of pathology in the Alzheimer's disease (AD brain. Because complement activation proteins have been demonstrated in vitro to exert both neuroprotective and neurotoxic effects, the significance of this process in the development and progression of AD is unclear. Studies in animal models of AD, in which brain complement activation can be experimentally altered, should be of value for clarifying this issue. However, surprisingly little is known about complement activation in the transgenic animal models that are popular for studying this disorder. An optimal animal model for studying the significance of complement activation on Alzheimer's – related neuropathology should have complete complement activation associated with senile plaques, neurofibrillary tangles (if present, and dystrophic neurites. Other desirable features include both classical and alternative pathway activation, increased neuronal synthesis of native complement proteins, and evidence for an increase in complement activation prior to the development of extensive pathology. In order to determine the suitability of different animal models for studying the role of complement activation in AD, the extent of complement activation and its association with neuropathology in these models must be understood.

  1. 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.

  2. 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.

  3. 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

  4. 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…

  5. 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 (...

  6. 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.

  7. 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.

  8. 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...

  9. 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…

  10. 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…

  11. Antisecretory and antimotility activity of Aconitum heterophyllum and its significance in treatment of diarrhea

    Directory of Open Access Journals (Sweden)

    Satyendra K Prasad

    2014-01-01

    Full Text Available Aim: The roots of the plant Aconitum heterophyllum (EAH are traditionally used for curing hysteria, throat infection, dyspepsia, abdominal pain, diabetes, and diarrhea. Therefore, the present study was undertaken to determine the mechanism involved in the anti-diarrheal activity of roots of A. heterophyllum. Materials and Methods: Ant-diarrheal activity of ethanol extract at 50, 100, and 200 mg/kg p.o. was evaluated using fecal excretion and castor oil-induced diarrhea models, while optimized dose, that is, 100 mg/kg p.o. was further subjected to small intestinal transit, intestinal fluids accumulation, PGE 2 -induced enteropooling and gastric emptying test. To elucidate the probable mechanism, various biochemical parameters and Na + , K + concentration in intestinal fluids were also determined. Further, antibacterial activity of extract along with its standardization using aconitine as a marker with the help of HPLC was carried out. Results: The results depicted a significant (P < 0.05 reduction in normal fecal output at 100 and 200 mg/kg p.o. of extract after 5 th and 7 th h of treatment. Castor oil-induced diarrhea model demonstrated a ceiling effect at 100 mg/kg p.o. with a protection of 60.185% from diarrhea. EAH at 100 mg/kg p.o. also showed significant activity in small intestinal transit, fluid accumulation, and PGE 2 -induced enteropooling models, which also restored the altered biochemical parameters and prevented Na + and K + loss. The extract with 0.0833% w/w of aconitine depicted a potential antibacterial activity of extract against microbes implicated in diarrhea. Conclusion: The study concluded antisecretory and antimotility effect of A. heterophyllum, which mediates through nitric oxide path way.

  12. 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.

  13. 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...

  14. 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.

  15. 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.

  16. Statistics Related Self-Efficacy A Confirmatory Factor Analysis Demonstrating a Significant Link to Prior Mathematics Experiences for Graduate Level Students

    Directory of Open Access Journals (Sweden)

    Karen Larwin

    2014-02-01

    Full Text Available The present study examined students' statistics-related self-efficacy, as measured with the current statistics self-efficacy (CSSE inventory developed by Finney and Schraw (2003. Structural equation modeling was used to check the confirmatory factor analysis of the one-dimensional factor of CSSE. Once confirmed, this factor was used to test whether a significant link to prior mathematics experiences exists. Additionally a new post-structural equation modeling (SEM application was employed to compute error-free latent variable score for CSSE in an effort to examine the ancillary effects of gender, age, ethnicity, department, degree level, hours completed, expected course grade, number of college-level math classes, current GPA on students' CSSE scores. Results support the one-dimensional construct and as expected, the model demonstrated a significant link between CSSE scores and prior mathematics experiences to CSSE. Additionally the students' department, expected grade, and number of prior math classes were found to have a significant effect on student's CSSE scores.

  17. 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

  18. 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.

  19. 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.

  20. 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.

  1. Risperidone significantly inhibits interferon-gamma-induced microglial activation in vitro.

    Science.gov (United States)

    Kato, Takahiro; Monji, Akira; Hashioka, Sadayuki; Kanba, Shigenobu

    2007-05-01

    Microglia has recently been regarded to be a mediator of neuroinflammation via the release of proinflammatory cytokines, nitric oxide (NO) and reactive oxygen species (ROS) in the central nervous system (CNS). Microglia has thus been reported to play an important role in the pathology of neurodegenerative disease, such as Alzheimer's disease (AD) and Parkinson's disease (PD). The pathological mechanisms of schizophrenia remain unclear while some recent neuroimaging studies suggest even schizophrenia may be a kind of neurodegenerative disease. Risperidone has been reported to decrease the reduction of MRI volume during the clinical course of schizophrenia. Many recent studies have demonstrated that immunological mechanisms via such as interferon (IFN)-gamma and cytokines might be relevant to the pathophysiology of schizophrenia. In the present study, we thus investigated the effects of risperidone on the generation of nitric oxide, inducible NO synthase (iNOS) expression and inflammatory cytokines: interleukin (IL)-1beta, IL-6 and tumor necrosis factor (TNF)-alpha by IFN-gamma-activated microglia by using Griess assay, Western blotting and ELISA, respectively. In comparison with haloperidol, risperidone significantly inhibited the production of NO and proinflammatory cytokines by activated microglia. The iNOS levels of risperidone-treated cells were much lower than those of the haloperidol-treated cells. Antipsychotics, especially risperidone may have an anti-inflammatory effect via the inhibition of microglial activation, which is not only directly toxic to neurons but also has an inhibitory effect on neurogenesis and oligodendrogenesis, both of which have been reported to play a crucial role in the pathology of schizophrenia.

  2. 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

  3. 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.

  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. 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

  6. 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.

  7. Vascular dysfunction by myofibroblast activation in patients with idiopathic pulmonary fibrosis and prognostic significance

    Directory of Open Access Journals (Sweden)

    E.R. Parra

    2012-07-01

    Full Text Available In this study, we demonstrated the importance of telomerase protein expression and determined the relationships among telomerase, endothelin-1 (ET-1 and myofibroblasts during early and late remodeling of parenchymal and vascular areas in usual interstitial pneumonia (UIP using 27 surgical lung biopsies from patients with idiopathic pulmonary fibrosis (IPF. Telomerase+, myofibroblasts α-SMA+, smooth muscle cells caldesmon+, endothelium ET-1+ cellularity, and fibrosis severity were evaluated in 30 fields covering normal lung parenchyma, minimal fibrosis (fibroblastic foci, severe (mural fibrosis, and vascular areas of UIP by the point-counting technique and a semiquantitative score. The impact of these markers was determined in pulmonary functional tests and follow-up until death from IPF. Telomerase and ET-1 expression was significantly increased in normal and vascular areas compared to areas of fibroblast foci. Telomerase and ET-1 expression was inversely correlated with minimal fibrosis in areas of fibroblast foci and directly associated with severe fibrosis in vascular areas. Telomerase activity in minimal fibrosis areas was directly associated with diffusing capacity of the lung for oxygen/alveolar volume and ET-1 expression and indirectly associated with diffusing capacity of the lungs for carbon monoxide and severe fibrosis in vascular areas. Cox proportional hazards regression revealed a low risk of death for females with minimal fibrosis displaying high telomerase and ET-1 expression in normal areas. Vascular dysfunction by telomerase/ET-1 expression was found earlier than vascular remodeling by myofibroblast activation in UIP with impact on IPF evolution, suggesting that strategies aimed at preventing the effect of these mediators may have a greater impact on patient outcome.

  8. 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.

  9. 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.

  10. 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.

  11. 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.

  12. Teaching physical activities to students with significant disabilities using video modeling.

    Science.gov (United States)

    Cannella-Malone, Helen I; Mizrachi, Sharona V; Sabielny, Linsey M; Jimenez, Eliseo D

    2013-06-01

    The objective of this study was to examine the effectiveness of video modeling on teaching physical activities to three adolescents with significant disabilities. The study implemented a multiple baseline across six physical activities (three per student): jumping rope, scooter board with cones, ladder drill (i.e., feet going in and out), ladder design (i.e., multiple steps), shuttle run, and disc ride. Additional prompt procedures (i.e., verbal, gestural, visual cues, and modeling) were implemented within the study. After the students mastered the physical activities, we tested to see if they would link the skills together (i.e., complete an obstacle course). All three students made progress learning the physical activities, but only one learned them with video modeling alone (i.e., without error correction). Video modeling can be an effective tool for teaching students with significant disabilities various physical activities, though additional prompting procedures may be needed.

  13. Future role and significance of space activities in reflection of global social, technological and economic trends

    Science.gov (United States)

    Diekmann, Andreas; Richarz, Hans.-Peter

    The paper describes the interrelation of space activities and global socio-economic trends like "globalisation of markets" and "renaissance of fine arts". The interrelation reveals the economic strategic, technological and scientific dimension of space activities and their benefits to mankind. Then, the significance and perspectives of space activities in these dimensions are examined in more detail. The paper calls (1) for a more visible initiative to employ space activities to tackle urgent questions of global change and development, and (2) for a stronger impetus to secure European economic position in space sector as a key industry of the 21st century.

  14. 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

  15. 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.

  16. 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.

  17. 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.

  18. 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.

  19. 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.

  20. Exo-inulinase of Aspergillus niger N402 : A hydrolytic enzyme with significant transfructosylating activity

    NARCIS (Netherlands)

    Goosen, C.; Van der Maarel, M. J. E. C.; Dijkhuizen, L.

    2008-01-01

    The purified exo-inulinase enzyme of Aspergillus niger N402 (AngInuE; heterologously expressed in Escherichia coli) displayed a sucrose:inulin (S/I) hydrolysis ratio of 2.3, characteristic for a typical exo-inulinase. The enzyme also had significant transfructosylating activity with increasing

  1. Risk Factors for Clinically Significant Intimate Partner Violence among Active-Duty Members

    Science.gov (United States)

    Smith Slep, Amy M.; Foran, Heather M.; Heyman, Richard E.; Snarr, Jeffery D.

    2011-01-01

    Hypothesized risk factors for men's and women's clinically significant intimate partner violence (CS-IPV) from four ecological levels (i.e., individual, family, workplace, community) were tested in a representative sample of active-duty U.S. Air Force members (N = 42,744). When considered together, we expected only individual and family factors to…

  2. Exo-inulinase of Aspergillus niger N402: A hydrolytic enzyme with significant transfructosylating activity

    NARCIS (Netherlands)

    Goosen, C.; Maarel, M.J. E.C. van der; Dijkhuizen, L.

    2008-01-01

    The purified exo-inulinase enzyme of Aspergillus niger N402 (AngInuE; heterologously expressed in Escherichia coli) displayed a sucrose:inulin (S/I) hydrolysis ratio of 2.3, characteristic for a typical exo-inulinase. The enzyme also had significant transfructosylating activity with increasing

  3. The statistical significance of the N-S asymmetry of solar activity revisited

    CERN Document Server

    Carbonell, M; Oliver, R; Ballester, J L

    2007-01-01

    The main aim of this study is to point out the difficulties found when trying to assess the statistical significance of the North-South asymmetry (hereafter SSNSA) of the most usually considered time series of solar activity. First of all, we distinguish between solar activity time series composed by integer or non-integer and dimensionless data, or composed by non-integer and dimensional data. For each of these cases, we discuss the most suitable statistical tests which can be applied and highlight the difficulties to obtain valid information about the statistical significance of solar activity time series. Our results suggest that, apart from the need to apply the suitable statistical tests, other effects such as the data binning, the considered units and the need, in some tests, to consider groups of data, affect substantially the determination of the statistical significance of the asymmetry. Our main conclusion is that the assessment of the statistical significance of the N-S asymmetry of solar activity ...

  4. Exo-inulinase of Aspergillus niger N402: A hydrolytic enzyme with significant transfructosylating activity

    NARCIS (Netherlands)

    Goosen, C.; Maarel, M.J. E.C. van der; Dijkhuizen, L.

    2008-01-01

    The purified exo-inulinase enzyme of Aspergillus niger N402 (AngInuE; heterologously expressed in Escherichia coli) displayed a sucrose:inulin (S/I) hydrolysis ratio of 2.3, characteristic for a typical exo-inulinase. The enzyme also had significant transfructosylating activity with increasing sucro

  5. 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.

  6. 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.

  7. 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.

  8. Are secular correlations between sunspots, geomagnetic activity, and global temperature significant?

    Science.gov (United States)

    Love, J.J.; Mursula, K.; Tsai, V.C.; Perkins, D.M.

    2011-01-01

    Recent studies have led to speculation that solar-terrestrial interaction, measured by sunspot number and geomagnetic activity, has played an important role in global temperature change over the past century or so. We treat this possibility as an hypothesis for testing. We examine the statistical significance of cross-correlations between sunspot number, geomagnetic activity, and global surface temperature for the years 1868-2008, solar cycles 11-23. The data contain substantial autocorrelation and nonstationarity, properties that are incompatible with standard measures of cross-correlational significance, but which can be largely removed by averaging over solar cycles and first-difference detrending. Treated data show an expected statistically- significant correlation between sunspot number and geomagnetic activity, Pearson p correlations between global temperature and sunspot number (geomagnetic activity) are not significant, p = 0.9954, (p = 0.8171). In other words, straightforward analysis does not support widely-cited suggestions that these data record a prominent role for solar-terrestrial interaction in global climate change. With respect to the sunspot-number, geomagnetic-activity, and global-temperature data, three alternative hypotheses remain difficult to reject: (1) the role of solar-terrestrial interaction in recent climate change is contained wholly in long-term trends and not in any shorter-term secular variation, or, (2) an anthropogenic signal is hiding correlation between solar-terrestrial variables and global temperature, or, (3) the null hypothesis, recent climate change has not been influenced by solar-terrestrial interaction. ?? 2011 by the American Geophysical Union.

  9. Pinelliae Rhizoma, a Toxic Chinese Herb, Can Significantly Inhibit CYP3A Activity in Rats

    Directory of Open Access Journals (Sweden)

    Jinjun Wu

    2015-01-01

    Full Text Available Raw Pinelliae Rhizoma (RPR is a representative toxic herb that is widely used for eliminating phlegm or treating cough and vomiting. Given its irritant toxicity, its processed products, including Pinelliae Rhizoma Praeparatum (PRP and Pinelliae Rhizoma Praeparatum cum Zingibere et Alumine (PRPZA, are more commonly applied and administered concomitantly with other chemical drugs, such as cough medications. This study aimed to investigate the effects of RPR, PRP, and PRPZA on CYP3A activity. Testosterone (Tes and buspirone (BP were used as specific probe substrates ex vivo and in vivo, respectively. CYP3A activity was determined by the metabolite formation ratios from the substrates. Ex vivo results show that the metabolite formation ratios from Tes significantly decreased, indicating that RPR, PRP, and PRPZA could inhibit CYP3A activity in rats. CYP3A protein and mRNA levels were determined to explore the underlying mechanism. These levels showed marked and consistent down-regulation with CYP3A activity. A significant decrease in metabolite formation ratios from BP was also found in PRPZA group in vivo, implying that PRPZA could inhibit CYP3A activity. Conclusively, co-administration of PR with other CYP3A-metabolizing drugs may cause drug–drug interactions. Clinical use of PR-related formulae should be monitored carefully to avoid adverse interactions.

  10. HIV-1 structural proteins serve as PAMPs for TLR2 heterodimers significantly increasing infection and innate immune activation

    Directory of Open Access Journals (Sweden)

    Kenneth Lee Rosenthal

    2015-08-01

    Full Text Available Immune activation is critical to HIV infection and pathogenesis; however, our understanding of HIV innate immune activation remains incomplete. Recently we demonstrated that soluble TLR2 (sTLR2 physically inhibited HIV-induced, NFκB activation and inflammation, as well as HIV-1 infection. In light of these findings, we hypothesized that HIV-1 structural proteins may serve as pathogen-associated molecular patterns (PAMPs for cellular TLR2 heterodimers. These studies made use of primary human T cells and TZMbl cells stably transformed to express TLR2 (TZMbl-2. Our results demonstrated that cells expressing TLR2 showed significantly increased proviral DNA compared to cells lacking TLR2, and mechanistically this may be due to a TLR2-mediated increased CCR5 expression. Importantly, we show that HIV-1 structural proteins, p17, p24, and gp41 act as viral PAMPs signalling through TLR2 and its heterodimers leading to significantly increased immune activation via the NFκB signaling pathway. Using co-immunoprecipitation and a dot blot method, we demonstrated direct protein interactions between these viral PAMPs and TLR2, while only p17 and gp41 bound to TLR1. Specifically, TLR2/1 heterodimer recognized p17 and gp41, while p24 lead to immune activation through TLR2/6. These results were confirmed using TLR2/1 siRNA knock down assays which ablated p17 and gp41-induced cellular activation and through studies of HEK293 cells expressing selected TLRs. Interestingly, our results show in the absence of TLR6, p24 bound to TLR2 and blocked p17 and gp41-induced activation, thus providing a novel mechanism by which HIV-1 can manipulate innate sensing. Taken together, our results identified, for the first time, novel HIV-1 PAMPs that play a role in TLR2-mediated cellular activation and increased proviral DNA. These findings have important implications for our fundamental understanding of HIV-1 immune activation and pathogenesis, as well as HIV-1 vaccine development.

  11. 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.

  12. 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.

  13. Therapeutic significance and pharmacological activities of antidiarrheal medicinal plants mention in Ayurveda: A review.

    Science.gov (United States)

    Mishra, Ashish; Seth, Ankit; Maurya, Santosh Kumar

    2016-01-01

    Diarrhea is a serious problem affecting 3-5 billion people per year around the world, especially children of below 5 years. 70% of the world population uses traditional and indigenous medicine for their primary health care. The facts of these indigenous remedies are passed verbally and sometimes as documents. Since ancient time, Ayurveda is the main system of healing in South East Asian countries. Indian literature from ayurvedic texts and other books claim the potency of several plants in the treatment of diarrhea. As the global prospective of ayurvedic medicine is increasing, interest regarding the scientific basis of their action is parallely increasing. Researchers are doing experiments to establish the relation between the claimed action and observed pharmacological activities. In the present article, an attempt was made to compile the scientific basis of medicinal plants used to cure diarrhea in Ayurveda. Literature was collected via electronic search (PubMed, ScienceDirect, Medline, and Google Scholar) from published articles that reports antidiarrheal activity of plants that were mentioned in Ayurveda classics. A total of 109 plant species belonging to 58 families were reported for their antidiarrheal activity. Several Indian medicinal plants have demonstrated promising antidiarrheal effects, but the studies on the antidiarrheal potentials of these plants are not taken beyond proof of concept stage. It is hoped that the article would stimulate future clinical studies because of the paucity of knowledge in this area.

  14. 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.

  15. Activation of Human Salivary Aldehyde Dehydrogenase by Sulforaphane: Mechanism and Significance

    Science.gov (United States)

    Alam, Md. Fazle; Laskar, Amaj Ahmed; Maryam, Lubna

    2016-01-01

    Cruciferous vegetables contain the bio-active compound sulforaphane (SF) which has been reported to protect individuals against various diseases by a number of mechanisms, including activation of the phase II detoxification enzymes. In this study, we show that the extracts of five cruciferous vegetables that we commonly consume and SF activate human salivary aldehyde dehydrogenase (hsALDH), which is a very important detoxifying enzyme in the mouth. Maximum activation was observed at 1 μg/ml of cabbage extract with 2.6 fold increase in the activity. There was a ~1.9 fold increase in the activity of hsALDH at SF concentration of ≥ 100 nM. The concentration of SF at half the maximum response (EC50 value) was determined to be 52 ± 2 nM. There was an increase in the Vmax and a decrease in the Km of the enzyme in the presence of SF. Hence, SF interacts with the enzyme and increases its affinity for the substrate. UV absorbance, fluorescence and CD studies revealed that SF binds to hsALDH and does not disrupt its native structure. SF binds with the enzyme with a binding constant of 1.23 x 107 M-1. There is one binding site on hsALDH for SF, and the thermodynamic parameters indicate the formation of a spontaneous strong complex between the two. Molecular docking analysis depicted that SF fits into the active site of ALDH3A1, and facilitates the catalytic mechanism of the enzyme. SF being an antioxidant, is very likely to protect the catalytic Cys 243 residue from oxidation, which leads to the increase in the catalytic efficiency and hence the activation of the enzyme. Further, hsALDH which is virtually inactive towards acetaldehyde exhibited significant activity towards it in the presence of SF. It is therefore very likely that consumption of large quantities of cruciferous vegetables or SF supplements, through their activating effect on hsALDH can protect individuals who are alcohol intolerant against acetaldehyde toxicity and also lower the risk of oral cancer

  16. 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.

  17. The temporal structures and functional significance of scale-free brain activity

    Science.gov (United States)

    He, Biyu J.; Zempel, John M.; Snyder, Abraham Z.; Raichle, Marcus E.

    2010-01-01

    SUMMARY Scale-free dynamics, with a power spectrum following P ∝ f-β, are an intrinsic feature of many complex processes in nature. In neural systems, scale-free activity is often neglected in electrophysiological research. Here, we investigate scale-free dynamics in human brain and show that it contains extensive nested frequencies, with the phase of lower frequencies modulating the amplitude of higher frequencies in an upward progression across the frequency spectrum. The functional significance of scale-free brain activity is indicated by task performance modulation and regional variation, with β being larger in default network and visual cortex and smaller in hippocampus and cerebellum. The precise patterns of nested frequencies in the brain differ from other scale-free dynamics in nature, such as earth seismic waves and stock market fluctuations, suggesting system-specific generative mechanisms. Our findings reveal robust temporal structures and behavioral significance of scale-free brain activity and should motivate future study on its physiological mechanisms and cognitive implications. PMID:20471349

  18. 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...

  19. Angiogenic activity in patients with psoriasis is significantly decreased by Goeckerman's therapy

    Energy Technology Data Exchange (ETDEWEB)

    Andrys, C.; Borska, L.; Pohl, D.; Fiala, Z.; Hamakova, K.; Krejsek, J. [Faculty Hospital, Hradec Kralove (Czech Republic). Dept. of Clinical Immunology & Allergy

    2007-03-15

    Goeckerman's therapy (GT) of psoriasis is based on daily application of pharmacy grade coal tar on affected skin with subsequent exposure to UV light. Goeckerman's therapy is still the first line therapy of psoriasis in the Czech Republic because of its low cost and long-term efficacy. Disturbances in angiogenic activity are characteristic for the immunopathogenesis of psoriasis. An abnormal spectrum of cytokines, growth factors and proangiogenic mediators is produced by keratinocytes and inflammatory cells in patients suffering from the disease. The aim of this study was to evaluate the influence of GT of psoriasis on angiogenic activities by comparing serum levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) in 44 patients with psoriasis in peripheral blood samples collected before and after therapy. It was found that the angiogenic potential which is abnormally increased in patients with psoriasis is significantly alleviated by GT.

  20. Activity in ventromedial prefrontal cortex during self-related processing: positive subjective value or personal significance?

    Science.gov (United States)

    Kim, Kyungmi; Johnson, Marcia K

    2015-04-01

    Well-being and subjective experience of a coherent world depend on our sense of 'self' and relations between the self and the environment (e.g. people, objects and ideas). The ventromedial prefrontal cortex (vMPFC) is involved in self-related processing, and disrupted vMPFC activity is associated with disruptions of emotional/social functioning (e.g. depression and autism). Clarifying precise function(s) of vMPFC in self-related processing is an area of active investigation. In this study, we sought to more specifically characterize the function of vMPFC in self-related processing, focusing on two alternative accounts: (i) assignment of positive subjective value to self-related information and (ii) assignment of personal significance to self-related information. During functional magnetic resonance imaging (fMRI), participants imagined owning objects associated with either their perceived ingroup or outgroup. We found that for ingroup-associated objects, vMPFC showed greater activity for objects with increased than decreased post-ownership preference. In contrast, for outgroup-associated objects, vMPFC showed greater activity for objects with decreased than increased post-ownership preference. Our findings support the idea that the function of vMPFC in self-related processing may not be to represent/evaluate the 'positivity' or absolute preference of self-related information but to assign personal significance to it based on its meaning/function for the self. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  1. 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.

  2. 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....

  3. 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.

  4. EXPRESSION AND SIGNIFICANCE OF UROKINASE-TYPE PLASMINOGEN ACTIVATOR IN BREAST CANCER

    Institute of Scientific and Technical Information of China (English)

    XIAO Jiping; ZHANG Guangde; XIA Wenhua; CHENG Deji

    1999-01-01

    Objective: To study the expression and clinical significance of urokinase-type plasminogen activator (uPA) in breast cancer. Methods: Applying streptavidin-biotin complex (SABC) immunohistochemical technique, expression of uPA was studied in 100 patients with primary breast cancer. Results: There were 55 patients with high uPA expression, and 45 with lower expression. There was significant correlation between uPA expression and TNM stage, lymph node status, and the tumor size. Neither age, menopausal status, nor ER status was significantly related with level of uPA expression. The patients with high expression of uPA had significantly shorter disease-free survival (DFS)and overall survival (OS) than did those with low expression of uPA. Univariate analysis showed that uPA as a prognostic factor was of similar magnitude to lymph node status and TNM stage, but stronger than that of ER status and tumor size. UPA was an independent prognostic factor affecting disease-free survival and overall survival. Conclusion: uPA appears to be a strong and independent biologic marker for predicting prognosis of breast cancer.

  5. 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.

  6. What basal ganglia changes underlie the parkinsonian state? The significance of neuronal oscillatory activity

    Science.gov (United States)

    Quiroga-Varela, A.; Walters, J.R.; Brazhnik, E.; Marin, C.; Obeso, J.A.

    2014-01-01

    One well accepted functional feature of the parkinsonian state is the recording of enhanced beta oscillatory activity in the basal ganglia. This has been demonstrated in patients with Parkinson's disease (PD) and in animal models such as the rat with 6-hydroxydopamine (6-OHDA)-induced lesion and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated monkeys, all of which are associated with severe striatal dopamine depletion. Neuronal hyper-synchronization in the beta (or any other) band is not present despite the presence of bradykinetic features in the rat and monkey models, suggesting that increased beta band power may arise when nigro-striatal lesion is advanced and that it is not an essential feature of the early parkinsonian state. Similar observations and conclusions have been previously made for increased neuronal firing rate in the subthalamic and globus pallidus pars interna nuclei. Accordingly, it is suggested that early parkinsonism may be associated with dynamic changes in basal ganglia output activity leading to reduced movement facilitation that may be an earlier feature of the parkinsonian state. PMID:23727447

  7. 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…

  8. 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…

  9. 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...

  10. 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)

  11. 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...

  12. 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

  13. Clinical significance of activity of ALT enzyme in patients with hepatitis C virus

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    AIM: To investigate serum alanine aminotransferase (ALT) levels in relation to the clinical, biochemical,ultrasonographic and histological characteristics of patients with hepatitis C virus.METHODS: Duration of disease, HCV-RNA, liver steatosis, and the hepatitis activity index (HAI) were correlated with serum ALT in 36 patients with HCV. ALT values were also investigated in 16 control subjects without any liver diseases.RESULTS: In bivariate analyses, ALT levels correlated with duration of HCV infection (P< 0.01), HCV-RNA (P<0.05), and the HAI(P<0.01). Among the components of the HAI, ALT concentrations were significantly associated with pedportal bridging/necrosis (P<0.01) and fibrosis (P<0.05). In multivariate analysis, periportal bridging/necrosis (β = 0.508; P < 0.01), duration of HCV infection (β = 0.413; P < 0.01), and HCV-RNA (β= 0.253; P < 0.05)were independently associated with ALT activity. The normal ALT activity for men and women was < 23 IU/L and < 22 IU/L, respectively.CONCLUSION: In patients with HCV, alterations in the liver tissue as reflected by ALT elevation are mainly associated with periportal bridging/necrosis, viral load and duration of disease. A cut-off value < 23 IU/L distinguished with high diagnostic accuracy healthy controls from patients with HCV.

  14. Significant antitumor activity in vivo following treatment with the microtubule agent ENMD-1198.

    Science.gov (United States)

    LaVallee, Theresa M; Burke, Patricia A; Swartz, Glenn M; Hamel, Ernest; Agoston, Gregory E; Shah, Jamshed; Suwandi, Lita; Hanson, Art D; Fogler, William E; Sidor, Carolyn F; Treston, Anthony M

    2008-06-01

    Clinical studies using the microtubule-targeting agent 2-methoxyestradiol (2ME2; Panzem) in cancer patients show that treatment is associated with clinical benefit, including prolonged stable disease, complete and partial responses, and an excellent safety profile. Studies have shown that 2ME2 is metabolized by conjugation at positions 3 and 17 and oxidation at position 17. To define structure-activity relationships for these positions of 2ME2 and to generate metabolically stable analogues with improved anti-tubulin properties, a series of analogues was generated and three lead analogues were selected, ENMD-1198, ENMD-1200, and ENMD-1237. These molecules showed improved metabolic stability with >65% remaining after 2-h incubation with hepatocytes. Pharmacokinetic studies showed that oral administration of the compounds resulted in increased plasma levels compared with 2ME2. All three analogues bind the colchicine binding site of tubulin, induce G(2)-M cell cycle arrest and apoptosis, and reduce hypoxia-inducible factor-1alpha levels. ENMD-1198 and ENMD-1200 showed improved in vitro antiproliferative activities. Significant reductions in tumor volumes compared with vehicle-treated mice were observed in an orthotopic breast carcinoma (MDA-MB-231) xenograft model following daily oral treatment with all compounds (ANOVA, P < 0.05). Significantly improved median survival time was observed with ENMD-1198 and ENMD-1237 (200 mg/kg/d) in a Lewis lung carcinoma metastatic model (P < 0.05). In both tumor models, the high-dose group of ENMD-1198 showed antitumor activity equivalent to that of cyclophosphamide. ENMD-1198 was selected as the lead molecule in this analogue series and is currently in a phase I clinical trial in patients with refractory solid tumors.

  15. 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.

  16. 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.

  17. 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...

  18. 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

  19. A Smartphone Application Significantly Improved Diabetes Self-Care Activities with High User Satisfaction

    Directory of Open Access Journals (Sweden)

    Yu Jin Kim

    2015-06-01

    Full Text Available BackgroundWe developed for the first time a smartphone application designed for diabetes self-management in Korea and registered a patent for the relevant algorithm. We also investigated the user satisfaction with the application and the change in diabetes related self-care activities after using the application.MethodsWe conducted a questionnaire survey on volunteers with diabetes who were using the application. Ninety subjects responded to the questionnaire between June 2012 and March 2013. A modified version of the Summary of Diabetes Self-Care Activities (SDSCA was used in this study.ResultsThe survey results exhibited a mean subject age of 44.0 years old, and males accounted for 78.9% of the subjects. Fifty percent of the subjects had diabetes for less than 3 years. The majority of respondents experienced positive changes in their clinical course after using the application (83.1% and were satisfied with the structure and completeness of the application (86.7%. Additionally, the respondents' answers indicated that the application was easy to use (96.7% and recommendable to others (97.7% and that they would continue using the application to manage their diabetes (96.7%. After using the Diabetes Notepad application, diabetes related self-care activities assessed by SDSCA displayed statistically significant improvements (P<0.05, except for the number of days of drinking.ConclusionThis smartphone-based application can be a useful tool leading to positive changes in diabetes related self-care activities and increase user satisfaction.

  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. 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

  2. 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.

  3. RESEARCH ON CONTROL OF FLYWHEEL SUSPENDED BY ACTIVE MAGNETIC BEARING SYSTEM WITH SIGNIFICANT GYROSCOPIC EFFECTS

    Institute of Scientific and Technical Information of China (English)

    Zhang Kai; Zhao Lei; Zhao Hongbin

    2004-01-01

    Traditional PID controllers are no longer suitable for magnetic-bearing-supported high-speed flywheels with significant gyroscopic effects.Because gyroscopic effects greatly influence the stability of the flywheel rotor,especially at high rotational speeds.Velocity cross feedback and displacement cross feedback are used to overcome harmful effects of nutation and precession modes, and stabilize the rotor at high rotational speeds.Theoretical analysis is given to show their effects.A control platform based on RTLinux and a PC is built to control the active magnetic bearing (AMB) system, and relevant results are reported.Using velocity cross feedback and displacement cross feedback in a closed loop control system, the flywheel successfully runs at over 20 000 r/min.

  4. Medicinal significance, pharmacological activities, and analytical aspects of solasodine: A concise report of current scientific literature

    Directory of Open Access Journals (Sweden)

    Kanika Patel

    2013-01-01

    Full Text Available Alkaloids are well known phytoconstituents for their diverse pharmacological properties. Alkaloids are found in all plant parts like roots, stems, leaves, flowers, fruits and seeds. Solasodine occurs as an aglycone part of glycoalkloids, which is a nitrogen analogue to sapogenins. Solanaceae family comprises of a number of plants with variety of natural products of medicinal significance mainly steroidal lactones, glycosides, alkaloids and flavanoids. It is a steroidal alkaloid based on a C27 cholestane skeleton. Literature survey reveals that solasodine has diuretic, anticancer, antifungal, cardiotonic, antispermatogenetic, antiandrogenic, immunomodulatory, antipyretic and various effects on central nervous system. Isolation and quantitative determination was achieved by several analytical techniques. Present review highlights the pharmacological activity of solasodine, with its analytical and tissue culture techniques, which may be helpful to the researchers to develop new molecules for the treatment of various disorders in the future.

  5. Female recreational athletes demonstrate different knee biomechanics from male counterparts during jumping rope and turning activities.

    Science.gov (United States)

    Tanikawa, Hidenori; Matsumoto, Hideo; Harato, Kengo; Kiriyama, Yoshimori; Suda, Yasunori; Toyama, Yoshiaki; Nagura, Takeo

    2014-01-01

    A variety of athletic exercises are performed in sports training or rehabilitation after knee injuries. However, it remains unclear whether males and females exhibit similar joint loading during the various athletic motions. The purpose of this study was to identify gender differences in knee biomechanics during the athletic motions. Three-dimensional knee kinematics and kinetics were investigated in 20 recreational athletes (10 males and 10 females) while jumping rope, backward running, side running, side-to-side running, side-to-forward running, inside turning, and outside turning. The strengths of the quadriceps and hamstring muscles, the knee joint force, the knee joint angle, and the knee joint moment were compared between males and females using one-tailed t tests. Peak knee anterior force was greater in female recreational athletes than in their male counterparts during jumping rope, side-to-forward running, inside turning, and outside turning. Female subjects displayed greater peak knee abduction angles and greater peak knee flexion moments while jumping rope compared to their male counterparts. There were no significant differences between the sexes in knee kinematics and kinetics in the frontal and transverse planes during running and turning motions. Female recreational athletes exhibited significantly different knee biomechanics compared with male counterparts during jumping rope and turning motions.

  6. Marine organism sulfated polysaccharides exhibiting significant antimalarial activity and inhibition of red blood cell invasion by Plasmodium.

    Science.gov (United States)

    Marques, Joana; Vilanova, Eduardo; Mourão, Paulo A S; Fernàndez-Busquets, Xavier

    2016-04-13

    The antimalarial activity of heparin, against which there are no resistances known, has not been therapeutically exploited due to its potent anticoagulating activity. Here, we have explored the antiplasmodial capacity of heparin-like sulfated polysaccharides from the sea cucumbers Ludwigothurea grisea and Isostichopus badionotus, from the red alga Botryocladia occidentalis, and from the marine sponge Desmapsamma anchorata. In vitro experiments demonstrated for most compounds significant inhibition of Plasmodium falciparum growth at low-anticoagulant concentrations. This activity was found to operate through inhibition of erythrocyte invasion by Plasmodium, likely mediated by a coating of the parasite similar to that observed for heparin. In vivo four-day suppressive tests showed that several of the sulfated polysaccharides improved the survival of Plasmodium yoelii-infected mice. In one animal treated with I. badionotus fucan parasitemia was reduced from 10.4% to undetectable levels, and Western blot analysis revealed the presence of antibodies against P. yoelii antigens in its plasma. The retarded invasion mediated by sulfated polysaccharides, and the ensuing prolonged exposure of Plasmodium to the immune system, can be explored for the design of new therapeutic approaches against malaria where heparin-related polysaccharides of low anticoagulating activity could play a dual role as drugs and as potentiators of immune responses.

  7. Marine organism sulfated polysaccharides exhibiting significant antimalarial activity and inhibition of red blood cell invasion by Plasmodium

    Science.gov (United States)

    Marques, Joana; Vilanova, Eduardo; Mourão, Paulo A. S.; Fernàndez-Busquets, Xavier

    2016-01-01

    The antimalarial activity of heparin, against which there are no resistances known, has not been therapeutically exploited due to its potent anticoagulating activity. Here, we have explored the antiplasmodial capacity of heparin-like sulfated polysaccharides from the sea cucumbers Ludwigothurea grisea and Isostichopus badionotus, from the red alga Botryocladia occidentalis, and from the marine sponge Desmapsamma anchorata. In vitro experiments demonstrated for most compounds significant inhibition of Plasmodium falciparum growth at low-anticoagulant concentrations. This activity was found to operate through inhibition of erythrocyte invasion by Plasmodium, likely mediated by a coating of the parasite similar to that observed for heparin. In vivo four-day suppressive tests showed that several of the sulfated polysaccharides improved the survival of Plasmodium yoelii-infected mice. In one animal treated with I. badionotus fucan parasitemia was reduced from 10.4% to undetectable levels, and Western blot analysis revealed the presence of antibodies against P. yoelii antigens in its plasma. The retarded invasion mediated by sulfated polysaccharides, and the ensuing prolonged exposure of Plasmodium to the immune system, can be explored for the design of new therapeutic approaches against malaria where heparin-related polysaccharides of low anticoagulating activity could play a dual role as drugs and as potentiators of immune responses. PMID:27071342

  8. Mechanisms of transcriptional regulation and prognostic significance of activated leukocyte cell adhesion molecule in cancer

    Directory of Open Access Journals (Sweden)

    Chen Hairu

    2010-10-01

    Full Text Available Abstract Background Activated leukocyte cell adhesion molecule (ALCAM is implicated in the prognosis of multiple cancers with low level expression associated with metastasis and early death in breast cancer. Despite this significance, mechanisms that regulate ALCAM gene expression and ALCAM's role in adhesion of pre-metastatic circulating tumor cells have not been defined. We studied ALCAM expression in 20 tumor cell lines by real-time PCR, western blot and immunochemistry. Epigenetic alterations of the ALCAM promoter were assessed using methylation-specific PCR and bisulfite sequencing. ALCAM's role in adhesion of tumor cells to the vascular wall was studied in isolated perfused lungs. Results A common site for transcription initiation of the ALCAM gene was identified and the ALCAM promoter sequenced. The promoter contains multiple cis-active elements including a functional p65 NF-κB motif, and it harbors an extensive array of CpG residues highly methylated exclusively in ALCAM-negative tumor cells. These CpG residues were modestly demethylated after 5-aza-2-deoxycytidine treatment. Restoration of high-level ALCAM expression using an ALCAM cDNA increased clustering of MDA-MB-435 tumor cells perfused through the pulmonary vasculature of ventilated rat lungs. Anti-ALCAM antibodies reduced the number of intravascular tumor cell clusters. Conclusion Our data suggests that loss of ALCAM expression, due in part to DNA methylation of extensive segments of the promoter, significantly impairs the ability of circulating tumor cells to adhere to each other, and may therefore promote metastasis. These findings offer insight into the mechanisms for down-regulation of ALCAM gene expression in tumor cells, and for the positive prognostic value of high-level ALCAM in breast cancer.

  9. 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.

  10. 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.

  11. Griflola frondosa (GF) produces significant antidepressant effects involving AMPA receptor activation in mice.

    Science.gov (United States)

    Bao, Hongkun; Ran, Pengzhan; Sun, Lijuan; Hu, Weihong; Li, Hongliang; Xiao, Chunjie; Zhu, Keming; Du, Jing

    2017-12-01

    Griflola frondosa (Fr) S.F. Gray (Meripilaceae) (GF) is a medical mushroom, and its regulation of the immune system is of interest for the treatment of mood disorders. α-Amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptors are the central mediator for the treatment of depression. This study examines the antidepressant effects of GF and the role of AMPA in these antidepressant effects. The CD-1 mice were fed with GF- or Pleurotus ostreatus [(Jacq.: Fr) Kumm (Pleurotaceae)] (PO)-containing food for 1 day or 5 days. The antidepressant effects was determined in the tail suspension test (TST), forced swim test (FST), and open field test (OFT). The involvement of AMPA receptors was determined by the application of the AMPA-specific blocker GYKI 52466. Treatments with 20%, 33% or 50% of GF-containing food significantly decreased the immobility time (63.6, 56.9, and 52.0% in TST; and 50.8, 43.2, and 38.2% in FST) after 1 day and (62.3, 51.8, and 52.8% in TST; and 49.5, 45.1, and 40.3% in FST) after 5 days. GF-containing food did not cause hyperactive effects in the OFT. The antidepressant effects of the 33% of GF-containing food (down-to 51.3% in 1-day TST and 46.8% in 5-day FST) were significantly stronger than that of the 33% of PO-containing food (down-to 85.5% in 1-day TST and 82.0% in 5-day FST). AMPA-specific blocker GYKI 52466 was able to block the antidepressant effects of the GF-containing food. GF demonstrated the potential as a safe medical food supplement for the patient with depression.

  12. 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.

  13. Activation of Big Grain1 significantly improves grain size by regulating auxin transport in rice.

    Science.gov (United States)

    Liu, Linchuan; Tong, Hongning; Xiao, Yunhua; Che, Ronghui; Xu, Fan; Hu, Bin; Liang, Chengzhen; Chu, Jinfang; Li, Jiayang; Chu, Chengcai

    2015-09-01

    Grain size is one of the key factors determining grain yield. However, it remains largely unknown how grain size is regulated by developmental signals. Here, we report the identification and characterization of a dominant mutant big grain1 (Bg1-D) that shows an extra-large grain phenotype from our rice T-DNA insertion population. Overexpression of BG1 leads to significantly increased grain size, and the severe lines exhibit obviously perturbed gravitropism. In addition, the mutant has increased sensitivities to both auxin and N-1-naphthylphthalamic acid, an auxin transport inhibitor, whereas knockdown of BG1 results in decreased sensitivities and smaller grains. Moreover, BG1 is specifically induced by auxin treatment, preferentially expresses in the vascular tissue of culms and young panicles, and encodes a novel membrane-localized protein, strongly suggesting its role in regulating auxin transport. Consistent with this finding, the mutant has increased auxin basipetal transport and altered auxin distribution, whereas the knockdown plants have decreased auxin transport. Manipulation of BG1 in both rice and Arabidopsis can enhance plant biomass, seed weight, and yield. Taking these data together, we identify a novel positive regulator of auxin response and transport in a crop plant and demonstrate its role in regulating grain size, thus illuminating a new strategy to improve plant productivity.

  14. 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…

  15. 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…

  16. 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.

  17. 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

  18. 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.

  19. Identification of AKN-032, a novel 2-aminopyrazine tyrosine kinase inhibitor, with significant preclinical activity in acute myeloid leukemia.

    Science.gov (United States)

    Eriksson, Anna; Höglund, Martin; Lindhagen, Elin; Aleskog, Anna; Hassan, Sadia Bashir; Ekholm, Carina; Fhölenhag, Karin; Jensen, Annika Jenmalm; Löthgren, Agneta; Scobie, Martin; Larsson, Rolf; Parrow, Vendela

    2010-11-15

    Aberrant signal transduction by mutant or overexpressed protein kinases has emerged as a promising target for treatment of acute myeloid leukemia (AML). We here present a novel low molecular weight kinase inhibitor, AKN-032, targeting the FMS-like tyrosine kinase 3 (FLT3) and discovered in a new type of screening funnel combining the target therapy approach with sequential cellular screens. AKN-032 was identified among 150 selected hits from three different high throughput kinase screens. Further characterization showed inhibitory activity on FLT3 enzyme with an IC(50) of 70 nM. Western blot analysis revealed reduced autophosphorylation of the FLT3-receptor in AML cell line MV4-11 cells after exposure to AKN-032. Flow cytometry disclosed cytotoxic activity against MV4-11, but not against non-malignant 3T3-L1 fibroblast cells. Using a fluorometric microculture cytotoxicity assay, AKN-032 was tested against 15 cell lines and displayed a potent cytotoxic activity in AML cell lines MV4-11 (IC(50)=0.4 μM) and Kasumi-1 (IC(50)=2.3 μM). AKN-032 was also highly cytotoxic in tumor cells from AML patients in vitro. Furthermore, AKN-032 demonstrated significant antileukemic effect in a relatively resistant in vivo hollow fiber mouse model. No major toxicity was observed in the animals. In conclusion, AKN-032 is a promising new kinase inhibitor with significant in vivo and in vitro activity in AML. Results from the hollow fiber mouse assay suggest a favorable toxicity profile. Future studies will focus on pharmacokinetic properties, toxicity as well as further clarifying the mechanisms of action of AKN-032 in AML.

  20. Clostridium sporogenes delivers interleukin-12 to hypoxic tumours, producing antitumour activity without significant toxicity.

    Science.gov (United States)

    Zhang, Y-L; Lü, R; Chang, Z-S; Zhang, W-Q; Wang, Q-B; Ding, S-Y; Zhao, W

    2014-12-01

    Clostridium sporogenes ATCC 3584 is an obligate anaerobe that has been reported to possess excellent tumour-targeting capacity. Here, we use Cl. sporogenes as a vector to deliver IL-12, a potent antitumour cytokine that bears numerous antitumour properties but that has limited clinical applications due to its strong toxicity when delivered systemically. In this study, Cl. sporogenes was genetically engineered to secrete murine IL-12, and its antitumour efficacy and toxicity were investigated in a murine EMT6 mammary carcinoma model. After intravenous injection, Cl. sporogenes was able to selectively settle and reproduce in the tumours without encroaching on normal tissues, resulting in a clear delay of tumour growth and a 14·3% cure rate. Importantly, the mice showed no obvious toxicity-associated side effects, such as diarrhoea and weight loss, during the treatment process. The significant antitumour efficacy and low toxicity of this treatment may be explained by the selective tumour-targeting properties of Cl. sporogenes and by the sustained release of IL-12 accompanying bacterial proliferation. This moderate local IL-12 concentration would not induce the severe response in the entire body, that is inevitable when IL-12 is administered directly. Interleukin-12 (IL-12) is a potent antitumour cytokine, but it is toxic when administrated systemically. This study demonstrates that murine IL-12 can be systemically delivered to hypoxic sites in solid tumours by Clostridium sporogenes, producing a clear delay in tumour growth and a 14·3% cure rate in a mouse tumour model. Importantly, there is no obvious toxicity associated with IL-12 during the treatment process. This result may be accounted for by the excellent tumour-targeting capacity of Cl. sporogenes, targeting IL-12 directly to the tumour site instead of to the entire body. © 2014 The Society for Applied Microbiology.

  1. Novel pyrazole derivatives as neutral CB₁ antagonists with significant activity towards food intake.

    Science.gov (United States)

    Manca, Ilaria; Mastinu, Andrea; Olimpieri, Francesca; Falzoi, Matteo; Sani, Monica; Ruiu, Stefania; Loriga, Giovanni; Volonterio, Alessandro; Tambaro, Simone; Bottazzi, Mirko Emilio Heiner; Zanda, Matteo; Pinna, Gérard Aimè; Lazzari, Paolo

    2013-04-01

    In spite of rimonabant's withdrawal from the European market due to its adverse effects, interest in the development of drugs based on CB1 antagonists is revamping on the basis of the peculiar properties of this class of compounds. In particular, new strategies have been proposed for the treatment of obesity and/or related risk factors through CB1 antagonists, i.e. by the development of selectively peripherally acting agents or by the identification of neutral CB1 antagonists. New compounds based on the lead CB1 antagonist/inverse agonist rimonabant have been synthesized with focus on obtaining neutral CB1 antagonists. Amongst the new derivatives described in this paper, the mixture of the two enantiomers (±)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-3-(2-cyclohexyl-1-hydroxyethyl)-4-methyl-1H-pyrazole ((±)-5), and compound 5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-3-[(Z)-2-cyclohexyl-1-fluorovinyl]-4-methyl-1H-pyrazole ((Z)-6), showed interesting pharmacological profiles. According to the preliminary pharmacological evaluation, these novel pyrazole derivatives showed in fact both neutral CB1 antagonism behaviour and significant in vivo activity towards food intake.

  2. 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.

  3. Significance of an Active Volcanic Front in the Far Western Aleutian Arc

    Science.gov (United States)

    Yogodzinski, G. M.; Kelemen, P. B.; Hoernle, K.

    2015-12-01

    Discovery of a volcanic front west of Buldir Volcano, the western-most emergent Aleutian volcano, demonstrates that the surface expression of Aleutian volcanism falls below sea level just west of 175.9° E longitude, but is otherwise continuous from mainland Alaska to Kamchatka. The newly discovered sites of western Aleutian seafloor volcanism are the Ingenstrem Depression, a 60 km-long structural depression just west of Buldir, and an unnamed area 300 km further west, referred to as the Western Cones. These locations fall along a volcanic front that stretches from Buldir to Piip Seamount near the Komandorsky Islands. Western Aleutian seafloor volcanic rocks include large quantities of high-silica andesite and dacite, which define a highly calc-alkaline igneous series and carry trace element signatures that are unmistakably subduction-related. This indicates that subducting oceanic lithosphere is present beneath the westernmost Aleutian arc. The rarity of earthquakes below depths of 200 km indicates that the subducting plate is unusually hot. Some seafloor volcanoes are 6-8 km wide at the base, and so are as large as many emergent Aleutian volcanoes. The seafloor volcanoes are submerged in water depths >3000 m because they sit on oceanic lithosphere of the Bering Sea. The volcanic front is thus displaced to the north of the ridge of arc crust that underlies the western Aleutian Islands. This displacement, which developed since approximately 6 Ma when volcanism was last active on the islands, must be a consequence of oblique convergence in a system where the subducting plate and large blocks of arc crust are both moving primarily in an arc-parallel sense. The result is a hot-slab system where low subduction rates probably limit advection of hot mantle to the subarc, and produce a relatively cool and perhaps stagnant mantle wedge. The oceanic setting and highly oblique subduction geometry also severely limit rates of sediment subduction, so the volcanic rocks, which

  4. Reusable sunlight activated photocatalyst Ag{sub 3}PO{sub 4} and its significant antibacterial activity

    Energy Technology Data Exchange (ETDEWEB)

    Thiyagarajan, Shankar; Singh, Sarika; Bahadur, D., E-mail: dhirenb@iitb.ac.in

    2016-04-15

    A simple and surfactant free soft chemical approach is adopted for the successful synthesis of Ag{sub 3}PO{sub 4} nanoparticles (NPs) at room temperature. The obtained Ag{sub 3}PO{sub 4} NPs are nearly spherical in shape with a size of 250 ± 50 nm. These NPs are highly efficient for the degradation of three organic dyes (methylene blue, rhodamine B and methyl orange) under four different types of light sources. In this case, the superior photocatalytic activity is mainly driven by singlet oxygen radicals and it is confirmed through the electron spin resonance (ESR) spin trapping technique, using several quenchers/sources. Notably, these NPs have the ability to absorb large portion of solar spectrum and therefore it displays higher efficiency under sunlight as compared to UV-C light and a 60 W household compact fluorescence lamp (CFL). Furthermore, these NPs exhibit excellent colloidal stability and recycling capability for the degradation of dyes. In addition, it possesses significant antibacterial activity with complete inhibition of bacterial pathogen, Escherichia coli at a very low concentration (0.01 mg/mL) after a mere 15 min of incubation time. The inhibition of bacterial growth is also suggested from the generation of intracellular reactive oxygen species (ROS) in E. coli by fluorescence microscopy. Thus, these NPs may provide a potential outcome for the environmental remediation. - Graphical abstract: Schematic representation of the mechanism involved in photodegradation of organic dyes and inhibition of bacterial growth using Ag{sub 3}PO{sub 4} nanoparticles. - Highlights: • Excellent catalytic activity for dyes degradation under different light sources. • Mechanism involving catalyst mediated ROS generation in photocatalysis suggested. • Good recycling capability of Ag{sub 3}PO{sub 4} even after the fifth cycles. • Extraordinary antibacterial activity of Ag{sub 3}PO{sub 4} after a very short incubation time. • Detection of intracellular

  5. Efflux pumps of Mycobacterium tuberculosis play a significant role in antituberculosis activity of potential drug candidates.

    Science.gov (United States)

    Balganesh, Meenakshi; Dinesh, Neela; Sharma, Sreevalli; Kuruppath, Sanjana; Nair, Anju V; Sharma, Umender

    2012-05-01

    Active efflux of drugs mediated by efflux pumps that confer drug resistance is one of the mechanisms developed by bacteria to counter the adverse effects of antibiotics and chemicals. To understand these efflux mechanisms in Mycobacterium tuberculosis, we generated knockout (KO) mutants of four efflux pumps of the pathogen belonging to different classes. We measured the MICs and kill values of two different compound classes on the wild type (WT) and the efflux pump (EP) KO mutants in the presence and absence of the efflux inhibitors verapamil and l-phenylalanyl-l-arginyl-β-naphthylamide (PAβN). Among the pumps studied, the efflux pumps belonging to the ABC (ATP-binding cassette) class, encoded by Rv1218c, and the SMR (small multidrug resistance) class, encoded by Rv3065, appear to play important roles in mediating the efflux of different chemical classes and antibiotics. Efflux pumps encoded by Rv0849 and Rv1258c also mediate the efflux of these compounds, but to a lesser extent. Increased killing is observed in WT M. tuberculosis cells by these compounds in the presence of either verapamil or PAβN. The efflux pump KO mutants were more susceptible to these compounds in the presence of efflux inhibitors. We have shown that these four efflux pumps of M. tuberculosis play a vital role in mediating efflux of different chemical scaffolds. Inhibitors of one or several of these efflux pumps could have a significant impact in the treatment of tuberculosis. The identification and characterization of Rv0849, a new efflux pump belonging to the MFS (major facilitator superfamily) class, are reported.

  6. Prognostic and biological significance of peroxisome proliferator-activated receptor-gamma in luminal breast cancer.

    Science.gov (United States)

    Abduljabbar, Rezvan; Al-Kaabi, Methaq Mueen; Negm, Ola H; Jerjees, Dena; Muftah, Abir A; Mukherjee, Abhik; Lai, Chun F; Buluwela, Laki; Ali, Simak; Tighe, Patrick J; Green, Andrew; Ellis, Ian; Rakha, Emad

    2015-04-01

    Peroxisome proliferator-activated receptor-gamma (PPARγ) is an adopted orphan receptor that belongs to the nuclear receptor superfamily of transcription factors. PPARγ is regarded as a differentiation factor and it plays an important role in regulating adipogenesis, cell growth, proliferation and tumour progression. In breast cancer (BC), PPARγ agonists were reported to inhibit proliferation and growth invasion and promote phenotypic changes associated with a less malignant and more differentiated status. This study aims to assess the prognostic and biological roles of PPARγ protein expression in a large cohort of BC patients (n = 1100) with emphasis on the luminal oestrogen receptor (ER) positive class. Immunohistochemistry was used to assess the levels of PPARγ expression in BC series prepared as tissue microarrays (TMAs). PPARγ antibody specificity was confirmed using Western blotting. PPARγ nuclear expression was detected in 79 % of the cases and its expression was positively correlated with the hormonal receptors (ER, progesterone receptor and androgen receptor). PPARγ levels were significantly higher in tumours with lobular subtype, smaller size and lower grade, while HER2-positive, ductal or medullary tumours were associated with lower PPARγ levels. Survival analysis showed that PPARγ is associated with better outcome in the whole series as well as in luminal ER-positive class. Cox regression model showed that PPARγ is an independent predictor of outcome. Higher PPARγ was associated with longer survival in patients with ER-positive tumours who did not receive hormone therapy. PPARγ is a good prognostic marker associated with hormone receptors. In patients with luminal BCs, PPARγ is a marker of better prognosis and is associated with longer survival.

  7. 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.

  8. 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....

  9. Clinical significance of isometric bite force versus electrical activity in temporal and masseter muscles

    DEFF Research Database (Denmark)

    Bakke, Merete; Michler, L; Han, K

    1989-01-01

    Bite force and activity in temporal and masseter muscles during biting and chewing were recorded in 19 control subjects and 23 subjects with symptoms and signs of functional disorders of the craniomandibular system. The entire group comprised 13 men and 29 women, 14-63 yr of age. Maximal unilater...... of mandibular elevator strength as a whole, but inadequate to disclose asymmetric conditions. During isometric contraction, relative strength of electromyographic activity fairly accurately imaged the output of mechanical activity....

  10. Hydrogenase activity in aged, nonviable Desulfovibrio vulgaris cultures and its significance in anaerobic biocorrosion.

    Science.gov (United States)

    Chatelus, C; Carrier, P; Saignes, P; Libert, M F; Berlier, Y; Lespinat, P A; Fauque, G; Legall, J

    1987-07-01

    Batch cultures of Desulfovibrio vulgaris stored at 32 degrees C for 10 months have been found to retain 50% of the hydrogenase activity of a 1-day culture. The hydrogenase found in old cultures needs reducing conditions for its activation. Viable cell counts are negative after 6 months, showing that the hydrogenase activity does not depend on the presence of viable cells. These observations are of importance in the understanding of anaerobic biocorrosion of metals caused by depolarization phenomena.

  11. Where did I put that? Patients with amnestic mild cognitive impairment demonstrate widespread reductions in activity during the encoding of ecologically relevant object-location associations

    Science.gov (United States)

    Hampstead, Benjamin M.; Stringer, Anthony Y.; Stilla, Randall F.; Amaraneni, Akshay; Sathian, K.

    2011-01-01

    Remembering the location of objects in the environment is both important in everyday life and difficult for patients with amnestic mild cognitive impairment (aMCI), a clinical precursor to Alzheimer’s disease. To test the hypothesis that memory impairment for object location in aMCI reflects hippocampal dysfunction, we used an event-related functional magnetic resonance imaging paradigm to compare patients with aMCI and healthy elderly controls (HEC) as they encoded 90 ecologically-relevant object-location associations (OLAs). Two additional OLAs, repeated a total of 45 times, served as control stimuli. Memory for these OLAs was assessed following a 1-hour delay. The groups were well matched on demographics and brain volumetrics. Behaviorally, HEC remembered significantly more OLAs than did aMCI patients. Activity differences were assessed by contrasting activation for successfully encoded novel stimuli vs. repeated stimuli. The HEC demonstrated activity within object-related (ventral visual stream), spatial location-related (dorsal visual stream), and feature binding-related cortical regions (hippocampus and other memory-related regions) as well as in frontal cortex and associated subcortical structures. Activity in most of these regions correlated with memory test performance. Although the aMCI patients demonstrated a similar activation pattern, the HEC showed significantly greater activity within each of these regions. Memory test performance in aMCI patients, in contrast to the HEC, was correlated with activity in regions involved in sensorimotor processing. We conclude that aMCI patients demonstrate widespread cerebral dysfunction, not limited to the hippocampus, and rely on encoding-related mechanisms that differ substantially from healthy individuals. PMID:21530556

  12. Significance of AT1 receptor independent activation of mineralocorticoid receptor in murine diabetic cardiomyopathy.

    Directory of Open Access Journals (Sweden)

    Yuji Nagatomo

    Full Text Available BACKGROUND: Diabetes mellitus (DM has deleterious influence on cardiac performance independent of coronary artery disease and hypertension. The objective of the present study was to investigate the role of the renin-angiotensin-aldosterone system, especially angiotensin II type 1a receptor (AT1aR and mineralocorticoid receptor (MR signaling, in left ventricular (LV dysfunction induced by diabetes mellitus (DM. METHODS AND RESULTS: DM was induced by intraperitoneal injection of streptozotocin (200 mg/kg BW in wild-type (WT or AT1aR knockout (KO male mice, and they were bred during 6 or 12 weeks. Some KO mice were administered the MR antagonist eplerenone (100 mg/kg body weight. At 6 weeks, LV diastolic function was impaired in WT-DM, but preserved in KO-DM. At that time point MR mRNA expression was upregulated, NADPH oxidase subunit (p47phox and glutathione peroxidase (GPx1 mRNA expression were upregulated, the staining intensities of LV tissue for 4-hydroxy-2-nonenal was stronger in immunohistochemistry, the number of terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL positive cells was increased, Bcl-2 protein expression was significantly downregulated, and the expression of SERCA2a and phosphorylated phospholamban was depressed in WT-DM, while these changes were not seen in KO-DM. At 12 weeks, however, these changes were also noted in KO-DM. Eplerenone arrested those changes. The plasma aldosterone concentration was elevated in WT-DM but not in KO-DM at 6 weeks. It showed 3.7-fold elevation at 12 weeks even in KO-DM, which suggests "aldosterone breakthrough" phenomenon. However, the aldosterone content in LV tissue was unchanged in KO-DM. CONCLUSIONS: DM induced diastolic dysfunction was observed even in KO at 12 weeks, which was ameliorated by minelarocorticoid receptor antagonist, eplerenone. AT1-independent MR activation in the LV might be responsible for the pathogenesis of diabetic cardiomyopathy.

  13. Coastal structural remains on the east coast of India: Evidence of maritime activities and their significance

    Digital Repository Service at National Institute of Oceanography (India)

    Tripati, S.

    such as dockyards, jetties, lighthouses, wharves and warehouses related to maritime activities of India. Lighthouses, warehouses and wharves have been located at Poompuhar, Arikamedu, Dharanikota, Chilika and Mahabalipuram on the east coast of India. Similarly...

  14. Stone anchors from Bet Dwarka Island, Gujarat, Coast, India: Significance to historical period maritime activities

    Digital Repository Service at National Institute of Oceanography (India)

    Sundaresh; Gaur, A.S.; Tripati, S.; Gudigar, P.; Bandodkar, S.N.

    Bet Dwarka Island is situated on the extreme west of Indian territory in Jamnagar district of Gujarat. Underwater, the most preserved remains of ancient maritime activity could be the stone anchors of different types, as every boat requires...

  15. 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.

  16. 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

  17. 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...

  18. Creation of a putative third metal binding site in type II dihydroorotases significantly enhances enzyme activity.

    Science.gov (United States)

    Huang, Yen-Hua; Huang, Cheng-Yang

    2015-01-01

    Dihydroorotase (DHOase) is the third enzyme in the de novo biosynthesis pathway of pyrimidine nucleotides. DHOase is divided into two types (I and II). Type II DHOase generally contains a binuclear metal center in its active site. Recently, the crystal structure of DHOase domain in human CAD protein (huDHOase) has revealed three metal ions in the protein's active site. However, whether type II DHOase can have the critical third metal ion, as observed in huDHOase, remains unknown. In the present study, the putative third metal binding site in type II enzymes, such as the prokaryotic Salmonella enterica serovar Typhimurium LT2 DHOase (StDHOase) and the eukaryotic Saccharomyces cerevisiae DHOase (ScDHOase), was created and identified. StDHOase T198E and ScDHOase T208E mutants had higher activities compared with their wild-type enzymes. The need for a higher DHOase stability and activity may drive creation of the third metal ion binding site in huDHOase, which can be achieved by mutating a highly conserved position T in type II dihydroorotases to E, similar to that in huDHOase.

  19. Base composition, selection, and phylogenetic significance of indels in the recombination activating gene-1 in vertebrates

    NARCIS (Netherlands)

    Chiari, Y.; Meijden, van der A.; Madsen, O.; Vences, M.; Meyer, A.

    2009-01-01

    Background: The Recombination Activating Proteins, RAG1 and RAG2, play a crucial role in the immune response in vertebrates. Among the nuclear markers currently used for phylogenetic purposes, Rag1 has especially enjoyed enormous popularity, since it successfully contributed to elucidating the relat

  20. [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.

  1. Significance of the compensation effect and the definition of active centres in metal catalysts

    Energy Technology Data Exchange (ETDEWEB)

    Bond, G.C.

    1985-01-01

    A linear correlation is often observed between the activation energy and the logarithm of the pre-exponential factor in catalysed reactions, although the root cause of this so-called compensation effect is still uncertain. Certain systems exhibit dual or multiple compensation lines, and it is argued that each line corresponds to a particular form of active centre; in monometallic systems each form is thought to have the same number of atoms in the same spatial arrangement. This concept is applied both to simple reactions yielding only one product (e.g. CO methanation, C/sub 2/H/sub 6/ hydrogenolysis) and to reactions forming a variety of products (e.g. cyclopropane hydrogenation), and also to sulphide catalysts for thiophene HDS.

  2. Using the Significant Learning Taxonomy and Active Learning to Improve Accounting Education

    Science.gov (United States)

    Killian, Larita J.; Brandon, Christopher D.

    2009-01-01

    Like other members of the academy, accounting professors are challenged to improve student learning. We must help students move beyond the "bean counter" role and develop higher-level skills such as analysis, synthesis, and problem-solving. The Significant Learning Taxonomy was used as a template to improve learning in an introductory accounting…

  3. Culture, Leadership, and Activism: Translating Fink's Taxonomy of Significant Learning into Pedagogical Practice

    Science.gov (United States)

    Jenkins, Toby S.

    2016-01-01

    Through the article, I share the theoretical foundations, structure, knowledge acquisition, and outcomes of a cultural leadership course. The process for course development integrates several theories and research methods into practice: L. Dee Fink's Taxonomy of Significant Learning, Feminist Theory, Critical Race Theory, and…

  4. Significantly enhanced base activation of peroxymonosulfate by polyphosphates: Kinetics and mechanism.

    Science.gov (United States)

    Lou, Xiaoyi; Fang, Changling; Geng, Zhuning; Jin, Yuming; Xiao, Dongxue; Wang, Zhaohui; Liu, Jianshe; Guo, Yaoguang

    2017-04-01

    Base activation of peroxydisulfate (PDS) is a common process aiming for water treatment, but requires high doses of PDS and strongly basic solutions. Peroxymonosulfate (PMS), another peroxygen of sulfurate derived from PDS, may also be activated by a less basic solution. However, enhancing the base-PMS reactivity is still challenging. Here it is reported that pyrophosphate (PA) and tripolyphosphate (PB) can efficiently enhance PMS activation under weakly alkaline conditions (pH 9.5) via the formation of superoxide anion radical (O2(•-)) and singlet oxygen ((1)O2). The rate constant of Acid Orange 7 (AO7) degradation in PA/PMS system (kPA/PMS) was nearly 4.4-15.9 fold higher than that in PMS/base system (kPMS/base) without any polyphosphates. Increases in PA (or PB) concentration, PMS dose and pH favored the rapid dye degradation. Gas chromatograph-mass spectrometer (GC-MS) data confirmed AO7 and 2,4,6-trichlorophenol (2,4,6-TCP) were decomposed to a series of organic intermediates. The radical quenching and probe oxidation experiments indicate the degradation of organic compounds in the PA/PMS and PB/PMS processes was not reliant on sulfate radical (SO4(•-)) and hydroxyl radical (OH) species but on O2(-) and (1)O2 reactive species. Comparison experiments show that the polyphosphate/PMS process was much more favorable than PDS/base process. The present work provides a novel way to activate PMS for contaminant removal using industrial polyphosphate wastewaters. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Medicinal significance, pharmacological activities, and analytical aspects of anthocyanidins ‘delphinidin’: A concise report

    Directory of Open Access Journals (Sweden)

    Kanika Patel

    2013-01-01

    Full Text Available Herbal medicines have been used for the treatment of various disorders in the world since a very early age due to easily available and less side effect. A large number of phytochemicals have been derived directly or indirectly from natural sources in the form of oils, food supplement, neutraceuticals, and colour pigments. Anthocyanins are classes of phytoconstituents mainly responsible for the different colors of plants material. Literature report revealed the presence of different anthocyanidins such as cyanidin, delphinidin, petunidin, peonidin, pelargonidin, malvidin, cyaniding etc. These anthocyanidins showed a wide range of pharmacological activities. Anthocyanins have an attractive profile in the food industry as natural colorants due to its possible health benefits and safety issues compared to the synthetic dye. Delphinidin is an important anthocyanidins mainly present in the epidermal tissues of flowers and fruits. Delphinidin showed various pharmacological activities such as antioxidant, antimutagenesis, anti-inflammatory and antiangiogenic etc. This review was aimed to elaborate the medicinal importance, pharmacological activities and analytical aspects of anthocyanidins ‘delphinidin’. This review will be benificial to the scientist, manufacturer and consumers in order to explore the potential health benefits of delphinidin.

  6. Significant Modules and Biological Processes between Active Components of Salvia miltiorrhiza Depside Salt and Aspirin

    Directory of Open Access Journals (Sweden)

    Yuan Li

    2016-01-01

    Full Text Available The aim of this study is to examine and compare the similarities and differences between active components of S. miltiorrhiza depside salt and aspirin using perspective of pharmacological molecular networks. Active components of S. miltiorrhiza depside salt and aspirin’s related genes were identified via the STITCH4.0 and GeneCards Database. A text search engine (Agilent Literature Search 2.71 and MCODE software were applied to construct network and divide modules, respectively. Finally, 32, 2, and 28 overlapping genes, modules, and pathways were identified between active components of S. miltiorrhiza depside salt and aspirin. A multidimensional framework of drug network showed that two networks reflected commonly in human aortic endothelial cells and atherosclerosis process. Aspirin plays a more important role in metabolism, such as the well-known AA metabolism pathway and other lipid or carbohydrate metabolism pathways. S. miltiorrhiza depside salt still plays a regulatory role in type II diabetes mellitus, insulin resistance, and adipocytokine signaling pathway. Therefore, this study suggests that aspirin combined with S. miltiorrhiza depside salt may be more efficient in treatment of CHD patients, especially those with diabetes mellitus or hyperlipidemia. Further clinical trials to confirm this hypothesis are still needed.

  7. Medicinal significance, pharmacological activities, and analytical aspects of anthocyanidins‘delphinidin’:A concise report

    Institute of Scientific and Technical Information of China (English)

    Kanika Patel; Achint Jain; Dinesh K Patel

    2013-01-01

    Herbal medicines have been used for the treatment of various disorders in the world since a very early age due to easily available and less side effect.A large number of phytochemicals have been derived directly or indirectly from natural sources in the form of oils, food supplement, neutraceuticals, and colour pigments.Anthocyanins are classes of phytoconstituents mainly responsible for the different colors of plants material.Literature report revealed the presence of different anthocyanidins such as cyanidin, delphinidin, petunidin, peonidin, pelargonidin, malvidin, cyaniding etc.These anthocyanidins showed a wide range of pharmacological activities.Anthocyanins have an attractive profile in the food industry as natural colorants due to its possible health benefits and safety issues compared to the synthetic dye.Delphinidin is an important anthocyanidins mainly present in the epidermal tissues of flowers and fruits. Delphinidin showed various pharmacological activities such as antioxidant, antimutagenesis, anti-inflammatory and antiangiogenic etc.This review was aimed to elaborate the medicinal importance, pharmacological activities and analytical aspects of anthocyanidins‘delphinidin’. This review will be benificial to the scientist, manufacturer and consumers in order to explore the potential health benefits of delphinidin.

  8. Significant Modules and Biological Processes between Active Components of Salvia miltiorrhiza Depside Salt and Aspirin.

    Science.gov (United States)

    Li, Yuan; Xie, Yanming; Wang, Lianxin; Zhang, Yingying; Gu, Hao; Chai, Yan

    2016-01-01

    The aim of this study is to examine and compare the similarities and differences between active components of S. miltiorrhiza depside salt and aspirin using perspective of pharmacological molecular networks. Active components of S. miltiorrhiza depside salt and aspirin's related genes were identified via the STITCH4.0 and GeneCards Database. A text search engine (Agilent Literature Search 2.71) and MCODE software were applied to construct network and divide modules, respectively. Finally, 32, 2, and 28 overlapping genes, modules, and pathways were identified between active components of S. miltiorrhiza depside salt and aspirin. A multidimensional framework of drug network showed that two networks reflected commonly in human aortic endothelial cells and atherosclerosis process. Aspirin plays a more important role in metabolism, such as the well-known AA metabolism pathway and other lipid or carbohydrate metabolism pathways. S. miltiorrhiza depside salt still plays a regulatory role in type II diabetes mellitus, insulin resistance, and adipocytokine signaling pathway. Therefore, this study suggests that aspirin combined with S. miltiorrhiza depside salt may be more efficient in treatment of CHD patients, especially those with diabetes mellitus or hyperlipidemia. Further clinical trials to confirm this hypothesis are still needed.

  9. Elicitor Mixtures Significantly Increase Bioactive Compounds, Antioxidant Activity, and Quality Parameters in Sweet Bell Pepper

    Directory of Open Access Journals (Sweden)

    Lina Garcia-Mier

    2015-01-01

    Full Text Available Sweet bell peppers are greatly appreciated for their taste, color, pungency, and aroma. Additionally, they are good sources of bioactive compounds with antioxidant activity, which can be improved by the use of elicitors. Elicitors act as metabolite-inducing factors (MIF by mimic stress conditions. Since plants rarely experience a single stress condition one by one but are more likely to be exposed to simultaneous stresses, it is important to evaluate the effect of elicitors on plant secondary metabolism as mixtures. Jasmonic acid (JA, hydrogen peroxide (HP, and chitosan (CH were applied to fruits and plants of bell pepper as mixtures. Bioactive compounds, antioxidant activity, and quality parameters were evaluated. The assessed elicitor cocktail leads to an increase in the variables evaluated (P ≤ 0.05 when applied to mature fruits after harvest, whereas the lowest values were observed in the treatment applied to immature fruits. Therefore, the application of the elicitor cocktail to harvested mature fruits is recommended in order to improve bioactive compounds and the antioxidant activity of sweet bell peppers.

  10. Significance of chymase-dependent matrix metalloproteinase-9 activation on indomethacin-induced small intestinal damages in rats.

    Science.gov (United States)

    Kakimoto, Kazuki; Takai, Shinji; Murano, Mitsuyuki; Ishida, Kumi; Yoda, Yukiko; Inoue, Takuya; Jin, Denan; Umegaki, Eiji; Higuchi, Kazuhide

    2010-02-01

    The side effects of nonsteroidal anti-inflammatory drugs (NSAIDs) include gastrointestinal damage not only in the stomach but also in the small intestine. Chymase converts promatrix metalloproteinase-9 to matrix metalloproteinase (MMP)-9, which plays an important role in NSAID-induced gastric damage, but it has been unclear whether chymase-dependent MMP-9 activation is involved in the NSAID-induced small intestinal damage. To clarify the involvement of chymase-dependent MMP-9 activation on NSAID-induced small intestinal damage, the effect of a chymase inhibitor, 2-[4-(5-fluoro-3-methylbenzo[b]thiophen-2-yl)sulfonamido-3-methanesulfonylphenyl] thiazole-4-carboxylic acid (TY-51469), on indomethacin-induced small intestinal damage in rats was evaluated. Until 6 h after oral administration of indomethacin in rats, intestinal MMP-9 activity was unchanged compared with normal rats, but significant increases in MMP-9 activity were observed 12 and 24 h after indomethacin administration. Significant increases in the small intestinal damage score were also observed 12 and 24 h after indomethacin administration. In the extract from the small intestine 24 h after indomethacin administration, the MMP-9 activation was significantly attenuated by TY-51469. Intraperitoneal injection of TY-51469 (10 mg/kg) 3 h before indomethacin administration significantly attenuated the MMP-9 activity in the small intestine compared with placebo treatment. Myeloperoxidase activity, which indicates accumulation of neutrophils, was significantly increased in the small intestine in the placebo-treated rats, but its activity was significantly attenuated by TY-51469 treatment. The area of small intestinal damage was also significantly ameliorated by TY-51469 treatment. These findings suggest that chymase-dependent MMP-9 activation has a significant role in indomethacin-induced small intestinal damage in rats.

  11. 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

  12. Zero Valent Iron Significantly Enhances Methane Production from Waste Activated Sludge by Improving Biochemical Methane Potential Rather Than Hydrolysis Rate

    Science.gov (United States)

    Liu, Yiwen; Wang, Qilin; Zhang, Yaobin; Ni, Bing-Jie

    2015-02-01

    Anaerobic digestion has been widely applied for waste activated sludge (WAS) treatment. However, methane production from anaerobic digestion of WAS is usually limited by the slow hydrolysis rate and/or poor biochemical methane potential of WAS. This work systematically studied the effects of three different types of zero valent iron (i.e., iron powder, clean scrap and rusty scrap) on methane production from WAS in anaerobic digestion, by using both experimental and mathematical approaches. The results demonstrated that both the clean and the rusty iron scrap were more effective than the iron powder for improving methane production from WAS. Model-based analysis showed that ZVI addition significantly enhanced methane production from WAS through improving the biochemical methane potential of WAS rather than its hydrolysis rate. Economic analysis indicated that the ZVI-based technology for enhancing methane production from WAS is economically attractive, particularly considering that iron scrap can be freely acquired from industrial waste. Based on these results, the ZVI-based anaerobic digestion process of this work could be easily integrated with the conventional chemical phosphorus removal process in wastewater treatment plant to form a cost-effective and environment-friendly approach, enabling maximum resource recovery/reuse while achieving enhanced methane production in wastewater treatment system.

  13. Zero valent iron significantly enhances methane production from waste activated sludge by improving biochemical methane potential rather than hydrolysis rate.

    Science.gov (United States)

    Liu, Yiwen; Wang, Qilin; Zhang, Yaobin; Ni, Bing-Jie

    2015-02-05

    Anaerobic digestion has been widely applied for waste activated sludge (WAS) treatment. However, methane production from anaerobic digestion of WAS is usually limited by the slow hydrolysis rate and/or poor biochemical methane potential of WAS. This work systematically studied the effects of three different types of zero valent iron (i.e., iron powder, clean scrap and rusty scrap) on methane production from WAS in anaerobic digestion, by using both experimental and mathematical approaches. The results demonstrated that both the clean and the rusty iron scrap were more effective than the iron powder for improving methane production from WAS. Model-based analysis showed that ZVI addition significantly enhanced methane production from WAS through improving the biochemical methane potential of WAS rather than its hydrolysis rate. Economic analysis indicated that the ZVI-based technology for enhancing methane production from WAS is economically attractive, particularly considering that iron scrap can be freely acquired from industrial waste. Based on these results, the ZVI-based anaerobic digestion process of this work could be easily integrated with the conventional chemical phosphorus removal process in wastewater treatment plant to form a cost-effective and environment-friendly approach, enabling maximum resource recovery/reuse while achieving enhanced methane production in wastewater treatment system.

  14. 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.

  15. UNESCO active learning approach in optics and photonics leads to significant change in Morocco

    Science.gov (United States)

    Berrada, K.; Channa, R.; Outzourhit, A.; Azizan, M.; Oueriagli, A.

    2014-07-01

    There are many difficulties in teaching science and technology in developing countries. Several different teaching strategies have to be applied in these cases. More specifically, for developing countries competencies in teaching science in the introductory classroom has attracted much attention. As a specific example we will consider the Moroccan system. In most developing countries everything is moving so slowly that the progress stays static for development. Also, any change needs time, effort and engagement. In our case we discovered that many teachers feel uncomfortable when introducing new teaching methods and evaluation in classes at introductory physics. However, the introduction of an Active Learning in our curricula showed difficulties that students have in understanding physics and especially concepts. Students were interested in having Active Learning courses much more than passive and traditional ones. Changing believes on physical phenomena and reality of the world students become more attractive and their way of thinking Science changed. The main philosophy of fostering modern hands-on learning techniques -adapted to local needs and availability of teaching resources- is elaborated. The Active Learning program provides the teachers with a conceptual evaluation instrument, drawn from relevant physics education research, giving teachers an important tool to measure student learning. We will try to describe the UNESCO Chair project in physics created in 2010 at Cadi Ayyad University since our first experience with UNESCO ALOP program. Many efforts have been done so far and the project helps now to develop more national and international collaborations between universities and Regional Academies of Education and Training. As a new result of these actions and according to our local needs, the translation of the ALOP program into Arabic is now available under the auspice of UNESCO and encouragement of international partners SPIE, ICTP, ICO and OSA.

  16. The 137Cs activity and its geographical significance in terrestrial ecosystem of Great Wall Station, Antarctica

    Institute of Scientific and Technical Information of China (English)

    2000-01-01

    The radioactive isotope——137 Cs is one of the important tracers for studying the physical processes and the human impacts on the environment. Based on the investigation results of the terrestrial ecosystem of Great Wall Station, Antarctica, it was shown that there are some artificial radioactive elements——137Cs in Antarctic terrestrial ecosystem. The sequence of 137Cs specific activities is as follows: crustaceous lichen>fruticose lichen>surface-moss>surface soil, and the crustaceous lichen is one of the most sensitive ways in monitoring the impact of the long-term diffusion of 137Cs on the environment.

  17. 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.

  18. Walking on high heels changes muscle activity and the dynamics of human walking significantly

    DEFF Research Database (Denmark)

    Simonsen, Erik Bruun; Svendsen, Morten B; Nørreslet, Andreas

    2012-01-01

    digital video cameras operating at 50 frames/second. Both barefooted walking and walking on high-heeled shoes (heel height: 9 cm) were recorded. Net joint moments were calculated by 3D inverse dynamics. EMG was recorded from eight leg muscles. The knee extensor moment peak in the first half of the stance...... joint abductor moment. Several EMG parameters increased significantly when walking on high-heels. The results indicate a large increase in bone-on-bone forces in the knee joint directly caused by the increased knee joint extensor moment during high-heeled walking, which may explain the observed higher...

  19. Medicinal significance, pharmacological activities, and analytical aspects of ricinine: A concise report

    Directory of Open Access Journals (Sweden)

    Kanika Patel

    2016-08-01

    Full Text Available Ricinine (3-cyano-4-methoxy-N-methyl-2-pyridone is an alkaloid present in leaves and seeds of castor plant i.e. Ricinus communis. It can cause vomiting, convulsions, hypotension, liver and kidney damage and several other complications in human. Ricinine presents mainly in young plant and it is the only cyano-substituted pyridine compounds occurred naturally. Ricinine also found in some other plants such as Piper nigrum, Discocleidion rufescens, Aparisthmium cordatum and Nicotiana tabacum. Accidental and intended Ricinus communis intoxications in humans and animals have been known for centuries. In the present review, we summarize the information regarding its medicinal uses, pharmacological activities, analytical techniques and intended and unintended poisoning cases in humans and animals. This review will be beneficial for the researcher in the field of herbal medicine and other allied sciences.

  20. 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.

  1. 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.

  2. 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

  3. Expression and significance of transforming growth factor β-activated kinase 1 in uterine myoma tissue

    Institute of Scientific and Technical Information of China (English)

    Xiao-Ping Chen; Li Zhao

    2016-01-01

    Objective:To compare the expression of TAK1 in normal myometrium and uterine leiomyoma tissue, and explore the relationship between these molecules and pathogenesis of uterine leiomyoma. Methods:Formaldehyde-fixed, paraffin-embedded specimen from 76 patients with uterine leiomyoma and normal myometrium adjacent were obtained from our hospital. The expression of TAK1 was detected by immunohistochemical staining and PCR analysis. Results:The expression of protein and mRNA levels TAK1 in uterine leiomyoma tissues were significantly increased when compared with normal myometrium, but not related to the number of leiomyoma. Furthermore, TAK1 expression was associated with the size of uterine leiomyoma. Conclusion:The present results suggest that the abundant expression of TAK1 protein may have a molecular basis characteristic of leiomyomas in the human uterus, and TAK1 may be a therapeutic target for the treatment of uterine leiomyoma.

  4. Patient with Macular Disease, Good Visual Acuity, and Central Visual Field Disruption and Significant Difficulties with Activities of Daily Living

    Science.gov (United States)

    Fletcher, Donald C.; Schuchard, Ronald A.; Walker, Joseph P.; Raskauskas, Paul A.

    2008-01-01

    It is generally appreciated that patients with macular disease frequently experience reduced visual acuity. It is not as widely appreciated that they often have significant central visual field disruption, which, by itself, can cause significant problems with activities of daily living, such as reading and driving, even when they maintain good…

  5. Patient with Macular Disease, Good Visual Acuity, and Central Visual Field Disruption and Significant Difficulties with Activities of Daily Living

    Science.gov (United States)

    Fletcher, Donald C.; Schuchard, Ronald A.; Walker, Joseph P.; Raskauskas, Paul A.

    2008-01-01

    It is generally appreciated that patients with macular disease frequently experience reduced visual acuity. It is not as widely appreciated that they often have significant central visual field disruption, which, by itself, can cause significant problems with activities of daily living, such as reading and driving, even when they maintain good…

  6. 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.

  7. 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.

  8. Significance of redox-active cysteines in human FAD synthase isoform 2.

    Science.gov (United States)

    Miccolis, Angelica; Galluccio, Michele; Nitride, Chiara; Giancaspero, Teresa Anna; Ferranti, Pasquale; Iametti, Stefania; Indiveri, Cesare; Bonomi, Francesco; Barile, Maria

    2014-12-01

    FAD synthase (FMN:ATP adenylyl transferase, FMNAT or FADS, EC 2.7.7.2) is the last enzyme in the pathway converting riboflavin into FAD. In humans, FADS is localized in different subcellular compartments and exists in different isoforms. Isoform 2 (490-amino acids) is organized in two domains: the 3'-phosphoadenosine-5'-phosphosulfate (PAPS) reductase domain, that is the FAD-forming catalytic domain, and one resembling a molybdopterin-binding (MPTb) domain, with a hypothetical regulatory role. hFADS2 contains ten Cys residues, seven of which located in the PAPS reductase domain, with a possible involvement either in FAD synthesis or in FAD delivery to cognate apo-flavoproteins. A homology model of the PAPS reductase domain of hFADS2 revealed a co-ordinated network among the Cys residues in this domain. In this model, C312 and C303 are very close to the flavin substrate, consistent with a significantly lowered FAD synthesis rate in C303A and C312A mutants. FAD synthesis is also inhibited by thiol-blocking reagents, suggesting the involvement of free cysteines in the hFADS2 catalytic cycle. Mass spectrometry measurements and titration with thiol reagents on wt hFADS2 and on several individual cysteine/alanine mutants allowed us to detect two stably reduced cysteines (C139 and C241, one for each protein domain), two stable disulfide bridges (C399-C402, C303-C312, both in the PAPS domain), and two unstable disulfides (C39-C50; C440-C464). Whereas the C39-C50 unstable disulfide is located in the MPTb domain and appears to have no catalytic relevance, a cysteine-based redox switch may involve formation and breakdown of a disulfide between C440 and C464 in the PAPS domain.

  9. Base composition, selection, and phylogenetic significance of indels in the recombination activating gene-1 in vertebrates

    Directory of Open Access Journals (Sweden)

    Vences Miguel

    2009-12-01

    Full Text Available Abstract Background The Recombination Activating Proteins, RAG1 and RAG2, play a crucial role in the immune response in vertebrates. Among the nuclear markers currently used for phylogenetic purposes, Rag1 has especially enjoyed enormous popularity, since it successfully contributed to elucidating the relationships among and within a large variety of vertebrate lineages. We here report on a comparative investigation of the genetic variation, base composition, presence of indels, and selection in Rag1 in different vertebrate lineages (Actinopterygii, Amphibia, Aves, Chondrichthyes, Crocodylia, Lepidosauria, Mammalia, and Testudines through the analysis of 582 sequences obtained from Genbank. We also analyze possible differences between distinct parts of the gene with different type of protein functions. Results In the vertebrate lineages studied, Rag1 is over 3 kb long. We observed a high level of heterogeneity in base composition at the 3rd codon position in some of the studied vertebrate lineages and in some specific taxa. This result is also paralleled by taxonomic differences in the GC content at the same codon position. Moreover, positive selection occurs at some sites in Aves, Lepidosauria and Testudines. Indels, which are often used as phylogenetic characters, are more informative across vertebrates in the 5' than in the 3'-end of the gene. When the entire gene is considered, the use of indels as phylogenetic character only recovers one major vertebrate clade, the Actinopterygii. However, in numerous cases insertions or deletions are specific to a monophyletic group. Conclusions Rag1 is a phylogenetic marker of undoubted quality. Our study points to the need of carrying out a preliminary investigation on the base composition and the possible existence of sites under selection of this gene within the groups studied to avoid misleading resolution. The gene shows highly heterogeneous base composition, which affects some taxa in particular and

  10. The significance of different health institutions and their respective contributions of active pharmaceutical ingredients to wastewater.

    Science.gov (United States)

    Herrmann, Manuel; Olsson, Oliver; Fiehn, Rainer; Herrel, Markus; Kümmerer, Klaus

    2015-12-01

    Active pharmaceutical ingredients (APIs) have been frequently found in the environment. It is, however, still not quite clear who is mainly responsible for API emissions. Hospitals have been considered to be the main contributing point sources for wastewater (WW) discharge of APIs. However, recent studies have shown that the contribution of hospitals to the input of APIs into the aquatic environment is quite low. Due to demographic change and the increase of psychiatric diseases, health institutions (HIs) such as psychiatric hospitals and nursing homes are likely to be important sources as well, but no data is available in this respect. This study aims to assess the impact of HIs and to provide a methodology to measure their respective contributions. Drawing on pharmaceutical consumption data for the years 2010, 2011, and 2012, this study identified API usage patterns for a psychiatric hospital (146 beds), a nursing home (286 inhabitants), and a general hospital (741 beds), the latter of which comprises three separate locations. All the HIs are located in two sub-regions of a county district with about 400,000 citizens in southwestern Germany. A selection of neurological drugs was quantified in the sewer of these facilities to evaluate the correlation between consumption and emission. The API contribution of HIs was assessed by comparing the specific consumption in the facilities with the consumption in households, expressed as the emission potential (IEP). The study shows that the usage patterns of APIs in the psychiatric hospital and the nursing home were different from the general hospital. Neurological drugs such as anticonvulsants, psycholeptics, and psychoanaleptics were mainly consumed in the psychiatric hospital and the nursing home (74% and 65%, respectively). Predicted and average measured concentrations in the effluent of the investigated HIs differed mostly by less than one order of magnitude. Therefore, the consumption-based approach is a useful method

  11. 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)

  12. 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

  13. 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.

  14. 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.

  15. Gene-carried hepatoma targeting complex induced high gene transfection efficiency with low toxicity and significant antitumor activity

    Directory of Open Access Journals (Sweden)

    Zhao QQ

    2012-06-01

    Full Text Available Qing-Qing Zhao,1,2 Yu-Lan Hu,1 Yang Zhou,3 Ni Li,1 Min Han,1 Gu-Ping Tang,4 Feng Qiu,2 Yasuhiko Tabata,5 Jian-Qing Gao,11Institute of Pharmaceutics, Zhejiang University, Hangzhou, China; 2Department of Pharmacy, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China; 3Institute of Biochemistry, Iowa State University, Ames, IA, USA; 4Institute of Chemical Biology and Pharmaceutical Chemistry, Zhejiang University, Hangzhou, China; 5Institute for Frontier Medical Sciences, Kyoto University, Kyoto, JapanBackground: The success of gene transfection is largely dependent on the development of a vehicle or vector that can efficiently deliver a gene to cells with minimal toxicity.Methods: A liver cancer-targeted specific peptide (FQHPSF sequence was successfully synthesized and linked with chitosan-linked polyethylenimine (CP to form a new targeted gene delivery vector called CPT (CP/peptide. The structure of CPT was confirmed by 1H nuclear magnetic resonance spectroscopy and ultraviolet spectrophotometry. The particle size of CPT/DNA complexes was measured using laser diffraction spectrometry and the cytotoxicity of the copolymer was evaluated by methylthiazol tetrazolium method. The transfection efficiency evaluation of the CP copolymer was performed using luciferase activity assay. Cellular internalization of the CP/DNA complex was observed under confocal laser scanning microscopy. The targeting specificity of the polymer coupled to peptide was measured by competitive inhibition transfection study. The liver targeting specificity of the CPT copolymer in vivo was demonstrated by combining the copolymer with a therapeutic gene, interleukin-12, and assessed by its abilities in suppressing the growth of ascites tumor in mouse model.Results: The results showed that the liver cancer-targeted specific peptide was successfully synthesized and linked with CP to form a new targeted gene delivery vector called CPT. The composition of CPT

  16. 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)

  17. Significance of plasma von Willebrand factor level and von Willebrand factor-cleaving protease activity in patients with chronic renal diseases

    Institute of Scientific and Technical Information of China (English)

    LU Guo-yuan; SHEN Lei; WANG Zhao-yue; GUO Xiao-fang; BAI Xia; SU Jian; RUAN Chang-geng

    2008-01-01

    Background yon Willebrand factor(vWF)mediates the initial capture of platelets to vascular subendothelium and is essential for platelet aggregation under high fluid shear stress as in arteriaI stenosis.On release frOm endothelial cells,vWF is rapidly cleaved by ADAMTSl 3/vWF-cleaving protease (vWF-CP).We investigated the clinical significance of changes in plasma vWF and vWF-CP activities in chronic renal disease.Methods Plasma vWF and vWF-CP activities were measured using enzyme-linked immunosorbent assay(ELISA)and residual collagen binding assay respectively in patients with lupus nephritis(n=31),primary nephritic syndrome(n=25),diabetic nephropathy(n=45),chronic glomerulonephritis(n=38)and 40 normal controls.The reIation of their levels with pathological and renal status was analyzed.Results In all diseased patients the levels of vWF were significantly higher and vWF-CP activity significantly lower than the controls(both P<0.01).vWF in the four subgroups did not correlate with the stage of disease but correlated negatively with vWF-CP activity.vWF-CP activity was not changed two weeks after renal transplantation.Renal biopsy demonstrated that the vWF level in stage Ⅳ was higher than in stages Ⅱ and Ⅲ while vWF-CP activity was lower in patients with lupus nephritis.After eight-week treatment,the vWF level significantly decreased and the vWF-CP activity significantly increased in systemic lupus erythema,disease activity index<9,but not with index≥9.Even though the vWF-CP activity was significantly lower in membranous nephropathy than in minimal change disease,mesangial proliferative glomerulonephritis or IgA glomerulonephritis,the vWF level was not significantly different.Conclusions The alterations of plasma vWF and vWF-CP activities were associated with different renal pathologies.Injury to endothelial cells and autoantibodies against vWF-CP activity may result in higher vWF Ievel and Iower vWF-CP activity in chronic renaI disease and thus a

  18. The clinical significance of K-Cl cotransport activity in red cells of patients with HbSC disease.

    Science.gov (United States)

    Rees, David C; Thein, Swee Lay; Osei, Anna; Drasar, Emma; Tewari, Sanjay; Hannemann, Anke; Gibson, John S

    2015-05-01

    HbSC disease is the second commonest form of sickle cell disease, with poorly understood pathophysiology and few treatments. We studied the role of K-Cl cotransport activity in determining clinical and laboratory features, and investigated its potential role as a biomarker. Samples were collected from 110 patients with HbSC disease and 41 with sickle cell anemia (HbSS). K-Cl cotransport activity was measured in the oxygenated (K-Cl cotransport(100)) and deoxygenated (K-Cl cotransport(0)) states, using radioactive tracer studies. K-Cl cotransport activity was high in HbSC and decreased significantly on deoxygenation. K-Cl cotransport activity correlated significantly and positively with the formation of sickle cells. On multiple regression analysis, K-Cl cotransport increased significantly and independently with increasing reticulocyte count and age. K-Cl cotransport activity was increased in patients who attended hospital with acute pain in 2011 compared to those who did not (K-Cl cotransport(100): mean 3.87 versus 3.20, P=0.009, independent samples T-test; K-Cl cotransport(0): mean 0.96 versus 0.68, P=0.037). On logistic regression only K-Cl cotransport was associated with hospital attendance. Increased K-Cl cotransport activity was associated with the presence of retinopathy, but this effect was confounded by age. This study links variability in a fundamental aspect of cellular pathology with a clinical outcome, suggesting that K-Cl cotransport is central to the pathology of HbSC disease. Increased K-Cl cotransport activity is associated with increasing age, which may be of pathophysiological significance. Effective inhibition of K-Cl cotransport activity is likely to be of therapeutic benefit.

  19. 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

  20. 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,…

  1. 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…

  2. 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…

  3. 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)

  4. 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)

  5. Huntingtons Disease Mice Infected with Toxoplasma gondii Demonstrate Early Kynurenine Pathway Activation, Altered CD8+ T-Cell Responses, and Premature Mortality

    Science.gov (United States)

    Donley, David W.; Olson, Andrew R.; Raisbeck, Merl F.; Fox, Jonathan H.; Gigley, Jason P.

    2016-01-01

    Huntington's disease (HD) is a progressive neurodegenerative disorder caused by a polyglutamine-repeat expansion in the huntingtin protein. Activation of the kynurenine pathway of tryptophan degradation is implicated in the pathogenesis of HD. Indoleamine-2,3-dioxygenase (IDO) catalyzes the oxidation of tryptophan to kynurenine, the first step in this pathway. The prevalent, neuroinvasive protozoal pathogen Toxoplasma gondii (T. gondii) results in clinically silent life-long infection in immune-competent individuals. T. gondii infection results in activation of IDO which provides some protection against the parasite by depleting tryptophan which the parasite cannot synthesize. The kynurenine pathway may therefore represent a point of synergism between HD and T. gondii infection. We show here that IDO activity is elevated at least four-fold in frontal cortex and striata of non-infected N171-82Q HD mice at 14-weeks corresponding to early–advanced HD. T. gondii infection at 5 weeks resulted in elevation of cortical IDO activity in HD mice. HD-infected mice died significantly earlier than wild-type infected and HD control mice. Prior to death, infected HD mice demonstrated decreased CD8+ T-lymphocyte proliferation in brain and spleen compared to wild-type infected mice. We demonstrate for the first time that HD mice have an altered response to an infectious agent that is characterized by premature mortality, altered immune responses and early activation of IDO. Findings are relevant to understanding how T. gondii infection may interact with pathways mediating neurodegeneration in HD. PMID:27611938

  6. Pomalidomide shows significant therapeutic activity against CNS lymphoma with a major impact on the tumor microenvironment in murine models.

    Science.gov (United States)

    Li, Zhimin; Qiu, Yushi; Personett, David; Huang, Peng; Edenfield, Brandy; Katz, Jason; Babusis, Darius; Tang, Yang; Shirely, Michael A; Moghaddam, Mehran F; Copland, John A; Tun, Han W

    2013-01-01

    Primary CNS lymphoma carries a poor prognosis. Novel therapeutic agents are urgently needed. Pomalidomide (POM) is a novel immunomodulatory drug with anti-lymphoma activity. CNS pharmacokinetic analysis was performed in rats to assess the CNS penetration of POM. Preclinical evaluation of POM was performed in two murine models to assess its therapeutic activity against CNS lymphoma. The impact of POM on the CNS lymphoma immune microenvironment was evaluated by immunohistochemistry and immunofluorescence. In vitro cell culture experiments were carried out to further investigate the impact of POM on the biology of macrophages. POM crosses the blood brain barrier with CNS penetration of ~ 39%. Preclinical evaluations showed that it had significant therapeutic activity against CNS lymphoma with significant reduction in tumor growth rate and prolongation of survival, that it had a major impact on the tumor microenvironment with an increase in macrophages and natural killer cells, and that it decreased M2-polarized tumor-associated macrophages and increased M1-polarized macrophages when macrophages were evaluated based on polarization status. In vitro studies using various macrophage models showed that POM converted the polarization status of IL4-stimulated macrophages from M2 to M1, that M2 to M1 conversion by POM in the polarization status of lymphoma-associated macrophages is dependent on the presence of NK cells, that POM induced M2 to M1 conversion in the polarization of macrophages by inactivating STAT6 signaling and activating STAT1 signaling, and that POM functionally increased the phagocytic activity of macrophages. Based on our findings, POM is a promising therapeutic agent for CNS lymphoma with excellent CNS penetration, significant preclinical therapeutic activity, and a major impact on the tumor microenvironment. It can induce significant biological changes in tumor-associated macrophages, which likely play a major role in its therapeutic activity against CNS

  7. 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.

  8. 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.

  9. 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

  10. 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

  11. 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)

  12. 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)

  13. 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)

  14. Relationship and significance between anti-β2-glycoprotein I antibodies and platelet activation state in patients with ulcerative colitis

    Institute of Scientific and Technical Information of China (English)

    Yan-Hang Gao; Pu-Jun Gao; Chun-Guang Wang; Xiao-Cong Wang; Yun-Feng Piao

    2008-01-01

    AIM:To study the relationship between anti-β2-glycoproteinⅠ(aβ2GPⅠ) antibodies and platelet activation state in patients with ulcerative colitis (UC)and its significance.METHODS:Peripheral blood samples were collected from 56 UC patients (34 males and 22 females,aged 43.5 years,range 21-66 years),including 36 at active stage and 20 at remission stage,and 25 sex-and age-matched controls.The level of aβ2GPⅠwas measured by ELISA.The platelet activation markers,platelet activation complex-I (PAC- I) and P-selectin (CD62P) were detected by flow cytometry.RESULTS:The A value for IgG aβzGPⅠin the active UC group was 0.61±0.13,significantly higher than that in the remittent UC and control groups (0.50±0.13 and 0.22±0.14,P<0.01).There was a significant difference between the two groups (P<0.01).The A value for IgM aβ2GPⅠin the active and remittent UC groups was 0.43±0.13 and 0.38±0.12,significantly higher than that in the control group (0.20±0.12,P<0.01).However,there was no significant difference between the two groups (P>0.05).The PAC-I positive rate for the active and remittent UC groups was 30.6%±7.6% and 19.6%±7.8% respectively,significantly higher than that for the control group (6.3%±1.7%,P<0.01).There was a significant difference between the two groups (P<0.01).The CD62P positive rate for the active and remittent UC groups was 45.0%±8.8% and 31.9%±7.8% respectively,significantly higher than that for the control group (9.2%±2.7%,P<0.01).There was a significant difference between the two groups (P<0.01).In the active UC group,the more severe the state of illness was,the higher the A value for IgG aβ2GPⅠwas,and the positive rate for PAC-I and CD62P was positively correlated with the state of illness (Faβ2GPⅠ= 3.679,P<0.05;FPAC-I (%) = 5.346,P<0.01;and FCD62P (%) = 5.418,P<0.01).Meanwhile,in the same state of illness,the A value for IgG aβ2GPⅠwas positively correlated to the positive rates for PAC-I and CD62P

  15. Clinical significance of telomerase activity in peritoneal lavage fluid from patients with gastric cancer and its relationship with cellular proliferation

    Institute of Scientific and Technical Information of China (English)

    Ming-Xu Da; Xiao-Ting Wu; Tian-Kang Guo; Zi-Guang Zhao; Ting Luo; Kun Qian; Ming-Ming Zhang; Jie Wang

    2007-01-01

    AIM: To evaluate the efficacy of telomerase activity assay and peritoneal lavage cytology (PLC) examination in peritoneal lavage fluid for the prediction of peritoneal metastasis in gastric cancer patients, and to explore the relationship between telomerase activity and proliferating cell nuclear antigen expression.METHODS: Telomeric repeated amplification protocol (TRAP)-enzyme-linked immunosorbent assay (ELISA) was performed to measure the telomerase activity in 60 patients with gastric cancer and 50 with peptic ulcer. PLC analysis of the 60 patients with gastric cancer was used for comparison. The proliferating cell nuclear antigen (PCNA) in gastric carcinoma was immunohistochemically examined.RESULTS: The telomerase activity and PLC positive rate in peritoneal lavage fluid from patients with gastric cancer was 41.7% (25/60), and 25.0% (15/60), respectively. The positive rate of telomerase activity was significantly higher than that of PLC in the group Of pT4 (15/16 vs 9/16, P < 0.05), P1-3 (13/13 vs 9/13, P < 0.05) and diffuse type (22/42 vs 13/42, P < 0.05). The patients with positive telomerase activity, peritoneal metastasis, and serosal invasion had significantly higher levels of average PCNA proliferation index (PI), (55.00 ± 6.59 vs 27.43 ± 7.72, 57.26 ± 10.18 vs 29.15 ± 8.31, and 49.82 ± 6.74 vs 24;65 ± 7.33, respectively, P < 0.05).CONCLUSION: The TRAP assay for telomerase activity is a useful adjunct for cytologic method in the diagnosis of peritoneal micrometastasis and well related to higher proliferating activity of gastric cancer. The results of this study also suggest a promising future therapeutic strategy for treating peritoneal dissemination based on telomerase inhibition.

  16. STUDY OF CORRELATION AND SIGNIFICANCE OF BIOCHEMICAL PARAMETERS IN THE ASSESSMENT OF ACTIVE PHASE OF THYROID EYE DISEASE

    Directory of Open Access Journals (Sweden)

    Ashok Kumar P

    2016-08-01

    Full Text Available AIM Role of Interleukin-6 and HS-CRP Levels in the assessment of active thyroid eye disease. MATERIALS & METHODS A prospective observational study of 30 patients from the age group of 20-60 years with thyroid eye disease done at Regional Institute of Ophthalmology. All patients were subjected to detailed history, ocular examination, systemic examination, biochemical analysis and Imaging. Patients are categorised as mild, moderate and severe active disease based on clinical activity score. For the period of two years, patients are followed at regular periodic intervals according to the severity of disease and results were analysed. RESULTS Out of 30 patients studied, majority of the patients were females (60%, and 70% of the patients had bilateral disease. Among 30 patients, 83.33% in hyperthyroid state, 3.33% in Hypothyroid state, 13.33% in Euthyroid state (Table 3. Smoking being important risk factor in 30% among males. 50% of patients presented with mild disease, 30% with moderate disease, 0% with severe disease. IL-6, HS-CRP levels are increased only in patients with severe active disease (Table 6. Remission attained in all patients when treated earlier with steroids. CONCLUSION Identifying disease activity early and aggressive treatment with systemic steroids in active phase of moderate and severe disease has reduced the morbidity associated with disease. Correlation of IL-6, HS-CRP, TFT levels are significantly increased only in patients with active phase of severe thyroid eye disease but not significantly elevated in active phase of moderate disease. Another pitfall is IL-6 is an expensive ELISA based diagnosis. Thus, IL-6 & HS-CRP cannot be routinely used to screen patients with Thyroid eye disease.

  17. 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.

  18. 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.

  19. Five-year results from a prospective multicentre study of percutaneous pulmonary valve implantation demonstrate sustained removal of significant pulmonary regurgitation, improved right ventricular outflow tract obstruction and improved quality of life.

    Science.gov (United States)

    Hager, Alfred; Schubert, Stephan; Ewert, Peter; Søndergaard, Lars; Witsenburg, Maarten; Guccione, Paolo; Benson, Lee N; Suárez de Lezo, José; Lung, Te-Hsin; Hess, John; Eicken, Andreas; Berger, Felix

    2017-02-20

    Percutaneous pulmonary valve implantation (PPVI) is used to treat patients with dysfunctional pulmonary valve conduits. Short- and longer-term results from multiple trials have outlined haemodynamic improvements. Our aim was to report the long-term results, including quality of life, from a multicentre trial in Europe and Canada. From October 2007 to April 2009, 71 patients (24 female; median age 19.0 [IQR: 14.0 to 25.0] years) were enrolled in a prospective cohort study. PPVI was performed successfully in 63 patients. At five-year follow-up four patients had died. Moderate and severe pulmonary regurgitation were completely resolved in all except one patient, who needed re-PPVI. Outflow tract obstruction improved significantly from a mean pressure gradient of 37.7±12.1 mmHg before PPVI to 17.3±9.7 mmHg at five-year follow-up; however, 11 patients needed treatment for restenosis. The EQ-5D quality of life utility index and visual analogue scale scores were both significantly improved six months post PPVI and remained so at five years. Five-year results following PPVI demonstrate resolved moderate or severe pulmonary regurgitation, improved right ventricular outflow tract obstruction, and improved quality of life.

  20. 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.

  1. Study of prognostic significance of antenatal ultrasonography and renin angiotensin system activation in predicting disease severity in posterior urethral valves

    Directory of Open Access Journals (Sweden)

    Divya Bhadoo

    2015-01-01

    Full Text Available Aims: Study on prognostic significance of antenatal ultrasonography and renin angiotensin system activation in predicting disease severity in posterior urethral valves. Materials and Methods: Antenatally diagnosed hydronephrosis patients were included. Postnatally, they were divided into two groups, posterior urethral valve (PUV and non-PUV. The studied parameters were: Gestational age at detection, surgical intervention, ultrasound findings, cord blood and follow up plasma renin activity (PRA values, vesico-ureteric reflux (VUR, renal scars, and glomerular filtration rate (GFR. Results: A total of 25 patients were included, 10 PUV and 15 non-PUV. All infants with PUV underwent primary valve incision. GFR was less than 60 ml/min/1.73 m 2 body surface area in 4 patients at last follow-up. Keyhole sign, oligoamnios, absent bladder cycling, and cortical cysts were not consistent findings on antenatal ultrasound in PUV. Cord blood PRA was significantly higher (P < 0.0001 in PUV compared to non-PUV patients. Gestational age at detection of hydronephrosis, cortical cysts, bladder wall thickness, and amniotic fluid index were not significantly correlated with GFR while PRA could differentiate between poor and better prognosis cases with PUV. Conclusions: Ultrasound was neither uniformly useful in diagnosing PUV antenatally, nor differentiating it from cases with non-PUV hydronephrosis. In congenital hydronephrosis, cord blood PRA was significantly higher in cases with PUV compared to non-PUV cases and fell significantly after valve ablation. Cord blood PRA could distinguish between poor and better prognosis cases with PUV.

  2. 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)

  3. 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...

  4. Significantly increased concentration of soluble urokinase-type plasminogen activator receptor in the blood of patients with pelvic inflammatory disease.

    Science.gov (United States)

    Yeh, Yuan-Hung; Wang, Po-Hui; Lin, Long-Yau; Tee, Yi-Torng; Chou, Ming-Chih; Yang, Shun-Fa; Tsai, Hsiu-Ting

    2013-01-16

    To determine expression levels of urokinase-type plasminogen activator (uPA), soluble urokinase-type plasminogen activator receptor (suPAR), plasminogen activator inhibitor-1 (PAI-1) in plasma and to identify gene polymorphisms specific to patients with pelvic inflammatory disease (PID) and healthy controls. Enzyme-linked immunosorbent assay and polymerase chain reaction-restriction fragment length polymorphism were used to measure plasma levels and polymorphisms in uPA, suPAR, and PAI-1 among seventy healthy controls and 64 PID patients before and after they received routine treatment protocols. The levels of plasma uPA (ng/ml) and soluble suPAR (pg/ml) were significantly increased in PID patients (uPA: 0.57±0.03; suPAR: 1372.04±68.20) when compared to that in normal controls (uPA: 0.55±0.06, p=0.002; suPAR: 1192.46±51.98, p=0.04); moreover, suPAR decreased significantly after treatment when compared to levels noted in the same patients (1220.06±58.14; p=0.003) after they received treatment. The increased expression of suPAR was significantly correlated with WBC counts (r=0.382, p=0.002, n=64) in blood as well as the plasma levels of CRP (r=0.441, ppelvic inflammatory disease. Copyright © 2012. Published by Elsevier B.V.

  5. In vitro antibacterial evaluation of Anabaena sp. against several clinically significant microflora and HPTLC analysis of its active crude extracts

    Directory of Open Access Journals (Sweden)

    Chauhan Abhishek

    2010-01-01

    Full Text Available The present study was conducted to evaluate the possible antibacterial activity of Anabaena extracts. Anabaena was isolated from a natural source and cultured in vitro. after suitable growth, cyanobacterial culture was harvested using different solvents. Extracts, thus prepared, were evaluated for their antibacterial potential by agar-well diffusion assay against bacterial species of clinical significance. MIC values were determined further to check the concentration ranges for significant inhibition. HPTLC analysis was done to separate the components of active crude extract in an attempt to identify the bio-active chemical entity. Methanol extract exhibited more potent activity than that of hexane and ethyl acetate extracts. No inhibitory effect was found against Pseudomonas aeruginosa, Salmonella typhi, and Klebsiella pneumoniae. Staphylococcus aureus required about 256 μg/ml of the crude methanol extract for effective inhibition. HPTLC evaluation at λ 254 nm was performed for the separation of a complex mixture of the methanol extract. The results provide evidence that Anabaena sp. extracts might indeed be potential sources of new antibacterial agents.

  6. 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)

  7. Clinical significance of fibromyalgia syndrome in different rheumatic diseases: Relation to disease activity and quality of life.

    Science.gov (United States)

    El-Rabbat M, Sarah; Mahmoud, Nermeen K; Gheita, Tamer A

    2017-04-11

    To describe the frequencies of fibromyalgia syndrome (FMS) in various rheumatic diseases; rheumatoid arthritis (RA), systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and Behçets disease (BD) patients and to study the relation to clinical manifestations and quality of life (QoL). 160 patients (50 RA, 50 SLE, 30 SSc and 30 BD) and matched corresponding healthy controls were included. Disease activity was assessed using disease activity score in 28 joints (DAS28) for RA, SLE Disease Activity index (SLEDAI), modified Rodnan skin score for SSc and BD Current Activity Form (BDCAF). The QoL was also recorded. Severity in FMS cases was estimated using the revised Fibromyalgia Impact Questionnaire score. In the RA, SLE, SSc and BD patients, FMS was found in 14%, 18%, 6.67% and 3.33% respectively compared to 2.1%, 3%, 3.3% and 0% in their corresponding controls. In RA patients, DAS28 was significantly higher in those with FMS (p=0.009) and significantly correlated with both Widespread Pain Index (WPI) (p=0.011) and Symptom Severity (SS) scale (p=0.012). The QoL scale in those with FMS was significantly worse (62.3±7.9) compared to those without (71.7±14.4) (p=0.023). In SLE patients, The WPI and SS both significantly correlated with the presence of thrombosis (r=0.28, p=0.049 and r=0.43, p=0.002 respectively). The SS scale tended to correlate with the SLEDAI (r=0.28, p=0.05). In BD patients, BDCAF and WPI significantly correlated (p=0.03). Fibromyalgia syndrome is more frequent in rheumatic diseases, could be related to the disease activity in RA and BD patients and to thrombosis in SLE and affected the QoL in RA. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  8. The hetero-transplantation of human bone marrow stromal cells carried by hydrogel unexpectedly demonstrates a significant role in the functional recovery in the injured spinal cord of rats.

    Science.gov (United States)

    Raynald; Li, Yanbin; Yu, Hao; Huang, Hua; Guo, Muyao; Hua, Rongrong; Jiang, Fenjun; Zhang, Kaihua; Li, Hailong; Wang, Fei; Li, Lusheng; Cui, FuZhai; An, Yihua

    2016-03-01

    Spinal cord injury (SCI) often causes a disturbance in the microenvironment in the lesion site resulting in sudden loss of sensory and motor function. Transplantation of stem cells provides a promising strategy in the treatment of SCI. But limited growth and immunological incompatibility of the stem cells with the host limits the application of this strategy. In order to get better survival and integration with the host, we employed a hyaluronic acid (HA) based scaffold covalently modified by poly-l-Lysine (PLL) as a vehicle to deliver the human bone marrow stromal cells (BMSCs) to the injured spinal cord of rats. The BMSCs were chosen as an ideal candidate for its advantage of low expression of major histocompatibility complex II. The data unexpectedly showed that the hetero-transplanted cells survived well in the lesion site even at 8 weeks post injury. Both the immunofluorescent and the electrophysiological assay indicated better survival of the transplanted cells and improved axonal growth in SCI rats transplanted with BMSCs in HA-PLL in contrast to the groups without either BMSCs or the HA scaffold transplantation. These promotions may account for the functional recovery assessed by Basso-Beattie-Bresnahan (BBB) locomotor rating scale in the HA-PLL seeded with BMSCs group. These data suggests that hetero-transplantation of human BMSCs delivered by HA scaffold demonstrates a significant role in the functional recovery in the injured spinal cord of rats.

  9. Activation of leukemia-associated RhoGEF by Galpha13 with significant conformational rearrangements in the interface.

    Science.gov (United States)

    Suzuki, Nobuchika; Tsumoto, Kouhei; Hajicek, Nicole; Daigo, Kenji; Tokita, Reiko; Minami, Shiro; Kodama, Tatsuhiko; Hamakubo, Takao; Kozasa, Tohru

    2009-02-20

    The transient protein-protein interactions induced by guanine nucleotide-dependent conformational changes of G proteins play central roles in G protein-coupled receptor-mediated signaling systems. Leukemia-associated RhoGEF (LARG), a guanine nucleotide exchange factor for Rho, contains an RGS homology (RH) domain and Dbl homology/pleckstrin homology (DH/PH) domains and acts both as a GTPase-activating protein (GAP) and an effector for Galpha(13). However, the molecular mechanism of LARG activation upon Galpha(13) binding is not yet well understood. In this study, we analyzed the Galpha(13)-LARG interaction using cellular and biochemical methods, including a surface plasmon resonance (SPR) analysis. The results obtained using various LARG fragments demonstrated that active Galpha(13) interacts with LARG through the RH domain, DH/PH domains, and C-terminal region. However, an alanine substitution at the RH domain contact position in Galpha(13) resulted in a large decrease in affinity. Thermodynamic analysis revealed that binding of Galpha(13) proceeds with a large negative heat capacity change (DeltaCp degrees ), accompanied by a positive entropy change (DeltaS degrees ). These results likely indicate that the binding of Galpha(13) with the RH domain triggers conformational rearrangements between Galpha(13) and LARG burying an exposed hydrophobic surface to create a large complementary interface, which facilitates complex formation through both GAP and effector interfaces, and activates the RhoGEF. We propose that LARG activation is regulated by an induced-fit mechanism through the GAP interface of Galpha(13).

  10. Significance of complement components C1q and C4 bound to circulating immune complexes in juvenile idiopathic arthritis: support for classical complement pathway activation.

    Science.gov (United States)

    Gilliam, Brooke E; Reed, Melinda R; Chauhan, Anil K; Dehlendorf, Amanda B; Moore, Terry L

    2011-01-01

    Immune complexes (ICs) from sera of juvenile idiopathic arthritis (JIA) patients show increased complement opsonisation; however, a definitive role for involvement of the classical or alternative pathway is not entirely clear. To delineate the role of these pathways, we measured activated complement products bound to circulating IC (CICs) in the sera of JIA patients. Sera from 100 JIA patients and 22 healthy children were collected. C1q, C4, C3, C3d, and membrane attack complex (MAC) bound to CICs were measured by enzyme-linked immunosorbent assay. Data was compared to IgM rheumatoid factor (RF), IgG anti-cyclic citrullinated peptide (CCP) antibodies, C-reactive protein (CRP), and erythrocyte sedimentation rate (ESR) levels. Mean levels of C1q, C4, and MAC bound to CICs were significantly elevated in JIA patients compared to healthy children. C1q correlated significantly with C4 and MAC bound to CICs and C4 and MAC also demonstrated significant correlation. No significant differences were noted in complement components bound to CICs when evaluating IgM RF, anti-CCP antibody, and CRP positivity. A significant correlation was noted between MAC bound to CICs and ESR. C1q and MAC bound to CICs mean levels were significantly higher in patients with an elevated ESR compared to those with a normal ESR level. JIA patients have elevated levels of complement components bound to CICs, particularly from the classical pathway. Moreover, classical pathway components were associated with ESR, a marker of disease activity. MAC bound to CICs also correlated significantly with ESR, further supporting the notion of complement-mediated tissue injury that is triggered by IC-mediated classical pathway activation.

  11. Quercetin phospholipid complex significantly protects against oxidative injury in ARPE-19 cells associated with activation of Nrf2 pathway.

    Science.gov (United States)

    Xu, Xin-Rong; Yu, Hai-Tao; Yang, Yan; Hang, Li; Yang, Xue-Wen; Ding, Shu-Hua

    2016-01-05

    Age-related macular degeneration (AMD) is a major cause of blindness worldwide. Oxidative stress plays a crucial role in the pathogenesis of dry AMD. Quercetin has potent anti-oxidative activities, but poor bioavailability limits its therapeutic application. Herein, we prepared the phospholipid complex of quercetin (quercetin-PC), characterized its structure by differential scanning calorimetry, infrared spectrum and x-ray diffraction. Quercetin-PC had equilibrium solubility of 38.36 and 1351.27μg/ml in water and chloroform, respectively, which was remarkably higher than those of quercetin alone. Then we established hydrogen peroxide (H2O2)-induced oxidative injury model in human ARPE-19 cells to examine the effects of quercetin-PC. Quercetin-PC, stronger than quercetin, promoted cell proliferation, and the proliferation rate was increased to be 78.89% when treated with Quercetin-PC at 400μM. Moreover, quercetin-PC effectively prevented ARPE-19 cells from apoptosis, and the apoptotic rate was reduced to be 3.1% when treated with Quercetin-PC at 200μM. In addition, quercetin-PC at 200μM significantly increased the activities of SOD, CAT and GSH-PX, and reduced the levels of reactive oxygen species and MDA in H2O2-treated ARPE-19 cells, but quercetin at 200μM failed to do so. Molecular examinations revealed that quercetin-PC at 200μM significantly activated Nrf2 nuclear translocation and significantly enhanced the expression of target genes HO-1, NQO-1 and GCL by different folds at both mRNA and protein levels. Our current data collectively indicated that quercetin-PC had stronger protective effects against oxidative-induced damages in ARPE-19 cells, which was associated with activation of Nrf2 pathway and its target genes implicated in antioxidant defense.

  12. Activating killer-cell immunoglobulin-like receptors (KIR) and their cognate HLA ligands are significantly increased in autism.

    Science.gov (United States)

    Torres, Anthony R; Westover, Jonna B; Gibbons, Cole; Johnson, Randall C; Ward, David C

    2012-10-01

    Killer-cell immunoglobulin-like receptor (KIR) proteins are expressed on natural killer (NK) cells and appear important in innate and adaptive immunity. There are about 14 KIR genes on chromosome 19q13.4, composed of those that inhibit and those that activate NK cell killing. Haplotypes have different combinations of these genes meaning that not all genes are present in a subject. There are two main classes of cognate human leukocyte antigen (HLA) ligands (HLA-Bw4 and HLA-C1/C2) that bind to the inhibitory/activating receptors. As a general rule, the inhibitory state is maintained except when virally infected or tumor cells are encountered; however, both increased activation and inhibition states have been associated with susceptibility and protection against numerous disease states including cancer, arthritis, and psoriasis. Utilizing DNA from 158 Caucasian subjects with autism and 176 KIR control subjects we show for the first time a highly significant increase in four activating KIR genes (2DS5, 3DS1, 2DS1 and 2DS4) as measured by chi square values and odds ratios. In addition, our data suggests a highly significant increase in the activating KIR gene 2DS1 and its cognate HLA-C2 ligand (2DS1+C2; p = 0.00003 [Odds ratio = 2.87]). This information ties together two major immune gene complexes, the human leukocyte complex and the leukocyte receptor complex, and may partially explain immune abnormalities observed in many subjects with autism.

  13. Changes of biogeochemical activities before and after significant mud displacement at the Håkon Mosby Mud Volcano (HMMV)

    Science.gov (United States)

    Felden, J.; Wenzhöfer, F.; Yoerger, D.; Camilli, R.; German, C.; Olu, K.; Feseker, T.; de Beer, D.; Boetius, A.

    2012-04-01

    The Håkon Mosby Mud Volcano (72°N, 14° 43' E, 1250 m water depth) was studied for a period of a year by the Long-term Observatory On Mud-volcano Eruptions (LOOME) in 2009-2010, to investigate temporal variations of mud volcanism and consequences for biogeochemical processes. The HMMV is a highly active methane cold seep ecosystem characterized by high rates of methane efflux. It hosts different chemosynthetic communities such as thiotrophic bacterial mats and siboglinid tubeworm assemblages. This study focuses on changes in community composition and biogeochemical activity such as methane emission, total benthic oxygen uptake, microbial methane and sulfate consumption before and after a major mud displacement recorded by LOOME. The sensor-enabled long-term observations of the HMMV habitats were combined with short-term analyses before and after the displacement events by ROVs QUEST (MARUM) and GENESIS (University of Gent), the AUV Sentry (WHOI) equipped with a multibeam and subbottom profiler, CTD and photographic unit as well as with a mass spectrometer. We found shifts in the distribution patterns of chemosynthetic communities and also substantial changes in their activity, consistent with changes in temperature gradients. This study was sponsored by the EU-Projects HERMIONE "Hotspot Ecosystem Research and Man's Impact on European Seas", and ESONET "European Seas Observatory Network" (Demonstration Mission LOOME "Long term observations on mud volcano eruptions").

  14. An Antimicrobial Metabolite from Bacillus sp.: Significant activity against pathogenic bacteria including multidrug-resistant clinical strains

    Directory of Open Access Journals (Sweden)

    AJAY GHOSH CHALASANI

    2015-12-01

    Full Text Available In this study, the cell free modified trypticase soya broth (pH 7.4+0.2 of Bacillus subtilis URID 12.1 showed significant antimicrobial activity against multidrug-resistant strains of Staphylococcus aureus, S. epidermidis, Streptococcus pyogenes and Enterococcus faecalis. The partially purified antimicrobial molecule was found to be resistant to extremes of pH and temperatures and also to higher concentrations of trypsin and proteinase K. The antimicrobial molecule was purified by a three-step method that included reverse-phased high performance liquid chromatography (RP-HPLC. The minimum inhibitory concentration (MIC values were determined for 11 species of bacteria using a microbroth dilution technique. The HPLC-purified fraction showed the MICs ranging from 0.5 to 1 µg/ml for methicillin and vancomycin resistant Staphylococcus aureus (MVRSA and methicillin-resistant Staphylococcus epidermidis (MRSE strains. The molecular mass of the antimicrobial compound was determined to be 842.37 Da. The same antimicrobial fraction showed negligible haemolytic activity against human red blood cells even at a concentration as high as 100µg/ml. Because of its significant antimicrobial activity at low MIC values coupled with its non-haemolytic property, it may prove to be a novel antimicrobial lead molecule.

  15. Walking with a four wheeled walker (rollator) significantly reduces EMG lower-limb muscle activity in healthy subjects.

    Science.gov (United States)

    Suica, Zorica; Romkes, Jacqueline; Tal, Amir; Maguire, Clare

    2016-01-01

    To investigate the immediate effect of four-wheeled- walker(rollator)walking on lower-limb muscle activity and trunk-sway in healthy subjects. In this cross-sectional design electromyographic (EMG) data was collected in six lower-limb muscle groups and trunk-sway was measured as peak-to-peak angular displacement of the centre-of-mass (level L2/3) in the sagittal and frontal-planes using the SwayStar balance system. 19 subjects walked at self-selected speed firstly without a rollator then in randomised order 1. with rollator 2. with rollator with increased weight-bearing. Rollator-walking caused statistically significant reductions in EMG activity in lower-limb muscle groups and effect-sizes were medium to large. Increased weight-bearing increased the effect. Trunk-sway in the sagittal and frontal-planes showed no statistically significant difference between conditions. Rollator-walking reduces lower-limb muscle activity but trunk-sway remains unchanged as stability is likely gained through forces generated by the upper-limbs. Short-term stability is gained but the long-term effect is unclear and requires investigation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  16. In vitro activity of colistin against biofilm by Pseudomonas aeruginosa is significantly improved under "cystic fibrosis-like" physicochemical conditions.

    Science.gov (United States)

    Pompilio, Arianna; Crocetta, Valentina; Pomponio, Stefano; Fiscarelli, Ersilia; Di Bonaventura, Giovanni

    2015-08-01

    The impact of physicochemical conditions observed in cystic fibrosis (CF) lung on colistin activity against both planktonic and biofilm P. aeruginosa cells was evaluated. MIC, minimum bactericidal concentration (MBC), and minimum biofilm eradication concentration (MBEC) values were assessed against 12 CF strains both under "CF-like" (anaerobiosis, pH6.4) and "standard" (aerobiosis, pH7.4) conditions. The activity of colistin was significantly higher under "CF-like" conditions compared to "standard" ones, both against planktonic (MIC90: 1 and 4 μg/mL, respectively) and biofilm (MBEC90: 512 and 1.024 μg/mL, respectively) cells, as confirmed by scanning electron microscopy. Improved activity was not related to biofilm matrix amount. It may be necessary to adequately "rethink" the protocols used for in vitro assessment of colistin activity, by considering physicochemical and microbiological features in the CF lung at the site of infection. This could provide a more favorable therapeutic index, rationale for administration of lower doses, probably resulting in reduced toxicity and emergence of resistant clones. Copyright © 2015 Elsevier Inc. All rights reserved.

  17. Fluid-enabled significant enhancement and active tuning of magnetic resonances in free-standing plasmonic metamaterials.

    Science.gov (United States)

    Leong, Eunice Sok Ping; Liu, Yan Jun; Deng, Jie; Fong, Yih Ting; Zhang, Nan; Wu, Si Ji; Teng, Jing Hua

    2014-10-07

    We report significantly enhanced magnetic resonance by fluid infiltration in a free-standing metamaterial that consists of metal-dielectric-metal films on an ultrathin Si3N4 membrane patterned with etched through nanohole arrays. When different fluids are drop-casted on the structure, the magnetic resonance has high sensitivities of 282 nm per RIU in peak shift and 12% per RIU in peak intensity change, whereas the electric resonance has nearly no changes. This work shows a promising way of using fluids to actively tune the magnetic resonance of metamaterial structures by combining with micro/nano-fluidic technologies.

  18. INVESTIGATION OF THROMBOMODULIN AND PLASMINOGEN ACTIVATOR INHIBITOR TYPE-I IN PREGNANCY INDUCED HYPERTENSION AND ITS CLINICAL SIGNIFICANCE

    Institute of Scientific and Technical Information of China (English)

    马水清; 白春梅; 边旭明

    2001-01-01

    Objective. To measure tbe circulating levels of thrombomodulin (TM) and plasminogen activator inhibitor type-Ⅰ(PAI-I) in women with pregnancy induced hypertension (PIH).``Methods. Blood samples were drawn from 97 pregnant women in their third trimester, grouped as 25 mild PIH, 26 moderate PIH, 22 severe PIH and 24 normotensive healthy pregnant women for determining levels of TM by ELISA, PAI-I by colorimetric assay methods, and creatinine (Cr) in serum by biochemical method.``Results. Circulating levels of TM, PAId and TM/Cr ratio increased with increasing severity of PIH. There were no significant differences between mild and normotensive pregnant women. The parameters were significantly changed in the moderate and severe PIH groups.``Conclv, sion. TM and PAI-Ⅰ may serve as meaningful clinical markers for the assessment of the endothelial damage in PIH,which is very important in evaluating and following the development of PIH.

  19. INVESTIGATION OF THROMBOMODULIN AND PLASMINOGEN ACTIVATOR INHIBITOR TYPE-I IN PREGNANCY INDUCED HYPERTENSION AND ITS CLINICAL SIGNIFICANCE

    Institute of Scientific and Technical Information of China (English)

    马水清; 白春梅; 边旭明

    2001-01-01

    Objective. To measure the circulating levels of thrombomodulin (TM) and plasminogen activator inhibitor type-I (PAI-I) inwomen with pregnancy induced hypertension (PIH). Methods. Blood samples were drawn from 97 pregnant women in their third trimester, grouped as 25 mild PIH, 26 moderate PIH, 22 severe PIH and 24 normotensive healthy pregnant women for determining levels of TM by ELISA, PAI-I by colorimetric assay methods, and creatinine (Cr) in serum by biochemical method. Results. Circulating levels of TM, PAI-I and TM/Cr ratio increased with increasing severity of PIH. There were no significant differences between mild and normotensive pregnant women. The parameters were significantly changed in the moderate and severe PIH groups. Conclusion. TM and PAI-I may serve as meaningful clinical markers for the assessment of the endothelial damage in PIH,which is very important in evaluating and following the development of PIH.

  20. Plasma Thrombin Generation and Sensitivity to Activated Protein C Among Patients With Myeloma and Monoclonal Gammopathy of Undetermined Significance.

    Science.gov (United States)

    Crowley, Maeve P; Kevane, Barry; O'Shea, Susan I; Quinn, Shane; Egan, Karl; Gilligan, Oonagh M; Ní Áinle, Fionnuala

    2016-09-01

    The etiology of the prothrombotic state in myeloma has yet to be definitively characterized. Similarly, while recent evidence suggests that patients with monoclonal gammopathy of undetermined significance (MGUS) may also be at increased risk of thrombosis, the magnitude and the etiology of this risk have also yet to be defined. The present study aims to characterize patterns of plasma thrombin generation and sensitivity to the anticoagulant activity of activated protein C (APC) at the time of initial diagnosis of myeloma and in response to therapy in comparison to that observed among patients with MGUS and matched, healthy volunteers. Patients presenting with newly diagnosed/newly relapsed myeloma (n = 8), MGUS (n = 8), and matched healthy volunteers (n = 8) were recruited. Plasma thrombin generation was determined by calibrated automated thrombography. Peak thrombin generation was significantly higher in patients with myeloma (383.4 ± 33.4 nmol/L) and MGUS (353.4 ± 16.5 nmol/L) compared to healthy volunteers (276.7 ± 20.8 nmol/L; P < .05). In the presence of APC, endogenous thrombin potential was significantly lower in control plasma (228.6 ± 44.5 nmol/L × min) than in either myeloma (866.2 ± 241.3 nmol/L × min, P = .01) or MGUS plasma (627 ± 91.5 nmol/L × min, P = .003). Within the myeloma cohort, peak thrombin generation was significantly higher at diagnosis (353.2 ± 15.9 nmol/L) than following completion of the third cycle of therapy (282.1 ± 15.2 nmol/L; P < .005). Moreover, sensitivity to APC increased progressively with each cycle of chemotherapy. Further study of the etiology and evolving patterns of hypercoagulability among patients with these conditions is warranted and may have future implications for thromboprophylaxis strategies. © The Author(s) 2016.

  1. Uncertainty of knee joint muscle activity during knee joint torque exertion: the significance of controlling adjacent joint torque.

    Science.gov (United States)

    Nozaki, Daichi; Nakazawa, Kimitaka; Akai, Masami

    2005-09-01

    In the single-joint torque exertion task, which has been widely used to control muscle activity, only the relevant joint torque is specified. However, the neglect of the neighboring joint could make the procedure unreliable, considering our previous result that even monoarticular muscle activity level is indefinite without specifying the adjacent joint torque. Here we examined the amount of hip joint torque generated with knee joint torque and its influence on the activity of the knee joint muscles. Twelve healthy subjects were requested to exert various levels of isometric knee joint torque. The knee and hip joint torques were obtained by using a custom-made device. Because no information about hip joint torque was provided to the subjects, the hip joint torque measured here was a secondary one associated with the task. The amount of hip joint torque varied among subjects, indicating that they adopted various strategies to achieve the task. In some subjects, there was a considerable internal variability in the hip joint torque. Such variability was not negligible, because the knee joint muscle activity level with respect to the knee joint torque, as quantified by surface electromyography (EMG), changed significantly when the subjects were requested to change the strategy. This change occurred in a very systematic manner: in the case of the knee extension, as the hip flexion torque was larger, the activity of mono- and biarticular knee extensors decreased and increased, respectively. These results indicate that the conventional single knee joint torque exertion has the drawback that the intersubject and/or intertrial variability is inevitable in the relative contribution among mono- and biarticular muscles because of the uncertainty of the hip joint torque. We discuss that the viewpoint that both joint torques need to be considered will bring insights into various controversial problems such as the shape of the EMG-force relationship, neural factors that help

  2. 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.

  3. Comparative proteomic analyses demonstrate enhanced Interferon and STAT-1 activation in reovirus T3D-infected HeLa cells

    Directory of Open Access Journals (Sweden)

    Peyman eEzzati

    2015-04-01

    Full Text Available As obligate intracellular parasites, viruses are exclusively and intimately dependent upon their host cells for replication. During replication viruses induce profound changes within cells, including: induction of signaling pathways, morphological changes, and cell death. Many such cellular perturbations have been analyzed at the transcriptomic level by gene arrays and recent efforts have begun to analyze cellular proteomic responses. We recently described comparative stable isotopic (SILAC analyses of reovirus, strain type 3 Dearing (T3D-infected HeLa cells. For the present study we employed the complementary labeling strategy of iTRAQ (isobaric tags for relative and absolute quantitation to examine HeLa cell changes induced by T3D, another reovirus strain, type 1 Lang, and UV-inactivated T3D (UV-T3D. Triplicate replicates of cytosolic and nuclear fractions identified a total of 2375 proteins, of which 50, 57, and 46 were significantly up-regulated, and 37, 26 and 44 were significantly down-regulated by T1L, T3D and UV-T3D, respectively. Several pathways, most notably the Interferon signaling pathway and the EIF2 and ILK signaling pathways, were induced by virus infection. Western blots confirmed that cells were more strongly activated by live T3D as demonstrated by elevated levels of key proteins like STAT-1, ISG-15, IFIT-1, IFIT-3 and Mx1. This study expands our understanding of reovirus-induced host responses.

  4. 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.

  5. Cloud condensation nucleus activity comparison of dry- and wet-generated mineral dust aerosol: the significance of soluble material

    Science.gov (United States)

    Garimella, S.; Huang, Y.-W.; Seewald, J. S.; Cziczo, D. J.

    2014-06-01

    This study examines the interaction of clay mineral particles and water vapor for determining the conditions required for cloud droplet formation. Droplet formation conditions are investigated for two common clay minerals, illite and sodium-rich montmorillonite, and an industrially derived sample, Arizona Test Dust. Using wet and dry particle generation coupled to a differential mobility analyzer (DMA) and cloud condensation nuclei counter, the critical activation of the clay mineral particles as cloud condensation nuclei is characterized. Electron microscopy (EM) is used in order to determine non-sphericity in particle shape. It is also used in order to determine particle surface area and account for transmission of multiply charged particles by the DMA. Single particle mass spectrometry and ion chromatography are used to investigate soluble material in wet-generated samples and demonstrate that wet and dry generation yield compositionally different particles. Activation results are analyzed in the context of both κ-Köhler theory (κ-KT) and Frenkel-Halsey-Hill (FHH) adsorption activation theory. This study has two main results: (1) κ-KT is the suitable framework to describe clay mineral nucleation activity. Apparent differences in κ with respect to size arise from an artifact introduced by improper size-selection methodology. For dust particles with mobility sizes larger than ~300 nm, i.e., ones that are within an atmospherically relevant size range, both κ-KT and FHH theory yield similar critical supersaturations. However, the former requires a single hygroscopicity parameter instead of the two adjustable parameters required by the latter. For dry-generated particles, the size dependence of κ is likely an artifact of the shape of the size distribution: there is a sharp drop-off in particle concentration at ~300 nm, and a large fraction of particles classified with a mobility diameter less than ~300 nm are actually multiply charged, resulting in a much

  6. 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.

  7. Relationship of RhoA signaling activity with ezrin expression and its significance in the prognosis for breast cancer patients

    Institute of Scientific and Technical Information of China (English)

    MA Li; LIU Yue-ping; ZHANG Xiang-hong; GENG Cui-zhi; LI Zeng-huai

    2013-01-01

    Background We have recently reported that RhoA may regulate the invasion and metastasis of breast cancer cells as an upstream signal of ezrin in vitro.In this study,we examined the relationship of RhoA signaling activity with ezrin expression in breast cancer and its prognostic significance in patients with breast cancer.Methods Paraffin tumor sections of breast cancer were collected retrospectively from 487 patients diagnosed between 2001 and 2004.Immunohistochemical methods were used to detect the expression of RhoA,phosphorylated (activated) RhoA,and ezrin.Results Ezrin overexpression was detectable in 15.2% of 487 invasive breast cancers.The majority (85.1%) of ezrin-overexpressing tumors coexpressed phosphorylated RhoA; 78.8% of tumors with phosphorylated RhoA cooverexpressed ezrin.Patients whose cancers showed overexpression of ezrin or expression of phosphorylated RhoA had shorter survival rates.Conclusions RhoA activation is important in human breast cancer due to its upregulation of ezrin; thus,agents that target phosphorylated RhoA may be useful in the treatment of tumors with ezrin overexpression.

  8. Antimicrobial activity of copaíba (Copaifera langsdorffii oleoresin on bacteria of clinical significance in cutaneous wounds

    Directory of Open Access Journals (Sweden)

    D.S. Masson

    2013-01-01

    Full Text Available The present study was designed to evaluate the in vitro antimicrobial activity of Copaifera langsdorffii oleoresin, which has been used in folk medicine as an anti-inflammatory, antibacterial, healing among others. The oleoresin was tested against Gram-positive (Staphylococcus aureus, Streptococcus pyogenes, Enterococcus faecalis and Gram-negative (Pseudomonas aeruginosa and Escherichia coli bacteria related to infections in cutaneous wounds. Antimicrobial activity was determined by the minimum inhibitory concentration (MIC and minimum bactericidal concentration (MBC assays. Copaiba oleoresin showed antimicrobial activity only against the Gram-positive bacteria with MIC of 200 μg/mL, 400 μg/mL and 1100 μg/mL for S. aureus, S. pyogenes and E. faecalis, respectively. MBC values were the same as MIC for S. aureus and S. pyogenes and for E. faecalis it was 1200 μg/mL. Considering that infection significantly impairs the wound healing process, we believe that the use of copaiba oleoresin as a component of a topical formulation could be a valuable adjunct in the treatment of infected wounds, mainly in the case of wounds infected by Gram-positive microorganisms.

  9. Antimicrobial Activities of Five Strains Of Lactococcus Isolated from Beef Against Indicator Organisms of Public Health Significance

    Directory of Open Access Journals (Sweden)

    Olusegun Ayodele Olaoye

    2016-10-01

    Full Text Available Five strains of Lactococcus, including L. garviae K2, L. piscium SU4, L. lactis subsp. cremoris E22, L. plantarum L7 and L. lactis subsp. hordinae E91 were screened for production of antimicrobial agents. The strains were also analysed for antimicrobial activities against spoilage and pathogenic organisms, including Staphylococcus aureus, Salmonella Typhimurium, Escherichia coli, Yersinia enterocolitica, Pseudomonas aeruginosa, Klebsiella pneumoniae, Listeria monocytogenes, Bacillus cereus and Pseudomonas fluorescens. Result revealed that L. piscium SU4, L. plantarum L7 and L. lactis subsp. cremoris E22 had lactic acid production (g/107 colony forming units, CFU of 7.23, 7.20 and 7.19. The value of 6.83 recorded as lactic acid produced by L. garviae K2 was significantly different from those obtained for others. The highest acetic acid production (3.55 g/107 CFU was recorded for L. garviae K2 while L. piscium SU4 had the lowest (2.99 g/107 CFU. L. lactis subsp. hordinae E91 had diacetyl production of 71.99 (µg/107 CFU, which was higher than those recorded for other Lactococcus strains. Test for antimicrobial activities showed that Escherichia coli NCTC 86, Yersinia enterocolitica NCTC 10460, Pseudomonas aeruginosa NCIMB 10848, Bacillus cereus NCTC 21113 and Pseudomonas flourescens recorded higher susceptibilities to the antimicrobial action of the Lactococcus strains than others; zones of inhibition of 5 mm and above were recorded for the indicator organisms compared to lower values (<5 mm obtained for others. Listeria monocytogenes also showed medium susceptibility (zones of inhibition <5 mm to the antimicrobial activities of the Lactococcus strains. It was concluded that the Lactococcus strains could be effective in the control of spoilage and pathogenic organisms; their antagonism recorded against Listeria monocytogenes, E. coli, Salmonella Typhimurium and Staphylococcus aureus may be of public health significance.

  10. 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.

  11. 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.

  12. 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.

  13. 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...

  14. 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.

  15. 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.

  16. 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.

  17. Significance of the carbonization of volatile pyrolytic products on the properties of activated carbons from phosphoric acid activation of lignocellulosic material

    Energy Technology Data Exchange (ETDEWEB)

    Zuo, Songlin; Yang, Jianxiao; Cai, Xuan [Faculty of Chemical Engineering, Nanjing Forestry University, Nanjing 210037 (China); Liu, Junli [Institute of Chemical Industry of Forest Products, CAF, Nanjing 210042 (China)

    2009-07-15

    Two series of activated carbons derived from China fir (Cunninghamia lanceolata) wood impregnated with phosphoric acid were prepared in a cylindrical container that was kept in a closed state covered with a lid (the covered case) or in an open state. The effects of the carbonization of volatile pyrolytic products of starting materials on the properties of activated carbon were investigated in the process of phosphoric acid activation. Elemental analysis and SEM observation showed that both activating in the covered case and increasing the mass of starting material used favored the carbonization of volatile pyrolytic products. An investigation of N{sub 2} adsorption isotherms revealed that the carbonization of volatile pyrolytic products significantly enhanced mesopore development in the final carbons, especially pores with a size range from 2.5 to 30 nm, with little influence on micropores, and therefore produced a large increase in the adsorption capacity to Vitamin B12 (with a molecular size of 2.09 nm). Activated carbons with highly developed mesopores could be obtained in the covered case. The carbonization mechanism of volatiles was discussed and two different carbonization pathways (in solid and gas phases) were proposed during phosphoric acid activation. (author)

  18. Increase of electrodermal activity of heart meridian during physical exercise: the significance of electrical values in acupuncture and diagnostic importance.

    Science.gov (United States)

    Pontarollo, Francesco; Rapacioli, Giuliana; Bellavite, Paolo

    2010-08-01

    Electric field measurements of skin potential and electrical currents are physiological indicators of electrodermal activity (EDA) and have been associated with a variety of sensory, cognitive and emotional stimuli. The aim of this study was to investigate the EDA at some hand acupoints before, during and after a physical exercise. EDA of eight points located at the corner of fingernails of hands was measured in 10 healthy young volunteers before, during and after a 14-min acute exercise in a bicycle ergometer. In pre-exercise resting state the parameters were stable and similar between the 8 different tested points, while during exercise a significant increase of current (from 1000-2000 to 4000-8000 nA) was observed, with the maximal values related to the point located on the ulnar side of the little finger, at the base of the nail, corresponding to the Shao chong (HT9) of heart meridian. Copyright 2010 Elsevier Ltd. All rights reserved.

  19. Significance of crystallinity on the photoelectrochemical and photocatalytic activity of TiO{sub 2} nanotube arrays

    Energy Technology Data Exchange (ETDEWEB)

    Nishanthi, S.T.; Iyyapushpam, S.; Sundarakannan, B. [Department of Physics, Manonmaniam Sundaranar University, Tirunelveli 627012, Tamil Nadu (India); Subramanian, E. [Department of Chemistry, Manonmaniam Sundaranar University, Tirunelveli 627012, Tamil Nadu (India); Pathinettam Padiyan, D., E-mail: dppadiyan@msuniv.ac.in [Department of Physics, Manonmaniam Sundaranar University, Tirunelveli 627012, Tamil Nadu (India)

    2014-09-15

    Highlights: • Increase in anodization time improves the crystallinity of nanotubes. • Higher crystalline one showed lower band gap for TiO{sub 2}. • Photoelectrochemical and photocatalytic activity depends on crystallinity. - Abstract: We report the significance of crystallinity on photoelectrochemical and the photocatalytic degradation of methyl orange of titanium dioxide (TiO{sub 2}) nanotube arrays. The TiO{sub 2} nanotube arrays are fabricated by electrochemical anodization of titanium substrates in fluoride based aqueous electrolyte for various anodization time. The degree of crystallinity and phase purity (anatase) is confirmed from X-ray diffraction and Raman spectra. High resolution scanning electron microscope is used to analyze the surface morphology of forming nanotubes. The UV–vis absorption spectrum shows the enhanced absorption in the visible region which is further confirmed using photoluminescence spectra. The photoelectrochemical properties of the prepared samples are studied from linear sweep photovoltammetry measurements and a maximum photocurrent density of 1.32 mA/cm{sup 2} is observed. The enhanced photoelectrochemical activity is attributed to the higher crystallinity which increases the charge carrier separation and extends its light absorption from ultraviolet to visible region owing to lower band gap of 2.751(7) eV.

  20. [Clinical significance of a physical activity index based on calorimetry in the assessment of quality of life after total gastrectomy].

    Science.gov (United States)

    Sakamoto, K; Nakano, G; Kato, R; Suzuki, T; Nagamachi, Y; Nakamura, T; Hashimoto, I

    1987-04-01

    In order to characterize the objective diagnostic criteria concerning quality of life (QL) of patients after total gastrectomy, a physical activity index (PAI) or a concept of daily physical activity was developed. Sixty patients of gastric cancer, of whom 38 patients underwent long loop Roux-en-Y gastrojejunostomy (LLRY) procedure after total gastrectomy, 13 patients gastroduodenostomy (Billroth I) and 9 patients gastrojejunostomy (Billroth II) after subtotal gastrectomy, respectively, were evaluated as part of this study. In addition, 3 cases of pancreatoduodenectomy (PD) and 5 cases of total esophagectomy were also evaluated. The evaluation of QL was based upon a clinical assessment and administration of patient questionnaire. The assessment of the PAI was performed by measuring the individual's whole day energy expenditure based upon 24 hour heart rate ratio (24h-HRR) method and the basal metabolic energy expenditure. The daily physical activity was graded into four categories according to the PAI value; light, moderate, moderately heavy and heavy. The results obtained were as follows: The value of the energy expenditure predicted by 24h-HRR method and that based on the results of bicycle ergometry (VO2/HR method) showed close correlation. There was no significant difference in the whole day energy expenditure among four operative procedure groups (Billroth I, Billroth II, LLRY and total esophagectomy). More than 80 per cent of LLRY patients, whose QL was evaluated as "excellent" or "good", showed no less than "moderate" PAI. In addition, one of the four patients whose QL was "fair" was categorized into "light" and the remaining three were "moderate".(ABSTRACT TRUNCATED AT 250 WORDS)

  1. 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.

  2. 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.

  3. 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.

  4. Significance of the hepatitis C virus (HCV core antigen as an alternative plasma marker of active HCV infection

    Directory of Open Access Journals (Sweden)

    Daniel HDJ

    2007-01-01

    Full Text Available Purpose: To evaluate the role of core antigen (Ortho trak-C assay as a marker of active HCV infection in comparison to HCV RNA as detected by reverse transcription polymerase chain reaction (RT-PCR. Methods: This evaluation was carried out during January 2000 to December 2003 in HCV infected individuals who were treatment naοve or were on anti-viral therapy. Additionally, sequential plasma samples from patients on clinical follow-up were included in this study. A total of 167 samples from 61 patients were tested by trak-C and RT-PCR. HCV RNA detection was achieved by a RT-PCR. Trak-C assay results were also compared in a limited proportion of these samples with known HCV viral load and genotype. Results: Of 167 samples tested, 56.9% were RNA positive and 43.1% were RNA negative while 50.3% were trak-C positive and 49.7% were trak-C negative, yielding a sensitivity of 85.3% and a specificity of 95.8% for the trak-C assay (Kappa co-efficient = 0.8. The concentration of HCVcAg and HCV RNA showed significant correlation (n=38, r=0.334, P =0.04. The trak-C assay detected the most prevalent HCV genotypes in India without significant difference ( P =0.335. The difference between mean absorbance values of HCV RNA positive samples compared to HCV RNA negative samples in the trak-C assay was highly significant ( P < 0.000. Qualitative results of trak-C assay and RT-PCR were comparable in 93% of follow-up samples. Conclusions: Trak-C assay can be recommended for confirmation of HCV infection and follow-up in laboratories with resource-poor facilities.

  5. Efficacious gene silencing in serum and significant apoptotic activity induction by survivin downregulation mediated by new cationic gemini tocopheryl lipids.

    Science.gov (United States)

    Kumar, Krishan; Maiti, Bappa; Kondaiah, Paturu; Bhattacharya, Santanu

    2015-02-02

    Nonviral gene delivery offers cationic liposomes as promising instruments for the delivery of double-stranded RNA (ds RNA) molecules for successful sequence-specific gene silencing (RNA interference). The efficient delivery of siRNA (small interfering RNA) to cells while avoiding unexpected side effects is an important prerequisite for the exploitation of the power of this excellent tool. We present here six new tocopherol based cationic gemini lipids, which induce substantial gene knockdown without any obvious cytotoxicity. All the efficient coliposomal formulations derived from each of these geminis and a helper lipid, dioleoylphosphatidylethanolamine (DOPE), were well characterized using physical methods such as atomic force microscopy (AFM) and dynamic light scattering (DLS). Zeta potential measurements were conducted to estimate the surface charge of these formulations. Flow cytometric analysis showed that the optimized coliposomal formulations could transfect anti-GFP siRNA efficiently in three different GFP expressing cell lines, viz., HEK 293T, HeLa, and Caco-2, significantly better than a potent commercial standard Lipofectamine 2000 (L2K) both in the absence and in the presence of serum (FBS). Notably, the knockdown activity of coliposomes of gemini lipids was not affected even in the presence of serum (10% and 50% FBS) while it dropped down for L2K significantly. Observations under a fluorescence microscope, RT-PCR, and Western blot analysis substantiated the flow cytometry results. The efficient cellular entry of labeled siRNA in GFP expressing cells as evidenced from confocal microscopy put forward these gemini lipids among the potent lipidic carriers for siRNA. The efficient transfection capabilities were also profiled in a more relevant fashion while performing siRNA transfections against survivin (an anti-apoptotic protein) which induced substantial apoptosis. Furthermore, the survivin downregulation improved the therapeutic efficacy levels of an

  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. 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.

  8. 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.

  9. 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.

  10. 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.

  11. Clinicopathological significance of plasminogen activator inhibitor-1 gene polymorphism in breast cancer patients from North West of Iran

    Directory of Open Access Journals (Sweden)

    M Younesi

    2016-06-01

    Full Text Available Introduction: A common polymorphism 4G/5G in the promoter region of the Plasminogen activator inhibitor-1 (PAI-1 gene has been reported to influence the expression levels of PAI-1. According to the evidence, progression of breast cancer can be associated with elevated levels of PAI-1, it seems that evaluation of a possible correlation between the polymorphism and clinical status of breast cancer patients is reasonable. Methods: This descriptive-analytical study included 160 unrelated patients from North West of Iran. According to established clinical criteria, these paitients were diagnosed with breast cancer. Based on previous study, PAI-1 4G/5G had been determined. In order to investigate the association of this polymorphism with clinicopathological features Fisher’s exact tests and SPSS software was used with a significance level of 0.05. Results: All declared features of breast cancer regarding PAI-1 4G/5G polymorphism were investigated. Results indicated that PAI-1 4G/5G polymorphism positive correlation with several traditional prognostic factors, including tumor size, lymph node metastases and tumor stage. Conclusion: Data showed that the patients with 5G/5G genotype are more susceptible to the development of breast cancer, while the paitients with 4G/4G and 4G/5G genotypes show lower sensitivity to the breast cancer. Therefore, the 4G allele likely has a protective role against the development of breast cancer in this cohort.

  12. Significant change of local atomic configurations at surface of reduced activation Eurofer steels induced by hydrogenation treatments

    Science.gov (United States)

    Greculeasa, S. G.; Palade, P.; Schinteie, G.; Kuncser, A.; Stanciu, A.; Lungu, G. A.; Porosnicu, C.; Lungu, C. P.; Kuncser, V.

    2017-04-01

    Reduced-activation steels such as Eurofer alloys are candidates for supporting plasma facing components in tokamak-like nuclear fusion reactors. In order to investigate the impact of hydrogen/deuterium insertion in their crystalline lattice, annealing treatments in hydrogen atmosphere have been applied on Eurofer slabs. The resulting samples have been analyzed with respect to local structure and atomic configuration both before and after successive annealing treatments, by X-ray diffractometry (XRD), scanning electron microscopy and energy dispersive spectroscopy (SEM-EDS), X-ray photoelectron spectroscopy (XPS) and conversion electron Mössbauer spectroscopy (CEMS). The corroborated data point out for a bcc type structure of the non-hydrogenated alloy, with an average alloy composition approaching Fe0.9Cr0.1 along a depth of about 100 nm. EDS elemental maps do not indicate surface inhomogeneities in concentration whereas the Mössbauer spectra prove significant deviations from a homogeneous alloying. The hydrogenation increases the expulsion of the Cr atoms toward the surface layer and decreases their oxidation, with considerable influence on the surface properties of the steel. The hydrogenation treatment is therefore proposed as a potential alternative for a convenient engineering of the surface of different Fe-Cr based alloys.

  13. Significance exaggerated of the activity of the construction in Spain; inflection and current decline? The difficult to their sostenibilitiy

    Directory of Open Access Journals (Sweden)

    José María Serrano

    2010-04-01

    Full Text Available For some time the activity of the construction, in its different sections, (housings, works with non residential ends, transport, public works… has had special significance inside the productive system in Spain. During the last decade it has reached an exaggerated weight, so much in their participation in the GDP like of people occupied in her. The some regions that proportion represents exaggerated ends. The current economic crisis has affected with intensity to the group of the sector of the construction, making more intense the consequences of the economic recession. Everything it, is not only as a consequence of a crisis of the situation. Rather she is due to structural reasons. It seems probable that, from now on, the group of the Spanish economic system, it should be articulated with a new organization, a new productive model, where the construction only means a more reduced part of the same one. That is easy to say, but very difficult of getting it. It represents a great challenge face to the future.

  14. Demonstration of natriuretic activity in urine of neurosurgical patients with renal salt wasting [v2; ref status: indexed, http://f1000r.es/1ax

    Directory of Open Access Journals (Sweden)

    Steven J Youmans

    2013-06-01

    Full Text Available We have utilized the persistent elevation of fractional excretion (FE of urate, > 10%, to differentiate cerebral/renal salt wasting (RSW from the syndrome of inappropriate antidiuretic hormone secretion (SIADH, in which a normalization of FEurate occurs after correction of hyponatremia.  Previous studies suggest as well  that an elevated FEurate with normonatremia, without pre-existing hyponatremia, is also consistent with RSW, including studies demonstrating induction of RSW in rats infused with plasma from normonatremic neurosurgical and Alzheimer’s disease patients.  The present studies were designed to test whether precipitates from the urine of normonatremic neurosurgical patients, with either normal or elevated FEurate, and patients with SIADH, display natriuretic activity.   Methods: Ammonium sulfate precipitates from the urine of 6 RSW and 5 non-RSW Control patients were dialyzed (10 kDa cutoff to remove the ammonium sulfate, lyophilized, and the reconstituted precipitate was tested for its effect on transcellular transport of 22Na across LLC-PK1 cells grown to confluency in transwells. Results: Precipitates from 5 of the 6 patients with elevated FEurate and normonatremia significantly inhibited the in vitro transcellular transport of 22Na above a concentration of 3 μg protein/ml, by 10-25%, versus to vehicle alone, and by 15-40% at concentrations of 5-20 μg/ml as compared to precipitates from 4 of the 5 non-RSW patients with either normal FEurate and normonatremia (2 patients or with SIADH (2 patients. Conclusion: These studies provide further evidence that an elevated FEurate with normonatremia is highly consistent with RSW.  Evidence in the urine of natriuretic activity suggests significant renal excretion of the natriuretic factor. The potentially large source of the natriuretic factor that this could afford, coupled with small analytical sample sizes required by the in-vitro bioassay used here, should facilitate future

  15. Demonstration of natriuretic activity in urine of neurosurgical patients with renal salt wasting [v1; ref status: indexed, http://f1000r.es/nu

    Directory of Open Access Journals (Sweden)

    Steven J Youmans

    2013-05-01

    Full Text Available We have utilized the persistent elevation of fractional excretion (FE of urate, > 10%, to differentiate cerebral/renal salt wasting (RSW from the syndrome of inappropriate antidiuretic hormone secretion (SIADH, in which a normalization of FEurate occurs after correction of hyponatremia.  Previous studies suggest as well  that an elevated FEurate with normonatremia, without pre-existing hyponatremia, is also consistent with RSW, including studies demonstrating induction of RSW in rats infused with plasma from normonatremic neurosurgical and Alzheimer’s disease patients.  The present studies were designed to test whether precipitates from the urine of normonatremic neurosurgical patients, with either normal or elevated FEurate, and patients with SIADH, display natriuretic activity.   Methods: Ammonium sulfate precipitates from the urine of 6 RSW and 5 non-RSW Control patients were dialyzed (10 kDa cutoff to remove the ammonium sulfate, lyophilized, and the reconstituted precipitate was tested for its effect on transcellular transport of 22Na across LLC-PK1 cells grown to confluency in transwells. Results: Precipitates from 5 of the 6 patients with elevated FEurate and normonatremia significantly inhibited the in vitro transcellular transport of 22Na above a concentration of 3 μg protein/ml, by 10-25%, versus to vehicle alone, and by 15-40% at concentrations of 5-20 μg/ml as compared to precipitates from 4 of the 5 non-RSW patients with either normal FEurate and normonatremia (2 patients or with SIADH (2 patients. Conclusion: These studies provide further evidence that an elevated FEurate with normonatremia is highly consistent with RSW.  Evidence in the urine of natriuretic activity suggests significant renal excretion of the natriuretic factor. The potentially large source of the natriuretic factor that this could afford, coupled with small analytical sample sizes required by the in-vitro bioassay used here, should facilitate future

  16. Antibody-Dependent Cell-Mediated Cytotoxicity Effector-Enhanced EphA2 Agonist Monoclonal Antibody Demonstrates Potent Activity against Human Tumors

    Directory of Open Access Journals (Sweden)

    Elizabeth M. Bruckheimer

    2009-06-01

    Full Text Available EphA2 is a receptor tyrosine kinase that has been shown to be overexpressed in a variety of human tumor types. Previous studies demonstrated that agonist monoclonal antibodies targeting EphA2 induced the internalization and degradation of the receptor, thereby abolishing its oncogenic effects. In this study, the in vitro and in vivo antibody-dependent cell-mediated cytotoxicity (ADCC activity of EphA2 effector-enhanced agonist monoclonal antibodies was evaluated. With tumor cell lines and healthy human peripheral blood monocytes, the EphA2 antibodies demonstrated ∼80% tumor cell killing. In a dose-dependent manner, natural killer (NK cells were required for the in vitro ADCC activity and became activated as demonstrated by the induction of cell surface expression of CD107a. To assess the role of NK cells on antitumor efficacy in vivo, the EphA2 antibodies were evaluated in xenograft models in severe compromised immunodeficient (SCID mice (which have functional NK cells and monocytes and SCID nonobese diabetic (NOD mice (which largely lack functional NK cells and monocytes. Dosing of EphA2 antibody in the SCID murine tumor model resulted in a 6.2-fold reduction in tumor volume, whereas the SCID/nonobese diabetic model showed a 1.6-fold reduction over the isotype controls. Together, these results demonstrate that the anti-EphA2 monoclonal antibodies may function through at least two mechanisms of action: EphA2 receptor activation and ADCC-mediated activity. These novel EphA2 monoclonal antibodies provide additional means by which host effector mechanisms can be activated for selective destruction of EphA2-expressing tumor cells.

  17. Silibinin and Paclitaxel Cotreatment Significantly Suppress the Activity and Lung Metastasis of Triple Negative 4T1 Mammary Tumor Cell in Mice

    Directory of Open Access Journals (Sweden)

    Bing-Ying Ho

    2012-10-01

    Full Text Available The in vitro and in vivo bioactivities of silibinin (SB, paclitaxel (PTX and SB and PTX in combination (SB+PTX against murine metastatic mammary 4T1 cancer cell line were investigated. Isobologram and combination index (CI analyses showed that SB and PTX can function synergistically in the inhibition of 4T1 cell proliferation with a CI value<1. Both SB and PTX alone or SB+PTX treatment inhibited 4T1 cell migration and motility possibly through downregulation of the serpin protease nexin-1 (PN-1 and N-cadherin expression, inhibition of matrix metalloprotease (MMP-9 activity, and upregulation of E-cadherin. Flow cytometry and Western blot analyses demonstrated that both drugs deregulated cell-cycle mediators and induced apoptosis in 4T1 cells. A real-time in vivo bioluminescence imaging system to monitor the breast cancer cell metastasis in syngeneic BALB/c mice was established using a stable 4T1pGL−COX−2/Luc cell clone carrying a COX-2 promoter driven-luciferase reporter gene. In vivo study using the allograft 4T1pGL−COX−2/Luc metastatic mouse model indicated that SB co-treated with PTX can significantly suppress lung metastasis of 4T1 cells likely through inhibiting cell proliferation and angiogenesis. Together, this study demonstrates that SB could act synergistically with PTX in 4T1 cells, providing a therapeutic option for highly metastatic triple negative breast cancer.

  18. Clinicopathological significance of plasminogen activator inhibitor-1 promoter 4G/5G polymorphism in breast cancer: a meta-analysis.

    Science.gov (United States)

    Lee, Ju-Han; Kim, Younghye; Choi, Jung-Woo; Kim, Young-Sik

    2013-01-01

    Plasminogen activator inhibitor type 1 (PAI-1) is associated with poor prognosis in breast cancer. Transcriptional expression of the PAI-1 can be controlled by PAI-1 promoter 4G/5G polymorphism. However, the significance of PAI-1 promoter 4G/5G polymorphism in breast cancer patients is contentious. To address this controversy, we conducted a meta-analysis for the relationships between PAI-1 promoter polymorphism and clinicopathological characteristics of breast cancer. Relevant published studies were identified using a search of PubMed, Embase, and the ISI Web of Science. The effect sizes of PAI-1 promoter 4G/5G polymorphism on breast cancer risk, lymph node metastasis, histologic grade, and overall survival were calculated by odds ratio (OR) or hazard ratio. The effect sizes were combined using a random-effects model. Individuals with 4G/4G genotype had a higher risk of breast cancer than those with the combined 4G/5G and 5G/5G genotypes (OR = 1.388; p = 0.031). Breast cancer patients with the 5G/5G genotype displayed lymph node metastasis more than patients with either the combined other genotypes (OR = 1.495; p = 0.027) or with the 4G/4G genotype (OR = 1.623; p = 0.018). However, the PAI-1 promoter 4G/5G polymorphism was not associated with histological grade or overall survival. PAI-1 promoter 4G/5G polymorphism is associated with a relatively increased risk of breast cancer development and lymph node metastasis. Copyright © 2013 IMSS. Published by Elsevier Inc. All rights reserved.

  19. 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

  20. Delaying discharge after the stimulus significantly decreases muscle activation thresholds with small impact on the selectivity: an in vivo study using TIME.

    Science.gov (United States)

    Maciejasz, Paweł; Badia, Jordi; Boretius, Tim; Andreu, David; Stieglitz, Thomas; Jensen, Winnie; Navarro, Xavier; Guiraud, David

    2015-04-01

    The number of devices for electrical stimulation of nerve fibres implanted worldwide for medical applications is constantly increasing. Stimulation charge is one of the most important parameters of stimulation. High stimulation charge may cause tissue and electrode damage and also compromise the battery life of the electrical stimulators. Therefore, the objective of minimizing stimulation charge is an important issue. Delaying the second phase of biphasic stimulation waveform may decrease the charge required for fibre activation, but its impact on stimulation selectivity is not known. This information is particularly relevant when transverse intrafascicular multichannel electrode (TIME) is used, since it has been designed to provide for high selectivity. In this in vivo study, the rat sciatic nerve was electrically stimulated using monopolar and bipolar configurations with TIME. The results demonstrated that the inclusion of a 100-μs delay between the cathodic and the anodic phase of the stimulus allows to reduce charge requirements by around 30 %, while only slightly affecting stimulation selectivity. This study shows that adding a delay to the typical stimulation waveform significantly ([Formula: see text]) reduces the charge required for nerve fibres activation. Therefore, waveforms with the delayed discharge phase are more suitable for electrical stimulation of nerve fibres.

  1. Choosing Outcomes of Significance.

    Science.gov (United States)

    Spady, William G.

    1994-01-01

    Outcomes are high-quality, culminating demonstrations of significant learning in context. The High Success Network uses the "Demonstration Mountain" to differentiate among three major "learning zones" and six different forms of learning demonstrations that increase in complexity, generalizability, and significance, along with…

  2. Genetically re-engineered K562 cells significantly expand and functionally activate cord blood natural killer cells: Potential for adoptive cellular immunotherapy.

    Science.gov (United States)

    Ayello, Janet; Hochberg, Jessica; Flower, Allyson; Chu, Yaya; Baxi, Laxmi V; Quish, William; van de Ven, Carmella; Cairo, Mitchell S

    2017-02-01

    Natural killer (NK) cells play a significant role in reducing relapse in patients with hematological malignancies after allogeneic stem cell transplantation, but NK cell number and naturally occurring inhibitory signals limit their capability. Interleukin-15 (IL-15) and 4-1BBL are important modulators of NK expansion and functional activation. To overcome these limitations, cord blood mononuclear cells (CB MNCs) were ex vivo expanded for 7 days with genetically modified K562-mbIL15-41BBL (MODK562) or wild-type K562 (WTK562). NK cell expansion; expression of lysosome-associated membrane protein-1 (LAMP-1), granzyme B, and perforin; and in vitro and in vivo cytotoxicity against B-cell non-Hodgkin lymphoma (B-NHL) were evaluated. In vivo tumor growth in B-NHL-xenografted nonobese diabetic severe combined immune deficient (NOD-scid) gamma (NSG) mice was monitored by tumor volume, cell number, and survival. CB MNCs cultured with MODK562 compared with WTK562 demonstrated significantly increased NK expansion (thirty-fivefold, p cell numbers (p cells to enhance B-NHL targeting in vitro and in vivo. Copyright © 2016 ISEH - International Society for Experimental Hematology. Published by Elsevier Inc. All rights reserved.

  3. Exploration Medical System Demonstration

    Science.gov (United States)

    Rubin, D. A.; Watkins, S. D.

    2014-01-01

    BACKGROUND: Exploration class missions will present significant new challenges and hazards to the health of the astronauts. Regardless of the intended destination, beyond low Earth orbit a greater degree of crew autonomy will be required to diagnose medical conditions, develop treatment plans, and implement procedures due to limited communications with ground-based personnel. SCOPE: The Exploration Medical System Demonstration (EMSD) project will act as a test bed on the International Space Station (ISS) to demonstrate to crew and ground personnel that an end-to-end medical system can assist clinician and non-clinician crew members in optimizing medical care delivery and data management during an exploration mission. Challenges facing exploration mission medical care include limited resources, inability to evacuate to Earth during many mission phases, and potential rendering of medical care by non-clinicians. This system demonstrates the integration of medical devices and informatics tools for managing evidence and decision making and can be designed to assist crewmembers in nominal, non-emergent situations and in emergent situations when they may be suffering from performance decrements due to environmental, physiological or other factors. PROJECT OBJECTIVES: The objectives of the EMSD project are to: a. Reduce or eliminate the time required of an on-orbit crew and ground personnel to access, transfer, and manipulate medical data. b. Demonstrate that the on-orbit crew has the ability to access medical data/information via an intuitive and crew-friendly solution to aid in the treatment of a medical condition. c. Develop a common data management framework that can be ubiquitously used to automate repetitive data collection, management, and communications tasks for all activities pertaining to crew health and life sciences. d. Ensure crew access to medical data during periods of restricted ground communication. e. Develop a common data management framework that

  4. Demonstration of extracellular peptidylarginine deiminase (PAD) activity in synovial fluid of patients with rheumatoid arthritis using a novel assay for citrullination of fibrinogen

    DEFF Research Database (Denmark)

    Damgaard, Dres; Senolt, Ladislav; Nielsen, Michael Friberg

    2014-01-01

    INTRODUCTION: Members of the peptidylarginine deiminase (PAD) family catalyse the posttranslational conversion of peptidylarginine to peptidylcitrulline. Citrullination of proteins is well described in rheumatoid arthritis (RA), and hypercitrullination of proteins may be related to inflammation...... in general. PAD activity has been demonstrated in various cell lysates, but so far not in synovial fluid. We aimed to develop an assay for detection of PAD activity, if any, in synovial fluid from RA patients. METHODS: An enzyme-linked immunosorbent assay using human fibrinogen as the immobilized substrate...... for citrullination and anti-citrullinated fibrinogen antibody as the detecting agent were used for measurement of PAD activity in synovial fluid samples from five RA patients. The concentrations of PAD2 and calcium were also determined. RESULTS: Approximately 150 times lower levels of recombinant human PAD2 (rhPAD2...

  5. Simultaneous production of l-lactic acid with high optical activity and a soil amendment with food waste that demonstrates plant growth promoting activity.

    Science.gov (United States)

    Kitpreechavanich, Vichien; Hayami, Arisa; Talek, Anfal; Chin, Clament Fui Seung; Tashiro, Yukihiro; Sakai, Kenji

    2016-07-01

    A unique method to produce highly optically-active l-lactic acid and soil amendments that promote plant growth from food waste was proposed. Three Bacillus strains Bacillus subtilis KBKU21, B. subtilis N3-9 and Bacillus coagulans T27, were used. Strain KBKU21 accumulated 36.9 g/L l-lactic acid with 95.7% optical activity and 98.2% l-lactic acid selectivity when fermented at 43°C for 84 h in a model kitchen refuse (MKR) medium. Residual precipitate fraction (anaerobically-fermented MKR (AFM) compost) analysis revealed 4.60%, 0.70% and 0.75% of nitrogen (as N), phosphorous (as P2O5), and potassium (as K2O), respectively. Additionally, the carbon to nitrogen ratio decreased from 13.3 to 10.6. AFM compost with KBKU21 promoted plant growth parameters, including leaf length, plant height and fresh weight of Brassica rapa (Komatsuna), than that by chemical fertilizers or commercial compost. The concept provides an incentive for the complete recycling of food waste, contributing towards a sustainable production system.

  6. Active Flow Control (AFC) and Insect Accretion and Mitigation (IAM) System Design and Integration on the Boeing 757 ecoDemonstrator

    Science.gov (United States)

    Alexander, Michael G.; Harris, F. Keith; Spoor, Marc A.; Boyland, Susannah R.; Farrell, Thomas E.; Raines, David M.

    2016-01-01

    This paper presents a systems overview of how the Boeing and NASA team designed, analyzed, fabricated, and integrated the Active Flow Control (AFC) technology and Insect Accretion Mitigation (IAM) systems on the Boeing 757 ecoDemonstrator. The NASA Environmentally Responsible Aviation (ERA) project partnered with Boeing to demonstrate these two technology systems on a specially outfitted Boeing 757 ecoDemonstrator during the spring of 2015. The AFC system demonstrated attenuation of flow separation on a highly deflected rudder and increased the side force generated. This AFC system may enable a smaller vertical tail to provide the control authority needed in the event of an engine failure during takeoff while still operating in a conventional manner over the rest of the flight envelope. The AFC system consisted of ducting to obtain air from the Auxiliary Power Unit (APU), a control valve to modulate the system mass flow, a heat exchanger to lower the APU air temperature, and additional ducting to deliver the air to the AFC actuators located on the vertical tail. The IAM system demonstrated how to mitigate insect residue adhesion on a wing's leading edge. Something as small as insect residue on a leading edge can cause turbulent wedges that interrupt laminar flow, resulting in an increase in drag and fuel use. The IAM system consisted of NASA developed Engineered Surfaces (ES) which were thin aluminum sheet substrate panels with coatings applied to the exterior. These ES were installed on slats 8 and 9 on the right wing of the 757 ecoDemonstrator. They were designed to support panel removal and installation in one crew shift. Each slat accommodated 4 panels. Both the AFC and IAM flight test were the culmination of several years of development and produced valuable data for the advancement of modern aircraft designs.

  7. Shortened telomere length is demonstrated in T-cell subsets together with a pronounced increased telomerase activity in CD4 positive T cells from blood of patients with mycosis fungoides and parapsoriasis.

    Science.gov (United States)

    Wu, K D; Hansen, E R

    2001-10-01

    We have recently demonstrated that telomerase activity is increased and telomere length shortened in lymphocytes from peripheral blood of patients with cutaneous T-cell lymphoma. In order to determine which cell type has increased telomerase activity and shortened telomere length, CD4+, CD8+, CLA+ CD3+ and CLA- CD3+ T cells were isolated from peripheral blood of 25 patients, including 15 patients with mycosis fungoides and 10 patients with parapsoriasis. Eleven healthy individuals were used as controls; CD19+ B cells were separated from each individual as an internal control. The results showed that the increased telomerase activity was significantly predominating in the CD4+ T-cell subset. Significantly shortened telomere length was found in CD4+ and CD8+ T-cell subsets from the patients compared with the same cell subsets obtained from healthy individuals. However, no difference was observed between the subsets; CD19+ B cells collected from patients and healthy control individuals had similar telomerase activity and telomere length which was significantly different from the values found in T cells. The telomere length was significantly shorter in CLA+ CD3+ subset than in CLA- CD3+ subset. Interestingly, increased telomerase activity and shortened telomere length was also detected in CD4+ T cells from patients with parapsoriasis indicating that alteration of telomerase activity and telomere length in CD4+ T cells is an early event in the pathogenesis of cutaneous T-cell lymphoma. Thus, the results indicate that a significant high level of telomerase activity and shortened telomere length frequently occur in T cells of patients with CTCL and may reflect tumorigenesis.

  8. The C-terminal region of the non-structural protein 2B from Hepatitis A Virus demonstrates lipid-specific viroporin-like activity

    Science.gov (United States)

    Shukla, Ashutosh; Dey, Debajit; Banerjee, Kamalika; Nain, Anshu; Banerjee, Manidipa

    2015-10-01

    Viroporins are virally encoded, membrane-active proteins, which enhance viral replication and assist in egress of viruses from host cells. The 2B proteins in the picornaviridae family are known to have viroporin-like properties, and play critical roles during virus replication. The 2B protein of Hepatitis A Virus (2B), an unusual picornavirus, is somewhat dissimilar from its analogues in several respects. HAV 2B is approximately 2.5 times the length of other 2B proteins, and does not disrupt calcium homeostasis or glycoprotein trafficking. Additionally, its membrane penetrating properties are not yet clearly established. Here we show that the membrane interacting activity of HAV 2B is localized in its C-terminal region, which contains an alpha-helical hairpin motif. We show that this region is capable of forming small pores in membranes and demonstrates lipid specific activity, which partially rationalizes the intracellular localization of full-length 2B. Using a combination of biochemical assays and molecular dynamics simulation studies, we also show that HAV 2B demonstrates a marked propensity to dimerize in a crowded environment, and probably interacts with membranes in a multimeric form, a hallmark of other picornavirus viroporins. In sum, our study clearly establishes HAV 2B as a bona fide viroporin in the picornaviridae family.

  9. Work activity in food service: The significance of customer relations, tipping practices and gender for preventing musculoskeletal disorders.

    Science.gov (United States)

    Laperrière, Ève; Messing, Karen; Bourbonnais, Renée

    2017-01-01

    Some evidence shows that food servers are exposed to an elevated risk of musculoskeletal disorders and injuries, and that their work activity varies by gender. Interviews of servers and observations of food service in Québec, Canada, were carried out in three restaurants and a questionnaire was administered to 64 workers from 44 other restaurants. The relationship with the customer has specific effects on work activity and transforms the physical, emotional and cognitive work. Strategies intended to speed service or otherwise related to the customer relationship can involve health risks. Women reported more direct food service (p disorders in this population and that women are at particular risk. Copyright © 2016 Elsevier Ltd. All rights reserved.

  10. Significant interaction between activated charcoal and antiretroviral therapy leading to subtherapeutic drug concentrations, virological breakthrough and development of resistance.

    Science.gov (United States)

    Tseng, Alice L; la Porte, Charles; Salit, Irving E

    2013-01-01

    A 42-year-old, treatment-experienced woman, virologically suppressed on tenofovir/emtricitabine and boosted atazanavir, experienced virological breakthrough, drop in CD4(+) T-cell count and undetectable drug concentrations. Adherence to treatment was confirmed, but repeat testing yielded similar results. After 2 months, the patient stated that she had been taking activated charcoal to manage gastrointestinal symptoms associated with her combination antiretroviral therapy, but she had recently discontinued the charcoal. Atazanavir concentrations were therapeutic but the patient's viral load rebounded and genotype testing revealed new reverse transcriptase mutations. The patient was changed to zidovudine, lamivudine, and boosted darunavir and achieved viral suppression. At 1 year follow-up, her viral load remained activated charcoal and atazanavir/ritonavir leading to virological breakthrough and development of resistance.

  11. Cloud condensation nucleus activity comparison of dry- and wet-generated mineral dust aerosol: the significance of soluble material

    OpenAIRE

    S. Garimella; Huang, Y.-W.; Seewald, J. S.; D. J. Cziczo

    2014-01-01

    This study examines the interaction of clay mineral particles and water vapor for determining the conditions required for cloud droplet formation. Droplet formation conditions are investigated for two common clay minerals, illite and sodium-rich montmorillonite, and an industrially derived sample, Arizona Test Dust. Using wet and dry particle generation coupled to a differential mobility analyzer (DMA) and cloud condensation nuclei counter, the critical activation of the cla...

  12. Atmospherically-promoted photosynthetic activity in a well-mixed ecosystem: Significance of wet deposition events of nitrogen compounds

    OpenAIRE

    2006-01-01

    Wet atmospheric deposition of dissolved N, P and Si species is studied in well-mixed coastal ecosystem to evaluate its potential to stimulate photosynthetic activities in nutrient-depleted conditions. Our results show that, during spring, seawater is greatly depleted in major nutrients: Dissolved Inorganic Nitrogen (DIN), Dissolved Inorganic Phosphorus (DIP) and Silicic acid (Si), in parallel with an increase of phytoplanktonic biomass. In spring (March-May) and summer (June-September), wet a...

  13. 情感管理在优质护理服务示范工程活动中的应用效果评价%Application evaluation of emotion management in quality care demonstration project activities

    Institute of Scientific and Technical Information of China (English)

    冯鹤媛; 何剑; 崔映娟

    2012-01-01

    目的 探讨情感管理在优质护理服务示范工程活动中的作用.方法 制订优质护理服务示范工程活动实施方案和考核标准,实施情感管理,通过护理工作质量考核、患者满意度测评进行效果评价.结果 实施前后的护理工作质量、患者满意度均显著提高,差异均有高度统计学意义(均P < 0.01).结论 优质护理服务示范工程活动中实施情感管理可以有效提高护理工作质量和患者满意度,促进优质护理示范工程活动的深入开展.%Objective To explore the role of emotional management in quality care demonstration project activities. Methods Quality care demonstration project activities implementation plan and evaluation standards were developed. The implementation of emotional management, through the quality of care assessment, patient satisfaction measurement for effect e-valuation. Results The quality of care, patient satisfaction before and after implementation were significantly improved, there were significant different (all P < 0.01). Conclusion In the quality care demonstration project activities in the implementation of the emotional management can improve the quality of care, improve patient satisfaction, so as to promote quality care demonstration project activities in depth.

  14. Physiological and clinical significance of enterochromaffin-like cell activation in the regulation of gastric acid secretion

    Institute of Scientific and Technical Information of China (English)

    Guanglin Cui; Helge L Waldum

    2007-01-01

    Gastric acid plays an important role in digesting food (especially protein), iron absorption, and destroying swallowed micro-organisms. H+ is secreted by the oxyntic parietal cells and its secretion is regulated by endocrine, neurocrine and paracrine mechanisms.Gastrin released from the antral G cell is the principal physiological stimulus of gastric acid secretion. Activation of the enterochromaffin-like (ECL) cell is accepted as the main source of histamine participating in the regulation of acid secretion and is functionally and trophically controlled by gastrin, which is mediated by gastrin/CCK-2 receptors expressed on the ECL cell. However, longterm hypergastrinemia will induce ECL cell hyperplasia and probably carcinoids. Clinically, potent inhibitors of acid secretion have been prescribed widely to patients with acid-related disorders. Long-term potent acid inhibition evokes a marked increase in plasma gastrin levels,leading to enlargement of oxyntic mucosa with ECL cell hyperplasia. Accordingly, the induction of ECL cell hyperplasia and carcinoids remains a topic of considerable concern, especially in long-term use. In addition, the activation of ECL cells also induces another clinical concern, i.e., rebound acid hypersecretion after acid inhibition. Recent experimental and clinical findings indicate that the activation of ECL cells plays a critical role both physiologically and clinically in the regulation of gastric acid secretion.

  15. LIMB Demonstration Project Extension and Coolside Demonstration

    Energy Technology Data Exchange (ETDEWEB)

    Goots, T.R.; DePero, M.J.; Nolan, P.S.

    1992-11-10

    This report presents results from the limestone Injection Multistage Burner (LIMB) Demonstration Project Extension. LIMB is a furnace sorbent injection technology designed for the reduction of sulfur dioxide (SO[sub 2]) and nitrogen oxides (NO[sub x]) emissions from coal-fired utility boilers. The testing was conducted on the 105 Mwe, coal-fired, Unit 4 boiler at Ohio Edison's Edgewater Station in Lorain, Ohio. In addition to the LIMB Extension activities, the overall project included demonstration of the Coolside process for S0[sub 2] removal for which a separate report has been issued. The primary purpose of the DOE LIMB Extension testing, was to demonstrate the generic applicability of LIMB technology. The program sought to characterize the S0[sub 2] emissions that result when various calcium-based sorbents are injected into the furnace, while burning coals having sulfur content ranging from 1.6 to 3.8 weight percent. The four sorbents used included calcitic limestone, dolomitic hydrated lime, calcitic hydrated lime, and calcitic hydrated lime with a small amount of added calcium lignosulfonate. The results include those obtained for the various coal/sorbent combinations and the effects of the LIMB process on boiler and plant operations.

  16. Implementation of the k{sub 0}-standardization Method for an Instrumental Neutron Activation Analysis: Use-k{sub 0}-IAEA Software as a Demonstration

    Energy Technology Data Exchange (ETDEWEB)

    Chung, Yong Sam; Moon, Jong Hwa; Kim, Sun Ha; Kim, Hark Rho [Korea Atomic Energy Research Institute, Taejon (Korea, Republic of); Ho, Manh Dung [Nuclear Research Institute, Dalat (Viet Nam)

    2006-03-15

    Under the RCA post-doctoral program, from May 2005 through February 2006, it was an opportunity to review the present work being carried out in the Neutron Activation Analysis Laboratory, HANARO Center, KAERI. The scope of this research included: a calibration of the counting system, a characterization of the irradiation facility ,a validation of the established k{sub o}-NAA procedure.The k{sub o}-standardization method for an Neutron Activation Analysis(k{sub o}-NAA), which is becoming increasingly popular and widespread,is an absolute calibration technique where the nuclear data are replaced by compound nuclear constants which are experimentally determined. The k{sub o}-IAEA software distributed by the IAEA in 2005 was used as a demonstration for this work. The NAA no. 3 irradiation hole in the HANARO research reactor and the gamma-ray spectrometers No. 1 and 5 in the NAA Laboratory were used.

  17. Significantly Enhanced Hydrogen Evolution Activity of Freestanding Pd-Ru Distorted Icosahedral Clusters with less than 600 Atoms.

    Science.gov (United States)

    Dai, Zhihui; Liu, Suli; Zhang, Qinghua; Bao, Jianchun; Li, Yafei; Gu, Lin

    2017-07-24

    Freestanding metal nanoclusters can tune, precisely and effectively, the Gibbs free energy (ΔGH) of atomic hydrogen on the surface of materials. This enables the enhancement of hydrogen evolution activity. In this paper, we report a study of freestanding Pd-Ru distorted icosahedral clusters (ico-clusters) with less than 600 atoms using a simple one-pot synthesis method. This Pd-Ru ico-cluster can be used as an efficient electrocatalyst for the hydrogen evolution reaction (HER) in acidic water, which is a promising alternative to Pt. The experimental and theoretical results suggest that the fcc freestanding Pd-Ru distorted ico-clusters with less than 600 atoms ensure increased active edges and distorted defect sites that reduce the coordination number for the atoms on the catalyst surface. Furthermore, Ru is a more effective hydrogen dissociation source, while Pd has a better hydrogen storage function. Pd-Ru can tune the ΔGH of atomic hydrogen adsorbed on a catalyst and reach an optimal equilibrium state that improves the HER performance. Our studies represent a robust approach towards the development of freestanding Pd-Ru distorted ico-clusters and advanced catalysts with non-Pt content for HER and many other heterogeneous reactions. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. High molecular weight FGF2 isoforms demonstrate canonical receptor-mediated activity and support human embryonic stem cell self-renewal

    Directory of Open Access Journals (Sweden)

    Denis Kole

    2017-05-01

    Full Text Available Basic fibroblast growth factor (FGF2 is a highly pleiotropic member of a large family of growth factors with a broad range of activities, including mitogenesis and angiogenesis (Ornitz et al., 1996; Zhang et al., 2006, and it is known to be essential for maintenance of balance between survival, proliferation, and self-renewal in human pluripotent stem cells (Eiselleova et al., 2009; Zoumaro-Djayoon et al., 2011. A single FGF2 transcript can be translated into five FGF2 protein isoforms, an 18 kDa low molecular weight (LMW isoform and four larger high molecular weight (HMW isoforms (Arese et al., 1999; Arnaud et al., 1999. As they are not generally secreted, high molecular weight (HMW FGF2 isoforms have predominantly been investigated intracellularly; only a very limited number of studies have investigated their activity as extracellular factors. Here we report over-expression, isolation, and biological activity of all recombinant human FGF2 isoforms. We show that HMW FGF2 isoforms can support self-renewal of human embryonic stem cells (hESCs in vitro. Exogenous supplementation with HMW FGF2 isoforms also activates the canonical FGFR/MAPK pathway and induces mitogenic activity in a manner similar to that of the 18 kDa FGF2 isoform. Though all HMW isoforms, when supplemented exogenously, are able to recapitulate LMW FGF2 activity to some degree, it appears that certain isoforms tend to do so more poorly, demonstrating a lesser functional response by several measures. A better understanding of isoform-specific FGF2 effects will lead to a better understanding of developmental and pathological FGF2 signaling.

  19. Dactyloditerpenol acetate, a new prenylbisabolane-type diterpene from Aplysia dactylomela with significant in vitro anti-neuroinflammatory activity

    Science.gov (United States)

    Jiménez-Romero, Carlos; Mayer, Alejandro M. S.; Rodríguez, Abimael D.

    2014-01-01

    A new regular diterpene possessing an unusual 1,6-anti-3-methylcyclohex-2-en-1-ol ring system, dactyloditerpenol acetate (1), has been extracted from the tropical sea hare Aplysia dactylomela and its stereostructure elucidated by spectroscopic methods. The absolute configuration of 1 was determined as 1S, 6S, 7R, 10S, and 11R by application of Kishi’s method for the assignment of absolute configuration of alcohols. The new diterpene potently inhibited in vitro thromboxane B2 (TXB2) (IC50 0.4 μM) and superoxide anion (O2−) (IC50 1 μM) generation from E. coli lipopolysaccharide (LPS)-activated rat neonatal microglia, with concomitant low short-term toxicity. PMID:24279991

  20. Phylogenetic and experimental characterization of an acyl-ACP thioesterase family reveals significant diversity in enzymatic specificity and activity

    Directory of Open Access Journals (Sweden)

    Yandeau-Nelson Marna D

    2011-08-01

    Full Text Available Abstract Background Acyl-acyl carrier protein thioesterases (acyl-ACP TEs catalyze the hydrolysis of the thioester bond that links the acyl chain to the sulfhydryl group of the phosphopantetheine prosthetic group of ACP. This reaction terminates acyl chain elongation of fatty acid biosynthesis, and in plant seeds it is the biochemical determinant of the fatty acid compositions of storage lipids. Results To explore acyl-ACP TE diversity and to identify novel acyl ACP-TEs, 31 acyl-ACP TEs from wide-ranging phylogenetic sources were characterized to ascertain their in vivo activities and substrate specificities. These acyl-ACP TEs were chosen by two different approaches: 1 24 TEs were selected from public databases on the basis of phylogenetic analysis and fatty acid profile knowledge of their source organisms; and 2 seven TEs were molecularly cloned from oil palm (Elaeis guineensis, coconut (Cocos nucifera and Cuphea viscosissima, organisms that produce medium-chain and short-chain fatty acids in their seeds. The in vivo substrate specificities of the acyl-ACP TEs were determined in E. coli. Based on their specificities, these enzymes were clustered into three classes: 1 Class I acyl-ACP TEs act primarily on 14- and 16-carbon acyl-ACP substrates; 2 Class II acyl-ACP TEs have broad substrate specificities, with major activities toward 8- and 14-carbon acyl-ACP substrates; and 3 Class III acyl-ACP TEs act predominantly on 8-carbon acyl-ACPs. Several novel acyl-ACP TEs act on short-chain and unsaturated acyl-ACP or 3-ketoacyl-ACP substrates, indicating the diversity of enzymatic specificity in this enzyme family. Conclusion These acyl-ACP TEs can potentially be used to diversify the fatty acid biosynthesis pathway to produce novel fatty acids.

  1. [Hepatitis non-A, non-B: epidemiological significance in acute viral hepatitis and chronic active hepatitis of hepatological consultation].

    Science.gov (United States)

    Jmelnitzky, A C; Basualdo, J A; Belloni, P O; Ponce de León, H H; García, C; Curciarello, J

    1987-01-01

    157 acute viral hepatitis and 60 chronic active ones have been analyzed focusing on NANB etiology. HAV was implicated in 36.3% of the hole acute viral hepatitis sample, HBV in 29.3%, and HNANBV was presumed as etiology in 31.2%, 5 patients (3.2%) had acute infection by HAV, on previous one by HBV, except for Epstein-Barr virus, no other test for viruses were determined (CMV, HSV, etc.). Male/female ratio was 1.4:1, 1.9:1, and 1.4:1 for HAV, HBV and HNANBV acute hepatitis respectively; HAV was the main etiology in the 0-9 age group (72.2%) although it only represents 11.5% of the sample; small occurrence of HAV hepatitis were found in patients over 40 (8.8%); HBV was clearly prevalent in patients over 50 (65.2%); the highest concentration of NANB etiology was found between 20-39 years old, but it was represented in all age-groups. Out of 49 NANB acute hepatitis, 12.2% had related transfusional antecedents, 12.2% belonged to health care worker group, and 4.1% had a close family NANB hepatitis contact; 71.5% had no reported antecedent. Viral source was presumably implicated in 75.0% of chronic active hepatitis, 25.0% attributable to HNANBV. Results seem not feasible to transfer to general population due to the facts that most patients were of specialized consult, and pediatric assistance is unusual to the authors practice.

  2. Fusion of protegrin-1 and plectasin to MAP30 shows significant inhibition activity against dengue virus replication.

    Directory of Open Access Journals (Sweden)

    Hussin A Rothan

    Full Text Available Dengue virus (DENV broadly disseminates in tropical and sub-tropical countries and there are no vaccine or anti-dengue drugs available. DENV outbreaks cause serious economic burden due to infection complications that requires special medical care and hospitalization. This study presents a new strategy for inexpensive production of anti-DENV peptide-fusion protein to prevent and/or treat DENV infection. Antiviral cationic peptides protegrin-1 (PG1 and plectasin (PLSN were fused with MAP30 protein to produce recombinant antiviral peptide-fusion protein (PG1-MAP30-PLSN as inclusion bodies in E. coli. High yield production of PG1-MAP30-PLSN protein was achieved by solubilization of inclusion bodies in alkaline buffer followed by the application of appropriate refolding techniques. Antiviral PG1-MAP30-PLSN protein considerably inhibited DENV protease (NS2B-NS3pro with half-maximal inhibitory concentration (IC50 0.5±0.1 μM. The real-time proliferation assay (RTCA and the end-point proliferation assay (MTT assay showed that the maximal-nontoxic dose of the peptide-fusion protein against Vero cells is approximately 0.67±0.2 μM. The cell-based assays showed considerable inhibition of the peptide-fusion protein against binding and proliferating stages of DENV2 into the target cells. The peptide-fusion protein protected DENV2-challeged mice with 100% of survival at the dose of 50 mg/kg. In conclusion, producing recombinant antiviral peptide-fusion protein by combining short antiviral peptide with a central protein owning similar activity could be useful to minimize the overall cost of short peptide production and take advantage of its synergistic antiviral activities.

  3. [Does physical activity produce clinically significant changes during discontinuation of insulin pump in type 1 diabetic patients?].

    Science.gov (United States)

    Jankovec, Z; Cechurová, D; Cesák, V; Krčma, M; Zourek, M; Rušavý, Z

    2013-09-01

    Discontinuation of insulin pump treatment (CSII) before, during and after physical activity is a common practice among a number of patients. The aim of the study was to evaluate the course of insulinemia during a 3- hour insulin pump suspension and after consecutive insulin bolus administration, and additionally, to assess the effect of physical activity (mid intensity aerobic exercise). We enrolled 12 patients with diabetes mellitus type 1 in the study (men, mean age 33.4 ± 8.66 years, diabetes duration 16.3 ± 8.76 years, CSII treatment duration 6.9 ± 4.60 years, BMI 25.7 ± 3.75 mg/ m2, HbA1c 8.4 ± 0.95%, total insulin dose 50.3 ± 12.50 IU/ day). The tests were performed after night fasting at usual insulin doses, without serving breakfast and morning bolus dose. In the course of the test, insulin administration by a pump was suspended for 3 hours. Blood for assessment of blood glucose and insulinemia was taken in 30- minute intervals during the test. A test with or without physical exercise on bicycle ergometer was performed in each patient 2 weeks later. We did not prove any influence of physical exercise on insulinemia during suspended insulin deli-very by an insulin pump. Insulinemia of approximately 50% of the original value persisted for another 90 minutes following insulin pump suspension. A rapid increase in insulinemia occurred after bolus administration in the 180th minute of the test. However, the decrease in blood glucose level did not occur until after another 90 minutes. When modifying CSII treatment by reduction or suspension of insulin delivery it is essential to bear in mind the gradual decrease in insulinemia as well as the delay in insulin action following bolus administration.

  4. Concentration of credit exposure as a significant source of risk in banking activities: the idea and methods of estimation

    Directory of Open Access Journals (Sweden)

    Sylwester Kozak

    2016-01-01

    Full Text Available The simultaneous activation of many sources of risk can slow bank operations and even lead to bankruptcy. Credit risk is the greatest threat to the orderly functioning of a bank. To protect against its materialization banks spend nearly 90% of their total capital requirement. Concentration of credit exposure to single entities, as well as to single economic sectors, can be a source of additional risks. Estimation of the additional portion of the capital requirement in selected banks in Poland in 2008-2013 indicates that banks should assign additional 4% and 2% of the capital requirement to cover the risk of exposure concentrations in: respectively, individual entities and individual economic sectors. For banks with a retail profile more important was the risk of large exposures in individual economic sectors, and for banks with a corporate profile in individual entities. Estimates were carried out according to the procedure used by the Bank of Spain and the Bank of Slovenia, and the data derived from the annual financial reports of selected banks listed on the WSE.

  5. Lipid droplets in activated mast cells - a significant source of triglyceride-derived arachidonic acid for eicosanoid production.

    Science.gov (United States)

    Dichlberger, Andrea; Schlager, Stefanie; Kovanen, Petri T; Schneider, Wolfgang J

    2016-08-15

    Mast cells are potent effectors of immune reactions and key players in various inflammatory diseases such as atherosclerosis, asthma, and rheumatoid arthritis. The cellular defense response of mast cells represents a unique and powerful system, where external signals can trigger cell activation resulting in a stimulus-specific and highly coordinated release of a plethora of bioactive mediators. The arsenal of mediators encompasses preformed molecules stored in cytoplasmic secretory granules, as well as newly synthesized proteinaceous and lipid mediators. The release of mediators occurs in strict chronological order and requires proper coordination between the endomembrane system and various enzymatic machineries. For the generation of lipid mediators, cytoplasmic lipid droplets have been shown to function as a major intracellular pool of arachidonic acid, the precursor for eicosanoid biosynthesis. Recent studies have revealed that not only phospholipids in mast cell membranes, but also triglycerides in mast cell lipid droplets are a substrate source for eicosanoid formation. The present review summarizes current knowledge about mast cell lipid droplet biology, and discusses expansions and challenges of traditional mechanistic models for eicosanoid production.

  6. Structures, chemotaxonomic significance, cytotoxic and Na(+),K(+)-ATPase inhibitory activities of new cardenolides from Asclepias curassavica.

    Science.gov (United States)

    Zhang, Rong-Rong; Tian, Hai-Yan; Tan, Ya-Fang; Chung, Tse-Yu; Sun, Xiao-Hui; Xia, Xue; Ye, Wen-Cai; Middleton, David A; Fedosova, Natalya; Esmann, Mikael; Tzen, Jason T C; Jiang, Ren-Wang

    2014-11-28

    Five new cardenolide lactates (1–5) and one new dioxane double linked cardenolide glycoside (17) along with 15 known compounds (6–16 and 18–21) were isolated from the ornamental milkweed Asclepias curassavica. Their structures were elucidated by extensive spectroscopic methods (IR, UV, MS, 1D- and 2D-NMR). The molecular structures and absolute configurations of 1–3 and 17 were further confirmed by single-crystal X-ray diffraction analysis. Simultaneous isolation of dioxane double linked cardenolide glycosides (17–21) and cardenolide lactates (1–5) provided unique chemotaxonomic markers for this genus. Compounds 1–21 were evaluated for the inhibitory activities against DU145 prostate cancer cells. The dioxane double linked cardenolide glycosides showed the most potent cytotoxic effect followed by normal cardenolides and cardenolide lactates, while the C21 steroids were non-cytotoxic. Enzymatic assay established a correlation between the cytotoxic effects in DU145 cancer cells and the Ki for the inhibition of Na(+),K(+)-ATPase. Molecular docking analysis revealed relatively strong H-bond interactions between the bottom of the binding cavity and compounds 18 or 20, and explained why the dioxane double linked cardenolide glycosides possessed higher inhibitory potency on Na(+),K(+)-ATPase than the cardenolide lactate.

  7. 4-nitroacetophenone-derived thiosemicarbazones and their copper(II) complexes with significant in vitro anti-trypanosomal activity.

    Science.gov (United States)

    Pérez-Rebolledo, Anayive; Teixeira, Letícia R; Batista, Alzir A; Mangrich, Antonio S; Aguirre, Gabriela; Cerecetto, Hugo; González, Mercedes; Hernández, Paola; Ferreira, Ana M; Speziali, Nivaldo L; Beraldo, Heloisa

    2008-05-01

    N(4)-methyl-4-nitroacetophenone thiosemicarbazone (H4NO(2)Ac4M, 1), N(4),N(4)-dimethyl-4-nitroacetophenone thiosemicarbazone (H4NO(2)Ac4DM, 2) and N(4)-piperidyl-4-nitroacetophenone thiosemicarbazone (H4NO(2)Ac4Pip, 3) and their copper(II) complexes [Cu(4NO(2)Ac4M)(2)] (4), [Cu(4NO(2)Ac4DM)(2)] (5) and [Cu(4NO(2)Ac4Pip)(2)] (6) were tested for their in vitro ability to inhibit the growth of Trypanosoma cruzi epimastigote forms. H4NO(2)Ac4DM (2), [Cu(4NO(2)Ac4M)(2)] (4) and [Cu(4NO(2)Ac4DM)(2)] (5) proved to be as active as the clinical reference drugs nifurtimox and benznidazol. Taking into consideration the serious side effects and the poor efficacy of the reference drugs, as well as the appearance of resistance during treatment, the studied compounds could constitute a new class of anti-trypanosomal drug candidates.

  8. Etk/Bmx regulates proteinase-activated-receptor1 (PAR1 in breast cancer invasion: signaling partners, hierarchy and physiological significance.

    Directory of Open Access Journals (Sweden)

    Irit Cohen

    Full Text Available BACKGROUND: While protease-activated-receptor 1 (PAR(1 plays a central role in tumor progression, little is known about the cell signaling involved. METHODOLOGY/PRINCIPAL FINDINGS: We show here the impact of PAR(1 cellular activities using both an orthotopic mouse mammary xenograft and a colorectal-liver metastasis model in vivo, with biochemical analyses in vitro. Large and highly vascularized tumors were generated by cells over-expressing wt hPar1, Y397Z hPar1, with persistent signaling, or Y381A hPar1 mutant constructs. In contrast, cells over-expressing the truncated form of hPar1, which lacks the cytoplasmic tail, developed small or no tumors, similar to cells expressing empty vector or control untreated cells. Antibody array membranes revealed essential hPar1 partners including Etk/Bmx and Shc. PAR(1 activation induces Etk/Bmx and Shc binding to the receptor C-tail to form a complex. Y/A mutations in the PAR(1 C-tail did not prevent Shc-PAR(1 association, but enhanced the number of liver metastases compared with the already increased metastases obtained with wt hPar1. We found that Etk/Bmx first binds via the PH domain to a region of seven residues, located between C378-S384 in PAR(1 C-tail, enabling subsequent Shc association. Importantly, expression of the hPar1-7A mutant form (substituted A, residues 378-384, which is incapable of binding Etk/Bmx, resulted in inhibition of invasion through Matrigel-coated membranes. Similarly, knocking down Etk/Bmx inhibited PAR(1-induced MDA-MB-435 cell migration. In addition, intact spheroid morphogenesis of MCF10A cells is markedly disrupted by the ectopic expression of wt hPar1. In contrast, the forced expression of the hPar1-7A mutant results in normal ball-shaped spheroids. Thus, by preventing binding of Etk/Bmx to PAR(1 -C-tail, hPar1 oncogenic properties are abrogated. CONCLUSIONS/SIGNIFICANCE: This is the first demonstration that a cytoplasmic portion of the PAR(1 C-tail functions as a scaffold

  9. Attenuation of Rhes activity significantly delays the appearance of behavioral symptoms in a mouse model of Huntington's disease.

    Directory of Open Access Journals (Sweden)

    Brandon A Baiamonte

    Full Text Available Huntington's disease (HD is a neuropsychiatric disorder characterized by choreiform movement of the limbs, cognitive disability, psychosis and dementia. It is invariably associated with an abnormally long CAG expansion within the IT15 gene on human chromosome 4. Although the mutant huntingtin protein is ubiquitously expressed in HD patients, cellular degeneration occurs predominantly in neurons within the corpus striatum and cerebral cortex. The Ras homolog Rhes is expressed very selectively in the precise brain areas affected by HD. Recent in vitro work suggests that Rhes may be a co-factor with mutant huntingtin in cell death. The objective of the present study was to examine whether the inhibition of Rhes would attenuate or delay the symptoms of HD in vivo. We used a transgenic mouse model of HD crossed with Rhes knockout mice to show that the behavioral symptoms of HD are regulated by Rhes. HD(+/Rhes(-/- mice showed significantly delayed expression of HD-like symptoms in this in vivo model. Drugs that block or inhibit the actions of Rhes may be useful as the first treatments for HD.

  10. Evaluation of Techniques to Detect Significant Network Performance Problems using End-to-End Active Network Measurements

    Energy Technology Data Exchange (ETDEWEB)

    Cottrell, R.Les; Logg, Connie; Chhaparia, Mahesh; /SLAC; Grigoriev, Maxim; /Fermilab; Haro, Felipe; /Chile U., Catolica; Nazir, Fawad; /NUST, Rawalpindi; Sandford, Mark

    2006-01-25

    End-to-End fault and performance problems detection in wide area production networks is becoming increasingly hard as the complexity of the paths, the diversity of the performance, and dependency on the network increase. Several monitoring infrastructures are built to monitor different network metrics and collect monitoring information from thousands of hosts around the globe. Typically there are hundreds to thousands of time-series plots of network metrics which need to be looked at to identify network performance problems or anomalous variations in the traffic. Furthermore, most commercial products rely on a comparison with user configured static thresholds and often require access to SNMP-MIB information, to which a typical end-user does not usually have access. In our paper we propose new techniques to detect network performance problems proactively in close to realtime and we do not rely on static thresholds and SNMP-MIB information. We describe and compare the use of several different algorithms that we have implemented to detect persistent network problems using anomalous variations analysis in real end-to-end Internet performance measurements. We also provide methods and/or guidance for how to set the user settable parameters. The measurements are based on active probes running on 40 production network paths with bottlenecks varying from 0.5Mbits/s to 1000Mbit/s. For well behaved data (no missed measurements and no very large outliers) with small seasonal changes most algorithms identify similar events. We compare the algorithms' robustness with respect to false positives and missed events especially when there are large seasonal effects in the data. Our proposed techniques cover a wide variety of network paths and traffic patterns. We also discuss the applicability of the algorithms in terms of their intuitiveness, their speed of execution as implemented, and areas of applicability. Our encouraging results compare and evaluate the accuracy of our

  11. Parents' dietary patterns are significantly correlated: findings from the Melbourne Infant Feeding Activity and Nutrition Trial Program.

    Science.gov (United States)

    Lioret, Sandrine; McNaughton, Sarah A; Crawford, David; Spence, Alison C; Hesketh, Kylie; Campbell, Karen J

    2012-08-01

    The objectives of the present study were to identify dietary patterns independently in first-time mothers and fathers, and to examine whether these patterns were correlated within families. Dietary intakes were collected at baseline in the Melbourne Infant Feeding Activity and Nutrition Trial Program using a validated FFQ in 454 pairs of first-time mothers and fathers. Education level was reported in associated questionnaires. Principal components analyses included frequencies of fifty-five food groups and were performed independently in mothers and fathers. Spearman's correlation coefficients were used to assess associations between dietary pattern scores. A total of four dietary patterns were identified in mothers and fathers. Of these, three dietary patterns had similar characteristics between these two populations, namely 'Fruits and vegetables', 'High-energy snack and processed foods', 'High-fat foods' in mothers; and 'Fruits', 'High-energy snack and processed foods', 'High-fat foods' in fathers. The following two additional patterns were identified: 'Cereals and sweet foods' in mothers and 'Potatoes and vegetables' in fathers. Patterns incorporating healthier food items were found to be positively associated with parent education. An inverse association with education was found for the 'High-fat foods' and 'High-energy snack and processed foods' dietary patterns. Qualitatively similar patterns between corresponding mothers and fathers were the most strongly correlated (ρ = 0·34-0·45, P dietary patterns between mothers and fathers, suggesting that it is worth deriving patterns separately when considering couples, and more generally between men and women. Exploring how these various patterns correlate within households provides important insights to guide the development and implementation of family-based interventions.

  12. 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

  13. Experimentally-induced immune activation in natural hosts of SIV induces significant increases in viral replication and CD4+ T cell depletion

    Energy Technology Data Exchange (ETDEWEB)

    Ribeiro, Ruy M [Los Alamos National Laboratory

    2008-01-01

    Chronically SIVagm-infected African green monkeys (AGMs) have a remarkably stable non-pathogenic disease course, with levels of immune activation in chronic SIVagm infection similar to those observed in uninfected monkeys and stable viral loads (VLs) for long periods of time. In vivo administration of lipopolysaccharide (LPS) or an IL-2/diphtheria toxin fusion protein (Ontak) to chronically SIVagm-infected AGMs triggered increases in immune activation and subsequently of viral replication and depletion of intestinal CD4{sup +} T cells. Our study indicates that circulating microbial products can increase viral replication by inducing immune activation and increasing the number of viral target cells, thus demonstrating that immune activation and T cell prolifeation are key factors in AIDS pathogenesis.

  14. Dahl SS rats demonstrate enhanced aortic perivascular adipose tissue-mediated buffering of vasoconstriction through activation of NOS in the endothelium.

    Science.gov (United States)

    Spradley, Frank T; Ho, Dao H; Pollock, Jennifer S

    2016-02-01

    Perivascular adipose tissue (PVAT) mediates buffering of vasoconstriction through activation of endothelium-derived factors. We hypothesized that the PVAT of Dahl salt-sensitive (Dahl SS) rats has reduced ability to buffer vasoconstriction. Vascular reactivity experiments were performed on aortic rings with PVAT intact (+PVAT) or removed (-PVAT), and endothelium intact (+ENDO) or removed (-ENDO) from Dahl SS rats and control SS.13(BN) rats (Dahl SS rats that have had chromosome 13 completely replaced with that of the Brown Norway rat, rendering this strain insensitive to high-salt or high-fat diet-induced hypertension). Endothelial dysfunction, assessed by ACh-mediated vasorelaxation, was confirmed in aortic rings of Dahl SS rats. The +PVAT+ENDO aortic rings had indistinguishable phenylephrine-induced vasoconstriction between genotypes. In both strains, removal of PVAT significantly enhanced vasoconstriction. Dahl SS rat -PVAT+ENDO aortic rings displayed exaggerated vasoconstriction to phenylephrine vs. SS.13(BN) rats, indicating that PVAT-mediated buffering of vasoconstriction was greater in Dahl SS rats. Removal of both the ENDO and PVAT restored vasoconstriction in both strains. The nitric oxide synthase (NOS) inhibitor, N(ω)-nitro-L-arginine methyl ester (L-NAME), produced a similar effect as that seen with -ENDO. These data indicate that the function of the PVAT to activate endothelium-derived NOS is enhanced in Dahl SS compared with SS.13(BN) rats and, most likely, occurs through a pathway that is distinct from ACh-mediated activation of NOS. PVAT weight and total PVAT leptin levels were greater in Dahl SS rats. Leptin induced a significantly decreased vasoconstriction in -PVAT+ENDO aortic rings from Dahl SS rats, but not SS.13(BN) rats. In contrast to our initial hypothesis, PVAT in Dahl SS rats buffers vasoconstriction by activating endothelial NOS via mechanisms that may include the involvement of leptin. Thus, the PVAT serves a vasoprotective role in

  15. Genetic and biochemical characterization of OXA-405, an OXA-48-type extended-spectrum β-lactamase without significant carbapenemase activity.

    Science.gov (United States)

    Dortet, Laurent; Oueslati, Saoussen; Jeannot, Katy; Tandé, Didier; Naas, Thierry; Nordmann, Patrice

    2015-07-01

    The epidemiology of carbapenemases worldwide is showing that OXA-48 variants are becoming the predominant carbapenemase type in Enterobacteriaceae in many countries. However, not all OXA-48 variants possess significant activity toward carbapenems (e.g., OXA-163). Two Serratia marcescens isolates with resistance either to carbapenems or to extended-spectrum cephalosporins were successively recovered from the same patient. A genomic comparison using pulsed-field gel electrophoresis and automated Rep-PCR typing identified a 97.8% similarity between the two isolates. Both strains were resistant to penicillins and first-generation cephalosporins. The first isolate was susceptible to expanded-spectrum cephalosporins, was resistant to carbapenems, and had a significant carbapenemase activity (positive Carba NP test) related to the expression of OXA-48. The second isolate was resistant to expanded-spectrum cephalosporins, was susceptible to carbapenems, and did not express a significant imipenemase activity, (negative for the Carba NP test) despite possessing a blaOXA-48-type gene. Sequencing identified a novel OXA-48-type β-lactamase, OXA-405, with a four-amino-acid deletion compared to OXA-48. The blaOXA-405 gene was located on a ca. 46-kb plasmid identical to the prototype IncL/M blaOXA-48-carrying plasmid except for a ca. 16.4-kb deletion in the tra operon, leading to the suppression of self-conjugation properties. Biochemical analysis showed that OXA-405 has clavulanic acid-inhibited activity toward expanded-spectrum activity without significant imipenemase activity. This is the first identification of a successive switch of catalytic activity in OXA-48-like β-lactamases, suggesting their plasticity. Therefore, this report suggests that the first-line screening of carbapenemase producers in Enterobacteriaceae may be based on the biochemical detection of carbapenemase activity in clinical settings. Copyright © 2015, American Society for Microbiology. All Rights

  16. Citrate-Linked Keto- and Aldo-Hexose Monosaccharide Cellulose Conjugates Demonstrate Selective Human Neutrophil Elastase-Lowering Activity in Cotton Dressings

    Directory of Open Access Journals (Sweden)

    Sonya Caston-Pierre

    2013-05-01

    Full Text Available Sequestration of harmful proteases as human neutrophil elastase (HNE from the chronic wound environment is an important goal of wound dressing design and function. Monosaccharides attached to cellulose conjugates as ester-appended aldohexoses and ketohexoses were prepared on cotton gauze as monosccharide-citrate-cellulose-esters for HNE sequestration. The monosaccharide-cellulose analogs demonstrated selective binding when the derivatized cotton dressings were measured for sequestration of HNE. Each monosaccharide-cellulose conjugate was prepared as a cellulose citrate-linked monosaccharide ester on the cotton wound dressing, and assayed under wound exudate-mimicked conditions for elastase sequestration activity. A series of three aldohexose and four ketohexose ester cellulose conjugates were prepared on cotton gauze through citric acid-cellulose cross linking esterification. The monosaccharide portion of the conjugate was characterized by hydrolysis of the citrate-monosaccharide ester bond, and subsequent analysis of the free monosaccharide with high performance anion exchange chromatography. The ketohexose and aldohexose conjugate levels on cotton were quantified on cotton using chromatography and found to be present in milligram/gram amounts. The citrate-cellulose ester bonds were characterized with FTIR. Ketohexose-citrate-cellulose conjugates sequestered more elastase activity than aldohexose-citrate-cellulose conjugates. The monosaccharide cellulose conjugate families each gave distinctive profiles in elastase-lowering effects. Possible mechanisms of elastase binding to the monosaccharide-cellulose conjugates are discussed.

  17. Serum GH and IGF-I are significant determinants of bone turnover but not bone mineral density in active acromegaly: a prospective study of more than 70 consecutive patients.

    Science.gov (United States)

    Ueland, T; Fougner, S L; Godang, K; Schreiner, T; Bollerslev, J

    2006-11-01

    Acromegaly is characterized by a persistent hypersecretion of GH and provides information on long-term effects of GH on bone metabolism. The aim of this study was to examine the effect of gonadal status and disease activity on bone metabolism in active acromegaly. Seventy-three consecutive patients with active acromegaly: 40 women and 33 men (50 +/- 13 (mean +/- s.d.) and 49 +/- 10 years respectively) were evaluated and compared with age-, sex-, and body mass index (BMI)-matched controls by X-ray absorptiometry and biochemical analysis (markers of disease activity and bone turnover). We found that bone turnover, as evaluated by biochemical bone markers, is coupled and markedly increased in relation to disease activity in active acromegaly. Acromegalic women, but not men, were characterized by an increased bone area and slightly decreased bone mineral content resulting in significantly decreased bone mineral density (BMD) in the ultradistal radius, proximal radius, and total body. No differences in bone turnover or BMD were found between eu-and hypogonadal subjects. Multivariate analysis identified age, BMI, and gender as independent predictors of total BMD in acromegaly. Our study demonstrates a decreased total body BMD in women, not men, with active acromegaly, regardless of gonadal status or disease activity. Bone turnover is markedly increased in relation to disease activity, possibly counteracting the anabolic effects of excess GH/IGF-I in these subjects. We suggest more focus on biomechanical analyses when investigating endocrine disorders affecting bone size and distribution between compartments.

  18. The vhs1 mutant form of herpes simplex virus virion host shutoff protein retains significant internal ribosome entry site-directed RNA cleavage activity.

    Science.gov (United States)

    Lu, P; Saffran, H A; Smiley, J R

    2001-01-01

    The virion host shutoff (vhs) protein of herpes simplex virus (HSV) triggers global shutoff of host protein synthesis and accelerated turnover of host and viral mRNAs during HSV infection. As well, it induces endoribonucleolytic cleavage of RNA substrates when produced in a rabbit reticulocyte lysate (RRL) in vitro translation system. The vhs1 point mutation (Thr 214-->Ile) eliminates vhs function during virus infection and in transiently transfected mammalian cells and was therefore previously considered to abolish vhs activity. Here we demonstrate that the vhs1 mutant protein induces readily detectable endoribonuclease activity on RNA substrates bearing the internal ribosome entry site of encephalomyocarditis virus in the RRL assay system. These data document that the vhs1 mutation does not eliminate catalytic activity and raise the possibility that the vhs-dependent endoribonuclease employs more than one mode of substrate recognition.

  19. Relationship and significance between anti-β2-glycoproteinI antibodies and platelet activation state in patients with ulcerative colitis

    Science.gov (United States)

    Gao, Yan-Hang; Gao, Pu-Jun; Wang, Chun-Guang; Wang, Xiao-Cong; Piao, Yun-Feng

    2008-01-01

    AIM: To study the relationship between anti-β2-glycoprotein I (aβ2GPI) antibodies and platelet activation state in patients with ulcerative colitis (UC) and its significance. METHODS: Peripheral blood samples were collected from 56 UC patients (34 males and 22 females, aged 43.5 years, range 21-66 years), including 36 at active stage and 20 at remission stage, and 25 sex-and age-matched controls. The level of aβ2GPI was measured by ELISA. The platelet activation markers, platelet activation complex-I (PAC-I) and P-selectin (CD62P) were detected by flow cytometry. RESULTS: The A value for IgG aβ2GPI in the active UC group was 0.61 ± 0.13, significantly higher than that in the remittent UC and control groups (0.50 ± 0.13 and 0.22 ± 0.14, P 0.05). The PAC-I positive rate for the active and remittent UC groups was 30.6% ± 7.6% and 19.6% ± 7.8% respectively, significantly higher than that for the control group (6.3% ± 1.7%, P FPAC-I (%) = 5.346, P < 0.01; and FCD62P (%) = 5. 418, P < 0.01). Meanwhile, in the same state of illness, the A value for IgG aβ2GPI was positively correlated to the positive rates for PAC-I and CD62P. CONCLUSION: aβ2GPI level, platelet activation state and their relationship of them are closely correlated with the pathogenesis and development of UC. PMID:18205270

  20. The first reported generation of several induced pluripotent stem cell lines from homozygous and heterozygous Huntington's disease patients demonstrates mutation related enhanced lysosomal activity.

    Science.gov (United States)

    Camnasio, Stefano; Delli Carri, Alessia; Lombardo, Angelo; Grad, Iwona; Mariotti, Caterina; Castucci, Alessia; Rozell, Björn; Lo Riso, Pietro; Castiglioni, Valentina; Zuccato, Chiara; Rochon, Christelle; Takashima, Yasuhiro; Diaferia, Giuseppe; Biunno, Ida; Gellera, Cinzia; Jaconi, Marisa; Smith, Austin; Hovatta, Outi; Naldini, Luigi; Di Donato, Stefano; Feki, Anis; Cattaneo, Elena

    2012-04-01

    Neuronal disorders, like Huntington's disease (HD), are difficult to study, due to limited cell accessibility, late onset manifestations, and low availability of material. The establishment of an in vitro model that recapitulates features of the disease may help understanding the cellular and molecular events that trigger disease manifestations. Here, we describe the generation and characterization of a series of induced pluripotent stem (iPS) cells derived from patients with HD, including two rare homozygous genotypes and one heterozygous genotype. We used lentiviral technology to transfer key genes for inducing reprogramming. To confirm pluripotency and differentiation of iPS cells, we used PCR amplification and immunocytochemistry to measure the expression of marker genes in embryoid bodies and neurons. We also analyzed teratomas that formed in iPS cell-injected mice. We found that the length of the pathological CAG repeat did not increase during reprogramming, after long term growth in vitro, and after differentiation into neurons. In addition, we observed no differences between normal and mutant genotypes in reprogramming, growth rate, caspase activation or neuronal differentiation. However, we observed a significant increase in lysosomal activity in HD-iPS cells compared to control iPS cells, both during self-renewal and in iPS-derived neurons. In conclusion, we have established stable HD-iPS cell lines that can be used for investigating disease mechanisms that underlie HD. The CAG stability and lysosomal activity represent novel observations in HD-iPS cells. In the future, these cells may provide the basis for a powerful platform for drug screening and target identification in HD.

  1. Significance and prognostic value of lysosomal enzyme activities measured in surgically operated adenocarcinomas of the gastroesophageal junction and squamous cell carcinomas of the lower third of esophagus

    Institute of Scientific and Technical Information of China (English)

    Aron Altorjay; Balazs Paal; Nicolette Sohar; Janos Kiss; Imre Szanto; Istvan Sohar

    2005-01-01

    AIM: To establish whether there are fundamental differences in the biochemistries of adenocarcinomas of the gastroesophageal junction (GEJ) and the squamous cell carcinomas of the lower third of the esophagus (LTE).METHODS: Between February 1, 1997 and February 1,2000, we obtained tissue samples at the moment of resection from 54 patients for biochemical analysis. The full set of data could be comprehensively analyzed in 47 of 54 patients' samples (81%). Of these, 29 were adenocarcinomas of the GEJ Siewert type Ⅰ (n = 8), type Ⅱ (n = 12), type Ⅲ (n = 9), and 18 presented as squamous cell carcinomas of the LTE. We evaluated the mean values of 11-lysosomal enzyme and 1-cytosol protease activities of the tumorous and surrounding mucosae as well as their relative activities, measured as the ratio of activity in tumor and normal tissues from the same patient.These data were further analyzed to establish the correlation with tumor localization, TNM stage (lymph-node involvement), histological type (papillary, signet-ring cell,tubular), state of differentiation (good, moderate, poor),and survival (≤24 or ≥24 mo).RESULTS: In adenocarcinomas, the activity of α-mannosidase (AMAN), cathepsin B (CB) and dipeptidyl-peptidase Ⅰ (DPP Ⅰ) increased significantly as compared to the normal gastric mucosa. In squamous cell carcinomas of the esophagus, we also found a significant difference in the activity of cathepsin L and tripeptidyl-peptidase I in addition to these three. There was a statistical correlation of AMAN,CB, and DPP Ⅰ activity between the level of differentiation of adenocarcinomas of the GEJ and lymph node involvement,because tumors with no lymph node metastases histologically confirmed as well-differentiated, showed a significantly lower activity. The differences in CB and DPP Ⅰ activity correlated well with the differences in survival rates, since the CB and DPP Ⅰ values of those who died within 24 mo following surgical intervention were

  2. A significant but rather mild contribution of T286 autophosphorylation to Ca2+/CaM-stimulated CaMKII activity.

    Directory of Open Access Journals (Sweden)

    Steven J Coultrap

    Full Text Available BACKGROUND: Autophosphorylation of the Ca(2+/calmodulin (CaM-dependent protein kinase II (CaMKII at T286 generates partially Ca(2+/CaM-independent "autonomous" activity, which is thought to be required for long-term potentiation (LTP, a form of synaptic plasticity thought to underlie learning and memory. A requirement for T286 autophosphorylation also for efficient Ca(2+/CaM-stimulated CaMKII activity has been described, but remains controversial. METHODOLOGY/PRINCIPAL FINDINGS: In order to determine the contribution of T286 autophosphorylation to Ca(2+/CaM-stimulated CaMKII activity, the activity of CaMKII wild type and its phosphorylation-incompetent T286A mutant was compared. As the absolute activity can vary between individual kinase preparations, the activity was measured in six different extracts for each kinase (expressed in HEK-293 cells. Consistent with measurements on purified kinase (from a baculovirus/Sf9 cell expression system, CaMKII T286A showed a mildly but significantly reduced rate of Ca(2+/CaM-stimulated phosphorylation for two different peptide substrates (to ~75-84% of wild type. Additional slower CaMKII autophosphorylation at T305/306 inhibits stimulation by Ca(2+/CaM, but occurs only minimally for CaMKII wild type during CaM-stimulated activity assays. Thus, we tested if the T286A mutant may show more extensive inhibitory autophosphorylation, which could explain its reduced stimulated activity. By contrast, inhibitory autophosphorylation was instead found to be even further reduced for the T286A mutant under our assay conditions. On a side note, the phospho-T305 antibody showed some basal background immuno-reactivity also with non-phosphorylated CaMKII, as indicated by T305/306A mutants. CONCLUSIONS/SIGNIFICANCE: These results indicate that Ca(2+/CaM-stimulated CaMKII activity is mildly (~1.2-1.3fold further increased by additional T286 autophosphorylation, but that this autophosphorylation is not required for the major

  3. Long-Term Demonstration of Hydrogen Production from Coal at Elevated Temperatures Year 6 - Activity 1.12 - Development of a National Center for Hydrogen Technology

    Energy Technology Data Exchange (ETDEWEB)

    Stanislowski, Joshua; Tolbert, Scott; Curran, Tyler; Swanson, Michael

    2012-04-30

    The Energy & Environmental Research Center (EERC) has continued the work of the National Center for Hydrogen Technology® (NCHT®) Program Year 6 Task 1.12 project to expose hydrogen separation membranes to coal-derived syngas. In this follow-on project, the EERC has exposed two membranes to coal-derived syngas produced in the pilot-scale transport reactor development unit (TRDU). Western Research Institute (WRI), with funding from the State of Wyoming Clean Coal Technology Program and the North Dakota Industrial Commission, contracted with the EERC to conduct testing of WRI’s coal-upgrading/gasification technology for subbituminous and lignite coals in the EERC’s TRDU. This gasifier fires nominally 200–500 lb/hour of fuel and is the pilot-scale version of the full-scale gasifier currently being constructed in Kemper County, Mississippi. A slipstream of the syngas was used to demonstrate warm-gas cleanup and hydrogen separation using membrane technology. Two membranes were exposed to coal-derived syngas, and the impact of coal-derived impurities was evaluated. This report summarizes the performance of WRI’s patent-pending coalupgrading/ gasification technology in the EERC’s TRDU and presents the results of the warm-gas cleanup and hydrogen separation tests. Overall, the WRI coal-upgrading/gasification technology was shown to produce a syngas significantly lower in CO2 content and significantly higher in CO content than syngas produced from the raw fuels. Warm-gas cleanup technologies were shown to be capable of reducing sulfur in the syngas to 1 ppm. Each of the membranes tested was able to produce at least 2 lb/day of hydrogen from coal-derived syngas.

  4. Visual Electricity Demonstrator

    Science.gov (United States)

    Lincoln, James

    2017-09-01

    The Visual Electricity Demonstrator (VED) is a linear diode array that serves as a dynamic alternative to an ammeter. A string of 48 red light-emitting diodes (LEDs) blink one after another to create the illusion of a moving current. Having the current represented visually builds an intuitive and qualitative understanding about what is happening in a circuit. In this article, I describe several activities for this device and explain how using this technology in the classroom can enhance the understanding and appreciation of physics.

  5. Non-clinical and Pre-clinical Testing to Demonstrate Safety of the Barostim Neo Electrode for Activation of Carotid Baroreceptors in Chronic Human Implants

    Directory of Open Access Journals (Sweden)

    Seth J. Wilks

    2017-08-01

    Full Text Available The Barostim neo™ electrode was developed by CVRx, Inc.to deliver baroreflex activation therapy (BAT™ to treat hypertension and heart failure. The neo electrode concept was designed to deliver electrical stimulation to the baroreceptors within the carotid sinus bulb, while minimizing invasiveness of the implant procedure. This device is currently CE marked in Europe, and in a Pivotal (akin to Phase III Trial in the United States. Here we present the in vitro and in vivo safety testing that was completed in order to obtain necessary regulatory approval prior to conducting human studies in Europe, as well as an FDA Investigational Device Exemption (IDE to conduct a Pivotal Trial in the United States. Stimulated electrodes (10 mA, 500 μs, 100 Hz were compared to unstimulated electrodes using optical microscopy and several electrochemical techniques over the course of 27 weeks. Electrode dissolution was evaluated by analyzing trace metal content of solutions in which electrodes were stimulated. Lastly, safety testing under Good Laboratory Practice guidelines was conducted in an ovine animal model over a 12 and 24 week time period, with results processed and evaluated by an independent histopathologist. Long-term stimulation testing indicated that the neo electrode with a sputtered iridium oxide coating can be stimulated at maximal levels for the lifetime of the implant without clinically significant dissolution of platinum or iridium, and without increasing the potential at the electrode interface to cause hydrolysis or significant tissue damage. Histological examination of tissue that was adjacent to the neo electrodes indicated no clinically significant signs of increased inflammation and no arterial stenosis as a result of 6 months of continuous stimulation. The work presented here involved rigorous characterization and evaluation testing of the neo electrode, which was used to support its safety for chronic implantation. The testing

  6. Multi-omics Analysis of Serum Samples Demonstrates Reprogramming of Organ Functions Via Systemic Calcium Mobilization and Platelet Activation in Metastatic Melanoma.

    Science.gov (United States)

    Muqaku, Besnik; Eisinger, Martin; Meier, Samuel M; Tahir, Ammar; Pukrop, Tobias; Haferkamp, Sebastian; Slany, Astrid; Reichle, Albrecht; Gerner, Christopher

    2017-01-01

    Pathophysiologies of cancer-associated syndromes such as cachexia are poorly understood and no routine biomarkers have been established, yet. Using shotgun proteomics, known marker molecules including PMEL, CRP, SAA, and CSPG4 were found deregulated in patients with metastatic melanoma. Targeted analysis of 58 selected proteins with multiple reaction monitoring was applied for independent data verification. In three patients, two of which suffered from cachexia, a tissue damage signature was determined, consisting of nine proteins, PLTP, CD14, TIMP1, S10A8, S10A9, GP1BA, PTPRJ, CD44, and C4A, as well as increased levels of glycine and asparagine, and decreased levels of polyunsaturated phosphatidylcholine concentrations, as determined by targeted metabolomics. Remarkably, these molecules are known to be involved in key processes of cancer cachexia. Based on these results, we propose a model how metastatic melanoma may lead to reprogramming of organ functions via formation of platelet activating factors from long-chain polyunsaturated phosphatidylcholines under oxidative conditions and via systemic induction of intracellular calcium mobilization. Calcium mobilization in platelets was demonstrated to alter levels of several of these marker molecules. Additionally, platelets from melanoma patients proved to be in a rather exhausted state, and platelet-derived eicosanoids implicated in tumor growth were found massively increased in blood from three melanoma patients. Platelets were thus identified as important source of serum protein and lipid alterations in late stage melanoma patients. As a result, the proposed model describes the crosstalk between lipolysis of fat tissue and muscle wasting mediated by oxidative stress, resulting in the metabolic deregulations characteristic for cachexia.

  7. [Long-term effect of a cognitive intervention on learning and participation in a significant leisure activity in early dementia of Alzheimer type: a case study].

    Science.gov (United States)

    Provencher, Véronique; Bier, Nathalie; Audet, Thérèse; Gagnon, Lise

    2009-06-01

    Decreased ability to accomplish significant leisure activities often occurs in early stages of dementia of Alzheimer type (DAT). As a long term effect, it may eventually affect the quality of life of the patient as well as that of the caregiver's. In a previous study, a woman with early DAT (77 years old, MMSE: 24/30) improved her participation in 2 leisure activities (listening to music and praying in a group) following the learning of a few tasks (e.g. using a radio cassette, remembering the significance of an pre-programmed ring) as a result of a cognitive intervention. The present study presents the long term effect of this intervention on the retention of the learned tasks and on spontaneous participation in both leisure activities of her daily living. Measures of tasks' learning and spontaneous participation in activities have been obtained through direct observation (ex: ability to use the tasks learned without assistance) and telephone conversations with the caregiver. The measures were taken 9 to 15 months post-intervention. Nine months after the end of the intervention, the participant could no longer use the radio cassette, but was able to remember the significance of the pre-programmed ring. Similarly, she stopped listening to music, but still attended her prayer group. The intervention appears to maintain participation in a leisure activity for several months in a patient with early DAT, in spite of expected functional decline. This functional impact can be achieved through retention of specific learned tasks as well as by strong external cues (daily pre-programmed ring), and can increase the quality of life for patients with DAT.

  8. Targeting CXCR1/2 Significantly Reduces Breast Cancer Stem Cell Activity and Increases the Efficacy of Inhibiting HER2 via HER2-dependent and -independent Mechanisms

    Science.gov (United States)

    Singh, Jagdeep K.; Farnie, Gillian; Bundred, Nigel J.; Simões, Bruno M; Shergill, Amrita; Landberg, Göran; Howell, Sacha; Clarke, Robert B.

    2012-01-01

    Purpose Breast cancer stem-like cells (CSCs) are an important therapeutic target as they are predicted to be responsible for tumour initiation, maintenance and metastases. Interleukin-8 (IL-8) is upregulated in breast cancer and associated with poor prognosis. Breast cancer cell line studies indicate that IL-8 via its cognate receptors, CXCR1 and CXCR2, is important in regulating breast CSC activity. We investigated the role of IL-8 in the regulation of CSC activity using patient-derived breast cancers and determined the potential benefit of combining CXCR1/2 inhibition with HER2-targeted therapy. Experimental design CSC activity of metastatic and invasive human breast cancers (n=19) was assessed ex vivo using the mammosphere colony forming assay. Results Metastatic fluid IL-8 level correlated directly with mammosphere formation (r=0.652; P<0.05; n=10). Recombinant IL-8 directly increased mammosphere formation/self-renewal in metastatic and invasive breast cancers (n=17). IL-8 induced activation of EGFR/HER2 and downstream signalling pathways and effects were abrogated by inhibition of SRC, EGFR/HER2, PI3K or MEK. Furthermore, lapatinib inhibited the mammosphere-promoting effect of IL-8 in both HER2-positive and negative patient-derived cancers. CXCR1/2 inhibition also blocked the effect of IL-8 on mammosphere formation and added to the efficacy of lapatinib in HER2-positive cancers. Conclusions These studies establish a role for IL-8 in the regulation of patient-derived breast CSC activity and demonstrate that IL-8/CXCR1/2 signalling is partly mediated via a novel SRC and EGFR/HER2-dependent pathway. Combining CXCR1/2 inhibitors with current HER2-targeted therapies has potential as an effective therapeutic strategy to reduce CSC activity in breast cancer and improve the survival of HER2-positive patients. PMID:23149820

  9. Discovery of Early Tertiary Hydrothermal Activity and Its Significance in Oil/Gas Geology,Dougpu Depression,Henan Province,China

    Institute of Scientific and Technical Information of China (English)

    朱家祥; 朱家蔚; 等

    1994-01-01

    Data from the super-deep wells(PS10,PS14 and YS1)led to the discovery of widespread met-al-bearing hydrothermal fluids (or hot brines) related to basic magmas in the Lower Tertiary clastic sequence in the Dongpu Depression .In terms of SEM and EDAX analyses, pore-casting thin section examination of sandstone ,the composition and forming temperature of fluid inclusions ,the trace ele-ment composition of mustone and kerogen and organic geochemical analyses, it is demonstrated that the hydrothermal fluids existing in the area studied are ejecting fluids, which have a close bearing on diagenesis and sedimentation, rather than intrusive veins along the tectonic fractures.The main indicators of hydrothermal activity are:(1)abnormal alteration of kerogen;(2) high-temperature altered mineral assemblage;(30abnormal distribution of hydrocarbons;(4) specific assemblages and abnormal contents of heavy metals in mudstone and kerogen;(5) specific composi-tion of complex compounds and assemblages of fluid inclusions in sandstone;(6) periodic basaltic magma activity.Results of geological observations and laboratory simulating experiments demonstrated that the hydrothermal fluids have a close bearing on hydrocarbon generation in the Dongpu Depression. Two aspects of the effect of hydrothermal fluids are noticed:hydrothermal hydrocarbon production and strong metal catalysis in oil and gas generation.

  10. Immunization of teenagers with a fifth dose of reduced DTaP-IPV induces high levels of pertussis antibodies with a significant increase in opsonophagocytic activity.

    Science.gov (United States)

    Aase, Audun; Herstad, Tove Karin; Merino, Samuel; Bolstad, Merete; Sandbu, Synne; Bakke, Hilde; Aaberge, Ingeborg S

    2011-08-01

    Waning vaccine-induced immunity against Bordetella pertussis is observed among adolescents and adults. A high incidence of pertussis has been reported in this population, which serves as a reservoir for B. pertussis. A fifth dose of reduced antigen of diphtheria-tetanus-acellular-pertussis and inactivated polio vaccine was given as a booster dose to healthy teenagers. The antibody activity against B. pertussis antigens was measured prior to and 4 to 8 weeks after the booster by different assays: enzyme-linked immunosorbent assays (ELISAs) of IgG and IgA against pertussis toxin (PT) and filamentous hemagglutinin (FHA), IgG against pertactin (PRN), opsonophagocytic activity (OPA), and IgG binding to live B. pertussis. There was a significant increase in the IgG activity against PT, FHA, and PRN following the booster immunization (P antibodies against FHA and PRN contribute the most to the OPA and IgG binding.

  11. Significant enhancement in the photocatalytic activity of N, W co-doped TiO2 nanomaterials for promising environmental applications.

    Science.gov (United States)

    Thind, Sapanbir S; Wu, Guosheng; Tian, Min; Chen, Aicheng

    2012-11-30

    In this work, a mesoporous N, W co-doped TiO(2) photocatalyst was synthesized via a one-step solution combustion method, which utilized urea as the nitrogen source and sodium tungstate as the tungsten source. The photocatalytic activity of the N, W co-doped TiO(2) photocatalyst was significantly enhanced by a facile UV pretreatment approach and was evaluated by measuring the rate of photodegradation of Rhodamine B under both UV and visible (λ > 420) light. Following the UV pretreatment, the UV photocatalytic activity of the N, W co-doped TiO(2) was doubled. In terms of visible light activity, the UV pretreatment resulted in an extraordinary >12 fold improvement. In order to gain insight into this substantial enhancement, the N, W co-doped TiO(2) photocatalysts were studied using x-ray diffraction, transmission electron microscopy, N(2) physisorption, UV-vis absorbance spectroscopy and x-ray photoelectron spectroscopy prior to and following the UV pretreatment. Our experimental results have revealed that this significant augmentation of photocatalytic activity may be attributed to several synergetic factors, including increase of the specific surface area, reduction of the band gap energy and the removal of carbon impurities.

  12. Two new proanthocyanidin trimers isolated from Cistus incanus L. demonstrate potent anti-inflammatory activity and selectivity to cyclooxygenase isoenzymes inhibition.

    Science.gov (United States)

    Mansoor, K A; Matalka, K Z; Qa'dan, F S; Awad, R; Schmidt, M

    2016-09-01

    Two new proanthocyanidin trimers have been isolated from Cistus incanus herb; gallocatechin-(4α→6)-gallocatechin-(4α→8)-gallocatechin (compound 1) and epigallocatechin-3-O-gallate-(4ß→8)-epigallocatechin-3-O-gallate-(4ß→8)-gallocatechin (compound 2). The structures were determined on the basis of 1D- and 2D-NMR (HSQC, HMBC) of their peracetylated derivatives, MALDI-TOF-MS and by acid-catalysed degradation with phloroglucinol. A more abundant proanthocyanidin oligomer was also isolated, purified and its chemical constitution studied by (13)C-NMR and phloroglucinol degradation. The mean molecular weight of the polymer was estimated to be about 7 to 8 flavan-3-ol-units with a ratio of procyanidin : prodelphinidin units at 1:5, some of which are derivatised by gallic acid. Water extract and higher oligomeric proanthocyanidin fractions of C. incanus significantly inhibited TPA-induced oedema when applied topically at doses of 0.5 and 1 mg/ear in mice. Furthermore, the extracts and the pure compounds inhibited COX-1 and COX-2 activities. In addition, compound 2 exhibited an IC50 of 4.5 μM against COX-2 indicating its high selectivity towards COX-2.

  13. Thyrotropin receptor antibody activities significantly correlate with the outcome of radioiodine ( sup 131 I) therapy for hyperthyroid Graves' disease

    Energy Technology Data Exchange (ETDEWEB)

    Kaise, Kazuro; Kaise, Nobuko; Yoshida, Katsumi; Fukazawa, Hiroshi; Mori, Koki; Yamamoto, Makiko; Sakurada, Toshiro; Saito, Shintaro; Yoshinaga, Kaoru (Tohoku Univ., Sendai (Japan). School of Medicine)

    1991-08-01

    The outcome of {sup 131}I therapy for 109 patients with Graves' disease was analysed according to pretreatment laboratory data including thyrotropin receptor antibody (TRAb) activities. Forty-five percent of patients became euthyroid, and 13% of patients became hypothyroid within one year after {sup 131}I therapy. Forty-two percent of patients remained hyperthyroid one year after {sup 131}I therapy. Pretreatment values for serum T{sub 4}, T{sub 3}, and the estimated weight of the thyroid were significantly higher in the hyperthyroid group. The mean for the TRAb index of the hyperthyroid group was significantly higher than that of the euthyroid group. Life table analysis revealed a significant effect of the TRAb index on the rate of hyperthyroidism after 3 months or later. These results appear to suggest that the TRAb index is one of the factors which influence the outcome of {sup 131}I therapy for Graves' disease. (author).

  14. Integrating the public in mosquito management: active education by community peers can lead to significant reduction in peridomestic container mosquito habitats.

    Directory of Open Access Journals (Sweden)

    Kristen Healy

    Full Text Available Mosquito species that utilize peridomestic containers for immature development are commonly aggressive human biters, and because they often reach high abundance, create significant nuisance. One of these species, the Asian tiger mosquito Aedes albopictus, is an important vector of emerging infectious diseases, such as dengue, chikungunya, and Zika fevers. Integrated mosquito management (IMM of Ae. albopictus is particularly difficult because it requires access to private yards in urban and suburban residences. It has become apparent that in the event of a public health concern due to this species, homeowners will have to be active participants in the control process by reducing mosquito habitats in their properties, an activity known as source reduction. However, limited attempts at quantifying the effect of source reduction by homeowners have had mixed results. Of note, many mosquito control programs in the US have some form of education outreach, however the primary approach is often passive focusing on the distribution of education materials as flyers. In 2010, we evaluated the use of active community peer education in a source reduction program, using AmeriCorps volunteers. The volunteers were mobilized over a 4-week period, in two areas with approximately 1,000 residences each in urban Mercer and suburban Monmouth counties in New Jersey, USA. The volunteers were first provided training on peridomestic mosquitoes and on basic approaches to reducing the number of container habitats for mosquito larvae in backyards. Within the two treatment areas the volunteers successfully engaged 758 separate homes. Repeated measures analysis of variance showed a significant reduction in container habitats in the sites where the volunteers actively engaged the community compared to untreated control areas in both counties. Our results suggest that active education using community peer educators can be an effective means of source reduction, and a critical

  15. Integrating the public in mosquito management: active education by community peers can lead to significant reduction in peridomestic container mosquito habitats.

    Science.gov (United States)

    Healy, Kristen; Hamilton, George; Crepeau, Taryn; Healy, Sean; Unlu, Isik; Farajollahi, Ary; Fonseca, Dina M

    2014-01-01

    Mosquito species that utilize peridomestic containers for immature development are commonly aggressive human biters, and because they often reach high abundance, create significant nuisance. One of these species, the Asian tiger mosquito Aedes albopictus, is an important vector of emerging infectious diseases, such as dengue, chikungunya, and Zika fevers. Integrated mosquito management (IMM) of Ae. albopictus is particularly difficult because it requires access to private yards in urban and suburban residences. It has become apparent that in the event of a public health concern due to this species, homeowners will have to be active participants in the control process by reducing mosquito habitats in their properties, an activity known as source reduction. However, limited attempts at quantifying the effect of source reduction by homeowners have had mixed results. Of note, many mosquito control programs in the US have some form of education outreach, however the primary approach is often passive focusing on the distribution of education materials as flyers. In 2010, we evaluated the use of active community peer education in a source reduction program, using AmeriCorps volunteers. The volunteers were mobilized over a 4-week period, in two areas with approximately 1,000 residences each in urban Mercer and suburban Monmouth counties in New Jersey, USA. The volunteers were first provided training on peridomestic mosquitoes and on basic approaches to reducing the number of container habitats for mosquito larvae in backyards. Within the two treatment areas the volunteers successfully engaged 758 separate homes. Repeated measures analysis of variance showed a significant reduction in container habitats in the sites where the volunteers actively engaged the community compared to untreated control areas in both counties. Our results suggest that active education using community peer educators can be an effective means of source reduction, and a critical tool in the arsenal

  16. Cry1Ac Transgenic Sugarcane Does Not Affect the Diversity of Microbial Communities and Has No Significant Effect on Enzyme Activities in Rhizosphere Soil within One Crop Season

    Directory of Open Access Journals (Sweden)

    Dinggang eZhou

    2016-03-01

    Full Text Available Cry1Ac transgenic sugarcane provides a promising way to control stem-borer pests. Biosafety assessment of soil ecosystem for cry1Ac transgenic sugarcane is urgently needed because of the important role of soil microorganisms in nutrient transformations and element cycling, however little is known. This study aimed to explore the potential impact of cry1Ac transgenic sugarcane on rhizosphere soil enzyme activities and microbial community diversity, and also to investigate whether the gene flow occurs through horizontal gene transfer. We found no horizontal gene flow from cry1Ac sugarcane to soil. No significant difference in the population of culturable microorganisms between the non-GM and cry1Ac transgenic sugarcane was observed, and there were no significant interactions between the sugarcane lines and the growth stages. A relatively consistent trend at community-level, represented by the functional diversity index, was found between the cry1Ac sugarcane and the non-transgenic lines. Most soil samples showed no significant difference in the activities of four soil enzymes: urease, protease, sucrose, and acid phosphate monoester between the non-transgenic and cry1Ac sugarcane lines. We conclude, based on one crop season, that the cry1Ac sugarcane lines may not affect the microbial community structure and functional diversity of the rhizosphere soil and have few negative effects on soil enzymes.

  17. Cry1Ac Transgenic Sugarcane Does Not Affect the Diversity of Microbial Communities and Has No Significant Effect on Enzyme Activities in Rhizosphere Soil within One Crop Season.

    Science.gov (United States)

    Zhou, Dinggang; Xu, Liping; Gao, Shiwu; Guo, Jinlong; Luo, Jun; You, Qian; Que, Youxiong

    2016-01-01

    Cry1Ac transgenic sugarcane provides a promising way to control stem-borer pests. Biosafety assessment of soil ecosystem for cry1Ac transgenic sugarcane is urgently needed because of the important role of soil microorganisms in nutrient transformations and element cycling, however little is known. This study aimed to explore the potential impact of cry1Ac transgenic sugarcane on rhizosphere soil enzyme activities and microbial community diversity, and also to investigate whether the gene flow occurs through horizontal gene transfer. We found no horizontal gene flow from cry1Ac sugarcane to soil. No significant difference in the population of culturable microorganisms between the non-GM and cry1Ac transgenic sugarcane was observed, and there were no significant interactions between the sugarcane lines and the growth stages. A relatively consistent trend at community-level, represented by the functional diversity index, was found between the cry1Ac sugarcane and the non-transgenic lines. Most soil samples showed no significant difference in the activities of four soil enzymes: urease, protease, sucrose, and acid phosphate monoester between the non-transgenic and cry1Ac sugarcane lines. We conclude, based on one crop season, that the cry1Ac sugarcane lines may not affect the microbial community structure and functional diversity of the rhizosphere soil and have few negative effects on soil enzymes.

  18. Inseparable phone books demonstration

    Science.gov (United States)

    Balta, Nuri; Çetin, Ali

    2017-05-01

    This study is aimed at first introducing a well-known discrepant event; inseparable phone books and second, turning it into an experiment for high school or middle school students. This discrepant event could be used especially to indicate how friction force can be effective in producing an unexpected result. Demonstration, discussion, explanation and experiment steps are presented on how to turn a simple discrepant event into an instructional activity. Results showed the relationships between number of pages and force, as well as between amounts of interleave and force. In addition to these, the mathematical equation for the total force between all interleaved pages is derived. As a conclusion, this study demonstrated that not only can phone books be used, but also ordinary books, to investigate this discrepant event. This experiment can be conducted as an example to show the agreement between theoretical and experimental results along with the confounding variables. This discrepant event can be used to create a cognitive conflict in students’ minds about the concepts of ‘force and motion’ and ‘friction force’.

  19. PFBC Utility Demonstration Project

    Energy Technology Data Exchange (ETDEWEB)

    1992-11-01

    This report provides a summary of activities by American Electric Power Service Corporation during the first budget period of the PFBC Utility Demonstration Project. In April 1990, AEP signed a Cooperative Agreement with the US Department of Energy to repower the Philip Sporn Plant, Units 3 4 in New Haven, West Virginia, with a 330 KW PFBC plant. The purpose of the program was to demonstrate and verify PFBC in a full-scale commercial plant. The technical and cost baselines of the Cooperative Agreement were based on a preliminary engineering and design and a cost estimate developed by AEP subsequent to AEP's proposal submittal in May 1988, and prior to the signing of the Cooperative Agreement. The Statement of Work in the first budget period of the Cooperative Agreement included a task to develop a preliminary design and cost estimate for erecting a Greenfield plant and to conduct a comparison with the repowering option. The comparative assessment of the options concluded that erecting a Greenfield plant rather than repowering the existing Sporn Plant could be the technically and economically superior alternative. The Greenfield plant would have a capacity of 340 MW. The ten additional MW output is due to the ability to better match the steam cycle to the PFBC system with a new balance of plant design. In addition to this study, the conceptual design of the Sporn Repowering led to several items which warranted optimization studies with the goal to develop a more cost effective design.

  20. Zephycandidine A, the First Naturally Occurring Imidazo[1,2-f]phenanthridine Alkaloid from Zephyranthes candida, Exhibits Significant Anti-tumor and Anti-acetylcholinesterase Activities

    Science.gov (United States)

    Zhan, Guanqun; Qu, Xiaolan; Liu, Junjun; Tong, Qingyi; Zhou, Junfei; Sun, Bin; Yao, Guangmin

    2016-09-01

    Zephycandidine A (1), the first naturally occurring imidazo[1,2-f]phenanthridine alkaloid, was isolated from Zephyranthes candida (Amaryllidaceae). The structure of 1 was elucidated by spectroscopic analyses and NMR calculation, and a plausible biogenetic pathway for zephycandidine A (1) was proposed. Zephycandidine A (1) exhibited significant cytotoxicity against five cancer cell lines with IC50 values ranging from 1.98 to 7.03 μM with selectivity indices as high as 10 when compared to the normal Beas-2B cell. Further studies suggested that zephycandidine A (1) induces apoptosis in leukemia cells by the activation of caspase-3, upregulation of Bax, downregulation of Bcl-2, and degradation of PARP expression. In addition, zephycandidine A (1) showed acetylcholinesterase (AChE) inhibitory activity, and the docking studies of zephycandidine A (1) and galanthamine (2) with AChE revealed that interactions with W286 and Y337 are necessary.

  1. Zolpidem, A Clinical Hypnotic that Affects Electronic Transfer, Alters Synaptic Activity Through Potential Gaba Receptors in the Nervous System Without Significant Free Radical Generation

    Directory of Open Access Journals (Sweden)

    Peter Kovacic

    2009-01-01

    Full Text Available Zolpidem (trade name Ambien has attracted much interest as a sleep-inducing agent and also in research. Attention has been centered mainly on receptor binding and electrochemistry in the central nervous system which are briefly addressed herein. A novel integrated approach to mode of action is presented. The pathways to be discussed involve basicity, reduction potential, electrostatics, cell signaling, GABA receptor binding, electron transfer (ET, pharmacodynamics, structure activity relationships (SAR and side effects. The highly conjugated pyridinium salt formed by protonation of the amidine moiety is proposed to be the active form acting as an ET agent. Extrapolation of reduction potentials for related compounds supports the premise that zolpidem may act as an ET species in vivo. From recent literature reports, electrostatics is believed to play a significant role in drug action.

  2. Quantitative Metaproteomics and Activity-Based Probe Enrichment Reveals Significant Alterations in Protein Expression from a Mouse Model of Inflammatory Bowel Disease.

    Science.gov (United States)

    Mayers, Michael D; Moon, Clara; Stupp, Gregory S; Su, Andrew I; Wolan, Dennis W

    2017-02-03

    Tandem mass spectrometry based shotgun proteomics of distal gut microbiomes is exceedingly difficult due to the inherent complexity and taxonomic diversity of the samples. We introduce two new methodologies to improve metaproteomic studies of microbiome samples. These methods include the stable isotope labeling in mammals to permit protein quantitation across two mouse cohorts as well as the application of activity-based probes to enrich and analyze both host and microbial proteins with specific functionalities. We used these technologies to study the microbiota from the adoptive T cell transfer mouse model of inflammatory bowel disease (IBD) and compare these samples to an isogenic control, thereby limiting genetic and environmental variables that influence microbiome composition. The data generated highlight quantitative alterations in both host and microbial proteins due to intestinal inflammation and corroborates the observed phylogenetic changes in bacteria that accompany IBD in humans and mouse models. The combination of isotope labeling with shotgun proteomics resulted in the total identification of 4434 protein clusters expressed in the microbial proteomic environment, 276 of which demonstrated differential abundance between control and IBD mice. Notably, application of a novel cysteine-reactive probe uncovered several microbial proteases and hydrolases overrepresented in the IBD mice. Implementation of these methods demonstrated that substantial insights into the identity and dysregulation of host and microbial proteins altered in IBD can be accomplished and can be used in the interrogation of other microbiome-related diseases.

  3. Conjugation of 10 kDa Linear PEG onto Trastuzumab Fab' Is Sufficient to Significantly Enhance Lymphatic Exposure while Preserving in Vitro Biological Activity.

    Science.gov (United States)

    Chan, Linda J; Ascher, David B; Yadav, Rajbharan; Bulitta, Jürgen B; Williams, Charlotte C; Porter, Christopher J H; Landersdorfer, Cornelia B; Kaminskas, Lisa M

    2016-04-01

    The lymphatic system is a major conduit by which many diseases spread and proliferate. There is therefore increasing interest in promoting better lymphatic drug targeting. Further, antibody fragments such as Fabs have several advantages over full length monoclonal antibodies but are subject to rapid plasma clearance, which can limit the lymphatic exposure and activity of Fabs against lymph-resident diseases. This study therefore explored ideal PEGylation strategies to maximize biological activity and lymphatic exposure using trastuzumab Fab' as a model. Specifically, the Fab' was conjugated with single linear 10 or 40 kDa PEG chains at the hinge region. PEGylation led to a 3-4-fold reduction in binding affinity to HER2, but antiproliferative activity against HER2-expressing BT474 cells was preserved. Lymphatic pharmacokinetics were then examined in thoracic lymph duct cannulated rats after intravenous and subcutaneous dosing at 2 mg/kg, and the data were evaluated via population pharmacokinetic modeling. The Fab' displayed limited lymphatic exposure, but conjugation of 10 kDa PEG improved exposure by approximately 11- and 5-fold after intravenous (15% dose collected in thoracic lymph over 30 h) and subcutaneous (9%) administration, respectively. Increasing the molecular weight of the PEG to 40 kDa, however, had no significant impact on lymphatic exposure after intravenous (14%) administration and only doubled lymphatic exposure after subcutaneous administration (18%) when compared to 10 kDa PEG-Fab'. The data therefore suggests that minimal PEGylation has the potential to enhance the exposure and activity of Fab's against lymph-resident diseases, while no significant benefit is achieved with very large PEGs.

  4. Clinical significance of complement as a biomarker of disease activity in 4 cases of IgG4-related disease with retroperitoneal fibrosis.

    Science.gov (United States)

    Kihara, Mari; Sugihara, Takahiko; Hosoya, Tadashi; Miyasaka, Nobuyuki

    2013-01-01

    Hypocomplementaemia is frequently observed in IgG4-related diseases, however the clinical significance is unclear. We describe herein the clinical courses of 4 patients with IgG4-related disease with hypocomplementaemia. Our cases showed autoimmune pancreatitis, retroperitoneal fibrosis, Mikulicz's disease, interstitial lung disease, lymphadenopathy and mesenteric fibrosis around the aorta. A decrease in serum complement preceded deterioration of the disease and clinical improvement was observed in accordance with normalisation of serum complement. These clinical courses suggest that serum complement is a biomarker of the disease activity.

  5. Slant Borehole Demonstration Summary Report

    Energy Technology Data Exchange (ETDEWEB)

    GARDNER, M.G.

    2000-07-19

    This report provides a summary of the demonstration project for development of a slant borehole to retrieve soil samples from beneath the SX-108 single-shell tank. It provides a summary of the findings from the demonstration activities and recommendations for tool selection and methods to deploy into the SX Tank Farm. Daily work activities were recorded on Drilling and Sampling Daily Work Record Reports. The work described in this document was performed during March and April 2000.

  6. RADIOACTIVE DEMONSTRATIONS OF FLUIDIZED BED STEAM REFORMING AS A SUPPLEMENTARY TREATMENT FOR HANFORD'S LOW ACTIVITY WASTE AND SECONDARY WASTES

    Energy Technology Data Exchange (ETDEWEB)

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

    2011-02-24

    The U.S. Department of Energy's Office of River Protection (ORP) 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 (RPP) cleanup mission is to construct and operate the Waste Treatment and Immobilization Plant (WTP). The WTP will separate the tank waste into high-level 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 RPP mission in the time frame required by the Hanford Federal Facility Agreement and Consent Order, also known as the Tri-Party Agreement (TPA), i.e. December 31, 2047. 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. The Supplemental Treatment chosen will immobilize that portion of the retrieved LAW that is not sent to the WTP's LAW Vitrification facility into a solidified waste form. The solidified waste will then be disposed on the Hanford site in the Integrated Disposal Facility (IDF). In addition, the WTP LAW vitrification facility off-gas condensate known as WTP Secondary Waste (WTP-SW) will be generated and enriched in volatile components such as Cs-137, I-129, Tc-99, Cl, F, and SO4 that volatilize at the vitrification temperature of 1150 C in the absence of a continuous cold cap. The current waste disposal path for the WTP-SW is to recycle it to the supplemental LAW treatment to avoid a large steady state accumulation in the pretreatment-vitrification loop. Fluidized Bed Steam Reforming (FBSR) offers a moderate temperature (700-750 C) continuous method by which LAW and/or WTP-SW wastes can be processed irrespective of whether they contain organics, nitrates, sulfates

  7. Significance of postgrowth processing of ZnO nanostructures on antibacterial activity against gram-positive and gram-negative bacteria.

    Science.gov (United States)

    Mehmood, Shahid; Rehman, Malik A; Ismail, Hammad; Mirza, Bushra; Bhatti, Arshad S

    2015-01-01

    In this work, we highlighted the effect of surface modifications of one-dimensional (1D) ZnO nanostructures (NSs) grown by the vapor-solid mechanism on their antibacterial activity. Two sets of ZnO NSs were modified separately - one set was modified by annealing in an Ar environment, and the second set was modified in O2 plasma. Annealing in Ar below 800°C resulted in a compressed lattice, which was due to removal of Zn interstitials and increased O vacancies. Annealing above 1,000°C caused the formation of a new prominent phase, Zn2SiO4. Plasma oxidation of the ZnO NSs caused an expansion in the lattice due to the removal of O vacancies and incorporation of excess O. Photoluminescence (PL) spectroscopy was employed for the quantification of defects associated with Zn and O in the as-grown and processed ZnO NS. Two distinct bands were observed, one in the ultraviolet (UV) region, due to interband transitions, and other in the visible region, due to defects associated with Zn and O. PL confirmed the surface modification of ZnO NS, as substantial decrease in intensities of visible band was observed. Antibacterial activity of the modified ZnO NSs demonstrated that the surface modifications by Ar annealing limited the antibacterial characteristics of ZnO NS against Staphylococcus aureus. However, ZnO NSs annealed at 1,000°C or higher showed a remarkable antibacterial activity against Escherichia coli. O2 plasma-treated NS showed appreciable antibacterial activity against both E. coli and S. aureus. The minimum inhibition concentration was determined to be 0.5 mg/mL and 1 mg/mL for Ar-annealed and plasma-oxidized ZnO NS, respectively. It was thus proved that the O content at the surface of the ZnO NS was crucial to tune the antibacterial activity against both selected gram-negative (E. coli) and gram-positive (S. aureus) bacterial species.

  8. Radioactive Demonstration Of Mineralized Waste Forms Made From Hanford Low Activity Waste (Tank Farm Blend) By Fluidized Bed Steam Reformation (FBSR)

    Energy Technology Data Exchange (ETDEWEB)

    Jantzen, C. M. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Crawford, C. L. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Bannochie, C. J. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Burket, P. R. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Cozzi, A. D. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Daniel, W. E. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Hall, H. K. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Miller, D. H. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Missimer, D. M. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Nash, C. A. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Williams, M. F. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL)

    2013-08-01

    The U.S. Department of Energy’s Office of River Protection (ORP) is responsible for the retrieval, treatment, immobilization, and disposal of Hanford’s tank waste. A key aspect of the River Protection Project (RPP) cleanup mission is to construct and operate the Hanford Tank Waste Treatment and Immobilization Plant (WTP). The WTP will separate the tank waste into high-level 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 RPP mission in the time frame required by the Hanford Federal Facility Agreement and Consent Order, also known as the Tri-Party Agreement (TPA), i.e. December 31, 2047. Supplemental Treatment is likely to be required both to meet the TPA treatment requirements as well as to more cost effectively complete the tank waste treatment mission. The Supplemental Treatment chosen will immobilize that portion of the retrieved LAW that is not sent to the WTP’s LAW Vitrification facility into a solidified waste form. The solidified waste will then be disposed on the Hanford site in the Integrated Disposal Facility (IDF). Fluidized Bed Steam Reforming (FBSR) offers a moderate temperature (700-750°C) continuous method by which LAW can be processed irrespective of whether the waste contain organics, nitrates, sulfates/sulfides, chlorides, fluorides, volatile radionuclides or other aqueous components. The FBSR technology can process these wastes into a crystalline ceramic (mineral) waste form. The mineral waste form that is produced by co-processing waste with kaolin clay in an FBSR process has been shown to be comparable to LAW glass, i.e. leaches Tc-99, Re and Na at <2g/m2 during ASTM C1285 (Product Consistency) durability testing. Monolithing of the granular FBSR product was investigated to prevent dispersion during transport or burial/storage. Monolithing in an inorganic geopolymer binder, which is

  9. In vitro exposure to the herbicide atrazine inhibits T cell activation, proliferation, and cytokine production and significantly increases the frequency of Foxp3+ regulatory T cells.

    Science.gov (United States)

    Thueson, Lindsay E; Emmons, Tiffany R; Browning, Dianna L; Kreitinger, Joanna M; Shepherd, David M; Wetzel, Scott A

    2015-02-01

    The herbicide atrazine (2-chloro-4-[ethylamino]-6-[isopropylamino]-s-triazine) is the most common water contaminant in the United States. Atrazine is a phosphodiesterase inhibitor and is classified as an estrogen disrupting compound because it elevates estrogen levels via induction of the enzyme aromatase. Previous studies have shown that atrazine exposure alters the function of innate immune cells such as NK cells, DC, mast cells, and macrophages. In this study we have examined the impact of in vitro atrazine exposure on the activation, proliferation, and effector cytokine production by primary murine CD4(+) T lymphocytes. We found that atrazine exposure significantly inhibited CD4(+) T cell proliferation and accumulation as well as the expression of the activation markers CD25 and CD69 in a dose-dependent manner. Interestingly, the effects were more pronounced in cells from male animals. These effects were partially mimicked by pharmacological reagents that elevate intracellular cAMP levels and addition of exogenous rmIL-2 further inhibited proliferation and CD25 expression. Consistent with these findings, atrazine exposure during T cell activation resulted in a 2- to 5-fold increase in the frequency of Foxp3(+) CD4(+) T cells. © The Author 2014. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  10. Interactions outside the proteinase-binding loop contribute significantly to the inhibition of activated coagulation factor XII by its canonical inhibitor from corn.

    Science.gov (United States)

    Korneeva, Vera A; Trubetskov, Mikhail M; Korshunova, Alena V; Lushchekina, Sofya V; Kolyadko, Vladimir N; Sergienko, Olga V; Lunin, Vladimir G; Panteleev, Mikhail A; Ataullakhanov, Fazoil I

    2014-05-16

    Activated factor XII (FXIIa) is selectively inhibited by corn Hageman factor inhibitor (CHFI) among other plasma proteases. CHFI is considered a canonical serine protease inhibitor that interacts with FXIIa through its protease-binding loop. Here we examined whether the protease-binding loop alone is sufficient for the selective inhibition of serine proteases or whether other regions of a canonical inhibitor are involved. Six CHFI mutants lacking different N- and C-terminal portions were generated. CHFI-234, which lacks the first and fifth disulfide bonds and 11 and 19 amino acid residues at the N and C termini, respectively, exhibited no significant changes in FXIIa inhibition (Ki = 3.2 ± 0.4 nm). CHFI-123, which lacks 34 amino acid residues at the C terminus and the fourth and fifth disulfide bridges, inhibited FXIIa with a Ki of 116 ± 16 nm. To exclude interactions outside the FXIIa active site, a synthetic cyclic peptide was tested. The peptide contained residues 20-45 (Protein Data Bank code 1BEA), and a C29D substitution was included to avoid unwanted disulfide bond formation between unpaired cysteines. Surprisingly, the isolated protease-binding loop failed to inhibit FXIIa but retained partial inhibition of trypsin (Ki = 11.7 ± 1.2 μm) and activated factor XI (Ki = 94 ± 11 μm). Full-length CHFI inhibited trypsin with a Ki of 1.3 ± 0.2 nm and activated factor XI with a Ki of 5.4 ± 0.2 μm. Our results suggest that the protease-binding loop is not sufficient for the interaction between FXIIa and CHFI; other regions of the inhibitor also contribute to specific inhibition.

  11. Treatment of rheumatoid arthritis with tumor necrosis factor inhibitors may predispose to significant increase in tuberculosis risk: a multicenter active-surveillance report.

    Science.gov (United States)

    Gómez-Reino, Juan J; Carmona, Loreto; Valverde, Vicente Rodríguez; Mola, Emilio Martín; Montero, Maria Dolores

    2003-08-01

    The long-term safety of therapeutic agents that neutralize tumor necrosis factor (TNF) is uncertain. Recent evidence based on spontaneous reporting shows an association with active tuberculosis (TB). We undertook this study to determine and describe the long-term safety of 2 of these agents, infliximab and etanercept, in rheumatic diseases based on a national active-surveillance system following the commercialization of the drugs. We analyzed the safety data actively collected in the BIOBADASER (Base de Datos de Productos Biológicos de la Sociedad Española de Reumatología) database, which was launched in February 2000 by the Spanish Society of Rheumatology. For the estimation of TB risk, the annual incidence rate in patients treated with these agents was compared with the background rate and with the rate in a cohort of patients with rheumatoid arthritis (RA) assembled before the era of anti-TNF treatment. Seventy-one participating centers sent data on 1,578 treatments with infliximab (86%) or etanercept (14%) in 1,540 patients. Drug survival rates (reported as the cumulative percentage of patients still receiving medication) for infliximab and etanercept pooled together were 85% and 81% at 1 year and 2 years, respectively. Instances of discontinuation were essentially due to adverse events. Seventeen cases of TB were found in patients treated with infliximab. The estimated incidence of TB associated with infliximab in RA patients was 1,893 per 100,000 in the year 2000 and 1,113 per 100,000 in the year 2001. These findings represent a significant increased risk compared with background rates. In the first 5 months of 2002, after official guidelines were established for TB prevention in patients treated with biologics, only 1 new TB case was registered (in January). Therapy with infliximab is associated with an increased risk of active TB. Proper measures are needed to prevent and manage this adverse event.

  12. Exploration Medical System Demonstration Project

    Science.gov (United States)

    Chin, D. A.; McGrath, T. L.; Reyna, B.; Watkins, S. D.

    2011-01-01

    A near-Earth Asteroid (NEA) mission will present significant new challenges including hazards to crew health created by exploring a beyond low earth orbit destination, traversing the terrain of asteroid surfaces, and the effects of variable gravity environments. Limited communications with ground-based personnel for diagnosis and consultation of medical events require increased crew autonomy when diagnosing conditions, creating treatment plans, and executing procedures. Scope: The Exploration Medical System Demonstration (EMSD) project will be a test bed on the International Space Station (ISS) to show an end-to-end medical system assisting the Crew Medical Officers (CMO) in optimizing medical care delivery and medical data management during a mission. NEA medical care challenges include resource and resupply constraints limiting the extent to which medical conditions can be treated, inability to evacuate to Earth during many mission phases, and rendering of medical care by a non-clinician. The system demonstrates the integration of medical technologies and medical informatics tools for managing evidence and decision making. Project Objectives: The objectives of the EMSD project are to: a) Reduce and possibly eliminate the time required for a crewmember and ground personnel to manage medical data from one application to another. b) Demonstrate crewmember's ability to access medical data/information via a software solution to assist/aid in the treatment of a medical condition. c) Develop a common data management architecture that can be ubiquitously used to automate repetitive data collection, management, and communications tasks for all crew health and life sciences activities. d) Develop a common data management architecture that allows for scalability, extensibility, and interoperability of data sources and data users. e) Lower total cost of ownership for development and sustainment of peripheral hardware and software that use EMSD for data management f) Provide

  13. Zolpidem, a clinical hypnotic that affects electronic transfer, alters synaptic activity through potential GABA receptors in the nervous system without significant free radical generation.

    Science.gov (United States)

    Kovacic, Peter; Somanathan, Ratnasamy

    2009-01-01

    Zolpidem (trade name Ambien) has attracted much interest as a sleep-inducing agent and also in research. Attention has been centered mainly on receptor binding and electrochemistry in the central nervous system which are briefly addressed herein. A novel integrated approach to mode of action is presented. The pathways to be discussed involve basicity, reduction potential, electrostatics, cell signaling, GABA receptor binding, electron transfer (ET), pharmacodynamics, structure activity relationships (SAR) and side effects. The highly conjugated pyridinium salt formed by protonation of the amidine moiety is proposed to be the active form acting as an ET agent. Extrapolation of reduction potentials for related compounds supports the premise that zolpidem may act as an ET species in vivo. From recent literature reports, electrostatics is believed to play a significant role in drug action. The pyridinium cation displays molecular electrostatic potential which may well play a role energetically or as a bridging mechanism. An SAR analysis points to analogy with other physiologically active xenobiotics, namely benzodiazepines and paraquat in the conjugated iminium category. Inactivity of metabolites indicates that the parent is the active form of zolpidem. Absence of reactive oxygen species and oxidative stress is in line with minor side effects. In contrast, generally, the prior literature contains essentially no discussion of these fundamental biochemical relationships. Pharmacodynamics may play an important role. Concerning behavior at the blood-brain barrier, useful insight can be gained from investigations of the related cationic anesthetics that are structurally related to acetyl choline. Evidently, the neutral form of the drug penetrates the neuronal membrane, with the salt form operating at the receptor. The pathways of zolpidem have several clinical implications since the agent affects sedation, electroencephalographic activity, oxidative metabolites and

  14. Radioactive Demonstration Of Mineralized Waste Forms Made From Hanford Low Activity Waste (Tank Farm Blend) By Fluidized Bed Steam Reformation (FBSR)

    Energy Technology Data Exchange (ETDEWEB)

    Jantzen, C. M. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Crawford, C. L. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Bannochie, C. J. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Burket, P. R. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Cozzi, A. D. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Daniel, W. E. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Hall, H. K. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Miller, D. H. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Missimer, D. M. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Nash, C. A. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL); Williams, M. F. [Savannah River Site (SRS), Aiken, SC (United States). Savannah River National Lab. (SRNL)

    2013-08-01

    The U.S. Department of Energy’s Office of River Protection (ORP) is responsible for the retrieval, treatment, immobilization, and disposal of Hanford’s tank waste. A key aspect of the River Protection Project (RPP) cleanup mission is to construct and operate the Hanford Tank Waste Treatment and Immobilization Plant (WTP). The WTP will separate the tank waste into high-level 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 RPP mission in the time frame required by the Hanford Federal Facility Agreement and Consent Order, also known as the Tri-Party Agreement (TPA), i.e. December 31, 2047. Supplemental Treatment is likely to be required both to meet the TPA treatment requirements as well as to more cost effectively complete the tank waste treatment mission. The Supplemental Treatment chosen will immobilize that portion of the retrieved LAW that is not sent to the WTP’s LAW Vitrification facility into a solidified waste form. The solidified waste will then be disposed on the Hanford site in the Integrated Disposal Facility (IDF). Fluidized Bed Steam Reforming (FBSR) offers a moderate temperature (700-750°C) continuous method by which LAW can be processed irrespective of whether the waste contain organics, nitrates, sulfates/sulfides, chlorides, fluorides, volatile radionuclides or other aqueous components. The FBSR technology can process these wastes into a crystalline ceramic (mineral) waste form. The mineral waste form that is produced by co-processing waste with kaolin clay in an FBSR process has been shown to be comparable to LAW glass, i.e. leaches Tc-99, Re and Na at <2g/m2 during ASTM C1285 (Product Consistency) durability testing. Monolithing of the granular FBSR product was investigated to prevent dispersion during transport or burial/storage. Monolithing in an inorganic geopolymer binder, which is

  15. Field studies of beach cones as coastal erosion control/reversal devices for areas with significant oil and gas activities. Final report, February 24, 1992--September 18, 1995

    Energy Technology Data Exchange (ETDEWEB)

    Law, V.J.

    1995-09-18

    The primary objective of this project was to evaluate the utility of a device called the {open_quotes}beach cone{close_quotes} in combating coastal erosion. Seven initial sites were selected for testing beach cones in a variety of geometric configurations. Permits were obtained from the State of Louisiana and the U.S. Army Corps of Engineers to perform the work associated with this study. Six hundred beach cones were actually installed at six of the sites in late July and early August, 1992. Findings indicate that beach cones accreted significant amounts of materials along the beach of a barrier island, and they might have been instrumental in repairing an approximately 200 meter gap in the island. At the eighth installation the amount of accreted material was measured by surveys to be 2200 cubic meters (2900 cubic yards) in February of 1993, when the cones were found to have been completely covered by the material. At other test sites, accretion rates have been less dramatic but importantly, no significant additional erosion has occurred, which is a positive result. The cost of sediment accretion using beach cones was found to be about $13.72 per cubic yard, which would be much lower if the cones were mass produced (on the order of $3.00 per cubic yard). The survival of the cones through the fringes of Hurricane Andrew indicates that they can be anchored sufficiently to survive significant storms. The measurements of the cones settling rates indicate that this effect is not significant enough to hinder their effectiveness. A subcontract to Xavier University to assess the ecological quality of the experimental sites involved the study of the biogeochemical cycle of trace metals. The highest concentration of heavy metals were near a fishing camp while the lowest levels were in the beach sand of a barrier island. This suggests that the metals do not occur naturally in these areas, but have been placed in the sediments by man`s activities.

  16. Fuel Cell Demonstration Program

    Energy Technology Data Exchange (ETDEWEB)

    Gerald Brun

    2006-09-15

    In an effort to promote clean energy projects and aid in the commercialization of new fuel cell technologies the Long Island Power Authority (LIPA) initiated a Fuel Cell Demonstration Program in 1999 with six month deployments of Proton Exchange Membrane (PEM) non-commercial Beta model systems at partnering sites throughout Long Island. These projects facilitated significant developments in the technology, providing operating experience that allowed the manufacturer to produce fuel cells that were half the size of the Beta units and suitable for outdoor installations. In 2001, LIPA embarked on a large-scale effort to identify and develop measures that could improve the reliability and performance of future fuel cell technologies for electric utility applications and the concept to establish a fuel cell farm (Farm) of 75 units was developed. By the end of October of 2001, 75 Lorax 2.0 fuel cells had been installed at the West Babylon substation on Long Island, making it the first fuel cell demonstration of its kind and size anywhere in the world at the time. Designed to help LIPA study the feasibility of using fuel cells to operate in parallel with LIPA's electric grid system, the Farm operated 120 fuel cells over its lifetime of over 3 years including 3 generations of Plug Power fuel cells (Lorax 2.0, Lorax 3.0, Lorax 4.5). Of these 120 fuel cells, 20 Lorax 3.0 units operated under this Award from June 2002 to September 2004. In parallel with the operation of the Farm, LIPA recruited government and commercial/industrial customers to demonstrate fuel cells as on-site distributed generation. From December 2002 to February 2005, 17 fuel cells were tested and monitored at various customer sites throughout Long Island. The 37 fuel cells operated under this Award produced a total of 712,635 kWh. As fuel cell technology became more mature, performance improvements included a 1% increase in system efficiency. Including equipment, design, fuel, maintenance

  17. Gene Expression and Activity Profiling Reveal a Significant Contribution of Exo-Phosphotransferases to the Extracellular Nucleotides Metabolism in HUVEC Endothelial Cells.

    Science.gov (United States)

    Wujak, Magdalena; Hetmann, Anna; Porowińska, Dorota; Roszek, Katarzyna

    2017-06-01

    Purinergic signaling maintains local tissue homeostasis in blood vessels via the regulation of vascular tone, blood platelet aggregation, cell proliferation, and differentiation as well as inflammatory responses. Extracellular purines are important signaling molecules in the vasculature, and both purine-hydrolysing as well as -phosphorylating enzymes are considered to selectively govern extracellular nucleotide/nucleoside metabolism. Recent studies have provided some evidence for the existence of these enzymes in a soluble form in human blood and their secretion into the extracellular space under physiological and pathological conditions. However, the comprehensive analysis of endothelium-derived enzymes involved in purine metabolic pathways has received no attention so far. In the presented study, in vitro cultured human umbilical vein endothelial cells (HUVEC) are shown to be an abundant source of exo-nucleotidases comprising 5'-nucleotidase (exo-5'-NT), and nucleoside triphosphate diphosphohydrolases (exo-NTPDase) as well as phosphotransferases, represented by nucleoside diphosphate kinase (exo-NDPK) and adenylate kinase (exo-AK). An attempt is also made to demonstrate that, in contrast to the metabolic pattern determined on the endothelial cell surface, exo-phosphorylating activities markedly predominate over exo-hydrolytic ones. We present for the first time the expression profiles of genes encoding isoenzymes belonging to distinct nucleotide kinase and nucleotidase families. The genes encoding NDPK1, NDPK2, AK1, and AK2 phosphotransferases have been shown to be expressed at the highest level in HUVEC cells. The data indicate the coexistence of secreted and cell-associated factors of endothelial origin mediating ATP-consuming and ATP-generating pathways with the predominance of exo-phosphotransferases activity. The described enzymes contribute to the regulation of purinergic signal duration and extent in the venous vasculature. J. Cell. Biochem. 118: 1341

  18. Inhibition of Plasmepsin V activity demonstrates its essential role in protein export, PfEMP1 display, and survival of malaria parasites

    DEFF Research Database (Denmark)

    Sleebs, Brad E; Lopaticki, Sash; Marapana, Danushka S;

    2014-01-01

    The malaria parasite Plasmodium falciparum exports several hundred proteins into the infected erythrocyte that are involved in cellular remodeling and severe virulence. The export mechanism involves the Plasmodium export element (PEXEL), which is a cleavage site for the parasite protease......, Plasmepsin V (PMV). The PMV gene is refractory to deletion, suggesting it is essential, but definitive proof is lacking. Here, we generated a PEXEL-mimetic inhibitor that potently blocks the activity of PMV isolated from P. falciparum and Plasmodium vivax. Assessment of PMV activity in P. falciparum revealed...... surface, and cytoadherence. The inhibitor killed parasites at the trophozoite stage and knockdown of PMV enhanced sensitivity to the inhibitor, while overexpression of PMV increased resistance. This provides the first direct evidence that PMV activity is essential for protein export in Plasmodium spp...

  19. Powerful Complex Immunoadjuvant Based on Synergistic Effect of Combined TLR4 and NOD2 Activation Significantly Enhances Magnitude of Humoral and Cellular Adaptive Immune Responses.

    Science.gov (United States)

    Tukhvatulin, Amir I; Dzharullaeva, Alina S; Tukhvatulina, Natalia M; Shcheblyakov, Dmitry V; Shmarov, Maxim M; Dolzhikova, Inna V; Stanhope-Baker, Patricia; Naroditsky, Boris S; Gudkov, Andrei V; Logunov, Denis Y; Gintsburg, Alexander L

    2016-01-01

    Binding of pattern recognition receptors (PRRs) by pathogen-associated molecular patterns (PAMPs) activates innate immune responses and contributes to development of adaptive immunity. Simultaneous stimulation of different types of PRRs can have synergistic immunostimulatory effects resulting in enhanced production of molecules that mediate innate immunity such as inflammatory cytokines, antimicrobial peptides, etc. Here, we evaluated the impact of combined stimulation of PRRs from different families on adaptive immunity by generating alum-based vaccine formulations with ovalbumin as a model antigen and the Toll-like receptor 4 (TLR4) agonist MPLA and the Nucleotide-binding oligomerization domain-containing protein 2 (NOD2) agonist MDP adsorbed individually or together on the alum-ovalbumin particles. Multiple in vitro and in vivo readouts of immune system activation all showed that while individual PRR agonists increased the immunogenicity of vaccines compared to alum alone, the combination of both PRR agonists was significantly more effective. Combined stimulation of TLR4 and NOD2 results in a stronger and broader transcriptional response in THP-1 cells compared to individual PRR stimulation. Immunostimulatory composition containing both PRR agonists (MPLA and MDP) in the context of the alum-based ovalbumin vaccine also enhanced uptake of vaccine particles by bone marrow derived dendritic cells (BMDCs) and promoted maturation (up-regulation of expression of CD80, CD86, MHCII) and activation (production of cytokines) of BMDCs. Finally, immunization of mice with vaccine particles containing both PRR agonists resulted in enhanced cellular immunity as indicated by increased proliferation and activation (IFN-γ production) of splenic CD4+ and CD8+ T cells following in vitro restimulation with ovalbumin and enhanced humoral immunity as indicated by higher titers of ovalbumin-specific IgG antibodies. These results indicate that combined stimulation of TLR4 and NOD2

  20. The POSEIDON Demonstrator

    NARCIS (Netherlands)

    Laar, P.J.L.J. van de

    2013-01-01

    In this chapter, we discuss the Poseidon demonstrator: a demonstrator that integrates the individual research results of all partners of the Poseidon project. After describing how the Poseidon demonstrator was built, deployed, and operated, we will not only show many results obtained from the demons

  1. Overhead Projector Demonstrations.

    Science.gov (United States)

    Kolb, Doris, Ed.

    1988-01-01

    Details two demonstrations for use with an overhead projector in a chemistry lecture. Includes "A Very Rapidly Growing Silicate Crystal" and "A Colorful Demonstration to Simulate Orbital Hybridization." The materials and directions for each demonstration are included as well as a brief explanation of the essential learning involved. (CW)

  2. The Activating NKG2C Receptor Is Significantly Reduced in NK Cells after Allogeneic Stem Cell Transplantation in Patients with Severe Graft-versus-Host Disease

    Directory of Open Access Journals (Sweden)

    Lambros Kordelas

    2016-10-01

    Full Text Available Natural killer (NK cells play a central role in the innate immune system. In allogeneic stem cell transplantation (alloSCT, alloreactive NK cells derived by the graft are discussed to mediate the elimination of leukemic cells and dendritic cells in the patient and thereby to reduce the risk for leukemic relapses and graft-versus-host reactions. The alloreactivity of NK cells is determined by various receptors including the activating CD94/NKG2C and the inhibitory CD94/NKG2A receptors, which both recognize the non-classical human leukocyte antigen E (HLA-E. Here we analyze the contribution of these receptors to NK cell alloreactivity in 26 patients over the course of the first year after alloSCT due to acute myeloid leukemia, myelodysplastic syndrome and T cell Non-Hodgkin-Lymphoma. Our results show that NK cells expressing the activating CD94/NKG2C receptor are significantly reduced in patients after alloSCT with severe acute and chronic graft-versus-host disease (GvHD. Moreover, the ratio of CD94/NKG2C to CD94/NKG2A was reduced in patients with severe acute and chronic GvHD after receiving an HLA-mismatched graft. Collectively, these results provide evidence for the first time that CD94/NKG2C is involved in GvHD prevention.

  3. The Activating NKG2C Receptor Is Significantly Reduced in NK Cells after Allogeneic Stem Cell Transplantation in Patients with Severe Graft-versus-Host Disease

    Science.gov (United States)

    Kordelas, Lambros; Steckel, Nina-Kristin; Horn, Peter A.; Beelen, Dietrich W.; Rebmann, Vera

    2016-01-01

    Natural killer (NK) cells play a central role in the innate immune system. In allogeneic stem cell transplantation (alloSCT), alloreactive NK cells derived by the graft are discussed to mediate the elimination of leukemic cells and dendritic cells in the patient and thereby to reduce the risk for leukemic relapses and graft-versus-host reactions. The alloreactivity of NK cells is determined by various receptors including the activating CD94/NKG2C and the inhibitory CD94/NKG2A receptors, which both recognize the non-classical human leukocyte antigen E (HLA-E). Here we analyze the contribution of these receptors to NK cell alloreactivity in 26 patients over the course of the first year after alloSCT due to acute myeloid leukemia, myelodysplastic syndrome and T cell Non-Hodgkin-Lymphoma. Our results show that NK cells expressing the activating CD94/NKG2C receptor are significantly reduced in patients after alloSCT with severe acute and chronic graft-versus-host disease (GvHD). Moreover, the ratio of CD94/NKG2C to CD94/NKG2A was reduced in patients with severe acute and chronic GvHD after receiving an HLA-mismatched graft. Collectively, these results provide evidence for the first time that CD94/NKG2C is involved in GvHD prevention. PMID:27801784

  4. Echinacea purpurea significantly induces cytochrome P450 3A activity but does not alter lopinavir-ritonavir exposure in healthy subjects.

    Science.gov (United States)

    Penzak, Scott R; Robertson, Sarah M; Hunt, Jennifer D; Chairez, Cheryl; Malati, Christine Y; Alfaro, Raul M; Stevenson, James M; Kovacs, Joseph A

    2010-08-01

    . To determine the influence of Echinacea purpurea on the pharmacokinetics of lopinavir-ritonavir and on cytochrome P450 (CYP) 3A and P-glycoprotein activity by using the probe substrates midazolam and fexofenadine, respectively. Open-label, single-sequence pharmacokinetic study. Outpatient clinic in a federal government research center. Thirteen healthy volunteers (eight men, five women). Subjects received lopinavir 400 mg-ritonavir 100 mg twice/day with meals for 29.5 days. On day 16, subjects received E. purpurea 500 mg 3 times/day for 28 days: 14 days in combination with lopinavir-ritonavir and 14 days of E. purpurea alone. In order to assess CYP3A and P-glycoprotein activity, subjects received single oral doses of midazolam 8 mg and fexofenadine 120 mg, respectively, before and after the 28 days of E. purpurea. On days 15 and 30 of lopinavir-ritonavir administration (before and after E. purpurea administration, respectively), serial blood samples were collected over 12 hours to determine lopinavir and ritonavir concentrations and subsequent pharmacokinetic parameters by using noncompartmental methods. Neither lopinavir nor ritonavir pharmacokinetics were significantly altered by 14 days of E. purpurea coadministration. The post-echinacea: pre-echinacea geometric mean ratios (GMRs) for lopinavir area under the concentration-time curve (AUC) from 0-12 hours and for maximum concentration were 0.96 (90% confidence interval [CI] 0.83-1.10, p=0.82) and 1.00 (90% CI 0.88-1.12, p=0.72), respectively. Conversely, GMRs for midazolam AUC from time zero extrapolated to infinity and oral clearance were 0.73 (90% CI 0.61-0.85, p=0.008) and 1.37 (90% CI 1.10-1.63, p=0.02), respectively. Fexofenadine pharmacokinetics did not significantly differ before and after E. purpurea administration (p>0.05). Echinacea purpurea induced CYP3A activity but did not alter lopinavir concentrations, most likely due to the presence of the potent CYP3A inhibitor, ritonavir. Echinacea purpurea

  5. Strategy Guideline: Demonstration Home

    Energy Technology Data Exchange (ETDEWEB)

    Savage, C.; Hunt, A.

    2012-12-01

    This guideline will provide a general overview of the different kinds of demonstration home projects, a basic understanding of the different roles and responsibilities involved in the successful completion of a demonstration home, and an introduction into some of the lessons learned from actual demonstration home projects. Also, this guideline will specifically look at the communication methods employed during demonstration home projects. And lastly, we will focus on how to best create a communication plan for including an energy efficient message in a demonstration home project and carry that message to successful completion.

  6. Strategy Guideline. Demonstration Home

    Energy Technology Data Exchange (ETDEWEB)

    Hunt, A.; Savage, C.

    2012-12-01

    This guideline will provide a general overview of the different kinds of demonstration home projects, a basic understanding of the different roles and responsibilities involved in the successful completion of a demonstration home, and an introduction into some of the lessons learned from actual demonstration home projects. Also, this guideline will specifically look at the communication methods employed during demonstration home projects. And lastly, we will focus on how to best create a communication plan for including an energy efficient message in a demonstration home project and carry that message to successful completion.

  7. Tidd PFBC demonstration project

    Energy Technology Data Exchange (ETDEWEB)

    Marrocco, M. [American Electric Power, Columbus, OH (United States)

    1997-12-31

    The Tidd project was one of the first joint government-industry ventures to be approved by the US Department of Energy (DOE) in its Clean Coal Technology Program. In March 1987, DOE signed an agreement with the Ohio Power Company, a subsidiary of American Electric Power, to refurbish the then-idle Tidd plant on the banks of the Ohio River with advanced pressurized fluidized bed technology. Testing ended after 49 months of operation, 100 individual tests, and the generation of more than 500,000 megawatt-hours of electricity. The demonstration plant has met its objectives. The project showed that more than 95 percent of sulfur dioxide pollutants could be removed inside the advanced boiler using the advanced combustion technology, giving future power plants an attractive alternative to expensive, add-on scrubber technology. In addition to its sulfur removal effectiveness, the plant`s sustained periods of steady-state operation boosted its availability significantly above design projections, heightening confidence that pressurized fluidized bed technology will be a reliable, baseload technology for future power plants. The technology also controlled the release of nitrogen oxides to levels well below the allowable limits set by federal air quality standards. It also produced a dry waste product that is much easier to handle than wastes from conventional power plants and will likely have commercial value when produced by future power plants.

  8. ISSUES AND FEASIBILITY DEMONSTRATION OF CLIC SUPPORTING SYSTEM CHAIN ACTIVE PRE-ALIGNMENT USING A MULTI-MODULE TEST SETUP (MOCK-UP)

    CERN Document Server

    Sosin, Mateusz

    2016-01-01

    The implementation study of the CLIC (Compact LInear Collider) is under way at CERN with a focus on the challenging issues. The pre-alignment precision and accuracy requirements are part of these technical challenges: the permissible transverse position errors of the linac components are typically 14 micrometers over sliding windows of 200m. To validate the proposed methods and strategies, the Large Scale Metrology section at CERN has performed campaigns of measurements on the CLIC Two Beam Test Modules, focusing inter alia on the alignment performance of the CLIC “snake”- girders configuration and the Main Beam Quadrupoles supporting structures. This paper describes the activities and results of tests which were performed on the test mock-up for the qualification of the CLIC supporting system chain for active pre-alignment. The lessons learnt (“know how”), the issues encountered in the girder position determination as well as the behaviour of the mechanical components are presented.

  9. Phenotyping of peripheral blood mononuclear cells during acute dengue illness demonstrates infection and increased activation of monocytes in severe cases compared to classic dengue fever.

    Science.gov (United States)

    Durbin, Anna P; Vargas, Maria José; Wanionek, Kimberli; Hammond, Samantha N; Gordon, Aubree; Rocha, Crisanta; Balmaseda, Angel; Harris, Eva

    2008-07-05

    In vitro studies have attempted to identify dengue virus (DEN) target cells in peripheral blood; however, extensive phenotyping of peripheral blood mononuclear cells (PBMCs) from dengue patients has not been reported. PBMCs collected from hospitalized children suspected of acute dengue were analyzed for DEN prM, CD32, CD86, CD14, CD11c, CD16, CD209, CCR7, CD4, and CD8 by flow cytometry to detect DEN antigen in PBMCs and to phenotype DEN-positive cells. DEN prM was detected primarily in activated monocytes (CD14(+), CD32(+), CD86(+), CD11c(+)). A subset of samples analyzed for DEN nonstructural protein 3 (NS3) confirmed that approximately half of DEN antigen-positive cells contained replicating virus. A higher percentage of PBMCs from DHF patients expressed prM, CD86, CD32, and CD11c than did those from DF patients. Increased activation of monocytes and greater numbers of DEN-infected cells were associated with more severe dengue, implicating a role for monocyte activation in dengue immunopathogenesis.

  10. Demonstrating the use of high-volume electronic medical claims data to monitor local and regional influenza activity in the US.

    Directory of Open Access Journals (Sweden)

    Cécile Viboud

    Full Text Available Fine-grained influenza surveillance data are lacking in the US, hampering our ability to monitor disease spread at a local scale. Here we evaluate the performances of high-volume electronic medical claims data to assess local and regional influenza activity.We used electronic medical claims data compiled by IMS Health in 480 US locations to create weekly regional influenza-like-illness (ILI time series during 2003-2010. IMS Health captured 62% of US outpatient visits in 2009. We studied the performances of IMS-ILI indicators against reference influenza surveillance datasets, including CDC-ILI outpatient and laboratory-confirmed influenza data. We estimated correlation in weekly incidences, peak timing and seasonal intensity across datasets, stratified by 10 regions and four age groups (<5, 5-29, 30-59, and 60+ years. To test IMS-Health performances at the city level, we compared IMS-ILI indicators to syndromic surveillance data for New York City. We also used control data on laboratory-confirmed Respiratory Syncytial Virus (RSV activity to test the specificity of IMS-ILI for influenza surveillance.Regional IMS-ILI indicators were highly synchronous with CDC's reference influenza surveillance data (Pearson correlation coefficients rho≥0.89; range across regions, 0.80-0.97, P<0.001. Seasonal intensity estimates were weakly correlated across datasets in all age data (rho≤0.52, moderately correlated among adults (rho≥0.64 and uncorrelated among school-age children. IMS-ILI indicators were more correlated with reference influenza data than control RSV indicators (rho = 0.93 with influenza v. rho = 0.33 with RSV, P<0.05. City-level IMS-ILI indicators were highly consistent with reference syndromic data (rho≥0.86.Medical claims-based ILI indicators accurately capture weekly fluctuations in influenza activity in all US regions during inter-pandemic and pandemic seasons, and can be broken down by age groups and fine geographical areas

  11. Manufacturing Demonstration Facility (MDF)

    Data.gov (United States)

    Federal Laboratory Consortium — The U.S. Department of Energy Manufacturing Demonstration Facility (MDF) at Oak Ridge National Laboratory (ORNL) provides a collaborative, shared infrastructure to...

  12. Identification of novel α4β2-nicotinic acetylcholine receptor (nAChR) agonists based on an isoxazole ether scaffold that demonstrate antidepressant-like activity.

    Science.gov (United States)

    Yu, Li-Fang; Tückmantel, Werner; Eaton, J Brek; Caldarone, Barbara; Fedolak, Allison; Hanania, Taleen; Brunner, Dani; Lukas, Ronald J; Kozikowski, Alan P

    2012-01-26

    There is considerable evidence to support the hypothesis that the blockade of nAChR is responsible for the antidepressant action of nicotinic ligands. The nicotinic acetylcholine receptor (nAChR) antagonist, mecamylamine, has been shown to be an effective add-on in patients that do not respond to selective serotonin reuptake inhibitors. This suggests that nAChR ligands may address an unmet clinical need by providing relief from depressive symptoms in refractory patients. In this study, a new series of nAChR ligands based on an isoxazole-ether scaffold have been designed and synthesized for binding and functional assays. Preliminary structure-activity relationship (SAR) efforts identified a lead compound 43, which possesses potent antidepressant-like activity (1 mg/kg, IP; 5 mg/kg, PO) in the classical mouse forced swim test. Early stage absorption, distribution, metabolism, excretion, and toxicity (ADME-Tox) studies also suggested favorable drug-like properties, and broad screening toward other common neurotransmitter receptors indicated that compound 43 is highly selective for nAChRs over the other 45 neurotransmitter receptors and transporters tested.

  13. Surface tensions of multi-component mixed inorganic/organic aqueous systems of atmospheric significance: measurements, model predictions and importance for cloud activation predictions

    Directory of Open Access Journals (Sweden)

    D. O. Topping

    2006-11-01

    multi-component surface tensions involving compounds used in this study one requires the use of appropriate binary data. The effect of deviations between predicted and measured surface tensions on predicted cloud activation properties was quantified, by incorporating the surface tension models into an existing thermodynamic framework. Critical saturation ratios as a function of dry size for all of the multi-component systems were computed and it was found that deviations between predictions increased with decreasing particle dry size.  As expected, use of the surface tension of pure water, rather than calculate the influence of the solutes explicitly, led to a consistently higher value of the critical saturation ratio indicating that neglect of the compositional effects will lead to significant differences in predicted activation behaviour even at large particle dry sizes.

  14. Apparatus and method for time-integrated, active sampling of contaminants in fluids demonstrated by monitoring of hexavalent chromium in groundwater.

    Science.gov (United States)

    Roll, Isaac B; Driver, Erin M; Halden, Rolf U

    2016-06-15

    Annual U.S. expenditures of $2B for site characterization invite the development of new technologies to improve data quality while reducing costs and minimizing uncertainty in groundwater monitoring. This work presents a new instrument for time-integrated sampling of environmental fluids using in situ solid-phase extraction (SPE). The In Situ Sampler (IS2) is an automated submersible device capable of extracting dissolved contaminants from water (100s-1000smL) over extended periods (hours to weeks), retaining the analytes, and rejecting the processed fluid. A field demonstration of the IS2 revealed 28-day average concentration of hexavalent chromium in a shallow aquifer affected by tidal stresses via sampling of groundwater as both liquid and sorbed composite samples, each obtained in triplicate. In situ SPE exhibited 75±6% recovery and an 8-fold improvement in reporting limit. Relative to use of conventional methods (100%), beneficial characteristics of the device and method included minimal hazardous material generation (2%), transportation cost (10%), and associated carbon footprint (2%). The IS2 is compatible with commercial SPE resins and standard extraction methods, and has been certified for more general use (i.e., inorganics and organics) by the Environmental Security Technology Certification Program (ESTCP) of the U.S. Department of Defense.

  15. Clobazam and its active metabolite N-desmethylclobazam display significantly greater affinities for α₂- versus α₁-GABA(A-receptor complexes.

    Directory of Open Access Journals (Sweden)

    Henrik Sindal Jensen

    Full Text Available Clobazam (CLB, a 1,5-benzodiazepine (BZD, was FDA-approved in October 2011 for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS in patients 2 years and older. BZDs exert various CNS effects through allosteric modulation of GABAA receptors. The structurally distinct, 1,4-BZD clonazepam (CLN is also approved to treat LGS. The precise mechanisms of action and clinical efficacy of both are unknown. Data show that the GABAA α₁-subunit-selective compound zolpidem [ZOL] exhibits hypnotic/sedative effects. Conversely, data from knock-in mice carrying BZD binding site mutations suggest that the α₂ subunit mediates anticonvulsant effects, without sedative actions. Hence, the specific pattern of interactions across the GABAA receptor complexes of BZDs might be reflected in their clinical efficacies and adverse effect profiles. In this study, GABAA-receptor binding affinities of CLB, N-desmethylclobazam (N-CLB, the major metabolite of CLB, CLN, and ZOL were characterized with native receptors from rat-brain homogenates and on cloned receptors from HEK293 cells transfected with combinations of α (α₁, α₂, α₃, or α₅, β₂, and γ₂ subtypes. Our results demonstrate that CLB and N-CLB have significantly greater binding affinities for α₂- vs. α₁-receptor complexes, a difference not observed for CLN, for which no distinction between α₂ and α₁ receptors was observed. Our experiments with ZOL confirmed the high preference for α₁ receptors. These results provide potential clues to a new understanding of the pharmacologic modes of action of CLB and N-CLB.

  16. Clobazam and its active metabolite N-desmethylclobazam display significantly greater affinities for α₂- versus α₁-GABA(A)-receptor complexes.

    Science.gov (United States)

    Jensen, Henrik Sindal; Nichol, Kathryn; Lee, Deborah; Ebert, Bjarke

    2014-01-01

    Clobazam (CLB), a 1,5-benzodiazepine (BZD), was FDA-approved in October 2011 for the adjunctive treatment of seizures associated with Lennox-Gastaut syndrome (LGS) in patients 2 years and older. BZDs exert various CNS effects through allosteric modulation of GABAA receptors. The structurally distinct, 1,4-BZD clonazepam (CLN) is also approved to treat LGS. The precise mechanisms of action and clinical efficacy of both are unknown. Data show that the GABAA α₁-subunit-selective compound zolpidem [ZOL] exhibits hypnotic/sedative effects. Conversely, data from knock-in mice carrying BZD binding site mutations suggest that the α₂ subunit mediates anticonvulsant effects, without sedative actions. Hence, the specific pattern of interactions across the GABAA receptor complexes of BZDs might be reflected in their clinical efficacies and adverse effect profiles. In this study, GABAA-receptor binding affinities of CLB, N-desmethylclobazam (N-CLB, the major metabolite of CLB), CLN, and ZOL were characterized with native receptors from rat-brain homogenates and on cloned receptors from HEK293 cells transfected with combinations of α (α₁, α₂, α₃, or α₅), β₂, and γ₂ subtypes. Our results demonstrate that CLB and N-CLB have significantly greater binding affinities for α₂- vs. α₁-receptor complexes, a difference not observed for CLN, for which no distinction between α₂ and α₁ receptors was observed. Our experiments with ZOL confirmed the high preference for α₁ receptors. These results provide potential clues to a new understanding of the pharmacologic modes of action of CLB and N-CLB.

  17. AGN-2979, an inhibitor of tryptophan hydroxylase activation, does not affect serotonin synthesis in Flinders Sensitive Line rats, a rat model of depression, but produces a significant effect in Flinders Resistant Line rats.

    Science.gov (United States)

    Kanemaru, Kazuya; Nishi, Kyoko; Diksic, Mirko

    2009-12-01

    The neurotransmitter, serotonin, is involved in several brain functions, including both normal, physiological functions, and pathophysiological functions. Alterations in any of the normal parameters of serotonergic neurotransmission can produce several different psychiatric disorders, including major depression. In many instances, brain neurochemical variables are not able to be studied properly in humans, thus making the use of good animal models extremely valuable. One of these animal models is the Flinders Sensitive Line (FSL) of rats, which has face, predictive and constructive validities in relation to human depression. The objective of this study was to quantify the effect of the tryptophan hydroxylase (TPH) activation inhibitor, AGN-2979, on the FSL rats (rats with depression-like behaviour), and compare it to the effect on the Flinders Resistant Line (FRL) of rats used as the control rats. The effect was evaluated by measuring changes in regional serotonin synthesis in the vehicle treated rats (FSL-VEH and FRL-VEH) relative to those measured in the AGN-2979 treated rats (FSL-AGN and FRL-AGN). Regional serotonin synthesis was measured autoradiographically in more than 30 brain regions. The measurements were performed using alpha-[(14)C]methyl-l-tryptophan as the tracer. The results indicate that AGN-2979 did not produce a significant reduction of TPH activity in the AGN-2979 group relative to the vehicle group (a reduction would have been observed if there had been an activation of TPH by the experimental setup) in the FSL rats. On the other hand, there was a highly significant reduction of synthesis in the FRL rats treated by AGN-2979, relative to the vehicle group. Together, the results demonstrate that in the FSL rats, AGN-2979 does not affect serotonin synthesis. This suggests that there was no activation of TPH in the FSL rats during the experimental procedure, but such activation did occur in the FRL rats. Because of this finding, it could be

  18. Toy Demonstrator's "VISIT" Handbook.

    Science.gov (United States)

    Levenstein, Phyllis

    The role of the toy demonstrator in a home-based, mother-involved intervention effort (Verbal Interaction Project) is presented in this handbook for staff members. It is believed that the prerequisites for functioning in the toy demonstrator's role are a sense of responsibility, patience with the children and their mothers, and willingness to be…

  19. Levitation Kits Demonstrate Superconductivity.

    Science.gov (United States)

    Worthy, Ward

    1987-01-01

    Describes the "Project 1-2-3" levitation kit used to demonstrate superconductivity. Summarizes the materials included in the kit. Discusses the effect demonstrated and gives details on how to obtain kits. Gives an overview of the documentation that is included. (CW)

  20. Kinetics and Catalysis Demonstrations.

    Science.gov (United States)

    Falconer, John L.; Britten, Jerald A.

    1984-01-01

    Eleven videotaped kinetics and catalysis demonstrations are described. Demonstrations include the clock reaction, oscillating reaction, hydrogen oxidation in air, hydrogen-oxygen explosion, acid-base properties of solids, high- and low-temperature zeolite reactivity, copper catalysis of ammonia oxidation and sodium peroxide decomposition, ammonia…

  1. Better Ira Remsen Demonstration

    Science.gov (United States)

    Dalby, David K.; Maynard, James H.; Moore, John W.

    2011-01-01

    Many versions of the classic Ira Remsen experience involving copper and concentrated nitric acid have been used as lecture demonstrations. Remsen's original reminiscence from 150 years ago is included in the Supporting Information, and his biography can be found on the Internet. This article presents a new version that makes the demonstration more…

  2. Levitation Kits Demonstrate Superconductivity.

    Science.gov (United States)

    Worthy, Ward

    1987-01-01

    Describes the "Project 1-2-3" levitation kit used to demonstrate superconductivity. Summarizes the materials included in the kit. Discusses the effect demonstrated and gives details on how to obtain kits. Gives an overview of the documentation that is included. (CW)

  3. Basic rhythm of myoelectric activities of sphcter of Oddi and its biological significance%Oddi括约肌肌电活动的基本方式

    Institute of Scientific and Technical Information of China (English)

    李虎城; 董家鸿; 陈飞; 邹一平; 李为民

    2010-01-01

    Objective To observe the basic rhythm of myoelectrie activities of sphcter of Oddi (SO)and explore its biological significance.Methods Healthy adult rabbits(n=32)were randomized into 4 groups with 8 in each.The first group was for recording of myoelectric activities of SO after keeping fast for 18 hours.The second group was manipulated to observe the myoelectric activities of SO after food infusion through the stoma in stomach.The myoelectric activities of SO in the third group were monitored after the classical Nardi test was performed on these rabbits.The fourth group was used to observe the myoelectric activities of SO after the cholinergic receptors had been blocked.Using the double claw metal electrodes which were put into SO and duodenum through the plasma membrance,the myoelectric signal were recorded with RM6240 multi-channel physiologic recording and signal processing system and non-stop recording was conducted for 120-150 mins.Results 1)Spike Potentials of SO with the frequency was observed in rabbits that had been fasting.2)Myoelectronic activity of SO was observed in rabbits infused with 50 ml milk through stoma.3)After the administration of 1 mg morphine and 1 mg neostigmine i.v,the myoelectric activities of SO were noted as long-lasting persistent MASO.4)Administration of anisodamine 1 mg(i.v.)in the empty abdomen group dismissed SPSO and MASO.This state lasted for 120 min before SPSO gradually reconverted to the state of empty abdomen.Conclusion There are four patterns of myoelectric activities of SO,i.e,tensional waves under empty abdomen indicating a state in which the SO kept a basic tension level.Peristaltic waves under intake of food.Spastic waves under the stimulation of drugs and relaxant waves under the post-ganglionic block of cholinergic receptors were observed in the present study.Correspondingly,their mechanic locomotion is inferred as the basic tensional state to faciliate the deposition and condensation of bile,the peristalsis for the

  4. 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.

  5. Radioactive Demonstration Of Mineralized Waste Forms Made From Hanford Low Activity Waste (Tank SX-105 And AN-103) By Fluidized Bed Steam Reformation

    Energy Technology Data Exchange (ETDEWEB)

    Jantzen, Carol; Herman, Connie; Crawford, Charles; Bannochie, Christopher; Burket, Paul; Daniel, Gene; Cozzi, Alex; Nash, Charles; Miller, Donald; Missimer, David

    2014-01-10

    One of the immobilization technologies under consideration as a Supplemental Treatment for Hanford’s Low Activity Waste (LAW) is Fluidized Bed Steam Reforming (FBSR). The FBSR technology forms a mineral waste form at moderate processing temperatures thus retaining and atomically bonding the halides, sulfates, and technetium in the mineral phases (nepheline, sodalite, nosean, carnegieite). Additions of kaolin clay are used instead of glass formers and the minerals formed by the FBSR technology offers (1) atomic bonding of the radionuclides and constituents of concern (COC) comparable to glass, (2) short and long term durability comparable to glass, (3) disposal volumes comparable to glass, and (4) higher Na2O and SO{sub 4} waste loadings than glass. The higher FBSR Na{sub 2}O and SO{sub 4} waste loadings contribute to the low disposal volumes but also provide for more rapid processing of the LAW. Recent FBSR processing and testing of Hanford radioactive LAW (Tank SX-105 and AN-103) waste is reported and compared to previous radioactive and non-radioactive LAW processing and testing.

  6. Demonstrating usefulness of real-time monitoring at streambank wells coupled with active streamgages - Pilot studies in Wyoming, Montana, and Mississippi

    Science.gov (United States)

    Eddy-Miller, Cheryl A.; Constantz, Jim; Wheeler, Jerrod D.; Caldwell, Rodney R.; Barlow, Jeannie R.B.

    2012-01-01

    Groundwater and surface water in many cases are considered separate resources, but there is growing recognition of a need to treat them as a single resource. For example, groundwater inflow during low streamflow is vitally important to the health of a stream for many reasons, including buffering temperature, providing good quality water to the stream, and maintaining flow for aquatic organisms. The U.S. Geological Survey (USGS) has measured stream stage and flow at thousands of locations since 1889 and has the ability to distribute the information to the public within hours of collection, but collecting shallow groundwater data at co-located measuring sites is a new concept. Recently developed techniques using heat as a tracer to quantify groundwater and surface-water exchanges have shown the value of coupling these resources to increase the understanding of the water resources of an area. In 2009, the USGS Office of Groundwater began a pilot study to examine the feasibility and utility of widespread use of real-time groundwater monitoring at streambank wells coupled with real-time surface-water monitoring at active streamgages to assist in understanding the exchange of groundwater and surface water in a cost effective manner.

  7. IMPROVED LIGHT MICROSCOPIC DEMONSTRATION OF D-AMINO-ACID OXIDASE ACTIVITY IN CRYOTOME SECTIONS USING CERIUM IONS AS CAPTURING AND AMPLIFYING AGENT - THE CE/CE-H2O2-DAB PROCEDURE

    NARCIS (Netherlands)

    HALBHUBER, KJ; FEUERSTEIN, H; ZIMMERMANN, N; KLINGER, M; KALICHARAN, D; HUPFER, U

    1991-01-01

    The light microscopical demonstration of D-amino acid oxidase (AAOX) activity with cerium (Ce III) as the capturing agent was improved. The incubation medium was stabilized by the employment of triethanolamine and detrane complexed cerium. A considerable increase in intensity of the reaction was

  8. LIGHT AND ELECTRON-MICROSCOPIC DEMONSTRATION OF THE OUABAIN-SENSITIVE, POTASSIUM-DEPENDENT P-NITROPHENYLPHOSPHATASE ACTIVITY (K-NPPASE) USING A CE-MG-DOUBLE CAPTURE TECHNIQUE

    NARCIS (Netherlands)

    GLIESING, M; KALICHARAN, D; HALBHUBER, KJ

    The cerium-based method of Kobayashi et al. for the histochemical demonstration of K-NPPase activity was improved. Besides Ce3+ additionally Mg2+ ions as orthophosphate capture were employed (double capture technique). For light microscopical purposes the Mg-phosphate was converted into Ce-phosphate

  9. Methanol Cannon Demonstrations Revisited.

    Science.gov (United States)

    Dolson, David A.; And Others

    1995-01-01

    Describes two variations on the traditional methanol cannon demonstration. The first variation is a chain reaction using real metal chains. The second example involves using easily available components to produce sequential explosions that can be musical in nature. (AIM)

  10. TENCompetence tool demonstration

    NARCIS (Netherlands)

    Kluijfhout, Eric

    2010-01-01

    Kluijfhout, E. (2009). TENCompetence tool demonstration. Presented at Zorgacademie Parkstad (Health Academy Parkstad), Limburg Leisure Academy, Life Long Learning Limburg and a number of regional educational institutions. May, 18, 2009, Heerlen, The Netherlands: Open University of the Netherlands, T

  11. Land Management Research Demonstration

    Data.gov (United States)

    US Fish and Wildlife Service, Department of the Interior — In 2002, Neal Smith National Wildlife Refuge became one of the first Land Management and Research Demonstration (LMRD) sites. These sites are intended to serve as...

  12. Buparlisib, a PI3K inhibitor, demonstrates acceptable tolerability and preliminary activity in a phase I trial of patients with advanced leukemias.

    Science.gov (United States)

    Ragon, Brittany Knick; Kantarjian, Hagop; Jabbour, Elias; Ravandi, Farhad; Cortes, Jorge; Borthakur, Gautam; DeBose, LaKiesha; Zeng, Zhihong; Schneider, Heather; Pemmaraju, Naveen; Garcia-Manero, Guillermo; Kornblau, Steven; Wierda, William; Burger, Jan; DiNardo, Courtney D; Andreeff, Michael; Konopleva, Marina; Daver, Naval

    2017-01-01

    Phosphatidylinositol-3-kinase (PI3K) signaling plays a crucial role in oncogene-mediated tumor growth and proliferation. Buparlisib (BKM120) is an oral pan-class I PI3K inhibitor. This phase I study was conducted to determine the dose limiting toxicity (DLT) and maximum tolerated dose (MTD) of BKM120 in patients (pts) with relapsed/refractory acute leukemias. Fourteen pts (12 acute myeloid leukemia, 1 acute lymphoblastic leukemia, and 1 mixed phenotype leukemia) were enrolled. Twelve pts received BKM-120 80 mg/day and two 100 mg/day. The MTD was 80 mg/day. Of the 14 patients treated, the best response was stable disease in one patient that lasted 82 days. The median survival for all patients was 75 days (range 10-568). Three patients with a 3q26 chromosome abnormality had a significantly improved median survival of 360 days (range 278-568) as compared to a median survival of 57 days (range, 10-125) among the 11 other patients. The most frequent drug-related toxicities included confusion, mucositis, dysphagia, and fatigue. Western blot profiling revealed a decrease in p-pS6K/total pS6K in 5/7 (71%) available patient samples with a mean quantitative inhibition of 65% (range, 32-100%) and a decrease in p-FOXO3/total FOXO3 in 4/6 (67%) samples with a mean quantitative inhibition of 93% (range, 89-100%). BKM120 administered at 80 mg/day showed modest efficacy and was tolerable in advanced acute leukemias. Am. J. Hematol. 92:7-11, 2017. © 2016 Wiley Periodicals, Inc.

  13. Pancreaticopleural fistula : CT demonstration

    Energy Technology Data Exchange (ETDEWEB)

    Hahm, Jin Kyeung [Chuncheon Medical Center, ChunChon (Korea, Republic of)

    1997-03-01

    In patients with chronic pancreatitis, the pancreaticopleural fistula is known to cause recurrent exudative or hemorrhagic pleural effusions. These are often large in volume and require treatment, unlike the effusions in acute pancreatitis. Diagnosis can be made either by the finding of elevated pleural fluid amylase level or, using imaging studies, by the direct demonstration of the fistulous tract. We report two cases of pancreaticopleural fistula demonstrated by computed tomography.

  14. Education Payload Operation - Demonstrations

    Science.gov (United States)

    Keil, Matthew

    2009-01-01

    Education Payload Operation - Demonstrations (EPO-Demos) are recorded video education demonstrations performed on the International Space Station (ISS) by crewmembers using hardware already onboard the ISS. EPO-Demos are videotaped, edited, and used to enhance existing NASA education resources and programs for educators and students in grades K-12. EPO-Demos are designed to support the NASA mission to inspire the next generation of explorers.

  15. The crystal structure of rice (Oryza sativa L.) Os4BGlu12, an oligosaccharide and tuberonic acid glucoside-hydrolyzing β-glucosidase with significant thioglucohydrolase activity.

    Science.gov (United States)

    Sansenya, Sompong; Opassiri, Rodjana; Kuaprasert, Buabarn; Chen, Chun-Jung; Cairns, James R Ketudat

    2011-06-01

    Rice Os4BGlu12, a glycoside hydrolase family 1 (GH1) β-glucosidase, hydrolyzes β-(1,4)-linked oligosaccharides of 3-6 glucosyl residues and the β-(1,3)-linked disaccharide laminaribiose, as well as certain glycosides. The crystal structures of apo Os4BGlu12, and its complexes with 2,4-dinitrophenyl-2-deoxyl-2-fluoroglucoside (DNP2FG) and 2-deoxy-2-fluoroglucose (G2F) were solved at 2.50, 2.45 and 2.40Å resolution, respectively. The overall structure of rice Os4BGlu12 is typical of GH1 enzymes, but it contains an extra disulfide bridge in the loop B region. The glucose ring of the G2F in the covalent intermediate was found in a (4)C(1) chair conformation, while that of the noncovalently bound DNP2FG had a (1)S(3) skew boat, consistent with hydrolysis via a (4)H(3) half-chair transition state. The position of the catalytic nucleophile (Glu393) in the G2F structure was more similar to that of the Sinapsis alba myrosinase G2F complex than to that in covalent intermediates of other O-glucosidases, such as rice Os3BGlu6 and Os3BGlu7 β-glucosidases. This correlated with a significant thioglucosidase activity for Os4BGlu12, although with 200- to 1200-fold lower k(cat)/K(m) values for S-glucosides than the comparable O-glucosides, while hydrolysis of S-glucosides was undetectable for Os3BGlu6 and Os3BGlu7.

  16. Edible Astronomy Demonstrations

    Science.gov (United States)

    Lubowich, Donald A.

    2007-12-01

    Astronomy demonstrations with edible ingredients are an effective way to increase student interest and knowledge of astronomical concepts. This approach has been successful with all age groups from elementary school through college students - and the students remember these demonstrations after they are presented. In this poster I describe edible demonstrations I have created to simulate the expansion of the universe (using big-bang chocolate chip cookies); differentiation during the formation of the Earth and planets (using chocolate or chocolate milk with marshmallows, cereal, candy pieces or nuts); and radioactivity/radioactive dating (using popcorn). Other possible demonstrations include: plate tectonics (crackers with peanut butter and jelly); convection (miso soup or hot chocolate); mud flows on Mars (melted chocolate poured over angel food cake); formation of the Galactic disk (pizza); formation of spiral arms (coffee with cream); the curvature of Space (Pringles); constellations patterns with chocolate chips and chocolate chip cookies; planet shaped cookies; star shaped cookies with different colored frostings; coffee or chocolate milk measurement of solar radiation; Oreo cookie lunar phases. Sometimes the students eat the results of the astronomical demonstrations. These demonstrations are an effective teaching tool and can be adapted for cultural, culinary, and ethnic differences among the students.

  17. Surface tensions of multi-component mixed inorganic/organic aqueous systems of atmospheric significance: measurements, model predictions and importance for cloud activation predictions

    Directory of Open Access Journals (Sweden)

    D. O. Topping

    2007-01-01

    , it would appear that in order to model multi-component surface tensions involving compounds used in this study one requires the use of appropriate binary data. However, results indicate that the use of theoretical frameworks which contain parameters derived from binary data may predict unphysical behaviour when taken beyond the concentration ranges used to fit such parameters. The effect of deviations between predicted and measured surface tensions on predicted critical saturation ratios was quantified, by incorporating the surface tension models into an existing thermodynamic framework whilst firstly neglecting bulk to surface partitioning. Critical saturation ratios as a function of dry size for all of the multi-component systems were computed and it was found that deviations between predictions increased with decreasing particle dry size. As expected, use of the surface tension of pure water, rather than calculate the influence of the solutes explicitly, led to a consistently higher value of the critical saturation ratio indicating that neglect of the compositional effects will lead to significant differences in predicted activation behaviour even at large particle dry sizes. Following this two case studies were used to study the possible effect of bulk to surface partitioning on critical saturation ratios. By employing various assumptions it was possible to perform calculations not only for a binary system but also for a mixed organic system. In both cases this effect lead to a significant increase in the predicted critical supersaturation ratio compared to the above treatment. Further analysis of this effect will form the focus of future work.

  18. Significance of platelet activating factor receptor expression in pancreatic tissues of rats with severe acute pancreatitis and effects of BN52021

    Institute of Scientific and Technical Information of China (English)

    Shi-Hai Xia; Chun-Xiu Hu; Zhi-Ling Zhao; Guo-Dong Xia; Yao Di

    2007-01-01

    AIM: To investigate the dynamic changes and significance of platelet activating factor receptor (PAF-R)mRNA and protein in pancreatic tissues of rats with severe acute pancreatitis (SAP) and effects of BN52021(Ginkgolide B).METHODS: Wistar male rats were randomly assigned to the negative control group (NC group), SAP model group (SAP group), and BN52051-remedy group (BN group), and each of the groups was divided into 6 subgroups at different time points after operation (1 h,2 h, 3 h, 6 h, 12 h, and 24 h) (n = 10 in each). PT-PCR and Western blot methods were used to detect PAFRmRNA and protein expression in pancreatic tissues of rats respectively. Pathological examination of pancreatic tissues was performed and the serum amylase change was detected.RESULTS: Serum amylase and pathological results showed the that SAP model was successfully prepared,BN52021 was able to decrease serum amylase, and the pathological ratings in BN group at 3 h, 6 h, and 12 h significantly decreased compared with those in the SAP group (8.85 ± 0.39 vs 5.95 ± 0.19, 9.15 ± 0.55 vs 5.55 ± 0.36, 10.10 ± 0.65 vs 6.72 ± 0.30, P < 0.05). The result of PAF-mRNA showed dynamic changes in SAP and BN groups, which increased gradually in early stage,reached a peak at 3 h (0.71 ± 0.14 vs 0.54 ± 0.14,0.69 ± 0.13 vs 0.59 ± 0.04, P < 0.05), and decreased gradually later. There were significant differences at each time point except 1 h and 2 h, when compared with those in the NC group (0.71 ± 0.14 or 0.69 ± 0.13 vs 0.47 ± 0.10, 0.38 ± 0.08 or 0.59 ± 0.04 vs 0.47 ± 0.09, 0.25 ± 0.07 or 0.29 ± 0.05 vs 0.46 ± 0.10, 0.20 ± 0.06 or 0.20 ± 0.04 vs 0.43 ± 0.09, P < 0.05), whereas there was no significant difference between BN and SAP groups at each time point. The result of PAF-R protein showed that the change of PAF-R protein in the SAP group and the BN group was consistent with that of PAF-R mRNA.There were significant differences at each time point except 1 h, when compared with

  19. Offsite demonstrations for MWLID technologies

    Energy Technology Data Exchange (ETDEWEB)

    Williams, C. [Sandia National Labs., Albuquerque, NM (United States); Gruebel, R. [Tech. Reps., Inc., Albuquerque, NM (United States)

    1995-04-01

    The goal of the Offsite Demonstration Project for Mixed Waste Landfill Integrated Demonstration (MWLID)-developed environmental site characterization and remediation technologies is to facilitate the transfer, use, and commercialization of these technologies to the public and private sector. The meet this goal, the project identified environmental restoration needs of mixed waste and/or hazardous waste landfill owners (Native American, municipal, DOE, and DoD); documenting potential demonstration sites and the contaminants present at each site; assessing the environmental regulations that would effect demonstration activities; and evaluating site suitability for demonstrating MWLID technologies at the tribal and municipal sites identified. Eighteen landfill sites within a 40.2-km radius of Sandia National Laboratories are listed on the CERCLIS Site/Event Listing for the state of New Mexico. Seventeen are not located within DOE or DoD facilities and are potential offsite MWLID technology demonstration sites. Two of the seventeen CERCLIS sites, one on Native American land and one on municipal land, were evaluated and identified as potential candidates for off-site demonstrations of MWLID-developed technologies. Contaminants potentially present on site include chromium waste, household/commercial hazardous waste, volatile organic compounds, and petroleum products. MWLID characterization technologies applicable to these sites include Magnetometer Towed Array, Cross-borehole Electromagnetic Imaging, SitePlanner {trademark}/PLUME, Hybrid Directional Drilling, Seamist{trademark}/Vadose Zone Monitoring, Stripping Analyses, and x-ray Fluorescence Spectroscopy for Heavy Metals.

  20. Solar renovation demonstration projects

    Energy Technology Data Exchange (ETDEWEB)

    Bruun Joergensen, O. [ed.

    1998-10-01

    In the framework of the IEA SHC Programme, a Task on building renovation was initiated, `Task 20, Solar Energy in Building Renovation`. In a part of the task, Subtask C `Design of Solar Renovation Projects`, different solar renovation demonstration projects were developed. The objective of Subtask C was to demonstrate the application of advanced solar renovation concepts on real buildings. This report documents 16 different solar renovation demonstration projects including the design processes of the projects. The projects include the renovation of houses, schools, laboratories, and factories. Several solar techniques were used: building integrated solar collectors, glazed balconies, ventilated solar walls, transparent insulation, second skin facades, daylight elements and photovoltaic systems. These techniques are used in several simple as well as more complex system designs. (au)

  1. Weed Identification Field Training Demonstrations.

    Science.gov (United States)

    Murdock, Edward C.; And Others

    1986-01-01

    Reviews efforts undertaken in weed identification field training sessions for agriprofessionals in South Carolina. Data over a four year period (1980-1983) revealed that participants showed significant improvement in their ability to identify weeds. Reaffirms the value of the field demonstration technique. (ML)

  2. Weed Identification Field Training Demonstrations.

    Science.gov (United States)

    Murdock, Edward C.; And Others

    1986-01-01

    Reviews efforts undertaken in weed identification field training sessions for agriprofessionals in South Carolina. Data over a four year period (1980-1983) revealed that participants showed significant improvement in their ability to identify weeds. Reaffirms the value of the field demonstration technique. (ML)

  3. Demonstrating marketing accountability.

    Science.gov (United States)

    Gombeski, William R; Britt, Jason; Taylor, Jan; Riggs, Karen; Wray, Tanya; Adkins, Wanda; Springate, Suzanne

    2008-01-01

    Pressure on health care marketers to demonstrate effectiveness of their strategies and show their contribution to organizational goals is growing. A seven-tiered model based on the concepts of structure (having the right people, systems), process (doing the right things in the right way), and outcomes (results) is discussed. Examples of measures for each tier are provided and the benefits of using the model as a tool for measuring, organizing, tracking, and communicating appropriate information are provided. The model also provides a framework for helping management understand marketing's value and can serve as a vehicle for demonstrating marketing accountability.

  4. Demonstrating Supernova Remnant Evolution

    Science.gov (United States)

    Leahy, Denis A.; Williams, Jacqueline

    2017-01-01

    We have created a software tool to calculate at display supernova remnant evolution which includes all stages from early ejecta dominated phase to late-time merging with the interstellar medium. The software was created using Python, and can be distributed as Python code, or as an executable file. The purpose of the software is to demonstrate the different phases and transitions that a supernova remnant undergoes, and will be used in upper level undergraduate astrophysics courses as a teaching tool. The usage of the software and its graphical user interface will be demonstrated.

  5. Gigashot Optical Laser Demonstrator

    Energy Technology Data Exchange (ETDEWEB)

    Deri, R. J. [Lawrence Livermore National Lab. (LLNL), Livermore, CA (United States)

    2015-10-13

    The Gigashot Optical Laser Demonstrator (GOLD) project has demonstrated a novel optical amplifier for high energy pulsed lasers operating at high repetition rates. The amplifier stores enough pump energy to support >10 J of laser output, and employs conduction cooling for thermal management to avoid the need for expensive and bulky high-pressure helium subsystems. A prototype amplifier was fabricated, pumped with diode light at 885 nm, and characterized. Experimental results show that the amplifier provides sufficient small-signal gain and sufficiently low wavefront and birefringence impairments to prove useful in laser systems, at repetition rates up to 60 Hz.

  6. Role of the HSP90-associated cochaperone p23 in enhancing activity of the androgen receptor and significance for prostate cancer.

    Science.gov (United States)

    Reebye, Vikash; Querol Cano, Laia; Lavery, Derek N; Brooke, Greg N; Powell, Sue M; Chotai, Deepa; Walker, Marjorie M; Whitaker, Hayley C; Wait, Robin; Hurst, Helen C; Bevan, Charlotte L

    2012-10-01

    Prostate tumor growth initially depends on androgens, which act via the androgen receptor (AR). Despite androgen ablation therapy, tumors eventually progress to a castrate-resistant stage in which the AR remains active. The mechanisms are poorly understood but it may be that changes in levels or activity of AR coregulators affect trafficking and activation of the receptor. A key stage in AR signaling occurs in the cytoplasm, where unliganded receptor is associated with the heat shock protein (HSP)90 foldosome complex. p23, a key component of this complex, is best characterized as a cochaperone for HSP90 but also has HSP90-independent activity and has been reported as having differential effects on the activity of different steroid receptors. Here we report that p23 increases activity of the AR, and this appears to involve steps both in the cytoplasm (increasing ligand-binding capacity, possibly via direct interaction with AR) and the nucleus (enhancing AR occupancy at target promoters). We show, for the first time, that AR and p23 can interact, perhaps directly, when HSP90 is not present in the same complex. The effects of p23 on AR activity are at least partly HSP90 independent because a mutant form of p23, unable to bind HSP90, nevertheless increases AR activity. In human prostate tumors, nuclear p23 was higher in malignant prostate cells compared with benign/normal cells, supporting the utility of p23 as a therapeutic target in prostate cancer.

  7. Lycorine, the Main Phenanthridine Amaryllidaceae Alkaloid, Exhibits Significant Anti-Tumor Activity in Cancer Cells that Display Resistance to Proapoptotic Stimuli: an Investigation of Structure-Activity Relationship and Mechanistic Insight

    Science.gov (United States)

    Lamoral-Theys, Delphine; Andolfi, Anna; Van Goietsenoven, Gwendoline; Cimmino, Alessio; Le Calvé, Benjamin; Wauthoz, Nathalie; Mégalizzi, Véronique; Gras, Thierry; Bruyère, Céline; Dubois, Jacques; Mathieu, Véronique; Kornienko, Alexander; Kiss, Robert; Evidente, Antonio

    2011-01-01

    Twenty-two lycorine-related compounds were investigated for in vitro anti-tumor activity using four cancer cell lines displaying different levels of resistance to pro-apoptotic stimuli and two cancer cell lines sensitive to pro-apoptotic stimuli. Lycorine and six of its congeners exhibited potency in the single-digit micromolar range, while no compound appeared more active than lycorine. Lycorine also displayed the highest potential (in vitro) therapeutic ratio, being at least 15 times more active against cancer than normal cells. Our studies also showed that lycorine exerts its in vitro anti-tumor activity through cytostatic rather than cytotoxic effects. Furthermore, lycorine provided significant therapeutic benefit in mice bearing brain grafts of the B16F10 melanoma model at non-toxic doses. Thus, the results of the current study make lycorine an excellent lead for the generation of compounds able to combat cancers, which are naturally resistant to pro-apoptotic stimuli, such as glioblastoma, melanoma, non-small-cell-lung cancers, metastatic cancers, among others. PMID:19788245

  8. Lycorine, the main phenanthridine Amaryllidaceae alkaloid, exhibits significant antitumor activity in cancer cells that display resistance to proapoptotic stimuli: an investigation of structure-activity relationship and mechanistic insight.

    Science.gov (United States)

    Lamoral-Theys, Delphine; Andolfi, Anna; Van Goietsenoven, Gwendoline; Cimmino, Alessio; Le Calvé, Benjamin; Wauthoz, Nathalie; Mégalizzi, Véronique; Gras, Thierry; Bruyère, Céline; Dubois, Jacques; Mathieu, Véronique; Kornienko, Alexander; Kiss, Robert; Evidente, Antonio

    2009-10-22

    Twenty-two lycorine-related compounds were investigated for in vitro antitumor activity using four cancer cell lines displaying different levels of resistance to proapoptotic stimuli and two cancer cell lines sensitive to proapoptotic stimuli. Lycorine and six of its congeners exhibited potency in the single-digit micromolar range, while no compound appeared more active than lycorine. Lycorine also displayed the highest potential (in vitro) therapeutic ratio, being at least 15 times more active against cancer than normal cells. Our studies also showed that lycorine exerts its in vitro antitumor activity through cytostatic rather than cytotoxic effects. Furthermore, lycorine provided significant therapeutic benefit in mice bearing brain grafts of the B16F10 melanoma model at nontoxic doses. Thus, the results of the current study make lycorine an excellent lead for the generation of compounds able to combat cancers, which are naturally resistant to proapoptotic stimuli, such as glioblastoma, melanoma, non-small-cell-lung cancers, and metastatic cancers, among others.

  9. [Significance of detecting the EBV-DNA level in peripheral blood mononuclear cells and the EBV-infected cell type in patients with chronic active EBV infection].

    Science.gov (United States)

    Xing, Yan; Song, Hong-mei; Wu, Xiao-yan; Wang, Wei; Wei, Min

    2011-07-01

    To study the difference in the EBV-DNA level in peripheral blood mononuclear cells (PBMC) and the type of Epstein-Barr virus (EBV)-infected cells in pediatric patients with chronic active EBV (CAEBV) infection, acute EBV infection (AEBV) and healthy children, and to analyze the relationship between the above difference and the clinical manifestation of CAEBV. Real-time fluorescent quantitative polymerase chain reaction (PCR) was used to detect the EBV-DNA levels in peripheral blood mononuclear cells (PBMC) in 12 normal children, 10 pediatric patients with CAEBV infection and 13 pediatric patients with AEBV infection in our hospital between March 2004 and April 2008. Immunomagnetic bead cell fractionation and fluorescent in situ hybridization (FISH) by EBV encoding RNA-1 ( EBER-1) probe were used in the healthy children, EBV-DNA positive CAEBV patients and AEBV patients to detect the type of EBV-infected cells. The average EBV-DNA level in CAEBV patients' PBMC was (6.8 x 10(7) +/- 1.1 x 10(8)) copies/ml, while the average EBV-DNA level of AEBV patients' PBMC was (1.3 x 10(6) +/- 1.6 x 10(6)) copies/ml. The average EBV-DNA level of CAEBV infected patients' PBMC was significantly higher than that of AEBV infected patients' PBMC (Pblood cells. In 1 CAEBV patient the infection was mainly found in NK cells, who presented with hypersensitivity to mosquito biting and high IgE level (2500 U/ml). But EBV in seven AEBV patients infection was found only in B cells who presented with only IM for one time and no EBV-infected PBMC were found in the remaining 6 healthy children. There are much more EBV replications and different EBV-infected cell types in CAEBV patients. Detection of EBV-DNA level by real-time fluorescent quantitative PCR and the detection of the type of EBV-infected cells may help in diagnosis, treatment and development evaluation of children with CAEBV infection.

  10. Probability of Detection Demonstration Transferability

    Science.gov (United States)

    Parker, Bradford H.

    2008-01-01

    The ongoing Mars Science Laboratory (MSL) Propellant Tank Penetrant Nondestructive Evaluation (NDE) Probability of Detection (POD) Assessment (NESC activity) has surfaced several issues associated with liquid penetrant POD demonstration testing. This presentation lists factors that may influence the transferability of POD demonstration tests. Initial testing will address the liquid penetrant inspection technique. Some of the factors to be considered in this task are crack aspect ratio, the extent of the crack opening, the material and the distance between the inspection surface and the inspector's eye.

  11. Monty Roberts’ public demonstrations

    NARCIS (Netherlands)

    Loftus, Loni; Marks, Kelly; Jones-McVey, Rosie; Gonzales, Jose L.; Fowler, Veronica L.

    2016-01-01

    Effective training of horses relies on the trainer’s awareness of learning theory and equine ethology, and should be undertaken with skill and time. Some trainers, such as Monty Roberts, share their methods through the medium of public demonstrations. This paper describes the opportunistic analys

  12. Arctic Craft Demonstration Report

    Science.gov (United States)

    2012-11-01

    it received a lot of attention from the local population. Demonstration personnel, both Coast Guard and contractors, were asked to be receptive to...www.uscg.mil/top/missions/ . Counter-Drug Interdiction and Alien Migrant Interdiction operations are currently not included. In the non-Polar regions

  13. Participatory Lecture Demonstrations.

    Science.gov (United States)

    Battino, Rubin

    1979-01-01

    The use of participatory lecture demonstrations in the classroom is described. Examples are given for the following topics: chromatography, chemical kinetics, balancing equations, the gas laws, kinetic molecular theory, Henry's law of gas solubility, electronic energy levels in atoms, and translational, vibrational, and rotational energies of…

  14. Demonstrating the Gas Laws.

    Science.gov (United States)

    Holko, David A.

    1982-01-01

    Presents a complete computer program demonstrating the relationship between volume/pressure for Boyle's Law, volume/temperature for Charles' Law, and volume/moles of gas for Avagadro's Law. The programing reinforces students' application of gas laws and equates a simulated moving piston to theoretical values derived using the ideal gas law.…

  15. Polarized Light: Three Demonstrations.

    Science.gov (United States)

    Goehmann, Ruth; Welty, Scott

    1984-01-01

    Describes three demonstrations used in the Chicago Museum of Science and Industry polarized light show. The procedures employed are suitable for the classroom by using smaller polarizers and an overhead projector. Topic areas include properties of cellophane tape, nondisappearing arrows, and rope through a picket fence. (JN)

  16. Passive damping technology demonstration

    Science.gov (United States)

    Holman, Robert E.; Spencer, Susan M.; Austin, Eric M.; Johnson, Conor D.

    1995-05-01

    A Hughes Space Company study was undertaken to (1) acquire the analytical capability to design effective passive damping treatments and to predict the damped dynamic performance with reasonable accuracy; (2) demonstrate reasonable test and analysis agreement for both baseline and damped baseline hardware; and (3) achieve a 75% reduction in peak transmissibility and 50% reduction in rms random vibration response. Hughes Space Company teamed with CSA Engineering to learn how to apply passive damping technology to their products successfully in a cost-effective manner. Existing hardware was selected for the demonstration because (1) previous designs were lightly damped and had difficulty in vibration test; (2) multiple damping concepts could be investigated; (3) the finite element model, hardware, and test fixture would be available; and (4) damping devices could be easily implemented. Bracket, strut, and sandwich panel damping treatments that met the performance goals were developed by analysis. The baseline, baseline with damped bracket, and baseline with damped strut designs were built and tested. The test results were in reasonable agreement with the analytical predictions and demonstrated that the desired reduction in dynamic response could be achieved. Having successfully demonstrated this approach, it can now be used with confidence for future designs as a means for reducing weight and enhancing reliability.

  17. PHARUS ASAR demonstrator

    NARCIS (Netherlands)

    Smith, A.J.E.; Bree, R.J.P. van; Calkoen, C.J.; Dekker, R.J.; Otten, M.P.G.; Rossum, W.L. van

    2001-01-01

    PHARUS is a polarimetric phased array C-band Synthetic Aperture Radar (SAR), designed and built for airborne use. Advanced SAR (ASAR) data in image and alternating polarization mode have been simulated with PHARUS to demonstrate the use of Envisat for a number of typical SAR applications that are no

  18. Distance Learning Environment Demonstration.

    Science.gov (United States)

    1996-11-01

    The Distance Learning Environment Demonstration (DLED) was a comparative study of distributed multimedia computer-based training using low cost high...measurement. The DLED project provides baseline research in the effective use of distance learning and multimedia communications over a wide area ATM/SONET

  19. Calculus Demonstrations Using MATLAB

    Science.gov (United States)

    Dunn, Peter K.; Harman, Chris

    2002-01-01

    The note discusses ways in which technology can be used in the calculus learning process. In particular, five MATLAB programs are detailed for use by instructors or students that demonstrate important concepts in introductory calculus: Newton's method, differentiation and integration. Two of the programs are animated. The programs and the…

  20. Polarized Light: Three Demonstrations.

    Science.gov (United States)

    Goehmann, Ruth; Welty, Scott

    1984-01-01

    Describes three demonstrations used in the Chicago Museum of Science and Industry polarized light show. The procedures employed are suitable for the classroom by using smaller polarizers and an overhead projector. Topic areas include properties of cellophane tape, nondisappearing arrows, and rope through a picket fence. (JN)

  1. Copy number variation in sulfotransferase isoform 1A1 (SULT1A1 is significantly associated with enzymatic activity in Japanese subjects

    Directory of Open Access Journals (Sweden)

    Yu X

    2013-03-01

    Full Text Available Xinfeng Yu,1 Takahiro Kubota,2 Ishwori Dhakal,1 Setsuo Hasegawa,3 Suzanne Williams,1 Shogo Ozawa,4 Susan Kadlubar11Division of Medical Genetics, College of Medicine, University of Arkansas for Medical Sciences, Little Rock, Arkansas, USA; 2Chiba Institute of Science, Chiba, Japan; 3Sekino Clinical Pharmacology Clinic, Tokyo, Japan; 4Iwate Medical University, Iwate, JapanAbstract: Sulfotransferase isoform 1A1 (SULT1A1 plays a key role in the metabolism of a variety of endo- and xenobiotics and it's activity could influence response to drugs. Our previous studies have focused on the impact of genetic variants of SULT1A1 on enzymatic activity in Caucasians and African-Americans. However, the contribution of genetic variants to SULT1A1 activity in Asians has not been explored. In this study, we investigated the collective effects of both SULT1A1 copy number variants (CNVs and single nucleotide polymorphisms (SNPs in the promoter region, coding region, and 3´ untranslated region on SULT1A1 activity in Japanese subjects. SNPs in the SULT1A1 promoter and 3´ untranslated region were not associated with SULT1A1 activity (P > 0.05. SULT1A1*1/2 (Arg213His was marginally associated with SULT1A1 activity (P = 0.037. However, SULT1A1 CNVs were strongly associated with SULT1A1 activity (trend test P = 0.008 and accounted for 10% of the observed variability in activity for Japanese subjects. In conclusion, SULT1A1 CNVs play a pivotal role in determination of SULT1A1 activity in Japanese subjects, highlighting the influence of ethnic differences in SULT1A1 genetic variants on drug metabolism and therapeutic efficacy.Keywords: CNV, genotype, phenotype, SULT1A1, single nucleotide polymorphisms

  2. Nucla CFB Demonstration Project

    Energy Technology Data Exchange (ETDEWEB)

    1990-12-01

    This report documents Colorado-Ute Electric Association's Nucla Circulating Atmospheric Fluidized-Bed Combustion (AFBC) demonstration project. It describes the plant equipment and system design for the first US utility-size circulating AFBC boiler and its support systems. Included are equipment and system descriptions, design/background information and appendices with an equipment list and selected information plus process flow and instrumentation drawings. The purpose of this report is to share the information gathered during the Nucla circulating AFBC demonstration project and present it so that the general public can evaluate the technical feasibility and cost effectiveness of replacing pulverized or stoker-fired boiler units with circulating fluidized-bed boiler units. (VC)

  3. IGCC technology and demonstration

    Energy Technology Data Exchange (ETDEWEB)

    Palonen, J. [A. Ahlstrom Corporation, Karhula (Finland). Hans Ahlstrom Lab.; Lundqvist, R.G. [A. Ahlstrom Corporation, Helsinki (Finland); Staahl, K. [Sydkraft AB, Malmoe (Sweden)

    1996-12-31

    Future energy production will be performed by advanced technologies that are more efficient, more environmentally friendly and less expensive than current technologies. Integrated gasification combined cycle (IGCC) power plants have been proposed as one of these systems. Utilising biofuels in future energy production will also be emphasised since this lowers substantially carbon dioxide emissions into the atmosphere due to the fact that biomass is a renewable form of energy. Combining advanced technology and biomass utilisation is for this reason something that should and will be encouraged. A. Ahlstrom Corporation of Finland and Sydkraft AB of Sweden have as one part of company strategies adopted this approach for the future. The companies have joined their resources in developing a biomass-based IGCC system with the gasification part based on pressurised circulating fluidized-bed technology. With this kind of technology electrical efficiency can be substantially increased compared to conventional power plants. As a first concrete step, a decision has been made to build a demonstration plant. This plant, located in Vaernamo, Sweden, has already been built and is now in commissioning and demonstration stage. The system comprises a fuel drying plant, a pressurised CFB gasifier with gas cooling and cleaning, a gas turbine, a waste heat recovery unit and a steam turbine. The plant is the first in the world where the integration of a pressurised gasifier with a gas turbine will be realised utilising a low calorific gas produced from biomass. The capacity of the Vaernamo plant is 6 MW of electricity and 9 MW of district heating. Technology development is in progress for design of plants of sizes from 20 to 120 MWe. The paper describes the Bioflow IGCC system, the Vaernamo demonstration plant and experiences from the commissioning and demonstration stages. (orig.)

  4. The Majorana Demonstrator

    CERN Document Server

    Aguayo, E; Hoppe, E W; Keillor, M E; Kephart, J D; Kouzes, R T; LaFerriere, B D; Merriman, J; Orrell, J L; Overman, N R; Avignone, F T; Back, H O; Combs, D C; Leviner, L E; Young, A R; Barabash, A S; Konovalov, S I; Vanyushin, I; Yumatov, V; Bergevin, M; Chan, Y-D; Detwiler, J A; Loach, J C; Martin, R D; Poon, A W P; Prior, G; Vetter, K; Bertrand, F E; Cooper, R J; Radford, D C; Varner, R L; Yu, C -H; Boswell, M; Elliott, S R; Gehman, V M; Hime, A; Kidd, M F; LaRoque, B H; Rielage, K; Ronquest, M C; Steele, D; Brudanin, V; Egorov, V; Gusey, K; Kochetov, O; Shirchenko, M; Timkin, V; Yakushev, E; Busch, M; Esterline, J; Tornow, W; Christofferson, C D; Horton, M; Howard, S; Sobolev, V; Collar, J I; Fields, N; Creswick, R J; Doe, P J; Johnson, R A; Knecht, A; Leon, J; Marino, M G; Miller, M L; Robertson, R G H; Schubert, A G; Wolfe, B A; Efremenko, Yu; Ejiri, H; Hazama, R; Nomachi, M; Shima, T; Finnerty, P; Fraenkle, F M; Giovanetti, G K; Green, M P; Henning, R; Howe, M A; MacMullin, S; Phillips, D G; Snavely, K J; Strain, J; Vorren, K; Guiseppe, V E; Keller, C; Mei, D -M; Perumpilly, G; Thomas, K; Zhang, C; Hallin, A L; Keeter, K J; Mizouni, L; Wilkerson, J F

    2011-01-01

    A brief review of the history and neutrino physics of double beta decay is given. A description of the MAJORANA DEMONSTRATOR research and development program including background reduction techniques is presented in some detail. The application of point contact (PC) detectors to the experiment is discussed, including the effectiveness of pulse shape analysis. The predicted sensitivity of a PC detector array enriched to 86% in 76Ge is given.

  5. The Majorana Demonstrator

    Energy Technology Data Exchange (ETDEWEB)

    Aguayo, Estanislao; Fast, James E.; Hoppe, Eric W.; Keillor, Martin E.; Kephart, Jeremy D.; Kouzes, Richard T.; LaFerriere, Brian D.; Merriman, Jason H.; Orrell, John L.; Overman, Nicole R.; Avignone, Frank T.; Back, Henning O.; Combs, Dustin C.; Leviner, L.; Young, A.; Barabash, Alexander S.; Konovalov, S.; Vanyushin, I.; Yumatov, Vladimir; Bergevin, M.; Chan, Yuen-Dat; Detwiler, Jason A.; Loach, J. C.; Martin, R. D.; Poon, Alan; Prior, Gersende; Vetter, Kai; Bertrand, F.; Cooper, R. J.; Radford, D. C.; Varner, R. L.; Yu, Chang-Hong; Boswell, M.; Elliott, S.; Gehman, Victor M.; Hime, Andrew; Kidd, M. F.; LaRoque, B. H.; Rielage, Keith; Ronquest, M. C.; Steele, David; Brudanin, V.; Egorov, Viatcheslav; Gusey, K.; Kochetov, Oleg; Shirchenko, M.; Timkin, V.; Yakushev, E.; Busch, Matthew; Esterline, James H.; Tornow, Werner; Christofferson, Cabot-Ann; Horton, Mark; Howard, S.; Sobolev, V.; Collar, J. I.; Fields, N.; Creswick, R.; Doe, Peter J.; Johnson, R. A.; Knecht, A.; Leon, Jonathan D.; Marino, Michael G.; Miller, M. L.; Robertson, R. G. H.; Schubert, Alexis G.; Wolfe, B. A.; Efremenko, Yuri; Ejiri, H.; Hazama, R.; Nomachi, Masaharu; Shima, T.; Finnerty, P.; Fraenkle, Florian; Giovanetti, G. K.; Green, M.; Henning, Reyco; Howe, M. A.; MacMullin, S.; Phillips, D.; Snavely, Kyle J.; Strain, J.; Vorren, Kris R.; Guiseppe, Vincente; Keller, C.; Mei, Dong-Ming; Perumpilly, Gopakumar; Thomas, K.; Zhang, C.; Hallin, A. L.; Keeter, K.; Mizouni, Leila; Wilkerson, J. F.

    2011-09-03

    A brief review of the history and neutrino physics of double beta decay is given. A description of the MAJORANA DEMONSTRATOR research and development program, including background reduction techniques, is presented in some detail. The application of point contact (PC) detectors to the experiment is discussed, including the effectiveness of pulse shape analysis. The predicted sensitivity of a PC detector array enriched to 86% to 76Ge is given.

  6. Natural Hazard Demonstrations for Teaching

    Science.gov (United States)

    Malamud, B. D.

    2005-12-01

    This paper presents several demonstrations that have been developed or gathered from other sources in the general area of natural hazards (e.g. landslides, earthquakes, volcanoes, wildfires, tsunamis, mass movements, asteroid impacts, etc.). There are many methods of teaching, but as university lecturers, particularly for large class sizes, we find ourselves too often presenting material to students by direct speaking, or some combination of blackboard/whiteboard/slide projector/digital projector. There are certainly a number of techniques to more actively involve students, so that teaching is not just `receiving of information', including breaking up students into small group discussions, encouraging students to actively participate in class through comments and questions, and/or some combination of hands-on activities and demonstrations. It is this latter which is concentrated on here. As a teaching tool, the students themselves became much more excited about what they are learning if use is made of 5--10 minute demonstrations, even if only peripherally related to the subject at hand. The resultant discussion with questions and comments by students keeps both the students and the lecturer (in this case the author) motivated and intrigued about the subjects being discussed. Days, weeks, and months later, the students remember these `demonstrations', but to set these up takes time, effort, and resources of equipment, although not necessarily a large amount of the latter. Several natural hazards demonstrations are presented here, most inexpensive, that have been used in front of large university classes and smaller `break-out groups', and which can also be adapted for secondary-school students.

  7. Structural Assembly Demonstration Experiment (SADE)

    Science.gov (United States)

    Akin, David L.; Mills, Raymond A.; Bowden, Mary L.

    1987-01-01

    The purpose of the Structural Assembly Demonstration Experiment (SADE) was to create a near-term Shuttle flight experiment focusing on the deployment and erection of structural truss elements. The activities of the MIT Space Systems Laboratory consist of three major areas: preparing and conducting neutral buoyancy simulation test series; producing a formal SADE Experiment plan; and studying the structural dynamics issues of the truss structure. Each of these areas is summarized.

  8. Final Demonstrator Status

    DEFF Research Database (Denmark)

    Workspace

    2003-01-01

    The WorkSPACE project aims to create an integrated environment for collaborative  work activities that can be distributed over a variety of spaces and that mixes digital  and physical materials. We have termed this ‘spatial computing’ because much of the  functionality is provided through...

  9. Demonstration: Genetic Jewelry

    Science.gov (United States)

    Atkins, Thomas; Roderick, Joyce

    2006-01-01

    In order for students to understand genetics and evolution, they must first understand the structure of the DNA molecule. The function of DNA proceeds from its unique structure, a structure beautifully adapted for information storage, transcription, translation into amino acid sequences, replication, and time travel. The activity described in this…

  10. Learning From Demonstration?

    DEFF Research Database (Denmark)

    Koch, Christian; Bertelsen, Niels Haldor

    2014-01-01

    . This paper reports on an early demonstration project, the Building of a passive house dormitory in the Central Region of Denmark in 2006-2009. The project was supposed to deliver value, lean design, prefabrication, quality in sustainability, certification according to German standards for passive houses...... of control, driven by such challenges as complying with cost goals, the need to choose a German prefab supplier, and local contractors. Energy calculations, indoor climate, issues related to square meter requirements, and the hydrogen element became problematic. The aim to obtain passive house certification...

  11. Learning From Demonstration?

    DEFF Research Database (Denmark)

    Koch, Christian; Bertelsen, Niels Haldor

    2014-01-01

    , and micro combined heat and power using hydrogen. Using sociological and business economic theories of innovation, the paper discusses how early movers of innovation tend to obtain only partial success when demonstrating their products and often feel obstructed by minor details. The empirical work...... encompasses both an evaluation of the design and Construction process as well as a post-occupancy evaluation. Process experiences include the use of a multidisciplinary competence group and performance measurement. The commencement of the project was enthusiastic, but it was forced into more traditional forms...

  12. NAVAJO ELECTRIFICATION DEMONSTRATION PROJECT

    Energy Technology Data Exchange (ETDEWEB)

    Terry W. Battiest

    2008-06-11

    The Navajo Electrification Demonstration Project (NEDP) is a multi-year project which addresses the electricity needs of the unserved and underserved Navajo Nation, the largest American Indian tribe in the United States. The program serves to cumulatively provide off-grid electricty for families living away from the electricty infrastructure, line extensions for unserved families living nearby (less than 1/2 mile away from) the electricity, and, under the current project called NEDP-4, the construction of a substation to increase the capacity and improve the quality of service into the central core region of the Navajo Nation.

  13. Glycosylation of Thermomyces lanuginosa lipase enhances surface binding towards phospholipids, but does not significantly influence the catalytic activity

    DEFF Research Database (Denmark)

    Peters, Günther H.J.; Svendsen, Allan; Langbjerg, H.;

    2002-01-01

    or PG matrix than Tll. Addition of the substrate analog benzene boronic acid (BBA) increases the binding affinity of the S146A and N33Q mutants, while only small changes are observed for Tll suggesting that the dynamics of the active-site lid influences the binding affinity and that the flexibility...

  14. [The significance of activities in the Imperial Orthodox Palestine Society for progression of medicine in the Middle East (to the 130th anniversary of foundation)].

    Science.gov (United States)

    Gorelova, L Ye; Afanasiyeva, Ye A

    2012-01-01

    The article deals with the history of foundation of the Imperial Orthodox Palestine Society in Jerusalem and its input into progression of medicine in the Middle east. The medical activity of Russian physicians in medical institutions of the Society is reflected too.

  15. The significance of the European beaver (Castor fibre activity for the process of renaturalization of river valleys in the era of increasing

    Directory of Open Access Journals (Sweden)

    Kusztal Piotr

    2017-03-01

    Full Text Available Changes in the environment that are caused by the activity of beavers bring numerous advantages. They affect the increase in biodiversity, contribute to improving the condition of cleanliness of watercourses, improve local water relations and restore the natural landscape of river valleys.

  16. Buried Waste Integrated Demonstration Plan

    Energy Technology Data Exchange (ETDEWEB)

    Kostelnik, K.M.

    1991-12-01

    This document presents the plan of activities for the Buried Waste Integrated Demonstration (BWID) program which supports the environmental restoration (ER) objectives of the Department of Energy (DOE) Complex. Discussed in this plan are the objectives, organization, roles and responsibilities, and the process for implementing and managing BWID. BWID is hosted at the Idaho National Engineering Laboratory (INEL), but involves participants from throughout the DOE Complex, private industry, universities, and the international community. These participants will support, demonstrate, and evaluate a suite of advanced technologies representing a comprehensive remediation system for the effective and efficient remediation of buried waste. The processes for identifying technological needs, screening candidate technologies for applicability and maturity, selecting appropriate technologies for demonstration, field demonstrating, evaluation of results and transferring technologies to environmental restoration programs are also presented. This document further describes the elements of project planning and control that apply to BWID. It addresses the management processes, operating procedures, programmatic and technical objectives, and schedules. Key functions in support of each demonstration such as regulatory coordination, safety analyses, risk evaluations, facility requirements, and data management are presented.

  17. Education Demonstration Equipment

    Science.gov (United States)

    Nagy, A.; Lee, R. L.

    2003-10-01

    The General Atomics fusion education program ``Scientist in the Classroom" (SIC) now in its sixth year, uses scientists and engineers to present plasma as a state of matter to students in the classroom. Using hands-on equipment, students see how magnets, gas pressure changes, and different gases are turned into plasmas. A piston, sealed volume, and vacuum chamber illuminate ideal gas laws. Liquid nitrogen is used to explore thermodynamic temperature effects and changes in states of matter. Light bulbs are excited with a Tesla coil to ionize gases, thus becoming an inexpensive plasma devices and a plasma tube shows magnetic interactions with plasma. The demonstration equipment used in this program is built with simple designs and common commercial equipment keeping in mind a teacher's tight budget. The SIC program ( ˜25 school presentations per year) has become very popular and has acquired an enthusiastic group of regular teacher clientele requesting repeat visits. In addition, three very popular and successful ``Build-It" days, sponsored by the General Atomics Fusion Education Outreach Program, enables teachers to build and keep in their classroom some of this equipment. The demonstration devices will be presented along with their ``build-it" details.

  18. Smart Grid Demonstration Project

    Energy Technology Data Exchange (ETDEWEB)

    Miller, Craig [National Rural Electric Cooperative Association, Arlington, VA (United States); Carroll, Paul [National Rural Electric Cooperative Association, Arlington, VA (United States); Bell, Abigail [National Rural Electric Cooperative Association, Arlington, VA (United States)

    2015-03-11

    The National Rural Electric Cooperative Association (NRECA) organized the NRECA-U.S. Department of Energy (DOE) Smart Grid Demonstration Project (DE-OE0000222) to install and study a broad range of advanced smart grid technologies in a demonstration that spanned 23 electric cooperatives in 12 states. More than 205,444 pieces of electronic equipment and more than 100,000 minor items (bracket, labels, mounting hardware, fiber optic cable, etc.) were installed to upgrade and enhance the efficiency, reliability, and resiliency of the power networks at the participating co-ops. The objective of this project was to build a path for other electric utilities, and particularly electrical cooperatives, to adopt emerging smart grid technology when it can improve utility operations, thus advancing the co-ops’ familiarity and comfort with such technology. Specifically, the project executed multiple subprojects employing a range of emerging smart grid technologies to test their cost-effectiveness and, where the technology demonstrated value, provided case studies that will enable other electric utilities—particularly electric cooperatives— to use these technologies. NRECA structured the project according to the following three areas: Demonstration of smart grid technology; Advancement of standards to enable the interoperability of components; and Improvement of grid cyber security. We termed these three areas Technology Deployment Study, Interoperability, and Cyber Security. Although the deployment of technology and studying the demonstration projects at coops accounted for the largest portion of the project budget by far, we see our accomplishments in each of the areas as critical to advancing the smart grid. All project deliverables have been published. Technology Deployment Study: The deliverable was a set of 11 single-topic technical reports in areas related to the listed technologies. Each of these reports has already been submitted to DOE, distributed to co-ops, and

  19. Ultraviolet B-exposed major histocompatibility complex class II positive keratinocytes and antigen-presenting cells demonstrate a differential capacity to activate T cells in the presence of staphylococcal superantigens

    Energy Technology Data Exchange (ETDEWEB)

    Skov, L.; Baadsgaard, O. [Gentofte Hospital, Copenhagen (Denmark). Dept. of Dermatology

    1996-05-01

    In this study we tested the capacity of ultraviolet B (UVB)-irradiated major histocompatability complex (MHC) class II{sup +} keratinocytes, monocytes and dendritic cells to activate T cells in the presence of Staphylococcus enterotoxin B. We demonstrated that UVB irradiation of MHC class II{sup +} keratinocytes does not change their capacity to activate T cells in the presence of Staphylococcus enterotoxin B. In contrast, UVB irradiation of antigen-presenting cells decreases their capacity to activate T cells. The differential capacity to activate T cells after UVB irradiation was not due to factors released from UVB-irradiated cells. The interferon-{gamma} induced upregulation of HLA-DR and intercellular adhesion molecule-1 on keratinocytes does not seem to be the only explanation, since UVB irradiation decreased the accessory cell function of interferon-{gamma} pretreated monocytes. Differential requirements for and UVB regulation of costimulatory molecules may be involved, since blocking of the B7/CD28 pathway affects the capacity of dendritic cells but not keratinocytes to activate T cells in the presence of Staphylococcus enterotoxin B. Thus, MHC class II{sup +} keratinocytes in the presence of superantigens released from staphylococci may activate T cells and maintain inflammation despite UVB treatment. (Author).

  20. [16S rDNA diversity analysis of 30 Streptomycetes isolates displaying significant cytotoxic activity against B16 cell from near-shore sediments of Hainan Island].

    Science.gov (United States)

    Yan, Li-Ping; Hong, Kui; Hu, Shen-cai; Liu, Li-hua

    2005-04-01

    A total of 354 isolates of actinomycetes, of which 76 were detected cytotoxic activity was isolated from near-shore marine samples collected at Wenchang mangrove, DanZhou harbor and YanPu harbor. Four isolation methods were employed, which are SDS pretreatment, phenol pretreatment, heating pretreatment and potassium dichromate selection culture, and media such as'Yeast extract-Malt extract (YE), Glucose-Asprine (GA), Starch-Casin (SC), Starch-KNO3 (Gause) were used. It was showed that heating pretreatment and potassium dichromate selection culture were more considerable methods for extensive isolation of actinomycetes. Medium YE and Gause showed best results in both the total number of actinomycetes and the number of active isolates against tumor cell B16. The genotypic diversity of 30 strains of Streptomycetes possessing strong cytotoxic activity against B16 cell (ID50 > or =200) was analyzed by 16S ARDRA, which resulted in 17 RFLP types, and indicated relatively rich genotypic diversity among these Streptomycetes. 16S rDNA sequence analysis of three strains, 050642, 060386 and 060524 (ID50 > or = 1200) further confirmed that they all belong to Streptomyces genus and strain 050642 was suggested a novel Streptomyces. Spp with the highest similarity of 95% to Streptomyces cattleya.

  1. Jennings Demonstration PLant

    Energy Technology Data Exchange (ETDEWEB)

    Russ Heissner

    2010-08-31

    Verenium operated a demonstration plant with a capacity to produce 1.4 million gallons of cellulosic ethanol from agricultural resiues for about two years. During this time, the plant was able to evaluate the technical issues in producing ethanol from three different cellulosic feedstocks, sugar cane bagasse, energy cane, and sorghum. The project was intended to develop a better understanding of the operating parameters that would inform a commercial sized operation. Issues related to feedstock variability, use of hydrolytic enzymes, and the viability of fermentative organisms were evaluated. Considerable success was achieved with pretreatment processes and use of enzymes but challenges were encountered with feedstock variability and fermentation systems. Limited amounts of cellulosic ethanol were produced.

  2. The macrophage activation marker sCD163 combined with markers of the Enhanced Liver Fibrosis (ELF) score predicts clinically significant portal hypertension in patients with cirrhosis

    DEFF Research Database (Denmark)

    Sandahl, T D; McGrail, R; Møller, Holger Jon

    2016-01-01

    BACKGROUND: Noninvasive identification of significant portal hypertension in patients with cirrhosis is needed in hepatology practice. AIM: To investigate whether the combination of sCD163 as a hepatic inflammation marker and the fibrosis markers of the Enhanced Liver Fibrosis score (ELF) can...... predict portal hypertension in patients with cirrhosis. METHODS: We measured sCD163 and the ELF components (hyaluronic acid, tissue inhibitor of metalloproteinase-1 and procollagen-III aminopeptide) in two separate cohorts of cirrhosis patients that underwent hepatic vein catheterisation. To test...... the predictive accuracy we developed a CD163-fibrosis portal hypertension score in an estimation cohort (n = 80) and validated the score in an independent cohort (n = 80). A HVPG ≥10 mmHg was considered clinically significant. RESULTS: Both sCD163 and the ELF components increased in a stepwise manner...

  3. Increased levels of IL-6 in the cerebrospinal fluid of patients with chronic schizophrenia — significance for activation of the kynurenine pathway

    Science.gov (United States)

    Schwieler, Lilly; Larsson, Markus K.; Skogh, Elisabeth; Kegel, Magdalena E.; Orhan, Funda; Abdelmoaty, Sally; Finn, Anja; Bhat, Maria; Samuelsson, Martin; Lundberg, Kristina; Dahl, Marja-Liisa; Sellgren, Carl; Schuppe-Koistinen, Ina; Svensson, Camilla I.; Erhardt, Sophie; Engberg, Göran

    2015-01-01

    Background Accumulating evidence indicates that schizophrenia is associated with brain immune activation. While a number of reports suggest increased cytokine levels in patients with schizophrenia, many of these studies have been limited by their focus on peripheral cytokines or confounded by various antipsychotic treatments. Here, well-characterized patients with schizophrenia, all receiving olanzapine treatment, and healthy volunteers were analyzed with regard to cerebrospinal fluid (CSF) levels of cytokines. We correlated the CSF cytokine levels to previously analyzed metabolites of the kynurenine (KYN) pathway. Methods We analyzed the CSF from patients and controls using electrochemiluminescence detection with regard to cytokines. Cell culture media from human cortical astrocytes were analyzed for KYN and kynurenic acid (KYNA) using high-pressure liquid chromatography or liquid chromatography/mass spectrometry. Results We included 23 patients and 37 controls in our study. Patients with schizophrenia had increased CSF levels of interleukin (IL)-6 compared with healthy volunteers. In patients, we also observed a positive correlation between IL-6 and the tryptophan:KYNA ratio, indicating that IL-6 activates the KYN pathway. In line with this, application of IL-6 to cultured human astrocytes increased cell medium concentration of KYNA. Limitations The CSF samples had been frozen and thawed twice before analysis of cytokines. Median age differed between patients and controls. When appropriate, all present analyses were adjusted for age. Conclusion We have shown that IL-6, KYN and KYNA are elevated in patients with chronic schizophrenia, strengthening the idea of brain immune activation in patients with this disease. Our concurrent cell culture and clinical findings suggest that IL-6 induces the KYN pathway, leading to increased production of the N-methyl-d-aspartate receptor antagonist KYNA in patients with schizophrenia. PMID:25455350

  4. Significant neutralizing activities against H2N2 influenza A viruses in human intravenous immunoglobulin lots manufactured from 1993 to 2010

    Directory of Open Access Journals (Sweden)

    Ikuta K

    2012-07-01

    Full Text Available Ritsuko Kubota-Koketsu,1,2 Mikihiro Yunoki,2,3 Yoshinobu Okuno,1 Kazuyoshi Ikuta21Kanonji Institute, The Research Foundation for Microbial Diseases of Osaka University, Kagawa; 2Department of Virology, Research Institute for Microbial Diseases, Osaka University, 3Pathogenic Risk Management, Benesis Corporation, Osaka, JapanAbstract: Influenza A H2N2 virus, also known as the Asian flu, spread worldwide from 1957 to 1967, although there have been no cases reported in humans in the past 40 years. A vaccination program was introduced in Japan in the 1960s. Older Japanese donors could have been naturally infected with the H2N2 virus or vaccinated in the early 1960s. Human intravenous immunoglobulin (IVIG reflects the epidemiological status of the donating population in a given time period. Here, the possible viral neutralizing (VN activities of IVIG against the H2N2 virus were examined. Hemagglutination inhibition (HI and VN activities of IVIG lots manufactured from 1993 to 2010 in Japan and the United States were evaluated against H2N2 viruses. High HI and VN activities against H2N2 viruses were found in all the IVIG lots investigated. HI titers were 32–64 against the isolate in 1957 and 64–128 against the isolates in 1965. VN titers were 80–320 against the isolate in 1957 and 1280–5120 against the isolates in 1965. Both the HI and VN titers were higher against the isolate in 1965 than in 1957. Thus, antibody titers of IVIG against influenza viruses are well correlated with the history of infection and the vaccine program in Japan. Therefore, evaluation of antibody titers provides valuable information about IVIGs, which could be used for immune stimulation when a new influenza virus emerges in the human population.Keywords: IVIG, influenza, H2N2, neutralization

  5. A Significantly Twisted Spirocyclic Phosphine Oxide as a Universal Host for High-Efficiency Full-Color Thermally Activated Delayed Fluorescence Diodes.

    Science.gov (United States)

    Li, Jing; Ding, Dongxue; Tao, Youtian; Wei, Ying; Chen, Runfeng; Xie, Linghai; Huang, Wei; Xu, Hui

    2016-04-01

    A universal thermally activated delayed fluorescence (TADF) host, 4'-diphenylphosphinoylspiro[fluorene-9,9'-xanthene] (SFXSPO), is constructed with a highly distorted and asymmetric configuration and disordered molecular packing in its solid state. SFXSPO successfully endows its full-color TADF diodes with state-of-the-art performance, e.g., the record external quantum efficiency of 22.5% and 19.1% and internal quantum efficiency of ≈100% for its yellow TADF diodes and single-host full-TADF nearly-white-emitting devices, respectively.

  6. Brain functional network connectivity based on a visual task: visual information processing-related brain regions are significantly activated in the task state.

    Science.gov (United States)

    Yang, Yan-Li; Deng, Hong-Xia; Xing, Gui-Yang; Xia, Xiao-Luan; Li, Hai-Fang

    2015-02-01

    It is not clear whether the method used in functional brain-network related research can be applied to explore the feature binding mechanism of visual perception. In this study, we investigated feature binding of color and shape in visual perception. Functional magnetic resonance imaging data were collected from 38 healthy volunteers at rest and while performing a visual perception task to construct brain networks active during resting and task states. Results showed that brain regions involved in visual information processing were obviously activated during the task. The components were partitioned using a greedy algorithm, indicating the visual network existed during the resting state. Z-values in the vision-related brain regions were calculated, confirming the dynamic balance of the brain network. Connectivity between brain regions was determined, and the result showed that occipital and lingual gyri were stable brain regions in the visual system network, the parietal lobe played a very important role in the binding process of color features and shape features, and the fusiform and inferior temporal gyri were crucial for processing color and shape information. Experimental findings indicate that understanding visual feature binding and cognitive processes will help establish computational models of vision, improve image recognition technology, and provide a new theoretical mechanism for feature binding in visual perception.

  7. Significant in vivo anti-inflammatory activity of Pytren4Q-Mn a superoxide dismutase 2 (SOD2 mimetic scorpiand-like Mn (II complex.

    Directory of Open Access Journals (Sweden)

    Carolina Serena

    Full Text Available The clinical use of purified SOD enzymes has strong limitations due to their large molecular size, high production cost and immunogenicity. These limitations could be compensated by using instead synthetic SOD mimetic compounds of low molecular weight.We have recently reported that two SOD mimetic compounds, the Mn(II complexes of the polyamines Pytren2Q and Pytren4Q, displayed high antioxidant activity in bacteria and yeast. Since frequently molecules with antioxidant properties or free-radical scavengers also have anti-inflammatory properties we have assessed the anti-inflammatory potential of Pytren2Q and Pytren4Q Mn(II complexes, in cultured macrophages and in a murine model of inflammation, by measuring the degree of protection they could provide against the cellular injury produced by lipopolisacharide, a bacterial endotoxin.In this report we show that the Mn(II complex of Pytren4Q but not that of Pytren2Q effectively protected human cultured THP-1 macrophages and whole mice from the inflammatory effects produced by LPS. These results obtained with two molecules that are isomers highlight the importance of gathering experimental data from animal models of disease in assessing the potential of candidate molecules.The effective anti-inflammatory activity of the Mn(II complex of Pytren4Q in addition to its low toxicity, water solubility and ease of production would suggest it is worth taking into consideration for future pharmacological studies.

  8. Clinical significance of variations in levels of Epstein-Barr Virus (EBV) antigen and adaptive immune response during chronic active EBV infection in children.

    Science.gov (United States)

    Xing, Yan; Song, Hong Mei; Wei, Min; Liu, Yu; Zhang, Yu Hua; Gao, Li

    2013-01-01

    Pediatric patients were recruited to analyze differences in Epstein-Barr virus (EBV) copy numbers and adaptive immune reactions in children with chronic active vs acute EBV infection (CAEBVI vs AEBVI), as well as to examine the relationship between these parameters and the pathogenesis of CAEBVI. Fluorescent qPCR was used to assess EBV-DNA levels, while ELISA, antibody affinity, flow cytometry, and heterophil agglutination (HA) assays were used to evaluate patient EBV-adaptive humoral and cellular immunity. Lastly, ELISPOT was employed to assess interferon (IFN)-γ secretory functions of EBV-specific cytotoxic T-lymphocytes (CTL) as a marker of subject EBV-specific adaptive cellular immunity. The results indicated that, compared with AEBVI patients or normal children, there was a dramatic elevation in viral copy levels, viral capsid antigen (VCA)-IgA, early antigen (EA)-IgA, and EA-IgG, but a lack of EBV nuclear antigen (EBNA)-IgG and a negative HA in CAEBVI patients (p EBV-specific CTL function compared with normal children (p EBV antigen availability and in both the adaptive humoral and cellular immune responses in patients with CAEBVI, and that these outcomes may be associated with the chronic active re-infection process itself associated with CAEBVI.

  9. Brain functional network connectivity based on a visual task: visual information processing-related brain regions are significantly activated in the task state

    Directory of Open Access Journals (Sweden)

    Yan-li Yang

    2015-01-01

    Full Text Available It is not clear whether the method used in functional brain-network related research can be applied to explore the feature binding mechanism of visual perception. In this study, we investigated feature binding of color and shape in visual perception. Functional magnetic resonance imaging data were collected from 38 healthy volunteers at rest and while performing a visual perception task to construct brain networks active during resting and task states. Results showed that brain regions involved in visual information processing were obviously activated during the task. The components were partitioned using a greedy algorithm, indicating the visual network existed during the resting state. Z-values in the vision-related brain regions were calculated, confirming the dynamic balance of the brain network. Connectivity between brain regions was determined, and the result showed that occipital and lingual gyri were stable brain regions in the visual system network, the parietal lobe played a very important role in the binding process of color features and shape features, and the fusiform and inferior temporal gyri were crucial for processing color and shape information. Experimental findings indicate that understanding visual feature binding and cognitive processes will help establish computational models of vision, improve image recognition technology, and provide a new theoretical mechanism for feature binding in visual perception.

  10. NASA Bioreactor Demonstration System

    Science.gov (United States)

    2002-01-01

    Leland W. K. Chung (left), Director, Molecular Urology Therapeutics Program at the Winship Cancer Institute at Emory University, is principal investigator for the NASA bioreactor demonstration system (BDS-05). With him is Dr. Jun Shu, an assistant professor of Orthopedics Surgery from Kuming Medical University China. The NASA Bioreactor provides a low turbulence culture environment which promotes the formation of large, three-dimensional cell clusters. Due to their high level of cellular organization and specialization, samples constructed in the bioreactor more closely resemble the original tumor or tissue found in the body. The Bioreactor is rotated to provide gentle mixing of fresh and spent nutrient without inducing shear forces that would damage the cells. The work is sponsored by NASA's Office of Biological and Physical Research. The bioreactor is managed by the Biotechnology Cell Science Program at NASA's Johnson Space Center (JSC). NASA-sponsored bioreactor research has been instrumental in helping scientists to better understand normal and cancerous tissue development. In cooperation with the medical community, the bioreactor design is being used to prepare better models of human colon, prostate, breast and ovarian tumors. Cartilage, bone marrow, heart muscle, skeletal muscle, pancreatic islet cells, liver and kidney are just a few of the normal tissues being cultured in rotating bioreactors by investigators. Credit: Emory University.

  11. Nuclear power demonstrating

    Energy Technology Data Exchange (ETDEWEB)

    Basmajian, V. V.; Haldeman, C. W.

    1980-08-12

    Apparatus for demonstrating the operation of a closed loop nuclear steam electric generating plant includes a transparent boiler assembly having immersion heating elements, which may be quartz lamps or stainless steel encased resistive immersion heating units with a quartz iodide lamp providing a source of visible radiation when using the encased immersion heating units. A variable voltage autotransformer is geared to a support rod for simulated reactor control rods for controlling the energy delivered to the heating elements and arranged so that when the voltage is high, the rods are withdrawn from the boiler to produce increased heating and illumination proportional to rod position, thereby simulating nuclear reaction. A relief valve, steam outlet pipe and water inlet pipe are connected to the boiler with a small stainless steel resistive heating element in the steam outlet pipe providing superheat. This heater is connected in series with a rheostat mounted on the front panel to provide superheat adjustments and an interlock switch that prevents the superheater from being energized when the steam valve is off with with no flow through the superheater. A heavy blue plastic radiation shield surrounds the boiler inside a bell jar.

  12. A Demonstration of Lusail

    KAUST Repository

    Mansour, Essam

    2017-05-10

    There has been a proliferation of datasets available as interlinked RDF data accessible through SPARQL endpoints. This has led to the emergence of various applications in life science, distributed social networks, and Internet of Things that need to integrate data from multiple endpoints. We will demonstrate Lusail; a system that supports the need of emerging applications to access tens to hundreds of geo-distributed datasets. Lusail is a geo-distributed graph engine for querying linked RDF data. Lusail delivers outstanding performance using (i) a novel locality-aware query decomposition technique that minimizes the intermediate data to be accessed by the subqueries, and (ii) selectivityawareness and parallel query execution to reduce network latency and to increase parallelism. During the demo, the audience will be able to query actually deployed RDF endpoints as well as large synthetic and real benchmarks that we have deployed in the public cloud. The demo will also show that Lusail outperforms state-of-the-art systems by orders of magnitude in terms of scalability and response time.

  13. Solar Thermal Demonstration Project

    Energy Technology Data Exchange (ETDEWEB)

    Biesinger, K; Cuppett, D; Dyer, D

    2012-01-30

    HVAC Retrofit and Energy Efficiency Upgrades at Clark High School, Las Vegas, Nevada The overall objectives of this project are to increase usage of alternative/renewable fuels, create a better and more reliable learning environment for the students, and reduce energy costs. Utilizing the grant resources and local bond revenues, the District proposes to reduce electricity consumption by installing within the existing limited space, one principal energy efficient 100 ton adsorption chiller working in concert with two 500 ton electric chillers. The main heating source will be primarily from low nitrogen oxide (NOX), high efficiency natural gas fired boilers. With the use of this type of chiller, the electric power and cost requirements will be greatly reduced. To provide cooling to the information technology centers and equipment rooms of the school during off-peak hours, the District will install water source heat pumps. In another measure to reduce the cooling requirements at Clark High School, the District will replace single pane glass and metal panels with Kalwall building panels. An added feature of the Kalwall system is that it will allow for natural day lighting in the student center. This system will significantly reduce thermal heat/cooling loss and control solar heat gain, thus delivering significant savings in heating ventilation and air conditioning (HVAC) costs.

  14. Environmental Assessment and Finding of No Significant Impact: Waste Remediation Activities at Elk Hills (Former Naval petroleum Reserve No. 1), Kern County, California

    Energy Technology Data Exchange (ETDEWEB)

    N/A

    1999-12-17

    DOE proposes to conduct a variety of post-sale site remediation activities, such as characterization, assessment, clean-up, and formal closure, at a number of inactive waste sites located at Elk Hills. The proposed post-sale site remediation activities, which would be conducted primarily in developed portions of the oil field, currently are expected to include clean-up of three basic categories of waste sites: (1) nonhazardous solid waste surface trash scatters, (2) produced wastewater sumps, and (3) small solid waste landfills. Additionally, a limited number of other inactive waste sites, which cannot be typified under any of these three categories, have been identified as requiring remediation. Table 2.1-1 presents a summary, organized by waste site category, of the inactive waste sites that require remediation per the PSA, the ASA, and/or the UPCTA. The majority of these sites are known to contain no hazardous waste. However, one of the surface scatter sites (2G) contains an area of burn ash with hazardous levels of lead and zinc, another surface scatter site (25S) contains an area with hazardous levels of lead, a produced wastewater sump site (23S) and a landfill (42-36S) are known to contain hazardous levels of arsenic, and some sites have not yet been characterized. Furthermore, additional types of sites could be discovered. For example, given the nature of oil field operations, sites resulting from either spills or leaks of hazardous materials could be discovered. Given the nature of the agreements entered into by DOE regarding the required post-sale clean-up of the inactive waste sites at Elk Hills, the Proposed Action is the primary course of action considered in this EA. The obligatory remediation activities included in the Proposed Action are standard procedures such that possible variations of the Proposed Action would not vary substantially enough to require designation as a separate, reasonable alternative. Thus, the No Action Alternative is the only

  15. The MAJORANA DEMONSTRATOR radioassay program

    Energy Technology Data Exchange (ETDEWEB)

    Abgrall, N. [Nuclear Science Division, Lawrence Berkeley National Laboratory, Berkeley, CA (United States); Shanghai Jiao Tong University, Shanghai (China); Arnquist, I.J. [Pacific Northwest National Laboratory, Richland, WA (United States); Avignone, F.T. [Department of Physics and Astronomy, University of South Carolina, Columbia, SC (United States); Oak Ridge National Laboratory, Oak Ridge, TN (United States); Back, H.O. [Department of Physics, North Carolina State University, Raleigh, NC (United States); Triangle Universities Nuclear Laboratory, Durham, NC (United States); Barabash, A.S. [National Research Center, “Kurchatov Institute” Institute for Theoretical and Experimental Physics, Moscow (Russian Federation); Bertrand, F.E. [Oak Ridge National Laboratory, Oak Ridge, TN (United States); Boswell, M. [Los Alamos National Laboratory, Los Alamos, NM (United States); Bradley, A.W. [Nuclear Science Division, Lawrence Berkeley National Laboratory, Berkeley, CA (United States); Brudanin, V. [Joint Institute for Nuclear Research, Dubna (Russian Federation); Busch, M. [Department of Physics, Duke University, Durham, NC (United States); Triangle Universities Nuclear Laboratory, Durham, NC (United States); Buuck, M. [Center for Experimental Nuclear Physics and Astrophysics, and Department of Physics, University of Washington, Seattle, WA (United States); Byram, D. [Department of Physics, University of South Dakota, Vermillion, SD (United States); Caldwell, A.S. [South Dakota School of Mines and Technology, Rapid City, SD (United States); Chan, Y.-D. [Nuclear Science Division, Lawrence Berkeley National Laboratory, Berkeley, CA (United States); Christofferson, C.D. [South Dakota School of Mines and Technology, Rapid City, SD (United States); Chu, P.-H. [Los Alamos National Laboratory, Los Alamos, NM (United States); and others

    2016-08-21

    The MAJORANA collaboration is constructing the MAJORANA DEMONSTRATOR at the Sanford Underground Research Facility at the Homestake gold mine, in Lead, SD. The apparatus will use Ge detectors, enriched in isotope {sup 76}Ge, to demonstrate the feasibility of a large-scale Ge detector experiment to search for neutrinoless double beta decay. The long half-life of this postulated process requires that the apparatus be extremely low in radioactive isotopes whose decays may produce backgrounds to the search. The radioassay program conducted by the collaboration to ensure that the materials comprising the apparatus are sufficiently pure is described. The resulting measurements from gamma-ray counting, neutron activation and mass spectroscopy of the radioactive-isotope contamination for the materials studied for use in the detector are reported. We interpret these numbers in the context of the expected background for the experiment.

  16. The MAJORANA DEMONSTRATOR radioassay program

    Science.gov (United States)

    Abgrall, N.; Arnquist, I. J.; Avignone, F. T.; Back, H. O.; Barabash, A. S.; Bertrand, F. E.; Boswell, M.; Bradley, A. W.; Brudanin, V.; Busch, M.; Buuck, M.; Byram, D.; Caldwell, A. S.; Chan, Y.-D.; Christofferson, C. D.; Chu, P.-H.; Cuesta, C.; Detwiler, J. A.; Dunmore, J. A.; Efremenko, Yu.; Ejiri, H.; Elliott, S. R.; Finnerty, P.; Galindo-Uribarri, A.; Gehman, V. M.; Gilliss, T.; Giovanetti, G. K.; Goett, J.; Green, M. P.; Gruszko, J.; Guinn, I. S.; Guiseppe, V. E.; Henning, R.; Hoppe, E. W.; Howard, S.; Howe, M. A.; Jasinski, B. R.; Johnson, R. A.; Keeter, K. J.; Kidd, M. F.; Kochetov, O.; Konovalov, S. I.; Kouzes, R. T.; LaFerriere, B. D.; Leon, J.; Loach, J. C.; MacMullin, J.; MacMullin, S.; Martin, R. D.; Massarczyk, R.; Meijer, S.; Mertens, S.; Miller, M. L.; Orrell, J. L.; O'Shaughnessy, C.; Overman, N. R.; Poon, A. W. P.; Pushkin, K.; Radford, D. C.; Rager, J.; Rielage, K.; Robertson, R. G. H.; Romero-Romero, E.; Ronquest, M. C.; Schubert, A. G.; Shanks, B.; Shirchenko, M.; Snavely, K. J.; Snyder, N.; Steele, D.; Suriano, A. M.; Tedeschi, D.; Trimble, J. E.; Varner, R. L.; Vasilyev, S.; Vetter, K.; Vorren, K.; White, B. R.; Wilkerson, J. F.; Wiseman, C.; Xu, W.; Yakushev, E.; Yu, C.-H.; Yumatov, V.; Zhitnikov, I.

    2016-08-01

    The MAJORANA collaboration is constructing the MAJORANA DEMONSTRATOR at the Sanford Underground Research Facility at the Homestake gold mine, in Lead, SD. The apparatus will use Ge detectors, enriched in isotope 76Ge, to demonstrate the feasibility of a large-scale Ge detector experiment to search for neutrinoless double beta decay. The long half-life of this postulated process requires that the apparatus be extremely low in radioactive isotopes whose decays may produce backgrounds to the search. The radioassay program conducted by the collaboration to ensure that the materials comprising the apparatus are sufficiently pure is described. The resulting measurements from gamma-ray counting, neutron activation and mass spectroscopy of the radioactive-isotope contamination for the materials studied for use in the detector are reported. We interpret these numbers in the context of the expected background for the experiment.

  17. Significant effect of electron transfer between current collector and active material on high rate performance of Li4Ti5O12

    Institute of Scientific and Technical Information of China (English)

    Pan Hui-Lin; Hu Yong-Sheng; Li Hong; Chen Li-Quan

    2011-01-01

    The rate and cycling performances of the electrode materials are affected by many factors in a practical complicated electrode process.Learning about the limiting step in a practical electrochemical reaction is very important to effectively improve the electrochemical performances of the electrode materials.Li4TisO12,as a zero-strain material,has been considered as a promising anode material for long life Li-ion batteries.In this study,our results show that the Li4Ti5O12 pasted on Cu or graphite felt current collector exhibits unexpectedly higher rate performance than on Al current collector.For Li4Ti5O12,the electron transfer between current collector and active material is the critical factor that affects its rate and cycling performances.

  18. Field studies of beach cones as coastal erosion control/reversal devices for areas with significant oil and gas activities. [Annual report], February 24, 1992--February 23, 1993

    Energy Technology Data Exchange (ETDEWEB)

    Law, V.J.

    1993-03-15

    The primary objective of this project is to evaluate the utility of a device called the ``beach cone`` in combating coastal erosion. Seven initial sites were selected for testing beach cones in a variety of geometric configurations. Permits were obtained from the State of Louisiana and the US Army Corps of Engineers to perform the work associated with this study. Six hundred beach cones were actually installed at six of the sites in late July and early August, 1992. One of the initial sites was abandoned because it was found to be unsuitable for beach cone placement. The test sites have been observed for six months and preliminary findings indicate that beach cones accreted significant amounts of materials along the beach of a barrier island. At other test sites, accretion rates have been less dramatic but importantly, no significant additional erosion has occurred, which is a positive result. It is too soon to state the categorical success of the beach cones, but results to date are encouraging.

  19. Significant blockade of multiple receptor tyrosine kinases by MGCD516 (Sitravatinib), a novel small molecule inhibitor, shows potent anti-tumor activity in preclinical models of sarcoma.

    Science.gov (United States)

    Patwardhan, Parag P; Ivy, Kathryn S; Musi, Elgilda; de Stanchina, Elisa; Schwartz, Gary K

    2016-01-26

    Sarcomas are rare but highly aggressive mesenchymal tumors with a median survival of 10-18 months for metastatic disease. Mutation and/or overexpression of many receptor tyrosine kinases (RTKs) including c-Met, PDGFR, c-Kit and IGF1-R drive defective signaling pathways in sarcomas. MGCD516 (Sitravatinib) is a novel small molecule inhibitor targeting multiple RTKs involved in driving sarcoma cell growth. In the present study, we evaluated the efficacy of MGCD516 both in vitro and in mouse xenograft models in vivo. MGCD516 treatment resulted in significant blockade of phosphorylation of potential driver RTKs and induced potent anti-proliferative effects in vitro. Furthermore, MGCD516 treatment of tumor xenografts in vivo resulted in significant suppression of tumor growth. Efficacy of MGCD516 was superior to imatinib and crizotinib, two other well-studied multi-kinase inhibitors with overlapping target specificities, both in vitro and in vivo. This is the first report describing MGCD516 as a potent multi-kinase inhibitor in different models of sarcoma, superior to imatinib and crizotinib. Results from this study showing blockade of multiple driver signaling pathways provides a rationale for further clinical development of MGCD516 for the treatment of patients with soft-tissue sarcoma.

  20. The success of {sup 131}I ablation in thyroid cancer patients is significantly reduced after a diagnostic activity of 40 MBq {sup 131}I

    Energy Technology Data Exchange (ETDEWEB)

    Verburg, F.A. [Dept. of Nuclear Medicine, Univ. Medical Center Utrecht (Netherlands); Dept. of Nuclear Medicine, Univ. Hospital Wuerzburg (Germany); Verkooijen, R.B.T. [Div. of Nuclear Medicine, Dept. of Radiology, Leiden Univ. Medical Center (Netherlands); Dept. of Nuclear Medicine, Maxima Medical Centre (Netherlands); Stokkel, M.P.M. [Div. of Nuclear Medicine, Dept. of Radiology, Leiden Univ. Medical Center (Netherlands); Isselt, J.W. van [Dept. of Nuclear Medicine, Univ. Medical Center Utrecht (Netherlands)

    2009-07-01

    Objective: Dosimetry studies have shown that activities of {sup 131}I as small as 10-20 MBq may cause a stunning effect. A result of this stunning effect may be a lower success rate of the ablative {sup 131}I therapy for differentiated thyroid carcinoma (DTC). The aim of this study was to determine whether pre-therapeutic uptake measurement with 40 MBq {sup 131}I causes a lower success rate of ablation. Design: retrospective chart review study. Patients, methods: In two hospitals the ablation protocols differed in one respect only: in the one hospital no diagnostic {sup 131}I was applied before ablation (group 1, n = 48), whereas in the other hospital a 24-h uptake-measurement with 40 MBq {sup 131}I was performed (group 2, n = 51). Included were all DTC patients without distant metastases who had undergone {sup 131}I ablation between July 2002 and December 2005, and who had returned for {sup 131}I follow-up. Successful ablation was defined as absence of pathological {sup 131}I uptake on diagnostic whole-body scintigraphy and undetectable thyroglobulin-levels under TSH stimulation. Results: Overall, ablation was successful in 31/48 patients (65%) in group 1 and in 17/51 patients (33%) in group 2 (p=0.002). Multivariate analysis showed that pre-therapeutic uptake measurement using 40 MBq {sup 131}I was an independant determinant for success of ablation (p = 0.002). Conclusions: After applying a diagnostic activity of 40 MBq {sup 131}I before ablation, the success rate of ablation is severely reduced. Consequently, the routine application of {sup 131}I for diagnostic scintigraphy or uptake measurement prior to {sup 131}I ablation is best avoided. (orig.)

  1. Evaluation of metal and radionuclide data from neutron activation and acid-digestion-based spectrometry analyses of background soils: Significance in environmental restoration

    Energy Technology Data Exchange (ETDEWEB)

    Lee, S.Y.; Watkins, D.R.; Jackson, B.L.; Schmoyer, R.L. [Oak Ridge National Lab., TN (United States); Lietzke, D.A.; Burgoa, B.B.; Branson, J.T.; Ammons, J.T. [Univ. of Tennessee, Knoxville, TN (United States)

    1995-12-31

    A faster, more cost-effective, and higher-quality data acquisition procedure for natural background-level metals and radionuclides in soils is needed for remedial investigations of contaminated sites. In this project, a total of 120 soil samples were collected from uncontaminated areas on and near the Oak Ridge Reservation. The samples were taken at three different depths and from three different geologic groups to establish background concentrations of metals and radionuclides. The objective of this presentation is to discuss the advantages and disadvantages of neutron activation analysis (NAA) compared with those of acid-digestion-based spectrometry (ADS) methods; the advantages and disadvantages were evaluated from Al, Sb, As, Cr, Co, Fe, Mg, Mn, Hg, K, Ag, {sup 232}Th, {sup 235}U, {sup 238}U, V, and Zn data. The ADS methods used for this project were inductively coupled plasma (ICP), ICP-mass spectrometry (ICP-MS), and alpha spectrometry. The scatter plots showed that the NAA results for As, Co, Fe, Mn, {sup 232}Th, and {sup 238}U are reasonably correlated with the results from the other analytical methods. Compared to NAA, however, the ADS methods underestimated Al, Cr, Mg, K, V, and Zn. The skew distributions were caused by incomplete dissolution of the analytes during acid digestion of the soil samples. Because of the high detection limits of the spectrometric methods, the NAA results and the ADS results for some elements, including Sb, Hg, and Ag, did not show a definite relationship. The NAA results were highly correlated with the alpha spectrometry results for {sup 232}Th and {sup 238}U but poorly correlated for {sup 235}U, probably because of a larger counting error associated with the lower activity of the isotope. The NAA methods, including the delayed neutron counting method, were far superior techniques for quantifying background levels of radionuclides ({sup 232}Th, {sup 235}U, and {sup 238}U) and metals (Al, Cr, Mg, K, V, and Zn) in soils.

  2. Prognostic significance of urokinase plasminogen activator receptor and its cleaved forms in blood from patients with non-small cell lung cancer

    DEFF Research Database (Denmark)

    Almasi, Charlotte Elberling; Høyer-Hansen, Gunilla; Christensen, Ib Jarle

    2009-01-01

    in lung tumour extracts. Here we analyse uPAR forms in blood from patients with non-small cell lung cancer (NSCLC). Preoperatively sampled plasma/serum from 32 patients with NSCLC was analysed. Three time-resolved fluoroimmunoassays (TR-FIAs) measuring intact uPAR(I-III) (TR-FIA 1), uPAR(I-III) + u...... survival. Adjusted for histological subtype high plasma uPAR(I-III) and uPAR(I) levels as well as serum uPAR(I) levels were significantly associated with shorter OS (hazards ratios = 4.3, 2.8 and 3.8 respectively). High blood levels of intact uPAR and its cleaved forms are associated with poor prognosis...

  3. LIMB Demonstration Project Extension and Coolside Demonstration. [Final report

    Energy Technology Data Exchange (ETDEWEB)

    Goots, T.R.; DePero, M.J.; Nolan, P.S.

    1992-11-10

    This report presents results from the limestone Injection Multistage Burner (LIMB) Demonstration Project Extension. LIMB is a furnace sorbent injection technology designed for the reduction of sulfur dioxide (SO{sub 2}) and nitrogen oxides (NO{sub x}) emissions from coal-fired utility boilers. The testing was conducted on the 105 Mwe, coal-fired, Unit 4 boiler at Ohio Edison`s Edgewater Station in Lorain, Ohio. In addition to the LIMB Extension activities, the overall project included demonstration of the Coolside process for S0{sub 2} removal for which a separate report has been issued. The primary purpose of the DOE LIMB Extension testing, was to demonstrate the generic applicability of LIMB technology. The program sought to characterize the S0{sub 2} emissions that result when various calcium-based sorbents are injected into the furnace, while burning coals having sulfur content ranging from 1.6 to 3.8 weight percent. The four sorbents used included calcitic limestone, dolomitic hydrated lime, calcitic hydrated lime, and calcitic hydrated lime with a small amount of added calcium lignosulfonate. The results include those obtained for the various coal/sorbent combinations and the effects of the LIMB process on boiler and plant operations.

  4. Smart Sensor Demonstration Payload

    Science.gov (United States)

    Schmalzel, John; Bracey, Andrew; Rawls, Stephen; Morris, Jon; Turowski, Mark; Franzl, Richard; Figueroa, Fernando

    2010-01-01

    Sensors are a critical element to any monitoring, control, and evaluation processes such as those needed to support ground based testing for rocket engine test. Sensor applications involve tens to thousands of sensors; their reliable performance is critical to achieving overall system goals. Many figures of merit are used to describe and evaluate sensor characteristics; for example, sensitivity and linearity. In addition, sensor selection must satisfy many trade-offs among system engineering (SE) requirements to best integrate sensors into complex systems [1]. These SE trades include the familiar constraints of power, signal conditioning, cabling, reliability, and mass, and now include considerations such as spectrum allocation and interference for wireless sensors. Our group at NASA s John C. Stennis Space Center (SSC) works in the broad area of integrated systems health management (ISHM). Core ISHM technologies include smart and intelligent sensors, anomaly detection, root cause analysis, prognosis, and interfaces to operators and other system elements [2]. Sensor technologies are the base fabric that feed data and health information to higher layers. Cost-effective operation of the complement of test stands benefits from technologies and methodologies that contribute to reductions in labor costs, improvements in efficiency, reductions in turn-around times, improved reliability, and other measures. ISHM is an active area of development at SSC because it offers the potential to achieve many of those operational goals [3-5].

  5. A significant proportion of normal resting B cells are induced to secrete immunoglobulin through contact with anti-receptor antibody-activated helper T cells in clonal cultures

    DEFF Research Database (Denmark)

    Riedel, C; Owens, T; Nossal, G J

    1988-01-01

    cell line E9.D4 was stimulated with the anti-V beta 8 antibody F23.1 bound to the plastic of Terasaki 10-ul culture wells. When an excess of T helper lymphocytes was used (1,000 X-irradiated or 600 unirradiated, stimulated E9.D4 cells), 10-25% of B cells responded by antibody formation as judged......This report describes single-cell techniques to address the nature of a cellular interaction in which activated T lymphocytes stimulate small resting B cells to develop into antibody-forming cell clones in the absence of any surface immunoglobulin ligand or an antigen bridge. The cloned T helper...... by an enzyme-linked immunosorbent assay performed after 5 days of culture. When one of a very small number of B cells were present, the rate-limiting step to antibody-forming cell formation was the number of T cells present. Far fewer T cells sufficed for stimulation when culture trays were tilted to force T...

  6. Novel g-C3N4/CoO Nanocomposites with Significantly Enhanced Visible-Light Photocatalytic Activity for H2 Evolution.

    Science.gov (United States)

    Mao, Zhiyong; Chen, Jingjing; Yang, Yanfang; Wang, Dajian; Bie, Lijian; Fahlman, Bradley D

    2017-04-12

    Novel g-C3N4/CoO nanocomposite application for photocatalytic H2 evolution were designed and fabricated for the first time in this work. The structure and morphology of g-C3N4/CoO were investigated by a wide range of characterization methods. The obtained g-C3N4/CoO composites exhibited more-efficient utilization of solar energy than pure g-C3N4 did, resulting in higher photocatalytic activity for H2 evolution. The optimum photoactivity in H2 evolution under visible-light irradiation for g-C3N4/CoO composites with a CoO mass content of 0.5 wt % (651.3 μmol h(-1) g(-1)) was up to 3 times as high as that of pure g-C3N4 (220.16 μmol h(-1) g(-1)). The remarkably increased photocatalytic performance of g-C3N4/CoO composites was mainly attributed to the synergistic effect of the junction or interface formed between g-C3N4 and CoO.

  7. Optical Measurement Technologies for High Temperature, Radiation Exposure, and Corrosive Environments—Significant Activities and Findings: In-vessel Optical Measurements for Advanced SMRs

    Energy Technology Data Exchange (ETDEWEB)

    Anheier, Norman C.; Cannon, Bret D.; Qiao, Hong (Amy); Suter, Jonathan D.

    2012-09-01

    Development of advanced Small Modular Reactors (aSMRs) is key to providing the United States with a sustainable, economically viable, and carbon-neutral energy source. The aSMR designs have attractive economic factors that should compensate for the economies of scale that have driven development of large commercial nuclear power plants to date. For example, aSMRs can be manufactured at reduced capital costs in a factory and potentially shorter lead times and then be shipped to a site to provide power away from large grid systems. The integral, self-contained nature of aSMR designs is fundamentally different than conventional reactor designs. Future aSMR deployment will require new instrumentation and control (I&C) architectures to accommodate the integral design and withstand the extreme in-vessel environmental conditions. Operators will depend on sophisticated sensing and machine vision technologies that provide efficient human-machine interface for in-vessel telepresence, telerobotic control, and remote process operations. The future viability of aSMRs is dependent on understanding and overcoming the significant technical challenges involving in-vessel reactor sensing and monitoring under extreme temperatures, pressures, corrosive environments, and radiation fluxes

  8. The first human epitope map of the alphaviral E1 and E2 proteins reveals a new E2 epitope with significant virus neutralizing activity.

    Directory of Open Access Journals (Sweden)

    Ann R Hunt

    2010-07-01

    Full Text Available Venezuelan equine encephalitis virus (VEEV is responsible for VEE epidemics that occur in South and Central America and the U.S. The VEEV envelope contains two glycoproteins E1 (mediates cell membrane fusion and E2 (binds receptor and elicits virus neutralizing antibodies. Previously we constructed E1 and E2 epitope maps using murine monoclonal antibodies (mMAbs. Six E2 epitopes (E2(c,d,e,f,g,h bound VEEV-neutralizing antibody and mapped to amino acids (aa 182-207. Nothing is known about the human antibody repertoire to VEEV or epitopes that engage human virus-neutralizing antibodies. There is no specific treatment for VEE; however virus-neutralizing mMAbs are potent protective and therapeutic agents for mice challenged with VEEV by either peripheral or aerosol routes. Therefore, fully human MAbs (hMAbs with virus-neutralizing activity should be useful for prevention or clinical treatment of human VEE.We used phage-display to isolate VEEV-specific hFabs from human bone marrow donors. These hFabs were characterized by sequencing, specificity testing, VEEV subtype cross-reactivity using indirect ELISA, and in vitro virus neutralization capacity. One E2-specific neutralizing hFAb, F5n, was converted into IgG, and its binding site was identified using competitive ELISA with mMAbs and by preparing and sequencing antibody neutralization-escape variants.Using 11 VEEV-reactive hFabs we constructed the first human epitope map for the alphaviral surface proteins E1 and E2. We identified an important neutralization-associated epitope unique to the human immune response, E2 aa115-119. Using a 9 A resolution cryo-electron microscopy map of the Sindbis virus E2 protein, we showed the probable surface location of this human VEEV epitope.The VEEV-neutralizing capacity of the hMAb F5 nIgG is similar to that exhibited by the humanized mMAb Hy4 IgG. The Hy4 IgG has been shown to limit VEEV infection in mice both prophylactically and therapeutically. Administration

  9. The first human epitope map of the alphaviral E1 and E2 proteins reveals a new E2 epitope with significant virus neutralizing activity.

    Directory of Open Access Journals (Sweden)

    Ann R Hunt

    Full Text Available BACKGROUND: Venezuelan equine encephalitis virus (VEEV is responsible for VEE epidemics that occur in South and Central America and the U.S. The VEEV envelope contains two glycoproteins E1 (mediates cell membrane fusion and E2 (binds receptor and elicits virus neutralizing antibodies. Previously we constructed E1 and E2 epitope maps using murine monoclonal antibodies (mMAbs. Six E2 epitopes (E2(c,d,e,f,g,h bound VEEV-neutralizing antibody and mapped to amino acids (aa 182-207. Nothing is known about the human antibody repertoire to VEEV or epitopes that engage human virus-neutralizing antibodies. There is no specific treatment for VEE; however virus-neutralizing mMAbs are potent protective and therapeutic agents for mice challenged with VEEV by either peripheral or aerosol routes. Therefore, fully human MAbs (hMAbs with virus-neutralizing activity should be useful for prevention or clinical treatment of human VEE. METHODS: We used phage-display to isolate VEEV-specific hFabs from human bone marrow donors. These hFabs were characterized by sequencing, specificity testing, VEEV subtype cross-reactivity using indirect ELISA, and in vitro virus neutralization capacity. One E2-specific neutralizing hFAb, F5n, was converted into IgG, and its binding site was identified using competitive ELISA with mMAbs and by preparing and sequencing antibody neutralization-escape variants. FINDINGS: Using 11 VEEV-reactive hFabs we constructed the first human epitope map for the alphaviral surface proteins E1 and E2. We identified an important neutralization-associated epitope unique to the human immune response, E2 aa115-119. Using a 9 A resolution cryo-electron microscopy map of the Sindbis virus E2 protein, we showed the probable surface location of this human VEEV epitope. CONCLUSIONS: The VEEV-neutralizing capacity of the hMAb F5 nIgG is similar to that exhibited by the humanized mMAb Hy4 IgG. The Hy4 IgG has been shown to limit VEEV infection in mice both

  10. Significant Scales in Community Structure

    CERN Document Server

    Traag, V A; Van Dooren, P

    2013-01-01

    Many complex networks show signs of modular structure, uncovered by community detection. Although many methods succeed in revealing various partitions, it remains difficult to detect at what scale some partition is significant. This problem shows foremost in multi-resolution methods. We here introduce an efficient method for scanning for resolutions in one such method. Additionally, we introduce the notion of "significance" of a partition, based on subgraph probabilities. Significance is independent of the exact method used, so could also be applied in other methods, and can be interpreted as the gain in encoding a graph by making use of a partition. Using significance, we can determine "good" resolution parameters, which we demonstrate on benchmark networks. Moreover, optimizing significance itself also shows excellent performance. We demonstrate our method on voting data from the European Parliament. Our analysis suggests the European Parliament has become increasingly ideologically divided and that nationa...

  11. The Kwajalein bioremediation demonstration: Final technical report

    Energy Technology Data Exchange (ETDEWEB)

    Walker, J.R. Jr.; Walker, A.B.

    1994-12-01

    The US Army Kwajalein Atoll (USAKA) Base, located in the Republic of the Marshall Islands (RMI) in the east-central Pacific Ocean, has significant petroleum hydrocarbon contamination resulting from years of military activities. Because of its remoteness, the lack of on-site sophisticated remediation or waste disposal facilities, the amenability of petroleum hydrocarbons to biodegradation, and the year-round temperature favorable for microbial activity, USAKA requested, through the Hazardous Waste Remedial Actions Program (HAZWRAP), that a project be conducted to evaluate the feasibility of using bioremediation for environmental restoration of contaminated sites within the atoll. The project was conducted in four distinct phases: (1) initial site characterization and on-site biotreatability studies, (2) selection of the demonstration area and collection of soil columns, (3) laboratory column biotreatability studies, and (4) an on-site bioremediation demonstration. The results of phases (1) and (3) have been detailed in previous reports. This report summarizes the results of phases (1) and (3) and presents phases (2) and (4) in detail.

  12. The significance of community hospital actively develop children's vision screening%社区医院积极开展儿童视力筛查的意义

    Institute of Scientific and Technical Information of China (English)

    杨亮; 李娟; 彭美琳

    2016-01-01

    目的:探讨区医院积极开展儿童视力筛查意义。方法:某社区中心针对本社区的1591例儿童进行视力筛查,并且对其视力测试结果进行分析和研究。结果:在1591例本社区儿童中;其中有共计检查出242例视力异常的儿童,占15.2%的比例;经过视力筛查之后,建议其中的227例儿童3个月后进行复查,占93.8%的比例;建议另外15例儿童转到上级医院就诊,占6.2%的比例。3个月之后对其进行复查,其中共计有227例儿童的视力得以好转,占93.8%的比例。结论:通过儿童视力筛查的工作可以及时的发现社区儿童存在的散光、远视和近视等视力异常问题,有利于做好早期干预治疗的工作。%Objective:The community hospital actively carry out the important role of children's eyesight screening was analyzed and discussed.Methods:My community center for this community vision screening, 1591 cases of children and the vision test result analysis and research.Results:In view of this community in 1 year, 1591 cases of children in the vision screening;There are a total of detected 242 cases of abnormal vision of children, the proportion of 15.2%;After a vision screening, it is suggested that after three months with 227 cases of children in the process of reviewing the proportion of 93.8%;Suggest another 15 cases of children turn to higher level hospital, the proportion of 6.2%.Three months later to review, including a total of 227 cases of children's eyesight improved, accounted for 93.8% of the proportion.Conclusion:For community hospital outpatient service in child care, early childhood vision screening belongs to a very important work, work can be found timely through children's vision screening community children hyperopia astigmatism, and abnormal vision problems such as myopia, and do a good job early intervention treatment.

  13. Demonstration of cost effective low-energy buildings. Final report of the project 'Danish activities in the EU-CONCERTO project CLASS 1 in Stenloese'; Demonstration af omkostningseffektive lavenergibygninger. Afslutningsrapport fra EFP 2007 projektet 'Dansk indsats i EU-CONCERTO projektet CLASS 1 i Stenloese Syd'

    Energy Technology Data Exchange (ETDEWEB)

    Moerck, O. (Cenergia Energy Consultants, Herlev (Denmark)); Engelund Thomsen, K.; Rose, J. (SBi, Aalborg (Denmark)); Dates Joergensen, M. (Egedal Kommune, Stenloese (Denmark))

    2011-01-15

    The municipality of Egedal decided in 2006 to strengthen the energy requirements for a new settlement to be erected in the municipality. During the years 2007-2011 a total of 442 dwellings was to be designed and constructed with a heating demand corresponding to the new Danish low-energy standard referred to as 'low-energy class 1' in a new settlement called Stenloese Syd. 65 dwellings were to be designed and constructed with a yearly heating demand of 15 kWh/m{sup 2}. Furthermore the Concerto community includes a kindergarten and an activity centre for elderly people. After 3 years the kindergarten, the centre for elderly people, 65 dense lowrise housing units and 30 single family houses have been constructed. In parallel 15 deliverables/reports have been produced covering a number of different aspects: User preferences, proactive planning processes, product development, design guidelines, ecolabelling and training activities. A comparison was made of the calculated and measured energy consumption in a single-family house and in the KAB social housing project (65 dwellings). In the coming months the next demonstration buildings are to be completed, the extended district heating network (Plan B) including a woodchip furnace and a large array of solar collectors is to be implemented and the monitoring continued. The users will be followed and assisted and the lessons learned will be documented. It is expected that the experiences, lessons learned and R and D carried out as part of the Class 1 project will pave the way for the development, design and construction of sustainable, low or zero CO2-emission communities in the future. Further information about the Class1 project is to be found on the project website: www.class1.dk. (Author)

  14. Demonstration of cost effective low-energy buildings. Final report of the project 'Danish activities in the EU-CONCERTO project CLASS 1 in Stenloese'; Demonstration af omkostningseffektive lavenergibygninger. Afslutningsrapport fra EFP 2007 projektet 'Dansk indsats i EU-CONCERTO projektet CLASS 1 i Stenloese Syd'

    Energy Technology Data Exchange (ETDEWEB)

    Moerck, O. (Cenergia Energy Consultants, Herlev (Denmark)); Engelund Thomsen, K.; Rose, J. (SBi, Aalborg (Denmark)); Dates Joergensen, M. (Egedal Kommune, Stenloese (Denmark))

    2011-01-15

    The municipality of Egedal decided in 2006 to strengthen the energy requirements for a new settlement to be erected in the municipality. During the years 2007-2011 a total of 442 dwellings was to be designed and constructed with a heating demand corresponding to the new Danish low-energy standard referred to as 'low-energy class 1' in a new settlement called Stenloese Syd. 65 dwellings were to be designed and constructed with a yearly heating demand of 15 kWh/m{sup 2}. Furthermore the Concerto community includes a kindergarten and an activity centre for elderly people. After 3 years the kindergarten, the centre for elderly people, 65 dense lowrise housing units and 30 single family houses have been constructed. In parallel 15 deliverables/reports have been produced covering a number of different aspects: User preferences, proactive planning processes, product development, design guidelines, ecolabelling and training activities. A comparison was made of the calculated and measured energy consumption in a single-family house and in the KAB social housing project (65 dwellings). In the coming months the next demonstration buildings are to be completed, the extended district heating network (Plan B) including a woodchip furnace and a large array of solar collectors is to be implemented and the monitoring continued. The users will be followed and assisted and the lessons learned will be documented. It is expected that the experiences, lessons learned and R and D carried out as part of the Class 1 project will pave the way for the development, design and construction of sustainable, low or zero CO2-emission communities in the future. Further information about the Class1 project is to be found on the project website: www.class1.dk. (Author)

  15. A Demonstration of the Uncertainty in Predicting the Estrogenic Activity of Individual Chemicals and Mixtures From an In Vitro Estrogen Receptor Transcriptional Activation Assay (T47D-KBluc) to the In Vivo Uterotrophic Assay Using Oral Exposure.

    Science.gov (United States)

    Conley, Justin M; Hannas, Bethany R; Furr, Johnathan R; Wilson, Vickie S; Gray, L Earl

    2016-10-01

    In vitro estrogen receptor assays are valuable tools for identifying environmental samples and chemicals that display estrogenic activity. However, in vitro potency cannot necessarily be extrapolated to estimates of in vivo potency because in vitro assays are currently unable to fully account for absorption, distribution, metabolism, and excretion. To explore this issue, we calculated relative potency factors (RPF), using 17α-ethinyl estradiol (EE2) as the reference compound, for several chemicals and mixtures in the T47D-KBluc estrogen receptor transactivation assay. In vitro RPFs were used to predict rat oral uterotrophic assay responses for these chemicals and mixtures. EE2, 17β-estradiol (E2), benzyl-butyl phthalate (BBP), bisphenol-A (BPA), bisphenol-AF (BPAF), bisphenol-C (BPC), bisphenol-S (BPS), and methoxychlor (MET) were tested individually, while BPS + MET, BPAF + MET, and BPAF + BPC + BPS + EE2 + MET were tested as equipotent mixtures. In vivo ED50 values for BPA, BPAF, and BPC were accurately predicted using in vitro data; however, E2 was less potent than predicted, BBP was a false positive, and BPS and MET were 76.6 and 368.3-fold more active in vivo than predicted from the in vitro potency, respectively. Further, mixture ED50 values were more accurately predicted by the dose addition model using individual chemical in vivo uterotrophic data (0.7-1.5-fold difference from observed) than in vitro data (1.4-86.8-fold). Overall, these data illustrate the potential for both underestimating and overestimating in vivo potency from predictions made with in vitro data for compounds that undergo substantial disposition following oral administration. Accounting for aspects of toxicokinetics, notably metabolism, in in vitro models will be necessary for accurate in vitro-to-in vivo extrapolations.

  16. Aerospace Communications Security Technologies Demonstrated

    Science.gov (United States)

    Griner, James H.; Martzaklis, Konstantinos S.

    2003-01-01

    In light of the events of September 11, 2001, NASA senior management requested an investigation of technologies and concepts to enhance aviation security. The investigation was to focus on near-term technologies that could be demonstrated within 90 days and implemented in less than 2 years. In response to this request, an internal NASA Glenn Research Center Communications, Navigation, and Surveillance Aviation Security Tiger Team was assembled. The 2-year plan developed by the team included an investigation of multiple aviation security concepts, multiple aircraft platforms, and extensively leveraged datalink communications technologies. It incorporated industry partners from NASA's Graphical Weather-in-the-Cockpit research, which is within NASA's Aviation Safety Program. Two concepts from the plan were selected for demonstration: remote "black box," and cockpit/cabin surveillance. The remote "black box" concept involves real-time downlinking of aircraft parameters for remote monitoring and archiving of aircraft data, which would assure access to the data following the loss or inaccessibility of an aircraft. The cockpit/cabin surveillance concept involves remote audio and/or visual surveillance of cockpit and cabin activity, which would allow immediate response to any security breach and would serve as a possible deterrent to such breaches. The datalink selected for the demonstrations was VDL Mode 2 (VHF digital link), the first digital datalink for air-ground communications designed for aircraft use. VDL Mode 2 is beginning to be implemented through the deployment of ground stations and aircraft avionics installations, with the goal of being operational in 2 years. The first demonstration was performed December 3, 2001, onboard the LearJet 25 at Glenn. NASA worked with Honeywell, Inc., for the broadcast VDL Mode 2 datalink capability and with actual Boeing 757 aircraft data. This demonstration used a cockpitmounted camera for video surveillance and a coupling to

  17. A randomised, double-blind, parallel-group study to demonstrate equivalence in efficacy and safety of CT-P13 compared with innovator infliximab when coadministered with methotrexate in patients with active rheumatoid arthritis: the PLANETRA study

    Science.gov (United States)

    Yoo, Dae Hyun; Hrycaj, Pawel; Miranda, Pedro; Ramiterre, Edgar; Piotrowski, Mariusz; Shevchuk, Sergii; Kovalenko, Volodymyr; Prodanovic, Nenad; Abello-Banfi, Mauricio; Gutierrez-Ureña, Sergio; Morales-Olazabal, Luis; Tee, Michael; Jimenez, Renato; Zamani, Omid; Lee, Sang Joon; Kim, HoUng; Park, Won; Müller-Ladner, Ulf

    2013-01-01

    Objectives To compare the efficacy and safety of innovator infliximab (INX) and CT-P13, an INX biosimilar, in active rheumatoid arthritis patients with inadequate response to methotrexate (MTX) treatment. Methods Phase III randomised, double-blind, multicentre, multinational, parallel-group study. Patients with active disease despite MTX (12.5–25 mg/week) were randomised to receive 3 mg/kg of CT-P13 (n=302) or INX (n=304) with MTX and folic acid. The primary endpoint was the American College of Rheumatology 20% (ACR20) response at week 30. Therapeutic equivalence of clinical response according to ACR20 criteria was concluded if the 95% CI for the treatment difference was within ±15%. Secondary endpoints included ACR response criteria, European League Against Rheumatism (EULAR) response criteria, change in Disease Activity Score 28 (DAS28), Medical Outcomes Study Short-Form Health Survey (SF-36), Simplified Disease Activity Index, Clinical Disease Activity Index, as well as pharmacokinetic (PK) and pharmacodynamic (PD) parameters, safety and immunogenicity. Results At week 30, ACR20 responses were 60.9% for CT-P13 and 58.6% for INX (95% CI −6% to 10%) in the intention-to-treat population. The proportions in CT-P13 and INX groups achieving good or moderate EULAR responses (C reactive protein (CRP)) at week 30 were 85.8% and 87.1%, respectively. Low disease activity or remission according to DAS28–CRP, ACR–EULAR remission rates, ACR50/ACR70 responses and all other PK and PD endpoints were highly similar at week 30. Incidence of drug-related adverse events (35.2% vs 35.9%) and detection of antidrug antibodies (48.4% vs 48.2%) were highly similar for CT-P13 and INX, respectively. Conclusions CT-P13 demonstrated equivalent efficacy to INX at week 30, with a comparable PK profile and immunogenicity. CT-P13 was well tolerated, with a safety profile comparable with that of INX. ClinicalTrials.gov Identifier NCT01217086 PMID:23687260

  18. Codes & standards research, development & demonstration Roadmap

    Energy Technology Data Exchange (ETDEWEB)

    None, None

    2008-07-22

    This Roadmap is a guide to the Research, Development & Demonstration activities that will provide data required for SDOs to develop performance-based codes and standards for a commercial hydrogen fueled transportation sector in the U.S.

  19. Decreased myo-inositol to chiro-inositol (M/C) ratios and increased M/C epimerase activity in PCOS theca cells demonstrate increased insulin sensitivity compared to controls.

    Science.gov (United States)

    Heimark, Douglas; McAllister, Jan; Larner, Joseph

    2014-01-01

    Previous studies from our and other labs have shown that insulin resistance is associated with an inositol imbalance of excess myo-inositol and deficient chiro-inositol together with a deficiency of myo-inositol to chiro-inositol epimerase in vivo and in vitro. In this report, we utilized well characterized theca cells from normal cycling women, with normal insulin sensitivity, and theca cells from women with polycystic ovary syndrome (PCOS), with increased insulin sensitivity to examine the myo-inositol to chiro-inisitol (M/C) ratio and the myo-inositol to chiro-inositol epimerase activity. PCOS theca cells with increased insulin sensitivity were specifically used to investigate whether the inositol imbalance and myo-inositol to chiro-inositol epimerase are regulated in a similar or the opposite direction than that observed in insulin resistant cells. The results of these studies are the first to demonstrate that in insulin sensitive PCOS theca cells the inositol imbalance goes in the opposite direction to that observed in insulin resistant cells, and there is a decreased M/C ratio and an increased myo-inositol to chiro-inositol epimerase activity. Further biochemical and genetic studies will probe the mechanisms involved.

  20. Protective effect of HSV-mediated gene transfer of nerve growth factor in pyridoxine neuropathy demonstrates functional activity of trkA receptors in large sensory neurons of adult animals.

    Science.gov (United States)

    Chattopadhyay, Munmun; Goss, James; Lacomis, David; Goins, William C; Glorioso, Joseph C; Mata, Marina; Fink, David J

    2003-02-01

    The distinct distribution of trkA receptors on small neurons and trkC receptors on large neurons in the dorsal root ganglion correlates with the dependence of these two classes of neurons on nerve growth factor and neurotrophin-3, respectively, for survival during development. In adult animals, the distribution of high affinity neurotrophin (trk) is complex and overlapping; neurotrophins are not required for cell survival, but may influence cell phenotype and the response to injury. In order to test the functional activity of trkA receptors in the sensory ganglia of adult animals in vivo, we examined the ability of a nerve growth factor-expressing recombinant replication-defective herpes simplex virus-based vector to prevent the selective degeneration of large sensory fibres caused by intoxication with pyridoxine. Transduction of dorsal root ganglion neurons in vivo by subcutaneous inoculation of the nerve growth factor-expressing vector prevented the development of pyridoxine-induced neuropathy measured by electrophysiological, morphological and behavioural measures. These results demonstrate a functional activity of trkA receptors expressed on large neurons in the dorsal root ganglion in mature animals; this observation has important implications for the choice of neurotrophic factors for treatment of peripheral nerve disease.

  1. The Edgewater Coolside process demonstration

    Energy Technology Data Exchange (ETDEWEB)

    McCoy, D.C.; Scandrol, R.O.; Statnick, R.M.; Stouffer, M.R.; Winschel, R.A.; Withum, J.A.; Wu, M.M.; Yoon, H. [CONSOL, Inc., Pittsburgh, PA (United States)

    1992-02-01

    The Edgewater Coolside process demonstration met the program objectives which were to determine Coolside SO{sub 2} removal performance, establish short-term process operability, and evaluate the economics of the process versus a limestone wet scrubber. On a flue gas produced from the combustion of 3% sulfur coal, the Coolside process achieved 70% SO{sub 2} removal using commercially-available hydrated lime as the sorbent. The operating conditions were Ca/S mol ratio 2.0, Na/Ca mol ratio 0.2, and 20{degree}F approach to adiabatic saturation temperature ({del}T). During tests using fresh plus recycle