Science.gov

Sample records for active surtass lfa

  1. Effects of surveillance towed array sensor system (SURTASS) low frequency active sonar on fish

    NASA Astrophysics Data System (ADS)

    Popper, Arthur N.; Halvorsen, Michele B.; Miller, Diane; Smith, Michael E.; Song, Jiakun; Wysocki, Lidia E.; Hastings, Mardi C.; Kane, Andrew S.; Stein, Peter

    2005-04-01

    We investigated the effects of exposure to Low Frequency Active (LFA) sonar on rainbow trout (a hearing non-specialist related to several endangered salmonids) and channel catfish (a hearing specialist), using an element of the standard SURTASS LFA source array. We measured hearing sensitivity using auditory brainstem response, effects on inner ear structure using scanning electron microscopy, effects on non-auditory tissues using general pathology and histopathology, and behavioral effects with video monitoring. Exposure to 193 dB re 1 microPa (rms received level) in the LFA frequency band for 324 seconds resulted in a TTS of 20 dB at 400 Hz in rainbow trout, with less TTS at 100 and 200 Hz. TTS in catfish ranged from 6 to 12 dB at frequencies from 200 to 1000 Hz. Both species recovered from hearing loss in several days. Inner ears sensory tissues appeared unaffected by acoustic exposure. Gross pathology indicated no damage to non-auditory tissues, including the swim bladder. Both species showed consistent startle responses at sound onsets and changed their position relative to the sound source during exposures. There was no fish death attributable to sound exposure even up to four days post-exposure. [Work supported by Chief of Naval Operations.

  2. 77 FR 52317 - Record of Decision for Surveillance Towed Array Sensor System Low Frequency Active Sonar

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-29

    ... From the Federal Register Online via the Government Publishing Office DEPARTMENT OF DEFENSE Department of the Navy Record of Decision for Surveillance Towed Array Sensor System Low Frequency Active... Array Sensor System Low Frequency Active (SURTASS LFA) sonar systems with certain...

  3. 76 FR 51972 - Environmental Impacts Statements; Notice of Availability

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-19

    ... Frequency Active (SURTASS LFA) Sonar Systems, Updated and Additional Information on Employment of Four SURTASS LFA Sonar Systems for Routine Training, Testing, and Military Operation, Implementation,...

  4. Kinetics of LFA-1 mediated adhesion of human neutrophils to ICAM-1-role of E-selectin signaling post-activation.

    Technology Transfer Automated Retrieval System (TEKTRAN)

    LFA-1 and Mac-1 are the two integrins involved in the arrest and firm adhesion of neutrophils. LFA-1 plays a role in the early stage of cell arrest while Mac-1 stabilizes firm adhesion. Here, we further elucidated the kinetics of LFA-1 activation and its role in mediating neutrophil adhesion to ICAM...

  5. Structural basis of activation-dependent binding of ligand-mimetic antibody AL-57 to integrin LFA-1

    SciTech Connect

    Zhang, Hongmin; Liu, Jin-huan; Yang, Wei; Springer, Timothy; Shimaoka, Motomu; Wang, Jia-huai

    2010-09-21

    The activity of integrin LFA-1 ({alpha}{sub L}{beta}{sub 2}) to its ligand ICAM-1 is regulated through the conformational changes of its ligand-binding domain, the I domain of {alpha}{sub L} chain, from an inactive, low-affinity closed form (LA), to an intermediate-affinity form (IA), and then finally, to a high-affinity open form (HA). A ligand-mimetic human monoclonal antibody AL-57 (activated LFA-1 clone 57) was identified by phage display to specifically recognize the affinity-upregulated I domain. Here, we describe the crystal structures of the Fab fragment of AL-57 in complex with IA, as well as in its unligated form. We discuss the structural features conferring AL-57's strong selectivity for the high affinity, open conformation of the I domain. The AL-57-binding site overlaps the ICAM-1 binding site on the I domain. Furthermore, an antibody Asp mimics an ICAM Glu by forming a coordination to the metal-ion dependent adhesion site (MIDAS). The structure also reveals better shape complementarity and a more hydrophobic interacting interface in AL-57 binding than in ICAM-1 binding. The results explain AL-57's antagonistic mimicry of LFA-1's natural ligands, the ICAM molecules.

  6. 50 CFR 218.235 - Requirements for monitoring.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Low Frequency Active (SURTASS LFA) Sonar § 218.235 Requirements for monitoring. (a) The Holder of a...) during operations that employ SURTASS LFA sonar in the active mode. The SURTASS vessels shall have... frequency passive SURTASS sonar to listen for vocalizing marine mammals; and (3) Use the HF/M3 active...

  7. 50 CFR 218.235 - Requirements for monitoring.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Low Frequency Active (SURTASS LFA) Sonar § 218.235 Requirements for monitoring. (a) The Holder of a...) during operations that employ SURTASS LFA sonar in the active mode. The SURTASS vessels shall have... frequency passive SURTASS sonar to listen for vocalizing marine mammals; and (3) Use the HF/M3 active...

  8. 50 CFR 218.235 - Requirements for monitoring.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Low Frequency Active (SURTASS LFA) Sonar § 218.235 Requirements for monitoring. (a) The Holder of a...) during operations that employ SURTASS LFA sonar in the active mode. The SURTASS vessels shall have... frequency passive SURTASS sonar to listen for vocalizing marine mammals; and (3) Use the HF/M3 active...

  9. 50 CFR 218.237 - Applications for Letters of Authorization.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Array Sensor System Low Frequency Active (SURTASS LFA) Sonar § 218.237 Applications for Letters of... scheduled to begin conducting SURTASS LFA sonar operations or the previous Letter of Authorization...

  10. 50 CFR 218.241 - Adaptive management.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Low Frequency Active (SURTASS LFA) Sonar § 218.241 Adaptive management. NMFS may modify (including...) Results from the Navy's monitoring from the previous year's operation of SURTASS LFA sonar. (b)...

  11. 50 CFR 216.187 - Applications for Letters of Authorization.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Array Sensor System Low Frequency Active (SURTASS LFA sonar) Sonar § 216.187 Applications for Letters of... scheduled to begin conducting SURTASS LFA sonar operations or the previous Letter of Authorization...

  12. 50 CFR 218.232 - Permissible methods of taking.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Low Frequency Active (SURTASS LFA) Sonar § 218.232 Permissible methods of taking. (a) Under Letters of.... This annual per-stock cap of 12 percent applies regardless of the number of SURTASS LFA sonar...

  13. 50 CFR 218.232 - Permissible methods of taking.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Low Frequency Active (SURTASS LFA) Sonar § 218.232 Permissible methods of taking. (a) Under Letters of.... This annual per-stock cap of 12 percent applies regardless of the number of SURTASS LFA sonar...

  14. 50 CFR 218.237 - Applications for Letters of Authorization.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Array Sensor System Low Frequency Active (SURTASS LFA) Sonar § 218.237 Applications for Letters of... scheduled to begin conducting SURTASS LFA sonar operations or the previous Letter of Authorization...

  15. 50 CFR 216.187 - Applications for Letters of Authorization.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Array Sensor System Low Frequency Active (SURTASS LFA sonar) Sonar § 216.187 Applications for Letters of... scheduled to begin conducting SURTASS LFA sonar operations or the previous Letter of Authorization...

  16. 50 CFR 218.241 - Adaptive management.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Low Frequency Active (SURTASS LFA) Sonar § 218.241 Adaptive management. NMFS may modify (including...) Results from the Navy's monitoring from the previous year's operation of SURTASS LFA sonar. (b)...

  17. 50 CFR 218.232 - Permissible methods of taking.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Low Frequency Active (SURTASS LFA) Sonar § 218.232 Permissible methods of taking. (a) Under Letters of.... This annual per-stock cap of 12 percent applies regardless of the number of SURTASS LFA sonar...

  18. 50 CFR 218.230 - Specified activity, level of taking, and species.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... acutus), Baird's beaked whale (Berardius bairdii), Beluga whale (Dephinapterus leucas), Blainville's... sounds from the SURTASS LFA sonar system and the transmission of high frequency sounds from the... the following species and species groups: (1) Mysticetes-blue whale (Balaenoptera musculus),...

  19. 50 CFR 218.230 - Specified activity, level of taking, and species.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... acutus), Baird's beaked whale (Berardius bairdii), Beluga whale (Dephinapterus leucas), Blainville's... sounds from the SURTASS LFA sonar system and the transmission of high frequency sounds from the... the following species and species groups: (1) Mysticetes-blue whale (Balaenoptera musculus),...

  20. 50 CFR 218.230 - Specified activity, level of taking, and species.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... acutus), Baird's beaked whale (Berardius bairdii), Beluga whale (Dephinapterus leucas), Blainville's... sounds from the SURTASS LFA sonar system and the transmission of high frequency sounds from the... the following species and species groups: (1) Mysticetes-blue whale (Balaenoptera musculus),...

  1. 50 CFR 216.189 - Renewal of Letters of Authorization.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Array Sensor System Low Frequency Active (SURTASS LFA sonar) Sonar § 216.189 Renewal of Letters of... each SURTASS LFA sonar operation; (3) Timely receipt of the monitoring reports required under § 216.185... comment on the proposed modification. Amending the areas for upcoming SURTASS LFA sonar operations is...

  2. 50 CFR 216.189 - Renewal of Letters of Authorization.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Array Sensor System Low Frequency Active (SURTASS LFA sonar) Sonar § 216.189 Renewal of Letters of... each SURTASS LFA sonar operation; (3) Timely receipt of the monitoring reports required under § 216.185... comment on the proposed modification. Amending the areas for upcoming SURTASS LFA sonar operations is...

  3. 50 CFR 216.185 - Requirements for monitoring.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Low Frequency Active (SURTASS LFA sonar) Sonar § 216.185 Requirements for monitoring. (a) In order to mitigate the taking of marine mammals by SURTASS LFA sonar to the greatest extent practicable, the Holder... sunset); (2) Use low frequency passive SURTASS sonar to listen for vocalizing marine mammals; and (3)...

  4. 50 CFR 216.185 - Requirements for monitoring.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Low Frequency Active (SURTASS LFA sonar) Sonar § 216.185 Requirements for monitoring. (a) In order to mitigate the taking of marine mammals by SURTASS LFA sonar to the greatest extent practicable, the Holder... sunset); (2) Use low frequency passive SURTASS sonar to listen for vocalizing marine mammals; and (3)...

  5. Expression of the T-cell surface molecule CD2 and an epitope-loss CD2 mutant to define the role of lymphocyte function-associated antigen 3 (LFA-3) in T-cell activation.

    PubMed Central

    Bierer, B E; Peterson, A; Barbosa, J; Seed, B; Burakoff, S J

    1988-01-01

    To define the role of the CD2-lymphocyte function-associated antigen 3 (LFA-3) interaction in T-cell activation, we have expressed a cDNA encoding the human CD2 molecule in a murine antigen-specific T-cell hybridoma. Expression of the CD2 molecule greatly enhances T-cell responsiveness to antigen; this enhancement is inhibited by anti-CD2 and anti-LFA-3 monoclonal antibodies (mAbs). CD2+ hybridomas produce interleukin 2 in response to combinations of anti-CD2 mAbs 9.6 and 9-1 and, in the presence of mAb 9-1, to sheep erythrocytes or to the LFA-3 antigen. Furthermore, hybridomas expressing a mutant CD2 molecule that has lost mAb 9.6 binding do not exhibit the enhanced response to antigen or the ability to respond to LFA-3 plus mAb 9-1, but these hybridomas retain the ability to respond to combinations of anti-CD2 mAbs. The role of the CD2-LFA-3 interaction in T-cell activation and the potential for other physiologic ligands for CD2 are discussed. PMID:2448792

  6. Nonmuscle myosin heavy chain IIA mediates integrin LFA-1 de-adhesion during T lymphocyte migration.

    PubMed

    Morin, Nicole A; Oakes, Patrick W; Hyun, Young-Min; Lee, Dooyoung; Chin, Y Eugene; Chin, Eugene Y; King, Michael R; Springer, Timothy A; Shimaoka, Motomu; Tang, Jay X; Reichner, Jonathan S; Kim, Minsoo

    2008-01-21

    Precise spatial and temporal regulation of cell adhesion and de-adhesion is critical for dynamic lymphocyte migration. Although a great deal of information has been learned about integrin lymphocyte function-associated antigen (LFA)-1 adhesion, the mechanism that regulates efficient LFA-1 de-adhesion from intercellular adhesion molecule (ICAM)-1 during T lymphocyte migration is unknown. Here, we show that nonmuscle myosin heavy chain IIA (MyH9) is recruited to LFA-1 at the uropod of migrating T lymphocytes, and inhibition of the association of MyH9 with LFA-1 results in extreme uropod elongation, defective tail detachment, and decreased lymphocyte migration on ICAM-1, without affecting LFA-1 activation by chemokine CXCL-12. This defect was reversed by a small molecule antagonist that inhibits both LFA-1 affinity and avidity regulation, but not by an antagonist that inhibits only affinity regulation. Total internal reflection fluorescence microscopy of the contact zone between migrating T lymphocytes and ICAM-1 substrate revealed that inactive LFA-1 is selectively localized to the posterior of polarized T lymphocytes, whereas active LFA-1 is localized to their anterior. Thus, during T lymphocyte migration, uropodal adhesion depends on LFA-1 avidity, where MyH9 serves as a key mechanical link between LFA-1 and the cytoskeleton that is critical for LFA-1 de-adhesion.

  7. Large format array controller (aLFA-C): tests and characterisation at ESA

    NASA Astrophysics Data System (ADS)

    Lemmel, Frédéric; ter Haar, Jörg; van der Biezen, John; Duvet, Ludovic; Nelms, Nick; Blommaert, Sander; Butler, Bart; van der Luijt, Cornelis; Heijnen, Jerko; Smit, Hans; Visser, Ivo

    2016-08-01

    For future near infrared astronomy missions, ESA is developing a complete detection and conversion chain (photon to SpaceWire chain system): Large Format Array (aLFA-N) based on MCT type detectors. aLFA-C (Astronomy Large Format Array Controller): a versatile cryogenic detector controller. An aLFA-C prototype was developed by Caeleste (Belgium) under ESA contract (400106260400). To validate independently the performances of the aLFA-C prototype and consolidate the definition of the follow-on activity, a dedicated test bench has been designed and developed in ESTEC/ESA within the Payload Technology Validation group. This paper presents the test setup and the performance validation of the first prototype of this controller at room and cryogenic temperature. Test setup and software needed to test the HAWAII-2RG and aLFA-N detectors with the aLFA-C prototype at cryogenic temperature will be also presented.

  8. 50 CFR 216.180 - Specified activity.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... whales—harbor porpoise (Phocoena phocoena), spectacled porpoise (Phocoena dioptrica), beluga... §§ 216.106 and 216.188, include the transmission of low frequency sounds from the SURTASS LFA sonar and the transmission of high frequency sounds from the mitigation sonar described in § 216.185...

  9. LFA-1/ICAM-1 Interaction as a Therapeutic Target in Dry Eye Disease.

    PubMed

    Pflugfelder, Stephen C; Stern, Michael; Zhang, Steven; Shojaei, Amir

    Dry eye disease (DED) is a common ocular disorder associated with inflammation of the lacrimal gland and ocular surface. The interaction of the integrin lymphocyte function-associated antigen-1 (LFA-1) with its cognate ligand intercellular adhesion molecule-1 (ICAM-1) is known to have important roles in the interaction of a variety of cells involved in immune responses and inflammation, including those prominent in ocular surface inflammation. Lifitegrast, an LFA-1 antagonist that blocks binding of ICAM-1 to LFA-1, has recently been approved in the United States for the treatment of signs and symptoms of DED. In this review, we evaluate research findings to explore the potential role of LFA-1/ICAM-1 interaction in the pathophysiology of DED, and the evidence supporting LFA-1/ICAM-1 interaction as a rational therapeutic target in DED. The results of our review suggest that LFA-1/ICAM-1 interaction may play important roles in the cell-mediated immune response and inflammation associated with DED, including facilitating the homing of dendritic cells to the lymph nodes, interaction of dendritic cells with T cells and subsequent T cell activation/differentiation, migration of activated CD4(+) T cells from the lymph nodes to the ocular surface, reactivation of T cells by resident antigen-presenting cells at the ocular surface, and recruitment and retention of LFA-1-expressing T cells in the conjunctival epithelium. Based on the available evidence, inhibition of LFA-1/ICAM-1 interaction represents a rational targeted approach in treating DED. Notably, inhibition of LFA-1/ICAM-1 binding with lifitegrast offers a novel approach to reducing ocular surface inflammation in this condition.

  10. LFA-1/ICAM-1 Interaction as a Therapeutic Target in Dry Eye Disease

    PubMed Central

    Stern, Michael; Zhang, Steven; Shojaei, Amir

    2017-01-01

    Abstract Dry eye disease (DED) is a common ocular disorder associated with inflammation of the lacrimal gland and ocular surface. The interaction of the integrin lymphocyte function-associated antigen-1 (LFA-1) with its cognate ligand intercellular adhesion molecule-1 (ICAM-1) is known to have important roles in the interaction of a variety of cells involved in immune responses and inflammation, including those prominent in ocular surface inflammation. Lifitegrast, an LFA-1 antagonist that blocks binding of ICAM-1 to LFA-1, has recently been approved in the United States for the treatment of signs and symptoms of DED. In this review, we evaluate research findings to explore the potential role of LFA-1/ICAM-1 interaction in the pathophysiology of DED, and the evidence supporting LFA-1/ICAM-1 interaction as a rational therapeutic target in DED. The results of our review suggest that LFA-1/ICAM-1 interaction may play important roles in the cell-mediated immune response and inflammation associated with DED, including facilitating the homing of dendritic cells to the lymph nodes, interaction of dendritic cells with T cells and subsequent T cell activation/differentiation, migration of activated CD4+ T cells from the lymph nodes to the ocular surface, reactivation of T cells by resident antigen-presenting cells at the ocular surface, and recruitment and retention of LFA-1-expressing T cells in the conjunctival epithelium. Based on the available evidence, inhibition of LFA-1/ICAM-1 interaction represents a rational targeted approach in treating DED. Notably, inhibition of LFA-1/ICAM-1 binding with lifitegrast offers a novel approach to reducing ocular surface inflammation in this condition. PMID:27906544

  11. A lateral flow assay (LFA) for the rapid detection of extraparenchymal neurocysticercosis using cerebrospinal fluid.

    PubMed

    Fleury, Agnes; Sastre, Patricia; Sciutto, Edda; Correia, Silvia; Monedero, Alejandro; Toledo, Andrea; Hernandez, Maricela; Harrison, Leslie J S; Parkhouse, R Michael E

    2016-10-27

    A lateral flow assay (LFA) for the diagnosis and monitoring of extraparenchymal neurocysticercosis, has been developed. The assay is based on the use of the monoclonal antibody HP10, and when applied to cerebrospinal fluid, correctly identified 34 cases of active extraparenchymal neurocysticercosis, but was negative with 26 samples from treated and cured neurocysticercosis patients and with 20 samples from unrelated neurological diseases. There was complete agreement between the HP10 Ag-ELISA results and the HP10-LFA. The HP10-LFA thus has utility for diagnosis and treatment of extraparenchymal neurocysticercosis, frequently a more dangerous form of the infection.

  12. 50 CFR 218.240 - Modifications to Letters of Authorization.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... Array Sensor System Low Frequency Active (SURTASS LFA) Sonar § 218.240 Modifications to Letters of... sonar system from one ship to another, is not considered a substantial modification. (b) If...

  13. 50 CFR 218.240 - Modifications to Letters of Authorization.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... Array Sensor System Low Frequency Active (SURTASS LFA) Sonar § 218.240 Modifications to Letters of... sonar system from one ship to another, is not considered a substantial modification. (b) If...

  14. 50 CFR 216.190 - Modifications to Letters of Authorization.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... Array Sensor System Low Frequency Active (SURTASS LFA sonar) Sonar § 216.190 Modifications to Letters of... sonar system from one ship to another, is not considered a substantial modification. (b) If the...

  15. 50 CFR 216.190 - Modifications to Letters of Authorization.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... Array Sensor System Low Frequency Active (SURTASS LFA sonar) Sonar § 216.190 Modifications to Letters of... sonar system from one ship to another, is not considered a substantial modification. (b) If the...

  16. 50 CFR 218.240 - Modifications to Letters of Authorization.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Array Sensor System Low Frequency Active (SURTASS LFA) Sonar § 218.240 Modifications to Letters of... sonar system from one ship to another, is not considered a substantial modification. (b) If...

  17. 50 CFR 218.231 - Effective dates.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... and Importing of Marine Mammals; Navy Operations of Surveillance Towed Array Sensor System Low Frequency Active (SURTASS LFA) Sonar § 218.231 Effective dates. Regulations are effective August 15,...

  18. 50 CFR 218.231 - Effective dates.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... and Importing of Marine Mammals; Navy Operations of Surveillance Towed Array Sensor System Low Frequency Active (SURTASS LFA) Sonar § 218.231 Effective dates. Regulations are effective August 15,...

  19. 50 CFR 218.231 - Effective dates.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... and Importing of Marine Mammals; Navy Operations of Surveillance Towed Array Sensor System Low Frequency Active (SURTASS LFA) Sonar § 218.231 Effective dates. Regulations are effective August 15,...

  20. LFA-1-dependent Ca2+ entry following suboptimal T cell receptor triggering proceeds without mobilization of intracellular Ca2+.

    PubMed

    Kim, Kwangmi; Wang, Lin; Hwang, Inkyu

    2009-08-14

    A surge in cytosolic calcium ion concentration by entry of extracellular Ca2+ is a hallmark of T cell activation. According to store-operated Ca2+ entry mechanism, the Ca2+ entry is preceded by activation of phospholipase C-gamma1 (PLC-gamma1) and the consequent mobilization of intracellular Ca2+. Using membrane vesicles expressing the mouse class I major histocompatibility complex, i.e. Ld plus costimulatory ligands, i.e. B7-1 and intercellular adhesion molecule-1 along with 2C T cell receptor transgenic T cells, we investigated the roles of CD28 and LFA-1 (lymphocyte function-associated antigen-1) in the activation of PLC-gamma1 and Ca2+ signaling. Both CD28 and LFA-1 made significant and comparable contributions to the activation of PLC-gamma1 as gauged by the level of its phosphorylation at tyrosine 783. In contrast, their roles in Ca2+ signaling were quite distinct so that LFA-1/intercellular adhesion molecule-1 interaction exerted a determining role, whereas CD28/B7-1 interaction played only a minimal role. In particular, when the T cells were activated by suboptimal T cell receptor stimulation, LFA-1 played an indispensable role in the Ca2+ signaling. Further experiments using Ca2+-free medium demonstrated that the entry of extracellular Ca2+ was not always accompanied by mobilization of intracellular Ca2+. Thus, intracellular Ca2+ mobilization was hardly detected under the condition that LFA-1 played the indispensable role in the entry of extracellular Ca2+, while a distinct level of intracellular Ca2+ mobilization was readily detected under the condition that LFA-1 played only the supporting role. These results ensure the unique role of LFA-1 in T cell Ca2+ signaling and reveal that LFA-1-dependent Ca2+ entry proceeds via a mechanism separate from store-operated Ca2+ entry.

  1. Fundamentally different roles for LFA-1, Mac-1 and alpha4-integrin in neutrophil chemotaxis.

    PubMed

    Heit, Bryan; Colarusso, Pina; Kubes, Paul

    2005-11-15

    Although the LFA-1, Mac-1 and alpha(4) integrins are required for chemotaxis, it is unknown how they are regulated or what specific role they play. Previously we demonstrated that fMLP and IL-8 induce chemotaxis via the p38 MAPK and phosphoinositide 3-kinase (PI3K) pathways, respectively. Here we show that these chemoattractants also activate and use Mac-1 and LFA-1 in a differential manner during chemotaxis. Using integrin-specific substrata, we demonstrate that cell movement in response to IL-8 is mediated by Mac-1, whereas LFA-1 is required for directional migration. By contrast, chemotaxis to fMLP requires Mac-1 for cell movement, whereas LFA-1 and alpha(4)-integrin are required for directional migration. On serum protein, which contains ligands for LFA-1, Mac-1 and alpha(4)-integrin, chemotaxis to fMLP is dependent on Mac-1, whereas chemotaxis to IL-8 is dependent on LFA-1. These results suggest that Mac-1 is the dominant integrin involved in chemotaxis to fMLP, and LFA-1 is the dominant integrin involved in chemotaxis to IL-8. Consistent with these observations, higher quantities of high-affinity Mac-1 are found on cells chemotaxing to fMLP then on cells chemotaxing to IL-8. Moreover, a much larger quantity of clustered LFA-1 was found on cells migrating to IL-8 compared to cells moving towards fMLP. When cells are presented with competing gradients of fMLP and IL-8, they preferentially migrate towards fMLP and activate/utilize integrins in a manner identical to fMLP alone. Under the same conditions, p38 MAPK inhibition abolishes the preferential migration to fMLP; instead, the cells migrate preferentially towards IL-8. The activation and utilization of integrins under these conditions are consistent with patterns observed with IL-8 alone. Together, these data suggest that fMLP and IL-8 differentially activate integrins for use during chemotaxis, that p38 MAPK is a major mediator in the activation and utilization of integrins, and selective integrin

  2. Impact of NKT Cells and LFA-1 on Liver Regeneration under Subseptic Conditions

    PubMed Central

    Fehlner, Karin; Weisser, Tanja; Cheng, Zhangjun; Lu, Miao; Höchst, Bastian; Bolzer, Andreas; Wang, Baocai; Hartmann, Daniel; Assfalg, Volker; Sunami, Yoshiaki; Schlitter, Anna Melissa; Friess, Helmut; Hüser, Norbert; Laschinger, Melanie

    2016-01-01

    Background Activation of the immune system in terms of subseptic conditions during liver regeneration is of paramount clinical importance. However, little is known about molecular mechanisms and their mediators that control hepatocyte proliferation. We sought to determine the functional role of immune cells, especially NKT cells, in response to partial hepatectomy (PH), and to uncover the impact of the integrin lymphocyte function-associated antigen-1 (LFA-1) on liver regeneration in a subseptic setting. Methods Wild-type (WT) and LFA-1-/- mice underwent a 2/3 PH and low-dose lipopolysaccharid (LPS) application. Hepatocyte proliferation, immune cell infiltration, and cytokine profile in the liver parenchyma were determined. Results Low-dose LPS application after PH results in a significant delay of liver regeneration between 48h and 72h, which is associated with a reduced number of CD3+ cells within the regenerating liver. In absence of LFA-1, an impaired regenerative capacity was observed under low-dose LPS application. Analysis of different leukocyte subpopulations showed less CD3+NK1.1+ NKT cells in the liver parenchyma of LFA-1-/- mice after PH and LPS application compared to WT controls, while CD3-NK1.1+ NK cells markedly increased. Concordantly with this observation, lower levels of NKT cell related cytokines IL-12 and IL-23 were expressed in the regenerating liver of LFA-1-/- mice, while the expression of NK cell-associated CCL5 and IL-10 was increased compared to WT mice. Conclusion A subseptic situation negatively alters hepatocyte proliferation. Within this scenario, we suggest an important impact of NKT cells and postulate a critical function for LFA-1 during processes of liver regeneration. PMID:27977747

  3. Priming by chemokines restricts lateral mobility of the adhesion receptor LFA-1 and restores adhesion to ICAM-1 nano-aggregates on human mature dendritic cells.

    PubMed

    Borgman, Kyra J E; van Zanten, Thomas S; Manzo, Carlo; Cabezón, Raquel; Cambi, Alessandra; Benítez-Ribas, Daniel; Garcia-Parajo, Maria F

    2014-01-01

    LFA-1 is a leukocyte specific β2 integrin that plays a major role in regulating adhesion and migration of different immune cells. Recent data suggest that LFA-1 on mature dendritic cells (mDCs) may function as a chemokine-inducible anchor during homing of DCs through the afferent lymphatics into the lymph nodes, by transiently switching its molecular conformational state. However, the role of LFA-1 mobility in this process is not yet known, despite that the importance of lateral organization and dynamics for LFA-1-mediated adhesion regulation is broadly recognized. Using single particle tracking approaches we here show that LFA-1 exhibits higher mobility on resting mDCs compared to monocytes. Lymphoid chemokine CCL21 stimulation of the LFA-1 high affinity state on mDCs, led to a significant reduction of mobility and an increase on the fraction of stationary receptors, consistent with re-activation of the receptor. Addition of soluble monomeric ICAM-1 in the presence of CCL21 did not alter the diffusion profile of LFA-1 while soluble ICAM-1 nano-aggregates in the presence of CCL21 further reduced LFA-1 mobility and readily bound to the receptor. Overall, our results emphasize the importance of LFA-1 lateral mobility across the membrane on the regulation of integrin activation and its function as adhesion receptor. Importantly, our data show that chemokines alone are not sufficient to trigger the high affinity state of the integrin based on the strict definition that affinity refers to the adhesion capacity of a single receptor to its ligand in solution. Instead our data indicate that nanoclustering of the receptor, induced by multi-ligand binding, is required to maintain stable cell adhesion once LFA-1 high affinity state is transiently triggered by inside-out signals.

  4. LFA-1 Engagement Triggers T Cell Polarization at the HIV-1 Virological Synapse

    PubMed Central

    Starling, Shimona

    2016-01-01

    ABSTRACT HIV-1 efficiently disseminates by cell-cell spread at intercellular contacts called virological synapses (VS), where the virus preferentially assembles and buds. Cell-cell contact triggers active polarization of organelles and viral proteins within infected cells to the contact site to support efficient VS formation and HIV-1 spread; critically, however, which cell surface protein triggers contact-induced polarization at the VS remains unclear. Additionally, the mechanism by which the HIV-1 envelope glycoprotein (Env) is recruited to the VS remains ill defined. Here, we use a reductionist bead-coupled antibody assay as a model of the VS and show that cross-linking the integrin LFA-1 alone is sufficient to induce active T cell polarization and recruitment of the microtubule organizing center (MTOC) in HIV-1-infected cells. Mutant cell lines coupled with inhibitors demonstrated that LFA-1-induced polarization was dependent on the T cell kinase ZAP70. Notably, immunofluorescent staining of viral proteins revealed an accumulation of surface Env at sites of LFA-1 engagement, with intracellular Env localized to a Golgi compartment proximal to the polarized MTOC. Furthermore, blocking LFA-1-induced MTOC polarization through ZAP70 inhibition prevented intracellular Env polarization. Taken together, these data reveal that LFA-1 is a key determinant in inducing dynamic T cell remodeling to the VS and suggest a model in which LFA-1 engagement triggers active polarization of the MTOC and the associated Env-containing secretory apparatus to sites of cell-cell contact to support polarized viral assembly and egress for efficient cell-cell spread. IMPORTANCE HIV-1 causes AIDS by spreading within immune cells and depletion of CD4 T lymphocytes. Rapid spread between these cells occurs by highly efficient cell-cell transmission that takes place at virological synapses (VS). VS are characterized by striking T cell remodeling that is spatially associated with polarized virus

  5. Lymphocyte crawling and transendothelial migration require chemokine triggering of high-affinity LFA-1 integrin.

    PubMed

    Shulman, Ziv; Shinder, Vera; Klein, Eugenia; Grabovsky, Valentin; Yeger, Orna; Geron, Erez; Montresor, Alessio; Bolomini-Vittori, Matteo; Feigelson, Sara W; Kirchhausen, Tomas; Laudanna, Carlo; Shakhar, Guy; Alon, Ronen

    2009-03-20

    Endothelial chemokines are instrumental for integrin-mediated lymphocyte adhesion and transendothelial migration (TEM). By dissecting how chemokines trigger lymphocyte integrins to support shear-resistant motility on and across cytokine-stimulated endothelial barriers, we found a critical role for high-affinity (HA) LFA-1 integrin in lymphocyte crawling on activated endothelium. Endothelial-presented chemokines triggered HA-LFA-1 and adhesive filopodia at numerous submicron dots scattered underneath crawling lymphocytes. Shear forces applied to endothelial-bound lymphocytes dramatically enhanced filopodia density underneath crawling lymphocytes. A fraction of the adhesive filopodia invaded the endothelial cells prior to and during TEM and extended large subluminal leading edge containing dots of HA-LFA-1 occupied by subluminal ICAM-1. Memory T cells generated more frequent invasive filopodia and transmigrated more rapidly than their naive counterparts. We propose that shear forces exerted on HA-LFA-1 trigger adhesive and invasive filopodia at apical endothelial surfaces and thereby promote lymphocyte crawling and probing for TEM sites.

  6. Different states of integrin LFA-1 aggregation are controlled through its association with tetraspanin CD9.

    PubMed

    Reyes, Raquel; Monjas, Alicia; Yánez-Mó, María; Cardeñes, Beatriz; Morlino, Giulia; Gilsanz, Alvaro; Machado-Pineda, Yesenia; Lafuente, Esther; Monk, Peter; Sánchez-Madrid, Francisco; Cabañas, Carlos

    2015-10-01

    The tetraspanin CD9 has been shown to interact with different members of the β1 and β3 subfamilies of integrins, regulating through these interactions cell adhesion, migration and signaling. Based on confocal microscopy co-localization and on co-immunoprecipitation results, we report here that CD9 associates with the β2 integrin LFA-1 in different types of leukocytes including T, B and monocytic cells. This association is resistant to stringent solubilization conditions which, together with data from chemical crosslinking, in situ Proximity Ligation Assays and pull-down experiments, suggest a primary/direct type of interaction mediated by the Large Extracellular Loop of the tetraspanin. CD9 exerts inhibitory effects on the adhesive function of LFA-1 and on LFA-1-dependent leukocyte cytotoxic activity. The mechanism responsible for this negative regulation exerted by CD9 on LFA-1 adhesion does not involve changes in the affinity state of this integrin but seems to be related to alterations in its state of aggregation.

  7. Effector and Suppressor Roles for LFA-1 During the Development of Experimental Autoimmune Encephalomyelitis

    PubMed Central

    Dugger, Kari J.; Zinn, Kurt R.; Weaver, Casey; Bullard, Daniel C.; Barnum, Scott R.

    2009-01-01

    LFA-1 (CD11a/CD18) is a member of the β2-integrin family of adhesion molecules important in leukocyte trafficking and activation. Although LFA-1 is thought to contribute to the development of experimental autoimmune encephalomyelitis (EAE) primarily through its functions on effector T cells, its importance on other leukocyte populations remains unexplored. To address this question, we performed both adoptive transfer EAE experiments involving CD11a-/- mice and trafficking studies using bioluminescent T cells expressing luciferase under the control of a CD2 promoter (T-lux cells). Transfer of encephalitogenic CD11a-/- T cells to wild type mice resulted in a significant reduction in overall EAE severity compared to control transfers. We also observed, using in vivo imaging techniques, that CD11a-/- T-lux cells readily infiltrated lymph nodes and the CNS of wild type recipients with kinetics comparable to CD11a+/+ transfers, although their overall numbers in these organs were reduced. Surprisingly, transfer of encephalitogenic wild type T cells to CD11a-/- mice induced a severe and sometimes fatal EAE disease course, associated with massive T cell infiltration and proliferation in the CNS. These data indicate that LFA-1 expression on leukocytes in recipient mice plays an important immunomodulatory role in EAE. Thus, LFA-1 acts as a key regulatory adhesion molecule during the development of EAE, serving both pro- and anti-inflammatory roles in disease pathogenesis. PMID:19010554

  8. Interleukin-15-activated natural killer cells kill autologous osteoclasts via LFA-1, DNAM-1 and TRAIL, and inhibit osteoclast-mediated bone erosion in vitro.

    PubMed

    Feng, Shan; Madsen, Suzi H; Viller, Natasja N; Neutzsky-Wulff, Anita V; Geisler, Carsten; Karlsson, Lars; Söderström, Kalle

    2015-07-01

    Osteoclasts reside on bone and are the main bone resorbing cells playing an important role in bone homeostasis, while natural killer (NK) cells are bone-marrow-derived cells known to play a crucial role in immune defence against viral infections. Although mature NK cells traffic through bone marrow as well as to inflammatory sites associated with enhanced bone erosion, including the joints of patients with rheumatoid arthritis, little is known about the impact NK cells may have on mature osteoclasts and bone erosion. We studied the interaction between human NK cells and autologous monocyte-derived osteoclasts from healthy donors in vitro. We show that osteoclasts express numerous ligands for receptors present on activated NK cells. Co-culture experiments revealed that interleukin-15-activated, but not resting, NK cells trigger osteoclast apoptosis in a dose-dependent manner, resulting in drastically decreased bone erosion. Suppression of bone erosion requires contact between NK cells and osteoclasts, but soluble factors also play a minor role. Antibodies masking leucocyte function-associated antigen-1, DNAX accessory molecule-1 or tumour necrosis factor-related apoptosis-inducing ligand enhance osteoclast survival when co-cultured with activated NK cells and restore the capacity of osteoclasts to erode bone. These results suggest that interleukin-15-activated NK cells may directly affect bone erosion under physiological and pathological conditions.

  9. IL-18 Is Involved in Eosinophil-Mediated Tumoricidal Activity against a Colon Carcinoma Cell Line by Upregulating LFA-1 and ICAM-1.

    PubMed

    Gatault, Solène; Delbeke, Marie; Driss, Virginie; Sarazin, Aurore; Dendooven, Arnaud; Kahn, Jean-Emmanuel; Lefèvre, Guillaume; Capron, Monique

    2015-09-01

    Eosinophils are multifunctional leukocytes that are involved in innate and adaptive immune responses through the expression of various receptors and mediators. Previously, we showed that human eosinophils and T cells shared cytotoxic activities against tumor cells that involved the γ-δ TCR and cell-cell contact. In this study, we investigated the molecules involved in eosinophil-tumor cell interactions. Given the role of IL-18 in cell adhesion and in protecting against colon cancer, we evaluated its role in eosinophil-mediated cytotoxicity against Colo-205, a human colon carcinoma cell line. We found that human eosinophils exerted dose- and time-dependent tumoricidal activity against Colo-205 cells. Neutralization of IL-18 significantly reduced eosinophil-mediated Colo-205 apoptosis and inhibited cell-cell adhesion. Moreover, addition of rIL-18 led to upregulation of CD11a and ICAM-1 adhesion molecules, which were involved in the contact between eosinophils and Colo-205 cells. Our results indicated that IL-18 was involved in the eosinophil-mediated death of Colo-205 by facilitating contact between effector and target cells. These data underscored the involvement of an additional mediator in eosinophil-mediated antitumor cytotoxicity. Our findings support existing evidence that eosinophils could play a beneficial role in the context of colon cancer.

  10. Endothelial cells proactively form microvilli-like membrane projections upon intercellular adhesion molecule 1 engagement of leukocyte LFA-1.

    PubMed

    Carman, Christopher V; Jun, Chang-Duk; Salas, Azucena; Springer, Timothy A

    2003-12-01

    Specific leukocyte/endothelial interactions are critical for immunity and inflammation, yet the molecular details of this interaction interface remain poorly understood. Thus, we investigated, with confocal microscopy, the distribution dynamics of the central adhesion molecules ICAM-1 and LFA-1 in this context. Monolayers of activated HUVECs stained with fluorescent anti-ICAM-1 Fabs or Chinese hamster ovary-K1 cells expressing ICAM-1-green fluorescent protein were allowed to bind LFA-1-bearing monocytes, neutrophils, or K562 LFA-1 transfectants. ICAM-1 was rapidly relocalized to newly formed microvilli-like membrane projections in response to binding LFA-1 on leukocytes. These ICAM-1-enriched projections encircled the leukocytes extending up their sides and clustered LFA-1 underneath into linear tracks. Projections formed independently of VCAM-1/very late Ag 4 interactions, shear, and proactive contributions from the LFA-1-bearing cells. In the ICAM-1-bearing endothelial cells, projections were enriched in actin but not microtubules, required intracellular calcium, and intact microfilament and microtubule cytoskeletons and were independent of Rho/Rho kinase signaling. Disruption of these projections with cytochalasin D, colchicine, or BAPTA-AM had no affect on firm adhesion. These data show that in response to LFA-1 engagement the endothelium proactively forms an ICAM-1-enriched cup-like structure that surrounds adherent leukocytes but is not important for firm adhesion. This finding leaves open a possible role in leukocyte transendothelial migration, which would be consistent with the geometry and kinetics of formation of the cup-like structure.

  11. F-actin flow drives affinity maturation and spatial organization of LFA-1 at the immunological synapse

    PubMed Central

    Comrie, William A.; Babich, Alexander

    2015-01-01

    Integrin-dependent interactions between T cells and antigen-presenting cells are vital for proper T cell activation, effector function, and memory. Regulation of integrin function occurs via conformational change, which modulates ligand affinity, and receptor clustering, which modulates valency. Here, we show that conformational intermediates of leukocyte functional antigen 1 (LFA-1) form a concentric array at the immunological synapse. Using an inhibitor cocktail to arrest F-actin dynamics, we show that organization of this array depends on F-actin flow and ligand mobility. Furthermore, F-actin flow is critical for maintaining the high affinity conformation of LFA-1, for increasing valency by recruiting LFA-1 to the immunological synapse, and ultimately for promoting intracellular cell adhesion molecule 1 (ICAM-1) binding. Finally, we show that F-actin forces are opposed by immobilized ICAM-1, which triggers LFA-1 activation through a combination of induced fit and tension-based mechanisms. Our data provide direct support for a model in which the T cell actin network generates mechanical forces that regulate LFA-1 activity at the immunological synapse. PMID:25666810

  12. D120 and K152 within the PH Domain of T Cell Adapter SKAP55 Regulate Plasma Membrane Targeting of SKAP55 and LFA-1 Affinity Modulation in Human T Lymphocytes.

    PubMed

    Witte, Amelie; Meineke, Bernhard; Sticht, Jana; Philipsen, Lars; Kuropka, Benno; Müller, Andreas J; Freund, Christian; Schraven, Burkhart; Kliche, Stefanie

    2017-04-01

    The β2-integrin lymphocyte function-associated antigen 1 (LFA-1) is needed for the T cell receptor (TCR)-induced activation of LFA-1 to promote T cell adhesion and interaction with antigen-presenting cells (APCs). LFA-1-mediated cell-cell interactions are critical for proper T cell differentiation and proliferation. The Src kinase-associated phosphoprotein of 55 kDa (SKAP55) is a key regulator of TCR-mediated LFA-1 signaling (inside-out/outside-in signaling). To gain an understanding of how SKAP55 controls TCR-mediated LFA-1 activation, we assessed the functional role of its pleckstrin homology (PH) domain. We identified two critical amino acid residues within the PH domain of SKAP55, aspartic acid 120 (D120) and lysine 152 (K152). D120 facilitates the retention of SKAP55 in the cytoplasm of nonstimulated T cells, while K152 promotes SKAP55 membrane recruitment via actin binding upon TCR triggering. Importantly, the K152-dependent interaction of the PH domain with actin promotes the binding of talin to LFA-1, thus facilitating LFA-1 activation. These data suggest that K152 and D120 within the PH domain of SKAP55 regulate plasma membrane targeting and TCR-mediated activation of LFA-1.

  13. Induction of tyrosine phosphorylation during ICAM-3 and LFA-1-mediated intercellular adhesion, and its regulation by the CD45 tyrosine phosphatase

    PubMed Central

    1994-01-01

    Intercellular adhesion molecule (ICAM)-3, a recently described counter- receptor for the lymphocyte function-associated antigen (LFA)-1 integrin, appears to play an important role in the initial phase of immune response. We have previously described the involvement of ICAM-3 in the regulation of LFA-1/ICAM-1-dependent cell-cell interaction of T lymphoblasts. In this study, we further investigated the functional role of ICAM-3 in other leukocyte cell-cell interactions as well as the molecular mechanisms regulating these processes. We have found that ICAM-3 is also able to mediate LFA-1/ICAM-1-independent cell aggregation of the leukemic JM T cell line and the LFA-1/CD18-deficient HAFSA B cell line. The ICAM-3-induced cell aggregation of JM and HAFSA cells was not affected by the addition of blocking mAb specific for a number of cell adhesion molecules such as CD1 1a/CD18, ICAM-1 (CD54), CD2, LFA-3 (CD58), very late antigen alpha 4 (CD49d), and very late antigen beta 1 (CD29). Interestingly, some mAb against the leukocyte tyrosine phosphatase CD45 were able to inhibit this interaction. Moreover, they also prevented the aggregation induced on JM T cells by the proaggregatory anti-LFA-1 alpha NKI-L16 mAb. In addition, inhibitors of tyrosine kinase activity also abolished ICAM-3 and LFA-1- mediated cell aggregation. The induction of tyrosine phosphorylation through ICAM-3 and LFA-1 antigens was studied by immunofluorescence, and it was found that tyrosine-phosphorylated proteins were preferentially located at intercellular boundaries upon the induction of cell aggregation by either anti-ICAM-3 or anti-LFA-1 alpha mAb. Western blot analysis revealed that the engagement of ICAM-3 or LFA-1 with activating mAb enhanced tyrosine phosphorylation of polypeptides of 125, 70, and 38 kD on JM cells. This phenomenon was inhibited by preincubation of JM cells with those anti-CD45 mAb that prevented cell aggregation. Altogether these results indicate that CD45 tyrosine phosphatase

  14. LFA-1 and Mac-1 define characteristically different intralumenal crawling and emigration patterns for monocytes and neutrophils in situ.

    PubMed

    Sumagin, Ronen; Prizant, Hen; Lomakina, Elena; Waugh, Richard E; Sarelius, Ingrid H

    2010-12-01

    To exit blood vessels, most (∼80%) of the lumenally adhered monocytes and neutrophils crawl toward locations that support transmigration. Using intravital confocal microscopy of anesthetized mouse cremaster muscle, we separately examined the crawling and emigration patterns of monocytes and neutrophils in blood-perfused unstimulated or TNF-α-activated venules. Most of the interacting cells in microvessels are neutrophils; however, in unstimulated venules, a greater percentage of the total monocyte population is adherent compared with neutrophils (58.2 ± 6.1% versus 13.6 ± 0.9%, adhered/total interacting), and they crawl for significantly longer distances (147.3 ± 13.4 versus 61.8 ± 5.4 μm). Intriguingly, after TNF-α activation, monocytes crawled for significantly shorter distances (67.4 ± 9.6 μm), resembling neutrophil crawling. Using function-blocking Abs, we show that these different crawling patterns were due to CD11a/CD18 (LFA-1)- versus CD11b/CD18 (Mac-1)-mediated crawling. Blockade of either Mac-1 or LFA-1 revealed that both LFA-1 and Mac-1 contribute to monocyte crawling; however, the LFA-1-dependent crawling in unstimulated venules becomes Mac-1 dependent upon inflammation, likely due to increased expression of Mac-1. Mac-1 alone was responsible for neutrophil crawling in both unstimulated and TNF-α-activated venules. Consistent with the role of Mac-1 in crawling, Mac-1 block (compared with LFA-1) was also significantly more efficient in blocking TNF-α-induced extravasation of both monocytes and neutrophils in cremaster tissue and the peritoneal cavity. Thus, mechanisms underlying leukocyte crawling are important in regulating the inflammatory responses by regulating the numbers of leukocytes that transmigrate.

  15. A major secretory defect of tumour-infiltrating T lymphocytes due to galectin impairing LFA-1-mediated synapse completion

    PubMed Central

    Petit, Anne-Elisabeth; Demotte, Nathalie; Scheid, Benoît; Wildmann, Claude; Bigirimana, René; Gordon-Alonso, Monica; Carrasco, Javier; Valitutti, Salvatore; Godelaine, Danièle; van der Bruggen, Pierre

    2016-01-01

    Surface galectin has been shown to contribute to dysfunctions of human tumour-infiltrating lymphocytes (TILs). We show here that galectin-covered CD8 TILs produce normal amounts of intracellular cytokines, but fail to secrete them because of defective actin rearrangements at the synapse. The non-secreting TILs also display reduced adhesion to their targets, together with defective LFA-1 recruitment and activation at the synapse. These defects are relieved by releasing surface galectin. As mild LFA-1 blockade on normal blood T cells emulate the defects of galectin-covered TILs, we conclude that galectin prevents the formation of a functional secretory synapse by preventing optimal LFA-1 triggering. Our results highlight a major secretory defect of TILs that is not revealed by widely used intracellular cytokine immunomonitoring assays. They also provide additional insights into the T-cell response, by showing that different thresholds of LFA-1 triggering are required to promote the intracellular production of cytokines and their secretion. PMID:27447355

  16. CCR7-mediated LFA-1 functions in T cells are regulated by 2 independent ADAP/SKAP55 modules.

    PubMed

    Kliche, Stefanie; Worbs, Tim; Wang, Xiaoqian; Degen, Janine; Patzak, Irene; Meineke, Bernhard; Togni, Mauro; Moser, Markus; Reinhold, Annegret; Kiefer, Friedemann; Freund, Christian; Förster, Reinhold; Schraven, Burkhart

    2012-01-19

    The β2-integrin lymphocyte function-associated antigen-1 (LFA-1) plays a crucial role within the immune system. It regulates the interaction between T cells and antigen-presenting cells and facilitates T-cell adhesion to the endothelium, a process that is important for lymphocyte extravasation and homing. Signals mediated via the T-cell receptor and the chemokine receptor CCR7 activate LFA-1 through processes known as inside-out signaling. The molecular mechanisms underlying inside-out signaling are not completely understood. Here, we have assessed the role of the ADAP/SKAP55 module for CCR7-mediated signaling. We show that loss of the module delays homing and reduces intranodal T-cell motility in vivo. This is probably because of a defect in CCR7-mediated adhesion that affects both affinity and avidity regulation of LFA-1. Further analysis of how the ADAP/SKAP55 module regulates CCR7-induced integrin activation revealed that 2 independent pools of the module are expressed in T cells. One pool interacts with a RAPL/Mst1 complex, whereas the other pool is linked to a RIAM/Mst1/Kindlin-3 complex. Importantly, both the RAPL/Mst1 and the RIAM/Mst1/Kindlin-3 complexes require ADAP/SKAP55 for binding to LFA-1 upon CCR7 stimulation. Hence, 2 independent ADAP/SKAP55 modules are essential components of the signaling machinery that regulates affinity and avidity of LFA-1 in response to CCR7.

  17. LFA-1 and ICAM-1 expression induced during melanoma-endothelial cell co-culture favors the transendothelial migration of melanoma cell lines in vitro

    PubMed Central

    2012-01-01

    Background Patients with metastatic melanoma have a poor median rate of survival. It is therefore necessary to increase our knowledge about melanoma cell dissemination which includes extravasation, where cancer cells cross the endothelial barrier. Extravasation is well understood during travelling of white blood cells, and involves integrins such as LFA-1 (composed of two chains, CD11a and CD18) expressed by T cells, while ICAM-1 is induced during inflammation by endothelial cells. Although melanoma cell lines cross endothelial cell barriers, they do not express LFA-1. We therefore hypothesized that melanoma-endothelial cell co-culture might induce the LFA-1/ICAM ligand/receptor couple during melanoma transmigration. Methods A transwell approach has been used as well as blocking antibodies against CD11a, CD18 and ICAM-1. Data were analyzed with an epifluorescence microscope. Fluorescence intensity was quantified with the ImageJ software. Results We show here that HUVEC-conditioned medium induce cell-surface expression of LFA-1 on melanoma cell lines. Similarly melanoma-conditioned medium activates ICAM-1 expression in endothelial cells. Accordingly blocking antibodies of ICAM-1, CD11a or CD18 strongly decrease melanoma transmigration. We therefore demonstrate that melanoma cells can cross endothelial monolayers in vitro due to the induction of ICAM-1 and LFA-1 occurring during the co-culture of melanoma and endothelial cells. Our data further suggest a role of LFA-1 and ICAM-1 in the formation of melanoma cell clumps enhancing tumor cell transmigration. Conclusion Melanoma-endothelial cell co-culture induces LFA-1 and ICAM-1 expression, thereby favoring in vitro melanoma trans-migration. PMID:23039186

  18. LFA-1 is critical for regulatory T cell homeostasis and function.

    PubMed

    Wohler, Jillian; Bullard, Dan; Schoeb, Trent; Barnum, Scott

    2009-07-01

    Cellular adhesion molecules involved in cell-to-cell mediated suppression by Tregs are not well characterized. We found that the majority of Tregs expressed LFA-1 but most strikingly that the frequency of Tregs in LFA-1(-/-) mice was significantly lower (approximately 50%) in the spleen, lymph nodes, and Peyer's patches compared to wild type controls. The reduction in LFA-1(-/-) Treg cells appears due in part to a reduced capacity of LFA-1(-/-) CD4(+)CD25(-) cells to be induced to become Tregs in the lymph nodes. Importantly, we found that LFA-1(-/-) Tregs fail to suppress T cell responses in vitro and have reduced function in vivo. Treg-mediated suppression does not depend on LFA-1 interactions with ICAM-1 on the surface of responder cells. Our data demonstrate that LFA-1 plays a critical role in regulatory T cell homeostasis and function.

  19. [Overexpression of B7-1 amd B7-2 by LFA-1 positive lymphocytes in chronic inflammatory bowel diseases].

    PubMed

    Isbert, C; Germer, C T; Albrecht, D; Thomsen-Mund, K; Schuppan, D; Buhr, H J

    1998-01-01

    The B7/CD28 pathway is essential for initiating antigen-specific T-cell activation. LFA-1 (CD11a/CD18) is required for sufficient migration into inflammatory tissue. The aim of this study was to evaluate the role of B7 and LFA-1 in inflammatory bowel disease. Immunohistological single and double staining (PAP/APAAP) with monoclonal antibodies against HLA I/II, CD4, CD8, CD28, B7-1, B7-2, LFA-1 and CD68 were performed in tissue samples from patients with crohn's disease (n = 15), ulcerative colitis (n = 14), colorectal carcinoma (n = 5) and FAP (n = 3). The expression of B7-1 and B7-2 was generally much higher in ulcerative colitis and crohn's disease than in colorectal carcinoma and FAP. In crohn's disease multinucleated gigant cells in the granulomas express B7-1 and B7-2. Double staining showed a higher B7-1/B7-2 coexpression for CD4+ than for CD8+ T cells. In colitis ulcerosa and crohn's disease LFA-1 positive leucocytes showed a high coexpression of B7-1 and B7-2 in contrast to CD68 positive macrophages. These data suggest that overexpression of B7-1 and B7-2 on LFA-1 positive Leucocyts seems to play an important role in the pathogenesis of inflammatory bowel disease.

  20. Combination of anti-ICAM-1 and anti-LFA-1 monoclonal antibody therapy prolongs allograft survival in rat hind-limb transplants.

    PubMed

    Ozer, K; Siemionow, M

    2001-10-01

    Immunosuppressive effects of monoclonal antibodies against adhesion molecules were validated in solid organ transplants. There have been only a few reports on the effect of these antibodies on limb transplantation. In this study, the authors investigated the effects of anti-ICAM-1 and anti-LFA-1 therapy in the rat hind-limb-cremaster transplantation model. Twenty transplantations were performed across a major histocompatibility barrier between Lewis Brown Norway (LBN, RT-1(l+n)) and Lewis (LEW, RT-1(l)) rats in four experimental groups of five animals each. Group 1 animals received only vehicle solution; Groups 2 and 3 received monoclonal antibodies against ICAM-1 and LFA-1, respectively; Group 4 received a combination dose. Treatments were continued for 7 days. Clinical signs of rejection were noted daily, and correlated with in vivo microcirculatory measurements. The activation of adhering leukocytes was significantly lower in rats treated with anti-ICAM-1, anti-LFA-1, and combination than in controls (p < 0.05). Transmigrating leukocytes were also reduced in antibody-treated groups, when compared to the control group (p < 0.05). The mean number of rolling lymphocytes was significantly reduced only in the combination group (p < 0.05). Endothelial edema index, a measure of endothelial swelling, was lowest in the combination group (p < 0.05). The first clinical signs of rejection were noted between the 5(th) and 9(th) days in the control group, on the 9(th) day in the anti-ICAM-1 or anti-LFA-1 groups, and on the 13(th) day with combination therapy. Monoclonal antibodies against LFA-1 or ICAM-1 alone inhibit the activation of leukocytes at the microcirculatory level but do not prolong graft survival. However, the combination of anti-ICAM-1 and anti-LFA-1 monoclonal antibodies significantly prolonged allograft survival in this composite tissue transplantation model.

  1. Extract from Acanthopanax senticosus prevents LPS-induced monocytic cell adhesion via suppression of LFA-1 and Mac-1.

    PubMed

    Kim, Hyun Jeong; McLean, Danielle; Pyee, Jaeho; Kim, Jongmin; Park, Heonyong

    2014-04-01

    A crude extract from Acanthopanax senticosus (AS) has drawn increased attention because of its potentially beneficial activities, including anti-fatigue, anti-stress, anti-gastric-ulcer, and immunoenhancing effects. We previously reported that AS crude extract exerts anti-inflammatory activity through blockade of monocytic adhesion to endothelial cells. However, the underlying mechanisms remained unknown, and so this study was designed to investigate the pathways involved. It was confirmed that AS extract inhibited lipopolysaccharide (LPS)-induced adhesion of monocytes to endothelial cells, and we found that whole extract was superior to eleutheroside E, a principal functional component of AS. A series of PCR experiments revealed that AS extract inhibited LPS-induced expression of genes encoding lymphocyte function-associated antigen-1 (LFA-1) and macrophage-1 antigen (Mac-1) in THP-1 cells. Consistently, protein levels and cell surface expression of LFA-1 and Mac-1 were noticeably reduced upon treatment with AS extract. This inhibitory effect was mediated by the suppression of LPS-induced degradation of IκB-α, a known inhibitor of nuclear factor-κB (NF-κB). In conclusion, AS extract exerts anti-inflammatory activity via the suppression of LFA-1 and Mac-1, lending itself as a potential therapeutic galenical for the prevention and treatment of various inflammatory diseases.

  2. Th17 Cells Induce Dopaminergic Neuronal Death via LFA-1/ICAM-1 Interaction in a Mouse Model of Parkinson's Disease.

    PubMed

    Liu, Zhan; Huang, Yan; Cao, Bei-Bei; Qiu, Yi-Hua; Peng, Yu-Ping

    2016-11-14

    T helper (Th)17 cells, a subset of CD4(+) T lymphocytes, have strong pro-inflammatory property and appear to be essential in the pathogenesis of many inflammatory diseases. However, the involvement of Th17 cells in Parkinson's disease (PD) that is characterized by a progressive degeneration of dopaminergic (DAergic) neurons in the nigrostriatal system is unclear. Here, we aimed to demonstrate that Th17 cells infiltrate into the brain parenchyma and induce neuroinflammation and DAergic neuronal death in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)- or 1-methyl-4-phenylpyridinium (MPP(+))-induced PD models. Blood-brain barrier (BBB) disruption in the substantia nigra (SN) was assessed by the signal of FITC-labeled albumin that was injected into blood circulation via the ascending aorta. Live cell imaging system was used to observe a direct contact of Th17 cells with neurons by staining these cells using the two adhesion molecules, leukocyte function-associated antigen (LFA)-1 and intercellular adhesion molecule (ICAM)-1, respectively. Th17 cells invaded into the SN where BBB was disrupted in MPTP-induced PD mice. Th17 cells exacerbated DAergic neuronal loss and pro-inflammatory/neurotrophic factor disorders in MPP(+)-treated ventral mesencephalic (VM) cell cultures. A direct contact of LFA-1-stained Th17 cells with ICAM-1-stained VM neurons was dynamically captured. Either blocking LFA-1 in Th17 cells or blocking ICAM-1 in VM neurons with neutralizing antibodies abolished Th17-induced DAergic neuronal death. These results establish that Th17 cells infiltrate into the brain parenchyma of PD mice through lesioned BBB and exert neurotoxic property by promoting glial activation and importantly by a direct damage to neurons depending on LFA-1/ICAM-1 interaction.

  3. T Cell Migration from Inflamed Skin to Draining Lymph Nodes Requires Intralymphatic Crawling Supported by ICAM-1/LFA-1 Interactions.

    PubMed

    Teijeira, Alvaro; Hunter, Morgan C; Russo, Erica; Proulx, Steven T; Frei, Thomas; Debes, Gudrun F; Coles, Marc; Melero, Ignacio; Detmar, Michael; Rouzaut, Ana; Halin, Cornelia

    2017-01-24

    T cells are the most abundant cell type found in afferent lymph, but their migration through lymphatic vessels (LVs) remains poorly understood. Performing intravital microscopy in the murine skin, we imaged T cell migration through afferent LVs in vivo. T cells entered into and actively migrated within lymphatic capillaries but were passively transported in contractile collecting vessels. Intralymphatic T cell number and motility were increased during contact-hypersensitivity-induced inflammation and dependent on ICAM-1/LFA-1 interactions. In vitro, blockade of endothelial cell-expressed ICAM-1 reduced T cell adhesion, crawling, and transmigration across lymphatic endothelium and decreased T cell advancement from capillaries into lymphatic collectors in skin explants. In vivo, T cell migration to draining lymph nodes was significantly reduced upon ICAM-1 or LFA-1 blockade. Our findings indicate that T cell migration through LVs occurs in distinct steps and reveal a key role for ICAM-1/LFA-1 interactions in this process.

  4. 76 FR 56407 - Notice of Availability of a Draft Supplemental Environmental Impact Statement/Supplemental...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-09-13

    ... Frequency Active Sonar AGENCY: Department of the Navy, DoD. ACTION: Notice. SUMMARY: Pursuant to Section 102... Quality regulations (40 CFR parts 1500-1508) and Executive Order 12114 (Environmental Effects Abroad of... employment of Surveillance Towed Array Sensor System Low Frequency Active (SURTASS LFA) sonar systems....

  5. LFA-1 is Critical for Regulatory T cell Homeostasis and Function

    PubMed Central

    Wohler, Jillian; Bullard, Dan; Schoeb, Trent; Barnum, Scott

    2015-01-01

    Cellular adhesion molecules involved in cell-to-cell mediated suppression by Tregs are not well characterized. We found that the majority of Tregs expressed LFA-1 but most strikingly that the frequency of Tregs in LFA-1−/− mice was significantly lower (~50%) in the spleen, lymph nodes, and Peyer’s Patches compared to wild type controls. The reduction in LFA-1−/− Treg cells appears due in part to a reduced capacity of LFA-1−/− CD4+CD25− cells to be induced to become Tregs in the lymph nodes. Importantly, we found that LFA-1−/− Tregs fail to suppress T cell responses in vitro and have reduced function in vivo. Treg mediated-suppression does not depend on LFA-1 interactions with ICAM-1 on the surface of responder cells. Our data demonstrate that LFA-1 plays a critical role in regulatory T cell homeostasis and function. PMID:19428111

  6. 78 FR 57368 - Taking and Importing Marine Mammals: Taking Marine Mammals Incidental to Navy Operations of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-09-18

    ... Marine Mammals Incidental to Navy Operations of Surveillance Towed Array Sensor System Low Frequency... accordance with regulations issued under the Marine Mammal Protection Act, as amended, we hereby give... Surveillance Towed Array Sensor System Low Frequency Active (SURTASS LFA) sonar within the northwest...

  7. 77 FR 51969 - Taking and Importing Marine Mammals: Taking Marine Mammals Incidental to Navy Operations of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-08-28

    ... Marine Mammals Incidental to Navy Operations of Surveillance Towed Array Sensor System Low Frequency... accordance with the Marine Mammal Protection Act (MMPA), as amended, and implementing regulations... Low Frequency Active (SURTASS LFA) sonar operations to the Chief of Naval Operations, Department...

  8. 75 FR 51443 - Taking and Importing Marine Mammals: Taking Marine Mammals Incidental to Navy Operations of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-20

    ... Marine Mammals Incidental to Navy Operations of Surveillance Towed Array Sensor System Low Frequency... accordance with the Marine Mammal Protection Act (MMPA), as amended, and implementing regulations... Low Frequency Active (SURTASS LFA) sonar operations to the Chief of Naval Operations, Department...

  9. 76 FR 53884 - Taking and Importing Marine Mammals; Taking Marine Mammals Incidental to U.S. Navy Operations of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-30

    ... Marine Mammals Incidental to U.S. Navy Operations of Surveillance Towed Array Sensor System Low Frequency... Array Sensor System (SURTASS) Low Frequency Active (LFA) sonar for the period beginning August 2012 and ending August 2017. Pursuant to the implementing regulations of the Marine Mammal Protection Act...

  10. 76 FR 51352 - Taking and Importing Marine Mammals: Taking Marine Mammals Incidental to Navy Operations of...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-08-18

    ... Marine Mammals Incidental to Navy Operations of Surveillance Towed Array Sensor System Low Frequency... accordance with the Marine Mammal Protection Act (MMPA), as amended, and implementing regulations... Low Frequency Active (SURTASS LFA) sonar operations to the Chief of Naval Operations, Department...

  11. Monocyte migration and LFA-1 mediated attachment to brain microvascular endothelia is regulated by SDF-1α through Lyn kinase

    PubMed Central

    Malik, Mobeen; Chen, Ying-Yu; Kienzle, Martha F.; Tomkowicz, Brian E.; Collman, Ronald G.; Ptasznik, Andrzej

    2009-01-01

    Infiltration of activated monocytes into the brain is a prerequisite for the development of various neurological disorders such as HIV associated dementia, multiple sclerosis and other inflammatory processes. In these pathologies the chemokine SDF-1α (CXCL12) is over-expressed and might attract monocytes into the central nervous system. We demonstrate here that SDF-1α stimulates migration of monocytes through its receptor CXCR4, and decreases monocyte adherence to surfaces coated with ICAM-1, a ligand for β2 integrins. SDF-1α also decreases monocyte adherence to brain microvascular endothelial cells (BMVEC) that are activated with TNF-α, IL-1β or recombinant envelope glycoprotein from HIV-1, which increase BMVEC expression of ICAM-1. The decreased adherence is linked to down-regulation on monocytes of the activation-dependent epitope of the β2 integrin LFA-1 by SDF-1α. Knockdown of Lyn in monocytes using siRNA decreases SDF-1α-mediated migration and prevents its inhibition of monocyte attachment to ICAM-1 and activated BMVEC. Thus, in SDF-1α-stimulated monocytes, Lyn acts as a positive regulator of migration, and a negative regulator of adhesion to BMVEC through the LFA-1 integrin. These results provide a novel Lyn-mediated signaling mechanism for the regulation of monocyte movement at the blood-brain barrier. PMID:18802065

  12. LFA-1 binding destabilizes the JAM-A homophilic interaction during leukocyte transmigration.

    PubMed

    Wojcikiewicz, Ewa P; Koenen, Rory R; Fraemohs, Line; Minkiewicz, Julia; Azad, Hashem; Weber, Christian; Moy, Vincent T

    2009-01-01

    Leukocyte transendothelial migration into inflamed areas is regulated by the integrity of endothelial cell junctions and is stabilized by adhesion molecules including junctional adhesion molecule-A (JAM-A). JAM-A has been shown to participate in homophilic interactions with itself and in heterophilic interactions with leukocyte function-associated antigen-1 (LFA-1) via its first and second immunoglobulin domains, respectively. Using competitive binding assays in conjunction with atomic force microscopy adhesion measurements, we provide compelling evidence that the second domain of JAM-A stabilizes the homophilic interaction because its deletion suppresses the dynamic strength of the JAM-A homophilic interaction. Moreover, binding of the LFA-1 inserted domain to the second domain of JAM-A reduces the dynamic strength of the JAM-A homophilic interaction to the level measured with the JAM-A domain 2 deletion mutant. This finding suggests that LFA-1 binding cancels the stabilizing effects of the second immunoglobulin domain of JAM-A. Finally, our atomic force microscopy measurements reveal that the interaction of JAM-A with LFA-1 is stronger than the JAM-A homophilic interaction. Taken together, these results suggest that LFA-1 binding to JAM-A destabilizes the JAM-A homophilic interaction. In turn, the greater strength of the LFA-1/JAM-A complex permits it to support the tension needed to disrupt the JAM-A homophilic interaction, thus allowing transendothelial migration to proceed.

  13. Aggregatibacter actinomycetemcomitans leukotoxin induces cytosol acidification in LFA-1 expressing immune cells.

    PubMed

    Balashova, N; Dhingra, A; Boesze-Battaglia, K; Lally, E T

    2016-02-01

    Studies have suggested that Aggregatibacter actinomycetemcomitans leukotoxin (LtxA) kills human lymphocyte function-associated antigen 1 (LFA-1; CD11a/CD18)-bearing immune cells through a lysosomal-mediated mechanism. Lysosomes are membrane-bound cellular organelles that contain an array of acid hydrolases that are capable of breaking down biomolecules. The lysosomal membrane bilayer confines the pH-sensitive enzymes within an optimal acidic (pH 4.8) environment thereby protecting the slightly basic cytosol (pH 6.8-7.5). In the current study, we have probed the effect of LtxA-induced cytolysis on lysosomal integrity in two different K562 erythroleukemia cell lines. K562-puro/LFA-1 cells were stably transfected with CD11a and CD18 cDNA to express LFA-1 on the cell surface while K562-puro, which does not express LFA-1, served as a control. Following treatment with 100 ng ml(-1) LtxA cells were analyzed by live cell imaging in conjunction with time-lapse confocal microscopy and by flow cytometry. Using a pH-sensitive indicator (pHrodo(®)) we demonstrated that the toxin causes a decrease in the intracellular pH in K562-puro/LFA-1 cells that is noticeable within the first 15 min of treatment. This process correlated with the disappearance of lysosomes in the cytosol as determined by both acridine orange and LysoTracker(®) Red DND-99 staining. These changes were not observed in K562-puro cells or when heat inactivated toxin was added to K562-puro/LFA-1. Our results suggest that LtxA induces lysosomal damage, cytosol acidification, which is followed by cell death in K562-puro/LFA-1 cells.

  14. Aggregatibacter actinomycetemcomitans leukotoxin induces cytosol acidification in LFA-1 expressing immune cells

    PubMed Central

    Balashova, Nataliya; Dhingra, Anuradha; Boesze-Battaglia, Kathleen; Lally, Edward T.

    2015-01-01

    Summary Studies have suggested that Aggregatibacter actinomycetemcomitans leukotoxin (LtxA) kills human LFA-1(CD11a/CD18)-bearing immune cells through a lysosomal-mediated mechanism. Lysosomes are membrane-bound cellular organelles that contain an array of acid hydrolases that are capable of breaking down biomolecules. The lysosomal membrane bilayer confines the pH-sensitive enzymes within an optimal acidic (pH 4.8) environment thereby protecting the slightly basic cytosol (pH 6.8–7.5). In the current study, we have probed the effect of LtxA-induced cytolysis on lysosomal integrity in two different K562 erythroleukemia cell lines. K562-puro/LFA-1 cells were stably transfected with CD11a and CD18 cDNA to express LFA-1 on the cell surface while K562-puro, which does not express LFA-1, served as a control. Following treatment with 100 ng/ml LtxA cells were analyzed by live cell imaging in conjunction with time-lapse confocal microscopy and by flow cytometry. Using a pH sensitive indicator (pHrodo®, Life Technologies) we demonstrated that the toxin causes a decrease in the intracellular pH in K562-puro/LFA-1 cells noticeable within the first 15 min of treatment. This process correlated with the disappearance of lysosomes in the cytosol as determined by both acridine orange and LysoTracker® Red DND-99 (Life Technologies) staining. These changes were not observed in K562-puro cells or when heat inactivated toxin was added to K562-puro/LFA-1. Our results suggest that LtxA induces lysosomal damage, cytosol acidification, which is followed by cell death in K562-puro/LFA-1 cells. PMID:26361372

  15. LFA-1 on Leukemic Cells as a Target for Therapy or Drug Delivery

    PubMed Central

    Phongpradist, Rungsinee; Chittasupho, Chuda; Okonogi, Siriporn; Siahaan, Teruna; Anuchapreeda, Songyot; Ampasavate, Chadarat; Berkland, Cory

    2014-01-01

    Leukemia therapeutics are aiming for improved efficacy by targeting molecular markers differentially expressed on cancerous cells. Lymphocyte function-associated antigen-1 (LFA-1) expression on various types of leukemia has been well studied. Here, the role and expression of LFA-1 on leukemic cells and the possibility of using this integrin as a target for drug delivery is reviewed. To support this rationale, experimental results were also included where cIBR, a cyclic peptide derived from a binding site of LFA-1, was conjugated to the surface of polymeric nanoparticles and used as a targeting ligand. These studies revealed a correlation of LFA-1 expression level on leukemic cell lines and binding and internalization of cIBR-NPs suggesting a differential binding and internalization of cIBR-NPs to leukemic cells overexpressing LFA-1. Nanoparticles conjugated with a cyclic peptide against an accessible molecular marker of disease hold promise as a selective drug delivery system for leukemia treatment. PMID:20618153

  16. Neutrophils promote Alzheimer's disease-like pathology and cognitive decline via LFA-1 integrin.

    PubMed

    Zenaro, Elena; Pietronigro, Enrica; Della Bianca, Vittorina; Piacentino, Gennj; Marongiu, Laura; Budui, Simona; Turano, Ermanna; Rossi, Barbara; Angiari, Stefano; Dusi, Silvia; Montresor, Alessio; Carlucci, Tommaso; Nanì, Sara; Tosadori, Gabriele; Calciano, Lucia; Catalucci, Daniele; Berton, Giorgio; Bonetti, Bruno; Constantin, Gabriela

    2015-08-01

    Inflammation is a pathological hallmark of Alzheimer's disease, and innate immune cells have been shown to contribute to disease pathogenesis. In two transgenic models of Alzheimer's disease (5xFAD and 3xTg-AD mice), neutrophils extravasated and were present in areas with amyloid-β (Aβ) deposits, where they released neutrophil extracellular traps (NETs) and IL-17. Aβ42 peptide triggered the LFA-1 integrin high-affinity state and rapid neutrophil adhesion to integrin ligands. In vivo, LFA-1 integrin controlled neutrophil extravasation into the CNS and intraparenchymal motility. In transgenic Alzheimer's disease models, neutrophil depletion or inhibition of neutrophil trafficking via LFA-1 blockade reduced Alzheimer's disease-like neuropathology and improved memory in mice already showing cognitive dysfunction. Temporary depletion of neutrophils for 1 month at early stages of disease led to sustained improvements in memory. Transgenic Alzheimer's disease model mice lacking LFA-1 were protected from cognitive decline and had reduced gliosis. In humans with Alzheimer's disease, neutrophils adhered to and spread inside brain venules and were present in the parenchyma, along with NETs. Our results demonstrate that neutrophils contribute to Alzheimer's disease pathogenesis and cognitive impairment and suggest that the inhibition of neutrophil trafficking may be beneficial in Alzheimer's disease.

  17. LFA-1 (CD11a/CD18) triggers hydrogen peroxide production by canine neutrophils.

    PubMed

    Lu, H; Ballantyne, C; Smith, C W

    2000-07-01

    The respiratory burst of neutrophils stimulated by chemotactic factors is markedly augmented by Mac-1-dependent adhesion such as the interaction of Mac-1 (CD11b/CD18) with intercellular adhesion molecule-1 (ICAM-1; CD54) expressed on the surface of parenchymal cells (e.g., cardiac myocytes). In the current study, we evaluate the hypothesis that lymphocyte function-associated antigen-1 (LFA-1; CD11a/CD18) can also trigger the respiratory burst in neutrophils. To isolate LFA-1/ICAM-1 interactions from Mac-1/ ICAM-1 interactions, full-length chimeric ICAM-1 was developed and expressed in L cells with domains 1 and 2 from canine ICAM-1 and domains 3-5 from human ICAM-1 (C1,2;H3-5). We have shown that canine neutrophils do not bind to human ICAM-1. We demonstrated that chimeric ICAM-1 C1,2;H3-5 supported only LFA-1-dependent adhesion of canine neutrophils and that such adhesion triggered rapid onset of H2O2 production from canine neutrophils. The following seven experimental conditions distinguished LFA-1-dependent H2O2 production from Mac-1-dependent production: It did not require exogenous chemotactic stimulation; H2O2 release was more rapid, but the amount released was <40% of that mediated by Mac-1 adhesion; it was inhibited by anti-CD11a and anti-ICAM-1 antibodies; in contrast to that mediated by Mac-1, it was not inhibited by anti-CD11b antibody, neutrophil inhibitory factor (NIF), or cytochalasin B or H7. Thus, canine neutrophils seem to be able to utilize two members of the beta2 integrin family to interact with ICAM-1 and signal H2O2 production, with LFA-1 at an early stage without prior chemotactic stimulation and Mac-1 at a later stage requiring chemotactic stimulation.

  18. CD103 or LFA-1 engagement at the immune synapse between cytotoxic T cells and tumor cells promotes maturation and regulates T-cell effector functions.

    PubMed

    Franciszkiewicz, Katarzyna; Le Floc'h, Audrey; Boutet, Marie; Vergnon, Isabelle; Schmitt, Alain; Mami-Chouaib, Fathia

    2013-01-15

    T-cell adhesion/costimulatory molecules and their cognate receptors on target cells play a major role in T-cell receptor (TCR)-mediated activities. Here, we compared the involvement of CD103 and LFA-1, and their respective ligands, in the maturation of the cytotoxic immune synapse (cIS) and in the activation of CTL effector functions. Our results indicate that cytotoxicity toward cancer cells and, to a lesser extent, cytokine production by specific CTL require, together with TCR engagement, the interaction of either CD103 with E-cadherin or LFA-1 with ICAM-1. Flow-based adhesion assay showed that engagement of CD103 or LFA-1, together with TCR, enhances the strength of the T-cell/target cell interaction. Moreover, electron microscopic analyses showed that integrin-dependent mature cIS (mcIS) displays a cohesive ultrastructure, with tight membrane contacts separated by extensive clefts. In contrast, immature cIS (icIS), which is unable to trigger target cell lysis, is loose, with multiple protrusions in the effector cell membrane. Experiments using confocal microscopy revealed polarized cytokine release and degranulation at the mcIS associated with target cell killing, whereas icIS is characterized by failure of IFN-γ and granzyme B relocalization. Thus, interactive forces between CTL and epithelial tumor cells, mainly regulated by integrin engagement, correlate with maturity and the ultrastructure of the cIS and influence CTL effector functions. These results provide new insights into molecular mechanisms regulating antitumor CTL responses and may lead to the development of more efficient cancer immunotherapy strategies.

  19. LFA-1 is sufficient in mediating neutrophil emigration in Mac-1-deficient mice.

    PubMed Central

    Lu, H; Smith, C W; Perrard, J; Bullard, D; Tang, L; Shappell, S B; Entman, M L; Beaudet, A L; Ballantyne, C M

    1997-01-01

    To better define the specific function of Mac-1 (CD11b) versus LFA-1 (CD11a) and the other CD11 integrins in vivo, we have disrupted murine CD11b by targeted homologous recombination in embryonic stem cells and generated mice which are homozygous for a mutation in CD11b. A null mutation was confirmed by Southern blotting, RNase protection assay, immunohistochemistry, and flow cytometry. Neutrophils isolated from mice deficient in Mac-1 were defective in adherence to keyhole limpet hemocyanin-coated glass, iC3b-mediated phagocytosis, and homotypic aggregation. When challenged by thioglycollate intraperitoneally, Mac-1-deficient mice had similar levels of neutrophil accumulation in the peritoneal cavity at 1, 2, and 4 h. Treatment with mAb to LFA-1 blocked 78% of neutrophil accumulation in Mac-1-deficient mice and 58% in wild-type mice. Neutrophil emigration into the peritoneal cavity 16 h after the implantation of fibrinogen-coated disks was not reduced in Mac-1-deficient mice whereas neutrophil adhesion to the fibrinogen-coated disks was reduced by > 90%. Neutrophils from Mac-1-deficient mice also showed reduced degranulation. Our results demonstrate that Mac-1 plays a critical role in mediating binding of neutrophils to fibrinogen and neutrophil degranulation, but is not necessary for effective neutrophil emigration, which is more dependent upon LFA-1. PMID:9077544

  20. Visualization of CD2 interaction with LFA-3 and determination of the two-dimensional dissociation constant for adhesion receptors in a contact area

    PubMed Central

    1996-01-01

    Many adhesion receptors have high three-dimensional dissociation constants (Kd) for counter-receptors compared to the KdS of receptors for soluble extracellular ligands such as cytokines and hormones. Interaction of the T lymphocyte adhesion receptor CD2 with its counter- receptor, LFA-3, has a high solution-phase Kd (16 microM at 37 degrees C), yet the CD2/LFA-3 interaction serves as an effective adhesion mechanism. We have studied the interaction of CD2 with LFA-3 in the contact area between Jurkat T lymphoblasts and planar phospholipid bilayers containing purified, fluorescently labeled LFA-3. Redistribution and lateral mobility of LFA-3 were measured in contact areas as functions of the initial LFA-3 surface density and of time after contact of the cells with the bilayers. LFA-3 accumulated at sites of contact with a half-time of approximately 15 min, consistent with the previously determined kinetics of adhesion strengthening. The two-dimensional Kd for the CD2/LFA-3 interaction was 21 molecules/microns 2, which is lower than the surface densities of CD2 on T cells and LFA-3 on most target or stimulator cells. Thus, formation of CD2/LFA-3 complexes should be highly favored in physiological interactions. Comparison of the two-dimensional (membrane- bound) and three-dimensional (solution-phase) KdS suggest that cell- cell contact favors CD2/LFA-3 interaction to a greater extent than that predicted by the three-dimensional Kd and the intermembrane distance at the site of contact. LFA-3 molecules in the contact site were capable of lateral diffusion in the plane of the phospholipid bilayer and did not appear to be irreversibly trapped in the contact area, consistent with a rapid off-rate. These data provide insights into the function of low affinity interactions in adhesion. PMID:8636222

  1. Expression of LFA-1/ICAM-1 in CNS lymphomas: possible mechanism for lymphoma homing into the brain.

    PubMed

    Bashir, R; Coakham, H; Hochberg, F

    1992-02-01

    We examined a possible role for the adhesion molecules LFA-1 and ICAM-1 in localizing central nervous system non-Hodgkin's lymphomas (CNS-NHLs) to the brain. Fresh frozen sections from 12 monoclonal CNS NHLs (11 primary, one secondary) were stained with monoclonal antibodies to LFA-1 alpha chain (CD11a), beta chain (CD18) and, ICAM-1 (CD54). Additional staining made use of rat monoclonal antibodies to the human and mouse high endothelial venule antigens HECA 452 and MECA 79 and mouse ICAM-1. The expression of these same molecules was also studied in mice with severe combined immunodeficiency (SCID) mice, bearing intracranial human lymphoblastoid cells. Eleven of the CNS-NHL tumors expressed LFA-1 alpha (one strongly, one intermediate, nine weakly). Nine of the tumors weakly expressed LFA-1 beta.. Nine of twelve tumors weakly expressed ICAM-1. In six of seven tumors definite blood vessels stained for ICAM-1. Non-tumor brain from two patients and non-tumor cerebral blood vessels showed no staining with CD11a, CD18 or CD54 antibodies. Strong expression of LFA-alpha and LFA-beta as well as ICAM-1 was noted in human lymphoblastoid cells (LCLs)/SCID mouse CNS lymphomas. Tumor blood vessels in these mice stained for mouse ICAM-1. Normal SCID mouse brains showed no staining with CD11a, CD18, CD54 or mouse ICAM-1 antibodies. Human, human/mouse CNS lymphomas, normal human, and mouse brains showed no staining with either HECA 452 or MECA 79.(ABSTRACT TRUNCATED AT 250 WORDS)

  2. Genomic clone encoding the. cap alpha. chain of the OKM1, LFA-1, and platelet glycoprotein IIb-IIIa molecules

    SciTech Connect

    Cosgrove, L.J.; Sandrin, M.S.; Rajasekariah, P.; McKenzie, I.F.C.

    1986-02-01

    LFA-1, an antigen involved in cytolytic T lymphocyte-mediated killing, and Mac-1, the receptor for complement component C3bi, constitute a family of structurally and functionally related cell surface glycoproteins involved in cellular interactions. In both mouse and man, Mac-1 (OKM1) and LFA-1 share a common 95-kDa ..beta.. subunit but are distinguished by their ..cap alpha.. chains, which have different cellular distributions, apparent molecular masses (165 and 177 kDa, respectively), and peptide maps. The authors report the isolation of a genomic clone from a human genomic library that on transfection into mouse fibroblasts produced a molecule(s) reactive with monoclonal antibodies to OKM1, to LFA-1, and to platelet glycoprotein IIb-IIIa. This gene was cloned by several cycles of transfection of L cells with a human genomic library cloned in lambda phase Charon 4A and subsequent rescue of the lambda phage. Transfection with the purified recombinant lambda DNA yielded a transfectant that expressed the three human ..cap alpha.. chains of OKM1, LFA-1, and glycoprotein IIb-IIIa, presumably in association with the murine ..beta.. chain.

  3. The interaction of CD2 with its LFA-3 ligand expressed by autologous erythrocytes results in enhancement of B cell responses.

    PubMed

    Virella, G; Rugeles, M T; Hyman, B; La Via, M; Goust, J M; Frankis, M; Bierer, B E

    1988-10-15

    The addition of autologous erythrocytes to unfractionated human mononuclear cell cultures results in enhancement of B cell responses to antigens and mitogens. This costimulating effect of red cells is abrogated by their preincubation with anti-LFA-3 monoclonal antibody. Preincubation of mononuclear cells with anti-CD2 monoclonal antibodies (anti-Leu 5b, OKT11, used singly) has a down-regulating effect on B cell activation and no enhancement of B cell responses is seen when red cells are added to anti-CD2-treated cultures. These results demonstrate a functional effect on B cells of the interaction between the CD2 molecule on T lymphocytes and its natural ligand, LFA-3. The precise mechanism by which this costimulating effect on B lymphocytes takes place is unclear. The study of T cell populations and T cell activation markers shows that the addition of erythrocytes causes a small but reproducible increase in the number of cells expressing the IL-2 receptor and the addition of IL-2 enhances the response of mononuclear cells to antigenic stimulation in the presence of erythrocytes. However, the supernatants of mononuclear cell cultures stimulated with pokeweed mitogen in the presence of autologous erythrocytes show decreased levels of IL-2, compared to supernatants of cells stimulated with pokeweed mitogen alone. The same supernatants show increased levels of interferon-gamma, but the addition of this lymphokine to cultures stimulated with pokeweed mitogen has no potentiating effect. It is possible that the effect of erythrocytes is mediated by other growth and/or differentiation factors, and additional studies will be required to clarify this point.

  4. Involvement of leukocyte function-associated antigen-1 (LFA-1) in the invasion of hepatocyte cultures by lymphoma and T-cell hybridoma cells

    PubMed Central

    1987-01-01

    We studied the interaction of MB6A lymphoma and TAM2D2 T cell hybridoma cells with hepatocyte cultures as an in vitro model for in vivo liver invasion by these tumor cells. A monoclonal antibody against leukocyte function-associated antigen-1 (LFA-1) inhibited adhesion of the tumor cells to the surface of hepatocytes and consequently strongly reduced invasion. This effect was specific since control antibodies, directed against Thy.1 and against T200, of the same isotype, similar affinity, and comparable binding to these cells, did not inhibit adhesion. This suggests that LFA-1 is involved in the formation of liver metastases by lymphoma cells. TAM2D2 T cell hybridoma cells were agglutinated by anti- LFA-1, but not by control antibodies. Reduction of adhesion was not due to this agglutination since monovalent Fab fragments inhibited adhesion as well, inhibition was also seen under conditions where agglutination was minimal, and anti-LFA-1 similarly affected adhesion of MB6A lymphoma cells that were not agglutinated. The two cell types differed in LFA-1 surface density. TAM2D2 cells exhibited 400,000 surface LFA-1 molecules, 10 times more than MB6A cells. Nevertheless, the level of adhesion and the extent of inhibition by the anti-LFA-1 antibody were only slightly larger for the TAM2D2 cells. PMID:3301869

  5. Disruption of tumour-host communication by downregulation of LFA-1 reduces COX-2 and e-NOS expression and inhibits brain metastasis growth

    PubMed Central

    Soto, Manuel Sarmiento; O'Brien, Emma R.; Andreou, Kleopatra; Scrace, Simon F.; Zakaria, Rasheed; Jenkinson, Michael D.; O'Neill, Eric; Sibson, Nicola R.

    2016-01-01

    Over 20% of cancer patients will suffer metastatic spread to the brain, and prognosis remains poor. Communication between tumour cells and host tissue is essential during metastasis, yet little is known of the processes underlying such interactions in the brain. Here we test the hypothesis that cross-talk between tumour cells and host brain cells, through tumour cell leukocyte function associated protein-1 (LFA-1), is critical in metastasis development. Temporal expression of LFA-1 and its major ligand intercellular adhesion molecule-1 (ICAM-1) was determined in two different mouse models of brain metastasis. Marked upregulation of both proteins was found, co-localising with astrocytes, microglia and tumour cells themselves. Silencing of LFA-1 expression in MDA231Br-GFP cells prior to intracerebral injection resulted in > 70% reduction in tumour burden compared to control MDA231Br-GFP cells (p < 0.005, n = 5). Subsequent qRT-PCR analysis of brain tissue revealed significant reductions in COX-2, VEGF and eNOS from host brain tissue, but not tumour cells, in mice injected with LFA-1 knockdown cells (p < 0.0001, n = 5). Finally, expression of both LFA-1 and ICAM-1 was demonstrated in human brain metastasis samples. The results of this study suggest LFA-1 as a new target in brain metastasis therapy and highlight the potential synergy with current anti-COX-2 and anti-NOS therapies. PMID:27447568

  6. Treatment with anti-LFA-1 alpha monoclonal antibody selectively interferes with the maturation of CD4- 8+ thymocytes.

    PubMed

    Revilla, C; González, A L; Conde, C; López-Hoyos, M; Merino, J

    1997-04-01

    Maturation of T lymphocytes in the thymus is driven by signals provided by soluble factors and by the direct interaction between thymocytes and stromal cells. Although the interaction between T-cell receptor (TCR) and major histocompalibility complex (MHC) molecules on stromal cells is crucial for T-cell development, other accessory molecules seem to play a role in this process. In order to better understand the role of lymphocyte function-associated antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) molecules in thymocyte maturation, mice were treated from birth with saturating doses of non-cytolytic-specific monoclonal antibodies. The effect of this treatment on thymocyte subpopulations and the expression of CD3 and TCR-alpha beta by these cells was investigated by flow cytometry. Our data demonstrated that the effective saturation of LFA-1 alpha chain in the thymus, but not ICAM-I or LFA-I beta chain, selectively interfered with the maturation of CD8+ T cells, as manifested by a marked reduction in the frequency of CD4-8+ thymocytes expressing high levels of CD3 and TCR-alpha beta. This selective reduction was also observed in peripheral blood mononuclear cells and spleen cells. The analysis of the frequencies of various V beta TCR showed that CD4-8+ thymocytes were globally affected by the treatment. These results underline the importance of the interaction between LFA-1 and its ligands in the maturation of CD8+ T cells and document the existence of different molecular requirements for the differentiation of CD4+ and CD8+ T cells.

  7. Crystal structure of isoflurane bound to integrin LFA-1 supports a unified mechanism of volatile anesthetic action in the immune and central nervous systems

    SciTech Connect

    Zhang, Hongmin; Astrof, Nathan S.; Liu, Jin-Huan; Wang, Jia-huai; Shimaoka, Motomu

    2009-09-15

    Volatile anesthetics (VAs), such as isoflurane, induce a general anesthetic state by binding to specific targets (i.e., ion channels) in the central nervous system (CNS). Simultaneously, VAs modulate immune functions, possibly via direct interaction with alternative targets on leukocytes. One such target, the integrin lymphocyte function-associated antigen-1 (LFA-1), has been shown previously to be inhibited by isoflurane. A better understanding of the mechanism by which isoflurane alters protein function requires the detailed information about the drug-protein interaction at an atomic level. Here, we describe the crystal structure of the LFA-1 ligand-binding domain (I domain) in complex with isoflurane at 1.6 {angstrom}. We discovered that isoflurane binds to an allosteric cavity previously implicated as critical for the transition of LFA-1 from the low- to the high-affinity state. The isoflurane binding site in the I domain involves an array of amphiphilic interactions, thereby resembling a 'common anesthetic binding motif' previously predicted for authentic VA binding sites. These results suggest that the allosteric modulation of protein function by isoflurane, as demonstrated for the integrin LFA-1, might represent a unified mechanism shared by the interactions of volatile anesthetics with targets in the CNS. Crystal structure of isoflurane bound to integrin LFA-1 supports a unified mechanism of volatile anesthetic action in the immune and central nervous systems.

  8. Cysteine protease cathepsin X modulates immune response via activation of β2 integrins

    PubMed Central

    Obermajer, Nataša; Repnik, Urška; Jevnikar, Zala; Turk, Boris; Kreft, Marko; Kos, Janko

    2008-01-01

    Cathepsin X is a lysosomal, cysteine dependent carboxypeptidase. Its expression is restricted to cells of the immune system, suggesting a function related to the processes of inflammatory and immune responses. It has been shown to stimulate macrophage antigen-1 (Mac-1) receptor-dependent adhesion and phagocytosis via interaction with integrin β2 subunit. Here its potential role in regulating lymphocyte proliferation via Mac-1 and the other β2 integrin receptor, lymphocyte function-associated antigen-1 (LFA-1) has been investigated. Cathepsin X has been shown to suppress proliferation of human peripheral blood mononuclear cells, by activation of Mac-1, known as a suppressive factor for lymphocyte proliferation. On the other hand, co-localization of cathepsin X and LFA-1 supports the role of cathepsin X in regulating LFA-1 activity, which enhances lymphocyte proliferation. As shown by fluorescence resonance energy transfer, using U-937 and Jurkat cells transfected with αL-mCFP and β2-mYFP, recombinant cathepsin X directly activates LFA-1. The activation was confirmed by increased binding of monoclonal antibody 24, recognizing active LFA-1. We demonstrate that cathepsin X is involved in the regulation of two β2 integrin receptors, LFA-1 and Mac-1, which exhibit opposing roles in lymphocyte activation. PMID:18194276

  9. Hyperketonemia increases monocyte adhesion to endothelial cells and is mediated by LFA-1 expression in monocytes and ICAM-1 expression in endothelial cells.

    PubMed

    Rains, Justin L; Jain, Sushil K

    2011-08-01

    Frequent episodes of hyperketonemia are associated with a higher incidence of vascular disease. The objective of this study was to examine the hypothesis that hyperketonemia increases monocyte-endothelial cell (EC) adhesion and the development of vascular disease in diabetes. Human U937 and THP-1 monocyte cell lines and human umbilical vein endothelial cells (HUVECs) were cultured with acetoacetate (AA) (0-10 mM) or β-hydroxybutyrate (BHB) (0-10 mM) for 24 h prior to evaluating adhesion and adhesion molecule expression. The results demonstrate a significant (P < 0.01) increase in both U937 and THP-1 adhesion to HUVEC monolayers treated with 4 mM AA compared with control. Equal concentrations of BHB resulted in similar increases in monocyte-EC adhesion. Similarly, treatments of AA or BHB to isolated monocytes from human blood also show increases in adhesion to endothelial cells. intercellular adhesion molecule-1 (ICAM-1) was significantly increased on the surface of HUVECs and an increase in total protein expression with AA treatment compared with control. The expression level of lymphocyte function-associated antigen-1 (LFA-1) was increased in monocytes treated with AA, and LFA-1 affinity was altered from low to high affinity following treatment with both AA and BHB. Monocyte adhesion could be blocked when cells were preincubated with an antibody to ICAM-1 or LFA-1. Results also show a significant increase in IL-8 and MCP-1 secretion in monocytes and HUVECs treated with 0-10 mM AA. These results suggest that hyperketonemia can induce monocyte adhesion to endothelial cells and that it is mediated via increased ICAM-1 expression in endothelial cells and increased expression and affinity of LFA-1 in monocytes.

  10. Hyperketonemia increases monocyte adhesion to endothelial cells and is mediated by LFA-1 expression in monocytes and ICAM-1 expression in endothelial cells

    PubMed Central

    Rains, Justin L.

    2011-01-01

    Frequent episodes of hyperketonemia are associated with a higher incidence of vascular disease. The objective of this study was to examine the hypothesis that hyperketonemia increases monocyte-endothelial cell (EC) adhesion and the development of vascular disease in diabetes. Human U937 and THP-1 monocyte cell lines and human umbilical vein endothelial cells (HUVECs) were cultured with acetoacetate (AA) (0–10 mM) or β-hydroxybutyrate (BHB) (0–10 mM) for 24 h prior to evaluating adhesion and adhesion molecule expression. The results demonstrate a significant (P < 0.01) increase in both U937 and THP-1 adhesion to HUVEC monolayers treated with 4 mM AA compared with control. Equal concentrations of BHB resulted in similar increases in monocyte-EC adhesion. Similarly, treatments of AA or BHB to isolated monocytes from human blood also show increases in adhesion to endothelial cells. intercellular adhesion molecule-1 (ICAM-1) was significantly increased on the surface of HUVECs and an increase in total protein expression with AA treatment compared with control. The expression level of lymphocyte function-associated antigen-1 (LFA-1) was increased in monocytes treated with AA, and LFA-1 affinity was altered from low to high affinity following treatment with both AA and BHB. Monocyte adhesion could be blocked when cells were preincubated with an antibody to ICAM-1 or LFA-1. Results also show a significant increase in IL-8 and MCP-1 secretion in monocytes and HUVECs treated with 0–10 mM AA. These results suggest that hyperketonemia can induce monocyte adhesion to endothelial cells and that it is mediated via increased ICAM-1 expression in endothelial cells and increased expression and affinity of LFA-1 in monocytes. PMID:21540444

  11. Monocyte migration to arthritis in the rat utilizes both CD11/CD18 and very late activation antigen 4 integrin mechanisms

    PubMed Central

    1995-01-01

    In human and experimental models of arthritis, blood monocytes migrate into the inflamed synovium and joint space. The mechanisms required for monocyte migration across the vascular endothelium in joints is poorly defined. Radiolabeled rat blood monocytes were used to measure monocyte migration to the inflamed joints of rats with adjuvant arthritis, and the role of monocyte adhesion molecules was analyzed. Monocyte accumulation in the inflamed joints was maximal 14-21 d after immunization with adjuvant, when arthritis had fully developed. Blocking mAbs to lymphocyte function-associated antigen 1 (LFA-1), Mac- 1, and very late activation antigen 4 (VLA-4) were used to evaluate the role of these integrins in the migration. Migration to the joints was not inhibited by treatment of the animals with mAb to LFA-1, Mac-1, or VLA-4 alone, and was partially (50%) inhibited in only the most arthritic joint, the talar joint, by the combination of mAb to LFA-1 plus Mac-1. In contrast, this combination inhibited migration to dermal inflammation induced by C5ades Arg, endotoxin, tumor necrosis factor alpha, and polyinosine-cytosine by 60-70%. When mAbs to LFA-1 and VLA-4 were combined, migration to all the inflamed joints was strongly inhibited (80-98%, depending on the joint). Treatment with the combination of the three mAbs to LFA-1, Mac-1, and VLA-4 completely eliminated monocyte migration to all joints and dermal inflammation. The results show that 51Cr blood monocytes can be used to quantify monocyte migration to arthritic joints in the rat. LFA-1 alone or VLA-4 alone is sufficient to mediate most of this migration, and either LFA-1 or VLA-4 is required for monocyte migration to joint inflammation. These results indicate that both the VLA-4 and LFA-1 integrins should be therapeutic targets for suppression of monocyte infiltration of joints in arthritis. PMID:7532681

  12. Kinin B1 receptor regulates interactions between neutrophils and endothelial cells by modulating the levels of Mac-1, LFA-1 and intercellular adhesion molecule-1.

    PubMed

    Figueroa, Carlos D; Matus, Carola E; Pavicic, Francisca; Sarmiento, Jose; Hidalgo, Maria A; Burgos, Rafael A; Gonzalez, Carlos B; Bhoola, Kanti D; Ehrenfeld, Pamela

    2015-04-01

    Kinins are pro-inflammatory peptides that mimic the cardinal features of inflammation. We examined the concept that expression levels of endothelial intercellular adhesion molecule-1 (ICAM-1) and neutrophil integrins Mac-1 and LFA-1 are modulated by the kinin B1 receptor (B1R) agonist, Lys-des[Arg(9)]bradykinin (LDBK). Stimulation of endothelial cells with LDBK increased the levels of ICAM-1 mRNA transcripts/protein, and also of E-selectin and platelet endothelial adhesion molecule-1. ICAM-1 levels increased in a magnitude comparable with that produced by TNF-α. This stimulatory effect was reduced when endothelial cells, which had been previously transfected with a B1R small interfering RNA, were stimulated with LDBK, under comparable conditions. Similarly, LDBK produced a significant increase in protein levels of LFA-1 and Mac-1 integrins in human neutrophils, an effect that was reversed by pretreatment of cells with 10 µg/ml cycloheximide or a B1R antagonist. Functional experiments performed with post-confluent monolayers of endothelial cells stimulated with LDBK and neutrophils primed with TNF-α, and vice versa, resulted in enhanced adhesiveness between both cells. Neutralizing Abs to ICAM-1 and Mac-1 reduced the adhesion between them. Our results indicate that kinin B1R is a novel modulator that promotes adhesion of leukocytes to endothelial cells, critically enhancing the movement of neutrophils from the circulation to sites of inflammation.

  13. 50 CFR 216.184 - Mitigation.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ....54 nm) buffer zone extending beyond the 180-dB zone), SURTASS LFA sonar transmissions will be... mammals have left the area of the mitigation and buffer zones; and (2) There is no further detection of any marine mammal within the mitigation and buffer zones as determined by the visual and/or passive...

  14. 50 CFR 218.234 - Mitigation.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... kilometers (km)) from any coastline, including offshore islands; (ii) The SURTASS LFA sonar sound field....860″ E July to August, annually. (xvi) Hawaiian Islands Humpback Whale NMS and Penguin Bank 21°10′02..., annually. (xvii) Costa Rica Dome Centered at 9°N and 88°W Year-round. (xviii) Great Barrier Reef Between...

  15. JAK tyrosine kinases promote hierarchical activation of Rho and Rap modules of integrin activation.

    PubMed

    Montresor, Alessio; Bolomini-Vittori, Matteo; Toffali, Lara; Rossi, Barbara; Constantin, Gabriela; Laudanna, Carlo

    2013-12-23

    Lymphocyte recruitment is regulated by signaling modules based on the activity of Rho and Rap small guanosine triphosphatases that control integrin activation by chemokines. We show that Janus kinase (JAK) protein tyrosine kinases control chemokine-induced LFA-1- and VLA-4-mediated adhesion as well as human T lymphocyte homing to secondary lymphoid organs. JAK2 and JAK3 isoforms, but not JAK1, mediate CXCL12-induced LFA-1 triggering to a high affinity state. Signal transduction analysis showed that chemokine-induced activation of the Rho module of LFA-1 affinity triggering is dependent on JAK activity, with VAV1 mediating Rho activation by JAKs in a Gαi-independent manner. Furthermore, activation of Rap1A by chemokines is also dependent on JAK2 and JAK3 activity. Importantly, activation of Rap1A by JAKs is mediated by RhoA and PLD1, thus establishing Rap1A as a downstream effector of the Rho module. Thus, JAK tyrosine kinases control integrin activation and dependent lymphocyte trafficking by bridging chemokine receptors to the concurrent and hierarchical activation of the Rho and Rap modules of integrin activation.

  16. Integrin activation by P-Rex1 is required for selectin-mediated slow leukocyte rolling and intravascular crawling.

    PubMed

    Herter, Jan M; Rossaint, Jan; Block, Helena; Welch, Heidi; Zarbock, Alexander

    2013-03-21

    Integrin activation is essential for the function of leukocytes. Impaired integrin activation on leukocytes is the hallmark of the leukocyte adhesion deficiency syndrome in humans, characterized by impaired leukocyte recruitment and recurrent infections. In inflammation, leukocytes collect different signals during the contact with the microvasculature, which activate signaling pathways leading to integrin activation and leukocyte recruitment. We report the role of P-Rex1, a Rac-specific guanine nucleotide exchanging factor, in integrin activation and leukocyte recruitment. We find that P-Rex1 is required for inducing selectin-mediated lymphocyte function-associated antigen-1 (LFA-1) extension that corresponds to intermediate affinity and induces slow leukocyte rolling, whereas P-Rex1 is not involved in the induction of the high-affinity conformation of LFA-1 obligatory for leukocyte arrest. Furthermore, we demonstrate that P-Rex1 is involved in Mac-1-dependent intravascular crawling. In vivo, both LFA-1-dependent slow rolling and Mac-1-dependent crawling are defective in P-Rex1(-/-) leukocytes, whereas chemokine-induced arrest and postadhesion strengthening remain intact in P-Rex1-deficient leukocytes. Rac1 is involved in E-selectin-mediated slow rolling and crawling. In vivo, in an ischemia-reperfusion-induced model of acute kidney injury, abolished selectin-mediated integrin activation contributed to decreased neutrophil recruitment and reduced kidney damage in P-Rex1-deficient mice. We conclude that P-Rex1 serves distinct functions in LFA-1 and Mac-1 activation.

  17. Distribution of LCA protein subspecies and the cellular adhesion molecules LFA-1, ICAM-1 and p150,95 within human foetal thymus.

    PubMed Central

    Harvey, J E; Jones, D B

    1990-01-01

    The distribution of leucocyte common antigen (LCA) protein subspecies and the cellular adhesion molecules LFA-1 (CD11a), ICAM-1 (CD54) and p150,95 (CD11c) has been established within frozen sections of human foetal thymus. Whereas over 95% of foetal cortical thymocytes and approximately 85% of medullary thymocytes were CD45RO positive, CD45RA was only expressed by approximately 29% of medullary thymocytes. The majority of foetal thymocytes also expressed CD11a, whereas CD54 was expressed by thymic epithelial and accessory cells and also apparently by some cortical thymocytes adjacent to epithelial cells. The distribution of CD54 and the major histocompatibility complex (MHC) class II molecule HLA-DR, demonstrated with a monoclonal antibody to a monomorphic determinant, was similar. The CD11c molecule was present on a population of dendritic-type accessory cells, but was absent from the large, scavenger, KiM8-positive macrophages occurring throughout the thymic cortex. Images Figure 1 Figure 2 PMID:1973681

  18. Are orchids left and dandelions right? Frontal brain activation asymmetry and its sensitivity to developmental context.

    PubMed

    Fortier, Paz; Van Lieshout, Ryan J; Waxman, Jordana A; Boyle, Michael H; Saigal, Saroj; Schmidt, Louis A

    2014-08-01

    To clarify long-standing conceptual and empirical inconsistencies in models describing the relation between frontal brain asymmetry and emotion, we tested a theory of biological sensitivity to context. We examined whether asymmetry of alpha activation in frontal brain regions, as measured by resting electroencephalography, is sensitive to early developmental contexts. Specifically, we investigated whether frontal asymmetry moderates the association between birth weight and adult outcomes. Adults with left frontal asymmetry (LFA) who were born at extremely low birth weight exhibited high levels of attention problems and withdrawn behaviors in their 30s, whereas normal-birth-weight adults with LFA had low levels of these problem behaviors. Adults with right frontal asymmetry (RFA) displayed a relatively moderate amount of problem behavior regardless of birth weight. Our findings suggest that LFA is associated with sensitivity to developmental context and may help explain why LFA is associated with both positive and negative outcomes, whereas RFA seems to be associated with a more canalized process in some contexts.

  19. Phenotypic Approaches to Identify Inhibitors of B Cell Activation

    PubMed Central

    Kim, Suzie; Wiener, Jake; Rao, Navin L.; Milla, Marcos E.; DiSepio, Daniel

    2015-01-01

    An EPIC label-free phenotypic platform was developed to explore B cell receptor (BCR) and CD40R-mediated B cell activation. The phenotypic assay measured the association of RL non-Hodgkin’s lymphoma B cells expressing lymphocyte function-associated antigen 1 (LFA-1) to intercellular adhesion molecule 1 (ICAM-1)-coated EPIC plates. Anti-IgM (immunoglobulin M) mediated BCR activation elicited a response that was blocked by LFA-1/ICAM-1 specific inhibitors and a panel of Bruton’s tyrosine kinase (BTK) inhibitors. LFA-1/ICAM-1 association was further increased on coapplication of anti-IgM and mega CD40L when compared to individual application of either. Anti-IgM, mega CD40L, or the combination of both displayed distinct kinetic profiles that were inhibited by treatment with a BTK inhibitor. We also established a FLIPR-based assay to measure B cell activation in Ramos Burkitt’s lymphoma B cells and an RL cell line. Anti-IgM-mediated BCR activation elicited a robust calcium response that was inhibited by a panel of BTK inhibitors. Conversely, CD40R activation did not elicit a calcium response in the FLIPR assay. Compared to the FLIPR, the EPIC assay has the propensity to identify inhibitors of both BCR and CD40R-mediated B cell activation and may provide more pharmacological depth or novel mechanisms of action for inhibition of B cell activation. PMID:25948491

  20. AMP kinase activation with AICAR further increases fatty acid oxidation and blunts triacylglycerol hydrolysis in contracting rat soleus muscle.

    PubMed

    Smith, Angela C; Bruce, Clinton R; Dyck, David J

    2005-06-01

    Muscle contraction increases glucose uptake and fatty acid (FA) metabolism in isolated rat skeletal muscle, due at least in part to an increase in AMP-activated kinase activity (AMPK). However, the extent to which AMPK plays a role in the regulation of substrate utilization during contraction is not fully understood. We examined the acute effects of 5-aminoimidazole-4-carboxamide riboside (AICAR; 2 mm), a pharmacological activator of AMPK, on FA metabolism and glucose oxidation during high intensity tetanic contraction in isolated rat soleus muscle strips. Muscle strips were exposed to two different FA concentrations (low fatty acid, LFA, 0.2 mm; high fatty acid, HFA, 1 mm) to examine the role that FA availability may play in both exogenous and endogenous FA metabolism with contraction and AICAR. Synergistic increases in AMPK alpha2 activity (+45%; P<0.05) were observed after 30 min of contraction with AICAR, which further increased exogenous FA oxidation (LFA: +71%, P<0.05; HFA: +46%, P<0.05) regardless of FA availability. While there were no changes in triacylglycerol (TAG) esterification, AICAR did increase the ratio of FA partitioned to oxidation relative to TAG esterification (LFA: +65%, P<0.05). AICAR significantly blunted endogenous TAG hydrolysis (LFA: -294%, P<0.001; HFA: -117%, P<0.05), but had no effect on endogenous oxidation rates, suggesting a better matching between TAG hydrolysis and subsequent oxidative needs of the muscle. There was no effect of AICAR on the already elevated rates of glucose oxidation during contraction. These results suggest that FA metabolism is very sensitive to AMPK alpha2 stimulation during contraction.

  1. Celecoxib increases lung cancer cell lysis by lymphokine-activated killer cells via upregulation of ICAM-1.

    PubMed

    Schellhorn, Melina; Haustein, Maria; Frank, Marcus; Linnebacher, Michael; Hinz, Burkhard

    2015-11-17

    The antitumorigenic mechanism of the selective cyclooxygenase-2 (COX-2) inhibitor celecoxib is still a matter of debate. Using lung cancer cell lines (A549, H460) and metastatic cells derived from a lung cancer patient, the present study investigates the impact of celecoxib on the expression of intercellular adhesion molecule 1 (ICAM-1) and cancer cell lysis by lymphokine-activated killer (LAK) cells. Celecoxib, but not other structurally related selective COX-2 inhibitors (i.e., etoricoxib, rofecoxib, valdecoxib), was found to cause a substantial upregulation of ICAM-1 protein levels. Likewise, ICAM-1 mRNA expression was increased by celecoxib. Celecoxib enhanced the susceptibility of cancer cells to be lysed by LAK cells with the respective effect being reversed by a neutralizing ICAM-1 antibody. In addition, enhanced killing of celecoxib-treated cancer cells was reversed by preincubation of LAK cells with an antibody to lymphocyte function associated antigen 1 (LFA-1), suggesting intercellular ICAM-1/LFA-1 crosslink as crucial event within this process. Finally, celecoxib elicited no significant increase of LAK cell-mediated lysis of non-tumor bronchial epithelial cells, BEAS-2B, associated with a far less ICAM-1 induction as compared to cancer cells. Altogether, our data demonstrate celecoxib-induced upregulation of ICAM-1 on lung cancer cells to be responsible for intercellular ICAM-1/LFA-1 crosslink that confers increased cancer cell lysis by LAK cells. These findings provide proof for a novel antitumorigenic mechanism of celecoxib.

  2. Celecoxib increases lung cancer cell lysis by lymphokine-activated killer cells via upregulation of ICAM-1

    PubMed Central

    Frank, Marcus; Linnebacher, Michael; Hinz, Burkhard

    2015-01-01

    The antitumorigenic mechanism of the selective cyclooxygenase-2 (COX-2) inhibitor celecoxib is still a matter of debate. Using lung cancer cell lines (A549, H460) and metastatic cells derived from a lung cancer patient, the present study investigates the impact of celecoxib on the expression of intercellular adhesion molecule 1 (ICAM-1) and cancer cell lysis by lymphokine-activated killer (LAK) cells. Celecoxib, but not other structurally related selective COX-2 inhibitors (i.e., etoricoxib, rofecoxib, valdecoxib), was found to cause a substantial upregulation of ICAM-1 protein levels. Likewise, ICAM-1 mRNA expression was increased by celecoxib. Celecoxib enhanced the susceptibility of cancer cells to be lysed by LAK cells with the respective effect being reversed by a neutralizing ICAM-1 antibody. In addition, enhanced killing of celecoxib-treated cancer cells was reversed by preincubation of LAK cells with an antibody to lymphocyte function associated antigen 1 (LFA-1), suggesting intercellular ICAM-1/LFA-1 crosslink as crucial event within this process. Finally, celecoxib elicited no significant increase of LAK cell-mediated lysis of non-tumor bronchial epithelial cells, BEAS-2B, associated with a far less ICAM-1 induction as compared to cancer cells. Altogether, our data demonstrate celecoxib-induced upregulation of ICAM-1 on lung cancer cells to be responsible for intercellular ICAM-1/LFA-1 crosslink that confers increased cancer cell lysis by LAK cells. These findings provide proof for a novel antitumorigenic mechanism of celecoxib. PMID:26513172

  3. High-fat feeding induces angiogenesis in skeletal muscle and activates angiogenic pathways in capillaries.

    PubMed

    Silvennoinen, Mika; Rinnankoski-Tuikka, Rita; Vuento, Mikael; Hulmi, Juha J; Torvinen, Sira; Lehti, Maarit; Kivelä, Riikka; Kainulainen, Heikki

    2013-04-01

    High-fat diet (HFD) increases fatty acid oxidation in skeletal muscles. We hypothesized that this leads to increased oxygen demand and thus to increased capillarization. We determined the effects of high-fat diet on capillarization and angiogenic factors in skeletal muscles of mice that were either active or sedentary. Fifty-eight C57BL/6 J mice were divided into four groups: low-fat diet sedentary (LFS), low-fat diet active (LFA), high-fat diet sedentary (HFS), and high-fat diet active (HFA). The mice in active groups were housed in cages with running wheels and the sedentary mice were housed in similar cages without running wheels. After 19 weeks HFS, LFA and HFA had higher capillary density and capillary-to-fiber-ratio in quadriceps femoris muscles than LFS. Capillarization was similar in HFS and HFA. To reveal possible mechanisms of HFD induced angiogenesis, we measured protein and mRNA levels of angiogenic factors VEGF-A, HIF-1α, PGC-1α and ERRα. VEGF-A protein levels were higher in muscles of HFS, LFA and HFA compared to LFS. However, no significant differences were observed between HFA and HFS. Protein levels of HIF-1α, PGC-1α, and ERRα were similar in all groups. However, the mRNA expression of HIF-1α and VEGF-A was up-regulated in capillaries but not in muscle fibers of HFS. The sedentary and active mice groups had similar mRNA expression levels of angiogenesis regulators studied. We conclude that high-fat feeding induces angiogenesis in skeletal muscle and up-regulates the gene expression of HIF-1α and VEGF-A in capillaries.

  4. HS1 deficiency impairs neutrophil recruitment in vivo and activation of the small GTPases Rac1 and Rap1.

    PubMed

    Latasiewicz, Joanna; Artz, Annette; Jing, Ding; Blanco, Mariana Pacheco; Currie, Silke M; Avila, Martha Velázquez; Schnoor, Michael; Vestweber, Dietmar

    2017-01-25

    Neutrophil extravasation is a critical step of the innate immune system's response to inflammation. This multistep process is tightly regulated by adhesion and signaling molecules in the endothelium and neutrophils. Activation of the β2 integrin LFA-1 is critical for adhesion of leukocytes to postcapillary venules. This step requires coordinated activation of signaling pathways in chemokine-stimulated neutrophils, including GTPase activation and cytoskeletal remodeling, leading to conformational changes in LFA-1. Hematopoietic cell-specific lyn substrate 1 (HS1) is a cortactin-related and leukocyte-specific actin-binding protein (ABP) that regulates several processes in various immune cells. It has been shown in vitro that HS1 is important for neutrophil chemotaxis and transendothelial migration of NK cells, but its role in neutrophil extravasation in vivo has not been investigated yet. Intravital microscopy of CXCL1-stimulated cremaster venules revealed an increased rolling velocity and reduced neutrophil adhesion and transmigration in HS1 knockout (KO) mice. CXCL1-induced rapid neutrophil arrest in vivo and adhesion under flow conditions in vitro were also reduced significantly. Whereas random motility of neutrophils was unaffected, chemotaxis toward a CXCL1 gradient was reduced in the absence of HS1. Further analysis of the underlying mechanisms demonstrated that HS1 controls CXCL1-induced activation of the small GTPases Ras-related C3 botulinum toxin substrate 1 (Rac1) and Ras-related protein 1 (Rap1), thus supporting LFA-1-mediated neutrophil adhesion. Importantly, with the use of Rac1 KO neutrophils, we could show that Rac1 acts upstream of Rap1. Our results establish HS1 as an important regulator of proper Rac1 and Rap1 activation and neutrophil extravasation.

  5. SNX17 Affects T Cell Activation by Regulating T Cell Receptor and Integrin Recycling

    PubMed Central

    Osborne, Douglas G.; Piotrowski, Joshua T.; Dick, Christopher J.; Zhang, Jin-San; Billadeau, Daniel D.

    2015-01-01

    A key component in T cell activation is the endosomal recycling of receptors to the cell surface, thereby allowing continual integration of signaling and antigen recognition. One protein potentially involved in T cell receptor transport is sorting nexin 17 (SNX17). SNX proteins have been found to bind proteins involved in T cell activation, but specifically the role of SNX17 in receptor recycling and T cell activation is unknown. Using immunofluorescence, we find that SNX17 co-localizes with TCR and localizes to the immune synapse in T-APC conjugates. Significantly, knockdown of the SNX17 resulted in fewer T-APC conjugates, lower CD69, TCR, and LFA-1 surface expression, as well as lower overall TCR recycling compared to control T cells. Lastly, we identified the FERM-domain of SNX17 as being responsible in the binding and trafficking of TCR and LFA-1 to the cell surface. These data suggest that SNX17 plays a role in the maintenance of normal surface levels of activating receptors and integrins to permit optimum T cell activation at the immune synapse. PMID:25825439

  6. Molecular interactions between T cells and fibroblast-like synoviocytes: role of membrane tumor necrosis factor-alpha on cytokine-activated T cells.

    PubMed

    Tran, Chinh N; Lundy, Steven K; White, Peter T; Endres, Judith L; Motyl, Christopher D; Gupta, Raj; Wilke, Cailin M; Shelden, Eric A; Chung, Kevin C; Urquhart, Andrew G; Fox, David A

    2007-11-01

    The mechanism of fibroblast-like synoviocyte (FLS) transformation into an inflammatory phenotype in rheumatoid arthritis (RA) is not fully understood. FLS interactions with invading leukocytes, particularly T cells, are thought to be a critical component of this pathological process. Resting T cells and T cells activated through the T-cell receptor have previously been shown to induce inflammatory cytokine production by FLS. More recently, a distinct population of T cells has been identified in RA synovium that phenotypically resembles cytokine-activated T (Tck) cells. Using time lapse microscopy, the interactions of resting, superantigen-activated, and cytokine-activated T cells with FLS were visualized. Rapid and robust adhesion of Tck and superantigen-activated T cells to FLS was observed that resulted in flattening of the T cells and a crawling movement on the FLS surface. Tck also readily activated FLS to produce interleukin IL-6 and IL-8 in a cell contact-dependent manner that was enhanced by exogenous IL-17. Although LFA-1 and ICAM-1 co-localized at the Tck-FLS synapse, blocking the LFA-1/ICAM-1 interaction did not substantially inhibit Tck effector function. However, antibody blocking of membrane tumor necrosis factor (TNF)-alpha on the Tck surface did inhibit FLS cytokine production, thus illustrating a novel mechanism for involvement of TNF-alpha in cell-cell interactions in RA synovium and for the effectiveness of TNF-alpha blockade in the treatment of RA.

  7. CXCL13/CXCR5 signaling enhances BCR-triggered B-cell activation by shaping cell dynamics.

    PubMed

    Sáez de Guinoa, Julia; Barrio, Laura; Mellado, Mario; Carrasco, Yolanda R

    2011-08-11

    Continuous migration of B cells at the follicle contrasts with their stable arrest after encounter with antigen. Two main ligand/receptor pairs are involved in these cell behaviors: the chemokine CXCL13/chemokine receptor CXCR5 and antigen/BCR. Little is known regarding the interplay between CXCR5 and BCR signaling in the modulation of B-cell dynamics and its effect on B-cell activation. We used a 2-dimensional model to study B-cell migration and antigen recognition in real time, and found that BCR signaling strength alters CXCL13-mediated migration, leading to a heterogeneous B-cell behavior pattern. In addition, we demonstrate that CXCL13/CXCR5 signaling does not impair BCR-triggered immune synapse formation and that CXCR5 is excluded from the central antigen cluster. CXCL13/CXCR5 signaling enhances BCR-mediated B-cell activation in at least 2 ways: (1) it assists antigen gathering at the synapse by promoting membrane ruffling and lymphocyte function-associated antigen 1 (LFA-1)-supported adhesion, and (2) it allows BCR signaling integration in motile B cells through establishment of LFA-1-supported migratory junctions. Both processes require functional actin cytoskeleton and non-muscle myosin II motor protein. Therefore, the CXCL13/CXCR5 signaling effect on shaping B-cell dynamics is an effective mechanism that enhances antigen encounter and BCR-triggered B-cell activation.

  8. Coordinated integrin activation by actin-dependent force during T-cell migration.

    PubMed

    Nordenfelt, Pontus; Elliott, Hunter L; Springer, Timothy A

    2016-10-10

    For a cell to move forward it must convert chemical energy into mechanical propulsion. Force produced by actin polymerization can generate traction across the plasma membrane by transmission through integrins to their ligands. However, the role this force plays in integrin activation is unknown. Here we show that integrin activity and cytoskeletal dynamics are reciprocally linked, where actin-dependent force itself appears to regulate integrin activity. We generated fluorescent tension-sensing constructs of integrin αLβ2 (LFA-1) to visualize intramolecular tension during cell migration. Using quantitative imaging of migrating T cells, we correlate tension in the αL or β2 subunit with cell and actin dynamics. We find that actin engagement produces tension within the β2 subunit to induce and stabilize an active integrin conformational state and that this requires intact talin and kindlin motifs. This supports a general mechanism where localized actin polymerization can coordinate activation of the complex machinery required for cell migration.

  9. Interaction between human lung fibroblasts and T-lymphocytes prevents activation of CD4+ cells

    PubMed Central

    Vancheri, Carlo; Mastruzzo, Claudio; Trovato-Salinaro, Elisa; Gili, Elisa; Lo Furno, Debora; Pistorio, Maria P; Caruso, Massimo; La Rosa, Cristina; Crimi, Claudia; Failla, Marco; Crimi, Nunzio

    2005-01-01

    Background T lymphocytes are demonstrated to play an important role in several chronic pulmonary inflammatory diseases. In this study we provide evidence that human lung fibroblasts are capable of mutually interacting with T-lymphocytes leading to functionally significant responses by T-cells and fibroblasts. Methods Human lung fibroblast were co-cultured with PMA-ionomycin activated T-CD4 lymphocytes for 36 hours. Surface as well as intracellular proteins expression, relevant to fibroblasts and lymphocytes activation, were evaluated by means of flow cytometry and RT-PCR. Proliferative responses of T lymphocytes to concanavalin A were evaluated by the MTT assay. Results In lung fibroblasts, activated lymphocytes promote an increase of expression of cyclooxygenase-2 and ICAM-1, expressed as mean fluorescence intensity (MFI), from 5.4 ± 0.9 and 0.7 ± 0.15 to 9.1 ± 1.5 and 38.6 ± 7.8, respectively. Fibroblasts, in turn, induce a significant reduction of transcription and protein expression of CD69, LFA-1 and CD28 in activated lymphocytes and CD3 in resting lymphocytes. In activated T lymphocytes, LFA-1, CD28 and CD69 expression was 16.6 ± 0.7, 18.9 ± 1.9 and 6.6 ± 1.3, respectively, and was significantly reduced by fibroblasts to 9.4 ± 0.7, 9.4 ± 1.4 and 3.5 ± 1.0. CD3 expression in resting lymphocytes was 11.9 ± 1.4 and was significantly reduced by fibroblasts to 6.4 ± 1.1. Intracellular cytokines, TNF-alpha and IL-10, were evaluated in T lymphocytes. Co-incubation with fibroblasts reduced the number of TNF-alpha positive lymphocytes from 54,4% ± 6.12 to 30.8 ± 2.8, while IL-10 positive cells were unaffected. Finally, co-culture with fibroblasts significantly reduced Con A proliferative response of T lymphocytes, measured as MTT absorbance, from 0.24 ± 0.02 nm to 0.16 ± 0.02 nm. Interestingly, while the activation of fibroblasts is mediated by a soluble factor, a cognate interaction ICAM-1 mediated was demonstrated to be responsible for the modulation

  10. Interactions between interleukin-2-activated lymphocytes and vascular endothelium: binding to and migration across specialized and non-specialized endothelia.

    PubMed Central

    Pankonin, G; Reipert, B; Ager, A

    1992-01-01

    A prerequisite for the successful immunotherapy of solid tumours with interleukin-2 (IL-2)-activated lymphocytes is their ability to home to the tumour tissue. Lymphocyte homing is a complex process which is known to involve at least two independently regulated events: adhesion to the luminal surface of vascular endothelium and the subsequent transendothelial migration of lymphocytes. In this study we have used an in vitro model of lymphocyte homing which employs specialized high endothelium to ask whether IL-2-activated lymphocytes are able to migrate across vascular endothelium in order to leave the blood vessel. Both the adhesion of IL-2-activated cells and their migration across monolayers of cultured high endothelial cells (HEC) were increased in comparison with non-activated lymphocytes. The adhesion of IL-2-activated lymphocytes was mediated by lymphocyte function-associated antigen-1 (LFA-1) and a very late activation antigen-4 (VLA-4)-related pathway. LFA-1-dependent adhesion was mediated by ligands on HEC other than the intercellular adhesion molecule-1 (ICAM-1) and the VLA-4-related pathway was mediated by ligands other than the CS1 domain of fibronectin. HEC-adherent lymphocytes were enriched in natural killer (NK) cells and CD8+ T cells which are known to be the tumour-cytotoxic cells in IL-2-activated lymphocytes. However, there was no evidence of cytotoxicity towards the endothelial layer using a syngeneic model. The interaction of IL-2-activated lymphocytes and endothelial cells was not specific for high endothelium since equal numbers of activated lymphocytes bound to and migrated across aortic endothelium. The inability of IL-2-activated lymphocytes to discriminate between high endothelium and non-specialized 'flat' endothelium could be responsible for the widespread dissemination of the cells throughout the body following their adoptive transfer and the unwanted side-effects at non-involved sites. Images Figure 2 PMID:1398764

  11. Activity.

    ERIC Educational Resources Information Center

    Clearing: Nature and Learning in the Pacific Northwest, 1984

    1984-01-01

    Presents three activities: (1) investigating succession in a schoolground; (2) investigating oak galls; and (3) making sun prints (photographs made without camera or darkroom). Each activity includes a list of materials needed and procedures used. (JN)

  12. Establishing a cost-per-result of laboratory-based, reflex Cryptococcal antigenaemia screening (CrAg) in HIV+ patients with CD4 counts less than 100 cells/μl using a Lateral Flow Assay (LFA) at a typical busy CD4 laboratory in South Africa

    PubMed Central

    Cassim, Naseem; Schnippel, Kathryn; Coetzee, Lindi Marie

    2017-01-01

    Introduction Cryptococcal meningitis is a major cause of mortality and morbidity in countries with high HIV prevalence, primarily affecting patients whose CD4 are < = 100 cells/μl. Routine Cryptococcal Antigen (CrAg) screening is thus recommended in the South African HIV treatment guidelines for all patients with CD4 counts < = 100 cells/μl, followed by pre-emptive anti-fungal therapy where CrAg results are positive. A laboratory-based reflexed CrAg screening approach, using a Lateral Flow Assay (LFA) on remnant EDTA CD4 blood samples, was piloted at three CD4 laboratories. Objectives This study aimed to assess the cost-per-result of laboratory-based reflexed CrAg screening at one pilot CD4 referral laboratory. Methods CD4 test volumes from 2014 were extracted to estimate percentage of CD4 < = 100 cells/μl. Daily average volumes were derived, assuming 12 months per/year and 21.73 working days per/month. Costing analyses were undertaken using Microsoft Excel and Stata with a provider prospective. The cost-per-result was estimated using a bottom-up method, inclusive of test kits and consumables (reagents), laboratory equipment and technical effort costs. The ZAR/$ exchange of 14.696/$1 was used, where applicable. One-way sensitivity analyses on the cost-per-result were conducted for possible error rates (3%– 8%, reductions or increases in reagent costs as well as test volumes (ranging from -60% to +60%). Results The pilot CD4 laboratory performed 267000 CD4 tests in 2014; ~ 9.3% (27500) reported CD4< = 100 cells/μl, equivalent to 106 CrAg tests performed daily. A batch of 30-tests could be performed in 1.6 hours, including preparation and analysis time. A cost-per-result of $4.28 was reported, with reagents contributing $3.11 (72.8%), while technical effort and laboratory equipment overheads contributed $1.17 (27.2%) and $0.03 (<1%) respectively. One-way sensitivity analyses including increasing or decreasing test volumes by 60% revealed a cost-per-result range

  13. Grapefruit-Derived Nanovectors Use an Activated Leukocyte Trafficking Pathway to Deliver Therapeutic Agents to Inflammatory Tumor Sites.

    PubMed

    Wang, Qilong; Ren, Yi; Mu, Jingyao; Egilmez, Nejat K; Zhuang, Xiaoyin; Deng, Zhongbin; Zhang, Lifeng; Yan, Jun; Miller, Donald; Zhang, Huang-Ge

    2015-06-15

    Inflammation is a hallmark of cancer. Activated immune cells are intrinsically capable of homing to inflammatory sites. Using three inflammatory-driven disease mouse models, we show that grapefruit-derived nanovectors (GNV) coated with inflammatory-related receptor enriched membranes of activated leukocytes (IGNVs) are enhanced for homing to inflammatory tumor tissues. Blocking LFA-1 or CXCR1 and CXCR2 on the IGNVs significantly inhibits IGNV homing to the inflammatory tissue. The therapeutic potential of IGNVs was further demonstrated by enhancing the chemotherapeutic effect as shown by inhibition of tumor growth in two tumor models and inhibiting the inflammatory effects of dextran sulfate sodium-induced mouse colitis. The fact that IGNVs are capable of homing to inflammatory tissue and that chemokines are overexpressed in diseased human tissue provides the rationale for using IGNVs to more directly deliver therapeutic agents to inflammatory tumor sites and the rationale for the use of IGNVs as treatment for certain cancers in personalized medicine.

  14. Grapefruit-derived nanovectors use an activated leukocyte trafficking pathway to deliver therapeutic agents to inflammatory tumor sites

    PubMed Central

    Wang, Qilong; Ren, Yi; Mu, Jingyao; Egilmez, Nejat; Zhuang, Xiaoyin; Deng, Zhongbin; Zhang, Lifeng; Yan, Jun; Miller, Donald; Zhang, Huang-Ge

    2015-01-01

    Inflammation is a hallmark of cancer. Activated immune cells are intrinsically capable of homing to inflammatory sites. Using three inflammatory driven disease mouse models, we show that grapefruit-derived nanovectors (GNVs) coated with inflammatory related receptor enriched membranes of activated leukocytes (IGNVs) are enhanced for homing to inflammatory tumor tissues. Blocking LFA-1 or CXCR1 and CXCR2 on the IGNVs significantly inhibits IGNV homing to the inflammatory tissue. The therapeutic potential of IGNVs was further demonstrated by enhancing the chemotherapeutic effect as shown by inhibition of tumor growth in two tumor models and inhibiting the inflammatory effects of DSS induced mouse colitis. The fact that IGNVs are capable of homing to inflammatory tissue and that there is an overexpression of chemokines in diseased human tissue provides the rationale for using IGNVs to more directed delivery of therapeutic agents to inflammatory tumor sites and the use of IGNVs as personalized medicine for treatment of certain cancers. PMID:25883092

  15. The Light Weight Body Structure Technologies of Lexus LFA

    DTIC Science & Technology

    2011-11-01

    The original document contains color images. 14. ABSTRACT Lexus LFAs CFRP body structure has been developed from the ground level within Toyota...The development team has spent countless hours on technical discussions, especially as most of the member were not experienced at all in CFRP material...better, the key characteristics of the composite material. In fact, Toyota is one of the few automotive companies who manufacture CFRP body structure

  16. Activities.

    ERIC Educational Resources Information Center

    Bippert, Judy

    1993-01-01

    Presents activities designed to give students an opportunity to solve concrete problems involving spatial relationships and logical thinking utilizing hands-on manipulatives. Provides teacher instructions and four reproducible worksheets. (MDH)

  17. Activities.

    ERIC Educational Resources Information Center

    Kincaid, Charlene; And Others

    1993-01-01

    Presents an activity in which students collect and organize data from a real-world simulation of the scientific concept of half life. Students collect data using a marble sifter, analyze the data using a graphing calculator, and determine an appropriate mathematical model. Includes reproducible worksheets. (MDH)

  18. Coordinated integrin activation by actin-dependent force during T-cell migration

    PubMed Central

    Nordenfelt, Pontus; Elliott, Hunter L.; Springer, Timothy A.

    2016-01-01

    For a cell to move forward it must convert chemical energy into mechanical propulsion. Force produced by actin polymerization can generate traction across the plasma membrane by transmission through integrins to their ligands. However, the role this force plays in integrin activation is unknown. Here we show that integrin activity and cytoskeletal dynamics are reciprocally linked, where actin-dependent force itself appears to regulate integrin activity. We generated fluorescent tension-sensing constructs of integrin αLβ2 (LFA-1) to visualize intramolecular tension during cell migration. Using quantitative imaging of migrating T cells, we correlate tension in the αL or β2 subunit with cell and actin dynamics. We find that actin engagement produces tension within the β2 subunit to induce and stabilize an active integrin conformational state and that this requires intact talin and kindlin motifs. This supports a general mechanism where localized actin polymerization can coordinate activation of the complex machinery required for cell migration. PMID:27721490

  19. Aplotaxene blocks T cell activation by modulation of protein kinase C-θ-dependent pathway.

    PubMed

    Na, Bo-Ra; Kim, Hye-Ran; Kwon, Min-Sung; Lee, Hyun-Su; Piragyte, Indre; Choi, Eun-Ju; Choi, Hyun-Kyu; Han, Weon-Cheol; Lee, Seung-Ho; Jun, Chang-Duk

    2013-12-01

    Aplotaxene, (8Z, 11Z, 14Z)-heptadeca-1, 8, 11, 14-tetraene, is one of the major components of essential oil obtained from Inula helenium root, which is used in Oriental medicine. However, the effects of aplotaxene on immunity have not been investigated. Here, we show that aplotaxene inhibits T cell activation in terms of IL-2 and CD69 expression. Aplotaxene, at a concentration that optimally inhibits IL-2 production, has little effect on apoptotic or necrotic cell death, suggesting that apoptosis is not a mechanism for aplotaxene-mediated inhibition of T cell activation. Aplotaxene affects neither superantigeninduced conjugate formation between Jurkat T cells and Raji B cells nor clustering of CD3 and LFA-1 at the immunological synapse. Aplotaxene significantly inhibits PKC-θ phosphorylation and translocation to the immunological synapse, and blocks PMA-induced T-cell receptor internalization. Furthermore, aplotaxene leads to inhibition of mitogen-activated protein kinases (JNK, ERK and p38) phosphorylation and NF-κB, NF-AT, and AP-1 promoter activities in Jurkat T cells. Taken together, our findings provide evidence for the immunosuppressive effect of aplotaxene on activated T cells through the modulation of the PKC-θ and MAPK pathways, suggesting that aplotaxene may be a novel immunotherapeutic agent for immunological diseases related to the overactivation of T cells.

  20. Effect of recombinant human tumour necrosis factor beta (TNF beta) on activation, proliferation and differentiation of human B lymphocytes.

    PubMed Central

    Zola, H; Nikoloutsopoulos, A

    1989-01-01

    Activation, proliferation and differentiation of B lymphocytes are processes controlled by T cells, and the control is mediated in part by the action of lymphokines derived from T cells. In this study we have examined the ability of tumour necrosis factor-beta (TNF beta), a T-cell product, to induce a state of activation in resting B cells, to induce proliferation of already activated B cells, and to stimulate differentiation. Recombinant tumour necrosis factor beta (rTNF beta) was used alone and in conjunction with known stimulators. As judged by several markers of activation (CD23, CDw40, LFA-1, 4F2, MHC class I and class II), rTNF beta did not contribute to the activation of resting B cells, either alone or in conjunction with anti-IgM and IL-4. However, the activation marker detected by the monoclonal antibody Leu 21 did show a greater degree of up-regulation by anti-IgM + IL-4 + rTNF beta when compared with anti-IgM + IL-4. rTNF beta induced proliferation of B cells, but only if activating stimuli were also present. Two other factors which induce proliferation of activated B cells, low molecular weight B-cell growth factor (LMW-BCGF) and IL-2, showed additive effects with rTNF beta. No evidence of changes in differentiation status of the B cells was seen. PMID:2787779

  1. Identification of the binding site in intercellular adhesion molecule 1 for its receptor, leukocyte function-associated antigen 1.

    PubMed Central

    Fisher, K L; Lu, J; Riddle, L; Kim, K J; Presta, L G; Bodary, S C

    1997-01-01

    Intercellular adhesion molecule 1 (ICAM-1, CD54) is a member of the Ig superfamily and is a counterreceptor for the beta 2 integrins: lymphocyte function-associated antigen 1 (LFA-1, CD11a/CD18), complement receptor 1 (MAC-1, CD11b/CD18), and p150,95 (CD11c/CD18). Binding of ICAM-1 to these receptors mediates leukocyte-adhesive functions in immune and inflammatory responses. In this report, we describe a cell-free assay using purified recombinant extracellular domains of LFA-1 and a dimeric immunoadhesin of ICAM-1. The binding of recombinant secreted LFA-1 to ICAM-1 is divalent cation dependent (Mg2+ and Mn2+ promote binding) and sensitive to inhibition by antibodies that block LFA-1-mediated cell adhesion, indicating that its conformation mimics that of LFA-1 on activated lymphocytes. We describe six novel anti-ICAM-1 monoclonal antibodies, two of which are function blocking. Thirty-five point mutants of the ICAM-1 immunoadhesin were generated and residues important for binding of monoclonal antibodies and purified LFA-1 were identified. Nineteen of these mutants bind recombinant LFA-1 equivalently to wild type. Sixteen mutants show a 66-2500-fold decrease in LFA-1 binding yet, with few exceptions, retain binding to the monoclonal antibodies. These mutants, along with modeling studies, define the LFA-1 binding site on ICAM-1 as residues E34, K39, M64, Y66, N68, and Q73, that are predicted to lie on the CDFG beta-sheet of the Ig fold. The mutant G32A also abrogates binding to LFA-1 while retaining binding to all of the antibodies, possibly indicating a direct interaction of this residue with LFA-1. These data have allowed the generation of a highly refined model of the LFA-1 binding site of ICAM-1. Images PMID:9188101

  2. Lectin histochemistry and alkaline phosphatase activity in the pia mater vessels of spontaneously hypertensive rats (SHR).

    PubMed

    Szumańska, G; Gadamski, R

    1992-01-01

    Some lectins were used to study the localization of sugar residues on the endothelial cell surface in the pia mater blood vessels of control (WKY) and hypertensive rats (SHR). The lectins tested recognized the following residues: beta-D-galactosyl (Ricinus communis agglutinin 120, RCA-1), alpha-L-fucosyl (Ulex europaeus agglutinin, UEA-1), N-acetylglucosaminyl and sialyl (Wheat germ agglutinin, WGA), N-glycolyl-neuraminic acid (Limax flavus agglutinin, LFA), and N-acetyl-D-galactosaminyl (Helix pomatia agglutinin, HPA). Several differences were revealed in the presence of sugar receptors on the surface of endothelial cells between the control and the hypertensive rats. Our studies showed also differences in the localization of the tested glycoconjugates between pial capillaries, small, medium-size and large pial arteries. The histochemical evaluation of alkaline phosphatase revealed an increased activity of the enzyme in the pial vessels of SHRs as compared with control rats with a similar localization of the enzyme activity. Some differences in the distribution of lectin binding sites and alkaline phosphatase activity could be associated with the different functions of particular segments of the pial vascular network.

  3. Activated CD4+ T cells preferentially take up lipid microspheres, but resting cells do not.

    PubMed Central

    Suzuki, K

    1995-01-01

    Lipid microspheres (LM) used as drug carriers increase the effectiveness and reduce the toxicity of incorporated drugs. The present study is designed to determine whether or not activated T lymphocytes, which were the cells chosen first from the 'inflammatory cells', can take up LM in vitro. LM were labelled with a fluorescent probe, DiI (DiI-LM), to examine the kinetics. Flow cytometric analysis demonstrated that in freshly isolated peripheral blood mononuclear cells (PBMC), monocytes principally took up DiI-LM, while lymphocytes and granulocytes did not. When PBMC were stimulated with immobilized anti-CD3 MoAb and IL-2, cells expressing CD3, CD4, CD8 and CD16 incorporated DiI-LM. Purified CD4+ T cells, obtained by positive panning selection, were stimulated with this system. They were CD25, CD71, LFA-1-positive, and also showed an ability to take up DiI-LM, which resting cells did not. The findings were confirmed by flow cytometry and quantitative analysis of DiI. Confocal micrographs showed fluorescent granules from the probe in the cytoplasm of stimulated CD4+ T cells after incubation with DiI-LM. These results suggest that immunomodulatory agents incorporated into LM might selectively regulate the function of CD4+ or CD8+ T cells when these are activated. Images Fig. 4 PMID:7882572

  4. Recruitment of calcineurin to the TCR positively regulates T cell activation.

    PubMed

    Dutta, Debjani; Barr, Valarie A; Akpan, Itoro; Mittelstadt, Paul R; Singha, Laishram I; Samelson, Lawrence E; Ashwell, Jonathan D

    2017-02-01

    Calcineurin is a phosphatase whose primary targets in T cells are NFAT transcription factors, and inhibition of calcineurin activity by treatment with cyclosporin A (CsA) or FK506 is a cornerstone of immunosuppressive therapies. Here we found that calcineurin was recruited to the T cell antigen receptor (TCR) signaling complex, where it reversed inhibitory phosphorylation of the tyrosine kinase Lck on Ser59 (Lck(S59)). Loss of calcineurin activity impaired phosphorylation of Tyr493 of the tyrosine kinase ZAP-70 (ZAP-70(Y493)), as well as some downstream pathways in a manner consistent with signaling in cells expressing Lck(S59A) (Lck that cannot be phosphorylated) or Lck(S59E) (a phosphomimetic mutant). Notably, CsA inhibited integrin-LFA-1-dependent and NFAT-independent adhesion of T cells to the intercellular adhesion molecule ICAM-1, with little effect on cells expressing mutant Lck. These results provide new understanding of how widely used immunosuppressive drugs interfere with essential processes in the immune response.

  5. Tension on JAM-A activates RhoA via GEF-H1 and p115 RhoGEF.

    PubMed

    Scott, David W; Tolbert, Caitlin E; Burridge, Keith

    2016-05-01

    Junctional adhesion molecule A (JAM-A) is a broadly expressed adhesion molecule that regulates cell-cell contacts and facilitates leukocyte transendothelial migration. The latter occurs through interactions with the integrin LFA-1. Although we understand much about JAM-A, little is known regarding the protein's role in mechanotransduction or as a modulator of RhoA signaling. We found that tension imposed on JAM-A activates RhoA, which leads to increased cell stiffness. Activation of RhoA in this system depends on PI3K-mediated activation of GEF-H1 and p115 RhoGEF. These two GEFs are further regulated by FAK/ERK and Src family kinases, respectively. Finally, we show that phosphorylation of JAM-A at Ser-284 is required for RhoA activation in response to tension. These data demonstrate a direct role of JAM-A in mechanosignaling and control of RhoA and implicate Src family kinases in the regulation of p115 RhoGEF.

  6. Tension on JAM-A activates RhoA via GEF-H1 and p115 RhoGEF

    PubMed Central

    Scott, David W.; Tolbert, Caitlin E.; Burridge, Keith

    2016-01-01

    Junctional adhesion molecule A (JAM-A) is a broadly expressed adhesion molecule that regulates cell–cell contacts and facilitates leukocyte transendothelial migration. The latter occurs through interactions with the integrin LFA-1. Although we understand much about JAM-A, little is known regarding the protein’s role in mechanotransduction or as a modulator of RhoA signaling. We found that tension imposed on JAM-A activates RhoA, which leads to increased cell stiffness. Activation of RhoA in this system depends on PI3K-mediated activation of GEF-H1 and p115 RhoGEF. These two GEFs are further regulated by FAK/ERK and Src family kinases, respectively. Finally, we show that phosphorylation of JAM-A at Ser-284 is required for RhoA activation in response to tension. These data demonstrate a direct role of JAM-A in mechanosignaling and control of RhoA and implicate Src family kinases in the regulation of p115 RhoGEF. PMID:26985018

  7. Stable Research Platform Workshop

    DTIC Science & Technology

    1988-04-01

    to vertical (and return) 287 times. Originally equipped with hydrophones attached to steel girders extending from the hull, FLIP has had sensors...mounted at various locations on her hull, deployed from eO’-lOO’ booms extending out from the superstructure, and deployed vertically on cables down to...reverberation. Low Frequency Active. 6. Gound truth for SURTASS. 7. Propagation addressing 2D/3D acoustic-ocean models/validation. 8. Rainfall rates

  8. VLA-4 integrin concentrates at the peripheral supramolecular activation complex of the immune synapse and drives T helper 1 responses

    NASA Astrophysics Data System (ADS)

    Mittelbrunn, María; Molina, Ana; Escribese, María M.; Yáñez-Mó, María; Escudero, Ester; Ursa, Ángeles; Tejedor, Reyes; Mampaso, Francisco; Sánchez-Madrid, Francisco

    2004-07-01

    The integrin 41 (VLA-4) not only mediates the adhesion and transendothelial migration of leukocytes, but also provides costimulatory signals that contribute to the activation of T lymphocytes. However, the behavior of 41 during the formation of the immune synapse is currently unknown. Here, we show that 41 is recruited to both human and murine antigen-dependent immune synapses, when the antigen-presenting cell is a B lymphocyte or a dendritic cell, colocalizing with LFA-1 at the peripheral supramolecular activation complex. However, when conjugates are formed in the presence of anti-4 antibodies, VLA-4 colocalizes with the CD3- chain at the center of the synapse. In addition, antibody engagement of 4 integrin promotes polarization toward a T helper 1 (Th1) response in human in vitro models of CD4+ T cell differentiation and naïve T cell priming by dendritic cells. The in vivo administration of anti-4 integrin antibodies also induces an immune deviation to Th1 response that dampens a Th2-driven autoimmune nephritis in Brown Norway rats. These data reveal a regulatory role of 4 integrins on T lymphocyte-antigen presenting cell cognate immune interactions.

  9. VLA-4 integrin concentrates at the peripheral supramolecular activation complex of the immune synapse and drives T helper 1 responses.

    PubMed

    Mittelbrunn, María; Molina, Ana; Escribese, María M; Yáñez-Mó, María; Escudero, Ester; Ursa, Angeles; Tejedor, Reyes; Mampaso, Francisco; Sánchez-Madrid, Francisco

    2004-07-27

    The integrin alpha 4 beta 1 (VLA-4) not only mediates the adhesion and transendothelial migration of leukocytes, but also provides costimulatory signals that contribute to the activation of T lymphocytes. However, the behavior of alpha 4 beta 1 during the formation of the immune synapse is currently unknown. Here, we show that alpha 4 beta 1 is recruited to both human and murine antigen-dependent immune synapses, when the antigen-presenting cell is a B lymphocyte or a dendritic cell, colocalizing with LFA-1 at the peripheral supramolecular activation complex. However, when conjugates are formed in the presence of anti-alpha 4 antibodies, VLA-4 colocalizes with the CD3-zeta chain at the center of the synapse. In addition, antibody engagement of alpha 4 integrin promotes polarization toward a T helper 1 (Th1) response in human in vitro models of CD4(+) T cell differentiation and naïve T cell priming by dendritic cells. The in vivo administration of anti-alpha 4 integrin antibodies also induces an immune deviation to Th1 response that dampens a Th2-driven autoimmune nephritis in Brown Norway rats. These data reveal a regulatory role of alpha 4 integrins on T lymphocyte-antigen presenting cell cognate immune interactions.

  10. Induction of Mast Cell Accumulation by Tryptase via a Protease Activated Receptor-2 and ICAM-1 Dependent Mechanism

    PubMed Central

    Liu, Xin; Wang, Junling; Zhang, Huiyun; Zhan, Mengmeng; Chen, Hanqiu; Fang, Zeman; Xu, Chiyan; Chen, Huifang; He, Shaoheng

    2016-01-01

    Mast cells are primary effector cells of allergy, and recruitment of mast cells in involved tissue is one of the key events in allergic inflammation. Tryptase is the most abundant secretory product of mast cells, but little is known of its influence on mast cell accumulation. Using mouse peritoneal model, cell migration assay, and flow cytometry analysis, we investigated role of tryptase in recruiting mast cells. The results showed that tryptase induced up to 6.7-fold increase in mast cell numbers in mouse peritoneum following injection. Inhibitors of tryptase, an antagonist of PAR-2 FSLLRY-NH2, and pretreatment of mice with anti-ICAM-1, anti-CD11a, and anti-CD18 antibodies dramatically diminished tryptase induced mast cell accumulation. On the other hand, PAR-2 agonist peptides SLIGRL-NH2 and tc-LIGRLO-NH2 provoked mast cell accumulation following injection. These implicate that tryptase induced mast cell accumulation is dependent on its enzymatic activity, activation of PAR-2, and interaction between ICAM-1 and LFA-1. Moreover, induction of trans-endothelium migration of mast cells in vitro indicates that tryptase acts as a chemoattractant. In conclusion, provocation of mast cell accumulation by mast cell tryptase suggests a novel self-amplification mechanism of mast cell accumulation. Mast cell stabilizers as well as PAR-2 antagonist agents may be useful for treatment of allergic reactions. PMID:27378825

  11. Quantal concept of T-cell activation: adhesion domains as immunological synapses

    NASA Astrophysics Data System (ADS)

    Sackmann, Erich

    2011-06-01

    Adhesion micro-domains (ADs) formed during encounters of lymphocytes with antigen-presenting cells (APC) mediate the genetic expression of quanta of cytokines interleukin-2 (IL-2). The IL-2-induced activation of IL-2 receptors promotes the stepwise progression of the T-cells through the cell cycle, hence their name, immunological synapses. The ADs form short-lived reaction centres controlling the recruitment of activators of the biochemical pathway (the kinases Lck and ZAP) while preventing the access of inhibitors (phosphatase CD45) through steric repulsion forces. CD45 acts as the generator of adhesion domains and, through its role as a spacer protein, also as the promoter of the reaction. In a second phase of T-cell-APC encounters, long-lived global reaction spaces (called supramolecular activation complexes (SMAC)) form by talin-mediated binding of the T-cell integrin (LFA-1) to the counter-receptor ICAM-1, resulting in the formation of ring-like tight adhesion zones (peripheral SMAC). The ADs move to the centre of the intercellular adhesion zone forming the central SMAC, which serve in the recycling of the AD. We propose that cell stimulation is triggered by integrating the effect evoked by the short-lived adhesion domains. Similar global reaction platforms are formed by killer cells to destruct APC. We present a testable mechanical model showing that global reaction spaces (SMAC or dome-like contacts between cytotoxic cells and APC) form by self-organization through delayed activation of the integrin-binding affinity and stabilization of the adhesion zones by F-actin recruitment. The mechanical stability and the polarization of the adhering T-cells are mediated by microtubule-actin cross-talk.

  12. Activated peripheral lymphocytes with increased expression of cell adhesion molecules and cytotoxic markers are associated with dengue fever disease.

    PubMed

    Azeredo, Elzinandes L; Zagne, Sonia M O; Alvarenga, Allan R; Nogueira, Rita M R; Kubelka, Claire F; de Oliveira-Pinto, Luzia M

    2006-06-01

    The immune mechanisms involved in dengue fever and dengue hemorrhagic/dengue shock syndrome are not well understood. The ex vivo activation status of immune cells during the dengue disease in patients was examined. CD4 and CD8 T cells were reduced during the acute phase. Interestingly, CD8 T cells co-expressing activation marker HLA-DR, Q, P, and cytolytic granule protein-Tia-1 were significantly higher in dengue patients than in controls. Detection of adhesion molecules indicated that in dengue patients the majority of T cells (CD4 and CD8) express the activation/memory phenotype, characterized as CD44HIGH and lack the expression of the naïve cell marker, CD62L LOW. Also, the levels of T cells co-expressing ICAM-1 (CD54), VLA-4, and LFA-1 (CD11a) were significantly increased. CD8 T lymphocytes expressed predominantly low levels of anti-apoptotic molecule Bcl-2 in the acute phase, possibly leading to the exhibition of a phenotype of activated/effector cells. Circulating levels of IL-18, TGF-b1 and sICAM-1 were significantly elevated in dengue patients. Early activation events occur during acute dengue infection which might contribute to viral clearance. Differences in expression of adhesion molecules among CD4 and CD8 T cells might underlie the selective extravasation of these subsets from blood circulation into lymphoid organs and/or tissues. In addition, activated CD8 T cells would be more susceptible to apoptosis as shown by the alteration in Bcl-2 expression. Cytokines such as IL-18, TGF-b1, and sICAM-1 may be contributing by either stimulating or suppressing the adaptative immune response, during dengue infection, thereby perhaps establishing a relationship with disease severity.

  13. Homeobox NKX2-3 promotes marginal-zone lymphomagenesis by activating B-cell receptor signalling and shaping lymphocyte dynamics

    PubMed Central

    Robles, Eloy F.; Mena-Varas, Maria; Barrio, Laura; Merino-Cortes, Sara V.; Balogh, Péter; Du, Ming-Qing; Akasaka, Takashi; Parker, Anton; Roa, Sergio; Panizo, Carlos; Martin-Guerrero, Idoia; Siebert, Reiner; Segura, Victor; Agirre, Xabier; Macri-Pellizeri, Laura; Aldaz, Beatriz; Vilas-Zornoza, Amaia; Zhang, Shaowei; Moody, Sarah; Calasanz, Maria Jose; Tousseyn, Thomas; Broccardo, Cyril; Brousset, Pierre; Campos-Sanchez, Elena; Cobaleda, Cesar; Sanchez-Garcia, Isidro; Fernandez-Luna, Jose Luis; Garcia-Muñoz, Ricardo; Pena, Esther; Bellosillo, Beatriz; Salar, Antonio; Baptista, Maria Joao; Hernandez-Rivas, Jesús Maria; Gonzalez, Marcos; Terol, Maria Jose; Climent, Joan; Ferrandez, Antonio; Sagaert, Xavier; Melnick, Ari M.; Prosper, Felipe; Oscier, David G.; Carrasco, Yolanda R.; Dyer, Martin J. S.; Martinez-Climent, Jose A.

    2016-01-01

    NKX2 homeobox family proteins have a role in cancer development. Here we show that NKX2-3 is overexpressed in tumour cells from a subset of patients with marginal-zone lymphomas, but not with other B-cell malignancies. While Nkx2-3-deficient mice exhibit the absence of marginal-zone B cells, transgenic mice with expression of NKX2-3 in B cells show marginal-zone expansion that leads to the development of tumours, faithfully recapitulating the principal clinical and biological features of human marginal-zone lymphomas. NKX2-3 induces B-cell receptor signalling by phosphorylating Lyn/Syk kinases, which in turn activate multiple integrins (LFA-1, VLA-4), adhesion molecules (ICAM-1, MadCAM-1) and the chemokine receptor CXCR4. These molecules enhance migration, polarization and homing of B cells to splenic and extranodal tissues, eventually driving malignant transformation through triggering NF-κB and PI3K-AKT pathways. This study implicates oncogenic NKX2-3 in lymphomagenesis, and provides a valid experimental mouse model for studying the biology and therapy of human marginal-zone B-cell lymphomas. PMID:27297662

  14. Cloning and characterization of the 2B4 gene encoding a molecule associated with non-MHC-restricted killing mediated by activated natural killer cells and T cells

    SciTech Connect

    Mathew, P.A.; Garni-Wagner, B.A.; Land, K.; Takashima, A.; Stoneman, E.; Bennett, M.; Kumar, V. )

    1993-11-15

    The authors have recently described a signal transducing molecule, 2B4, expressed on all NK and T cells that mediate non-MHC-restricted killing. The gene encoding this molecule was cloned and its nucleotide sequence determined. The encoded protein of 398 amino acids has a leader peptide of 18 amino acids and a transmembrane region of 24 amino acids. The predicted protein has eight N-linked glycosylation sites, suggesting that it is highly glycosylated. Comparison of 2B4 with sequences in the databanks indicates that 2B4 is a member of the Ig supergene family, and it shows homology to murine and rat CD48 and human LFA-3. Northern blot analysis has shown at least three transcripts for 2B4 in adherent lymphokine-activated killer cells of several mouse strains and TCR-[gamma]/[delta] dendritic epidermal T cell lines but not in allospecific T cell clones. These three mRNA are the products of differential splicing of heterogeneous nuclear RNA. Southern blot analysis of genomic DNA from several mouse strains revealed that 2B4 belongs to a family of closely related genes. The 2B4 gene has been mapped to mouse chromosome 1 by analysis of 2B4 expression in recombinant inbred mouse strains. 48 refs., 6 figs., 2 tabs.

  15. Biliary epithelium and liver B cells exposed to bacteria activate intrahepatic MAIT cells through MR1

    PubMed Central

    Jeffery, Hannah C.; van Wilgenburg, Bonnie; Kurioka, Ayako; Parekh, Krishan; Stirling, Kathryn; Roberts, Sheree; Dutton, Emma E.; Hunter, Stuart; Geh, Daniel; Braitch, Manjit K.; Rajanayagam, Jeremy; Iqbal, Tariq; Pinkney, Thomas; Brown, Rachel; Withers, David R.; Adams, David H.; Klenerman, Paul; Oo, Ye H.

    2016-01-01

    Background & Aims Mucosal-Associated Invariant T (MAIT) cells are innate-like T cells characterised by the invariant TCR-chain, Vα7.2-Jα33, and are restricted by MR1, which presents bacterial vitamin B metabolites. They are important for antibacterial immunity at mucosal sites; however, detailed characteristics of liver-infiltrating MAIT (LI-MAIT) and their role in biliary immune surveillance remain unexplored. Methods The phenotype and intrahepatic localisation of human LI-MAIT cells was examined in diseased and normal livers. MAIT cell activation in response to E. coli-exposed macrophages, biliary epithelial cells (BEC) and liver B cells was assessed with/without anti-MR1. Results Intrahepatic MAIT cells predominantly localised to bile ducts in the portal tracts. Consistent with this distribution, they expressed biliary tropic chemokine receptors CCR6, CXCR6, and integrin αEβ7. LI-MAIT cells were also present in the hepatic sinusoids and possessed tissue-homing chemokine receptor CXCR3 and integrins LFA-1 and VLA-4, suggesting their recruitment via hepatic sinusoids. LI-MAIT cells were enriched in the parenchyma of acute liver failure livers compared to chronic diseased livers. LI-MAIT cells had an activated, effector memory phenotype, expressed α4β7 and receptors for IL-12, IL-18, and IL-23. Importantly, in response to E. coli-exposed macrophages, liver B cells and BEC, MAIT cells upregulated IFN-γ and CD40 Ligand and degranulated in an MR1-dependent, cytokine-independent manner. In addition, diseased liver MAIT cells expressed T-bet and RORγt and the cytokines IFN-γ, TNF-α, and IL-17. Conclusions Our findings provide the first evidence of an immune surveillance effector response for MAIT cells towards BEC in human liver; thus they could be manipulated for treatment of biliary disease in the future. PMID:26743076

  16. Activation of Salmonella Typhi-specific regulatory T cells in typhoid disease in a wild-type S. Typhi challenge model.

    PubMed

    McArthur, Monica A; Fresnay, Stephanie; Magder, Laurence S; Darton, Thomas C; Jones, Claire; Waddington, Claire S; Blohmke, Christoph J; Dougan, Gordon; Angus, Brian; Levine, Myron M; Pollard, Andrew J; Sztein, Marcelo B

    2015-05-01

    Salmonella Typhi (S. Typhi), the causative agent of typhoid fever, causes significant morbidity and mortality worldwide. Currently available vaccines are moderately efficacious, and identification of immunological responses associated with protection or disease will facilitate the development of improved vaccines. We investigated S. Typhi-specific modulation of activation and homing potential of circulating regulatory T cells (Treg) by flow and mass cytometry using specimens obtained from a human challenge study. Peripheral blood mononuclear cells were obtained from volunteers pre- and at multiple time-points post-challenge with wild-type S. Typhi. We identified differing patterns of S. Typhi-specific modulation of the homing potential of circulating Treg between volunteers diagnosed with typhoid (TD) and those who were not (No TD). TD volunteers demonstrated up-regulation of the gut homing molecule integrin α4ß7 pre-challenge, followed by a significant down-regulation post-challenge consistent with Treg homing to the gut. Additionally, S. Typhi-specific Treg from TD volunteers exhibited up-regulation of activation molecules post-challenge (e.g., HLA-DR, LFA-1). We further demonstrate that depletion of Treg results in increased S. Typhi-specific cytokine production by CD8+ TEM in vitro. These results suggest that the tissue distribution of activated Treg, their characteristics and activation status may play a pivotal role in typhoid fever, possibly through suppression of S. Typhi-specific effector T cell responses. These studies provide important novel insights into the regulation of immune responses that are likely to be critical in protection against typhoid and other enteric infectious diseases.

  17. Activation of Salmonella Typhi-Specific Regulatory T Cells in Typhoid Disease in a Wild-Type S. Typhi Challenge Model

    PubMed Central

    McArthur, Monica A.; Fresnay, Stephanie; Magder, Laurence S.; Darton, Thomas C.; Jones, Claire; Waddington, Claire S.; Blohmke, Christoph J.; Dougan, Gordon; Angus, Brian; Levine, Myron M.; Pollard, Andrew J.; Sztein, Marcelo B.

    2015-01-01

    Salmonella Typhi (S. Typhi), the causative agent of typhoid fever, causes significant morbidity and mortality worldwide. Currently available vaccines are moderately efficacious, and identification of immunological responses associated with protection or disease will facilitate the development of improved vaccines. We investigated S. Typhi-specific modulation of activation and homing potential of circulating regulatory T cells (Treg) by flow and mass cytometry using specimens obtained from a human challenge study. Peripheral blood mononuclear cells were obtained from volunteers pre- and at multiple time-points post-challenge with wild-type S. Typhi. We identified differing patterns of S. Typhi-specific modulation of the homing potential of circulating Treg between volunteers diagnosed with typhoid (TD) and those who were not (No TD). TD volunteers demonstrated up-regulation of the gut homing molecule integrin α4ß7 pre-challenge, followed by a significant down-regulation post-challenge consistent with Treg homing to the gut. Additionally, S. Typhi-specific Treg from TD volunteers exhibited up-regulation of activation molecules post-challenge (e.g., HLA-DR, LFA-1). We further demonstrate that depletion of Treg results in increased S. Typhi-specific cytokine production by CD8+ TEM in vitro. These results suggest that the tissue distribution of activated Treg, their characteristics and activation status may play a pivotal role in typhoid fever, possibly through suppression of S. Typhi-specific effector T cell responses. These studies provide important novel insights into the regulation of immune responses that are likely to be critical in protection against typhoid and other enteric infectious diseases. PMID:26001081

  18. Active evasion of CTL mediated killing and low quality responding CD8+ T cells contribute to persistence of brucellosis.

    PubMed

    Durward, Marina; Radhakrishnan, Girish; Harms, Jerome; Bareiss, Claire; Magnani, Diogo; Splitter, Gary A

    2012-01-01

    Brucellosis is a common zoonotic disease that remains endemic in many parts of the world. Dissecting the host immune response during this disease provides insight as to why brucellosis is often difficult to resolve. We used a Brucella epitope specific in vivo killing assay to investigate the ability of CD8+ T cells to kill targets treated with purified pathogenic protein. Importantly, we found the pathogenic protein TcpB to be a novel effector of adaptive immune evasion by inhibiting CD8+ T cell killing of Brucella epitope specific target cells in mice. Further, BALB/c mice show active Brucella melitensis infection beyond one year, many with previously unreported focal infection of the urogenital area. A fraction of CD8+ T cells show a CD8+ Tmem phenotype of LFA-1hi, CD127hi, KLRG-1lo during the course of chronic brucellosis, while the CD8+ T cell pool as a whole had a very weak polyfunctional cytokine response with diminished co-expression of IFN-γ with TNFα and/or IL-2, a hallmark of exhaustion. When investigating the expression of these 3 cytokines individually, we observed significant IFN-γ expression at 90 and 180 days post-infection. TNFα expression did not significantly exceed or fall below background levels at any time. IL-2 expression did not significantly exceeded background, but, interestingly, did fall significantly below that of uninfected mice at 180 days post-infection. Brucella melitensis evades and blunts adaptive immunity during acute infection and our findings provide potential mechanisms for the deficit observed in responding CD8+ T cells during chronic brucellosis.

  19. Active-R filter

    DOEpatents

    Soderstrand, Michael A.

    1976-01-01

    An operational amplifier-type active filter in which the only capacitor in the circuit is the compensating capacitance of the operational amplifiers, the various feedback and coupling elements being essentially solely resistive.

  20. Get Active

    MedlinePlus

    ... Basics: Health Benefits What are the benefits of physical activity? Physical activity increases your chances of living longer. ... pain Help you feel better about yourself Is physical activity for everyone? Yes! Physical activity is good for ...

  1. BLOOD LEUKOCYTE EXPRESSION OF LFA-1 AND ICAM-1 AFTER INHALATION OF ULTRAFINE CARBON PARTICLES. (R826781)

    EPA Science Inventory

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  2. Rafting MHC-II domains in the APC (presynaptic) plasma membrane and the thresholds for T-cell activation and immunological synapse formation.

    PubMed

    Gombos, Imre; Detre, Cynthia; Vámosi, György; Matkó, János

    2004-03-29

    Glycosphingolipid- and cholesterol-rich membrane microdomains (rafts) in T-cells are important in triggering and regulation of T(H)-cell activation in immunological synapses (IS), which in turn may control the T-cell repertoire in lymph nodes and at the periphery. It is less known, however, how the "presynaptic side" controls formation and function of IS. We investigated here activation signals and synapse formation frequency of murine IP12-7 T(H) hybridoma cell specific to influenza virus HA-peptide upon stimulation with two B-lymphoma cells, A20 and 2PK3, pulsed with peptide antigen. Confocal microscopic colocalization and FRET data consonantly revealed clustered distribution and constitutive raft-association of a major fraction of MHC-II molecules in both APCs. Costimulatory molecules (CD80 and CD86), not associated constitutively with rafts, were expressed at much lower level in A20 cells. T-cells responded to 2PK3 APC with much higher signal strength than to A20 cells, in good correlation with the frequency of IS formation, as assessed by microscopic conjugation assay. Disruption of rafts by cholesterol depletion in 2PK3 cells largely decreased the magnitude of T(H) cell activation signals, especially at low peptide antigen doses, similarly to masking CD4 with mAb on T-cells. The frequency of IS formation was reduced by blocking LFA-1 on T-cells and CD80 on APCs, by lowering the temperature below the phase transition of the membrane or by disrupting actin cytoskeleton. These data together suggest that the surface density and affinity/stability of peptide-MHC-II complexes and the costimulatory level are primary determinants for an efficient TCR recognition and the strength of the subsequent T-cell signals, as well as of the IS formation, which additionally requires a cytoskeleton-dependent remodeling of APC surface after the initial TCR signal. The threshold of T-cell activation can be further set by rafting MHC-II domains via concentrating high affinity

  3. Activation detector

    DOEpatents

    Bell, Zane William [Oak Ridge, TN; Boatner, Lynn Allen [Oak Ridge, TN

    2009-12-08

    A method of detecting an activator, the method including impinging with an activator a receptor material lacking a photoluminescent material and generating a by-product of a radioactive decay due to the activator impinging the reeptor material. The method further including, generating light from the by-product via the Cherenkov effect and identifying a characteristic of the activator based on the light.

  4. Novel cell-free high-throughput screening method for pharmacological tools targeting K+ channels

    PubMed Central

    Su, Zhenwei; Brown, Emily C.; Wang, Weiwei; MacKinnon, Roderick

    2016-01-01

    K+ channels, a superfamily of ∼80 members, control cell excitability, ion homeostasis, and many forms of cell signaling. Their malfunctions cause numerous diseases including neuronal disorders, cardiac arrhythmia, diabetes, and asthma. Here we present a novel liposome flux assay (LFA) that is applicable to most K+ channels. It is robust, low cost, and high throughput. Using LFA, we performed small molecule screens on three different K+ channels and identified new activators and inhibitors for biological research on channel function and for medicinal development. We further engineered a hERG (human ether-à-go-go-related gene) channel, which, when used in LFA, provides a highly sensitive (zero false negatives on 50 hERG-sensitive drugs) and highly specific (zero false positives on 50 hERG-insensitive drugs), low-cost hERG safety assay. PMID:27091997

  5. Catalyst activator

    DOEpatents

    McAdon, Mark H.; Nickias, Peter N.; Marks, Tobin J.; Schwartz, David J.

    2001-01-01

    A catalyst activator particularly adapted for use in the activation of metal complexes of metals of Group 3-10 for polymerization of ethylenically unsaturated polymerizable monomers, especially olefins, comprising two Group 13 metal or metalloid atoms and a ligand structure including at least one bridging group connecting ligands on the two Group 13 metal or metalloid atoms.

  6. Outdoor Activities.

    ERIC Educational Resources Information Center

    Minneapolis Independent School District 275, Minn.

    Twenty-four activities suitable for outdoor use by elementary school children are outlined. Activities designed to make children aware of their environment include soil painting, burr collecting, insect and pond water collecting, studies of insect galls and field mice, succession studies, and a model of natural selection using dyed toothpicks. A…

  7. Physical activity

    MedlinePlus

    ... activity -- which includes an active lifestyle and routine exercise -- plus eating well, is the best way to stay healthy. ... goal. Your goal might be to: Manage a health condition Reduce stress ... other benefits, such as: Better control of your weight and ...

  8. Astronomy Activities.

    ERIC Educational Resources Information Center

    Greenstone, Sid

    This document consists of activities and references for teaching astronomy. The activities (which include objectives, list of materials needed, and procedures) focus on: observing the Big Dipper and locating the North Star; examining the Big Dipper's stars; making and using an astrolabe; examining retograde motion of Mars; measuring the Sun's…

  9. Activated Charcoal

    MedlinePlus

    ... is used to treat poisonings, reduce intestinal gas (flatulence), lower cholesterol levels, prevent hangover, and treat bile ... lower cholesterol levels in the blood. Decreasing gas (flatulence). Some studies show that activated charcoal is effective ...

  10. Activity Theory.

    ERIC Educational Resources Information Center

    Koschmann, Timothy; Roschelle, Jeremy; Nardi, Bonnie A.

    1998-01-01

    Includes three articles that discuss activity theory, based on "Context and Consciousness." Topics include human-computer interaction; computer interfaces; hierarchical structuring; mediation; contradictions and development; failure analysis; and designing educational technology. (LRW)

  11. Hydrogeology and water quality of the Floridan aquifer system and effects of Lower Floridan aquifer pumping on the Upper Floridan aquifer at Fort Stewart, Georgia

    USGS Publications Warehouse

    Clarke, John S.; Cherry, Gregory C.; Gonthier, Gerard J.

    2011-01-01

    Test drilling, field investigations, and digital modeling were completed at Fort Stewart, GA, during 2009?2010, to assess the geologic, hydraulic, and water-quality characteristics of the Floridan aquifer system and evaluate the effect of Lower Floridan aquifer (LFA) pumping on the Upper Floridan aquifer (UFA). This work was performed pursuant to the Georgia Environmental Protection Division interim permitting strategy for new wells completed in the LFA that requires simulation to (1) quantify pumping-induced aquifer leakage from the UFA to LFA, and (2) identify the equivalent rate of UFA pumping that would produce the same maximum drawdown in the UFA that anticipated pumping from LFA well would induce. Field investigation activities included (1) constructing a 1,300-foot (ft) test boring and well completed in the LFA (well 33P028), (2) constructing an observation well in the UFA (well 33P029), (3) collecting drill cuttings and borehole geophysical logs, (4) collecting core samples for analysis of vertical hydraulic conductivity and porosity, (5) conducting flowmeter and packer tests in the open borehole within the UFA and LFA, (6) collecting depth-integrated water samples to assess basic ionic chemistry of various water-bearing zones, and (7) conducting aquifer tests in new LFA and UFA wells to determine hydraulic properties and assess interaquifer leakage. Using data collected at the site and in nearby areas, model simulation was used to assess the effects of LFA pumping on the UFA. Borehole-geophysical and flowmeter data indicate the LFA at Fort Stewart consists of limestone and dolomitic limestone between depths of 912 and 1,250 ft. Flowmeter data indicate the presence of three permeable zones at depth intervals of 912-947, 1,090-1,139, and 1,211?1,250 ft. LFA well 33P028 received 50 percent of the pumped volume from the uppermost permeable zone, and about 18 and 32 percent of the pumped volume from the middle and lowest permeable zones, respectively. Chemical

  12. Plant metacaspase activation and activity.

    PubMed

    Minina, Elena A; Stael, Simon; Van Breusegem, Frank; Bozhkov, Peter V

    2014-01-01

    Metacaspases are essential for cell death regulation in plants. Further understanding of biochemistry of metacaspases and their molecular function in plant biology requires a set of robust methods for detection of metacaspase activation and quantitative analysis of corresponding proteolytic activity. Here we describe methods for purification of recombinant metacaspases, measurement of enzymatic activity of recombinant and endogenous metacaspases in vitro and in cell lysates, respectively, and finally detection of metacaspase activation in vivo. Additionally, an in vitro metacaspase protein substrate cleavage assay based on the cell-free production of substrate protein followed by proteolysis with recombinant metacaspase is presented. These methods have been originally developed for type II metacaspases from Arabidopsis and Norway spruce (Picea abies), but they can be used as templates for type I metacaspases, as well as for type II metacaspases from other species.

  13. Active colloids

    NASA Astrophysics Data System (ADS)

    Aranson, Igor S.

    2013-01-01

    A colloidal suspension is a heterogeneous fluid containing solid microscopic particles. Colloids play an important role in our everyday life, from food and pharmaceutical industries to medicine and nanotechnology. It is useful to distinguish two major classes of colloidal suspensions: equilibrium and active, i.e., maintained out of thermodynamic equilibrium by external electric or magnetic fields, light, chemical reactions, or hydrodynamic shear flow. While the properties of equilibrium colloidal suspensions are fairly well understood, active colloids pose a formidable challenge, and the research is in its early exploratory stage. One of the most remarkable properties of active colloids is the possibility of dynamic self-assembly, a natural tendency of simple building blocks to organize into complex functional architectures. Examples range from tunable, self-healing colloidal crystals and membranes to self-assembled microswimmers and robots. Active colloidal suspensions may exhibit material properties not present in their equilibrium counterparts, e.g., reduced viscosity and enhanced self-diffusivity, etc. This study surveys the most recent developments in the physics of active colloids, both in synthetic and living systems, with the aim of elucidation of the fundamental physical mechanisms governing self-assembly and collective behavior.

  14. Active microwaves

    NASA Technical Reports Server (NTRS)

    Evans, D.; Vidal-Madjar, D.

    1994-01-01

    Research on the use of active microwaves in remote sensing, presented during plenary and poster sessions, is summarized. The main highlights are: calibration techniques are well understood; innovative modeling approaches have been developed which increase active microwave applications (segmentation prior to model inversion, use of ERS-1 scatterometer, simulations); polarization angle and frequency diversity improves characterization of ice sheets, vegetation, and determination of soil moisture (X band sensor study); SAR (Synthetic Aperture Radar) interferometry potential is emerging; use of multiple sensors/extended spectral signatures is important (increase emphasis).

  15. Activated Sludge.

    ERIC Educational Resources Information Center

    Saunders, F. Michael

    1978-01-01

    Presents the 1978 literature review of wastewater treatment. This review covers: (1) activated sludge process; (2) process control; (3) oxygen uptake and transfer; (4) phosphorus removal; (5) nitrification; (6) industrial wastewater; and (7) aerobic digestion. A list of 136 references is also presented. (HM)

  16. Activities: Spirolaterals.

    ERIC Educational Resources Information Center

    Brannan, Richard; McFadden, Scott

    1981-01-01

    A set of activities designed to help students discover properties about order-3 spirolaterals on square grid paper is presented. The materials are prepared on worksheets designed for easy duplication. The lessons can lead to investigations involving spirolaterals of many other orders and shapes. (MP)

  17. Leaf Activities.

    ERIC Educational Resources Information Center

    Mingie, Walter

    Leaf activities can provide a means of using basic concepts of outdoor education to learn in elementary level subject areas. Equipment needed includes leaves, a clipboard with paper, and a pencil. A bag of leaves may be brought into the classroom if weather conditions or time do not permit going outdoors. Each student should pick a leaf, examine…

  18. Learning Activities.

    ERIC Educational Resources Information Center

    Tipton, Tom, Ed.

    1983-01-01

    Presents a flow chart for naming inorganic compounds. Although it is not necessary for students to memorize rules, preliminary skills needed before using the chart are outlined. Also presents an activity in which the mass of an imaginary atom is determined using lead shot, Petri dishes, and a platform balance. (JN)

  19. Activity report

    SciTech Connect

    Yu, S W

    2008-08-11

    This report is aimed to show the author's activities to support the LDRD. The title is 'Investigation of the Double-C Behavior in the Pu-Ga Time-Temperature-Transformation Diagram' The sections are: (1) Sample Holder Test; (2) Calculation of x-ray diffraction patterns; (3) Literature search and preparing publications; (4) Tasks Required for APS Experiments; and (5) Communications.

  20. Sedimentology of latero-frontal moraines and fans on the west coast of South Island, New Zealand

    NASA Astrophysics Data System (ADS)

    Evans, David J. A.; Shulmeister, James; Hyatt, Olivia

    2010-12-01

    Exposures through the LGM latero-frontal moraine loops at sites along the west coast of South Island, New Zealand reveal a depositional environment that was dominated by the progradation of steep fronted, debris flow-fed fans, manifest in crudely stratified to massive diamictons, arranged in sub-horizontal to steeply dipping clinoforms and containing discontinuous bodies of variably sorted, stratified sediment (LFA 1). The fans were constructed by debris-covered glaciers advancing over outwash plains, as recorded by well stratified and horizontally bedded gravels, sands and diamicts (LFA 0). The ice-contact slopes of the fans are offlapped by retreat phase deposits in the form of glacilacustrine depo-centres (LFA 2), which record the existence of moraine-dammed lakes. Interdigitation of lake rhythmites and subaerial to subaqueous sediment gravity flow deposits documents intense debris-flow activity on unstable moraine/fan surfaces. Glacier readvances in all catchments are documented by glacitectonic disturbance and localized hydrofracturing of LFA 2, followed by the emplacement of schist-dominated debris flow-fed fans (LFA 3) inside and over the top of the earlier latero-frontal moraine/fan loops. Contorted and disturbed bedding in LFA 3 reflects its partial deposition in supraglacial positions. Clast lithologies in LFAs 1 and 3 reveal that two distinct transport pathways operated during moraine construction, with an early period of latero-frontal fan construction involving mixed lithologies and a later period of ice-contact/supraglacial fan construction dominated by schist lithologies from the mountains. These two periods of deposition were separated by a period of moraine abandonment and paraglacial reworking of ice-contact slopes to produce LFA 2. The occurrence of LFA 3 at all sites indicates that the glacier readvance phase responsible for its deposition was not localized or glacier-specific, and involved the transfer of large volumes of schist, possibly due

  1. Antimicrobial Activity.

    PubMed

    2016-01-01

    Natural products of higher plants may possess a new source of antimicrobial agents with possibly novel mechanisms of action. They are effective in the treatment of infectious diseases while simultaneously mitigating many of the side effects that are often associated with conventional antimicrobials. A method using scanning electron microscope (SEM) to study the morphology of the bacterial and fungal microbes and thus determining antimicrobial activity is presented in the chapter.

  2. Analgesic Activity.

    PubMed

    2016-01-01

    Analgesics are agents which selectively relieve pain by acting in the CNS and peripheral pain mediators without changing consciousness. Analgesics may be narcotic or non-narcotic. The study of pain in animals raises ethical, philosophical, and technical problems. Both peripheral and central pain models are included to make the test more evident for the analgesic property of the plant. This chapter highlights methods such as hot plate and formalin and acetic acid-induced pain models to check the analgesic activity of medicinal plants.

  3. Active packaging with antifungal activities.

    PubMed

    Nguyen Van Long, N; Joly, Catherine; Dantigny, Philippe

    2016-03-02

    There have been many reviews concerned with antimicrobial food packaging, and with the use of antifungal compounds, but none provided an exhaustive picture of the applications of active packaging to control fungal spoilage. Very recently, many studies have been done in these fields, therefore it is timely to review this topic. This article examines the effects of essential oils, preservatives, natural products, chemical fungicides, nanoparticles coated to different films, and chitosan in vitro on the growth of moulds, but also in vivo on the mould free shelf-life of bread, cheese, and fresh fruits and vegetables. A short section is also dedicated to yeasts. All the applications are described from a microbiological point of view, and these were sorted depending on the name of the species. Methods and results obtained are discussed. Essential oils and preservatives were ranked by increased efficacy on mould growth. For all the tested molecules, Penicillium species were shown more sensitive than Aspergillus species. However, comparison between the results was difficult because it appeared that the efficiency of active packaging depended greatly on the environmental factors of food such as water activity, pH, temperature, NaCl concentration, the nature, the size, and the mode of application of the films, in addition to the fact that the amount of released antifungal compounds was not constant with time.

  4. Active tectonics

    SciTech Connect

    Not Available

    1986-01-01

    This study is part of a series of Studies in Geophysics that have been undertaken for the Geophysics Research Forum by the Geophysics Study Committee. One purpose of each study is to provide assessments from the scientific community to aid policymakers in decisions on societal problems that involve geophysics. An important part of such assessments is an evaluation of the adequacy of current geophysical knowledge and the appropriateness of current research programs as a source of information required for those decisions. The study addresses our current scientific understanding of active tectonics --- particularly the patterns and rates of ongoing tectonic processes. Many of these processes cannot be described reasonably using the limited instrumental or historical records; however, most can be described adequately for practical purposes using the geologic record of the past 500,000 years. A program of fundamental research focusing especially on Quaternary tectonic geology and geomorphology, paleoseismology, neotectonics, and geodesy is recommended to better understand ongoing, active tectonic processes. This volume contains 16 papers. Individual papers are indexed separately on the Energy Database.

  5. Novel Automated Tracking Analysis of Particles Subjected to Shear Flow: Kindlin-3 Role in B Cells

    PubMed Central

    Willenbrock, Frances; Zicha, Daniel; Hoppe, Andreas; Hogg, Nancy

    2013-01-01

    Shear flow assays are used to mimic the influence of physiological shear force in diverse situations such as leukocyte rolling and arrest on the vasculature, capture of nanoparticles, and bacterial adhesion. Analysis of such assays usually involves manual counting, is labor-intensive, and is subject to bias. We have developed the Leukotrack program that incorporates a novel (to our knowledge) segmentation routine capable of reliable detection of cells in phase contrast images. The program also automatically tracks rolling cells in addition to those that are more firmly attached and migrating in random directions. We demonstrate its use in the analysis of lymphocyte arrest mediated by one or more active conformations of the integrin LFA-1. Activation of LFA-1 is a multistep process that depends on several proteins including kindlin-3, the protein that is mutated in leukocyte adhesion deficiency-III patients. We find that the very first stage of LFA-1-mediated attaching is unable to proceed in the absence of kindlin-3. Our evidence indicates that kindlin-3-mediated high-affinity LFA-1 controls both the early transient integrin-dependent adhesions in addition to the final stable adhesions made under flow conditions. PMID:24010654

  6. IASS Activity

    NASA Astrophysics Data System (ADS)

    Hojaev, Alisher S.; Ibragimova, Elvira M.

    2015-08-01

    It’s well known, astronomy in Uzbekistan has ancient roots and traditions (e.g., Mirzo Ulugh Beg, Abū al-Rayhān al-Bīrūnī, Abū ‘Abdallāh al-Khwārizmī) and astronomical heritage carefully preserved. Nowadays uzbek astronomers play a key role in scientific research but also in OAD and Decadal Plan activity in the Central Asia region. International Aerospace School (IASS) is an amazing and wonderful event held annually about 30 years. IASS is unique project in the region, and at the beginning we spent the Summer and Winter Schools. At present in the summer camp we gather about 50 teenage and undergraduate students over the country and abroad (France, Malaysia, Turkey, Azerbaijan, Pakistan, Russia, etc.). They are selected on the basis of tests of astronomy and space issues. During two weeks of IASS camp the invited scientists, cosmonauts and astronauts as well as other specialists give lectures and engage in practical exercises with IASS students in astronomy, including daily observations of the Sun and night sky observations with meniscus telescope, space research and exploration, aerospace modelling, preparation and presentation of original projects. This is important that IASS gives not theoretical grounds only but also practically train the students and the hands-on training is the major aims of IASS. Lectures and practice in the field of astronomy carried out with the direct involvement and generous assistance of Uranoscope Association (Paris, France). The current 26-th IASS is planned to held in July 2015.

  7. Physical Activity (Exercise)

    MedlinePlus

    ... Physical activity (exercise) fact sheet ePublications Physical activity (exercise) fact sheet How can physical activity improve my ... recent hip surgery More information on physical activity (exercise) For more information about physical activity (exercise), call ...

  8. Activation Energy

    NASA Technical Reports Server (NTRS)

    Gadeken, Owen

    2002-01-01

    Teaming is so common in today's project management environment that most of us assume it comes naturally. We further assume that when presented with meaningful and challenging work, project teams will naturally engage in productive activity to complete their tasks. This assumption is expressed in the simple (but false) equation: Team + Work = Teamwork. Although this equation appears simple and straightforward, it is far from true for most project organizations whose reality is a complex web of institutional norms based on individual achievement and rewards. This is illustrated by the very first successful team experience from my early Air Force career. As a young lieutenant, I was sent to Squadron Officer School, which was the first in the series of Air Force professional military education courses I was required to complete during my career. We were immediately formed into teams of twelve officers. Much of the course featured competition between these teams. As the most junior member of my team, I quickly observed the tremendous pressure to show individual leadership capability. At one point early in the course, almost everyone in our group was vying to become the team leader. This conflict was so intense that it caused us to fail miserably in our first outdoor team building exercise. We spent so much time fighting over leadership that we were unable to complete any of the events on the outdoor obstacle course. This complete lack of success was so disheartening to me that I gave our team little hope for future success. What followed was a very intense period of bickering, conflict, and even shouting matches as our dysfunctional team tried to cope with our early failures and find some way to succeed. British physician and researcher Wilfred Bion (Experiences in Groups, 1961) discovered that there are powerful psychological forces inherent in all groups that divert from accomplishing their primary tasks. To overcome these restraining forces and use the potential

  9. Staying Active: Physical Activity and Exercise

    MedlinePlus

    ... How much physical activity should I do each week? The Centers for Disease Control and Prevention recommend ... 150 minutes of moderate-intensity aerobic activity a week, along with muscle-strengthening activities on 2 days ...

  10. Co-expression of ovine LPS receptor CD14 with Mannheimia haemolytica leukotoxin receptor LFA-1 or Mac-1 does not enhance leukotoxin-induced cytotoxicity

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Leukotoxin (Lkt) and LPS are the major virulence determinants of Mannheimia haemolytica that contribute to the pathogenesis of bovine and ovine pneumonic pasteurellosis. We have previously identified bovine and ovine CD18 as the functional receptor for Lkt. LPS complexes with Lkt resulting in incre...

  11. BLOOD LEUKOCYTE EXPRESSION OF LFA-1 AND INTRACELLULAR ADHESION MOLECULE-1 (ICAM-1) AFTER INHALATION OF ULTRAFINE CARBON PARTICLES. (R827354C003)

    EPA Science Inventory

    The perspectives, information and conclusions conveyed in research project abstracts, progress reports, final reports, journal abstracts and journal publications convey the viewpoints of the principal investigator and may not represent the views and policies of ORD and EPA. Concl...

  12. [Analogies between the thymus and epidermis].

    PubMed

    De Panfilis, G

    1990-11-01

    In this paper, similarities between epidermis and thymus are reviewed. Both epidermis and thymus deal with an epithelial stroma harbouring dendritic cells, which are bone-marrow derived. Both epithelia are keratinized, and a map can be constructed illustrating histo-topographic and antigenic similarities between thymic epithelial cells distributed in various thymic zones (i.e. subcapsular cortex, outer cortex, inner cortex, medulla, outer layers of Hassall's bodies, inner layers of Hassall's bodies) and keratinocytes of different epidermal layers. By contrast, a possible similarity between thymocytes and Langerhans cells is not so easy to demonstrate, although both cell types are CD1 positive. Rather, in our opinion a comparison is preferable of thymocytes to Thy-1 positive dendritic epidermal cells, due to morphological, antigenic, functional and especially lineage similarities. Similarities between thymus and epidermis are clearly important dealing with analogous molecular interactions, namely, thymic epithelial cells/thymocytes versus keratinocytes/T-lymphocytes. Indeed, our recent investigations demonstrated that a subset of keratinocytes is ICAM-1 positive, and the whole keratinocyte population is LFA-3 positive. Since the interaction thymic epithelial cells (ICAM-1 and LFA-3 positive)/thymocytes (LFA-1 and CD2 positive) has been shown to be necessary for promotion of activation and maturation of thymocytes, the interaction keratinocytes (ICAM-1 and LFA-3 positive, as we demonstrated)/T-lymphocytes (LFA-1 and CD2 positive as well) might be, by analogy, important not only for the "homing" of T-lymphocytes within the epidermis, but also for the epidermis being considered a peripheral inductive site for T-cell activation and maturation.

  13. T-lymphocyte responsiveness in murine schistosomiasis mansoni is dependent upon the adhesion molecules intercellular adhesion molecule-1, lymphocyte function-associated antigen-1, and very late antigen-4.

    PubMed Central

    Langley, J G; Boros, D L

    1995-01-01

    Granuloma formation in murine schistosomiasis is dependent on CD4+ Th lymphocytes and requires recruitment and accumulation of inflammatory cells at the site of egg deposition. The present study examined the role of three adhesion molecules, intercellular adhesion molecule-1 (ICAM-1), lymphocyte function-associated antigen-1 (LFA-1), and very late antigen-4 (VLA-4), that participate in cellular recruitment, interaction, and lymphocyte activation during in vitro activation of acutely and chronically infected spleen and liver granuloma lymphocytes. Blockade of ICAM-1, LFA-1, or VLA-4 by rat monoclonal antibody inhibited spleen and granuloma lymphocyte interleukin-2 (IL-2) and IL-4 production as well as lymphoproliferative responses at similar levels (66 to 87%). The down-modulated cytokine and proliferative responses of chronically infected lymphocytes were inhibited to the same extent as their acutely infected counterparts. Cell sorting analysis demonstrated that acutely and chronically infected splenic and granuloma lymphocytes expressed similar levels of LFA-1, ICAM-1, and VLA-4 and that more ICAM-1 was expressed on infected than on uninfected mouse lymphocytes. By exposure of cells to paired monoclonal antibodies at suboptimal doses, it was determined that whereas all three adhesion molecules may participate, only ICAM-1 and LFA-1 showed synergistic interactions in determining lymphocyte responsiveness. These data suggest that spleen and liver granuloma lymphocytes are equally well armed with functional adhesion receptors. Thus, ICAM-1, LFA-1, and VLA-4 play an important accessory role in inflammatory cytokine production and lymphocyte proliferation, and therefore these adhesion molecules may participate in the initiation and maintenance of the granulomatous inflammation. PMID:7558308

  14. High aspect ratio materials: role of surface chemistry vs. length in the historical "long and short amosite asbestos fibers".

    PubMed

    Tomatis, Maura; Turci, Francesco; Ceschino, Raffaella; Riganti, Chiara; Gazzano, Elena; Martra, Gianmario; Ghigo, Dario; Fubini, Bice

    2010-10-01

    In nanotoxicology the question arises whether high aspect ratio materials should be regarded as potentially pathogenic like asbestos, merely on the base of their biopersistence and length to diameter ratio. A higher pathogenicity of long asbestos fibers is associated to their slower clearance and frustrated phagocytosis. In the past decades, two amosite fibers were prepared and studied to confirm the role of fiber length in asbestos toxicity. Long fiber amosite (LFA) and short fiber amosite (SFA) have here been revisited, to check differences in their surface properties, known to modulate the biological responses elicited. We report: (i) micromorphology (abundance of exposed cylindrical vs. truncated surfaces; (ii) surface reactivity (oxidation and coordination state of surface iron, free radical generation and oxidizing potential); (iii) activation of nitric oxide (NO) synthase in lung epithelial cells, as representative of an inflammatory cell response. LFA shows a higher free radical yield, stimulates, more than SFA, NO production by cells and reacts with ascorbic acid, thus depriving the lung lining layer of its antioxidant defenses. The higher activity of LFA than SFA is ascribed to the presence of Fe2+ ions poorly coordinated to the surface. SFA shows only a large number of loosely bound Fe3+ ions, pristine Fe2+ ions having been oxidized during the grinding process converting LFA into SFA. Several factors determine a higher toxicity of LFA than SFA, beside length. The lesson from asbestos indicates that other features besides aspect ratio contribute to the pathogenic potential of a fiber type. All these aspects should be considered when predicting the possible hazard associated to any new fibrous material proposed to the market, let alone nanofibers.

  15. Interleukin-4 (IL-4) enhances homotypic adhesion of activated B-chronic lymphocytic leukaemia (B-CLL) cells via a selective up-regulation of CD54.

    PubMed

    Carlsson, M; Söderberg, O; Nilsson, K

    1993-04-01

    It is well established that cell-to-cell contact modifies cytokine signalling but little is known on the role of homotypic cell adhesion for proliferation and differentiation of B cells. Homotypic adhesion involves mainly the interaction between the adhesion molecules Leukocyte Function Antigen-1 (LFA-1) and its ligand CD54 (ICAM-1). A well-characterized B-chronic lymphocytic leukaemia (B-CLL) clone (I-83) was used as a source of monoclonal B cells inducible to DNA synthesis and differentiation by using 12-O-tetradecanoyl-phorbol-13-acetate (TPA) in combination with interleukin-4 (IL-4) and thioredoxin (Trx)-containing supernatant from a T-cell hybridoma (BSF-MP6). This paper shows that IL-4 alone was able to induce aggregation of B-CLL cells and to strongly enhance TPA+BSF-MP6-induced aggregation. The results from studying the expression of CD11a and CD18, the two subunits of LFA-1, and CD54 during stimulated DNA synthesis and differentiation suggest that IL-4-induced, or enhanced, aggregation was mainly mediated by a selective up-regulation of CD54. It was further demonstrated by antibody blockade to either CD11a, CD18 or CD54 that aggregation could be inhibited without affecting induced DNA synthesis or differentiation.

  16. Adolescent sexual activity.

    PubMed

    Braverman, P K; Strasburger, V C

    1993-11-01

    Adolescents are becoming sexually active at younger ages. One half of the adolescents in the United States are sexually active. This article reviews adolescent sexual activity, including rates of sexual activity, sexual practices, gay and lesbian youth, and factors affecting the initiation of sexual activity. In addition, adolescent pregnancy, with possible outcomes and effects on teen parents and their offspring, is discussed.

  17. Guide to Physical Activity

    MedlinePlus

    ... Families ( We Can! ) Health Professional Resources Guide to Physical Activity Physical activity is an important part of your ... to injury. Examples of moderate-intensity amounts of physical activity Common Chores Washing and waxing a car for ...

  18. Physical Activity Assessment

    Cancer.gov

    Current evidence convincingly indicates that physical activity reduces the risk of colon and breast cancer. Physical activity may also reduce risk of prostate cancer. Scientists are also evaluating potential relationships between physical activity and other cancers.

  19. Political activity for physical activity: health advocacy for active transport

    PubMed Central

    2011-01-01

    Effective health advocacy is a priority for efforts to increase population participation in physical activity. Local councils are an important audience for this advocacy. The aim of the current study was to describe features of advocacy for active transport via submissions to city council annual plans in New Zealand, and the impact of an information sheet to encourage the health sector to be involved in this process. Written submissions to city council's annual consultation process were requested for 16 city councils over the period of three years (2007/08, 2008/09, and 2009/10). Submissions were reviewed and categories of responses were created. An advocacy information sheet encouraging health sector participation and summarising some of the evidence-base related to physical activity, active transport and health was released just prior to the 2009/10 submission time. Over the period of the study, city councils received 47,392 submissions, 17% of which were related to active transport. Most submissions came from city residents, with a small proportion (2%) from the health sector. The largest category of submissions was in support of pedestrian and cycling infrastructure, design and maintenance of facilities and additional features to support use of these transport modes. Health arguments featured prominently in justifications for active transport initiatives, including concerns about injury risk, obesity, physical inactivity, personal safety and facilities for people with disabilities. There was evidence that the information sheet was utilised by some health sector submitters (12.5%), providing tentative support for initiatives of this nature. In conclusion, the study provides novel information about the current nature of health advocacy for active transport and informs future advocacy efforts about areas for emphasis, such as health benefits of active transport, and potential alliances with other sectors such as environmental sustainability, transport and urban

  20. Home Activities for Fours.

    ERIC Educational Resources Information Center

    Ferguson-Florissant School District, Ferguson, MO.

    These home learning activity guides have been developed for parents to use with their 4-year-old children. Most of the activities require only household items that are often thrown away and can be recycled for learning activities. Some require no materials at all. The guides frequently begin with a discussion of home activities; progress through…

  1. Active commuting to school

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Declines in physical activity levels have coincided with increasing rates of obesity in children. This is problematic because physical activity has been shown to attenuate weight gain in children. Active commuting to school is one way of increasing children's physical activity. However, given the hi...

  2. Civil Law: 12 Activities.

    ERIC Educational Resources Information Center

    Dresbach, Debra

    These learning activities on civil law are intended to supplement the secondary level Scholastic materials "Living Law." Case studies, simulations, and role-play activities are included. Information provided for each activity includes a brief overview, background information, teacher instructions and a description of each activity.…

  3. Increasing Youth Physical Activity with Activity Calendars

    ERIC Educational Resources Information Center

    Eckler, Seth

    2016-01-01

    Physical educators often struggle with ways to get their students to be active beyond the school day. One strategy to accomplish this is the use of physical activity calendars (PACs). The purpose of this article is to support the use of PACs and give practical advice for creating effective PACs.

  4. Cutting edge: DNAX accessory molecule 1-deficient CD8+ T cells display immunological synapse defects that impair antitumor immunity.

    PubMed

    Ramsbottom, Kelly M; Hawkins, Edwin D; Shimoni, Raz; McGrath, Mairi; Chan, Christopher J; Russell, Sarah M; Smyth, Mark J; Oliaro, Jane

    2014-01-15

    DNAX accessory molecule 1 (DNAM-1) is expressed on all CD8(+) T cells and promotes their activation and effector function. DNAM-1 interacts with LFA-1, a critical molecule for immunological synapse formation between T cells and APCs, and for cytotoxic killing of target cells. Mice that lack DNAM-1 display abnormal T cell responses and antitumor activity; however, the mechanism involved is unclear. In this article, we show that DNAM-1 deficiency results in reduced proliferation of CD8(+) T cells after Ag presentation and impaired cytotoxic activity. We also demonstrate that DNAM-1-deficient T cells show reduced conjugations with tumor cells and decreased recruitment of both LFA-1 and lipid rafts to the immunological synapse, which correlates with reduced tumor cell killing in vitro. This synapse defect may explain why DNAM-1-deficient mice cannot clear tumors in vivo, and highlights the importance of DNAM-1 and the immunological synapse in T cell-mediated antitumor immunity.

  5. Cultural Activation of Consumers.

    PubMed

    Siegel, Carole E; Reid-Rose, Lenora; Joseph, Adriana M; Hernandez, Jennifer C; Haugland, Gary

    2016-02-01

    This column discusses "cultural activation," defined as a consumer's recognition of the importance of providing cultural information to providers about cultural affiliations, challenges, views about, and attitudes toward behavioral health and general medical health care, as well as the consumer's confidence in his or her ability to provide this information. An aid to activation, "Cultural Activation Prompts," and a scale that measures a consumer's level of activation, the Cultural Activation Measurement Scale, are described. Suggestions are made about ways to introduce cultural activation as a component of usual care.

  6. Smoking, physical activity, and active life expectancy.

    PubMed

    Ferrucci, L; Izmirlian, G; Leveille, S; Phillips, C L; Corti, M C; Brock, D B; Guralnik, J M

    1999-04-01

    The effect of smoking and physical activity on active and disabled life expectancy was estimated using data from the Established Populations for Epidemiologic Studies of the Elderly (EPESE). Population-based samples of persons aged > or = 65 years from the East Boston, Massachusetts, New Haven, Connecticut, and Iowa sites of the EPESE were assessed at baseline between 1981 and 1983 and followed for mortality and disability over six annual follow-ups. A total of 8,604 persons without disability at baseline were classified as "ever" or "never" smokers and doing "low," "moderate," or "high" level physical activity. Active and disabled life expectancies were estimated using a Markov chain model. Compared with smokers, men and women nonsmokers survived 1.6-3.9 and 1.6-3.6 years longer, respectively, depending on level of physical activity. When smokers were disabled and close to death, most nonsmokers were still nondisabled. Physical activity, from low to moderate to high, was significantly associated with more years of life expectancy in both smokers (9.5, 10.5, 12.9 years in men and 11.1, 12.6, 15.3 years in women at age 65) and nonsmokers (11.0, 14.4, 16.2 years in men and 12.7, 16.2, 18.4 years in women at age 65). Higher physical activity was associated with fewer years of disability prior to death. These findings provide strong and explicit evidence that refraining from smoking and doing regular physical activity predict a long and healthy life.

  7. Population Education. Awareness Activities.

    ERIC Educational Resources Information Center

    Brouse, Deborah E.

    1990-01-01

    Described are awareness activities that deal with human population growth, resources, and the environment. Activities include simulations, mathematical exercises, and discussions of the topic. Specific examples of what individuals can do to help are listed. (KR)

  8. Major operations and activities

    SciTech Connect

    Black, D.G.

    1995-06-01

    This section of the 1994 Hanford Site Environmental Report summarizes the major operations and activities on the site. These operations and activities include site management, waste management, environmental restoration and corrective actions, and research and technology development.

  9. Family Activities for Fitness

    ERIC Educational Resources Information Center

    Grosse, Susan J.

    2009-01-01

    This article discusses how families can increase family togetherness and improve physical fitness. The author provides easy ways to implement family friendly activities for improving and maintaining physical health. These activities include: walking, backyard games, and fitness challenges.

  10. Active magnetic regenerator

    DOEpatents

    Barclay, John A.; Steyert, William A.

    1982-01-01

    The disclosure is directed to an active magnetic regenerator apparatus and method. Brayton, Stirling, Ericsson, and Carnot cycles and the like may be utilized in an active magnetic regenerator to provide efficient refrigeration over relatively large temperature ranges.

  11. ACS Community Activities Contests

    NASA Astrophysics Data System (ADS)

    Burgener, Marisa

    2007-08-01

    The Committee on Community Activities and the Office of Community Activities announce the winners of the Illustrated Haiku Contest, Earth Day 2007 and the Poster Contest, National Chemistry Week 2006.

  12. Activity Theory and Ontology

    ERIC Educational Resources Information Center

    Peim, Nick

    2009-01-01

    This paper seeks to re-examine Yrio Engestrom's activity theory as a technology of knowledge designed to enable positive transformations of specific practices. The paper focuses on a key paper where Engestrom defines the nature and present state of activity theory. Beginning with a brief account of the relations between activity theory and…

  13. Measurement of Physical Activity.

    ERIC Educational Resources Information Center

    Dishman, Rod K.; Washburn, Richard A.; Schoeller, Dale A.

    2001-01-01

    Valid assessment of physical activity must be unobtrusive, practical to administer, and specific about physical activity type, frequency, duration, and intensity. Assessment methods can be categorized according to whether they provide direct or indirect (e.g., self-report) observation of physical activity, body motion, physiological response…

  14. Horticultural Practices. Activity Guides.

    ERIC Educational Resources Information Center

    Bania, Kent; Cummings, John, Ed.

    The 88 activity guides in this document are intended to supplement the initial or organized instruction of the agricultural teacher at the secondary educational level. Some of the activities require one student to complete, others may need two or more students working in a team. Some activities also require followup checking within a few days to…

  15. Highlights of 1981 activities

    NASA Technical Reports Server (NTRS)

    1981-01-01

    The highlights of NASA's 1981 activities are presented, including the results of the two flights of the space shuttle Columbia and the Voyager 2 encounter with Saturn. Accomplishments in the areas of space transportation operations; space science; aeronautical, energy, and space research and development; as well as space tracking, international activities, and 1981 launch activities are discussed.

  16. Bonus Activity Book.

    ERIC Educational Resources Information Center

    Learning, 1992

    1992-01-01

    Provides on-task activities to fill in unexpected extra moments in elementary classes. The activities require little preparation and take 5-15 minutes to complete. There are activities for math, language arts, social science, science, critical thinking, and computer. An outer space board game is also included. (SM)

  17. Activity Sheets. Draft Copy.

    ERIC Educational Resources Information Center

    Duke Power Company, Educational Services Dept., Charlotte, NC.

    This document consists of energy vocabulary activities, three games, worksheets, laboratory activities/exercises, and an introductory classroom exercise designed to introduce energy concepts to students. Vocabulary activities focus on coal and energy consumption. The three games (with instructions) focus on various aspects of energy and energy…

  18. Technology Learning Activities I.

    ERIC Educational Resources Information Center

    International Technology Education Association, Reston, VA.

    This guide contains 30 technology learning activities. Activities may contain all or some of the following: an introduction, objectives, materials and equipment, challenges, limitations, notes and investigations, resources and references used, and evaluation ideas. Activity titles are: (1) Occupations in Construction Technology; (2) Designing a…

  19. Technology Systems. Laboratory Activities.

    ERIC Educational Resources Information Center

    Brame, Ray; And Others

    This guide contains 43 modules of laboratory activities for technology education courses. Each module includes an instructor's resource sheet and the student laboratory activity. Instructor's resource sheets include some or all of the following elements: module number, course title, activity topic, estimated time, essential elements, objectives,…

  20. Computers + Student Activities Handbook.

    ERIC Educational Resources Information Center

    Masie, Elliott; Stein, Michele

    Designed to provide schools with the tools to start utilizing computers for student activity programs without additional expenditures, this handbook provides beginning computer users with suggestions and ideas for using computers in such activities as drama clubs, yearbooks, newspapers, activity calendars, accounting programs, room utilization,…

  1. Climate Change: An Activity.

    ERIC Educational Resources Information Center

    Lewis, Garry

    1995-01-01

    Presents a segment of the Geoscience Education booklet, Climate Change, that contains information and activities that enable students to gain a better appreciation of the possible effects human activity has on the Earth's climate. Describes the Terrace Temperatures activity that leads students through an investigation using foraminifera data to…

  2. Advantages of time-resolved fluorescent nanobeads compared with fluorescent submicrospheres, quantum dots, and colloidal gold as label in lateral flow assays for detection of ractopamine.

    PubMed

    Hu, Li-Ming; Luo, Kai; Xia, Jun; Xu, Guo-Mao; Wu, Cheng-Hui; Han, Jiao-Jiao; Zhang, Gang-Gang; Liu, Miao; Lai, Wei-Hua

    2017-05-15

    Label selection is a critical factor for improving the sensitivity of lateral flow assay. Time-resolved fluorescent nanobeads, fluorescent submicrospheres, quantum dots, and colloidal gold-based lateral flow assay (TRFN-LFA, FM-LFA, QD-LFA, and CG-LFA) were first systematically compared for the quantitative detection of ractopamine in swine urine based on competitive format. The limits of detection (LOD) of TRFN-LFA, FM-LFA, QD-LFA, and CG-LFA were 7.2, 14.7, 23.6, and 40.1pg/mL in swine urine samples, respectively. The sensitivity of TRFN-LFA was highest. In the quantitative determination of ractopamine (RAC) in swine urine samples, TRFN-LFA exhibited a wide linear range of 5pg/mL to 2500pg/mL with a reliable coefficient of correlation (R(2)=0.9803). Relatively narrow linear ranges of 10-500pg/mL (FM-LFA) and 25-2500pg/mL (QD-LFA and CG-LFA) were acquired. Approximately 0.005µg of anti-RAC poly antibody (pAb) was used in each TRFN-LFA test strip, whereas 0.02, 0.054, and 0.15µg of pAb were used in each of the FM-LFA, QD-LFA, and CG-LFA test strips, respectively. In addition, TRFN-LFA required the least RAC-BSA antigens and exhibited the shortest detection time compared with the other lateral flow assays. Analysis of the RAC in swine urine samples showed that the result of TRFN-LFA was consistent with that of liquid chromatography-tandem mass spectrometry (LC-MS/MS) and a commercial enzyme-linked immunosorbent assay (ELISA) kit.

  3. Dual functions of Rap1 are crucial for T-cell homeostasis and prevention of spontaneous colitis

    PubMed Central

    Ishihara, Sayaka; Nishikimi, Akihiko; Umemoto, Eiji; Miyasaka, Masayuki; Saegusa, Makoto; Katagiri, Koko

    2015-01-01

    Rap1-GTP activates leukocyte function-associated antigen-1 (LFA-1) to induce arrest on the high endothelial venule (HEV). Here we show that Rap1-GDP restrains rolling behaviours of T cells on the peripheral lymph node addressin (PNAd), P-selectin and mucosal addressin cell adhesion molecule-1 (MadCAM-1) by inhibiting tether formation. Consequently, Rap1 deficiency impairs homing of naive T cells to peripheral lymph nodes, but accelerates homing of TH17 and TH1 cells to the colon, resulting in spontaneous colitis with tumours. Rap1-GDP associates with and activates lymphocyte-oriented kinase, which phosphorylates ERM (ezrin, radixin and moesin) in resting T cells. Phosphomimetic ezrin reduces the rolling of Rap1-deficient cells, and thereby decreases their homing into the colon. On the other hand, chemokines activate Rap1 at the plasma membrane within seconds, and Rap1-GTP binds to filamins, which diminishes its association with the β2 chain of LFA-1 and results in LFA-1 activation. This Rap1-dependent regulation of T-cell circulation prevents the onset of colitis. PMID:26634692

  4. Vestibular activation of sympathetic nerve activity

    NASA Technical Reports Server (NTRS)

    Ray, C. A.; Carter, J. R.

    2003-01-01

    AIM: The vestibulosympathetic reflex refers to sympathetic nerve activation by the vestibular system. Animal studies indicate that the vestibular system assists in blood pressure regulation during orthostasis. Although human studies clearly demonstrate activation of muscle sympathetic nerve activity (MSNA) during engagement of the otolith organs, the role of the vestibulosympathetic reflex in maintaining blood pressure during orthostasis is not well-established. Examination of the vestibulosympathetic reflex with other cardiovascular reflexes indicates that it is a powerful and independent reflex. Ageing, which is associated with an increased risk for orthostatic hypotension, attenuates the vestibulosympathetic reflex. The attenuated reflex is associated with a reduction in arterial pressure. CONCLUSION: These findings suggest that the vestibulosympathetic reflex assists in blood pressure regulation in humans, but future studies examining this reflex in other orthostatically intolerant populations are necessary to address this hypothesis.

  5. Metabolism Supports Macrophage Activation

    PubMed Central

    Langston, P. Kent; Shibata, Munehiko; Horng, Tiffany

    2017-01-01

    Macrophages are found in most tissues of the body, where they have tissue- and context-dependent roles in maintaining homeostasis as well as coordinating adaptive responses to various stresses. Their capacity for specialized functions is controlled by polarizing signals, which activate macrophages by upregulating transcriptional programs that encode distinct effector functions. An important conceptual advance in the field of macrophage biology, emerging from recent studies, is that macrophage activation is critically supported by metabolic shifts. Metabolic shifts fuel multiple aspects of macrophage activation, and preventing these shifts impairs appropriate activation. These findings raise the exciting possibility that macrophage functions in various contexts could be regulated by manipulating their metabolism. Here, we review the rapidly evolving field of macrophage metabolism, discussing how polarizing signals trigger metabolic shifts and how these shifts enable appropriate activation and sustain effector activities. We also discuss recent studies indicating that the mitochondria are central hubs in inflammatory macrophage activation. PMID:28197151

  6. Activated carbon from biomass

    NASA Astrophysics Data System (ADS)

    Manocha, S.; Manocha, L. M.; Joshi, Parth; Patel, Bhavesh; Dangi, Gaurav; Verma, Narendra

    2013-06-01

    Activated carbon are unique and versatile adsorbents having extended surface area, micro porous structure, universal adsorption effect, high adsorption capacity and high degree of surface reactivity. Activated carbons are synthesized from variety of materials. Most commonly used on a commercial scale are cellulosic based precursors such as peat, coal, lignite wood and coconut shell. Variation occurs in precursors in terms of structure and carbon content. Coir having very low bulk density and porous structure is found to be one of the valuable raw materials for the production of highly porous activated carbon and other important factor is its high carbon content. Exploration of good low cost and non conventional adsorbent may contribute to the sustainability of the environment and offer promising benefits for the commercial purpose in future. Carbonization of biomass was carried out in a horizontal muffle furnace. Both carbonization and activation were performed in inert nitrogen atmosphere in one step to enhance the surface area and to develop interconnecting porosity. The types of biomass as well as the activation conditions determine the properties and the yield of activated carbon. Activated carbon produced from biomass is cost effective as it is easily available as a waste biomass. Activated carbon produced by combination of chemical and physical activation has higher surface area of 2442 m2/gm compared to that produced by physical activation (1365 m2/gm).

  7. Factor XII Contact Activation.

    PubMed

    Naudin, Clément; Burillo, Elena; Blankenberg, Stefan; Butler, Lynn; Renné, Thomas

    2017-03-27

    Contact activation is the surface-induced conversion of factor XII (FXII) zymogen to the serine protease FXIIa. Blood-circulating FXII binds to negatively charged surfaces and this contact to surfaces triggers a conformational change in the zymogen inducing autoactivation. Several surfaces that have the capacity for initiating FXII contact activation have been identified, including misfolded protein aggregates, collagen, nucleic acids, and platelet and microbial polyphosphate. Activated FXII initiates the proinflammatory kallikrein-kinin system and the intrinsic coagulation pathway, leading to formation of bradykinin and thrombin, respectively. FXII contact activation is well characterized in vitro and provides the mechanistic basis for the diagnostic clotting assay, activated partial thromboplastin time. However, only in the past decade has the critical role of FXII contact activation in pathological thrombosis been appreciated. While defective FXII contact activation provides thromboprotection, excess activation underlies the swelling disorder hereditary angioedema type III. This review provides an overview of the molecular basis of FXII contact activation and FXII contact activation-associated disease states.

  8. Marine Biology Activities. Ocean Related Curriculum Activities.

    ERIC Educational Resources Information Center

    Pauls, John

    The ocean affects all of our lives. Therefore, awareness of and information about the interconnections between humans and oceans are prerequisites to making sound decisions for the future. Project ORCA (Ocean Related Curriculum Activities) has developed interdisciplinary curriculum materials designed to meet the needs of students and teachers…

  9. Patterns in Active Nematics

    NASA Astrophysics Data System (ADS)

    Yeomans, Julia M.

    Active systems, from bacterial suspensions to cellular monolayers, are continuously driven out of equilibrium by local injection of energy from their constituent elements and exhibit turbulent-like, chaotic patterns. We describe how active systems can be stabilised by tuning a physical feature of the system, friction. We demonstrate how the crossover between wet active systems, whose behaviour is dominated by hydrodynamics, and dry active matter where any flow is screened, can be achieved by using friction as a control parameter and demonstrate vortex ordering at the wet-dry crossover. We show that the self organisation of vortices into lattices is accompanied by the spatial ordering of topological defects leading to active crystal-like structures. The emergence of vortex lattices which leads to the positional ordering of topological defects may be a useful step towards the design and control of active materials.

  10. Bimolecular complex between rolling and firm adhesion receptors required for cell arrest; CD44 association with VLA-4 in T cell extravasation.

    PubMed

    Nandi, Animesh; Estess, Pila; Siegelman, Mark

    2004-04-01

    CD44 on activated T cells can initiate contact and mediate rolling on hyaluronan on endothelial cells. We have shown that the integrin VLA-4 is used preferentially over LFA-1 in conjunction with this rolling interaction for firm adhesion. Here, we show by coimmunoprecipitation and transfection studies that CD44 associates with VLA-4 but not LFA-1 on the plasma membrane of immune cells. Absence of the cytoplasmic portion of CD44 abrogates this coassociation and attendant firm adhesion. Moreover, in an in vivo model of lymphocyte homing, cells expressing only the truncated form of CD44 together with VLA-4 fail to traffic to an inflamed site, thereby defining a discrete biological role for the cytoplasmic domain. These studies demonstrate a molecular mechanism whereby coanchoring within a single bimolecular complex between a primary and secondary adhesion molecule regulates a cell's ability to firmly adhere, providing a fundamental alteration to the paradigm of leukocyte extravasation.

  11. Inhibitory effects of manassantin A and B isolated from the roots of Saururus chinensis on PMA-induced ICAM-1 expression.

    PubMed

    Rho, Mun-Chual; Kwon, Oh Eok; Kim, Koanhoi; Lee, Seung Woong; Chung, Mi Yeon; Kim, Young Ho; Hayashi, Masahiko; Lee, Hyun Sun; Kim, Young-Kook

    2003-12-01

    Cell adhesion inhibitors were isolated from the methanol extract of Saururus chinensis roots by bioactivity-guided fractionation. The active compounds were identified as manassantin A ( 1) and B ( 2), dineolignan compounds. Compounds 1 and 2 inhibited PMA-induced ICAM-1/LFA-1-mediated homotypic aggregation of the HL-60 cells without cytotoxicity with MIC values of 1.0 and 5.5 nM, respectively. Even though 1 and 2 did not affect the adhesion of ICAM-1 to LFA-1, these compounds inhibited PMA-induced ICAM-1 expression in HL-60 cells in a dose-dependent fashion. These results suggest that 1 and 2 inhibit cell aggregation through down-regulation of ICAM-1 expression.

  12. Activated recombinant adenovirus proteinases

    DOEpatents

    Anderson, C.W.; Mangel, W.F.

    1999-08-10

    This application describes methods and expression constructs for producing activatable recombinant adenovirus proteinases. Purified activatable recombinant adenovirus proteinases and methods of purification are described. Activated adenovirus proteinases and methods for obtaining activated adenovirus proteinases are further included. Isolated peptide cofactors of adenovirus proteinase activity, methods of purifying and identifying peptide cofactors are also described. Antibodies immunoreactive with adenovirus proteinases, immunospecific antibodies, and methods for preparing them are also described. Other related methods and materials are also described. 29 figs.

  13. Activated recombinant adenovirus proteinases

    DOEpatents

    Anderson, Carl W.; Mangel, Walter F.

    1999-08-10

    This application describes methods and expression constructs for producing activatable recombinant adenovirus proteinases. Purified activatable recombinant adenovirus proteinases and methods of purification are described. Activated adenovirus proteinases and methods for obtaining activated adenovirus proteinases are further included. Isolated peptide cofactors of adenovirus proteinase activity, methods of purifying and identifying said peptide cofactors are also described. Antibodies immunoreactive with adenovirus proteinases, immunospecific antibodies, and methods for preparing them are also described. Other related methods and materials are also described.

  14. Activity in distant comets

    NASA Technical Reports Server (NTRS)

    Luu, Jane X.

    1992-01-01

    Activity in distant comets remains a mystery in the sense that we still have no complete theory to explain the various types of activity exhibited by different comets at large distances. This paper explores the factors that should play a role in determining activity in a distant comet, especially in the cases of comet P/Tempel 2, comet Schwassmann-Wachmann 1, and 2060 Chiron.

  15. Thermally Activated Driver

    NASA Technical Reports Server (NTRS)

    Kinard, William H.; Murray, Robert C.; Walsh, Robert F.

    1987-01-01

    Space-qualified, precise, large-force, thermally activated driver (TAD) developed for use in space on astro-physics experiment to measure abundance of rare actinide-group elements in cosmic rays. Actinide cosmic rays detected using thermally activated driver as heart of event-thermometer (ET) system. Thermal expansion and contraction of silicone oil activates driver. Potential applications in fluid-control systems where precise valve controls are needed.

  16. [Biomedical activity of biosurfactants].

    PubMed

    Krasowska, Anna

    2010-07-23

    Biosurfactants, amphiphilic compounds, synthesized by microorganisms have surface, antimicrobial and antitumor properties. Biosurfactants prevent adhesion and biofilms formation by bacteria and fungi on various surfaces. For many years microbial surfactants are used as antibiotics with board spectrum of activity against microorganisms. Biosurfactants act as antiviral compounds and their antitumor activities are mediated through induction of apoptosis. This work presents the current state of knowledge related to biomedical activity of biosurfactants.

  17. NASA metrication activities

    NASA Technical Reports Server (NTRS)

    Vlannes, P. N.

    1978-01-01

    NASA's organization and policy for metrification, history from 1964, NASA participation in Federal agency activities, interaction with nongovernmental metrication organizations, and the proposed metrication assessment study are reviewed.

  18. Active Flow Control Activities at NASA Langley

    NASA Technical Reports Server (NTRS)

    Anders, Scott G.; Sellers, William L., III; Washburn, Anthony E.

    2004-01-01

    NASA Langley continues to aggressively investigate the potential advantages of active flow control over more traditional aerodynamic techniques. This paper provides an update to a previous paper and describes both the progress in the various research areas and the significant changes in the NASA research programs. The goals of the topics presented are focused on advancing the state of knowledge and understanding of controllable fundamental mechanisms in fluids as well as to address engineering challenges. An organizational view of current research activities at NASA Langley in active flow control as supported by several projects is presented. On-center research as well as NASA Langley funded contracts and grants are discussed at a relatively high level. The products of this research are to be demonstrated either in bench-top experiments, wind-tunnel investigations, or in flight as part of the fundamental NASA R&D program and then transferred to more applied research programs within NASA, DOD, and U.S. industry.

  19. Active Students in Webinars

    ERIC Educational Resources Information Center

    Kolås, Line; Nordseth, Hugo; Yri, Jørgen Sørlie

    2015-01-01

    To ensure student activity in webinars we have defined 10 learning tasks focusing on production and communication e.g. collaborative writing, discussion and polling, and investigated how the technology supports the learning activities. The three project partners in the VisPed-project use different video-conferencing systems, and we analyzed how it…

  20. [Field Learning Activities].

    ERIC Educational Resources Information Center

    Nolde Forest Environmental Education Center, Reading, PA.

    Seventy field activities, pertinent to outdoor, environmental studies, are described in this compilation. Designed for elementary and junior high school students, the activities cover many discipline areas--science, social studies, language arts, health, history, mathematics, and art--and many are multidisciplinary in use. Topics range from soil…

  1. Warm-Up Activities.

    ERIC Educational Resources Information Center

    Mingguang, Yang

    1999-01-01

    Discusses how warm-up activities can help to make the English-as-a-foreign-language classroom a lively and interesting place. Warm-up activities are games carried out at the beginning of each class to motivate students to make good use of class time. (Author/VWL)

  2. Nutrition Activities Resource Guide.

    ERIC Educational Resources Information Center

    New York City Board of Education, Brooklyn, NY. Div. of Special Education.

    The resource guide suggests activities to help special education students make appropriate choices about their nutritional habits. It is explained that the activities can be infused into other curriculum areas. The guide consists of five themes and includes performance objectives for each: foods eaten at school (planning a school lunch, keeping a…

  3. Science World Activities Book.

    ERIC Educational Resources Information Center

    Wisconsin Academy of Sciences, Arts and Letters, Madison.

    This document consists of three sections. Section I contains 19 activities developed by master teachers for the Science World '84 summer science program. These activities focus on studies involving airplane controls, trash bag kites, computers, meteorology, compass orienteering, soils, aquatic ecosystems, bogs, and others. Objectives, materials…

  4. The Journal Synthesizing Activity.

    ERIC Educational Resources Information Center

    Garber, Zev

    The journal synthesizing activity is intended to combine aspects of the formal essay with that of a diary. Activities associated with lecture topics are written up as short journal entries of approximately five typewritten pages and are turned in during the weekly class session at which the related topic is being discussed. The journal project…

  5. Activation of fly ash

    DOEpatents

    Corbin, D.R.; Velenyi, L.J.; Pepera, M.A.; Dolhyj, S.R.

    1986-08-19

    Fly ash is activated by heating a screened magnetic fraction of the ash in a steam atmosphere and then reducing, oxidizing and again reducing the hydrothermally treated fraction. The activated fly ash can be used as a carbon monoxide disproportionating catalyst useful in the production of hydrogen and methane.

  6. Activating Event Knowledge

    ERIC Educational Resources Information Center

    Hare, Mary; Jones, Michael; Thomson, Caroline; Kelly, Sarah; McRae, Ken

    2009-01-01

    An increasing number of results in sentence and discourse processing demonstrate that comprehension relies on rich pragmatic knowledge about real-world events, and that incoming words incrementally activate such knowledge. If so, then even outside of any larger context, nouns should activate knowledge of the generalized events that they denote or…

  7. Coordinating Shared Activities

    NASA Technical Reports Server (NTRS)

    Clement, Bradley

    2004-01-01

    Shared Activity Coordination (ShAC) is a computer program for planning and scheduling the activities of an autonomous team of interacting spacecraft and exploratory robots. ShAC could also be adapted to such terrestrial uses as helping multiple factory managers work toward competing goals while sharing such common resources as floor space, raw materials, and transports. ShAC iteratively invokes the Continuous Activity Scheduling Planning Execution and Replanning (CASPER) program to replan and propagate changes to other planning programs in an effort to resolve conflicts. A domain-expert specifies which activities and parameters thereof are shared and reports the expected conditions and effects of these activities on the environment. By specifying these conditions and effects differently for each planning program, the domain-expert subprogram defines roles that each spacecraft plays in a coordinated activity. The domain-expert subprogram also specifies which planning program has scheduling control over each shared activity. ShAC enables sharing of information, consensus over the scheduling of collaborative activities, and distributed conflict resolution. As the other planning programs incorporate new goals and alter their schedules in the changing environment, ShAC continually coordinates to respond to unexpected events.

  8. Activities: More Calculator Capers.

    ERIC Educational Resources Information Center

    Schmalz, Rosemary

    1983-01-01

    Provided is an activity designed to give grades 7-12 students opportunities to discover numerical patterns and to derive general conclusions from observing data. The activity focuses attention on patterns in products such as 33x34, 333x334, and 3333x3334. Three worksheets and answers are included. (JN)

  9. Choreography of AMPK activation.

    PubMed

    Langendorf, Christopher G; Kemp, Bruce E

    2015-01-01

    A recent study published in Cell Research by Li and colleagues reports a detailed biophysical and structural study of AMPK's intra-molecular interactions during activation. By employing subunit tagging and proximity analysis with the aid of AlphaScreen instrumentation, Li et al. add to our understanding of the choreography of activation of AMPK by both nucleotides and phosphorylation.

  10. Rainy Day Activities.

    ERIC Educational Resources Information Center

    Texas Child Care, 1997

    1997-01-01

    Experienced caregivers plan ahead for rainy days. This article describes specific rainy day activities for young children, such as books and crafts to learn about rain (rain in a jar, making a rainbow), simple cooking activities (taffy pull, cinnamon candy tea), and games (mummy wrap, hunt the thimble, rain lotto). (EV)

  11. Laboratory Activities in Israel

    ERIC Educational Resources Information Center

    Mamlok-Naaman, Rachel; Barnea, Nitza

    2012-01-01

    Laboratory activities have long had a distinctive and central role in the science curriculum, and science educators have suggested that many benefits accrue from engaging students in science laboratory activities. Many research studies have been conducted to investigate the educational effectiveness of laboratory work in science education in…

  12. Peak Longevity Physical Activity

    Cancer.gov

    People who engage in three to five times the recommended minimum level of leisure-time physical activity derive the greatest benefit in terms of mortality reduction when compared with people who do not engage in leisure-time physical activity.

  13. Curriculum Activities on Aging.

    ERIC Educational Resources Information Center

    Schmall, Vicki L.; Benge, Nancy

    This paper contains learning activities on aging for use with elementary, high school, and university students in health, family relationships, social studies, and art courses. The activities are intended to help youth develop a more realistic understanding of the aging process and to become aware of both the problems and benefits associated with…

  14. Students Active in Leadership.

    ERIC Educational Resources Information Center

    Brutcher, Robert

    2001-01-01

    Describes SAIL (Students Active in Leadership) as a school-based, youth-directed group. States that the program helps teenagers learn leadership skills by developing and implementing community service activities. SAIL finds partners with whom to collaborate among local businesses, government, and health associations, and these partners provide the…

  15. Ten Minute Writing Activities.

    ERIC Educational Resources Information Center

    Markus, Sharyn

    Designed with junior high school students in mind, the activities in this booklet are offered as ways to stimulate interest in writing using as little as ten minutes of class time. The activities are arranged in six sections: (1) developing observation skills and paying attention to details; (2) word play, descriptive words, and word collections…

  16. Nature's engines: active matter

    NASA Astrophysics Data System (ADS)

    Yeomans, Julia M.

    2017-03-01

    Active materials, bacteria, molecular motors, and self-propelled colloids, continuously transform chemical energy from the environment to mechanical work. Dense active matter, from layers of cells to flocks of birds, self-assembles into intricate patterns. Nature's engines are complex and efficient, and we would like to exploit her ideas to fabricate nano-machines.

  17. Activation of fly ash

    DOEpatents

    Corbin, David R.; Velenyi, Louis J.; Pepera, Marc A.; Dolhyj, Serge R.

    1986-01-01

    Fly ash is activated by heating a screened magnetic fraction of the ash in a steam atmosphere and then reducing, oxidizing and again reducing the hydrothermally treated fraction. The activated fly ash can be used as a carbon monoxide disproportionating catalyst useful in the production of hydrogen and methane.

  18. Activity Book: Ocean Ecology.

    ERIC Educational Resources Information Center

    Learning, 1992

    1992-01-01

    Presents a collection of activities to help elementary students study ocean ecology. The activities have students investigate ocean inhabitants, analyze animal adaptations, examine how temperature and saltiness affect ocean creatures, and learn about safeguarding the sea. Student pages offer reproducible learning sheets. (SM)

  19. [Biosignals of dermal activity].

    PubMed

    Rathkolb, O; Gallei, L

    1993-01-01

    Electrodermal activity (EDA) summarizes different electrophysiological dimensions of human skin. EDA is based on the activity of sweat glands and their innervation by the autonomic nervous system. EDA is used as indicator in the additional diagnostic assessment of patients in the fields of neurology and psychosomatic medicine.

  20. Active galactic nuclei

    PubMed Central

    Fabian, Andrew C.

    1999-01-01

    Active galactic nuclei are the most powerful, long-lived objects in the Universe. Recent data confirm the theoretical idea that the power source is accretion into a massive black hole. The common occurrence of obscuration and outflows probably means that the contribution of active galactic nuclei to the power density of the Universe has been generally underestimated. PMID:10220363

  1. Reflections on Activity Theory

    ERIC Educational Resources Information Center

    Bakhurst, David

    2009-01-01

    It is sometimes suggested that activity theory represents the most important legacy of Soviet philosophy and psychology. But what exactly "is" activity theory? The canonical account in the West is given by Engestrom, who identifies three stages in the theory's development: from Vygotsky's insights, through Leontiev's articulation of the…

  2. Student Activities. Managing Liability.

    ERIC Educational Resources Information Center

    Bennett, Barbara; And Others

    This monograph suggests ways that college or university administrations can undertake a systematic and careful review of the risks posed by students' activities. Its purpose is to provide guidance in integrating the risk management process into a school's existing approaches to managing student organizations and activities. It is noted that no…

  3. The Activity of Trypsin

    ERIC Educational Resources Information Center

    Russo, Salvatore F.; Holzman, Tom

    1977-01-01

    Describes an experiment that illustrates the following points concerning the experimental determination of trypsin activity: (1) there is a difference in basing enzyme concentration on weight, absorbance, or active sites; and (2) the method of expressing enzyme concentration determines the value of specific, molecular, and catalytic center…

  4. Metastasis and AKT activation.

    PubMed

    Qiao, Meng; Sheng, Shijie; Pardee, Arthur B

    2008-10-01

    Metastasis is responsible for 90% of cancer patient deaths. More information is needed about the molecular basis for its potential detection and treatment. The activated AKT kinase is necessary for many events of the metastatic pathway including escape of cells from the tumor's environment, into and then out of the circulation, activation of proliferation, blockage of apoptosis, and activation of angiogenesis. A series of steps leading to metastatic properties can be initiated upon activation of AKT by phosphorylation on Ser-473. These findings lead to the question of how this activation is connected to metastasis. Activated AKT phosphorylates GSK-3beta causing its proteolytic removal. This increases stability of the negative transcription factor SNAIL, thereby decreasing transcription of the transmembrane protein E-cadherin that forms adhesions between adjacent cells, thereby permitting their detachment. How is AKT hyperactivated in metastatic cells? Increased PI3K or TORC2 kinase activity- or decreased PHLPP phosphatase could be responsible. Furthermore, a positive feedback mechanism is that the decrease of E-cadherin lowers PTEN and thereby increases PIP3, further activating AKT and metastasis.

  5. Aging and Semantic Activation.

    ERIC Educational Resources Information Center

    Howard, Darlene V.

    Three studies tested the theory that long term memory consists of a semantically organized network of concept nodes interconnected by leveled associations or relations, and that when a stimulus is processed, the corresponding concept node is assumed to be temporarily activated and this activation spreads to nearby semantically related nodes. In…

  6. Activities of the ILO.

    ERIC Educational Resources Information Center

    Labour Education, 1984

    1984-01-01

    Seven articles on International Labour Organization (ILO) activities cover study groups at ILO headquarters, a Philippine rural workers seminar, women's participation in Central American union activities, worksite courses in India, and seminars and symposia in Cape Verde, Mauritius, and Sierra Leone. (SK)

  7. Learning Activities for Toddlers.

    ERIC Educational Resources Information Center

    Texas Child Care, 1996

    1996-01-01

    Suggests activities to help toddlers develop skills in the four important areas of self-help, creativity, world mastery, and coordination. Activities include hand washing, button practice, painting, movement and music, bubble making, creation of a nature mural, and a shoe print trail. (TJQ)

  8. Active and Healthy Schools

    ERIC Educational Resources Information Center

    Ball, Stephen; Kovarik, Jessica; Leidy, Heather

    2015-01-01

    The Active and Healthy School Program (AHS) can be used to alter the culture and environment of a school to help children make healthier choices. The purpose of this study was to determine the effectiveness of AHS to increase physical activity while decreasing total screen time, increase healthy food choices, and improve knowledge about physical…

  9. ZOOMsci Activity Guide.

    ERIC Educational Resources Information Center

    Wade, Meredith

    This activity guide is based on the Public Broadcasting System's (PBS) program "ZOOM." It is designed for educators with activities that are categorized into three themes: (1) Things That Go, which includes "Air" which explores air pressure, "Rubber Bands" which discovers the potential energy of rubber bands,…

  10. Emotionally Intense Science Activities

    ERIC Educational Resources Information Center

    King, Donna; Ritchie, Stephen; Sandhu, Maryam; Henderson, Senka

    2015-01-01

    Science activities that evoke positive emotional responses make a difference to students' emotional experience of science. In this study, we explored 8th Grade students' discrete emotions expressed during science activities in a unit on Energy. Multiple data sources including classroom videos, interviews and emotion diaries completed at the end of…

  11. Adhesion molecules in vernal keratoconjunctivitis

    PubMed Central

    El-Asrar, A.; Geboes, K.; Al-Kharashi, S.; Tabbara, K.; Missotten, L.; Desmet, V.

    1997-01-01

    AIMS/BACKGROUND—Adhesion molecules play a key role in the selective recruitment of different leucocyte population to inflammatory sites. The purpose of the present study was to investigate the presence and distribution of adhesion molecules in the conjunctiva of patients with vernal keratoconjunctivitis (VKC).
METHODS—The presence and distribution of adhesion molecules were studied in 14 conjunctival biopsy specimens from seven patients with active VKC and in four normal conjunctival biopsy specimens. We used a panel of specific monoclonal antibodies (mAbs) directed against intercellular adhesion molecule-1 (ICAM-1), intercellular adhesion molecule-3 (ICAM-3), lymphocyte function associated antigen-1 (LFA-1), very late activation antigen-4 (VLA-4), vascular cell adhesion molecule-1 (VCAM-1), and endothelial leucocyte adhesion molecule-1 (ELAM-1). In addition, a panel of mAbs were used to characterise the composition of the inflammatory infiltrate.
RESULTS—In the normal conjunctiva, ICAM-1 was expressed on the vascular endothelium only, LFA-1 and ICAM-3 on epithelial and stromal mononuclear cells , and VLA-4 on stromal mononuclear cells. The expression of VCAM-1 and ELAM-1 was absent. The number of cells expressing adhesion molecules was found to be markedly increased in all VKC specimens. This was concurrent with a heavy inflammatory infiltrate. Strong ICAM-1 expression was induced on the basal epithelial cells, and vascular endothelial cells. Furthermore, ICAM-1 was expressed on stromal mononuclear cells. LFA-1 and ICAM-3 were expressed on the majority of epithelial and stromal infiltrating mononuclear cells. VLA-4 expression was noted on stromal mononuclear cells. Compared with controls, VKC specimens showed significantly more ICAM-3+, LFA-1+, and VLA-4+ cells. VCAM-1 and ELAM-1 were induced on the vascular endothelial cells.
CONCLUSIONS—Increased expression of adhesion molecules may play an important role in the pathogenesis of VKC.

 PMID

  12. The pro-oxidative drug WF-10 inhibits serial killing by primary human cytotoxic T-cells.

    PubMed

    Wabnitz, G H; Balta, E; Schindler, S; Kirchgessner, H; Jahraus, B; Meuer, S; Samstag, Y

    2016-01-01

    Cytotoxic T-cells (CTLs) play an important role in many immune-mediated inflammatory diseases. Targeting cytotoxicity of CTLs would allow to interfere with immune-mediated tissue destruction. Here we demonstrate that WF-10, a pro-oxidative compound, inhibits CTL-mediated cytotoxicity. WF-10 did not influence early steps of target-cell killing, but impaired the ability of CTLs to detach from the initial target cell and to move to a second target cell. This reduced serial killing was accompanied by stronger enrichment of the adhesion molecule LFA-1 in the cytolytic immune synapse. LFA-1 clustering requires activation of the actin-bundling protein L-plastin and was accordingly diminished in L-plastin knockdown cells. Interestingly, WF-10 likely acts through regulating L-plastin: (I) It induced L-plastin activation through phosphorylation leading to enhanced LFA-1-mediated cell adhesion, and, importantly, (II) WF-10 lost its influence on target-cell killing in L-plastin knockdown cells. Finally, we demonstrate that WF-10 can improve immunosuppression by conventional drugs. Thus, while cyclosporine A alone had no significant effect on cytotoxicity of CTLs, a combination of cyclosporine A and WF-10 blocked target-cell killing synergistically. Together, our findings suggest that WF-10 - either alone or in combination with conventional immunosuppressive drugs - may be efficient to control progression of diseases, in which CTLs are crucially involved.

  13. Active optical zoom system

    DOEpatents

    Wick, David V.

    2005-12-20

    An active optical zoom system changes the magnification (or effective focal length) of an optical imaging system by utilizing two or more active optics in a conventional optical system. The system can create relatively large changes in system magnification with very small changes in the focal lengths of individual active elements by leveraging the optical power of the conventional optical elements (e.g., passive lenses and mirrors) surrounding the active optics. The active optics serve primarily as variable focal-length lenses or mirrors, although adding other aberrations enables increased utility. The active optics can either be LC SLMs, used in a transmissive optical zoom system, or DMs, used in a reflective optical zoom system. By appropriately designing the optical system, the variable focal-length lenses or mirrors can provide the flexibility necessary to change the overall system focal length (i.e., effective focal length), and therefore magnification, that is normally accomplished with mechanical motion in conventional zoom lenses. The active optics can provide additional flexibility by allowing magnification to occur anywhere within the FOV of the system, not just on-axis as in a conventional system.

  14. Emotionally Intense Science Activities

    NASA Astrophysics Data System (ADS)

    King, Donna; Ritchie, Stephen; Sandhu, Maryam; Henderson, Senka

    2015-08-01

    Science activities that evoke positive emotional responses make a difference to students' emotional experience of science. In this study, we explored 8th Grade students' discrete emotions expressed during science activities in a unit on Energy. Multiple data sources including classroom videos, interviews and emotion diaries completed at the end of each lesson were analysed to identify individual student's emotions. Results from two representative students are presented as case studies. Using a theoretical perspective drawn from theories of emotions founded in sociology, two assertions emerged. First, during the demonstration activity, students experienced the emotions of wonder and surprise; second, during a laboratory activity, students experienced the intense positive emotions of happiness/joy. Characteristics of these activities that contributed to students' positive experiences are highlighted. The study found that choosing activities that evoked strong positive emotional experiences, focused students' attention on the phenomenon they were learning, and the activities were recalled positively. Furthermore, such positive experiences may contribute to students' interest and engagement in science and longer term memorability. Finally, implications for science teachers and pre-service teacher education are suggested.

  15. List 9 - Active CERCLIS Sites:

    EPA Pesticide Factsheets

    The List 9 displays the sequence of activities undertaken at active CERCLIS sites. An active site is one at which site assessment, removal, remedial, enforcement, cost recovery, or oversight activities are being planned or conducted.

  16. THE ACTIVE CENTAURS

    SciTech Connect

    Jewitt, David

    2009-05-15

    The Centaurs are recent escapees from the Kuiper Belt that are destined either to meet fiery oblivion in the hot inner regions of the solar system or to be ejected to the interstellar medium by gravitational scattering from the giant planets. Dynamically evolved Centaurs, when captured by Jupiter and close enough to the Sun for near-surface water ice to sublimate, are conventionally labeled as 'short-period' (specifically, Jupiter-family) comets. Remarkably, some Centaurs show comet-like activity even when far beyond the orbit of Jupiter, suggesting mass loss driven by a process other than the sublimation of water ice. We observed a sample of 23 Centaurs and found nine to be active, with mass-loss rates measured from several kg s{sup -1} to several tonnes s{sup -1}. Considered as a group, we find that the 'active Centaurs' in our sample have perihelia smaller than the inactive Centaurs (median 5.9 AU versus 8.7 AU), and smaller than the median perihelion distance computed for all known Centaurs (12.4 AU). This suggests that their activity is thermally driven. We consider several possibilities for the origin of the mass loss from the active Centaurs. Most are too cold for activity at the observed levels to originate via the sublimation of crystalline water ice. Solid carbon monoxide and carbon dioxide have the opposite problem: they are so volatile that they should drive activity in Centaurs at much larger distances than observed. We consider the possibility that activity in the Centaurs is triggered by the conversion of amorphous ice into the crystalline form accompanied by the release of trapped gases, including carbon monoxide. By imposing the condition that crystallization should occur when the crystallization time is shorter than the orbital period we find a qualitative match to the perihelion distribution of the active Centaurs and conclude that the data are consistent with the hypothesis that the Centaurs contain amorphous ice.

  17. Physics of solar activity

    NASA Technical Reports Server (NTRS)

    Sturrock, Peter A.

    1993-01-01

    The aim of the research activity was to increase our understanding of solar activity through data analysis, theoretical analysis, and computer modeling. Because the research subjects were diverse and many researchers were supported by this grant, a select few key areas of research are described in detail. Areas of research include: (1) energy storage and force-free magnetic field; (2) energy release and particle acceleration; (3) radiation by nonthermal electrons; (4) coronal loops; (5) flare classification; (6) longitude distributions of flares; (7) periodicities detected in the solar activity; (8) coronal heating and related problems; and (9) plasma processes.

  18. Algorithm-development activities

    NASA Technical Reports Server (NTRS)

    Carder, Kendall L.

    1994-01-01

    The task of algorithm-development activities at USF continues. The algorithm for determining chlorophyll alpha concentration, (Chl alpha) and gelbstoff absorption coefficient for SeaWiFS and MODIS-N radiance data is our current priority.

  19. MARIHUANA ACTIVITY OF CANNABINOL.

    PubMed

    Loewe, S

    1945-12-14

    Cannabinol, generally believed to be an inert component of hemp oil, is shown to have marihuana activity. The significance of this observation with regard to the relationship between structure and mamactivity in the class of cannabinols is discussed.

  20. Balance Food and Activity

    MedlinePlus

    ... eNewsletters Calendar Balance Food and Activity What is Energy Balance? Energy is another word for "calories." Your ... adults, fewer calories are needed at older ages. Energy Balance in Real Life Think of it as ...

  1. Activities in Teaching Weather

    ERIC Educational Resources Information Center

    Tonn, Martin

    1977-01-01

    Presented is a unit composed of activities for teaching weather. Topics include cloud types and formation, simple weather instruments, and the weather station. Illustrations include a weather chart and instruments. A bibliography is given. (MA)

  2. Extravehicular activity technology discipline

    NASA Technical Reports Server (NTRS)

    Webbon, Bruce W.

    1990-01-01

    Viewgraphs on extravehicular activity technology discipline for Space Station Freedom are presented. Topics covered include: extravehicular mobility unit; airlock and EMU support equipment; tools, mobility aids, and workstations; and telerobotic work aids interfaces.

  3. French space activities

    NASA Technical Reports Server (NTRS)

    Blanc, R.

    1982-01-01

    The four main points of research and development of space programs by France are explained. The National Center of Space Studies is discussed, listing the missions of the Center and describing the activities of the staff.

  4. Active Fire Mapping Program

    MedlinePlus

    Active Fire Mapping Program Current Large Incidents (Home) New Large Incidents Fire Detection Maps MODIS Satellite Imagery VIIRS Satellite Imagery Fire Detection GIS Data Fire Data in Google Earth ...

  5. ERLN Activities Details

    EPA Pesticide Factsheets

    Environmental Response Laboratory Network activities include the All Hazard Receipt Facility and Screening Protocol, standardizing chemical methods, Chemical Warfare Agent Fixed Laboratory Pilot Project, microbial efforts, and WLA response plan.

  6. The Activity Centre.

    ERIC Educational Resources Information Center

    Australian Mathematics Teacher, 1989

    1989-01-01

    Presents four examples on arithmetic mean and harmonic mean. Provides solution of each of the examples and instructional activities related to the examples. Lists eight references on mathematical problem solving. (YP)

  7. Active at Any Size

    MedlinePlus

    ... a row. Your muscles need time to recover. Mind and body exercise Your local hospital or fitness, ... can be viewed at www.ClinicalTrials.gov . Additional Reading Tips to Help You Get Active Identifies and ...

  8. Exercise and activity - children

    MedlinePlus

    ... and most other organized sports (such as soccer, swimming, and dancing) Younger children cannot stick with the ... your child's preferences and abilities. Individual activities include swimming, running, skiing, or biking. Group sports are another ...

  9. Active terahertz metamaterials

    SciTech Connect

    Chen, Hou-tong

    2009-01-01

    We demonstrate planar terahertz metamaterial devices enabling actively controllable transmission amplitude, phase, or frequency at room temperature via carrier depletion or photoexcitation in the semiconductor substrate or in semiconductor materials incorporated into the metamaterial structure.

  10. Enrichment Activities for Geometry.

    ERIC Educational Resources Information Center

    Usiskin, Zalman

    1983-01-01

    Enrichment activities that teach about geometry as they instruct in geometry are given for some significant topics. The facets of geometry included are tessellations, round robin tournaments, geometric theorems on triangles, and connections between geometry and complex numbers. (MNS)

  11. Interactive Design Activism

    NASA Astrophysics Data System (ADS)

    Goulev, Petar; Farrer, Joan

    The following sections are included: * Introduction * Computers and Human Well-being * To Fuzzy or Yes (No)! * Interactive Design Activism * Sensing the Sun * Personalised Public Health Advice * Modifying Human Behaviour * Transdisciplinarity, Knowledge Transfer and Multi-domain

  12. Island Watershed Activity.

    ERIC Educational Resources Information Center

    Benson, Rod

    2003-01-01

    Describes a 90-minute "Island Watershed" activity to help earth science students understand the concept of the water cycle. Introduces a surface waters unit appropriate for students in grades 7-10. Includes watershed project guidelines. (Author/KHR)

  13. Active Limiters For Photodetectors

    NASA Technical Reports Server (NTRS)

    Katz, Joseph; Cheng, Li-Jen

    1990-01-01

    Active or "smart" electro-optical shutters proposed for protection of photodetectors, imaging devices, and other sensitive optical or optoelectronic elements. Responds rapidly and automatically to increase in illumination above prescribed level.

  14. Math Lab Activities

    ERIC Educational Resources Information Center

    Brumbaugh, Douglas K.; Hynes, Michael C.

    1974-01-01

    The goals, objects, materials and grade levels are specified in this description of a laboratory activity involving analytic geometry concepts. Students mark out bicycle gymkhana courses in which directions to participants are given by Cartesian coordinates. (JP)

  15. Low activation ferritic alloys

    DOEpatents

    Gelles, David S.; Ghoniem, Nasr M.; Powell, Roger W.

    1986-01-01

    Low activation ferritic alloys, specifically bainitic and martensitic stainless steels, are described for use in the production of structural components for nuclear fusion reactors. They are designed specifically to achieve low activation characteristics suitable for efficient waste disposal. The alloys essentially exclude molybdenum, nickel, nitrogen and niobium. Strength is achieved by substituting vanadium, tungsten, and/or tantalum in place of the usual molybdenum content in such alloys.

  16. Low activation ferritic alloys

    DOEpatents

    Gelles, D.S.; Ghoniem, N.M.; Powell, R.W.

    1985-02-07

    Low activation ferritic alloys, specifically bainitic and martensitic stainless steels, are described for use in the production of structural components for nuclear fusion reactors. They are designed specifically to achieve low activation characteristics suitable for efficient waste disposal. The alloys essentially exclude molybdenum, nickel, nitrogen and niobium. Strength is achieved by substituting vanadium, tungsten, and/or tantalum in place of the usual molybdenum content in such alloys.

  17. RAVEN Quality Assurance Activities

    SciTech Connect

    Cogliati, Joshua Joseph

    2015-09-01

    This report discusses the quality assurance activities needed to raise the Quality Level of Risk Analysis in a Virtual Environment (RAVEN) from Quality Level 3 to Quality Level 2. This report also describes the general RAVEN quality assurance activities. For improving the quality, reviews of code changes have been instituted, more parts of testing have been automated, and improved packaging has been created. For upgrading the quality level, requirements have been created and the workflow has been improved.

  18. Activated partial thromboplastin time.

    PubMed

    Ignjatovic, Vera

    2013-01-01

    Activated partial thromboplastin time (APTT) is a commonly used coagulation assay that is easy to perform, is affordable, and is therefore performed in most coagulation laboratories, both clinical and research, worldwide. The APTT is based on the principle that in citrated plasma, the addition of a platelet substitute, factor XII activator, and CaCl2 allows for formation of a stable clot. The time required for the formation of a stable clot is recorded in seconds and represents the actual APTT result.

  19. Active aperture phased arrays

    NASA Astrophysics Data System (ADS)

    Shenoy, R. P.

    1989-04-01

    Developments towards the realization of active aperture phased arrays are reviewed. The technology and cost aspects of the power amplifier and phase shifter subsystems are discussed. Consideration is given to research concerning T/R modules, MESFETs, side lobe control, beam steering, optical control techniques, and printed circuit antennas. Methods for configuring the array are examined, focusing on the tile and brick configurations. It is found that there is no technological impediment for introducing active aperture phased arrays.

  20. Intercreativity: Mapping Online Activism

    NASA Astrophysics Data System (ADS)

    Meikle, Graham

    How do activists use the Internet? This article maps a wide range of activist practice and research by applying and developing Tim Berners-Lee's concept of ‘intercreativity' (1999). It identifies four dimensions of Net activism: intercreative texts, tactics, strategies and networks. It develops these through examples of manifestations of Net activism around one cluster of issues: support campaigns for refugees and asylum seekers.

  1. Effects of dietary supplementation with an expressed fusion peptide bovine lactoferricin-lactoferrampin on performance, immune function and intestinal mucosal morphology in piglets weaned at age 21 d.

    PubMed

    Tang, Zhiru; Yin, Yulong; Zhang, Youming; Huang, Ruilin; Sun, Zhihong; Li, Tiejun; Chu, Wuying; Kong, Xiangfeng; Li, Lili; Geng, Meimei; Tu, Qiang

    2009-04-01

    Lactoferrin has antimicrobial activity associated with peptide fragments lactoferricin (LFC) and lactoferrampin (LFA) released on digestion. These two fragments have been expressed in Photorhabdus luminescens as a fusion peptide linked to protein cipB. The construct cipB-LFC-LFA was tested as an alternative to antimicrobial growth promoters in pig production. Sixty piglets with an average live body weight of 5.42 (sem 0.59) kg were challenged with enterotoxigenic Escherichia coli and randomly assigned to four treatment groups fed a maize-soyabean meal diet containing either no addition (C), cipB at 100 mg/kg (C+B), cipB-LFC-LFA at 100 mg/kg (C+L) or colistin sulfate at 100 mg/kg (C+CS) for 3 weeks. Compared with C, dietary supplementation with C+L for 3 weeks increased daily weight gain by 21 %, increased recovery from diarrhoea, enhanced serum glutathione peroxidase (GPx), peroxidase (POD) and total antioxidant content (T-AOC), liver GPx, POD, superoxide dismutase and T-AOC, Fe, total Fe-binding capacity, IgA, IgG and IgM levels (P < 0.05), decreased the concentration of E. coli in the ileum, caecum and colon (P < 0.05), increased the concentration of lactobacilli and bifidobacteria in the ileum, caecum and colon (P < 0.05), and promoted development of the villus-crypt architecture of the small intestine. Growth performance was similar between C+L- and C+CS-supplemented pigs. The present results indicate that LFC-LFA is an effective alternative to the feed antibiotic CS for enhancing growth performance in piglets weaned at age 21 d.

  2. ABB: active bandwidth broker

    NASA Astrophysics Data System (ADS)

    Wong, Kason; Law, Eddie

    2001-07-01

    In this paper, we shall discuss a novel design on the policy-based management for the Internet. This design deploys the concept of active networking. As opposed to the traditional network design, active network empowers network node with the ability to manipulate data and program code in packets, and configure the network properties according to the needs of different applications. The policy-based management can control network routers in order to realize end-to-end Quality of Service (QoS), such as differentiated and integrated services, across the Internet. For the moment, the Internet Engineering Task Force (IETF) has defined the framework of the policy-based management. It employs a simple client/server model that uses Common Open Policy Service (COPS) protocol to facilitate policy management and control. Our design of Active Bandwidth Broker (ABB) belongs to an active application. Our goals are to distribute centralized workload of the policy-based management over multiple active nodes in the active networks, introduce mobility of the bandwidth brokers, and allows load sharing to the policy-based management. This results a network-wide intelligent, highly available, and consistent QoS control that allows performance protection for voice, video and Internet business application while reducing costs for growing networks.

  3. Rheology of Active Gels

    NASA Astrophysics Data System (ADS)

    Chen, Daniel

    2015-03-01

    Active networks drive a diverse range of critical processes ranging from motility to division in living cells, yet a full picture of their rheological capabilities in non-cellular contexts is still emerging, e.g., How does the rheological response of a network capable of remodeling under internally-generated stresses differ from that of a passive biopolymer network? In order to address this and other basic questions, we have engineered an active gel composed of microtubules, bidirectional kinesin motors, and molecular depletant that self-organizes into a highly dynamic network of active bundles. The network continually remodels itself under ATP-tunable cycles of extension, buckling, fracturing, and self-healing. Using confocal rheometry we have simultaneously characterized the network's linear and non-linear rheological responses to shear deformation along with its dynamic morphology. We find several surprising and unique material properties for these active gels; most notably, rheological cloaking, the ability of the active gel to drive large-scale fluid mixing over several orders of flow magnitude while maintaining an invariant, solid-like rheological profile and spontaneous flow under confinement, the ability to exert micro-Newton forces to drive persistent directed motion of the rheometer tool. Taken together, these results and others to be discussed highlight the rich stress-structure-dynamics relationships in this class of biologically-derived active gels.

  4. Antimicrobial activity of flavonoids.

    PubMed

    Cushnie, T P Tim; Lamb, Andrew J

    2005-11-01

    Flavonoids are ubiquitous in photosynthesising cells and are commonly found in fruit, vegetables, nuts, seeds, stems, flowers, tea, wine, propolis and honey. For centuries, preparations containing these compounds as the principal physiologically active constituents have been used to treat human diseases. Increasingly, this class of natural products is becoming the subject of anti-infective research, and many groups have isolated and identified the structures of flavonoids possessing antifungal, antiviral and antibacterial activity. Moreover, several groups have demonstrated synergy between active flavonoids as well as between flavonoids and existing chemotherapeutics. Reports of activity in the field of antibacterial flavonoid research are widely conflicting, probably owing to inter- and intra-assay variation in susceptibility testing. However, several high-quality investigations have examined the relationship between flavonoid structure and antibacterial activity and these are in close agreement. In addition, numerous research groups have sought to elucidate the antibacterial mechanisms of action of selected flavonoids. The activity of quercetin, for example, has been at least partially attributed to inhibition of DNA gyrase. It has also been proposed that sophoraflavone G and (-)-epigallocatechin gallate inhibit cytoplasmic membrane function, and that licochalcones A and C inhibit energy metabolism. Other flavonoids whose mechanisms of action have been investigated include robinetin, myricetin, apigenin, rutin, galangin, 2,4,2'-trihydroxy-5'-methylchalcone and lonchocarpol A. These compounds represent novel leads, and future studies may allow the development of a pharmacologically acceptable antimicrobial agent or class of agents.

  5. Phytase activity in lichens.

    PubMed

    Higgins, Niall F; Crittenden, Peter D

    2015-10-01

    Phytase activity was investigated in 13 lichen species using a novel assay method. The work tested the hypothesis that phytase is a component of the suite of surface-bound lichen enzymes that hydrolyse simple organic forms of phosphorus (P) and nitrogen (N) deposited onto the thallus surface. Hydrolysis of inositol hexaphosphate (InsP6 , the substrate for phytase) and appearance of lower-order inositol phosphates (InsP5 -InsP1 ), the hydrolysis products, were measured by ion chromatography. Phytase activity in Evernia prunastri was compared among locations with contrasting rates of N deposition. Phytase activity was readily measurable in epiphytic lichens (e.g. 11.3 μmol InsP6 hydrolysed g(-1)  h(-1) in Bryoria fuscescens) but low in two terricolous species tested (Cladonia portentosa and Peltigera membranacea). Phytase and phosphomonoesterase activities were positively correlated amongst species. In E. prunastri both enzyme activities were promoted by N enrichment and phytase activity was readily released into thallus washings. InsP6 was not detected in tree canopy throughfall but was present in pollen leachate. Capacity to hydrolyse InsP6 appears widespread amongst lichens potentially promoting P capture from atmospheric deposits and plant leachates, and P cycling in forest canopies. The enzyme assay used here might find wider application in studies on plant root-fungal-soil systems.

  6. Degradation of Kidney and Psoas Muscle Proteins as Indicators of Post-Mortem Interval in a Rat Model, with Use of Lateral Flow Technology

    PubMed Central

    Lee, Dong-Gi; Yang, Kyeong Eun; Hwang, Jeong Won; Kang, Hwan-Soo; Lee, Seung-Yeul; Choi, Seoyeon; Shin, Joonchul; Jang, Ik-Soon; An, Hyun Joo; Chung, Heesun; Jung, Hyo-Il; Choi, Jong-Soon

    2016-01-01

    We investigated potential protein markers of post-mortem interval (PMI) using rat kidney and psoas muscle. Tissue samples were taken at 12 h intervals for up to 96 h after death by suffocation. Expression levels of eight soluble proteins were analyzed by Western blotting. Degradation patterns of selected proteins were clearly divided into three groups: short-term, mid-term, and long-term PMI markers based on the half maximum intensity of intact protein expression. In kidney, glycogen synthase (GS) and glycogen synthase kinase-3β were degraded completely within 48 h making them short-term PMI markers. AMP-activated protein kinase α, caspase 3 and GS were short-term PMI markers in psoas muscle. Glyceraldehyde 3-phosphate dehydrogenase (GAPDH) was a mid-term PMI marker in both tissues. Expression levels of the typical long-term PMI markers, p53 and β-catenin, were constant for at least 96 h post-mortem in both tissues. The degradation patterns of GS and caspase-3 were verified by immunohistochemistry in both tissues. GAPDH was chosen as a test PMI protein to perform a lateral flow assay (LFA). The presence of recombinant GAPDH was clearly detected in LFA and quantified in a concentration-dependent manner. These results suggest that LFA might be used to estimate PMI at a crime scene. PMID:27552165

  7. Two distinct factors interact with the promoter regions of several liver-specific genes.

    PubMed Central

    Hardon, E M; Frain, M; Paonessa, G; Cortese, R

    1988-01-01

    A segment of the human alpha 1-antitrypsin (alpha 1AT) 5'-flanking region comprising nucleotides -137 to -37 from the start of transcription is sufficient to drive liver-specific transcription from the homologous alpha 1AT promoter and from the heterologous SV40 promoter. In this paper we characterize two proteins, LF-A1 and LF-B1, whose ability to bind wild-type and mutant alpha 1AT promoter segments correlates with the ability of these segments to activate transcription in vivo. DNase I protection and methylation interference analysis reveals that LF-A1 recognizes sequences present in the regulatory region of the human alpha 1-antitrypsin, apolipoprotein A1 and haptoglobin-related genes. These sequences share a common 5' TGG/A A/C CC 3' motif. LF-B1 binds to the palindrome 5' TGGTTAAT/ATTCACCA 3' which is present in the human alpha 1-antitrypsin gene between positions -78 and -62 from the start of transcription. LF-B1 also recognizes a related sequence present in the human albumin gene between -66 and -50. These results suggest that LF-A1 and LF-B1 are common positive trans-acting factors which are required for the expression of several genes in the hepatocyte. Images PMID:2844524

  8. Affinity purification of the voltage-sensitive sodium channel from electroplax with resins selective for sialic acid

    SciTech Connect

    James, W.M.; Emerick, M.C.; Agnew, W.S. )

    1989-07-11

    The voltage-sensitive sodium channel present in the eel (Electrophorus electricus) has an unusually high content of sialic acid, including {alpha}-(2{yields}8)-linked polysialic acid, not found in other electroplax membrane glycopeptides. Lectins from Limax flavus (LFA) and wheat germ (WGA) proved the most effective of 11 lectin resins tried. The most selective resin was prepared from IgM antibodies against Neisseria meningitidis {alpha}-(2{yields}8)-polysialic acid which were affinity purified and coupled to Sepharose 4B. The sodium channel was found to bind to WGA, LFA, and IgM resins and was readily eluted with the appropriate soluble carbohydrates. Experiments with LFA and IgM resins demonstrated binding and unbinding rates and displacement kinetics, which suggest highly specific binding at multiple sites on the sodium channel protein. In preparative-scale purification of protein previously fractionated by anion-exchange chromatography, without stabilizing TTX, high yields were reproducibly obtained. Further, when detergent extracts were prepared from electroplax membranes fractionated by low-speed sedimentation, a single step over the IgM resin provided a 70-fold purification, yielding specific activities of 3,200 pmol of ({sup 3}H)TTX-binding sites/mg of protein and a single polypeptide of {approximately}285,000 Da on SDS-acrylamide gels. No small peptides were observed after this 5-h isolation. The authors describe a cation-dependent stabilization with millimolar levels of monovalent and micromolar levels of divalent species.

  9. Affinity purification of the voltage-sensitive sodium channel from electroplax with resins selective for sialic acid.

    PubMed

    James, W M; Emerick, M C; Agnew, W S

    1989-07-11

    The voltage-sensitive sodium channel present in the eel (Electrophorus electricus) has an unusually high content of sialic acid, including alpha-(2----8)-linked polysialic acid, not found in other electroplax membrane glycopeptides. Lectins from Limax flavus (LFA) and wheat germ (WGA) proved the most effective of 11 lectin resins tried. The most selective resin was prepared from IgM antibodies against Neisseria meningitidis alpha-(2----8)-polysialic acid which were affinity purified and coupled to Sepharose 4B. The sodium channel was found to bind to WGA, LFA, and IgM resins and was readily eluted with the appropriate soluble carbohydrates. Experiments with LFA and IgM resins demonstrated binding and unbinding rates and displacement kinetics, which suggest highly specific binding at multiple sites on the sodium channel protein. In preparative-scale purification of protein previously fractionated by anion-exchange chromatography, without stabilizing TTX, high yields were reproducibly obtained. Further, when detergent extracts were prepared from electroplax membranes fractionated by low-speed sedimentation, a single step over the IgM resin provided a 70-fold purification, yielding specific activities of 3200 pmol of [3H]TTX-binding sites/mg of protein and a single polypeptide of approximately 285,000 Da on SDS-acrylamide gels. No small peptides were observed after this 5-h isolation. We further describe a cation-dependent stabilization with millimolar levels of monovalent and micromolar levels of divalent species.

  10. T cell activation.

    PubMed

    Smith-Garvin, Jennifer E; Koretzky, Gary A; Jordan, Martha S

    2009-01-01

    This year marks the 25th anniversary of the first Annual Review of Immunology article to describe features of the T cell antigen receptor (TCR). In celebration of this anniversary, we begin with a brief introduction outlining the chronology of the earliest studies that established the basic paradigm for how the engaged TCR transduces its signals. This review continues with a description of the current state of our understanding of TCR signaling, as well as a summary of recent findings examining other key aspects of T cell activation, including cross talk between the TCR and integrins, the role of costimulatory molecules, and how signals may negatively regulate T cell function.Acronyms and DefinitionsAdapter protein: cellular protein that functions to bridge molecular interactions via characteristic domains able to mediate protein/protein or protein/lipid interactions Costimulation: signals delivered to T cells by cell surface receptors other than the TCR itself that potentiate T cell activation cSMAC: central supramolecular activation cluster Immunoreceptor tyrosine-based activation motif (ITAM): a short peptide sequence in the cytoplasmic tails of key surface receptors on hematopoietic cells that is characterized by tyrosine residues that are phosphorylated by Src family PTKs, enabling the ITAM to recruit activated Syk family kinases Inside-out signaling: signals initiated by engagement of immunoreceptors that lead to conformational changes and clustering of integrins, thereby increasing the affinity and avidity of the integrins for their ligands NFAT: nuclear factor of activated T cells PI3K: phosphoinositide 3-kinase PKC: protein kinase C PLC: phospholipase C pMHC: peptide major histocompatibility complex (MHC) complex pSMAC: peripheral supramolecular activation cluster PTK: protein tyrosine kinase Signal transduction: biochemical events linking surface receptor engagement to cellular responses TCR: T cell antigen receptor

  11. Sirtuin activators and inhibitors

    PubMed Central

    Villalba, José M.; Alcaín, Francisco J.

    2012-01-01

    Sirtuins 1-7 (SIRT1-7) belong to the third class of deacetylase enzymes, which are dependent on NAD+ for activity. Sirtuins activity is linked to gene repression, metabolic control, apoptosis and cell survival, DNA repair, development, inflammation, neuroprotection and healthy aging. Because sirtuins modulation could have beneficial effects on human diseases there is a growing interest in the discovery of small molecules modifying their activity. We review here those compounds known to activate or inhibit sirtuins, discussing the data that support the use of sirtuin-based therapies. Almost all sirtuin activators have been described only for SIRT1. Resveratrol is a natural compound which activates SIRT1, and may help in the treatment or prevention of obesity, and in preventing tumorigenesis and the aging-related decline in heart function and neuronal loss. Due to its poor bioavailability, reformulated versions of resveratrol with improved bioavailability have been developed (resVida, Longevinex®, SRT501). Molecules that are structurally unrelated to resveratrol (SRT1720, SRT2104, SRT2379, among others) have been also developed to stimulate sirtuin activities more potently than resveratrol. Sirtuin inhibitors with a wide range of core structures have been identified for SIRT1, SIRT2, SIRT3 and SIRT5 (splitomicin, sirtinol, AGK2, cambinol, suramin, tenovin, salermide, among others). SIRT1 inhibition has been proposed in the treatment of cancer, immunodeficiency virus infections, Fragile X mental retardation syndrome and for preventing or treating parasitic diseases, whereas SIRT2 inhibitors might be useful for the treatment of cancer and neurodegenerative diseases. PMID:22730114

  12. Antimutagenic activity of spearmint.

    PubMed

    Yu, Tian-Wei; Xu, Meirong; Dashwood, Roderick H

    2004-01-01

    The antimutagenic activity of spearmint (Mentha spicata), a popular food flavoring agent, was studied in the Salmonella assay. Spearmint leaves were brewed in hot water for 5 min at concentrations up to 5% (w/v), and the water extracts were tested against the direct-acting mutagens 4-nitro-1,2-phenylenediamine (NPD) and 2-hydroxyamino-3-methyl-3H-imidazo[4,5-f]quinoline (N-OH-IQ) using Salmonella typhimurium strain TA98. Nontoxic concentrations of spearmint extract inhibited the mutagenic activity of N-OH-IQ in a concentration-dependent fashion, but had no effect against NPD. These experiments by design focused on the water extract consumed commonly as an herbal tea, but chloroform and methanol extracts of spearmint also possessed antimutagenic activity against N-OH-IQ. Water extract of spearmint inhibited the mutagenic activity of the parent compound, 2-amino-3-methyl-3H-imidazo[4,5-f]quinoline (IQ), in the presence of rat liver S9; however, the concentration for 50% inhibition (IC50) against IQ was approximately 10-fold higher than in assays with N-OH-IQ minus S9. At concentrations similar to those used in the Salmonella assays, spearmint extract inhibited two of the major enzymes that play a role in the metabolic activation of IQ, namely, cytochromes P4501A1 and 1A2, based on ethoxyresorufin O-deethylase and methoxyresorufin O-demethylase assays in vitro. In vivo, rats were given spearmint water extract (2%; w/v) as the sole source of drinking fluid before, during, and after 2-week treatment with IQ; colonic aberrant crypt foci were inhibited significantly at 8 weeks (P < 0.05, compared with rats given IQ alone). Collectively, these findings suggest that spearmint tea protects against IQ and possibly other heterocyclic amines through inhibition of carcinogen activation and via direct effects on the activated metabolite(s).

  13. [Inflammasome: activation mechanisms].

    PubMed

    Suárez, Raibel; Buelvas, Neudo

    2015-03-01

    Inflammation is a rapid biologic response of the immune system in vascular tissues, directed to eliminate stimuli capable of causing damage and begin the process of repair. The macromolecular complexes known as "inflammasomes" are formed by a receptor, either NOD (NLR) or ALR, the receptor absent in melanoma 2 (AIM2). In addition, the inflammasome is formed by the speck-like protein associated to apoptosis (ASC) and procaspase-1, that may be activated by variations in the ionic and intracellular and extracellular ATP concentrations; and the loss of stabilization of the fagolisosomme by internalization of insoluble crystals and redox mechanisms. As a result, there is activation of the molecular platform and the processing of inflammatory prointerleukins to their active forms. There are two modalities of activation of the inflammasome: canonical and non-canonical, both capable of generating effector responses. Recent data associate NLRP 3, IL-1β and IL-18 in the pathogenesis of a variety of diseases, including atherosclerosis, type II diabetes, hyperhomocysteinemia, gout, malaria and hypertension. The inflammasome cascade is emerging as a new chemotherapeutic target in these diseases. In this review we shall discuss the mechanisms of activation and regulation of the inflammasome that stimulate, modulate and resolve inflammation.

  14. Chromatin as active matter

    NASA Astrophysics Data System (ADS)

    Agrawal, Ankit; Ganai, Nirmalendu; Sengupta, Surajit; Menon, Gautam I.

    2017-01-01

    Active matter models describe a number of biophysical phenomena at the cell and tissue scale. Such models explore the macroscopic consequences of driving specific soft condensed matter systems of biological relevance out of equilibrium through ‘active’ processes. Here, we describe how active matter models can be used to study the large-scale properties of chromosomes contained within the nuclei of human cells in interphase. We show that polymer models for chromosomes that incorporate inhomogeneous activity reproduce many general, yet little understood, features of large-scale nuclear architecture. These include: (i) the spatial separation of gene-rich, low-density euchromatin, predominantly found towards the centre of the nucleus, vis a vis. gene-poor, denser heterochromatin, typically enriched in proximity to the nuclear periphery, (ii) the differential positioning of individual gene-rich and gene-poor chromosomes, (iii) the formation of chromosome territories, as well as (iv), the weak size-dependence of the positions of individual chromosome centres-of-mass relative to the nuclear centre that is seen in some cell types. Such structuring is induced purely by the combination of activity and confinement and is absent in thermal equilibrium. We systematically explore active matter models for chromosomes, discussing how our model can be generalized to study variations in chromosome positioning across different cell types. The approach and model we outline here represent a preliminary attempt towards a quantitative, first-principles description of the large-scale architecture of the cell nucleus.

  15. Active flows on trees

    NASA Astrophysics Data System (ADS)

    Forrow, Aden; Woodhouse, Francis G.; Dunkel, Jörn

    2016-11-01

    Coherent, large scale dynamics in many nonequilibrium physical, biological, or information transport networks are driven by small-scale local energy input. We introduce and explore a generic model for compressible active flows on tree networks. In contrast to thermally-driven systems, active friction selects discrete states with only a small number of oscillation modes activated at distinct fixed amplitudes. This state selection can interact with graph topology to produce different localized dynamical time scales in separate regions of large networks. Using perturbation theory, we systematically predict the stationary states of noisy networks. Our analytical predictions agree well with a Bayesian state estimation based on a hidden Markov model applied to simulated time series data on binary trees. While the number of stable states per tree scales exponentially with the number of edges, the mean number of activated modes in each state averages 1 / 4 the number of edges. More broadly, these results suggest that the macroscopic response of active networks, from actin-myosin networks in cells to flow networks in Physarum polycephalum, can be dominated by a few select modes.

  16. Interpreting EEG alpha activity.

    PubMed

    Bazanova, O M; Vernon, D

    2014-07-01

    Exploring EEG alpha oscillations has generated considerable interest, in particular with regards to the role they play in cognitive, psychomotor, psycho-emotional and physiological aspects of human life. However, there is no clearly agreed upon definition of what constitutes 'alpha activity' or which of the many indices should be used to characterize it. To address these issues this review attempts to delineate EEG alpha-activity, its physical, molecular and morphological nature, and examine the following indices: (1) the individual alpha peak frequency; (2) activation magnitude, as measured by alpha amplitude suppression across the individual alpha bandwidth in response to eyes opening, and (3) alpha "auto-rhythmicity" indices: which include intra-spindle amplitude variability, spindle length and steepness. Throughout, the article offers a number of suggestions regarding the mechanism(s) of alpha activity related to inter and intra-individual variability. In addition, it provides some insights into the various psychophysiological indices of alpha activity and highlights their role in optimal functioning and behavior.

  17. Active thermal cloak

    NASA Astrophysics Data System (ADS)

    Nguyen, Dang Minh; Xu, Hongyi; Zhang, Youming; Zhang, Baile

    2015-09-01

    Thermal cloaking, as an ultimate thermal "illusion" phenomenon, is the result of advanced heat manipulation with thermal metamaterials—heat can be guided around a hidden object smoothly without disturbing the ambient thermal environment. However, all previous thermal metamaterial cloaks were passive devices, lacking the functionality of switching on/off and the flexibility of changing geometries. In this letter, we report an active thermal cloaking device that is controllable. Different from previous thermal cloaking approaches, this thermal cloak adopts active thermoelectric components to "pump" heat from one side to the other side of the hidden object, in a process controlled by input electric voltages. Our work not only incorporates active components in thermal cloaking but also provides controllable functionality in thermal metamaterials that can be used to construct more flexible thermal devices.

  18. Activity Cycles in Stars

    NASA Technical Reports Server (NTRS)

    Hathaway, David H.

    2009-01-01

    Starspots and stellar activity can be detected in other stars using high precision photometric and spectrometric measurements. These observations have provided some surprises (starspots at the poles - sunspots are rarely seen poleward of 40 degrees) but more importantly they reveal behaviors that constrain our models of solar-stellar magnetic dynamos. The observations reveal variations in cycle characteristics that depend upon the stellar structure, convection zone dynamics, and rotation rate. In general, the more rapidly rotating stars are more active. However, for stars like the Sun, some are found to be inactive while nearly identical stars are found to be very active indicating that periods like the Sun's Maunder Minimum (an inactive period from 1645 to 1715) are characteristic of Sun-like stars.

  19. Antimicrobial activity of spices.

    PubMed

    Arora, D S; Kaur, J

    1999-08-01

    Spices have been shown to possess medicinal value, in particular, antimicrobial activity. This study compares the sensitivity of some human pathogenic bacteria and yeasts to various spice extracts and commonly employed chemotherapeutic substances. Of the different spices tested only garlic and clove were found to possess antimicrobial activity. The bactericidal effect of garlic extract was apparent within 1 h of incubation and 93% killing of Staphylococcus epidermidis and Salmonella typhi was achieved within 3 h. Yeasts were totally killed in 1 h by garlic extract but in 5 h with clove. Some bacteria showing resistance to certain antibiotics were sensitive to extracts of both garlic and clove. Greater anti-candidal activity was shown by garlic than by nystatin. Spices might have a great potential to be used as antimicrobial agents.

  20. PRODUCTS OF ACTIVATED LYMPHOCYTES

    PubMed Central

    Sorg, Clemens; Bloom, Barry R.

    1973-01-01

    General methods were developed and applied to the biosynthesis and purification of products of activated lymphocytes available in minute quantities. The activity studied here was the migration inhibitory factor (MIF) produced by purified protein derivative (PPD)- or concanavalin A (Con A)-stimulated lymphocytes obtained from one guinea pig or less. The methods selected yielded results in terms of two chemical parameters characteristic of the molecules involved, namely Kd on Sephadex G-75 and isoionic point, pI, on isoelectric focusing. When supernatants were fractionated on G-75 columns, there were several areas even in control supernatants which produced migration inhibition relative to medium controls. However, in PPD- and Con A-stimulated supernatants, at least one peak of MIF activity was found solely in the stimulated cultures, with a Kd of 0.15. A double-labeling technique was used to characterize the proteins of this peak. Control, unstimulated cultures were labeled with [14C]leucine and stimulated cultures were labeled with [3H]leucine. After mixing the supernatants and G-75 filtration, a major "ratiolabeled" broad peak. i.e. one with increased 3H/14C ratio, was found. When a narrow portion of this peak about Kd 0.15, containing most of the MIF activity, was subjected to analytical isoelectric focusing, all of the label was associated with proteins of lower net charge than albumin. A unique ratiolabeled peak was found in PPD- and Con A-stimulated fractions with a pI of approx. 5.3. A micropreparative isoelectric focusing technique was developed and yielded MIF activity in the same region as the major ratiolabeled peak. Further study will be required to ascertain whether the ratiolabeled protein is MIF. By following the Kd, pI, and 3H/14C labeling ratio, at least 14 products of activated lymphocytes, synthesized either de novo or in increased amounts, could be distinguished. PMID:4688317

  1. Active cleaning technique device

    NASA Technical Reports Server (NTRS)

    Shannon, R. L.; Gillette, R. B.

    1973-01-01

    The objective of this program was to develop a laboratory demonstration model of an active cleaning technique (ACT) device. The principle of this device is based primarily on the technique for removing contaminants from optical surfaces. This active cleaning technique involves exposing contaminated surfaces to a plasma containing atomic oxygen or combinations of other reactive gases. The ACT device laboratory demonstration model incorporates, in addition to plasma cleaning, the means to operate the device as an ion source for sputtering experiments. The overall ACT device includes a plasma generation tube, an ion accelerator, a gas supply system, a RF power supply and a high voltage dc power supply.

  2. Actively coupled optical waveguides

    NASA Astrophysics Data System (ADS)

    Alexeeva, N. V.; Barashenkov, I. V.; Rayanov, K.; Flach, S.

    2014-01-01

    We consider light propagation through a pair of nonlinear optical waveguides with absorption, placed in a medium with power gain. The active medium boosts the in-phase component of the overlapping evanescent fields of the guides, while the nonlinearity of the guides couples it to the damped out-of-phase component creating a feedback loop. As a result, the structure exhibits stable stationary and oscillatory regimes in a wide range of gain-loss ratios. We show that the pair of actively coupled (AC) waveguides can act as a stationary or integrate-and-fire comparator sensitive to tiny differences in their input powers.

  3. MCO Monitoring activity description

    SciTech Connect

    SEXTON, R.A.

    1998-11-09

    Spent Nuclear Fuel remaining from Hanford's N-Reactor operations in the 1970s has been stored under water in the K-Reactor Basins. This fuel will be repackaged, dried and stored in a new facility in the 200E Area. The safety basis for this process of retrieval, drying, and interim storage of the spent fuel has been established. The monitoring of MCOS in dry storage is a currently identified issue in the SNF Project. This plan outlines the key elements of the proposed monitoring activity. Other fuel stored in the K-Reactor Basins, including SPR fuel, will have other monitoring considerations and is not addressed by this activity description.

  4. Inflammasomes and Their Activation

    PubMed Central

    Khare, Sonal; Luc, Nancy; Dorfleutner, Andrea; Stehlik, Christian

    2011-01-01

    The innate immune system relies on the recognition of pathogens by pattern recognition receptors as a first line of defense and to initiate the adaptive immune response. Substantial progress has been made in defining the role of Nod (nucleotide-binding oligimerization domain)-like receptors and AIM2 (absent in melanoma 2) as pattern recognition receptors that activate inflammasomes in macrophages. Inflammasomes are protein platforms essential for the activation of inflammatory caspases and subsequent maturation of their pro-inflammatory cytokine substrates and induction of pyroptosis. This paper summarizes recent developments regarding the function of Nod-like receptors in immunity and disease. PMID:21083527

  5. Activated carbon material

    DOEpatents

    Evans, A. Gary

    1978-01-01

    Activated carbon particles for use as iodine trapping material are impregnated with a mixture of selected iodine and potassium compounds to improve the iodine retention properties of the carbon. The I/K ratio is maintained at less than about 1 and the pH is maintained at above about 8.0. The iodine retention of activated carbon previously treated with or coimpregnated with triethylenediamine can also be improved by this technique. Suitable flame retardants can be added to raise the ignition temperature of the carbon to acceptable standards.

  6. Antibacterial activity of grepafloxacin.

    PubMed

    Wiedemann, B; Heisig, P

    1997-12-01

    Grepafloxacin has an extremely broad spectrum of activity. Its activity against Gram-positive bacteria exceeds that of currently available quinolones. Grepafloxacin-resistant mutants seem to occur less frequently than ciprofloxacin- or ofloxacin-resistant mutants, and the increase in MIC against the former mutants is less than that of the latter. This applies only to the relative differences (in dilution steps); the absolute values are similar. Grepafloxacin kills Gram-positive bacteria at concentrations little above the MIC. Its pharmacodynamic profile against pneumococci is promising, favouring use of this drug for respiratory tract infections.

  7. Active seismic experiment

    NASA Technical Reports Server (NTRS)

    Kovach, R. L.; Watkins, J. S.; Talwani, P.

    1972-01-01

    The Apollo 16 active seismic experiment (ASE) was designed to generate and monitor seismic waves for the study of the lunar near-surface structure. Several seismic energy sources are used: an astronaut-activated thumper device, a mortar package that contains rocket-launched grenades, and the impulse produced by the lunar module ascent. Analysis of some seismic signals recorded by the ASE has provided data concerning the near-surface structure at the Descartes landing site. Two compressional seismic velocities have so far been recognized in the seismic data. The deployment of the ASE is described, and the significant results obtained are discussed.

  8. Space construction activities

    NASA Technical Reports Server (NTRS)

    1991-01-01

    The Center for Space Construction at the University of Colorado at Boulder was established in 1988 as a University Space Engineering Research Center. The mission of the Center is to conduct interdisciplinary engineering research which is critical to the construction of future space structures and systems and to educate students who will have the vision and technical skills to successfully lead future space construction activities. The research activities are currently organized around two central projects: Orbital Construction and Lunar Construction. Summaries of the research projects are included.

  9. Cosmogenic activation of materials

    NASA Astrophysics Data System (ADS)

    Amaré, J.; Beltrán, B.; Capelli, S.; Capozzi, F.; Carmona, J. M.; Cebrián, S.; Cremonesi, O.; García, E.; Irastorza, I. G.; Gómez, H.; Luzón, G.; Martínez, M.; Morales, J.; Ortiz de Solórzano, A.; Pavan, M.; Pobes, C.; Puimedón, J.; Rodríguez, A.; Ruz, J.; Sarsa, M. L.; Torres, L.; Villar, J. A.

    2005-09-01

    The problem of cosmogenic activation produced at sea level in materials typically used in underground experiments looking for rare events is being studied. Several nuclear data libraries have been screened looking for relevant isotope production cross-sections and different codes which can be applied to activation studies have been reviewed. The excitation functions for some problems of interest like production of 60Co and 68Ge in germanium and production of 60Co in tellurium have been obtained taking into account both measurements and calculations and a preliminary estimate of the corresponding rates of production at sea level has been performed.

  10. [Problem Solving Activities.

    ERIC Educational Resources Information Center

    Wisconsin Univ. - Stout, Menomonie. Center for Vocational, Technical and Adult Education.

    The teacher directed problem solving activities package contains 17 units: Future Community Design, Let's Build an Elevator, Let's Construct a Catapult, Let's Design a Recreational Game, Let's Make a Hand Fishing Reel, Let's Make a Wall Hanging, Let's Make a Yo-Yo, Marooned in the Past, Metrication, Mousetrap Vehicles, The Multi System…

  11. [Biological activity of Spirulina].

    PubMed

    Blinkova, L P; Gorobets, O B; Baturo, A P

    2001-01-01

    In this review information of Spirulina platensis (SP), a blue-green alga (photosynthesizing cyanobacterium) having diverse biological activity is presented. Due to high content of highly valuable proteins, indispensable amino acids, vitamins, beta-carotene and other pigments, mineral substances, indispensable fatty acids and polysaccharides, PS has been found suitable for use as bioactive additive. SP produces an immunostimulating effect by enhancing the resistance of humans, mammals, chickens and fish to infections, the capacity of influencing hemopoiesis, stimulating the production of antibodies and cytokines. Under the influence of SP macrophages, T and B cells are activated. SP sulfolipids have proved to be effective against HIV. Preparations obtained from SP biomass have also been found active against herpesvirus, cytomegalovirus, influenza virus, etc. SP extracts are capable in inhibiting cancerogenesis. SP preparations are regarded as functional products contributing to the preservation of the resident intestinal microflora, especially lactic acid bacilli and bifidobacteria, and to a decrease in the level of Candida albicans. The biological activity of SP with respect to microorganisms holds good promise for using these microalgae as components of culture media.

  12. Active Authentication: Beyond Passwords

    DTIC Science & Technology

    2011-11-18

    semantic analysis (how you construct sentences); Forensic authorship Keystroke pattern; Mouse movement Fingerprint ; Iris pattern; Vein...Solutions Physiological Biometrics Sensors tracking the physical attributes of you • DNA • Ear Geometry • Facial Geometry • Fingerprint • Iris...Preview Fingerprint Forensic authorship2 Mouse tracking1 How you behave Physical aspects of you The context you exist in • The Active Authentication

  13. An Active Attraction.

    ERIC Educational Resources Information Center

    Burns, Joseph C.; Buzzelli, Cary

    1992-01-01

    Describes a unit on magnetism that utilizes hands-on activities in which students make hypotheses for discrepant behavior, discover whether a magnet attracts one object through another, measure the strength of magnets, explore levitating paper clips, and play a game dependent on magnetic attraction. (MDH)

  14. Active control system trends

    NASA Technical Reports Server (NTRS)

    Yore, E. E.; Gunderson, D. C.

    1976-01-01

    The active control concepts which achieve the benefit of improved mission performance and lower cost and generate system trends towards improved dynamic performance, more integration, and digital fly by wire mechanization are described. Analytical issues and implementation requirements and tools and approaches developed to address the analytical and implementation issues are briefly discussed.

  15. Arsenic activation neutron detector

    DOEpatents

    Jacobs, Eddy L.

    1981-01-01

    A detector of bursts of neutrons from a deuterium-deuteron reaction includes a quantity of arsenic adjacent a gamma detector such as a scintillator and photomultiplier tube. The arsenic is activated by the 2.5 Mev neutrons to release gamma radiation which is detected to give a quantitative representation of detected neutrons.

  16. Arsenic activation neutron detector

    DOEpatents

    Jacobs, E.L.

    1980-01-28

    A detector of bursts of neutrons from a deuterium-deuteron reaction includes a quantity of arsenic adjacent a gamma detector such as a scintillator and photomultiplier tube. The arsenic is activated by the 2.5-MeV neutrons to release gamma radiation which is detected to give a quantitative representation of detected neutrons.

  17. Earthfest. Activity Book.

    ERIC Educational Resources Information Center

    Weilbacher, Mike

    1991-01-01

    An activity book to help elementary teachers and students explore the environment offers information and questions about spaceships; an ecology primer and poster with questions; information on animal adaptation with poster and questions; ecological and dramatic arts projects; a script for performance; and suggestions to make Earth Day celebrations…

  18. Regional Activities Division. Papers.

    ERIC Educational Resources Information Center

    International Federation of Library Associations, The Hague (Netherlands).

    Papers on library network activities in Canada, the Third World, Japan, Malaysia, Brazil, and Sweden which were presented at the 1982 International Federation of Library Associations (IFLA) conference include: (1) "Canada: A Voluntary and Flexible Network," a review by Guy Sylvestre of the political, social, and economic structures…

  19. Learning Activity Package, Algebra.

    ERIC Educational Resources Information Center

    Evans, Diane

    A set of ten teacher-prepared Learning Activity Packages (LAPs) in beginning algebra and nine in intermediate algebra, these units cover sets, properties of operations, number systems, open expressions, solution sets of equations and inequalities in one and two variables, exponents, factoring and polynomials, relations and functions, radicals,…

  20. Educating for Political Activity

    ERIC Educational Resources Information Center

    Chitty, Clyde

    2010-01-01

    The term "political activity" can be interpreted in a myriad of different ways, but in this paper, it is taken to mean involvement in a variety of campaigns around issues affecting the way we live and the sort of society we want to live in. At a time when support for the main political parties has never been weaker, it is essential that…

  1. Active microwave water equivalence

    NASA Technical Reports Server (NTRS)

    Boyne, H. S.; Ellerbruch, D. A.

    1980-01-01

    Measurements of water equivalence using an active FM-CW microwave system were conducted over the past three years at various sites in Colorado, Wyoming, and California. The measurement method is described. Measurements of water equivalence and stratigraphy are compared with ground truth. A comparison of microwave, federal sampler, and snow pillow measurements at three sites in Colorado is described.

  2. Active Learning Methods

    ERIC Educational Resources Information Center

    Zayapragassarazan, Z.; Kumar, Santosh

    2012-01-01

    Present generation students are primarily active learners with varied learning experiences and lecture courses may not suit all their learning needs. Effective learning involves providing students with a sense of progress and control over their own learning. This requires creating a situation where learners have a chance to try out or test their…

  3. Bonus Activity Book.

    ERIC Educational Resources Information Center

    Learning, 1993

    1993-01-01

    Elementary level activity book presents suggestions for teaching students about endangered and threatened species worldwide. Students learn about what is causing the rapid extinction rate and what needs to be done. They also discover the value of rainforests and why conservationists are fighting to save them. (SM)

  4. Macrophage activation and polarization.

    PubMed

    Martinez, Fernando Oneissi; Sica, Antonio; Mantovani, Alberto; Locati, Massimo

    2008-01-01

    Macrophages are widely distributed immune system cells that play an indispensable role in homeostasis and defense. They can be phenotypically polarized by the microenvironment to mount specific functional programs. Polarized macrophages can be broadly classified in two main groups: classically activated macrophages (or M1), whose prototypical activating stimuli are IFNgamma and LPS, and alternatively activated macrophages (or M2), further subdivided in M2a (after exposure to IL-4 or IL-13), M2b (immune complexes in combination with IL-1beta or LPS) and M2c (IL-10, TGFbeta or glucocorticoids). M1 exhibit potent microbicidal properties and promote strong IL-12-mediated Th1 responses, whilst M2 support Th2-associated effector functions. Beyond infection M2 polarized macrophages play a role in resolution of inflammation through high endocytic clearance capacities and trophic factor synthesis, accompanied by reduced pro-inflammatory cytokine secretion. Similar functions are also exerted by tumor-associated macrophages (TAM), which also display an alternative-like activation phenotype and play a detrimental pro-tumoral role. Here we review the main functions of polarized macrophages and discuss the perspectives of this field.

  5. Active Ingredient - AZ

    EPA Pesticide Factsheets

    EPA Pesticide Chemical Search allows a user to easily find the pesticide chemical or active ingredient that they are interested in by using an array of simple to advanced search options. Chemical Search provides a single point of reference for easy access to information previously published in a variety of locations, including various EPA web pages and Regulations.gov.

  6. Shark Tagging Activities.

    ERIC Educational Resources Information Center

    Current: The Journal of Marine Education, 1998

    1998-01-01

    In this group activity, children learn about the purpose of tagging and how scientists tag a shark. Using a cut-out of a shark, students identify, measure, record data, read coordinates, and tag a shark. Includes introductory information about the purpose of tagging and the procedure, a data sheet showing original tagging data from Tampa Bay, and…

  7. Engineers and Active Responsibility.

    PubMed

    Pesch, Udo

    2015-08-01

    Knowing that technologies are inherently value-laden and systemically interwoven with society, the question is how individual engineers can take up the challenge of accepting the responsibility for their work? This paper will argue that engineers have no institutional structure at the level of society that allows them to recognize, reflect upon, and actively integrate the value-laden character of their designs. Instead, engineers have to tap on the different institutional realms of market, science, and state, making their work a 'hybrid' activity combining elements from the different institutional realms. To deal with this institutional hybridity, engineers develop routines and heuristics in their professional network, which do not allow societal values to be expressed in a satisfactory manner. To allow forms of 'active' responsibility, there have to be so-called 'accountability forums' that guide moral reflections of individual actors. The paper will subsequently look at the methodologies of value-sensitive design (VSD) and constructive technology assessment (CTA) and explore whether and how these methodologies allow engineers to integrate societal values into the design technological artifacts and systems. As VSD and CTA are methodologies that look at the process of technological design, whereas the focus of this paper is on the designer, they can only be used indirectly, namely as frameworks which help to identify the contours of a framework for active responsibility of engineers.

  8. Activities: Visualization, Estimation, Computation.

    ERIC Educational Resources Information Center

    Maletsky, Evan M.

    1982-01-01

    The material is designed to help students build a cone model, visualize how its dimensions change as its shape changes, estimate maximum volume position, and develop problem-solving skills. Worksheets designed for duplication for classroom use are included. Part of the activity involves student analysis of a BASIC program. (MP)

  9. Intermittent Activity in AGN

    NASA Astrophysics Data System (ADS)

    Janiuk, A.; Czerny, B.; Siemiginowska, A.

    2004-10-01

    There is a growing evidence that the AGN activity could be intermittent. It remains an open question if this behavior is caused by changes in the fuel sup- ply to the supermassive black hole from the large distances, or rather by a processes intrinsic to the active nucleus. We consider the possibility that ac- cretion onto a supermassive black hole is controlled by an accretion disk which is subject to the hydro- gen ionization instability. This drives the observed on-off activity cycle, since periodically the accretion flow becomes inefficient and the disk goes to quies- cence. We consider effects of the MHD turbulence on the viscosity during the evolution of a standard α - disk. We perform a self-consistency check of the α de- scription of the angular momentum transfer. Hav- ing shown that the viscosity parameter is constant throughout the whole instability cycle, as implied by the strength of the MHD turbulence, we calcu- late the time evolution of the disk under the influ- ence of the ionization instability. We demonstrate that if the accretion onto a supermassive black hole proceeds through an outer standard accretion disk and inner, radiatively inefficient and advection dom- inated flow, the modelled amplitudes of disk lumi- nosity variations are sufficiently high to account for the observations. Key words: accretion disks; galaxies: active.

  10. Highlights of 1976 activities

    NASA Technical Reports Server (NTRS)

    Fitzpatrick, M.

    1976-01-01

    Highlights of NASA's 1976 activities are summarized. Sixteen successful launches were made. Two landings of Viking spacecraft on Mars and rollout of the space shuttle orbiter are reviewed. Applications of aerospace science to education, health care, and community services are also discussed.

  11. Activities from Asia.

    ERIC Educational Resources Information Center

    Texas Child Care, 1995

    1995-01-01

    Notes that the best way to learn about another culture is to know how its habits, traditions, and environments differ from or resemble our own. Provides several activities to help young children understand Asian cultures, including cooking, origami, and games and festivals. (HTH)

  12. Highlights of 1978 activities

    NASA Technical Reports Server (NTRS)

    1978-01-01

    General highlights of NASA's activities for 1978 are presented. The highlights are categorized into topics such as space science, space transportation systems, space and terrestrial applications, environment, technology utilization, aeronautics, space research and technology, energy programs, and international. A list of the 1978 launches including: (1) launch date; (2) payload designation; (3) launch vehicle; (4) launch site and (5) mission remarks is also presented.

  13. Multidisciplinary Wildlife Teaching Activities.

    ERIC Educational Resources Information Center

    Hernbrode, William R., Ed.

    This guide provides information and activities descriptions designed to allow the teacher to use wildlife concepts in the teaching of various subjects. The author suggests that wildlife and animals are tremendous motivators for children and hold their attention. In the process, concepts of wildlife interaction with man and the environment are…

  14. Active-bridge oscillator

    DOEpatents

    Wessendorf, Kurt O.

    2001-01-01

    An active bridge oscillator is formed from a differential amplifier where positive feedback is a function of the impedance of one of the gain elements and a relatively low value common emitter resistance. This use of the nonlinear transistor parameter h stabilizes the output and eliminates the need for ALC circuits common to other bridge oscillators.

  15. Immunizations: Active vs. Passive

    MedlinePlus

    ... a certain type of wild animal bites a child. Passive immunizations for hepatitis A (gamma globulin) may be helpful ... A is common. They are typically given before children or adults leave on their ... active vaccination is preferable. Keep in mind that passive immunizations ...

  16. 85 Engaging Movement Activities.

    ERIC Educational Resources Information Center

    Weikart, Phyllis S.; Carlton, Elizabeth B.

    This book presents activities to keep K-6 students moving in a variety of ways as they learn. The movement experiences are planned around key curriculum concepts in movement and music as well as in academic curriculum areas. The experiences develop students' basic timing, language abilities, vocabulary, concentration, planning skills, and…

  17. Classification of Physical Activity

    PubMed Central

    Turksoy, Kamuran; Paulino, Thiago Marques Luz; Zaharieva, Dessi P.; Yavelberg, Loren; Jamnik, Veronica; Riddell, Michael C.; Cinar, Ali

    2015-01-01

    Physical activity has a wide range of effects on glucose concentrations in type 1 diabetes (T1D) depending on the type (ie, aerobic, anaerobic, mixed) and duration of activity performed. This variability in glucose responses to physical activity makes the development of artificial pancreas (AP) systems challenging. Automatic detection of exercise type and intensity, and its classification as aerobic or anaerobic would provide valuable information to AP control algorithms. This can be achieved by using a multivariable AP approach where biometric variables are measured and reported to the AP at high frequency. We developed a classification system that identifies, in real time, the exercise intensity and its reliance on aerobic or anaerobic metabolism and tested this approach using clinical data collected from 5 persons with T1D and 3 individuals without T1D in a controlled laboratory setting using a variety of common types of physical activity. The classifier had an average sensitivity of 98.7% for physiological data collected over a range of exercise modalities and intensities in these subjects. The classifier will be added as a new module to the integrated multivariable adaptive AP system to enable the detection of aerobic and anaerobic exercise for enhancing the accuracy of insulin infusion strategies during and after exercise. PMID:26443291

  18. Production Systems. Laboratory Activities.

    ERIC Educational Resources Information Center

    Gallaway, Ann, Ed.

    This production systems guide provides teachers with learning activities for secondary students. Introductory materials include an instructional planning outline and worksheet, an outline of essential elements, domains and objectives, a course description, and a content outline. The guide contains 30 modules on the following topics: production…

  19. Dissemination Activities Report

    ERIC Educational Resources Information Center

    Barclay, Hanna; Batatia, Hudj; Bauters, Merja; Ben Ami, Zvi; Drachman, Raul; Flouris, Giorgos; Jadin, Tanja; Jalonen, Satu; Karlgren, Klas; Karpati, Andrea; Kotzinos, Dimitris; Lakkala, Minna; Lallimo, Jiri; Moen, Anne; Nygard, Kathrine; Paavola, Sami; Padiglia, Sheila; Scapolla, Marina; Sins, Patrick; Vasileva, Tania

    2008-01-01

    In the first 24 months of the project, KP-Lab members were highly dedicated to dissemination and were engaged in various dissemination activities that contributed to the prime objective of the KP-Lab dissemination efforts which is "to make the project widely known to a variety of prospective users and, at a later stage, to promote the…

  20. Designing Metacognitive Activities.

    ERIC Educational Resources Information Center

    Lin, Xiaodong

    2001-01-01

    Proposes a framework for thinking about how metacognition research might apply to design activities. Examines two basic approaches to supporting metacognition: strategy training, and creation of a supportive social environment for metacognition. Identifies two kinds of content that are taught using these two approaches: knowledge about a specific…

  1. Geology: The Active Earth.

    ERIC Educational Resources Information Center

    Braus, Judy, Ed.

    1987-01-01

    Ranger Rick's NatureScope is a creative education series dedicated to inspiring in children an understanding and appreciation of the natural world while developing the skills they will need to make responsible decisions about the environment. The topic of this issue is "Geology: The Active Earth." Contents are organized into the…

  2. Marketing coprovided activities.

    PubMed

    Dickerson, Pamela S

    2014-05-01

    Coproviding is a wonderful way for two or more organizations to work together to provide continuing nursing education. To be transparent to the learners, marketing materials identify the parties involved and prominently note the name of the organization accountable for developing the activity and awarding the contact hours.

  3. Communication Systems. Laboratory Activities.

    ERIC Educational Resources Information Center

    Sutherland, Barbara, Ed.

    This communication systems guide provides teachers with learning activities for secondary students. Introductory materials include an instructional planning outline and worksheet, an outline of essential elements, a list of objectives, a course description, and a content outline. The guide contains 32 modules on the following topics: story…

  4. Chaperone activation by unfolding.

    PubMed

    Foit, Linda; George, Jenny S; Zhang, Bin W; Brooks, Charles L; Bardwell, James C A

    2013-04-02

    Conditionally disordered proteins can alternate between highly ordered and less ordered configurations under physiological conditions. Whereas protein function is often associated with the ordered conformation, for some of these conditionally unstructured proteins, the opposite applies: Their activation is associated with their unfolding. An example is the small periplasmic chaperone HdeA, which is critical for the ability of enteric bacterial pathogens like Escherichia coli to survive passage through extremely acidic environments, such as the human stomach. At neutral pH, HdeA is a chaperone-inactive dimer. On a shift to low pH, however, HdeA monomerizes, partially unfolds, and becomes rapidly active in preventing the aggregation of substrate proteins. By mutating two aspartic acid residues predicted to be responsible for the pH-dependent monomerization of HdeA, we have succeeded in isolating an HdeA mutant that is active at neutral pH. We find this HdeA mutant to be substantially destabilized, partially unfolded, and mainly monomeric at near-neutral pH at a concentration at which it prevents aggregation of a substrate protein. These results provide convincing evidence for direct activation of a protein by partial unfolding.

  5. Ocean Drilling Simulation Activity.

    ERIC Educational Resources Information Center

    Telese, James A.; Jordan, Kathy

    The Ocean Drilling Project brings together scientists and governments from 20 countries to explore the earth's structure and history as it is revealed beneath the oceans' basins. Scientific expeditions examine rock and sediment cores obtained from the ocean floor to learn about the earth's basic processes. The series of activities in this…

  6. Organizing Preservation Activities.

    ERIC Educational Resources Information Center

    Cloonan, Michele

    This resource guide considers issues in the staffing and organization of preservation activities. It provides guidance in implementing a systematic preservation program and evaluates the structures of various types of preservation programs. The following articles complement the discussion of program models and implementation: (1)…

  7. Activities: Some Colorful Mathematics.

    ERIC Educational Resources Information Center

    DeTemple, Duane W.; Walker, Dean A.

    1996-01-01

    Describes three activities in discrete mathematics that involve coloring geometric objects: counting colored regions of overlapping simple closed curves, counting colored triangulations of polygons, and determining the number of colors required to paint the plane so that no two points one inch apart are the same color. (MKR)

  8. Physical Activities for Preschool.

    ERIC Educational Resources Information Center

    Adkins, Dorothy C.; And Others

    The underlying premise of the University of Hawaii Physical Activities for Preschool curriculum is that important contributions to a positive self-concept are made by motor independence and a realistic body image. Program objectives include: (1) the development of strength, endurance, and flexibility in skills that involve the muscles,…

  9. Activating silent argonautes.

    PubMed

    Kidwell, Mary Anne; Doudna, Jennifer A

    2013-07-01

    Multiple Argonaute proteins are implicated in gene silencing by RNA interference (RNAi), but only one is known to be an endonuclease that can cleave target mRNAs. Chimeric Argonaute proteins now reveal an unexpected mechanism by which mutations distal to the catalytic center can unmask intrinsic catalytic activity, results hinting at structurally mediated regulation.

  10. Commission 10: Solar Activity

    NASA Astrophysics Data System (ADS)

    van Driel-Gesztelyi, Lidia; Schrijver, Carolus J.; Klimchuk, James A.; Charbonneau, Paul; Fletcher, Lyndsay; Hasan, S. Sirajul; Hudson, Hugh S.; Kusano, Kanya; Mandrini, Cristina H.; Peter, Hardi; Vršnak, Bojan; Yan, Yihua

    2012-04-01

    Commission 10 of the International Astronomical Union has more than 650 members who study a wide range of activity phenomena produced by our nearest star, the Sun. Solar activity is intrinsically related to solar magnetic fields and encompasses events from the smallest energy releases (nano- or even picoflares) to the largest eruptions in the Solar System, coronal mass ejections (CMEs), which propagate into the Heliosphere reaching the Earth and beyond. Solar activity is manifested in the appearance of sunspot groups or active regions, which are the principal sources of activity phenomena from the emergence of their magnetic flux through their dispersion and decay. The period 2008-2009 saw an unanticipated extended solar cycle minimum and unprecedentedly weak polar-cap and heliospheric field. Associated with that was the 2009 historical maximum in galactic cosmic rays flux since measurements begun in the middle of the 20th Century. Since then Cycle 24 has re-started solar activity producing some spectacular eruptions observed with a fleet of spacecraft and ground-based facilities. In the last triennium major advances in our knowledge and understanding of solar activity were due to continuing success of space missions as SOHO, Hinode, RHESSI and the twin STEREO spacecraft, further enriched by the breathtaking images of the solar atmosphere produced by the Solar Dynamic Observatory (SDO) launched on 11 February 2010 in the framework of NASA's Living with a Star program. In August 2012, at the time of the IAU General Assembly in Beijing when the mandate of this Commission ends, we will be in the unique position to have for the first time a full 3-D view of the Sun and solar activity phenomena provided by the twin STEREO missions about 120 degrees behind and ahead of Earth and other spacecraft around the Earth and ground-based observatories. These new observational insights are continuously posing new questions, inspiring and advancing theoretical analysis and

  11. 45 CFR 1226.8 - Prohibited activities.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... SERVICE PROHIBITIONS ON ELECTORAL AND LOBBYING ACTIVITIES Volunteer Activities § 1226.8 Prohibited activities. (a) Electoral Activity. Volunteers shall not engage in any activity which may, directly...

  12. Interdisciplinary Astronomy Activities

    NASA Astrophysics Data System (ADS)

    Nerantzis, Nikolaos; Mitrouda, Aikaterini; Reizopoulou, Ioanna; Sidiropoulou, Eirini; Hatzidimitriou, Antonios

    2016-04-01

    On November 9th, 2015, three didactical hours were dedicated to Interdisciplinary Astronomy Activities (http://wp.me/p6Hte2-1I). Our students and their teachers formed three groups and in rotation, were engaged with the following activities: (a) viewing unique images of the Cosmos in the mobile planetarium STARLAB (http://www.planitario.gr/tholos-starlab-classic-standard.html), (b) watching the following videos: Journey to the end of the universe (https://youtu.be/Ufl_Nwbl8xs), Rosetta update (https://youtu.be/nQ9ivd7wv30), The Solar System (https://youtu.be/d66dsagrTa0), Ambition the film (https://youtu.be/H08tGjXNHO4) in the school's library. Students and teachers were informed about our solar system, the Rosetta mission, the universe, etc. and (c) tactile activities such as Meet our home and Meet our neighbors (http://astroedu.iau.org, http://nuclio.org/astroneighbours/resources) and the creation of planets' 3D models (Geology-Geography A' Class Student's book, pg.15). With the activities above we had the pleasure to join the Cosmic Light Edu Kit / International Year of Light 2015 program. After our Interdisciplinary Astronomy Activities, we did a "small" research: our students had to fill an evaluation about their educational gains and the results can be found here http://wp.me/p6Hte2-2q. Moreover, we discussed about Big Ideas of Science (http://wp.me/p3oRiZ-dm) and through the "big" impact of the Rosetta mission & the infinity of our universe, we print posters with relevant topics and place them to the classrooms. We thank Rosa Doran (Nuclio - President of the Executive Council) for her continuous assistance and support on innovative science teaching proposals. She is an inspiration.

  13. Activities. Inductive and Deductive Reasoning.

    ERIC Educational Resources Information Center

    O'Daffer, Phares G.; And Others

    1990-01-01

    Provided are the activity sheets for students and the teaching guide for this middle school geometry activity. Materials, prerequisites, objectives, and procedures are listed. Extension activities are suggested. An answer key is included. (CW)

  14. Hydrogeology and water quality of the Floridan aquifer system and effect of Lower Floridan aquifer pumping on the Upper Floridan aquifer at Hunter Army Airfield, Chatham County, Georgia

    USGS Publications Warehouse

    Clarke, John S.; Williams, Lester J.; Cherry, Gregory C.

    2010-01-01

    Test drilling and field investigations, conducted at Hunter Army Airfield (HAAF), Chatham County, Georgia, during 2009, were used to determine the geologic, hydraulic, and water-quality characteristics of the Floridan aquifer system and to evaluate the effect of Lower Floridan aquifer (LFA) pumping on the Upper Floridan aquifer (UFA). Field investigation activities included (1) constructing a 1,168-foot (ft) test boring and well completed in the LFA, (2) collecting drill cuttings and borehole geophysical logs, (3) collecting core samples for analysis of vertical hydraulic conductivity and porosity, (4) conducting flowmeter and packer tests in the open borehole within the UFA and LFA, (5) collecting depth-integrated water samples to assess basic ionic chemistry of various water-bearing zones, and (6) conducting aquifer tests in the new LFA well and in an existing UFA well to determine hydraulic properties and assess interaquifer leakage. Using data collected at the site and in nearby areas, model simulation was used to quantify the effects of interaquifer leakage on the UFA and to determine the amount of pumping reduction required in the UFA to offset drawdown resulting from the leakage. Borehole-geophysical and flowmeter data indicate the LFA at HAAF consists of limestone and dolomitic limestone between depths of 703 and 1,080 ft, producing water from six major permeable zones: 723-731; 768-785; 818-837; 917-923; 1,027-1,052; and 1,060-1,080 ft. Data from a flowmeter survey, conducted at a pumping rate of 748 gallons per minute (gal/min), suggest that the two uppermost zones contributed 469 gal/min or 62.6 percent of the total flow during the test. The remaining four zones contributed from 1.7 to 18 percent of the total flow. Grab water samples indicate that with the exception of fluoride, constituent concentrations in the LFA increased with depth; water from the deepest interval (1,075 ft) contained chloride and sulfate concentrations of 480 and 240 milligrams per

  15. 101 Environmental Education Activities. Booklet 6--Social Studies Activities.

    ERIC Educational Resources Information Center

    Whitney, Helen, Comp.

    Based on the environment and directed at elementary and intermediate level students, 5 field trips are a significant part of the 12 social studies activities in the sixth booklet by the Upper Mississippi River ECO-Center outlining environmental and outdoor education activities. Most of the activities include objectives, activity description,…

  16. Integration of Active Video Games in Extracurricular Activity at Schools

    ERIC Educational Resources Information Center

    Lee, Jung Eun; Huang, Charles; Pope, Zachary; Gao, Zan

    2015-01-01

    Active video games require players to be physically active. Dance Dance Revolution (DDR) is an interactive dancing game that requires fast-foot movement coordinated with energetic music and visuals. The Wii and Xbox Kinect games have also become good active video games for the promotion of physical activity participation. These games are much more…

  17. Is Enhanced Physical Activity Possible Using Active Videogames?

    PubMed

    Baranowski, Tom; Baranowski, Janice; O'Connor, Teresia; Lu, Amy Shirong; Thompson, Debbe

    2012-06-01

    Our research indicated that 10-12-year-old children receiving two active Wii(™) (Nintendo(®); Nintendo of America, Inc., Redmond, WA) console videogames were no more physically active than children receiving two inactive videogames. Research is needed on how active videogames may increase physical activity.

  18. Active braze process

    SciTech Connect

    Levine, I.L.; Pike, R.A.

    1990-11-02

    Active metal bonding using Cusil (silver-copper) braze alloys is a well established method used at GE Neutron Devices (GEND) for bonding metal to metal, metal to ceramics, and ceramics to ceramics. However, there are many instances in which using a silver alloy for bonding is undesirable (e.g., in vacuum tube envelopes, or where sequential braze steps at different temperatures are required to complete an assembly). The Material and Processes Laboratory at GEND has discovered a new method of active brazing with non-silver alloys which has proved especially successful in ceramic-to-ceramic joints. This method has the added advantage of eliminating several steps which are required in conventional bonding techniques. 2 figs., 10 tabs.

  19. Myofilament length dependent activation.

    PubMed

    de Tombe, Pieter P; Mateja, Ryan D; Tachampa, Kittipong; Ait Mou, Younss; Farman, Gerrie P; Irving, Thomas C

    2010-05-01

    The Frank-Starling law of the heart describes the interrelationship between end-diastolic volume and cardiac ejection volume, a regulatory system that operates on a beat-to-beat basis. The main cellular mechanism that underlies this phenomenon is an increase in the responsiveness of cardiac myofilaments to activating Ca(2+) ions at a longer sarcomere length, commonly referred to as myofilament length-dependent activation. This review focuses on what molecular mechanisms may underlie myofilament length dependency. Specifically, the roles of inter-filament spacing, thick and thin filament based regulation, as well as sarcomeric regulatory proteins are discussed. Although the "Frank-Starling law of the heart" constitutes a fundamental cardiac property that has been appreciated for well over a century, it is still not known in muscle how the contractile apparatus transduces the information concerning sarcomere length to modulate ventricular pressure development.

  20. Mount Erebus activity

    NASA Astrophysics Data System (ADS)

    An international team of scientists reports that unusually high seismic activity joggled Mount Erebus last fall. However, the Antarctic volcano showed no external signs of an eruption.When scientists from the United States, Japan, and New Zealand returned to the world's southernmost active volcano last November for their annual field expedition, they found that seismic stations recorded 650 small tremors on October 8; prior to that, the number of quakes had averaged between 20 and 80 per day. The October 8 maximum was followed by 140 on October 9 and 120 on October 10. Philip R. Kyle, assistant professor of geochemistry at the New Mexico Institute of Mining and Technology in Socorro and leader of the team studying Mount Erebus, noted that some of the strongest earthquakes recorded during the team's 3 years of observations occurred on October 8; these registered less than 2 on the Richter scale.

  1. UNESCO's activities in ethics.

    PubMed

    ten Have, Henk A M J

    2010-03-01

    UNESCO is an intergovernmental organization with 193 Member States. It is concerned with a broad range of issues regarding education, science and culture. It is the only UN organisation with a mandate in science. Since 1993 it is addressing ethics of science and technology, with special emphasis on bioethics. One major objective of the ethics programme is the development of international normative standards. This is particularly important since many Member States only have a limited infrastructure in bioethics, lacking expertise, educational programs, bioethics committees and legal frameworks. UNESCO has recently adopted the Universal Declaration on Bioethics and Human Rights. The focus of current activities is now on implementation of this Declaration. Three activities are discussed that aim at improving and reinforcing the ethics infrastructure in relation to science and technology: the Global Ethics Observatory, the Ethics Education Programme and the Assisting Bioethics Committees project.

  2. LANSCE Activity Report

    SciTech Connect

    Amy Robinson; Audrey Archuleta; Barbara Maes; Dan Strottman; Earl Hoffman; Garth Tietjen; Gene Farnum; Geoff Greene; Joyce Roberts; Ken Johnson; Paul Lewis; Roger Pynn; Stan Schriber; Steve Sterbenz; Steve Wender; Sue Harper

    1999-02-01

    The Los Alamos Neutron Science Center Activity Report describes scientific and technological progress and achievements in LANSCE Division during the period of 1995 to 1998. This report includes a message from the Division Director, an overview of LANSCE, sponsor overviews, research highlights, advanced projects and facility upgrades achievements, experimental and user program accomplishments, news and events, and a list of publications. The research highlights cover the areas of condensed-matter science and engineering, accelerator science, nuclear science, and radiography. This report also contains a compact disk that includes an overview, the Activity Report itself, LANSCE operations progress reports for 1996 and 1997, experiment reports from LANSCE users, as well as a search capability.

  3. Myofilament length dependent activation

    SciTech Connect

    de Tombe, Pieter P.; Mateja, Ryan D.; Tachampa, Kittipong; Mou, Younss Ait; Farman, Gerrie P.; Irving, Thomas C.

    2010-05-25

    The Frank-Starling law of the heart describes the interrelationship between end-diastolic volume and cardiac ejection volume, a regulatory system that operates on a beat-to-beat basis. The main cellular mechanism that underlies this phenomenon is an increase in the responsiveness of cardiac myofilaments to activating Ca{sup 2+} ions at a longer sarcomere length, commonly referred to as myofilament length-dependent activation. This review focuses on what molecular mechanisms may underlie myofilament length dependency. Specifically, the roles of inter-filament spacing, thick and thin filament based regulation, as well as sarcomeric regulatory proteins are discussed. Although the 'Frank-Starling law of the heart' constitutes a fundamental cardiac property that has been appreciated for well over a century, it is still not known in muscle how the contractile apparatus transduces the information concerning sarcomere length to modulate ventricular pressure development.

  4. Techniques for active passivation

    SciTech Connect

    Roscioli, Joseph R.; Herndon, Scott C.; Nelson, Jr., David D.

    2016-12-20

    In one embodiment, active (continuous or intermittent) passivation may be employed to prevent interaction of sticky molecules with interfaces inside of an instrument (e.g., an infrared absorption spectrometer) and thereby improve response time. A passivation species may be continuously or intermittently applied to an inlet of the instrument while a sample gas stream is being applied. The passivation species may have a highly polar functional group that strongly binds to either water or polar groups of the interfaces, and once bound presents a non-polar group to the gas phase in order to prevent further binding of polar molecules. The instrument may be actively used to detect the sticky molecules while the passivation species is being applied.

  5. Nematicidal activity of terpenoids.

    PubMed

    Abdel-Rahman, Fawzia H; Alaniz, Nina M; Saleh, Mahmoud A

    2013-01-01

    Thirty four phytoterpenoids were evaluated for their nematicidal effect using the model nematode Caenorhabditis elegans. Nematicidal activities of the tested compounds at concentrations of 50 μg/mL showed wide variation in their effects ranging from no effect, weak, moderate and strong effects. Terpenoids exerting 50% or higher mortality at 50 μg/mL were further tested at five different concentrations to calculate the concentration that will kill 50% of the nematode population (LC(50)). Among the most effective terpenoids were carvacrol, thymol, nerolidol, α-terpinene, geraniol, citronellol, farnesol, limonene, pseudoionone and eugenol in a descending order. These compounds exhibited a dose-dependent effect. The results suggest that the selected monoterpenoids and essential oils with a high concentration of these compounds mayprovide potential natural nematicides and merit further study as botanical nematicides for the control of both plant and animal parasitic nematodes. In general, oxygenated terpenoids and phenolic terpenoids exhibited higher nematicidal activity than hydrocarbons terpenoids.

  6. Active region seismology

    NASA Technical Reports Server (NTRS)

    Bogdan, Tom; Braun, D. C.

    1995-01-01

    Active region seismology is concerned with the determination and interpretation of the interaction of the solar acoustic oscillations with near-surface target structures, such as magnetic flux concentration, sunspots, and plage. Recent observations made with a high spatial resolution and a long temporal duration enabled measurements of the scattering matrix for sunspots and solar active regions to be carried out as a function of the mode properties. Based on this information, the amount of p-mode absorption, partial-wave phase shift, and mode mixing introduced by the sunspot, could be determined. In addition, the possibility of detecting the presence of completely submerged magnetic fields was raised, and new procedures for performing acoustic holography of the solar interior are being developed. The accumulating evidence points to the mode conversion of p-modes to various magneto-atmospheric waves within the magnetic flux concentration as being the unifying physical mechanism responsible for these diverse phenomena.

  7. Cisplatin triggers platelet activation.

    PubMed

    Togna, G I; Togna, A R; Franconi, M; Caprino, L

    2000-09-01

    Clinical observations suggest that anticancer drugs could contribute to the thrombotic complications of malignancy in treated patients. Thrombotic microangiopathy, myocardial infarction, and cerebrovascular thrombotic events have been reported for cisplatin, a drug widely used in the treatment of many solid tumours. The aim of this study is to explore in vitro cisplatin effect on human platelet reactivity in order to define the potentially active role of platelets in the pathogenesis of cisplatin-induced thrombotic complications. Our results demonstrate that cisplatin increases human platelet reactivity (onset of platelet aggregation wave and thromboxane production) to non-aggregating concentrations of the agonists involving arachidonic acid metabolism. Direct or indirect activation of platelet phospholipase A(2) appears to be implicated. This finding contributes to a better understanding of the pathogenesis of thrombotic complications occurring during cisplatin-based chemotherapy.

  8. Active optical zoom system.

    PubMed

    Wang, Di; Wang, Qiong-Hua; Shen, Chuan; Zhou, Xin; Liu, Chun-Mei

    2014-11-01

    In this work, we propose an active optical zoom system. The zoom module of the system is formed by a liquid lens and a spatial light modulator (SLM). By controlling the focal lengths of the liquid lens and the encoded digital lens on the SLM panel, we can change the magnification of an image without mechanical moving parts and keep the output plane stationary. The magnification can change from 1/3 to 3/2 as the focal length of the encoded lens on the SLM changes from infinity to 24 cm. The proposed active zoom system is simple and flexible, and has widespread application in optical communications, imaging systems, and displays.

  9. Active microchannel heat exchanger

    DOEpatents

    Tonkovich, Anna Lee Y [Pasco, WA; Roberts, Gary L [West Richland, WA; Call, Charles J [Pasco, WA; Wegeng, Robert S [Richland, WA; Wang, Yong [Richland, WA

    2001-01-01

    The present invention is an active microchannel heat exchanger with an active heat source and with microchannel architecture. The microchannel heat exchanger has (a) an exothermic reaction chamber; (b) an exhaust chamber; and (c) a heat exchanger chamber in thermal contact with the exhaust chamber, wherein (d) heat from the exothermic reaction chamber is convected by an exothermic reaction exhaust through the exhaust chamber and by conduction through a containment wall to the working fluid in the heat exchanger chamber thereby raising a temperature of the working fluid. The invention is particularly useful as a liquid fuel vaporizer and/or a steam generator for fuel cell power systems, and as a heat source for sustaining endothermic chemical reactions and initiating exothermic reactions.

  10. Environmental health program activities

    NASA Technical Reports Server (NTRS)

    Bergtholdt, C. P.

    1969-01-01

    Activities reported include studies on toxic air contaminants, excessive noise, poor lighting, food sanitation, water pollution, and exposure to nonionizing radiation as health hazards. Formulations for a radiological health manual provide guidance to personnel in the procurement and safe handling of radiation producing equipment and Apollo mission planning. A literature search and development of a water analysis laboratory are outlined to obtain information regarding microbiological problems involving potable water, waste management, and personal hygiene.

  11. [Chronotropic activity of semax].

    PubMed

    Arushanian, E B; Popov, A V

    2008-01-01

    The chronic administration of nootropic drug Semax, a peptide analog of ACTH (4-10), normalized the circadian locomotor rhythm in rats (with an increase in its amplitude, a shift in the acrophase, and a change of the spectral characteristics) and reduced the integral chronobiological index. It is suggested that the rhythm-synchronizing chronotropic activity may be a part of the specific effect of this cognitive enhancer.

  12. Imaging nervous system activity.

    PubMed

    Fields, Douglas R; Shneider, Neil; Mentis, George Z; O'Donovan, Michael J

    2009-10-01

    This unit describes methods for loading ion- and voltage-sensitive dyes into neurons, with a particular focus on the spinal cord as a model system. In addition, we describe the use of these dyes to visualize neural activity. Although the protocols described here concern spinal networks in culture or an intact in vitro preparation, they can be, and have been, widely used in other parts of the nervous system.

  13. Assay of FAAH Activity.

    PubMed

    Bari, Monica; Feole, Monica; Maccarrone, Mauro

    2016-01-01

    Fatty acid amide hydrolase (FAAH) is an intracellular enzyme responsible for the hydrolysis of endogenous anandamide (AEA), a reaction that terminates the biological effects of this lipid mediator. The final products of this reaction are arachidonic acid and ethanolamine. In the method described herein, FAAH activity is measured through the use of a radioactive substrate by quantification of reaction products, that is, [(14)C]-ethanolamine from [(14)C-ethanolamine]-AEA.

  14. Active inference and learning.

    PubMed

    Friston, Karl; FitzGerald, Thomas; Rigoli, Francesco; Schwartenbeck, Philipp; O'Doherty, John; Pezzulo, Giovanni

    2016-09-01

    This paper offers an active inference account of choice behaviour and learning. It focuses on the distinction between goal-directed and habitual behaviour and how they contextualise each other. We show that habits emerge naturally (and autodidactically) from sequential policy optimisation when agents are equipped with state-action policies. In active inference, behaviour has explorative (epistemic) and exploitative (pragmatic) aspects that are sensitive to ambiguity and risk respectively, where epistemic (ambiguity-resolving) behaviour enables pragmatic (reward-seeking) behaviour and the subsequent emergence of habits. Although goal-directed and habitual policies are usually associated with model-based and model-free schemes, we find the more important distinction is between belief-free and belief-based schemes. The underlying (variational) belief updating provides a comprehensive (if metaphorical) process theory for several phenomena, including the transfer of dopamine responses, reversal learning, habit formation and devaluation. Finally, we show that active inference reduces to a classical (Bellman) scheme, in the absence of ambiguity.

  15. Active Brownian rods

    NASA Astrophysics Data System (ADS)

    Peruani, Fernando

    2016-11-01

    Bacteria, chemically-driven rods, and motility assays are examples of active (i.e. self-propelled) Brownian rods (ABR). The physics of ABR, despite their ubiquity in experimental systems, remains still poorly understood. Here, we review the large-scale properties of collections of ABR moving in a dissipative medium. We address the problem by presenting three different models, of decreasing complexity, which we refer to as model I, II, and III, respectively. Comparing model I, II, and III, we disentangle the role of activity and interactions. In particular, we learn that in two dimensions by ignoring steric or volume exclusion effects, large-scale nematic order seems to be possible, while steric interactions prevent the formation of orientational order at large scales. The macroscopic behavior of ABR results from the interplay between active stresses and local alignment. ABR exhibit, depending on where we locate ourselves in parameter space, a zoology of macroscopic patterns that ranges from polar and nematic bands to dynamic aggregates.

  16. Active polarization descattering.

    PubMed

    Treibitz, Tali; Schechner, Yoav Y

    2009-03-01

    Vision in scattering media is important but challenging. Images suffer from poor visibility due to backscattering and attenuation. Most prior methods for scene recovery use active illumination scanners (structured and gated), which can be slow and cumbersome, while natural illumination is inapplicable to dark environments. The current paper addresses the need for a non-scanning recovery method, that uses active scene irradiance. We study the formation of images under widefield artificial illumination. Based on the formation model, the paper presents an approach for recovering the object signal. It also yields rough information about the 3D scene structure. The approach can work with compact, simple hardware, having active widefield, polychromatic polarized illumination. The camera is fitted with a polarization analyzer. Two frames of the scene are taken, with different states of the analyzer or polarizer. A recovery algorithm follows the acquisition. It allows both the backscatter and the object reflection to be partially polarized. It thus unifies and generalizes prior polarization-based methods, which had assumed exclusive polarization of either of these components. The approach is limited to an effective range, due to image noise and illumination falloff. Thus, the limits and noise sensitivity are analyzed. We demonstrate the approach in underwater field experiments.

  17. Active quantum plasmonics.

    PubMed

    Marinica, Dana Codruta; Zapata, Mario; Nordlander, Peter; Kazansky, Andrey K; M Echenique, Pedro; Aizpurua, Javier; Borisov, Andrei G

    2015-12-01

    The ability of localized surface plasmons to squeeze light and engineer nanoscale electromagnetic fields through electron-photon coupling at dimensions below the wavelength has turned plasmonics into a driving tool in a variety of technological applications, targeting novel and more efficient optoelectronic processes. In this context, the development of active control of plasmon excitations is a major fundamental and practical challenge. We propose a mechanism for fast and active control of the optical response of metallic nanostructures based on exploiting quantum effects in subnanometric plasmonic gaps. By applying an external dc bias across a narrow gap, a substantial change in the tunneling conductance across the junction can be induced at optical frequencies, which modifies the plasmonic resonances of the system in a reversible manner. We demonstrate the feasibility of the concept using time-dependent density functional theory calculations. Thus, along with two-dimensional structures, metal nanoparticle plasmonics can benefit from the reversibility, fast response time, and versatility of an active control strategy based on applied bias. The proposed electrical manipulation of light using quantum plasmonics establishes a new platform for many practical applications in optoelectronics.

  18. THE ACTIVE ASTEROIDS

    SciTech Connect

    Jewitt, David

    2012-03-15

    Some asteroids eject dust, unexpectedly producing transient, comet-like comae and tails. First ascribed to the sublimation of near-surface water ice, mass-losing asteroids (also called 'main-belt comets') can in fact be driven by a surprising diversity of mechanisms. In this paper, we consider 11 dynamical asteroids losing mass, in nine of which the ejected material is spatially resolved. We address mechanisms for producing mass loss including rotational instability, impact ejection, electrostatic repulsion, radiation pressure sweeping, dehydration stresses, and thermal fracture, in addition to the sublimation of ice. In two objects (133P and 238P) the repetitive nature of the observed activity leaves ice sublimation as the only reasonable explanation, while in a third ((596) Scheila), a recent impact is the cause. Another impact may account for activity in P/2010 A2, but this tiny object can also be explained as having shed mass after reaching rotational instability. Mass loss from (3200) Phaethon is probably due to cracking or dehydration at extreme ({approx}1000 K) perihelion temperatures, perhaps aided by radiation pressure sweeping. For the other bodies, the mass-loss mechanisms remain unidentified, pending the acquisition of more and better data. While the active asteroid sample size remains small, the evidence for an astonishing diversity of mass-loss processes in these bodies is clear.

  19. Active quantum plasmonics

    PubMed Central

    Marinica, Dana Codruta; Zapata, Mario; Nordlander, Peter; Kazansky, Andrey K.; M. Echenique, Pedro; Aizpurua, Javier; Borisov, Andrei G.

    2015-01-01

    The ability of localized surface plasmons to squeeze light and engineer nanoscale electromagnetic fields through electron-photon coupling at dimensions below the wavelength has turned plasmonics into a driving tool in a variety of technological applications, targeting novel and more efficient optoelectronic processes. In this context, the development of active control of plasmon excitations is a major fundamental and practical challenge. We propose a mechanism for fast and active control of the optical response of metallic nanostructures based on exploiting quantum effects in subnanometric plasmonic gaps. By applying an external dc bias across a narrow gap, a substantial change in the tunneling conductance across the junction can be induced at optical frequencies, which modifies the plasmonic resonances of the system in a reversible manner. We demonstrate the feasibility of the concept using time-dependent density functional theory calculations. Thus, along with two-dimensional structures, metal nanoparticle plasmonics can benefit from the reversibility, fast response time, and versatility of an active control strategy based on applied bias. The proposed electrical manipulation of light using quantum plasmonics establishes a new platform for many practical applications in optoelectronics. PMID:26824066

  20. Sesterterpenoids with Anticancer Activity

    PubMed Central

    Evidente, Antonio; Kornienko, Alexander; Lefranc, Florence; Cimmino, Alessio; Dasari, Ramesh; Evidente, Marco; Mathieu, Véronique; Kiss, Robert

    2016-01-01

    Terpenes have received a great deal of attention in the scientific literature due to complex, synthetically challenging structures and diverse biological activities associated with this class of natural products. Based on the number of C5 isoprene units they are generated from, terpenes are classified as hemi- (C5), mono- (C10), sesqui- (C15), di- (C20), sester- (C25), tri (C30), and tetraterpenes (C40). Among these, sesterterpenes and their derivatives known as sesterterpenoids, are ubiquitous secondary metabolites in fungi, marine organisms, and plants. Their structural diversity encompasses carbotricyclic ophiobolanes, polycyclic anthracenones, polycyclic furan-2-ones, polycyclic hydroquinones, among many other carbon skeletons. Furthermore, many of them possess promising biological activities including cytotoxicity and the associated potential as anticancer agents. This review discusses the natural sources that produce sesterterpenoids, provides sesterterpenoid names and their chemical structures, biological properties with the focus on anticancer activities and literature references associated with these metabolites. A critical summary of the potential of various sesterterpenoids as anticancer agents concludes the review. PMID:26295461

  1. Transport to Rhebpress activity.

    PubMed

    Garrido, Amanda; Brandt, Marta; Djouder, Nabil

    2016-01-01

    The small GTPases from the rat sarcoma (Ras) superfamily are a heterogeneous group of proteins of about 21 kDa that act as molecular switches, modulating cell signaling pathways and controlling diverse cellular processes. They are active when bound to guanosine triphosphate (GTP) and inactive when bound to guanosine diphosphate (GDP). Ras homolog enriched in brain (Rheb) is a member of the Ras GTPase superfamily and a key activator of the mammalian/mechanistic target of rapamycin complex 1 (mTORC1). We recently determined that microspherule protein 1 (MCRS1) maintains Rheb at lysosomal surfaces in an amino acid-dependent manner. MCRS1 depletion promotes the formation of the GDP-bound form of Rheb, which is then delocalized from the lysosomal platform and transported to endocytic recycling vesicles, leading to mTORC1 inactivation. During this delocalization process, Rheb-GDP remains farnesylated and associated with cellular endomembranes. These findings provide new insights into the regulation of small GTPases, whose activity depends on both their GTP/GDP switch state and their capacity to move between different cellular membrane-bound compartments. Dynamic spatial transport between compartments makes it possible to alter the proximity of small GTPases to their activatory sites depending on the prevailing physiological and cellular conditions.

  2. Thermal activity on Enceladus

    NASA Astrophysics Data System (ADS)

    Tobie, G.; Besserer, J.; Behounkova, M.; Cadek, O.; Choblet, G.; Sotin, C.

    2009-04-01

    Observations by Cassini have revealed that Enceladus' souh pole is highly active, with jets of icy particles and water vapour emanated from narrow tectonic ridges, called "tiger stripes". This jet activity is associated to a very high thermal emission mainly focused along the tectonic ridges. Heat power required to sustain such an activity is probably related to the dissipation of mechanical energy due to tidal forces exerted by Saturn. However, the dissipation process and its relation to the tectonic features are not clearly established. Both shear heating along the tectonic ridges and viscous dissipation in the convective part of the ice shell could contribute to the energy budget (Nimmo et al. 2007, Tobie et al. 2008). Tobie et al. (2008) pointed out that only interior models with a liquid water layer at depth, covering at least ~2/3 of the southern hemisphere, can explain the observed magnitude of dissipation and its particular location at the south pole. However, the long term stability of such a liquid reservoir remains problematic (Roberts and Nimmo 2007) and the possible link between the liquid reservoir and the surface activities is unknown. Concentration of tidal stresses along the tiger ridges have also been invoked as a mechanism to trigger the eruptive processes (Hurtford et al. 2007, Smith-Konter et al. 2008). However, those models do not take into account a realistic rheological structure for the ice shell when computing the fluctuating stress field. Moreover, the effect of the faults on the background tidal stress is neglected. In particular, low viscosity values are expected to be associated with the shear zone along the tiger stripes and may have a significant impact of the global tidal stress field. In order to self-consistently determine the tidal deformation and its impact on the thermal activity on Enceladus, we are currently developing a 3D model that combines a thermal convection code in spherical geometry (Choblet et al. 2007) and a

  3. Gender Issues: An Activity File.

    ERIC Educational Resources Information Center

    Fountain, Susan

    This activity file grew out of research of an "Images of Women in Development" project of the Centre for Global Education at the University of York, England. The activities are intended for students in the 8- to 13-year-old range to learn more about gender issues. The activities are divided into four sections: (1) awareness-raising activities in…

  4. Metric Activities, Grades K-6.

    ERIC Educational Resources Information Center

    Draper, Bob, Comp.

    This pamphlet presents worksheets for use in fifteen activities or groups of activities designed for teaching the metric system to children in grades K through 6. The approach taken in several of the activities is one of conversion between metric and English units. The majority of the activities concern length, area, volume, and capacity. A…

  5. Changing Conceptions of Activation Energy.

    ERIC Educational Resources Information Center

    Pacey, Philip D.

    1981-01-01

    Provides background material which relates to the concept of activation energy, fundamental in the study of chemical kinetics. Compares the related concepts of the Arrhenius activation energy, the activation energy at absolute zero, the enthalpy of activation, and the threshold energy. (CS)

  6. Science Activities in Energy: Conservation.

    ERIC Educational Resources Information Center

    Oak Ridge Associated Universities, TN.

    Presented is a science activities in energy package which includes 14 activities relating to energy conservation. Activities are simple, concrete experiments for fourth, fifth and sixth grades, which illustrate principles and problems relating to energy. Each activity is outlined on a simple card which is introduced by a question. A teacher's…

  7. Epsiodic Activity in Radio Galaxies

    SciTech Connect

    Saikia, D.J.; Konar, C.; Jamrozy, M.; Machalski, J.; Gupta, Neeraj; Stawarz, L.; Mack, K.-H.; Siemiginowska, A.; /Harvard-Smithsonian Ctr. Astrophys.

    2007-10-15

    One of the interesting issues in our understanding of active galactic nuclei is the duration of their active phase and whether such activity is episodic. In this paper we summarize our recent results on episodic activity in radio galaxies obtained with the GMRT and the VLA.

  8. Large-scale clinical validation of a lateral flow immunoassay for detection of cryptococcal antigen in serum and cerebrospinal fluid specimens.

    PubMed

    Suwantarat, Nuntra; Dalton, Justin B; Lee, Richard; Green, Rachel; Memon, Warda; Carroll, Karen C; Riedel, Stefan; Zhang, Sean X

    2015-05-01

    We compared a lateral flow immunoassay (LFA) to a currently used enzyme immunoassay for detection of cryptococcal antigen in 396 sera and 651 cerebrospinal fluid specimens. We found 97% concordance between the 2 assays. The LFA detected an additional 22 positives. Overall, the LFA had sensitivity of 100% and specificity of 99.6% for the diagnosis of cryptococcosis. The LFA is rapid, accurate, and easy to perform, and it is suitable for routine patient care testing.

  9. The active asteroids

    NASA Astrophysics Data System (ADS)

    Jewitt, D.

    2014-07-01

    Active asteroids simultaneously possess the orbits of main-belt asteroids and the physical appearances of comets; they show transient dust comae and solar-radiation pressure-swept tails. Apart from the shear surprise at finding such strange objects in the asteroid belt, the active asteroids are scientifically interesting for several reasons. Although we are limited to scarcely more than a dozen examples, the active asteroids already reveal the distinct action of different physical processes, each previously unobserved and carrying big-picture importance for understanding the solar system. 1. IMPACT. An unambiguous asteroid-asteroid impact was observed in 2010, when a 30-m scale body struck 100-km diameter (596) Scheila. Direct observations of impacts hold scientific importance both by sampling this natural process at full scale (compared with laboratory impacts conducted at tiny scales) and because impact statistics will allow us to assess the erosion rate in the asteroid belt and the contribution of asteroid dust to the interplanetary medium. 2. CRITICAL ROTATION. Several objects have been observed in which the best explanation seems to lie with spin-up to critical periods, presumably (but not certainly) caused by YORP. Examples of both likely mass-shedding (P/2010 A2, P/2013 P5) and full break-up (P/2013 R3, shown below) exist. It has been suggested that, at sub-kilometer sizes, spin-up disruption rates may surpass impact disruption rates. Future observations will show whether or not this is true, and may ultimately lead to an improved understanding of the physics of break-up. 3. THERMAL DISINTEGRATION. Geminid parent (3200) Phaethon shows on-going mass-loss at perihelion, driven by the 1000-K surface temperatures found there. The mechanisms appear to be some combination of thermal fracture and desiccation stress. 4. SUBLIMATION. Two objects have shown repeated activity that appears to be correlated with position in the orbit. The best example is 133P, which has

  10. Asthma and physical activity.

    PubMed

    Oseid, S

    1982-01-01

    Physical activity regularly leads to a decline in lung function in children and adolescents with asthma. This decline is a consequence of what is known as exercise-induced asthma (EIA), and can be determined and graded with the help of lung function tests before and after submaximal workloads on the ergometer cycle or the treadmill. Typical EIA appears in asthmatic individuals with entirely normal lung function before the effort, but EIA may also become clinically manifest with exercise in patients who have a subclinical degree of obstruction. The grade of EIA is essentially dependent on the duration and intensity of effort but also on the type of exercise. For example, free running causes much greater bronchoconstriction than swimming. The temperature and humidity of the inspired air may partially explain this difference. At the Voksentoppen Allergy Institute we find that about 85% of children develop a fall in lung function of 15% or more after a six minute ergometer cycle test. With typical EIA the fall may be totally or partially abolished by prophylactic medication 10 minutes before the start of the test. Disodium cromoglycate (Intal) and/or beta-adrenergic drugs are regularly used before all physical activity. Training programmes must be based on the interval principle. Swimming, ball games, relay races and dancing are examples of useful activities in the training and rehabilitation of children and adolescents with asthma. Through prophylactic medication and physical training, the aerobic work capacity, muscle strength and lung function in asthmatic children is improved. Training also leads to a significant mobilisation of mental resources and an increase in social integration.

  11. Active travel intervention and physical activity behaviour: an evaluation.

    PubMed

    Norwood, Patricia; Eberth, Barbara; Farrar, Shelley; Anable, Jillian; Ludbrook, Anne

    2014-07-01

    A physically active lifestyle is an important contributor to individual health and well-being. The evidence linking higher physical activity levels with better levels of morbidity and mortality is well understood. Despite this, physical inactivity remains a major global risk factor for mortality and, consequently, encouraging individuals to pursue physically active lifestyles has been an integral part of public health policy in many countries. Physical activity promotion and interventions are now firmly on national health policy agendas, including policies that promote active travel such as walking and cycling. This study evaluates one such active travel initiative, the Smarter Choices, Smarter Places programme in Scotland, intended to encourage uptake of walking, cycling and the use of public transport as more active forms of travel. House to house surveys were conducted before and after the programme intervention, in May/June 2009 and 2012 (12,411 surveys in 2009 and 9542 in 2012), for the evaluation of the programme. This paper analyses the physical activity data collected, focussing on what can be inferred from the initiative with regards to adult uptake of physical activity participation and whether, for those who participated in physical activity, the initiative impacted on meeting recommended physical activity guidelines. The results suggest that the initiative impacted positively on the likelihood of physical activity participation and meeting the recommended physical activity guidelines. Individuals in the intervention areas were on average 6% more likely to meet the physical activity guidelines compared to individuals in the non intervention areas. However, the absolute prevalence of physical activity participation declined in both intervention and control areas over time. Our evaluation of this active transport initiative indicates that similar programmes may aid in contributing to achieving physical activity targets and adds to the international

  12. Rationales for regulatory activity

    SciTech Connect

    Perhac, R.M.

    1997-02-01

    The author provides an outline which touches on the types of concerns about risk evaluation which are addressed in the process of establishing regulatory guides. Broadly he says regulatory activity serves three broad constituents: (1) Paternalism (private risk); (2) Promotion of social welfare (public risks); (3) Protection of individual rights (public risks). He then discusses some of the major issues encountered in reaching a decision on what is an acceptable level of risk within each of these areas, and how one establishes such a level.

  13. GPS Activities at SLAC

    SciTech Connect

    Behrend, Dirk

    2002-11-19

    The Alignment Engineering Group of the Stanford Linear Accelerator Center (SLAC) started to use RTK (real-time kinematic) GPS equipment in order to perform structure mapping and GIS-related tasks on the SLAC campus. In a first step a continuously observing GPS station (SLAC M40) was set up. This station serves as master control station for all differential GPS activities on site and its coordinates have been determined in the well-defined global geodetic datum ITRF2000 at a given reference epoch. Some trials have been performed to test the RTK method. The tests have proven RTK to be very fast and efficient.

  14. Reuse of activated alumina

    SciTech Connect

    Hobensack, J.E.

    1991-12-31

    Activated alumina is used as a trapping media to remove trace quantities of UF{sub 6} from process vent streams. The current uranium recovery method employs concentrated nitric acid which destroys the alumina pellets and forms a sludge which is a storage and disposal problem. A recently developed technique using a distilled water rinse followed by three dilute acid rinses removes on average 97% of the uranium, and leaves the pellets intact with crush strength and surface area values comparable with new material. Trapping tests confirm the effectiveness of the recycled alumina as UF{sub 6} trapping media.

  15. Crew Activity Analyzer

    NASA Technical Reports Server (NTRS)

    Murray, James; Kirillov, Alexander

    2008-01-01

    The crew activity analyzer (CAA) is a system of electronic hardware and software for automatically identifying patterns of group activity among crew members working together in an office, cockpit, workshop, laboratory, or other enclosed space. The CAA synchronously records multiple streams of data from digital video cameras, wireless microphones, and position sensors, then plays back and processes the data to identify activity patterns specified by human analysts. The processing greatly reduces the amount of time that the analysts must spend in examining large amounts of data, enabling the analysts to concentrate on subsets of data that represent activities of interest. The CAA has potential for use in a variety of governmental and commercial applications, including planning for crews for future long space flights, designing facilities wherein humans must work in proximity for long times, improving crew training and measuring crew performance in military settings, human-factors and safety assessment, development of team procedures, and behavioral and ethnographic research. The data-acquisition hardware of the CAA (see figure) includes two video cameras: an overhead one aimed upward at a paraboloidal mirror on the ceiling and one mounted on a wall aimed in a downward slant toward the crew area. As many as four wireless microphones can be worn by crew members. The audio signals received from the microphones are digitized, then compressed in preparation for storage. Approximate locations of as many as four crew members are measured by use of a Cricket indoor location system. [The Cricket indoor location system includes ultrasonic/radio beacon and listener units. A Cricket beacon (in this case, worn by a crew member) simultaneously transmits a pulse of ultrasound and a radio signal that contains identifying information. Each Cricket listener unit measures the difference between the times of reception of the ultrasound and radio signals from an identified beacon

  16. Minor meteor shower activity

    NASA Astrophysics Data System (ADS)

    Rendtel, J.

    2016-01-01

    Video meteor observations provide us with data to analyze structures in minor meteor showers or weak features in flux profiles. Samples obtained independently by other techniques allow to calibrate the data sets and to improve the confidence of results as demonstrated with a few results. Both, the confirmation of events predicted by model calculation and the input of observational data to improve the modelling results may help to better understand meteoroid stream evolution processes. Furthermore, calibrated data series can be used for studies of the long-term evolution of meteor shower activity.

  17. Enceladus: Starting Hydrothermal Activity

    NASA Technical Reports Server (NTRS)

    Matson, D. L.; Castillo-Rogez, J. C.; Johnson, T. V.; Lunine, J. I.; Davies, A. G.

    2011-01-01

    We describe a process for starting the hydrothermal activity in Enceladus' South Polar Region. The process takes advantage of fissures that reach the water table, about 1 kilometer below the surface. Filling these fissures with fresh ocean water initiates a flow of water up from an ocean that can be self-sustaining. In this hypothesis the heat to sustain the thermal anomalies and the plumes comes from a slightly warm ocean at depth. The heat is brought to the surface by water that circulates up, through the crust and then returns to the ocean.

  18. Active terahertz metamaterials

    SciTech Connect

    Chen, Hou-tong; O' Hara, John F; Taylor, Antoinette J

    2009-01-01

    In this paper we present an overview of research in our group in terahertz (THz) metamaterials and their applications. We have developed a series of planar metamaterials operating at THz frequencies, all of which exhibit a strong resonant response. By incorporating natural materials, e.g. semiconductors, as the substrates or as critical regions of metamaterial elements, we are able to effectively control the metamaterial resonance by the application of external stimuli, e.g., photoexcitation and electrical bias. Such actively controllable metamaterials provide novel functionalities for solid-state device applications with unprecedented performance, such as THz spectroscopy, imaging, and many others.

  19. Athena: Assessment Phase Activities

    NASA Astrophysics Data System (ADS)

    Lumb, David; Ayre, Mark

    2015-09-01

    The Athena mission concept has been proposed by the community in response to science themes of the Hot and Energetic Universe. Unlike other, competitive, mission selection exercises this "Large" class observatory mission has essentially been pre-selected. Nevertheless it has to be demonstrated that Athena meets the programmatic constraints of 1Bn euro cost cap, and a readiness level appropriate for formal mission adoption by the end 2019. This should be confirmed through a Phase A study conducted with two parallel industry activities. We describe the technical and programmatic content of these and latest progress in space and ground segment definition.

  20. Activation of solar flares

    SciTech Connect

    Cargill, P.J.; Migliuolo, S.; Hood, A.W.

    1984-11-01

    The physics of the activation of two-ribbon solar flares via the MHD instability of coronal arcades is presented. The destabilization of a preflare magnetic field is necessary for a rapid energy release, characteristic of the impulsive phase of the flare, to occur. The stability of a number of configurations are examined, and the physical consequences and relative importance of varying pressure profiles and different sets of boundary conditions (involving field-line tying) are discussed. Instability modes, driven unstable by pressure gradients, are candidates for instability. Shearless vs. sheared equilibria are also discussed. (ESA)

  1. ECLSS medical support activities

    NASA Technical Reports Server (NTRS)

    Crump, William J.; Kilgore, Melvin V., Jr.

    1991-01-01

    During the period from April 10, 1990 to April 9, 1991, the Consortium for the Space Life Sciences provided technical assistance to the NASA/MSFC water recovery efforts. This assistance was in the form of literature reviews, technical recommendations, and presentations. This final report summarizes the activities completed during this period and identifies those areas requiring additional efforts. The tasks which the University of Alabama in Huntsville (UAH) water recovery team addressed were either identified by MSFC technical representatives or chosen from those outlined in the subject statement of work.

  2. Bioethics activities in India.

    PubMed

    Kumar, Nandini K

    2006-01-01

    The Indian Council of Medical Research formulates, coordinates and promotes biomedical research in India. In 1980, they formulated the first national ethical guidelines. They offer a number of different training programmes, from 1 day to 6 months. The council is developing a core curriculum for teaching bioethics, which would be applied uniformly in medical schools throughout the country. Drug development and ethics is also important in India, particularly now that the local pharmaceutical industry is expanding and so many drugs trials are outsourced to the country. The council is also very active in encouraging the development of ethics review committees.

  3. AMS Prototyping Activities

    NASA Technical Reports Server (NTRS)

    Burleigh, Scott

    2008-01-01

    This slide presentation reviews the activity around the Asynchronous Message Service (AMS) prototype. An AMS reference implementation has been available since late 2005. It is aimed at supporting message exchange both in on-board environments and over space links. The implementation incoroporates all mandatory elements of the draft recommendation from July 2007: (1) MAMS, AMS, and RAMS protocols. (2) Failover, heartbeats, resync. (3) "Hooks" for security, but no cipher suites included in the distribution. The performance is reviewed, and a Benchmark latency test over VxWorks Message Queues is shown as histograms of a count vs microseconds per 1000-byte message

  4. Imaging nervous system activity.

    PubMed

    Fields, R D; O'Donovan, M J

    2001-05-01

    Optical imaging methods rely upon visualization of three types of signals: (1) intrinsic optical signals, including light scattering and reflectance, birefringence, and spectroscopic changes of intrinsic molecules, such as NADH or oxyhemoglobin; (2) changes in fluorescence or absorbance of voltage-sensitive membrane dyes; and (3) changes in fluorescence or absorbance of calcium-sensitive indicator dyes. Of these, the most widely used approach is fluorescent microscopy of calcium-sensitive dyes. This unit describes protocols for the use of calcium-sensitive dyes and voltage-dependent dyes for studies of neuronal activity in culture, tissue slices, and en-bloc preparations of the central nervous system.

  5. ASTP RBCC Activities

    NASA Technical Reports Server (NTRS)

    Nelson, Karl W.; McArthur, Craig; Leopard, Larry (Technical Monitor)

    2000-01-01

    This presentation reviews the activities of the Advanced Space Transportation Program (ASTP) in the development of Rocket-Based Combined Cycle (RBCC)technology. The document consist of the presentation slides for a talk scheduled to be given to the World Aviation Congress and Exhibit of SAE. Included in the review is discussion of recent accomplishments in the area of Advanced Reusable technologies (ART), which includes work in flowpath testing, and system studies of the various vehicle/engine combinations including RBCC, Turbine Based Combined Cycle (TBCC) and Pulsed Detonation Engine (PDE). Pictures of the proposed RBCC Flowpaths are included. The next steps in the development process are reviewed.

  6. Hypnotic activity of brotizolam

    PubMed Central

    Uzzan, B.; Warot, D.; Chermat, P.; Dantlo, B.; Bornstein, S.; Simon, P.

    1983-01-01

    1 A double-blind, crossover study was carried out in general practice on the hypnotic activity of 0.25 mg brotizolam in patients aged between 18 and 70 years complaining of insomnia (11 men, 28 women). 2 Patients reported that they slept better, that they awoke less frequently and that they slept longer with brotizolam than with placebo. Overall the patients preferred brotizolam to placebo, and subjective assessments of well-being after brotizolam did not differ from those after placebo. Brotizolam was well tolerated and there were no incidents of note. PMID:6362701

  7. Monitoring international nuclear activity

    SciTech Connect

    Firestone, R.B.

    2006-05-19

    The LBNL Table of Isotopes website provides primary nuclearinformation to>150,000 different users annually. We have developedthe covert technology to identify users by IP address and country todetermine the kinds of nuclear information they are retrieving. Wepropose to develop pattern recognition software to provide an earlywarning system to identify Unusual nuclear activity by country or regionSpecific nuclear/radioactive material interests We have monitored nuclearinformation for over two years and provide this information to the FBIand LLNL. Intelligence is gleaned from the website log files. Thisproposal would expand our reporting capabilities.

  8. Neutron activation analysis system

    DOEpatents

    Taylor, M.C.; Rhodes, J.R.

    1973-12-25

    A neutron activation analysis system for monitoring a generally fluid media, such as slurries, solutions, and fluidized powders, including two separate conduit loops for circulating fluid samples within the range of radiation sources and detectors is described. Associated with the first loop is a neutron source that emits s high flux of slow and thermal neutrons. The second loop employs a fast neutron source, the flux from which is substantially free of thermal neutrons. Adjacent to both loops are gamma counters for spectrographic determination of the fluid constituents. Other gsmma sources and detectors are arranged across a portion of each loop for deterMining the fluid density. (Official Gazette)

  9. Physical Activity in Elderly

    PubMed Central

    Tirpakova, Veronika; Sedliak, Milan; Kern, Helmut; Mayr, Winfried; Hamar, Dušan

    2015-01-01

    Aging is a multifactorial irreversible process associated with significant decline in muscle mass and neuromuscular functions. One of the most efficient methods to counteract age-related changes in muscle mass and function is physical exercise. An alternative effective intervention to improve muscle structure and performance is electrical stimulation. In the present work we present the positive effects of physical activity in elderly and a study where the effects of a 8-week period of functional electrical stimulation and strength training with proprioceptive stimulation in elderly are compared. PMID:26913164

  10. Activities for the classroom

    NASA Astrophysics Data System (ADS)

    Stark, Joyce

    From my research experiences on board the R/V Atlantis, I have developed experiments that can be used in an integrated science program or for biology. These activities reflect life in extreme environments on Earth such as the hydrothermal vents and on other planets and moons in our solar system. Students can learn to map the oceans of Europa and discover how plants grow on Mars. Students have designed research projects from the experimentation that I was involved with through the REVEL program.

  11. The Active Solid Earth

    NASA Astrophysics Data System (ADS)

    Ebinger, Cynthia

    2016-04-01

    Dynamic processes in Earth's crust, mantle and core shape Earth's surface and magnetic field over time scales of seconds to millennia, and even longer time scales as recorded in the ca. 4 Ga rock record. Our focus is the earthquake-volcano deformation cycles that occur over human time scales, and their comparison with time-averaged deformation studies, with emphasis on mantle plume provinces where magma and volatile release and vertical tectonics are readily detectable. Active deformation processes at continental and oceanic rift and back arc zones provide critical constraints on mantle dynamics, the role of fluids (volatiles, magma, water), and plate rheology. For example, recent studies of the East African rift zone, which formed above one of Earth's largest mantle upwellings reveal that magma production and volatile release rates are comparable to those of magmatic arcs, the archetypal zones of continental crustal creation. Finite-length faults achieve some plate deformation, but magma intrusion in the form of dikes accommodates extension in continental, back-arc, and oceanic rifts, and intrusion as sills causes permanent uplift that modulates the local time-space scales of earthquakes and volcanoes. Volatile release from magma intrusion may reduce fault friction and permeability, facilitating aseismic slip and creating magma pathways. We explore the implications of active deformation studies to models of the time-averaged structure of plume and extensional provinces in continental and oceanic plate settings.

  12. Raman activated cell sorting.

    PubMed

    Song, Yizhi; Yin, Huabing; Huang, Wei E

    2016-08-01

    Single cell Raman spectra (SCRS) are intrinsic biochemical profiles and 'chemical images' of single cells which can be used to characterise phenotypic changes, physiological states and functions of cells. On the base of SCRS, Raman activated cell sorting (RACS) provides a label-free cell sorting approach, which can link single cells to their chemical or phenotypic profiles. Overcoming naturally weak Raman signals, establishing Raman biomarker as sorting criteria to RACS and improving specific sorting technology are three challenges of developing RACS. Advances on Raman spectroscopy such as stimulated Raman scattering (SRS) and pre-screening helped to increase RACS sorting speed. Entire SCRS can be characterised using pattern recognition methods, and specific Raman bands can be extracted as biomarkers for RACS. Recent advances on cell sorting technologies based on microfluidic device and surface-ejection enable accurate and reliable single cell sorting from complex samples. A high throughput RACS will be achievable in near future by integrating fast Raman detection system such as SRS with microfluidic RACS and Raman activated cell ejection (RACE).

  13. Microbiologically active nanocomposite media

    NASA Astrophysics Data System (ADS)

    Petranovskii, Vitalii; Panina, Lyudmila; Bogomolova, Eugenia; Belostotskaya, Galina

    2003-07-01

    The most recent approach to the development of novel antimicrobial and antifungal agents is based on the application of synthetic and natural zeolites, because zeolites are known to be the carrier and slow releaser of the heavy metals with olygodynamic properties. The microbiological activity of the ion-exchanged zeolites is attributed to the ionic state of the metal sreleased from the zeolites by ion re-exchange. In the present work we used low cost natural clinoptilolite (Cli) as a substrate for copper and silver in different states. The state of oxidation of the exchanged metal in zeolite with supported Cu and Ag species (in the form of cations, small clusters, sub-coloidal particles, large particles) in order to fit them to fulfill the following criteria: to demonstrate their high protective abilities against fungi and long-term stability. The study of structure of samples with XRD, UV-visible spectroscopy, FTIR, their stability with temperature and during storage was carried out for obtaining the correct correlation with microbiological activity.

  14. Activating event knowledge.

    PubMed

    Hare, Mary; Jones, Michael; Thomson, Caroline; Kelly, Sarah; McRae, Ken

    2009-05-01

    An increasing number of results in sentence and discourse processing demonstrate that comprehension relies on rich pragmatic knowledge about real-world events, and that incoming words incrementally activate such knowledge. If so, then even outside of any larger context, nouns should activate knowledge of the generalized events that they denote or typically play a role in. We used short stimulus onset asynchrony priming to demonstrate that (1) event nouns prime people (sale-shopper) and objects (trip-luggage) commonly found at those events; (2) location nouns prime people/animals (hospital-doctor) and objects (barn-hay) commonly found at those locations; and (3) instrument nouns prime things on which those instruments are commonly used (key-door), but not the types of people who tend to use them (hose-gardener). The priming effects are not due to normative word association. On our account, facilitation results from event knowledge relating primes and targets. This has much in common with computational models like LSA or BEAGLE in which one word primes another if they frequently occur in similar contexts. LSA predicts priming for all six experiments, whereas BEAGLE correctly predicted that priming should not occur for the instrument-people relation but should occur for the other five. We conclude that event-based relations are encoded in semantic memory and computed as part of word meaning, and have a strong influence on language comprehension.

  15. Active Near Earth Asteroids

    NASA Astrophysics Data System (ADS)

    Jenniskens, Peter

    2015-08-01

    Past activity from Near Earth Asteroids is recorded in the meteoroid streams that cause our meteor showers. Automated meteoroid orbit surveys by photographic, low-light video, specular radar, and head-echo radar reflections are providing the first maps of meteor shower activity at different particle sizes. There are distinct differences in particle size distributions among streams. The underlaying mechanisms that created these streams are illuminated: fragmentation from spin-up or thermal stresses, meteoroid ejection by water vapor drag, and ejection of icy particles by CO and CO2 sublimation. The distribution of the meteoroid orbital elements probe the subsequent evolution by planetary perturbations and sample the range of dynamical processes to which Near Earth Asteroids are exposed. The non-stream "sporadic" meteors probe early stages in the evolution from meteoroid streams into the zodiacal dust cloud. We see that the lifetime of large meteoroids is generally not limited by collisions. Results obtained by the CAMS video survey of meteoroid orbits are compared to those from other orbit surveys. Since October 2010, over 200,000 meteoroid orbits have been measured. First results from an expansion into the southern hemisphere are also presented, as are first results from the measurement of main element compositions. Among the many streams detected so far, the Geminid and Sextantid showers stand out by having a relatively high particle density and derive from parent bodies that appear to have originated in the main belt.

  16. Visualizing cellulase activity.

    PubMed

    Bubner, Patricia; Plank, Harald; Nidetzky, Bernd

    2013-06-01

    Commercial exploitation of lignocellulose for biotechnological production of fuels and commodity chemicals requires efficient-usually enzymatic-saccharification of the highly recalcitrant insoluble substrate. A key characteristic of cellulose conversion is that the actual hydrolysis of the polysaccharide chains is intrinsically entangled with physical disruption of substrate morphology and structure. This "substrate deconstruction" by cellulase activity is a slow, yet markedly dynamic process that occurs at different length scales from and above the nanometer range. Little is currently known about the role of progressive substrate deconstruction on hydrolysis efficiency. Application of advanced visualization techniques to the characterization of enzymatic degradation of different celluloses has provided important new insights, at the requisite nano-scale resolution and down to the level of single enzyme molecules, into cellulase activity on the cellulose surface. Using true in situ imaging, dynamic features of enzyme action and substrate deconstruction were portrayed at different morphological levels of the cellulose, thus providing new suggestions and interpretations of rate-determining factors. Here, we review the milestones achieved through visualization, the methods which significantly promoted the field, compare suitable (model) substrates, and identify limiting factors, challenges and future tasks.

  17. [Sport and physical activity].

    PubMed

    Bria, S; Zeppilli, P

    2010-01-01

    A regular sport activity involves physical and psychological benefits helping to improve the quality of life at any age. This aspect is even more important in the developing age, when the sport takes on a role of training and education. In this context, instances directed to allow adolescent and young adults with heart disease to practice sports seem justified, and they're becoming more pressing since when the diagnostic and therapeutic advances, especially in cardiac surgery and in interventional hemodynamics, allow an increasing number of patients, previously allocated to physical inactivity, to lead an active lifestyle. However, we have to keep in mind that congenital heart disease population is varied, not only by the nature of the malformation, but also because in the same cardiopathy you can find subjects in "natural history" or after surgery and, between them, subjects treated with several techniques and different outcomes. This justifies the need for a close collaboration between sports doctors, cardiologists and heart surgeons, particularly in the management of the most difficult and delicate problems.

  18. Active Astronomy Roadshow Haiti

    NASA Astrophysics Data System (ADS)

    Laycock, Silas; Oram, Kathleen; Alabre, Dayana; Douyon, Ralph; UMass Lowell Haiti Development Studies Center

    2016-01-01

    College-age Haitian students working with advisors and volunteers from UMass Lowell in 2015 developed and tested an activity-based K-8 curriculum in astronomy, space, and earth science. Our partner school is located in Les Cayes, Haiti a city where only 65% of children attend school, and only half of those will complete 6th grade. Astronomy provides an accessible and non-intimidating entry into science, and activity-based learning contrasts with the predominant traditional teaching techniques in use in Haiti, to reach and inspire a different cohort of learners. Teachers are predominantly women in Haiti, so part of the effort involves connecting them with scientists, engineers and teacher peers in the US. As a developing nation, it is vital for Haitian (as for all) children to grow up viewing women as leaders in science. Meanwhile in the US, few are aware of the reality of getting an education in a 3rd world nation (i.e. most of the world), so we also joined with teachers in Massachusetts to give US school children a peek at what daily life is like for their peers living in our vibrant but impoverished neighbor. Our Haitian partners are committed to helping their sister-schools with curriculum and educator workshops, so that the overall quality of education can rise, and not be limited to the very few schools with access to resources. We will describe the activites, motivation, and and the lessons learned from our first year of the project.

  19. Neutron activation for ITER

    SciTech Connect

    Barnes, C.W.; Loughlin, M.J.; Nishitani, Takeo

    1996-04-29

    There are three primary goals for the Neutron Activation system for ITER: maintain a robust relative measure of fusion power with stability and high dynamic range (7 orders of magnitude); allow an absolute calibration of fusion power (energy); and provide a flexible and reliable system for materials testing. The nature of the activation technique is such that stability and high dynamic range can be intrinsic properties of the system. It has also been the technique that demonstrated (on JET and TFTR) the highest accuracy neutron measurements in DT operation. Since the gamma-ray detectors are not located on the tokamak and are therefore amenable to accurate characterization, and if material foils are placed very close to the ITER plasma with minimum scattering or attenuation, high overall accuracy in the fusion energy production (7--10%) should be achievable on ITER. In the paper, a conceptual design is presented. A system is shown to be capable of meeting these three goals, also detailed design issues remain to be solved.

  20. Tracking dynamic team activity

    SciTech Connect

    Tambe, M.

    1996-12-31

    AI researchers are striving to build complex multi-agent worlds with intended applications ranging from the RoboCup robotic soccer tournaments, to interactive virtual theatre, to large-scale real-world battlefield simulations. Agent tracking - monitoring other agent`s actions and inferring their higher-level goals and intentions - is a central requirement in such worlds. While previous work has mostly focused on tracking individual agents, this paper goes beyond by focusing on agent teams. Team tracking poses the challenge of tracking a team`s joint goals and plans. Dynamic, real-time environments add to the challenge, as ambiguities have to be resolved in real-time. The central hypothesis underlying the present work is that an explicit team-oriented perspective enables effective team tracking. This hypothesis is instantiated using the model tracing technology employed in tracking individual agents. Thus, to track team activities, team models are put to service. Team models are a concrete application of the joint intentions framework and enable an agent to track team activities, regardless of the agent`s being a collaborative participant or a non-participant in the team. To facilitate real-time ambiguity resolution with team models: (i) aspects of tracking are cast as constraint satisfaction problems to exploit constraint propagation techniques; and (ii) a cost minimality criterion is applied to constrain tracking search. Empirical results from two separate tasks in real-world, dynamic environments one collaborative and one competitive - are provided.

  1. Regulation of inflammasome activation.

    PubMed

    Man, Si Ming; Kanneganti, Thirumala-Devi

    2015-05-01

    Inflammasome biology is one of the most exciting and rapidly growing areas in immunology. Over the past 10 years, inflammasomes have been recognized for their roles in the host defense against invading pathogens and in the development of cancer, auto-inflammatory, metabolic, and neurodegenerative diseases. Assembly of an inflammasome complex requires cytosolic sensing of pathogen-associated molecular patterns or danger-associated molecular patterns by a nucleotide-binding domain and leucine-rich repeat receptor (NLR) or absent in melanoma 2 (AIM2)-like receptors (ALR). NLRs and ALRs engage caspase-1, in most cases requiring the adapter protein apoptosis-associated speck-like protein containing a CARD (ASC), to catalyze proteolytic cleavage of pro-interleukin-1β (pro-IL-1β) and pro-IL-18 and drive pyroptosis. Recent studies indicate that caspase-8, caspase-11, IL-1R-associated kinases (IRAK), and receptor-interacting protein (RIP) kinases contribute to inflammasome functions. In addition, post-translational modifications, including ubiquitination, deubiquitination, phosphorylation, and degradation control almost every aspect of inflammasome activities. Genetic studies indicate that mutations in NLRP1, NLRP3, NLRC4, and AIM2 are linked with the development of auto-inflammatory diseases, enterocolitis, and cancer. Overall, these findings transform our understanding of the basic biology and clinical relevance of inflammasomes. In this review, we provide an overview of the latest development of inflammasome research and discuss how inflammasome activities govern health and disease.

  2. Activities in dementia care: A comparative assessment of activity types.

    PubMed

    Lokon, Elizabeth; Sauer, Philip E; Li, Yue

    2016-12-05

    This exploratory study compares the impact of five activity types on the well-being of institutionalized people with dementia: the intergenerational art program Opening Minds through Art, art and music therapies, creative activities, non-creative activities, and no activities at all. We validated the Scripps Modified Greater Cincinnati Chapter Well-Being Observational Tool, and used that instrument to systematically observe N = 67 people with dementia as they participated in different activity types. People with dementia showed the highest well-being scores during Opening Minds through Art compared to all other activities. No significant well-being differences were found between creative activities led by licensed art/music therapist versus regular activity staff. Furthermore, no significant well-being differences were found between creative and non-creative activities that were both led by regular activity staff. Overall, people with dementia benefit from participating in activities, regardless of the type (creative or non-creative), or who conducts them (licensed therapists or activity staff). However, in order for people with dementia to reach significantly high levels of overall well-being, we recommend that activities are specifically designed for people with dementia and incorporate a 1:1 ratio between people with dementia and well-trained volunteers/staff members.

  3. Memory in Autistic Spectrum Disorder

    ERIC Educational Resources Information Center

    Boucher, Jill; Mayes, Andrew; Bigham, Sally

    2012-01-01

    Behavioral evidence concerning memory in forms of high-functioning autism (HFA) and in moderately low-functioning autism (M-LFA) is reviewed and compared. Findings on M-LFA are sparse. However, it is provisionally concluded that memory profiles in HFA and M-LFA (relative to ability-matched controls) are similar but that declarative memory…

  4. Point-of-care diagnosis and prognostication of cryptococcal meningitis with the cryptococcal antigen lateral flow assay on cerebrospinal fluid.

    PubMed

    Kabanda, Taseera; Siedner, Mark J; Klausner, Jeffrey D; Muzoora, Conrad; Boulware, David R

    2014-01-01

    The cryptococcal antigen (CRAG) lateral flow assay (LFA) had 100% sensitivity and specificity on cerebrospinal fluid samples. Pretreatment LFA titers correlated with quantitative cultures (R(2) = 0.7) and predicted 2- and 10-week mortality. The CRAG LFA is an accurate diagnostic assay for CSF and should be considered for point-of-care diagnosis of cryptococcal meningitis.

  5. The active video games' narrative impact on children's physical activities

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Active video games (AVGs) capable of inducing physical activity offer an innovative approach to combating childhood obesity. Unfortunately, children's AVG game play decreases quickly, underscoring the need to identify novel methods for player engagement. Narratives have been demonstrated to influenc...

  6. Application of encoded library technology (ELT) to a protein-protein interaction target: discovery of a potent class of integrin lymphocyte function-associated antigen 1 (LFA-1) antagonists.

    PubMed

    Kollmann, Christopher S; Bai, Xiaopeng; Tsai, Ching-Hsuan; Yang, Hongfang; Lind, Kenneth E; Skinner, Steven R; Zhu, Zhengrong; Israel, David I; Cuozzo, John W; Morgan, Barry A; Yuki, Koichi; Xie, Can; Springer, Timothy A; Shimaoka, Motomu; Evindar, Ghotas

    2014-04-01

    The inhibition of protein-protein interactions remains a challenge for traditional small molecule drug discovery. Here we describe the use of DNA-encoded library technology for the discovery of small molecules that are potent inhibitors of the interaction between lymphocyte function-associated antigen 1 and its ligand intercellular adhesion molecule 1. A DNA-encoded library with a potential complexity of 4.1 billion compounds was exposed to the I-domain of the target protein and the bound ligands were affinity selected, yielding an enriched small-molecule hit family. Compounds representing this family were synthesized without their DNA encoding moiety and found to inhibit the lymphocyte function-associated antigen 1/intercellular adhesion molecule-1 interaction with submicromolar potency in both ELISA and cell adhesion assays. Re-synthesized compounds conjugated to DNA or a fluorophore were demonstrated to bind to cells expressing the target protein.

  7. Active Magnetic Regenerative Liquefier

    SciTech Connect

    Barclay, John A.; Oseen-Send, Kathryn; Ferguson, Luke; Pouresfandiary, Jamshid; Cousins, Anand; Ralph, Heather; Hampto, Tom

    2016-01-12

    This final report for the DOE Project entitled Active Magnetic Regenerative Liquefier (AMRL) funded under Grant DE-FG36-08GO18064 to Heracles Energy Corporation d.b.a. Prometheus Energy (Heracles/Prometheus) describes an active magnetic regenerative refrigerator (AMRR) prototype designed and built during the period from July 2008 through May 2011. The primary goal of this project was to make significant technical advances toward highly efficient liquefaction of hydrogen. Conventional hydrogen liquefiers at any scale have a maximum FOM of ~0.35 due primarily to the intrinsic difficulty of rapid, efficient compression of either hydrogen or helium working gases. Numerical simulation modeling of high performance AMRL designs indicates certain designs have promise to increase thermodynamic efficiency from a FOM of ~0.35 toward ~0.5 to ~0.6. The technical approach was the use of solid magnetic working refrigerants cycled in and out of high magnetic fields to build an efficient active regenerative magnetic refrigeration module providing cooling power for AMRL. A single-stage reciprocating AMRR with a design temperature span from ~290 K to ~120 K was built and tested with dual magnetic regenerators moving in and out of the conductively-cooled superconducting magnet subsystem. The heat transfer fluid (helium) was coupled to the process stream (refrigeration/liquefaction load) via high performance heat exchangers. In order to maximize AMRR efficiency a helium bypass loop with adjustable flow was incorporated in the design because the thermal mass of magnetic refrigerants is higher in low magnetic field than in high magnetic field. Heracles/Prometheus designed experiments to measure AMRR performance under a variety of different operational parameters such as cycle frequency, magnetic field strength, heat transfer fluid flow rate, amount of bypass flow of the heat transfer fluid while measuring work input, temperature span, cooling capability as a function of cold temperature

  8. Overview of Langley activities in active controls research

    NASA Technical Reports Server (NTRS)

    Abel, I.; Newsom, J. R.

    1981-01-01

    The application of active controls technology to reduce aeroelastic response of aircraft structures offers a potential for significant payoffs in terms of aerodynamic efficiency and weight savings. The activities of the Langley Research Center (laRC) in advancing active controls technology. Activities are categorized into the development of appropriate analysis tools, control law synthesis methodology, and experimental investigations aimed at verifying both analysis and synthesis methodology.

  9. Youth Physical Activity Resource Use and Activity Measured by Accelerometry

    ERIC Educational Resources Information Center

    Maslow, Andra L.; Colabianchi, Natalie

    2011-01-01

    Objectives: To examine whether use of physical activity resources (e.g., parks) was associated with daily physical activity measured by accelerometry. Methods: One hundred eleven adolescents completed a travel diary with concurrent accelerometry. The main exposure was self-reported use of a physical activity resource (none /1 resources). The main…

  10. Examining Activism in Practice: A Qualitative Study of Archival Activism

    ERIC Educational Resources Information Center

    Novak, Joy Rainbow

    2013-01-01

    While archival literature has increasingly discussed activism in the context of archives, there has been little examination of the extent to which archivists in the field have accepted or incorporated archival activism into practice. Scholarship that has explored the practical application of archival activism has predominately focused on case…

  11. Activity Based Curriculum for Elementary Education. Additional Activities, K-6.

    ERIC Educational Resources Information Center

    Wichita Public Schools, KS.

    This elementary curriculum is a vehicle to provide manipulative activities that reinforce academic skills through meaningful, relevant, activity-based awareness of modern society. The twenty-six activity plans included in the curriculum place a major emphasis upon realistic or concrete experiences that deal with the manipulation and exploration of…

  12. Active Play: Exploring the Influences on Children's School Playground Activities

    ERIC Educational Resources Information Center

    Hyndman, Brendon; Benson, Amanda; Telford, Amanda

    2016-01-01

    Because children spend so much of their time in schools, their playgrounds offer a good setting for promoting active play in young lives. Teachers, instead of considering active play a taxing demand on their busy day, have begun to develop an informal curriculum for it. The authors review the research on children's active play and explores its…

  13. 101 Environmental Education Activities. Booklet 2--Language Art Activities.

    ERIC Educational Resources Information Center

    Whitney, Helen, Comp.

    This booklet containing 20 language arts activities is the second in the series "101 Environmental Education Activities" produced by the Upper Mississippi River ECO-Center. The description of each activity contains learning objectives, directions, and suggested student evaluation standards. Elementary and intermediate level students…

  14. 101 Environmental Education Activities. Booklet 4--Science Activities.

    ERIC Educational Resources Information Center

    Whitney, Helen, Comp.

    Fourth in the series "101 Environmental Education Activities" by the Upper Mississippi River ECO-Center, the booklet contains 39 environment-based science activities directed to students in primary, intermediate, and junior high classes. Organization of the activities usually includes grade level, objectives, procedures, and materials,…

  15. 101 Environmental Education Activities. Booklet 1--Art and Music Activities.

    ERIC Educational Resources Information Center

    Whitney, Helen, Comp.

    First of a series of 6 publications containing environmental education activities, this booklet by the Upper Mississippi River ECO-Center describes 12 environmentally-based art and music activities for elementary and intermediate grades. Each activity description contains objectives, preparation, materials, directions, student evaluation, and…

  16. Is enhanced physical activity possible using active videogames?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Our research indicated that 10– to 12-year-old children receiving two active Wii (TM)(Nintendo (R); Nintendo of America, Inc., Redmond, WA) console videogames were no more physically active than children receiving two inactive videogames. Research is needed on how active videogames may increase phys...

  17. Summary of JPL Activities

    NASA Technical Reports Server (NTRS)

    Timmerman, Paul J.; Surampudi, Subbarao

    2000-01-01

    A viewgraph presentation outlines the Jet Propulsion Laboratory (JPL) flight programs, including past, present and future missions targeting Solar System exploration. Details, including launch dates and batteries used, are given for Deep Space 1 (Asteroid Rendezvous), Deep Space 2 (Mars Penetrator), Mars Global Surveyor, Mars Surveyor '98, Stardust, Europa Orbiter, Mars Surveyor 2001, Mars 2003 Lander and Rover, and Genesis (Solar Dust Return). Earth science projects are also outlined: Active Cavity Radiometer Irradiance Monitor (ARIMSAT), Ocean Topography Experiment (TOPEX/Poseidon), Jason-1 (TOPEX follow-on), and QuikScat/Seawinds (Ocean Winds Tracking). The status, background, and plans are given for several batteries: (1) 2.5 inch common pressure vessel (CPV), (2) 3.5 inch CPV, (3) Ni-H2, and (4) Li-Ion.

  18. P21 activated kinases

    PubMed Central

    Rane, Chetan K; Minden, Audrey

    2014-01-01

    The p21 activated kinases (Paks) are well known effector proteins for the Rho GTPases Cdc42 and Rac. The Paks contain 6 members, which fall into 2 families of proteins. The first family consists of Paks 1, 2, and 3, and the second consists of Paks 4, 5, and 6. While some of the Paks are ubiquitously expressed, others have more restrictive tissue specificity. All of them are found in the nervous system. Studies using cell culture, transgenic mice, and knockout mice, have revealed important roles for the Paks in cytoskeletal organization and in many aspects of cell growth and development. This review discusses the basic structures of the Paks, and their roles in cell growth, development, and in cancer. PMID:24658305

  19. Extravehicular activity welding experiment

    NASA Technical Reports Server (NTRS)

    Watson, J. Kevin

    1989-01-01

    The In-Space Technology Experiments Program (INSTEP) provides an opportunity to explore the many critical questions which can only be answered by experimentation in space. The objective of the Extravehicular Activity Welding Experiment definition project was to define the requirements for a spaceflight experiment to evaluate the feasibility of performing manual welding tasks during EVA. Consideration was given to experiment design, work station design, welding hardware design, payload integration requirements, and human factors (including safety). The results of this effort are presented. Included are the specific objectives of the flight test, details of the tasks which will generate the required data, and a description of the equipment which will be needed to support the tasks. Work station requirements are addressed as are human factors, STS integration procedures and, most importantly, safety considerations. A preliminary estimate of the cost and the schedule for completion of the experiment through flight and postflight analysis are given.

  20. Active Piezoelectric Diaphragms

    NASA Technical Reports Server (NTRS)

    Bryant, Robert G.; Effinger, Robert T., IV; Aranda, Isaiah, Jr.; Copeland, Ben M.; Covington, Ed W., III

    2002-01-01

    Several active piezoelectric diaphragms were fabricated by placing unelectroded piezoelectric disks between copper clad films patterned with Inter-Circulating Electrodes "ICE". When a voltage potential is applied to the electrodes, the result is radially distributed electric field that mechanically strains the piezo-ceramic along the Z-axis (perpendicular to the applied electric field), rather than the expected in-plane (XY-axis) direction. Unlike other out of plane piezoelectric actuators, which are benders, these Radial Field Diaphragms (RFDs) strain concentrically yet afford high displacements while maintaining a constant circumference. This paper covers the fabrication and characterization of these diaphragms as a function of poling field strength, ceramic diameter and line spacing, as well as the surface topography, the resulting strain field and displacement as a function of applied voltage ranging from DC to 10 Hz.

  1. Mechanically Activated Ion Channels

    PubMed Central

    Ranade, Sanjeev S.; Syeda, Ruhma; Patapoutian, Ardem

    2015-01-01

    Mechanotransduction, the conversion of physical forces into biochemical signals, is an essential component of numerous physiological processes including not only conscious senses of touch and hearing, but also unconscious senses such as blood pressure regulation. Mechanically activated (MA) ion channels have been proposed as sensors of physical force, but the identity of these channels and an understanding of how mechanical force is transduced has remained elusive. A number of recent studies on previously known ion channels along with the identification of novel MA ion channels have greatly transformed our understanding of touch and hearing in both vertebrates and invertebrates. Here, we present an updated review of eukaryotic ion channel families that have been implicated in mechanotransduction processes and evaluate the qualifications of the candidate genes according to specified criteria. We then discuss the proposed gating models for MA ion channels and highlight recent structural studies of mechanosensitive potassium channels. PMID:26402601

  2. DPAL activities in Japan

    NASA Astrophysics Data System (ADS)

    Endo, Masamori; Wani, Fumio

    2015-02-01

    Activities on diode pumped alkali laser (DPAL) in Japan is reviewed. We have started alkali laser works in 2011, and currently, we are the only players in Japan. Our interests are application oriented, and it is not only defense but also industrial. DPAL is a good candidate as a source of remote laser machining, thanks to its scalability and extremely good beam quality. We are studying on scientific and engineering problems of Cs DPAL with a small-scale apparatus. A commercial diode laser with volume Bragg grating outcoupler is used to pump the gain cell longitudinally. A 6.5 W continuous-wave output with optical to optical efficiency of 56% (based on the absorbed power) has been achieved. Numerical simulation codes are developed to understand the physics of DPAL and to help future developments.

  3. Active submarine volcano sampled

    USGS Publications Warehouse

    Taylor, B.

    1983-01-01

    On June 4, 1982, two full dredge hauls of fresh lava were recovered from the upper flanks of Kavachi submarine volcano, Solomon Islands, in the western Pacific Ocean, from the water depths of 1,200 and 2,700 feet. the shallower dredge site was within 0.5 mile of the active submarine vent shown at the surface by an area of slick water, probably caused by gas emissions. Kavachi is a composite stratovolcano that has been observed to erupt every year or two for at least the last 30 years (see photographs). An island formed in 1952, 1961, 1965, and 1978; but, in each case, it rapidly eroded below sea level. The latest eruption was observed by Solair pilots during the several weeks up to and including May 18, 1982. 

  4. Mechanically Activated Ion Channels.

    PubMed

    Ranade, Sanjeev S; Syeda, Ruhma; Patapoutian, Ardem

    2015-09-23

    Mechanotransduction, the conversion of physical forces into biochemical signals, is essential for various physiological processes such as the conscious sensations of touch and hearing, and the unconscious sensation of blood flow. Mechanically activated (MA) ion channels have been proposed as sensors of physical force, but the identity of these channels and an understanding of how mechanical force is transduced has remained elusive. A number of recent studies on previously known ion channels along with the identification of novel MA ion channels have greatly transformed our understanding of touch and hearing in both vertebrates and invertebrates. Here, we present an updated review of eukaryotic ion channel families that have been implicated in mechanotransduction processes and evaluate the qualifications of the candidate genes according to specified criteria. We then discuss the proposed gating models for MA ion channels and highlight recent structural studies of mechanosensitive potassium channels.

  5. Monitoring active volcanoes

    USGS Publications Warehouse

    Tilling, Robert I.

    1987-01-01

    One of the most spectacular, awesomely beautiful, and at times destructive displays of natural energy is an erupting volcano, belching fume and ash thousands of meters into the atmosphere and pouring out red-hot molten lava in fountains and streams. Countless eruptions in the geologic past have produced volcanic rocks that form much of the Earth's present surface. The gradual disintegration and weathering of these rocks have yielded some of the richest farmlands in the world, and these fertile soils play a significant role in sustaining our large and growing population. Were it not for volcanic activity, the Hawaiian Islands with their sugar cane and pineapple fields and magnificent landscapes and seascapes would not exist to support their residents and to charm their visitors. Yet, the actual eruptive processes are catastrophic and can claim life and property.

  6. CNES gondola development activities

    NASA Astrophysics Data System (ADS)

    Vargas, André; Verdier, Nicolas; Escarnot, Jean-Pierre; Vargas, André

    Recent safety rules and gondola obsolescence oblige CNES to initiate new developments to improve performances according scientific needs. A large project called NOSYCA will able to offer versatile housekeeping and science telemetry system for Zero Pressure Balloons. This concept is modular, use IP protocol for scientific high data rate and mix telemetry systems to perform long duration flight. To respect safety duties, the long duration flight ISBA gondola is modified. New functions are implemented to increase reliability for stratospheric super and zero Pressure balloons flights. "Pointed gondola activity" is also concerned by improvements. After the First Fireball flight, new equipment designs are in progress for future missions. At least, boundary layer balloons performances of science payload and housekeeping system increase with new instrumentation and network telemetry concepts.

  7. Factors regulating microglia activation

    PubMed Central

    Kierdorf, Katrin; Prinz, Marco

    2013-01-01

    Microglia are resident macrophages of the central nervous system (CNS) that display high functional similarities to other tissue macrophages. However, it is especially important to create and maintain an intact tissue homeostasis to support the neuronal cells, which are very sensitive even to minor changes in their environment. The transition from the “resting” but surveying microglial phenotype to an activated stage is tightly regulated by several intrinsic (e.g., Runx-1, Irf8, and Pu.1) and extrinsic factors (e.g., CD200, CX3CR1, and TREM2). Under physiological conditions, minor changes of those factors are sufficient to cause fatal dysregulation of microglial cell homeostasis and result in severe CNS pathologies. In this review, we discuss recent achievements that gave new insights into mechanisms that ensure microglia quiescence. PMID:23630462

  8. Implementation team activities

    NASA Astrophysics Data System (ADS)

    Linder, F.

    2002-12-01

    The implementation Team (IT) is a body reporting to the SCSB,. It has been assigned the task of preparing and harmonising policy, standards and specification proposals for evaluation, qualification and quality control, thus enabling a coherent and cost-effective ESCC Specification System for the procurement of EEE space components. Among the 10 recommendations issued by the SCAHC, 7 have been studied under the auspices of the Implementation Team. Its main activities have been the updating and modernising of the ESA/SCC system in order to meet user needs and to be compatible with market trends. In particular it updated the technical aspects of generic specifications for the different component families and introduced the QML concept into the SCC system. It has also studied and discussed other topics such as procurement standards, a reliability system, mutual recognition, databases and the preferred parts list. A summary of the progress made in all these fields will be presented below.

  9. Actively stressed marginal networks.

    PubMed

    Sheinman, M; Broedersz, C P; MacKintosh, F C

    2012-12-07

    We study the effects of motor-generated stresses in disordered three-dimensional fiber networks using a combination of a mean-field theory, scaling analysis, and a computational model. We find that motor activity controls the elasticity in an anomalous fashion close to the point of marginal stability by coupling to critical network fluctuations. We also show that motor stresses can stabilize initially floppy networks, extending the range of critical behavior to a broad regime of network connectivities below the marginal point. Away from this regime, or at high stress, motors give rise to a linear increase in stiffness with stress. Finally, we demonstrate that our results are captured by a simple, constitutive scaling relation highlighting the important role of nonaffine strain fluctuations as a susceptibility to motor stress.

  10. Lightning activity on Jupiter

    NASA Technical Reports Server (NTRS)

    Borucki, W. J.; Bar-Nun, A.; Scarf, F. L.; Look, A. F.; Hunt, G. E.

    1982-01-01

    Photographic observations of the nightside of Jupiter by the Voyager 1 spacecraft show the presence of extensive lightning activity. Detection of whistlers by the plasma wave analyzer confirms the optical observations and implies that many flashes were not recorded by the Voyager camera because the intensity of the flashes was below the threshold sensitivity of the camera. Measurements of the optical energy radiated per flash indicate that the observed flashes had energies similar to that for terrestrial superbolts. The best estimate of the lightning energy dissipation rate of 0.0004 W/sq m was derived from a consideration of the optical and radiofrequency measurements. The ratio of the energy dissipated by lightning compared to the convective energy flux is estimated to be between 0.000027 and 0.00005. The terrestrial value is 0.0001.

  11. Small Active Radiation Monitor

    NASA Technical Reports Server (NTRS)

    Badhwar, Gautam D.

    2004-01-01

    A device, named small active radiation monitor, allows on-orbit evaluations during periods of increased radiation, after extravehicular activities, or at predesignated times for crews on such long-duration space missions as on the International Space Station. It also permits direct evaluation of biological doses, a task now performed using a combination of measurements and potentially inaccurate simulations. Indeed the new monitor can measure a full array of radiation levels, from soft x-rays to hard galactic cosmic-ray particles. With refinement, it will benefit commercial (nuclear power-plant workers, airline pilots, medical technicians, physicians/dentists, and others) and military personnel as well as the astronauts for whom thermoluminescent dosimeters are inadequate. Civilian and military personnel have long since graduated from film badges to thermoluminescent dosimeters. Once used, most dosimeters must be returned to a central facility for processing, a step that can take days or even weeks. While this suffices for radiation workers for whom exposure levels are typically very low and of brief duration, it does not work for astronauts. Even in emergencies and using express mail, the results can often be delayed by as much as 24 hours. Electronic dosimeters, which are the size of electronic oral thermometers, and tattlers, small electronic dosimeters that sound an alarm when the dose/dose rate exceeds preset values, are also used but suffer disadvantages similar to those of thermoluminescent dosimeters. None of these devices fully answers the need of rapid monitoring during the space missions. Instead, radiation is monitored by passive detectors, which are read out after the missions. Unfortunately, these detectors measure only the absorbed dose and not the biologically relevant dose equivalent. The new monitor provides a real-time readout, a time history of radiation exposures (both absorbed dose and biologically relevant dose equivalent), and a count of the

  12. Earthquake activity in Oklahoma

    SciTech Connect

    Luza, K.V.; Lawson, J.E. Jr. )

    1989-08-01

    Oklahoma is one of the most seismically active areas in the southern Mid-Continent. From 1897 to 1988, over 700 earthquakes are known to have occurred in Oklahoma. The earliest documented Oklahoma earthquake took place on December 2, 1897, near Jefferson, in Grant County. The largest known Oklahoma earthquake happened near El Reno on April 9, 1952. This magnitude 5.5 (mb) earthquake was felt from Austin, Texas, to Des Moines, Iowa, and covered a felt area of approximately 362,000 km{sup 2}. Prior to 1962, all earthquakes in Oklahoma (59) were either known from historical accounts or from seismograph stations outside the state. Over half of these events were located in Canadian County. In late 1961, the first seismographs were installed in Oklahoma. From 1962 through 1976, 70 additional earthquakes were added to the earthquake database. In 1977, a statewide network of seven semipermanent and three radio-telemetry seismograph stations were installed. The additional stations have improved earthquake detection and location in the state of Oklahoma. From 1977 to 1988, over 570 additional earthquakes were located in Oklahoma, mostly of magnitudes less than 2.5. Most of these events occurred on the eastern margin of the Anadarko basin along a zone 135 km long by 40 km wide that extends from Canadian County to the southern edge of Garvin County. Another general area of earthquake activity lies along and north of the Ouachita Mountains in the Arkoma basin. A few earthquakes have occurred in the shelves that border the Arkoma and Anadarko basins.

  13. Science Activities for School Trips.

    ERIC Educational Resources Information Center

    Quint, Walter C.

    1980-01-01

    Describes ways in which physics-learning activity packets can be used by high school students participating in trips organized by other departments. Provides an example of physics activities incorporated into an airplane trip to Disney World. (CS)

  14. Antinociceptive activity of Helicteres isora.

    PubMed

    Venkatesh, Sama; Laxmi, K Sai; Reddy, B Madhava; Ramesh, M

    2007-02-01

    Helicteres isora root extracts were studied for antinociceptive activity on acetic acid-induced writhing test in mice, at a dose of 250 mg/kg. Petroleum ether, chloroform and aqueous ethanol extracts have shown significant activity.

  15. Physical Activity and Your Heart

    MedlinePlus

    ... more energy than resting. Walking, running, dancing, swimming, yoga, and gardening are a few examples of physical activity. According to the Department of Health and Human Services' 2008 Physical Activity Guidelines for ...

  16. Environmental Education Tips: Weather Activities.

    ERIC Educational Resources Information Center

    Brainard, Audrey H.

    1989-01-01

    Provides weather activities including questions, on weather, heating the earth's surface, air, tools of the meteorologist, clouds, humidity, wind, and evaporation. Shows an example of a weather chart activity. (RT)

  17. Physical activity extends life expectancy

    Cancer.gov

    Leisure-time physical activity is associated with longer life expectancy, even at relatively low levels of activity and regardless of body weight, according to a study by a team of researchers led by the NCI.

  18. Antiviral activities of photoactive perylenequinones.

    PubMed

    Hudson, J B; Imperial, V; Haugland, R P; Diwu, Z

    1997-02-01

    Nine perylenequinones (PQ), including some familiar naturally occurring pigments, were compared for their light-mediated antiviral efficacies. Calphostin C was the most active compound against the two target viruses, herpes simplex virus type 1 and Sindbis virus. Hypocrellins A and B were also very active. However, three cercosporin-like PQ were substantially less active in spite of their high quantum yields of singlet oxygen, whereas phleichrome, another efficient singlet oxygen producer, showed no detectable antiviral activity. One other PQ, which was a very weak singlet oxygen producer, also showed no antiviral activity. None of the active compounds showed significant antiviral activity in the dark. Thus, for some groups of PQ there was correlation between quantum yield of singlet oxygen (1O2) and antiviral efficacy, but there are evidently other structural features of PQ that influence activity.

  19. Papermaking as a Science Activity.

    ERIC Educational Resources Information Center

    Fetters, Marcia K.

    2000-01-01

    Describes a simple procedure for making paper and provides some suggestions for extending and modifying the activity. The activity is correlated to the National Science Standards and Benchmarks for Science Literacy. (SAH)

  20. Diabetes Diet, Eating, & Physical Activity

    MedlinePlus

    ... Disease, & Other Dental Problems Diabetes & Sexual & Urologic Problems Diabetes Diet, Eating, & Physical Activity Nutrition and physical activity ... What foods can I eat if I have diabetes? You may worry that having diabetes means going ...

  1. The Study of Animal Activity

    ERIC Educational Resources Information Center

    Westling, Bruce

    1971-01-01

    Describes how to measure the daily rhythm of activity (photoperiodism) of small mammals. Three methods for recording information are reviewed including instructions for making a recorder. Includes suggestions for activities and experiments. (PR)

  2. Organic active materials for batteries

    SciTech Connect

    Abouimrane, Ali; Weng, Wei; Amine, Khalil

    2016-08-16

    A rechargeable battery includes a compound having at least two active sites, R.sup.1 and R.sup.2; wherein the at least two active sites are interconnected by one or more conjugated moieties; each active site is coordinated to one or more metal ions M.sup.a+ or each active site is configured to coordinate to one or more metal ions; and "a" is 1, 2, or 3.

  3. Insight into hydroxides-activated coals: chemical or physical activation?

    SciTech Connect

    Alcaniz-Monge, J.; Illan-Gomez, M.J.

    2008-02-15

    The objective of this paper is to get an insight into the chemical activation mechanism using KOH and NaOH as activated agents. Three coals have been selected as carbon precursors. It was found that KOH and NaOH develop a similar narrow microporosity, independently of the coal rank, whereas only KOH generates supermicroporosity. Temperature-programmed desorption experiments, carried out with impregnated anthracite, show differences on the gas evolved during the activated carbon preparation using the two activating agents. Thus, whereas hydrogen profiles are quite similar for both activated agents, the CO and H{sub 2}O profiles are different. It is remarkable the high amount of H{sub 2}O evolved at the maximum treatment temperature for both activating agents. The results obtained to allow conclusion that the chemical activation is due to a combination of different process driving the development of material porosity.

  4. Assessing and Increasing Physical Activity

    ERIC Educational Resources Information Center

    Van Camp, Carole M.; Hayes, Lynda B.

    2012-01-01

    Increasing physical activity is a crucial component of any comprehensive approach to combat the growing obesity epidemic. This review summarizes recent behavioral research on the measurement of physical activity and interventions aimed at increasing physical activity and provides directions for future research.

  5. Encapsulation of new active ingredients

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The organic construct consumed as food comes packaged in units that carry the active components, protects the entrapped active materials until delivered to targeted human organ. The packaging and delivery role is mimicked in the microencapsulation tools used to deliver active ingredients in process...

  6. Art Activities for the Handicapped.

    ERIC Educational Resources Information Center

    Laurie, Frank, Comp.

    Intended for professionals interested in incorporating arts activities into the educational programs for disabled students, Part One of the document contains arts activities contributed by clinician-presenters in the 1978 Illinois series of Very Special Arts Festivals; while Part Two contains activities contributed by clinician-presenters and…

  7. Hospitality Services. Student Activity Book.

    ERIC Educational Resources Information Center

    Texas Tech Univ., Lubbock. Home Economics Curriculum Center.

    This student activity book contains pencil-and-paper activities for use in a hospitality services course focusing on the food and lodging segments of the hospitality and tourism industry. The activities are organized into 29 chapters on the following topics: hospitality services industry; professional ethics; organization/management structures in…

  8. Activation Cascading in Sign Production

    ERIC Educational Resources Information Center

    Navarrete, Eduardo; Peressotti, Francesca; Lerose, Luigi; Miozzo, Michele

    2017-01-01

    In this study, we investigated how activation unfolds in sign production by examining whether signs that are not produced have their representations activated by semantics (cascading of activation). Deaf signers were tested with a picture-picture interference task. Participants were presented with pairs of overlapping pictures and named the green…

  9. RELAXIN ACTIVATES PEROXISOME PROLIFERATOR-ACTIVATED RECEPTOR GAMMA

    PubMed Central

    Singh, Sudhir; Bennett, Robert G

    2009-01-01

    SUMMARY Relaxin is a polypeptide hormone that triggers multiple signaling pathways through its receptor RXFP1. Many of relaxin’s functions, including vascular and antifibrotic effects, are similar to those induced by activation of PPARγ. In this study, we tested the hypothesis that relaxin signaling through RXFP1 would activate PPARγ activity. In cells overexpressing RXFP1 (HEK-RXFP1), relaxin increased transcriptional activity through a PPAR response element (PPRE) in a concentration-dependent manner. In cells lacking RXFP1, relaxin had no effect. Relaxin increased both the baseline activity and the response to the PPARγ agonists rosiglitazone and 15d-PGJ2, but not to agonists of PPARα or PPARδ. In HEK-RXFP1 cells infected with adenovirus expressing PPARγ, relaxin increased transcriptional activity through PPRE, and this effect was blocked with an adenovirus expressing a dominant-negative PPARγ. Knockdown of PPARγ using siRNA resulted in a decrease in the response to both relaxin and rosiglitazone. Both relaxin and rosiglitazone increased expression of the PPARγ target genes CD36 and LXRα in HEK-RXFP1 and in THP-1 cells naturally expressing RXFP1. Relaxin did not increase PPARγ mRNA or protein levels. Treatment of cells with GW9662, an inhibitor of PPARγ ligand binding, effectively blocked rosiglitazone-induced PPARγ activation, but had no effect on relaxin activation of PPARγ. These results suggest that relaxin activates PPARγ activity, and increases the overall response in the presence PPARγ agonists. This activation is dependent on the presence of RXFP1. Furthermore, relaxin activates PPARγ via a ligand-independent mechanism. These studies represent the first report that relaxin can activate the transcriptional activity of PPARγ. PMID:19712722

  10. Oriented active shape models.

    PubMed

    Liu, Jiamin; Udupa, Jayaram K

    2009-04-01

    Active shape models (ASM) are widely employed for recognizing anatomic structures and for delineating them in medical images. In this paper, a novel strategy called oriented active shape models (OASM) is presented in an attempt to overcome the following five limitations of ASM: 1) lower delineation accuracy, 2) the requirement of a large number of landmarks, 3) sensitivity to search range, 4) sensitivity to initialization, and 5) inability to fully exploit the specific information present in the given image to be segmented. OASM effectively combines the rich statistical shape information embodied in ASM with the boundary orientedness property and the globally optimal delineation capability of the live wire methodology of boundary segmentation. The latter characteristics allow live wire to effectively separate an object boundary from other nonobject boundaries with similar properties especially when they come very close in the image domain. The approach leads to a two-level dynamic programming method, wherein the first level corresponds to boundary recognition and the second level corresponds to boundary delineation, and to an effective automatic initialization method. The method outputs a globally optimal boundary that agrees with the shape model if the recognition step is successful in bringing the model close to the boundary in the image. Extensive evaluation experiments have been conducted by utilizing 40 image (magnetic resonance and computed tomography) data sets in each of five different application areas for segmenting breast, liver, bones of the foot, and cervical vertebrae of the spine. Comparisons are made between OASM and ASM based on precision, accuracy, and efficiency of segmentation. Accuracy is assessed using both region-based false positive and false negative measures and boundary-based distance measures. The results indicate the following: 1) The accuracy of segmentation via OASM is considerably better than that of ASM; 2) The number of landmarks

  11. Distributed Active Archive Center

    NASA Technical Reports Server (NTRS)

    Bodden, Lee; Pease, Phil; Bedet, Jean-Jacques; Rosen, Wayne

    1993-01-01

    The Goddard Space Flight Center Version 0 Distributed Active Archive Center (GSFC V0 DAAC) is being developed to enhance and improve scientific research and productivity by consolidating access to remote sensor earth science data in the pre-EOS time frame. In cooperation with scientists from the science labs at GSFC, other NASA facilities, universities, and other government agencies, the DAAC will support data acquisition, validation, archive and distribution. The DAAC is being developed in response to EOSDIS Project Functional Requirements as well as from requirements originating from individual science projects such as SeaWiFS, Meteor3/TOMS2, AVHRR Pathfinder, TOVS Pathfinder, and UARS. The GSFC V0 DAAC has begun operational support for the AVHRR Pathfinder (as of April, 1993), TOVS Pathfinder (as of July, 1993) and the UARS (September, 1993) Projects, and is preparing to provide operational support for SeaWiFS (August, 1994) data. The GSFC V0 DAAC has also incorporated the existing data, services, and functionality of the DAAC/Climate, DAAC/Land, and the Coastal Zone Color Scanner (CZCS) Systems.

  12. Photoperiodism and Enzyme Activity

    PubMed Central

    Queiroz, Orlando; Morel, Claudine

    1974-01-01

    Metabolic readjustments after a change from long days to short days appear, in Kalanchoe blossfeldiana, to be achieved through the operation of two main mechanisms: variation in enzyme capacity, and circadian rhythmicity. After a lag time, capacity in phosphoenolpyruvate carboxylase and capacity in aspartate aminotransferase increase exponentially and appear to be allometrically linked during 50 to 60 short days; then a sudden fall takes place in the activity of the former. Malic enzyme and alanine aminotransferase behave differently. Thus, the operation of the two sections of the pathway (before and after the malate step) give rise to a continuously changing functional compartmentation in the pathway. Circadian rhythmicity, on the other hand, produces time compartmentation through phase shifts and variation in amplitude, independently for each enzyme. These characteristics suggest that the operation of a so-called biological clock would be involved. We propose the hypothesis that feedback regulation would be more accurate and efficient when applied to an already oscillating, clock-controlled enzyme system. PMID:16658749

  13. Optically active quantum dots

    NASA Astrophysics Data System (ADS)

    Gerard, Valerie; Govan, Joseph; Loudon, Alexander; Baranov, Alexander V.; Fedorov, Anatoly V.; Gun'ko, Yurii K.

    2015-10-01

    The main goal of our research is to develop new types of technologically important optically active quantum dot (QD) based materials, study their properties and explore their biological applications. For the first time chiral II-VI QDs have been prepared by us using microwave induced heating with the racemic (Rac), D- and L-enantiomeric forms of penicillamine as stabilisers. Circular dichroism (CD) studies of these QDs have shown that D- and L-penicillamine stabilised particles produced mirror image CD spectra, while the particles prepared with a Rac mixture showed only a weak signal. It was also demonstrated that these QDs show very broad emission bands between 400 and 700 nm due to defects or trap states on the surfaces of the nanocrystals. These QDs have demonstrated highly specific chiral recognition of various biological species including aminoacids. The utilisation of chiral stabilisers also allowed the preparation of new water soluble white emitting CdS nano-tetrapods, which demonstrated circular dichroism in the band-edge region of the spectrum. Biological testing of chiral CdS nanotetrapods displayed a chiral bias for an uptake of the D- penicillamine stabilised nano-tetrapods by cancer cells. It is expected that this research will open new horizons in the chemistry of chiral nanomaterials and their application in nanobiotechnology, medicine and optical chemo- and bio-sensing.

  14. VERA Geodetic Activities

    NASA Technical Reports Server (NTRS)

    Jike, Takaaki; Tamura, Yoshiaki; Shizugami, Makoto

    2013-01-01

    This report briefly describes the geodetic activities of VERA in the year 2012. The regular geodetic observations are carried out both in K- and S/X-bands. The frequency of regular observations is three times a month-twice for the VERA internal observations in K-band. The networks of the S/X sessions are JADE of GSI and IVS-T2. The raw data of the T2 and JADE sessions are electronically transferred to the Bonn, Haystack, and GSI correlators via Internet. Gravimetric observations are carried out at the VERA stations. An SG was installed at Mizusawa and placed in the vicinity of the VERA antenna in order to monitor vertical displacement at the end of 2008, and the observations continued throughout the year. Also at the VERA-Ishigakijima station, continuous operation of the SG started in 2012. The crustal movements generated by the 2011 earthquake off the Pacific coast of Tohoku continued during 2012, and displacement of the VERA-Mizusawa position by post-seismic creeping continued.

  15. Active control of convection

    NASA Astrophysics Data System (ADS)

    Singer, Jonathan; Bau, Haim H.

    1991-12-01

    It is demonstrated theoretically that active (feedback) control can be used to alter the characteristics of thermal convection in a toroidal, vertical loop heated from below and cooled from above. As the temperature difference between the heated and cooled sections of the loop increases, the flow in the uncontrolled loop changes from no motion to steady, time-independent motion to temporally oscillatory, chaotic motion. With the use of a feedback controller effecting small perturbations in the boundary conditions, one can maintain the no-motion state at significantly higher temperature differences than the critical one corresponding to the onset of convection in the uncontrolled system. Alternatively, one can maintain steady, time-independent flow under conditions in which the flow would otherwise be chaotic. That is, the controller can be used to suppress chaos. Likewise, it is possible to stabilize periodic nonstable orbits that exist in the chaotic regime of the uncontrolled system. Finally, the controller also can be used to induce chaos in otherwise laminar (fully predictable), nonchaotic flow.

  16. ADASY (Active Daylighting System)

    NASA Astrophysics Data System (ADS)

    Vázquez-Moliní, Daniel; González-Montes, Mario; Fernández-Balbuena, Antonio Á.; Bernabéu, Eusebio; García-Botella, Ángel; García-Rodríguez, Lucas; Pohl, Wilfried

    2009-08-01

    The main objective of ADASY (Active Daylighting System) work is to design a façade static daylighting system oriented to office applications, mainly. The goal of the project is to save energy by guiding daylight into a building for lighting purpose. With this approach we can reduce the electrical load for artificial lighting, completing it with sustainable energy. The collector of the system is integrated on a vertical façade and its distribution guide is always horizontal inside of the false ceiling. ADASY is designed with a specific patent pending caption system, a modular light-guide and light extractor luminaire system. Special care has been put on the final cost of the system and its building integration purpose. The current ADASY configuration is able to illuminate 40 m2 area with a 300lx-400lx level in the mid time work hours; furthermore it has a good enough spatial uniformity distribution and a controlled glare. The data presented in this study are the result of simulation models and have been confirmed by a physical scaled prototype. ADASY's main advantages over regular illumination systems are: -Low maintenance; it has not mobile pieces and therefore it lasts for a long time and require little attention once installed. - No energy consumption; solar light continue working even if there has been a power outage. - High quality of light: the colour rendering of light is very high - Psychological benefits: People working with daylight get less stress and more comfort, increasing productivity. - Health benefits

  17. Battery equalization active methods

    NASA Astrophysics Data System (ADS)

    Gallardo-Lozano, Javier; Romero-Cadaval, Enrique; Milanes-Montero, M. Isabel; Guerrero-Martinez, Miguel A.

    2014-01-01

    Many different battery technologies are available for the applications which need energy storage. New researches are being focused on Lithium-based batteries, since they are becoming the most viable option for portable energy storage applications. As most of the applications need series battery strings to meet voltage requirements, battery imbalance is an important matter to be taken into account, since it leads the individual battery voltages to drift apart over time, and premature cells degradation, safety hazards, and capacity reduction will occur. A large number of battery equalization methods can be found, which present different advantages/disadvantages and are suitable for different applications. The present paper presents a summary, comparison and evaluation of the different active battery equalization methods, providing a table that compares them, which is helpful to select the suitable equalization method depending on the application. By applying the same weight to the different parameters of comparison, switch capacitor and double-tiered switching capacitor have the highest ratio. Cell bypass methods are cheap and cell to cell ones are efficient. Cell to pack, pack to cell and cell to pack to cell methods present a higher cost, size, and control complexity, but relatively low voltage and current stress in high-power applications.

  18. Perspectives in active liquid crystals.

    PubMed

    Majumdar, Apala; Cristina, Marchetti M; Virga, Epifanio G

    2014-11-28

    Active soft matter is a young, growing field, with potential applications to a wide variety of systems. This Theme Issue explores this emerging new field by highlighting active liquid crystals. The collected contributions bridge theory to experiment, mathematical theories of passive and active nematics, spontaneous flows to defect dynamics, microscopic to continuum levels of description, spontaneous activity to biological activation. While the perspectives offered here only span a small part of this rapidly evolving field, we trust that they might provide the interested reader with a taste for this new class of non-equilibrium systems and their rich behaviour.

  19. Recurrent Activity in Radio Galaxies

    SciTech Connect

    Jamrozy, Marek; Konar, Chiranjib; Machalski, Jerzy; Mack, Karl-Heinz; Saikia, Dhruba; Siemiginowska, Aneta; Stawarz, Lukasz; /KIPAC, Menlo Park /Jagiellonian U.

    2007-10-15

    One of the outstanding issues concerning extragalactic radio sources is the total duration of their active phase and the possible existence of duty cycles of their nuclear activity. A duty cycle can be recognized if there is a mechanism which preserves the information of past activity for a sufficiently long time after a new activity has started up. If a new cycle starts before the radio lobes created during a former activity period have faded, we can recognize this by the observations of a young radio source embedded in an old relic structure.

  20. Activated sintering of zirconium dioxide

    NASA Astrophysics Data System (ADS)

    Panin, V. E.; Slosman, A. I.; Matrenin, S. V.

    1996-02-01

    A new phenomenon has been observed — the activated sintering of a zirconium ceramic in the hydrogen-nitrogen plasma of a glow discharge. It is shown that the activation energy is considerably lower than the activation energy for sintering in a vacuum furnace. This makes it possible to reduce sintering temperature, refine the grains, and improve the mechanical properties of the ceramic. It is proposed that the mechanism by which sintering is activated is connected with the activating effect of hydrogen during a structural transformation involving the formation of oxynitride phases.

  1. Global optogenetic activation of inhibitory interneurons during epileptiform activity.

    PubMed

    Ledri, Marco; Madsen, Marita Grønning; Nikitidou, Litsa; Kirik, Deniz; Kokaia, Merab

    2014-02-26

    Optogenetic techniques provide powerful tools for bidirectional control of neuronal activity and investigating alterations occurring in excitability disorders, such as epilepsy. In particular, the possibility to specifically activate by light-determined interneuron populations expressing channelrhodopsin-2 provides an unprecedented opportunity of exploring their contribution to physiological and pathological network activity. There are several subclasses of interneurons in cortical areas with different functional connectivity to the principal neurons (e.g., targeting their perisomatic or dendritic compartments). Therefore, one could optogenetically activate specific or a mixed population of interneurons and dissect their selective or concerted inhibitory action on principal cells. We chose to explore a conceptually novel strategy involving simultaneous activation of mixed populations of interneurons by optogenetics and study their impact on ongoing epileptiform activity in mouse acute hippocampal slices. Here we demonstrate that such approach results in a brief initial action potential discharge in CA3 pyramidal neurons, followed by prolonged suppression of ongoing epileptiform activity during light exposure. Such sequence of events was caused by massive light-induced release of GABA from ChR2-expressing interneurons. The inhibition of epileptiform activity was less pronounced if only parvalbumin- or somatostatin-expressing interneurons were activated by light. Our data suggest that global optogenetic activation of mixed interneuron populations is a more effective approach for development of novel therapeutic strategies for epilepsy, but the initial action potential generation in principal neurons needs to be taken in consideration.

  2. Trypsin activity is not involved in premature, intrapancreatic trypsinogen activation.

    PubMed

    Halangk, Walter; Krüger, Burkhard; Ruthenbürger, Manuel; Stürzebecher, Jörg; Albrecht, Elke; Lippert, Hans; Lerch, Markus M

    2002-02-01

    A premature and intracellular activation of digestive zymogens is thought to be responsible for the onset of pancreatitis. Because trypsin has a critical role in initiating the activation cascade of digestive enzymes in the gut, it has been assumed that trypsin also initiates intracellular zymogen activation in the pancreas. We have tested this hypothesis in isolated acini and lobules from rat pancreas. Intracellular trypsinogen activation was induced by supramaximal secretagogue stimulation and measured using either specific trypsin substrates or immunoreactivity of the trypsinogen activation peptide (TAP). To prevent a trypsin-induced trypsinogen activation, we used the cell-permeant, highly specific, and reversible inhibitor Nalpha-(2-naphthylsulfonyl)-3-amidinophenylalanine-carboxymethylpiperazide (S124), and to prevent cathepsin-induced trypsinogen activation, we used the cysteine protease inhibitor E-64d. Incubation of acini or lobules in the presence of S124 completely prevented the generation of trypsin activity in response to supramaximal caerulein but had no effect whatsoever on the generation of TAP. Conversely, when trypsin activity was recovered at the end of the experiment by either washout of S124 from acini or extensive dilution of lobule homogenates, it was up to 400% higher than after caerulein alone and corresponded, in molar terms, to the generation of TAP. Both trypsin activity and TAP release were inhibited in parallel by E-64d. We conclude that caerulein-induced trypsinogen activation in the pancreas is caused by an E-64d-inhibitable mechanism such as cathepsin-induced trypsinogen activation, and neither involves nor requires intracellular trypsin activity. Specific trypsin inhibition, on the other hand, prevents 80% of trypsin inactivation or autodegradation in the pancreas.

  3. Dynamic Patterns in Active Fluids

    NASA Astrophysics Data System (ADS)

    Jülicher, Frank

    2012-02-01

    Biological matter is inherently dynamic and exhibits active properties. A key example is the force generation by molecular motors in the cell cytoskeleton. Such active processes give rise to the generation of active mechanical stresses and spontaneous flows in gel-like cytoskeletal networks. Active material behaviors play a key role for the dynamics of cellular processes such as cell locomotion and cell division. We will discuss intracellular flow patterns that are created by active processes in the cell cortex. By combining theory with quantitative experiments we show that observed flow patterns result from profiles of active stress generation in the system. We will also consider the situation where active stress is regulated by a diffusing molecular species. In this case, spatial concentration patterns are generated by the interplay of stress regulation and self-generated flow fields.

  4. Active Kids Active Minds: A Physical Activity Intervention to Promote Learning?

    ERIC Educational Resources Information Center

    lisahunter; Abbott, Rebecca; Macdonald, Doune; Ziviani, Jennifer; Cuskelly, Monica

    2014-01-01

    This study assessed the feasibility and impact of introducing a programme of an additional 30 minutes per day of moderate physical activity within curriculum time on learning and readiness to learn in a large elementary school in south-east Queensland, Australia. The programme, Active Kids Active Minds (AKAM), involved Year 5 students (n = 107),…

  5. Strategy as active waiting.

    PubMed

    Sull, Donald N

    2005-09-01

    Successful executives who cut their teeth in stable industries or in developed countries often stumble when they face more volatile markets. They falter, in part, because they assume they can gaze deep into the future and develop a long-term strategy that will confer a sustainable competitive advantage. But visibility into the future of volatile markets is sharply limited because so many different variables are in play. Factors such as technological innovation, customers' evolving needs, government policy, and changes in the capital markets interact with one another to create unexpected outcomes. Over the past six years, Donald Sull, an associate professor at London Business School, has led a research project examining some of the world's most volatile markets, from national markets like China and Brazil to industries like enterprise software, telecommunications, and airlines. One of the most striking findings from this research is the importance of taking action during comparative lulls in the storm. Huge business opportunities are relatively rare; they come along only once or twice in a decade. And, for the most part, companies can't manufacture those opportunities; changes in the external environment converge to make them happen. What managers can do is prepare for these golden opportunities by managing smart during the comparative calm of business as usual. During these periods of active waiting, leaders must probe the future and remain alert to anomalies that signal potential threats or opportunities; exercise restraint to preserve their war chests; and maintain discipline to keep the troops battle ready. When a golden opportunity or"sudden death"threat emerges, managers must have the courage to declare the main effort and concentrate resources to seize the moment.

  6. Mechanically Active Electrospun Materials

    NASA Astrophysics Data System (ADS)

    Robertson, Jaimee M.

    Electrospinning, a technique used to fabricate small diameter polymer fibers, has been employed to develop unique, active materials falling under two categories: (1) shape memory elastomeric composites (SMECs) and (2) water responsive fiber mats. (1) Previous work has characterized in detail the properties and behavior of traditional SMECs with isotropic fibers embedded in an elastomer matrix. The current work has two goals: (i) characterize laminated anisotropic SMECs and (ii) develop a fabrication process that is scalable for commercial SMEC manufacturing. The former ((i)) requires electrospinning aligned polymer fibers. The aligned fibers are similarly embedded in an elastomer matrix and stacked at various fiber orientations. The resulting laminated composite has a unique response to tensile deformation: after stretching and releasing, the composite curls. This curling response was characterized based on fiber orientation. The latter goal ((ii)) required use of a dual-electrospinning process to simultaneously electrospin two polymers. This fabrication approach incorporated only industrially relevant processing techniques, enabling the possibility of commercial application of a shape memory rubber. Furthermore, the approach had the added benefit of increased control over composition and material properties. (2) The strong elongational forces experienced by polymer chains during the electrospinning process induce molecular alignment along the length of electrospun fibers. Such orientation is maintained in the fibers as the polymer vitrifies. Consequently, residual stress is stored in electrospun fiber mats and can be recovered by heating through the polymer's glass transition temperature. Alternatively, the glass transition temperature can be depressed by introducing a plasticizing agent. Poly(vinyl acetate) (PVAc) is plasticized by water, and its glass transition temperature is lowered below room temperature. Therefore, the residual stress can be relaxed at room

  7. AMPK activators: mechanisms of action and physiological activities

    PubMed Central

    Kim, Joungmok; Yang, Goowon; Kim, Yeji; Kim, Jin; Ha, Joohun

    2016-01-01

    AMP-activated protein kinase (AMPK) is a central regulator of energy homeostasis, which coordinates metabolic pathways and thus balances nutrient supply with energy demand. Because of the favorable physiological outcomes of AMPK activation on metabolism, AMPK has been considered to be an important therapeutic target for controlling human diseases including metabolic syndrome and cancer. Thus, activators of AMPK may have potential as novel therapeutics for these diseases. In this review, we provide a comprehensive summary of both indirect and direct AMPK activators and their modes of action in relation to the structure of AMPK. We discuss the functional differences among isoform-specific AMPK complexes and their significance regarding the development of novel AMPK activators and the potential for combining different AMPK activators in the treatment of human disease. PMID:27034026

  8. Fluidization and Active Thinning by Molecular Kinetics in Active Gels.

    PubMed

    Oriola, David; Alert, Ricard; Casademunt, Jaume

    2017-02-24

    We derive the constitutive equations of an active polar gel from a model for the dynamics of elastic molecules that link polar elements. Molecular binding kinetics induces the fluidization of the material, giving rise to Maxwell viscoelasticity and, provided that detailed balance is broken, to the generation of active stresses. We give explicit expressions for the transport coefficients of active gels in terms of molecular properties, including nonlinear contributions on the departure from equilibrium. In particular, when activity favors linker unbinding, we predict a decrease of viscosity with activity-active thinning-of kinetic origin, which could explain some experimental results on the cell cortex. By bridging the molecular and hydrodynamic scales, our results could help understand the interplay between molecular perturbations and the mechanics of cells and tissues.

  9. Being active when you have heart disease

    MedlinePlus

    Heart disease - activity; CAD - activity; Coronary artery disease - activity; Angina - activity ... Getting regular exercise when you have heart disease is important. Exercise can make your heart muscle stronger. It may also help you be more active without chest pain or ...

  10. Rest Rust ! Physical active for active and healthy ageing

    PubMed Central

    Vollenbroek-Hutten, M; Pais, S; Ponce, S; Dekker-van Weering, M; Jansen-Kosterink, S; Schena, F; Tabarini, N; Carotenuto, F; Iadicicco, V; Illario, M

    2015-01-01

    The aim of this paper is to give an insight on how physical activity can be defined, parameterized and measured in older adults and on different options to deal with citizen physical activity promotion at European level. Three relevant aspects are highlighted: When talking about physical activity, two different aspects are often unfairly mixed up: “physical activity” and “physical capacity”. Physical activity, is referred to as the level of physical activity someone is actually performing in daily life.Physical capacity is referred to as the maximum physical activity a person can perform.Both physical activity and physical capacity can be expressed in different dimensions such as time, frequency, or type of activity with the consequence that there are many tools and techniques available. In order to support people to choose an appropriate instrument in their everyday practice a list of 9 criteria that are considered important is defined.Older adults score differently across the various physical dimensions, so strategies to promote physical activity should consider individual differences, in order to adapt for these variations. PMID:27042429

  11. Activated coconut shell charcoal carbon using chemical-physical activation

    NASA Astrophysics Data System (ADS)

    Budi, Esmar; Umiatin, Nasbey, Hadi; Bintoro, Ridho Akbar; Wulandari, Futri; Erlina

    2016-02-01

    The use of activated carbon from natural material such as coconut shell charcoal as metal absorbance of the wastewater is a new trend. The activation of coconut shell charcoal carbon by using chemical-physical activation has been investigated. Coconut shell was pyrolized in kiln at temperature about 75 - 150 °C for about 6 hours in producing charcoal. The charcoal as the sample was shieved into milimeter sized granule particle and chemically activated by immersing in various concentration of HCl, H3PO4, KOH and NaOH solutions. The samples then was physically activated using horizontal furnace at 400°C for 1 hours in argon gas environment with flow rate of 200 kg/m3. The surface morphology and carbon content of activated carbon were characterized by using SEM/EDS. The result shows that the pores of activated carbon are openned wider as the chemical activator concentration is increased due to an excessive chemical attack. However, the pores tend to be closed as further increasing in chemical activator concentration due to carbon collapsing.

  12. Silicon active photonic devices

    NASA Astrophysics Data System (ADS)

    Dimitropoulos, Dimitrios

    Active photonic devices utilizing the optical nonlinearities of silicon have emerged in the last 5 years and the effort for commercial photonic devices in the material that has been the workhorse of electronics has been building up since. This dissertation presents the theory for some of these devices. We are concerned herein with CW lasers, amplifiers and wavelength converters that are based on the Raman effect. There have already been cursory experimental demonstrations of these devices and some of their limitations are already apparent. Most of the limitations observed are because of the appearance of effects that are competing with stimulated Raman scattering. Under the high optical powers that are necessary for the Raman effect (tens to hundrends of mW's) the process of optical two-photon (TPA) absorption occurs. The absorption of optical power that it causes itself is weak but in the process electrons and holes are generated which can further absorb light through the free-carrier absorption effect (FCA). The effective "lifetime" that these carriers have determines the magnitude of the FCA loss. We present a model for the carrier lifetime in Silicon-On-Insulator (SOI) waveguides and numerical simulations to understand how this critical parameter varies and how it can be controlled. A p-i-n junction built along SOI waveguides can help achieve lifetime of the order of 20--100 ps but the price one has to pay is on-chip electrical power consumption on the order of 100's of mWs. We model CW Raman lasers and we find that the carrier lifetime reduces the output power. If the carrier lifetime exceeds a certain "critical" value optical losses become overwhelming and lasing is impossible. As we show, in amplifiers, the nonlinear loss does not only result in diminished gain, but also in a higher noise figure. Finally the effect of Coherent anti-Stokes Raman scattering (CARS) is examined. The effect is important because with a pump frequency at 1434nm coherent power

  13. Rapid Active Sampling Package

    NASA Technical Reports Server (NTRS)

    Peters, Gregory

    2010-01-01

    A field-deployable, battery-powered Rapid Active Sampling Package (RASP), originally designed for sampling strong materials during lunar and planetary missions, shows strong utility for terrestrial geological use. The technology is proving to be simple and effective for sampling and processing materials of strength. Although this originally was intended for planetary and lunar applications, the RASP is very useful as a powered hand tool for geologists and the mining industry to quickly sample and process rocks in the field on Earth. The RASP allows geologists to surgically acquire samples of rock for later laboratory analysis. This tool, roughly the size of a wrench, allows the user to cut away swaths of weathering rinds, revealing pristine rock surfaces for observation and subsequent sampling with the same tool. RASPing deeper (.3.5 cm) exposes single rock strata in-situ. Where a geologist fs hammer can only expose unweathered layers of rock, the RASP can do the same, and then has the added ability to capture and process samples into powder with particle sizes less than 150 microns, making it easier for XRD/XRF (x-ray diffraction/x-ray fluorescence). The tool uses a rotating rasp bit (or two counter-rotating bits) that resides inside or above the catch container. The container has an open slot to allow the bit to extend outside the container and to allow cuttings to enter and be caught. When the slot and rasp bit are in contact with a substrate, the bit is plunged into it in a matter of seconds to reach pristine rock. A user in the field may sample a rock multiple times at multiple depths in minutes, instead of having to cut out huge, heavy rock samples for transport back to a lab for analysis. Because of the speed and accuracy of the RASP, hundreds of samples can be taken in one day. RASP-acquired samples are small and easily carried. A user can characterize more area in less time than by using conventional methods. The field-deployable RASP used a Ni

  14. Enhanced NIF neutron activation diagnostics.

    PubMed

    Yeamans, C B; Bleuel, D L; Bernstein, L A

    2012-10-01

    The NIF neutron activation diagnostic suite relies on removable activation samples, leading to operational inefficiencies and a fundamental lower limit on the half-life of the activated product that can be observed. A neutron diagnostic system measuring activation of permanently installed samples could remove these limitations and significantly enhance overall neutron diagnostic capabilities. The physics and engineering aspects of two proposed systems are considered: one measuring the (89)Zr/(89 m)Zr isomer ratio in the existing Zr activation medium and the other using potassium zirconate as the activation medium. Both proposed systems could improve the signal-to-noise ratio of the current system by at least a factor of 5 and would allow independent measurement of fusion core velocity and fuel areal density.

  15. CDPK Activation in PRR Signaling.

    PubMed

    Seybold, Heike; Boudsocq, Marie; Romeis, Tina

    2017-01-01

    Calcium-dependent protein kinases undergo a rapid biochemical activation in response to an intracellular Ca increase induced by the PRR-dependent perception of a pathogen-related stimulus. Based on SDS gel resolution, the in-gel kinase assay allows the analysis of multiple in vivo protein samples in parallel, combining the advantage of protein separation according to molecular mass with the activity read-out of a protein kinase assay. It thus enables to follow the transient CDPK activation and inactivation in response to in vivo elicitation with a time-wise resolution. In addition, changes of CDPK phosphorylation activity often correlate with slight shifts in the enzyme's apparent molecular mass, indicating posttranslational modifications and a conformational change of the active enzyme compared to its inactive resting form. These band shifts can be detected by a simple immunoblotting to monitor CDPK activation.

  16. Swim pressure of active matter

    NASA Astrophysics Data System (ADS)

    Takatori, Sho; Yan, Wen; Brady, John; Caltech Team

    2014-11-01

    Through their self-motion, all active matter systems generate a unique ``swim pressure'' that is entirely athermal in origin. This new source for the active stress exists at all scales in both living and nonliving active systems, and also applies to larger organisms where inertia is important (i.e., the Stokes number is not small). Here we explain the origin of the swim stress and develop a simple thermodynamic model to study the self-assembly and phase separation in active soft matter. Our new swim stress perspective can help analyze and exploit a wide class of active soft matter, from swimming bacteria and catalytic nanobots, schools of fish and birds, and molecular motors that activate the cellular cytoskeleton.

  17. Enhanced NIF neutron activation diagnostics

    SciTech Connect

    Yeamans, C. B.; Bleuel, D. L.; Bernstein, L. A.

    2012-10-15

    The NIF neutron activation diagnostic suite relies on removable activation samples, leading to operational inefficiencies and a fundamental lower limit on the half-life of the activated product that can be observed. A neutron diagnostic system measuring activation of permanently installed samples could remove these limitations and significantly enhance overall neutron diagnostic capabilities. The physics and engineering aspects of two proposed systems are considered: one measuring the {sup 89}Zr/{sup 89m}Zr isomer ratio in the existing Zr activation medium and the other using potassium zirconate as the activation medium. Both proposed systems could improve the signal-to-noise ratio of the current system by at least a factor of 5 and would allow independent measurement of fusion core velocity and fuel areal density.

  18. Active Cells for Multifunctional Structures

    DTIC Science & Technology

    2014-09-24

    techniques to explore a variety of cell designs.  Designed a simplified active cell using Nitinol as the actuation method and relying on Joule heating...for contraction of the cell.  Developed manufacturing techniques for reliably creating Nitinol spring coils in a variety of diameters and gauges...design of the active cells to maximum the stroked length of the active cells by tuning the stiffness of a passive spring in parallel with the Nitinol

  19. Antiangiogenic Activity of Glycyrrhiza Extract

    NASA Astrophysics Data System (ADS)

    Li, Ying-Qiu

    The bioactivity of extract of glycyrrhiza was detected by zebrafish antiangiogenic model after 70% ethanol extract of glycyrrhiza was extracted with petroleum ether, ethyl acetate, n-butanol. The inhibition of the extracts in antiangiogenic activity showed that the highest active components existed in ethyl acetate extract of glycyrrhiza. The ethyl acetate extract of glycyrrhiza was separated by polyamide column chromatography to obtain 7 fractions (Fr1-Fr7), which Fr5 and Fr6 showed antiangiogenic activity.

  20. In Situ Activation of Microcapsules

    NASA Technical Reports Server (NTRS)

    Morrison, Dennis R. (Inventor); Mosier, Benjamin (Inventor)

    2000-01-01

    Disclosed are microcapsules comprising a polymer shell enclosing two or more immiscible liquid phases in which a drug, or a prodrug and a drug activator are partitioned into separate phases. or prevented from diffusing out of the microcapsule by a liquid phase in which the drug is poorly soluble. Also disclosed are methods of using the microcapsules for in situ activation of drugs where upon exposure to an appropriate energy source the internal phases mix and the drug is activated in situ.