497 research outputs found

    United classification of cosmic gamma-ray bursts and their counterparts

    Full text link
    United classification of gamma-ray bursts and their counterparts is established on the basis of measured characteristics: photon energy E and emission duration T. The founded interrelation between the mentioned characteristics of events consists in that, as the energy increases, the duration decreases (and vice versa). The given interrelation reflects the nature of the phenomenon and forms the E-T diagram, which represents a natural classification of all observed events in the energy range from 10E9 to 10E-6 eV and in the corresponding interval of durations from about 10E-2 up to 10E8 s. The proposed classification results in the consequences, which are principal for the theory and practical study of the phenomenon.Comment: Keywords Gamma rays: burst

    Generation of a wave packet tailored to efficient free space excitation of a single atom

    Full text link
    We demonstrate the generation of an optical dipole wave suitable for the process of efficiently coupling single quanta of light and matter in free space. We employ a parabolic mirror for the conversion of a transverse beam mode to a focused dipole wave and show the required spatial and temporal shaping of the mode incident onto the mirror. The results include a proof of principle correction of the parabolic mirror's aberrations. For the application of exciting an atom with a single photon pulse we demonstrate the creation of a suitable temporal pulse envelope. We infer coupling strengths of 89% and success probabilities of up to 87% for the application of exciting a single atom for the current experimental parameters.Comment: to be published in Europ. Phys. J.

    Adaptive and reversible resistance to Kras inhibition in pancreatic cancer cells

    Get PDF
    Activating mutations in KRAS are the hallmark genetic alterations in pancreatic ductal adenocarcinoma (PDAC) and the key drivers of its initiation and progression. Longstanding efforts to develop novel KRAS inhibitors have been based on the assumption that PDAC cells are addicted to activated KRAS, but this assumption remains controversial. In this study, we analyzed the requirement of endogenous Kras to maintain survival of murine PDAC cells, using an inducible shRNA-based system that enables temporal control of Kras expression. We found that the majority of murine PDAC cells analyzed tolerated acute and sustained Kras silencing by adapting to a reversible cell state characterized by differences in cell morphology, proliferative kinetics, and tumor-initiating capacity. While we observed no significant mutational or transcriptional changes in the Kras-inhibited state, global phosphoproteomic profiling revealed significant alterations in cell signaling, including increased phosphorylation of focal adhesion pathway components. Accordingly, Kras-inhibited cells displayed prominent focal adhesion plaque structures, enhanced adherence properties, and increased dependency on adhesion for viability in vitro. Overall, our results call into question the degree to which PDAC cells are addicted to activated KRAS, by illustrating adaptive non-genetic and non-transcriptional mechanisms of resistance to Kras blockade. However, by identifying these mechanisms, our work also provides mechanistic directions to develop combination strategies that can help enforce the efficacy of KRAS inhibitors

    A deep dive into the ecology of Gamay (Botany Bay, Australia): current knowledge and future priorities for this highly modified coastal waterway

    Get PDF
    Context: Gamay is a coastal waterway of immense social, cultural and ecological value. Since European settlement, it has become a hub for industrialisation and human modification. There is growing desire for ecosystem-level management of urban waterways, but such efforts are often challenged by a lack of integrated knowledge. Aim and methods: We systematically reviewed published literature and traditional ecological knowledge (TEK), and consulted scientists to produce a review of Gamay that synthesises published knowledge of Gamay’s aquatic ecosystem to identify knowledge gaps and future research opportunities. Key results: We found 577 published resources on Gamay, of which over 70% focused on ecology. Intertidal rocky shores were the most studied habitat, focusing on invertebrate communities. Few studies considered multiple habitats or taxa. Studies investigating cumulative human impacts, long-term trends and habitat connectivity are lacking, and the broader ecological role of artificial substrate as habitat in Gamay is poorly understood. TEK of Gamay remains a significant knowledge gap. Habitat restoration has shown promising results and could provide opportunities to improve affected habitats in the future. Conclusion and implications: This review highlights the extensive amount of knowledge that exists for Gamay, but also identifies key gaps that need to be filled for effective management

    Coping with the effects of fear of failure in young elite athletes

    Get PDF
    Coping with stress is an important element in effective functioning at the elite level in sports, and fear of failure (FF) is an example of a stressor that athletes experience. Three issues underpin the present preliminary study. First, the prevalence of problems attributed to FF in achievement settings. Second, sport is a popular and significant achievement domain for children and adolescents. Third, there is a lack of research on FF in sport among this population. Therefore, the objectives of the study were to examine the effects of FF on young athletes and to find out their coping responses to the effects of FF. Interviews were conducted individually with nine young elite ath­letes (5 males, 4 females; ages 14-17 years). It was inferred from the data that FF affected the athletes' well-being, interpersonal behavior, sport performance, and schoolwork. The athletes employed a combination of problem-focused, emotion-fo­cused, and avoidance-focused coping strategies, with avoidance strategies being the most frequently reported

    Search for direct production of charginos and neutralinos in events with three leptons and missing transverse momentum in √s = 7 TeV pp collisions with the ATLAS detector

    Get PDF
    A search for the direct production of charginos and neutralinos in final states with three electrons or muons and missing transverse momentum is presented. The analysis is based on 4.7 fb−1 of proton–proton collision data delivered by the Large Hadron Collider and recorded with the ATLAS detector. Observations are consistent with Standard Model expectations in three signal regions that are either depleted or enriched in Z-boson decays. Upper limits at 95% confidence level are set in R-parity conserving phenomenological minimal supersymmetric models and in simplified models, significantly extending previous results

    Jet size dependence of single jet suppression in lead-lead collisions at sqrt(s(NN)) = 2.76 TeV with the ATLAS detector at the LHC

    Get PDF
    Measurements of inclusive jet suppression in heavy ion collisions at the LHC provide direct sensitivity to the physics of jet quenching. In a sample of lead-lead collisions at sqrt(s) = 2.76 TeV corresponding to an integrated luminosity of approximately 7 inverse microbarns, ATLAS has measured jets with a calorimeter over the pseudorapidity interval |eta| < 2.1 and over the transverse momentum range 38 < pT < 210 GeV. Jets were reconstructed using the anti-kt algorithm with values for the distance parameter that determines the nominal jet radius of R = 0.2, 0.3, 0.4 and 0.5. The centrality dependence of the jet yield is characterized by the jet "central-to-peripheral ratio," Rcp. Jet production is found to be suppressed by approximately a factor of two in the 10% most central collisions relative to peripheral collisions. Rcp varies smoothly with centrality as characterized by the number of participating nucleons. The observed suppression is only weakly dependent on jet radius and transverse momentum. These results provide the first direct measurement of inclusive jet suppression in heavy ion collisions and complement previous measurements of dijet transverse energy imbalance at the LHC.Comment: 15 pages plus author list (30 pages total), 8 figures, 2 tables, submitted to Physics Letters B. All figures including auxiliary figures are available at http://atlas.web.cern.ch/Atlas/GROUPS/PHYSICS/PAPERS/HION-2011-02

    Time evolution of in vivo articular cartilage repair induced by bone marrow stimulation and scaffold implantation in rabbits

    Full text link
    Purpose: Tissue engineering techniques were used to study cartilage repair over a 12-month period in a rabbit model. Methods: A full-depth chondral defect along with subchondral bone injury were originated in the knee joint, where a biostable porous scaffold was implanted, synthesized of poly(ethyl acrylate-co-hydroxyethyl acrylate) copolymer. Morphological evolution of cartilage repair was studied 1 and 2 weeks, and 1, 3, and 12 months after implantation by histological techniques. The 3-month group was chosen to compare cartilage repair to an additional group where scaffolds were preseeded with allogeneic chondrocytes before implantation, and also to controls, who underwent the same surgery procedure, with no scaffold implantation. Results: Neotissue growth was first observed in the deepest scaffold pores 1 week after implantation, which spread thereafter; 3 months later scaffold pores were filled mostly with cartilaginous tissue in superficial and middle zones, and with bone tissue adjacent to subchondral bone. Simultaneously, native chondrocytes at the edges of the defect started to proliferate 1 week after implantation; within a month those edges had grown centripetally and seemed to embed the scaffold, and after 3 months, hyaline-like cartilage was observed on the condylar surface. Preseeded scaffolds slightly improved tissue growth, although the quality of repair tissue was similar to non-preseeded scaffolds. Controls showed that fibrous cartilage was mainly filling the repair area 3 months after surgery. In the 12-month group, articular cartilage resembled the untreated surface. Conclusions: Scaffolds guided cartilaginous tissue growth in vivo, suggesting their importance in stress transmission to the cells for cartilage repair.This study was supported by the Spanish Ministry of Science and Innovation through MAT2010-21611-C03-00 project (including the FEDER financial support), by Conselleria de Educacion (Generalitat Valenciana, Spain) PROMETEO/2011/084 grant, and by CIBER-BBN en Bioingenieria, Biomateriales y Nanomedicina. The work of JLGR was partially supported by funds from the Generalitat Valenciana, ACOMP/2012/075 project. CIBER-BBN is an initiative funded by the VI National R&D&i Plan 2008-2011, Iniciativa Ingenio 2010, Consolider Program, CIBER Actions and financed by the - Instituto de Salud Carlos III with assistance from the European Regional Development Fund.Sancho-Tello Valls, M.; Forriol, F.; Gastaldi, P.; Ruiz Sauri, A.; MartĂ­n De Llano, JJ.; Novella-Maestre, E.; Antolinos TurpĂ­n, CM.... (2015). Time evolution of in vivo articular cartilage repair induced by bone marrow stimulation and scaffold implantation in rabbits. International Journal of Artificial Organs. 38(4):210-223. https://doi.org/10.5301/ijao.5000404S210223384Becerra, J., Andrades, J. A., Guerado, E., Zamora-Navas, P., LĂłpez-Puertas, J. M., & Reddi, A. H. (2010). Articular Cartilage: Structure and Regeneration. Tissue Engineering Part B: Reviews, 16(6), 617-627. doi:10.1089/ten.teb.2010.0191Nelson, L., Fairclough, J., & Archer, C. (2009). Use of stem cells in the biological repair of articular cartilage. Expert Opinion on Biological Therapy, 10(1), 43-55. doi:10.1517/14712590903321470MAINIL-VARLET, P., AIGNER, T., BRITTBERG, M., BULLOUGH, P., HOLLANDER, A., HUNZIKER, E., 
 STAUFFER, E. (2003). HISTOLOGICAL ASSESSMENT OF CARTILAGE REPAIR. The Journal of Bone and Joint Surgery-American Volume, 85, 45-57. doi:10.2106/00004623-200300002-00007Hunziker, E. B., Kapfinger, E., & Geiss, J. (2007). The structural architecture of adult mammalian articular cartilage evolves by a synchronized process of tissue resorption and neoformation during postnatal development. Osteoarthritis and Cartilage, 15(4), 403-413. doi:10.1016/j.joca.2006.09.010Onyekwelu, I., Goldring, M. B., & Hidaka, C. (2009). Chondrogenesis, joint formation, and articular cartilage regeneration. Journal of Cellular Biochemistry, 107(3), 383-392. doi:10.1002/jcb.22149Ahmed, T. A. E., & Hincke, M. T. (2010). Strategies for Articular Cartilage Lesion Repair and Functional Restoration. Tissue Engineering Part B: Reviews, 16(3), 305-329. doi:10.1089/ten.teb.2009.0590Hangody, L., Kish, G., KĂĄrpĂĄti, Z., Udvarhelyi, I., Szigeti, I., & BĂ©ly, M. (1998). Mosaicplasty for the Treatment of Articular Cartilage Defects: Application in Clinical Practice. Orthopedics, 21(7), 751-756. doi:10.3928/0147-7447-19980701-04Steinwachs, M. R., Guggi, T., & Kreuz, P. C. (2008). Marrow stimulation techniques. Injury, 39(1), 26-31. doi:10.1016/j.injury.2008.01.042Brittberg, M., Lindahl, A., Nilsson, A., Ohlsson, C., Isaksson, O., & Peterson, L. (1994). Treatment of Deep Cartilage Defects in the Knee with Autologous Chondrocyte Transplantation. New England Journal of Medicine, 331(14), 889-895. doi:10.1056/nejm199410063311401Richter, W. (2009). Mesenchymal stem cells and cartilagein situregeneration. Journal of Internal Medicine, 266(4), 390-405. doi:10.1111/j.1365-2796.2009.02153.xBartlett, W., Skinner, J. A., Gooding, C. R., Carrington, R. W. J., Flanagan, A. M., Briggs, T. W. R., & Bentley, G. (2005). Autologous chondrocyte implantationversusmatrix-induced autologous chondrocyte implantation for osteochondral defects of the knee. The Journal of Bone and Joint Surgery. British volume, 87-B(5), 640-645. doi:10.1302/0301-620x.87b5.15905Little, C. J., Bawolin, N. K., & Chen, X. (2011). Mechanical Properties of Natural Cartilage and Tissue-Engineered Constructs. Tissue Engineering Part B: Reviews, 17(4), 213-227. doi:10.1089/ten.teb.2010.0572Vikingsson, L., Gallego Ferrer, G., GĂłmez-Tejedor, J. A., & GĂłmez Ribelles, J. L. (2014). An «in vitro» experimental model to predict the mechanical behavior of macroporous scaffolds implanted in articular cartilage. Journal of the Mechanical Behavior of Biomedical Materials, 32, 125-131. doi:10.1016/j.jmbbm.2013.12.024Weber, J. F., & Waldman, S. D. (2014). Calcium signaling as a novel method to optimize the biosynthetic response of chondrocytes to dynamic mechanical loading. Biomechanics and Modeling in Mechanobiology, 13(6), 1387-1397. doi:10.1007/s10237-014-0580-xMauck, R. L., Soltz, M. A., Wang, C. C. B., Wong, D. D., Chao, P.-H. G., Valhmu, W. B., 
 Ateshian, G. A. (2000). Functional Tissue Engineering of Articular Cartilage Through Dynamic Loading of Chondrocyte-Seeded Agarose Gels. Journal of Biomechanical Engineering, 122(3), 252-260. doi:10.1115/1.429656Palmoski, M. J., & Brandt, K. D. (1984). Effects of static and cyclic compressive loading on articular cartilage plugs in vitro. Arthritis & Rheumatism, 27(6), 675-681. doi:10.1002/art.1780270611Khoshgoftar, M., Ito, K., & van Donkelaar, C. C. (2014). The Influence of Cell-Matrix Attachment and Matrix Development on the Micromechanical Environment of the Chondrocyte in Tissue-Engineered Cartilage. Tissue Engineering Part A, 20(23-24), 3112-3121. doi:10.1089/ten.tea.2013.0676Agrawal, C. M., & Ray, R. B. (2001). Biodegradable polymeric scaffolds for musculoskeletal tissue engineering. Journal of Biomedical Materials Research, 55(2), 141-150. doi:10.1002/1097-4636(200105)55:23.0.co;2-jPĂ©rez Olmedilla, M., Garcia-Giralt, N., Pradas, M. M., Ruiz, P. B., GĂłmez Ribelles, J. L., Palou, E. C., & GarcĂ­a, J. C. M. (2006). Response of human chondrocytes to a non-uniform distribution of hydrophilic domains on poly (ethyl acrylate-co-hydroxyethyl methacrylate) copolymers. Biomaterials, 27(7), 1003-1012. doi:10.1016/j.biomaterials.2005.07.030Horbett, T. A., & Schway, M. B. (1988). Correlations between mouse 3T3 cell spreading and serum fibronectin adsorption on glass and hydroxyethylmethacrylate-ethylmethacrylate copolymers. Journal of Biomedical Materials Research, 22(9), 763-793. doi:10.1002/jbm.820220903Kiremitçi, M., PeƟmen, A., Pulat, M., & GĂŒrhan, I. (1993). Relationship of Surface Characteristics to Cellular Attachment in PU and PHEMA. Journal of Biomaterials Applications, 7(3), 250-264. doi:10.1177/088532829300700304Lydon, M. ., Minett, T. ., & Tighe, B. . (1985). Cellular interactions with synthetic polymer surfaces in culture. Biomaterials, 6(6), 396-402. doi:10.1016/0142-9612(85)90100-0Campillo-Fernandez, A. J., Pastor, S., Abad-Collado, M., Bataille, L., Gomez-Ribelles, J. L., Meseguer-Dueñas, J. M., 
 Ruiz-Moreno, J. M. (2007). Future Design of a New Keratoprosthesis. Physical and Biological Analysis of Polymeric Substrates for Epithelial Cell Growth. Biomacromolecules, 8(8), 2429-2436. doi:10.1021/bm0703012Funayama, A., Niki, Y., Matsumoto, H., Maeno, S., Yatabe, T., Morioka, H., 
 Toyama, Y. (2008). Repair of full-thickness articular cartilage defects using injectable type II collagen gel embedded with cultured chondrocytes in a rabbit model. Journal of Orthopaedic Science, 13(3), 225-232. doi:10.1007/s00776-008-1220-zKitahara, S., Nakagawa, K., Sah, R. L., Wada, Y., Ogawa, T., Moriya, H., & Masuda, K. (2008). In Vivo Maturation of Scaffold-free Engineered Articular Cartilage on Hydroxyapatite. Tissue Engineering Part A, 14(11), 1905-1913. doi:10.1089/ten.tea.2006.0419Martinez-Diaz, S., Garcia-Giralt, N., Lebourg, M., GĂłmez-Tejedor, J.-A., Vila, G., Caceres, E., 
 Monllau, J. C. (2010). In Vivo Evaluation of 3-Dimensional Polycaprolactone Scaffolds for Cartilage Repair in Rabbits. The American Journal of Sports Medicine, 38(3), 509-519. doi:10.1177/0363546509352448Wang, Y., Bian, Y.-Z., Wu, Q., & Chen, G.-Q. (2008). Evaluation of three-dimensional scaffolds prepared from poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) for growth of allogeneic chondrocytes for cartilage repair in rabbits. Biomaterials, 29(19), 2858-2868. doi:10.1016/j.biomaterials.2008.03.021AliĂł del Barrio, J. L., Chiesa, M., Gallego Ferrer, G., Garagorri, N., Briz, N., Fernandez-Delgado, J., 
 De Miguel, M. P. (2014). Biointegration of corneal macroporous membranes based on poly(ethyl acrylate) copolymers in an experimental animal model. Journal of Biomedical Materials Research Part A, 103(3), 1106-1118. doi:10.1002/jbm.a.35249Diego, R. B., Olmedilla, M. P., Aroca, A. S., Ribelles, J. L. G., Pradas, M. M., Ferrer, G. G., & SĂĄnchez, M. S. (2005). Acrylic scaffolds with interconnected spherical pores and controlled hydrophilicity for tissue engineering. Journal of Materials Science: Materials in Medicine, 16(8), 693-698. doi:10.1007/s10856-005-2604-7Serrano Aroca, A., Campillo FernĂĄndez, A. J., GĂłmez Ribelles, J. L., MonleĂłn Pradas, M., Gallego Ferrer, G., & Pissis, P. (2004). Porous poly(2-hydroxyethyl acrylate) hydrogels prepared by radical polymerisation with methanol as diluent. Polymer, 45(26), 8949-8955. doi:10.1016/j.polymer.2004.10.033Diani, J., Fayolle, B., & Gilormini, P. (2009). A review on the Mullins effect. European Polymer Journal, 45(3), 601-612. doi:10.1016/j.eurpolymj.2008.11.017Mullins, L. (1969). Softening of Rubber by Deformation. Rubber Chemistry and Technology, 42(1), 339-362. doi:10.5254/1.3539210Jurvelin, J. S., Buschmann, M. D., & Hunziker, E. B. (2003). Mechanical anisotropy of the human knee articular cartilage in compression. Proceedings of the Institution of Mechanical Engineers, Part H: Journal of Engineering in Medicine, 217(3), 215-219. doi:10.1243/095441103765212712Shapiro, F., Koide, S., & Glimcher, M. J. (1993). Cell origin and differentiation in the repair of full-thickness defects of articular cartilage. The Journal of Bone & Joint Surgery, 75(4), 532-553. doi:10.2106/00004623-199304000-00009SELLERS, R. S., ZHANG, R., GLASSON, S. S., KIM, H. D., PELUSO, D., D’AUGUSTA, D. A., 
 MORRIS, E. A. (2000). Repair of Articular Cartilage Defects One Year After Treatment with Recombinant Human Bone Morphogenetic Protein-2 (rhBMP-2)*. The Journal of Bone and Joint Surgery-American Volume, 82(2), 151-160. doi:10.2106/00004623-200002000-00001Hunziker, E. B., Michel, M., & Studer, D. (1997). Ultrastructure of adult human articular cartilage matrix after cryotechnical processing. Microscopy Research and Technique, 37(4), 271-284. doi:10.1002/(sici)1097-0029(19970515)37:43.0.co;2-oAppelman, T. P., Mizrahi, J., Elisseeff, J. H., & Seliktar, D. (2009). The differential effect of scaffold composition and architecture on chondrocyte response to mechanical stimulation. Biomaterials, 30(4), 518-525. doi:10.1016/j.biomaterials.2008.09.063Chung, C., & Burdick, J. A. (2008). Engineering cartilage tissue. Advanced Drug Delivery Reviews, 60(2), 243-262. doi:10.1016/j.addr.2007.08.027HUNZIKER, E. B., & ROSENBERG, L. C. (1996). Repair of Partial-Thickness Defects in Articular Cartilage. The Journal of Bone & Joint Surgery, 78(5), 721-33. doi:10.2106/00004623-199605000-00012Schulze-Tanzil, G. (2009). Activation and dedifferentiation of chondrocytes: Implications in cartilage injury and repair. Annals of Anatomy - Anatomischer Anzeiger, 191(4), 325-338. doi:10.1016/j.aanat.2009.05.003Umlauf, D., Frank, S., Pap, T., & Bertrand, J. (2010). Cartilage biology, pathology, and repair. Cellular and Molecular Life Sciences, 67(24), 4197-4211. doi:10.1007/s00018-010-0498-0Karystinou, A., Dell’Accio, F., Kurth, T. B. A., Wackerhage, H., Khan, I. M., Archer, C. W., 
 De Bari, C. (2009). Distinct mesenchymal progenitor cell subsets in the adult human synovium. Rheumatology, 48(9), 1057-1064. doi:10.1093/rheumatology/kep192Sakaguchi, Y., Sekiya, I., Yagishita, K., & Muneta, T. (2005). Comparison of human stem cells derived from various mesenchymal tissues: Superiority of synovium as a cell source. Arthritis & Rheumatism, 52(8), 2521-2529. doi:10.1002/art.21212Schaefer, D., Martin, I., Jundt, G., Seidel, J., Heberer, M., Grodzinsky, A., 
 Freed, L. E. (2002). Tissue-engineered composites for the repair of large osteochondral defects. Arthritis & Rheumatism, 46(9), 2524-2534. doi:10.1002/art.1049

    Novel Druggable Hot Spots in Avian Influenza Neuraminidase H5N1 Revealed by Computational Solvent Mapping of a Reduced and Representative Receptor Ensemble

    Get PDF
    The influenza virus subtype H5N1 has raised concerns of a possible human pandemic threat because of its high virulence and mutation rate. Although several approved anti-influenza drugs effectively target the neuraminidase, some strains have already acquired resistance to the currently available anti-influenza drugs. In this study, we present the synergistic application of extended explicit solvent molecular dynamics (MD) and computational solvent mapping (CS-Map) to identify putative ‘hot spots’ within flexible binding regions of N1 neuraminidase. Using representative conformations of the N1 binding region extracted from a clustering analysis of four concatenated 40-ns MD simulations, CS-Map was utilized to assess the ability of small, solvent-sized molecules to bind within close proximity to the sialic acid binding region. Mapping analyses of the dominant MD conformations reveal the presence of additional hot spot regions in the 150- and 430-loop regions. Our hot spot analysis provides further support for the feasibility of developing high-affinity inhibitors capable of binding these regions, which appear to be unique to the N1 strain
    • 

    corecore