259 research outputs found

    Social justice praxis in education: Towards sustainable management strategies

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    Social justice, defined as an impetus towards a socially just educational world, is based on the assumption that all people, irrespective of belief or societal position, are entitled to be treated according to the values of human rights, human dignity and equality. Diverging from the classical positivist approach in social science research that takes injustice as its impetus, the researchers departed from a socio-rationalist approach into exploring sustainable management strategies for effective social justice praxis. This approach has enabled the construction of a conceptual-theoretical framework and an iterative qualitative inquiry, which has as its central principal the sustainable management strategies for effective social justice praxis. Four key findings affirmed the belief that good praxis was to be found in Gemeinschaft relationships, in the influence exerted by government and education systems and structures, where government and principals were found to be co-responsible in ensuring that the best interest of the child was served. This responsibility included practices found in collaborative efforts, where communities became the guardians of their schools due to a disciplined school that followed constitutional values. Lastly, these practitioners aligned their management strategies with human rights values, as well as human dignity and equality, and their strategies found pride of place in extant ubuntu principles.Keywords: determinants; education; human rights; management strategies; restorative; social justice praxis; sustainable development; transformative; ubunt

    Alkaline activation of ceramic waste materials

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    Ceramic materials represent around 45 % of construction and demolition waste, and originate not only from the building process, but also as rejected bricks and tiles from industry. Despite the fact that these wastes are mostly used as road sub-base or construction backfill materials, they can also be employed as supplementary cementitious materials, or even as raw material for alkali-activated binders This research aimed to investigate the properties and microstructure of alkali-activated cement pastes and mortars produced from ceramic waste materials of various origins. Sodium hydroxide and sodium silicate were used to prepare the activating solution. The compressive strength of the developed mortars ranged between 22 and 41 MPa after 7 days of curing at 65 C, depending on the sodium concentration in the solution and the water/binder ratio. These results demonstrate the possibility of using alkaliactivated ceramic materials in building applications.The authors are grateful to the Spanish Ministry of Science and Innovation for supporting this study through Project GEOCEDEM BIA 2011-26947, and also to FEDER funding. They also thank Universitat Jaume I for supporting this research through Lucia Reig's granted research stay.Reig Cerdá, L.; Mitsuuchi Tashima, M.; Soriano, L.; Borrachero Rosado, MV.; Monzó Balbuena, JM.; Paya Bernabeu, JJ. (2013). Alkaline activation of ceramic waste materials. Waste and Biomass Valorization. 4:729-736. https://doi.org/10.1007/s12649-013-9197-zS7297364Puertas, F., García-Díaz, I., Barba, A., Gazulla, M.F., Palacios, M., Gómez, M.P., Martínez-Ramírez, S.: Ceramic wastes as alternative raw materials for Portland cement clinker production. Cement Concrete Comp. 30(9), 798–805 (2008)Ministerio de Fomento de España, Catálogo de Residuos Utilizables en Construcción (2010). http://www.cedexmateriales.vsf.es/view/catalogo.aspx . Retrieved on 6 Dec 2012Stock, D.: World production and consumption of ceramic tiles. Tile Today 73, 50–58 (2011)Medina, C., Juan, A., Frías, M., Sánchez-de-Rojas, M.I., Morán, J.M., Guerra, M.I.: Characterization of concrete made with recycled aggregate from ceramic sanitary ware. Mater. Construcc. 61(304), 533–546 (2011)Pacheco-Torgal, F., Jalali, S.: Reusing ceramic wastes in concrete. Constr. Build. Mater. 24(5), 832–838 (2010)Lavat, A.E., Trezza, M.A., Poggi, M.: Characterization of ceramic roof tile wastes as pozzolanic admixture. Waste Manage. 29(5), 1666–1674 (2009)Nuran, A., Mevlut, U.: The use of waste ceramic tile in cement production. Cement Concrete Res. 30, 497–499 (2000)Pereira-de-Oliveira, L.A., Castro-Gomes, J.P., Santos, P.M.S.: The potential pozzolanic activity of glass and red-clay ceramic waste as cement mortars components. Constr. Build. Mater. 31, 197–203 (2012)Van Deventer, J.S.J., Provis, J.L., Duxson, P., Brice, D.G.: Chemical research and climate change as drivers in the commercial adoption of alkali activated materials. Waste Biomass Valor. 1, 145–155 (2010)van Deventer, J.S.J., Provis, J.L., Duxson, P., Lukey, G.C.: Reaction mechanisms in the geopolymeric conversion of inorganic waste to useful products. J. Hazard. Mater. A139, 506–513 (2007)Duxson, P., Fernández-Jiménez, A., Provis, J.L., Lukey, G.C., Palomo, A., van Deventer, J.S.J.: Geopolymer technology: the current state of the art. J. Mater. Sci. 42(9), 2917–2993 (2007)Bernal, S.A., Rodríguez, E.D., de Gutiérrez, R.M., Provis, J.L., Delvasto, S.: Activation of metakaolin/slag blends using alkaline solutions based on chemically modified silica fume and rice husk ash. Waste Biomass Valor. 3, 99–108 (2012)Fernández-Jiménez, A., Palomo, A., Criado, M.: Microstructure development of alkali-activated fly ash cement: a descriptive model. Cement Concrete Res 35, 1204–1209 (2005)Payá, J., Borrachero, M.V., Monzó, J., Soriano, L., Tashima, M.M.: A new geopolymeric binder from hydrated-carbonated cement. Mater. Lett. 74, 223–225 (2012)Kourti, I., Amutha-Rani, D., Deegan, D., Boccaccini, A.R., Cheeseman, C.R.: Production of geopolymers using glass produced from DC plasma treatment of air pollution control (APC) residues. J. Hazard. Mater. 176, 704–709 (2010)Puertas, F., Barba, A., Gazulla, M.F., Gómez, M.P., Palacios, M., Martínez-Ramírez, S.: Residuos cerámicos para su posible uso como materia prima en la fabricación de clínker de cemento Portland: caracterización y activación alcalina. Mater. Construcc. 56(281), 73–84 (2006)Reig, L., Tashima, M.M., Borrachero, M.V., Monzó, J., Payá, J.: Nuevas matrices cementantes generadas por Activación Alcalina de residuos cerámicos. II Simposio Aprovechamiento de residuos agro-industriales como fuente sostenible de materiales de construcción, November 8–9, Valencia, Spain, pp. 199–207 (2010)L. Reig, M.M. Tashima, M.V. Borrachero, J. Monzó, J. Payá: Residuos de ladrillos cerámicos en la producción de conglomerantes activados alcalinamente, I Pro-Africa Conference: Non-conventional Building Materials Based on Agroindustrial Wastes, October 18–19, Pirassununga, SP, Brazil, pp. 18–21 (2010)García Ten F.J. Descomposición durante la cocción del carbonato cálcico contenido en el soporte crudo de los azulejos. Tesis de doctorado, Departamento de Ingeniería química, UJI (2005)Baronio, G., Binda, L.: Study of the pozzolanicity of some bricks and clays. Constr. Build. Mater. 11(1), 41–46 (1997)Zanelli, C., Raimondo, M., Guarini, G., Dondi, M.: The vitreous phase of porcelain stoneware: composition, evolution during sintering and physical properties. J. Non-Cryst. Solids 357, 3251–3260 (2011)Carty, W.M., Senapati, U.: Porcelain-raw materials, processing, phase evolution, and mechanical behaviour. J. Am. Ceram. Soc. 81(1), 3–20 (1998)ASCER, COACV, COPUT, ITC-AICE, WEBER ET BROUTIN – CEMARKSA: Guía Baldosa Guía de la baldosa cerámica. IVE: Conselleria d’Obres Públiques, Urbanisme i Transports, 4ª Ed. Valencia (2003)Khater, H.M.: Effect of calcium on geopolimerization of aluminosilicate wastes. J. Mater. Civ. Eng. 24, 92–101 (2012)Bondar, D., Lynsdale, C.J., Milestone, N.B., Hassani, N., Ramezanianpour, A.A.: Effect of adding mineral additives to alkali-activated natural pozzolan paste. Constr. Build. Mater. 25, 2906–2910 (2011)Provis, J.L., Harrex, R.M., Bernal, A.S., Duxson, P., van Deventer, J.S.J.: Dilatometry of geopolymers as a means of selecting desirable fly ash sources. J. Non-Cryst. Solids 358, 1930–1937 (2012)Duxson, P., Provis, J.L., Lukey, G.C., Mallicoat, S.W., Kriven, W.M., van Deventer, J.S.J.: Understanding the relationship between geopolymer composition, microstructure and mechanical properties. Colloid Surf. A 269, 47–58 (2005)Tashima, M.M., Akasaki, J.L., Castaldelli, V.N., Soriano, L., Monzó, J., Payá, J., Borrachero, M.V.: New geopolymeric binder based on fluid catalytic cracking catalyst residue (FCC). Mater. Lett. 80, 50–52 (2012)Komnitsas, K., Zaharaki, D., Perdikatsis, V.: Geopolymerisation of low calcium ferronickel slags. J. Mater. Sci. 42, 3073–3082 (2007)Bernal, S.A., Gutierrez, R.M., Provis, J.L., Rose, V.: Effect of silicate modulus and metakaolin incorporation on the carbonation of alkali silicate-activated slags. Cement Concrete Res. 40, 898–907 (2010)Tashima, M.M. Produccion y caracterizacion de materiales cementantes a partir del silicoaluminato calcico vitreo (VCAS). Tesis de doctorado, Departamento de Ingeniería de la construcción y de proyectos de ingeniería civil, UPV (2012)Provis, J.L., van Deventer, J.S.J.: Geopolymerisation kinetics. 2. Reaction kinetic modelling. Chem. Eng. Sci. 62, 2318–2329 (2007

    Molecular therapy for obesity and diabetes based on a long-term increase in hepatic fatty-acid oxidation

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    Obesity-induced insulin resistance is associated with both ectopic lipid deposition and chronic, low-grade adipose tissue inflammation. Despite their excess fat, obese individuals show lower fatty-acid oxidation (FAO) rates. This has raised the question of whether burning off the excess fat could improve the obese metabolic phenotype. Here we used human-safe nonimmunoreactive adeno-associated viruses (AAV) to mediate long-term hepatic gene transfer of carnitine palmitoyltransferase 1A (CPT1A), the key enzyme in fatty-acid β-oxidation, or its permanently active mutant form CPT1AM, to high-fat diet-treated and genetically obese mice. High-fat diet CPT1A- and, to a greater extent, CPT1AM-expressing mice showed an enhanced hepatic FAO which resulted in increased production of CO(2) , adenosine triphosphate, and ketone bodies. Notably, the increase in hepatic FAO not only reduced liver triacylglyceride content, inflammation, and reactive oxygen species levels but also systemically affected a decrease in epididymal adipose tissue weight and inflammation and improved insulin signaling in liver, adipose tissue, and muscle. Obesity-induced weight gain, increase in fasting blood glucose and insulin levels, and augmented expression of gluconeogenic genes were restored to normal only 3 months after AAV treatment. Thus, CPT1A- and, to a greater extent, CPT1AM-expressing mice were protected against obesity-induced weight gain, hepatic steatosis, diabetes, and obesity-induced insulin resistance. In addition, genetically obese db/db mice that expressed CPT1AM showed reduced glucose and insulin levels and liver steatosis. Conclusion: A chronic increase in liver FAO improves the obese metabolic phenotype, which indicates that AAV-mediated CPT1A expression could be a potential molecular therapy for obesity and diabetes

    Inter-Destination Multimedia Synchronization; Schemes, Use Cases and Standardization

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    Traditionally, the media consumption model has been a passive and isolated activity. However, the advent of media streaming technologies, interactive social applications, and synchronous communications, as well as the convergence between these three developments, point to an evolution towards dynamic shared media experiences. In this new model, geographically distributed groups of consumers, independently of their location and the nature of their end-devices, can be immersed in a common virtual networked environment in which they can share multimedia services, interact and collaborate in real-time within the context of simultaneous media content consumption. In most of these multimedia services and applications, apart from the well-known intra and inter-stream synchronization techniques that are important inside the consumers playout devices, also the synchronization of the playout processes between several distributed receivers, known as multipoint, group or Inter-destination multimedia synchronization (IDMS), becomes essential. Due to the increasing popularity of social networking, this type of multimedia synchronization has gained in popularity in recent years. Although Social TV is perhaps the most prominent use case in which IDMS is useful, in this paper we present up to 19 use cases for IDMS, each one having its own synchronization requirements. Different approaches used in the (recent) past by researchers to achieve IDMS are described and compared. As further proof of the significance of IDMS nowadays, relevant organizations (such as ETSI TISPAN and IETF AVTCORE Group) efforts on IDMS standardization (in which authors have been and are participating actively), defining architectures and protocols, are summarized.This work has been financed, partially, by Universitat Politecnica de Valencia (UPV), under its R&D Support Program in PAID-05-11-002-331 Project and in PAID-01-10, and by TNO, under its Future Internet Use Research & Innovation Program. The authors also want to thank Kevin Gross for providing some of the use cases included in Sect. 1.2.Montagud, M.; Boronat Segui, F.; Stokking, H.; Van Brandenburg, R. (2012). Inter-Destination Multimedia Synchronization; Schemes, Use Cases and Standardization. Multimedia Systems. 18(6):459-482. https://doi.org/10.1007/s00530-012-0278-9S459482186Kernchen, R., Meissner, S., Moessner, K., Cesar, P., Vaishnavi, I., Boussard, M., Hesselman, C.: Intelligent multimedia presentation in ubiquitous multidevice scenarios. IEEE Multimedia 17(2), 52–63 (2010)Vaishnavi, I., Cesar, P., Bulterman, D., Friedrich, O., Gunkel, S., Geerts, D.: From IPTV to synchronous shared experiences challenges in design: distributed media synchronization. Signal Process Image Commun 26(7), 370–377 (2011)Geerts, D., Vaishnavi, I., Mekuria, R., Van Deventer, O., Cesar, P.: Are we in sync?: synchronization requirements for watching on-line video together, CHI ‘11, New York, USA (2011)Boronat, F., Lloret, J., García, M.: Multimedia group and inter-stream synchronization techniques: a comparative study. Inf. Syst. 34(1), 108–131 (2009)Chen, M.: A low-latency lip-synchronized videoconferencing system. In: SIGCHI Conference on Human Factors in Computing Systems, CHI’03, ACM, pp. 464–471, New York (2003)Ishibashi, Y., Tasaka, S., Ogawa, H.: Media synchronization quality of reactive control schemes. IEICE Trans. Commun. E86-B(10), 3103–3113 (2003)Ademoye, O.A., Ghinea, G.: Synchronization of olfaction-enhanced multimedia. IEEE Trans. Multimedia 11(3), 561–565 (2009)Cesar, P., Bulterman, D.C.A., Jansen, J., Geerts, D., Knoche, H., Seager, W.: Fragment, tag, enrich, and send: enhancing social sharing of video. ACM Trans. Multimedia Comput. Commun. Appl. 5(3), Article 19, 27 pages (2009)Van Deventer, M.O., Stokking, H., Niamut, O.A., Walraven, F.A., Klos, V.B.: Advanced Interactive Television Service Require Synchronization, IWSSIP 2008. Bratislava, June (2008)Premchaiswadi, W., Tungkasthan, A., Jongsawat, N.: Enhancing learning systems by using virtual interactive classrooms and web-based collaborative work. In: Proceedings of the IEEE Education Engineering Conference (EDUCON 2010), pp. 1531–1537. Madrid, Spain (2010)Diot, C., Gautier, L.: A distributed architecture for multiplayer interactive applications on the internet. IEEE Netw 13(4), 6–15 (1999)Mauve, M., Vogel, J., Hilt, V., Effelsberg, W.: Local-lag and timewarp: providing consistency for replicated continuous applications. IEEE Trans. Multimedia 6(1), 45–57 (2004)Hosoya, K., Ishibashi, Y., Sugawara, S., Psannis, K.E.: Group synchronization control considering difference of conversation roles. In: IEEE 13th International Symposium on Consumer Electronics, ISCE ‘09, pp. 948–952 (2009)Roccetti, M., Ferretti, S., Palazzi, C.: The brave new world of multiplayer online games: synchronization issues with smart solution. In: 11th IEEE Symposium on Object Oriented Real-Time Distributed Computing (ISORC), pp. 587–592 (2008)Ott, D.E., Mayer-Patel, K.: An open architecture for transport-level protocol coordination in distributed multimedia applications. ACM Trans. Multimedia Comput. Commun. Appl. 3(3), 17 (2007)Boronat, F., Montagud, M., Guerri, J.C.: Multimedia group synchronization approach for one-way cluster-to-cluster applications. In: IEEE 34th Conference on Local Computer Networks, LCN 2009, pp. 177–184, Zürich (2009)Boronat, F., Montagud, M., Vidal, V.: Smooth control of adaptive media playout to acquire IDMS in cluster-based applications. In: IEEE LCN 2011, pp. 617–625, Bonn (2011)Huang, Z., Wu, W., Nahrstedt, K., Rivas, R., Arefin, A.: SyncCast: synchronized dissemination in multi-site interactive 3D tele-immersion. In: Proceedings of MMSys, USA (2011)Kim, S.-J., Kuester, F., Kim, K.: A global timestamp-based approach for enhanced data consistency and fairness in collaborative virtual environments. ACM/Springer Multimedia Syst. J. 10(3), 220–229 (2005)Schooler, E.: Distributed music: a foray into networked performance. In: International Network Music Festival, Santa Monica, CA (1993)Miyashita, Y., Ishibashi, Y., Fukushima, N., Sugawara, S., Psannis K.E.: QoE assessment of group synchronization in networked chorus with voice and video. In: Proceedings of IEEE TENCON’11, pp. 393–397 (2011)Hesselman, C., Abbadessa, D., Van Der Beek, W., et al.: Sharing enriched multimedia experiences across heterogeneous network infrastructures. IEEE Commun. Mag. 48(6), 54–65 (2010)Montpetit, M., Klym, N., Mirlacher, T.: The future of IPTV—Connected, mobile, personal and social. Multimedia Tools Appl J 53(3), 519–532 (2011)Cesar, P., Bulterman, D.C.A., Jansen, J.: Leveraging the user impact: an architecture for secondary screens usage in an interactive television environment. ACM/Springer Multimedia Syst. 15(3), 127–142 (2009)Lukosch, S.: Transparent latecomer support for synchronous groupware. In: Proceedings of 9th International Workshop on Groupware (CRIWG), Grenoble, France, pp. 26–41 (2003)Steinmetz, R.: Human perception of jitter and media synchronization. IEEE J. Sel. 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ACM/Springer Multimedia Syst 7(1), 70–90 (1999)Xie, Y., Liu, C., Lee, M.J., Saadawi, T.N.: Adaptive multimedia synchronization in a teleconference system. ACM/Springer Multimedia Syst. 7(4), 326–337 (1999)Laoutaris, N., Stavrakakis, I.: Intrastream synchronization for continuous media streams: a survey of playout schedulers. IEEE Netw. Mag. 16(3), 30–40 (2002)Ishibashi, Y., Tsuji, A., Tasaka, S.: A group synchronization mechanism for stored media in multicast communications. In: Proceedings of the INFOCOM ‘97, Washington (1997)Ishibashi, Y., Tasaka, S.: A group synchronization mechanism for live media in multicast communications. IEEE GLOBECOM’97, pp. 746–752 (1997)Boronat, F., Guerri, J.C., Lloret, J.: An RTP/RTCP based approach for multimedia group and inter-stream synchronization. Multimedia Tools Appl. J. 40(2), 285–319 (2008)Ishibashi, I., Tasaka, S.: A distributed control scheme for group synchronization in multicast communications. In: Proceedings of International Symposium Communications, Kaohsiung, Taiwan, pp. 317–323 (1999)Lu, Y., Fallica, B., Kuipers, F.A., Kooij, R.E., Van Mieghem, P.: Assessing the quality of experience of SopCast. Int. J. Internet Protoc. Technol 4(1), 11–19 (2009)Shamma, D.A., Bastea-Forte, M., Joubert, N., Liu, Y.: Enhancing online personal connections through synchronized sharing of online video, ACM CHI’08 Extended Abstracts, Florence (2008)Ishibashi, Y., Tasaka, S.: A distributed control scheme for causality and media synchronization in networked multimedia games. In: Proceedings of 11th International Conference on Computer Communications and Networks, pp. 144–149, Miami, USA (2002)Ishibashi, Y., Tomaru, K., Tasaka, S., Inazumi, K.: Group synchronization in networked virtual environments. In: Proceedings of the 38th IEEE International Conference on Communications, pp. 885–890, Alaska, USA (2003)Tasaka, S., Ishibashi, Y., Hayashi, M.: Inter–destination synchronization quality in an integrated wired and wireless network with handover. IEEE GLOBECOM 2, 1560–1565 (2002)Kurokawa, Y., Ishibashi, Y., Asano, T.: Group synchronization control in a remote haptic drawing system. In: Proceedings of IEEE International Conference on Multimedia and Expo, pp. 572–575, Beijing, China (2007)Hashimoto, T., Ishibashi, Y.: Group Synchronization Control over Haptic Media in a Networked Real-Time Game with Collaborative Work, Netgames’06, Singapore (2006)Nunome, T., Tasaka, S.: Inter-destination synchronization quality in a multicast mobile ad hoc network. In: Proceedings of IEEE 16th International Symposium on Personal, Indoor and Mobile Radio Communications, pp. 1366–1370, Berlin, Germany (2005)Brandenburg, R., van Stokking, H., Van Deventer, M.O., Boronat, F., Montagud, M., Gross, K.: RTCP for inter-destination media synchronization, draft-brandenburg-avtcore-rtcp-for-idms-03.txt. In: IETF Audio/Video Transport Core Maintenance Working Group, Internet Draft, March 9 (2012)ETSI TS 181 016 V3.3.1 (2009-07) Telecommunications and Internet converged Services and Protocols for Advanced Networking (TISPAN); Service Layer Requirements to integrate NGN Services and IPTVETSI TS 182 027 V3.5.1 (2011-03) Telecommunications and Internet converged Services and Protocols for Advanced Networking (TISPAN); IPTV Architecture; IPTV functions supported by the IMS subsystemETSI TS 183 063 V3.5.2 (2011-03) Telecommunications and Internet converged Services and Protocols for Advanced Networking (TISPAN); IMS-based IPTV stage 3 specificationBrandenburg van, R., et al.: RTCP XR Block Type for inter-destination media synchronization, draft-brandenburg-avt-rtcp-for-idms-00.txt. In: IETF Audio/Video Transport Working Group, Internet Draft, Sept 24, 2010Williams, A., et al.: RTP Clock Source Signalling, draft-williams-avtcore-clksrc-00. 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    Different strategies for recovering metals from CARON process residue

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    http://dx.doi.org/10.1016/j.jhazmat.2011.03.048The capacity of Acidithiobacillus thiooxidans DMS 11478 to recover the heavy metals contained in the residue obtained from the CARON process has been evaluated. Different bioreactor configurations were studied: a two-stage batch system and two semi-continuous systems (stirred-tank reactor leaching and column leaching). In the two-stage system, 46.8% Co, 36.0% Mg, 26.3% Mn and 22.3% Ni were solubilised after 6 h of contact between the residue and the bacteria-free bioacid. The results obtained with the stirred-tank reactor and the column were similar: 50% of the Mg and Co and 40% of the Mn and Ni were solubilised after thirty one days. The operation in the column reactor allowed the solid–liquid ratio to be increased and the pH to be kept at low values (<1.0). Recirculation of the leachate in the column had a positive effect on metal removal; at sixty five days (optimum time) the solubilisation levels were as follows: 86% Co, 83% Mg, 72% Mn and Ni, 62% Fe and 23% Cr. The results corroborate the feasibility of the systems studied for the leaching of metals from CARON process residue and these methodologies can be considered viable for the recovery of valuable metals

    Chemokine (C-C motif) ligand 2 mediates direct and indirect fibrotic responses in human and murine cultured fibrocytes

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    <p>Abstract</p> <p>Background</p> <p>Fibrocytes are a population of circulating bone-marrow-derived cells that express surface markers for leukocytes and mesenchymal cells, and are capable of differentiating into myofibroblasts. They have been observed at sites of active fibrosis and increased circulating numbers correlate with mortality in idiopathic pulmonary fibrosis (IPF). Inhibition of chemokine (C-C motif) receptor 2 (CCR2) during experimental models of lung fibrosis reduces lung collagen deposition, as well as reducing lung fibrocyte accumulation. The aim of the present study was to determine whether human and mouse fibrocytes express functional CCR2.</p> <p>Results</p> <p>Following optimized and identical human and murine fibrocyte isolation, both cell sources were shown to be positive for CCR2 by flow cytometry and this expression colocalized with collagen I and CD45. Human blood fibrocytes stimulated with the CCR2 ligand chemokine (C-C motif) ligand 2 (CCL2), demonstrated increased proliferation (<it>P </it>< 0.005) and differentiation into myofibroblasts (<it>P </it>< 0.001), as well as a chemotactic response (<it>P </it>< 0.05). Murine fibrocytes also responded to CCR2 stimulation, with CCL12 being more potent than CCL2.</p> <p>Conclusions</p> <p>This study directly compares the functional responses of human and murine fibrocytes to CCR2 ligands, and following comparable isolation techniques. We have shown comparable biological effects, strengthening the translatability of the murine models to human disease with respect to targeting the CCR2 axis to ameliorate disease in IPF patients.</p

    Biomarkers of Therapeutic Response in the IL-23 Pathway in Inflammatory Bowel Disease

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    OBJECTIVES: Interleukin-23 (IL-23) has emerged as a new therapeutic target for the treatment of inflammatory bowel disease (IBD). As biomarkers of disease state and treatment efficacy are becoming increasingly important in drug development, we sought to identify efficacy biomarkers for anti-IL-23 therapy in Crohn's disease (CD). METHODS: Candidate IL-23 biomarkers, downstream of IL-23 signaling, were identified using shotgun proteomic analysis of feces and colon lavages obtained from a short-term mouse IBD model (anti-CD40 Rag2(-/-)) treated preventively with monoclonal antibodies (mAbs) to the IL-23 receptor (IL-23R). The biomarkers were then measured in an IBD T-cell transfer model treated therapeutically with a mAb to IL-23 (p19), confirming their association with IBD. To assess the clinical relevance of these markers, we assessed their concentrations in clinical serum, colon tissue, and feces from CD patients. RESULTS: We identified 57 proteins up or downregulated in diseased animals that returned to control values when the mice were treated with mAbs to IL-23R. Among those, S100A8, S100A9, regenerating protein 3β (REG), REG3γ, lipocalin 2 (LCN2), deleted in malignant tumor 1 (DMBT1), and macrophage migration inhibitory factor (MIF) mRNA levels correlated with disease score and dose titration of mAbs to IL-23R or IL-23(p19). All biomarkers, except DMBT1, were also downregulated after therapeutic administration of mAbs to IL-23(p19) in a T-cell transfer IBD mouse model. In sera from CD patients, we confirmed a significant upregulation of S100A8/A9 (43%), MIF (138%), pancreatitis-associated protein (PAP, human homolog of REG3β/γ; 49%), LCN2 (520%), and CCL20 (1280%), compared with control samples, as well as a significant upregulation of S100A8/A9 (887%), PAP (401%), and LCN2 (783%) in human feces from CD patients compared with normal controls. CONCLUSIONS: These studies identify multiple protein biomarkers downstream of IL-23 that could be valuable tools to assess the efficacy of this new therapeutic agent.Clinical and Translational Gastroenterology (2012) 3, e10; doi:10.1038/ctg.2012.2; published online 16 February 2012

    Hsa-miR-125a-3p and hsa-miR-125a-5p are downregulated in non-small cell lung cancer and have inverse effects on invasion and migration of lung cancer cells

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    <p>Abstract</p> <p>Background</p> <p>Two mature microRNAs (miRNAs), hsa-miR-125a-3p and hsa-miR-125a-5p (collectively referred to as hsa-miR-125a-3p/5p), are derived from 3' and 5' ends of pre-miR-125a, respectively. Although impaired regulation of hsa-miR-125a-5p has been observed in some tumors, the role of this miRNA in invasion and metastasis remains unclear, and few studies have examined the function of hsa-miR-125a-3p. In order to characterize the functions of hsa-miR-125a-3p/5p in invasion and metastasis of non-small cell lung cancer (NSCLC), we investigated the relationships between hsa-miR-125a-3p/5p expression and lymph node metastasis in NSCLC tissues. We also explored the impact of expression of these miRNAs on invasive and migratory capabilities of lung cancer cells.</p> <p>Methods</p> <p>Expression of hsa-miR-125a-3p/5p in NSCLC tissues was explored using real-time PCR. The relationships between hsa-miR-125a-3p/5p expression and pathological stage or lymph node metastasis were assessed using the Spearman correlation test. For in vitro studies, lung cancer cells were transfected with sense and antisense 2'-O-methyl oligonucleotides for gain-of-function and loss-of-function experiments. Transwell experiments were performed to evaluate cellular migration and invasion.</p> <p>Results</p> <p>Expression of hsa-miR-125a-3p/5p was lower in NSCLC tissues than in adjacent normal lung tissues (LAC). Furthermore, the results from the Spearman correlation test showed a negative relationship between hsa-miR-125a-3p expression and pathological stage or lymph node metastasis and an inverse relationship between hsa-miR-125a-5p expression and pathological stage or lymph node metastasis. In vitro gain-of-function experiments indicated that hsa-miR-125a-3p and hsa-miR-125a-5p function in an opposing manner, suppressing or enhancing cell migration and invasion in A549 and SPC-A-1 cell lines, respectively. These opposing functions were further validated by suppression of hsa-miR-125a-3p and hsa-miR-125a-5p expression in loss-of-function experiments.</p> <p>Conclusion</p> <p>Hsa-miR-125a-3p and hsa-miR-125a-5p play distinct roles in regulation of invasive and metastatic capabilities of lung cancer cells, consistent with the opposing correlations between the expression of these miRNAs and lymph node metastasis in NSCLC. These results provide new insights into the roles of miR-125a family members in the development of NSCLC.</p
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