Tissue Microenvironments Define and Get Reinforced by Macrophage Phenotypes in Homeostasis or during Inflammation, Repair and Fibrosis

Current macrophage phenotype classifications are based on distinct in vitro culture conditions that do not adequately mirror complex tissue environments. In vivo monocyte progenitors populate all tissues for immune surveillance which supports the maintenance of homeostasis as well as regaining homeostasis after injury. Here we propose to classify macrophage phenotypes according to prototypical tissue environments, e.g. as they occur during homeostasis as well as during the different phases of (dermal) wound healing. In tissue necrosis and/or infection, damage- and/or pathogen-associated molecular patterns induce proinflammatory macrophages by Toll-like receptors or inflammasomes. Such classically activated macrophages contribute to further tissue inflammation and damage. Apoptotic cells and antiinflammatory cytokines dominate in postinflammatory tissues which induce macrophages to produce more antiinflammatory mediators. Similarly, tumor-associated macrophages also confer immunosuppression in tumor stroma. Insufficient parenchymal healing despite abundant growth factors pushes macrophages to gain a profibrotic phenotype and promote fibrocyte recruitment which both enforce tissue scarring. Ischemic scars are largely devoid of cytokines and growth factors so that fibrolytic macrophages that predominantly secrete proteases digest the excess extracellular matrix. Together, macrophages stabilize their surrounding tissue microenvironments by adapting different phenotypes as feed-forward mechanisms to maintain tissue homeostasis or regain it following injury. Furthermore, macrophage heterogeneity in healthy or injured tissues mirrors spatial and temporal differences in microenvironments during the various stages of tissue injury and repair. Copyright (C) 2012 S. Karger AG, Base

Internet Governance: the State of Play

The Global Forum on Internet Governance held by the UNICT Task Force in New York on 25-26 March concluded that Internet governance issues were many and complex. The Secretary-General's Working Group on Internet Governance will have to map out and navigate this complex terrain as it makes recommendations to the World Summit on an Information Society in 2005. To assist in this process, the Forum recommended, in the words of the Deputy Secretary-General of the United Nations at the closing session, that a matrix be developed "of all issues of Internet governance addressed by multilateral institutions, including gaps and concerns, to assist the Secretary-General in moving forward the agenda on these issues." This paper takes up the Deputy Secretary-General's challenge. It is an analysis of the state of play in Internet governance in different forums, with a view to showing: (1) what issues are being addressed (2) by whom, (3) what are the types of consideration that these issues receive and (4) what issues are not adequately addressed

Enabling Communication Technologies for Automated Unmanned Vehicles in Industry 4.0

Within the context of Industry 4.0, mobile robot systems such as automated guided vehicles (AGVs) and unmanned aerial vehicles (UAVs) are one of the major areas challenging current communication and localization technologies. Due to stringent requirements on latency and reliability, several of the existing solutions are not capable of meeting the performance required by industrial automation applications. Additionally, the disparity in types and applications of unmanned vehicle (UV) calls for more flexible communication technologies in order to address their specific requirements. In this paper, we propose several use cases for UVs within the context of Industry 4.0 and consider their respective requirements. We also identify wireless technologies that support the deployment of UVs as envisioned in Industry 4.0 scenarios.Comment: 7 pages, 1 figure, 1 tabl

Characterization of a circulating PRRSV strain by means of random PCR cloning and full genome sequencing

RS is a pig disease of major economic importance that causes respiratory and reproductive problems in pigs. Over the last years it has become clear that PRRSV heterogeneity is increasing. Consequently, this has a potential impact on diagnosis and strategies to counter this disease. The use of sequence-independent PCR techniques for the detection and characterization of PRRSV could be useful to bypass problems associated with the heterogeneity of this virus. A random PCR cloning approach was tested for the characterization of PRRSV strain 07V063 of unknown genetic background that circulated on a Belgian farm. By using this approach, 7305 bp of sequence data were obtained, distributed randomly across the genome. Using RT-PCR with strain-specific primers, the full length sequence (15014 nt) was obtained. Phylogenetic relationships using ORF5 and ORF1a (NSP2) sequences showed that 07V063 was classified in type 1 subtype 1 and that 07V063 was genetically different from prototype Lelystad Virus (LV). 07V063 showed 87-93% aa identity with LV ORFs coding for structural proteins. Most variation (compared to LV) was noticed in Nsp2 (81% identity) with a deletion of 28 aa. This deletion was different from other known deletions in this ORF. In conclusion, it is shown that this random PCR cloning approach can be used for the characterization of new PRRSV strains of unknown genetic background

Development of an experimental inactivated PRRSV vaccine that induces virus-neutralizing antibodies

Porcine reproductive and respiratory syndrome virus (PRRSV) can induce reproductive disorders and is involved in the porcine respiratory disease complex, causing tremendous economic losses to the swine industry. Inactivated PRRSV vaccines are preferred over attenuated vaccines because of their safety and flexibility towards emerging virus strains, but the efficacy of current inactivated PRRSV vaccines is questionable. In this study, experimental inactivated PRRSV vaccines were developed, based on two formerly optimized inactivation procedures: UV irradiation and treatment with binary ethylenimine (BEI). In a first experiment, it was shown that vaccination with UV- or BEI-inactivated virus in combination with Incomplete Freund's Adjuvant induced virus-specific antibodies and strongly primed the virus-neutralizing (VN) antibody response. Subsequently, the influence of adjuvants on the immunogenicity of neutralizing epitopes on the inactivated virus was investigated. It was shown that vaccination with BEI-inactivated virus in combination with a commercial oil-in-water adjuvant induced high titers (3.4 log(2)) of VN antibodies in 6/6 pigs, instead of only priming the neutralizing antibody response. After challenge, neutralizing antibody titers in these vaccinated animals rose to a mean value of 5.5 log(2), and the duration of the viremia was reduced to an average of 1 week. This study shows that, by the use of an optimized inactivation procedure and a suitable adjuvant, inactivated PRRSV vaccines can be developed that induce VN antibodies and offer partial protection upon challenge

Breakdown and recovery of thin gate oxides

Breakdown events are studied in varying test set-ups with a high time resolution. Often a partial recovery from breakdown is observed\ud within a few ms. Parameters such as device area, stress conditions and parasitic elements prohibit the recovery if they result in a high system impedance. The results suggest the existence of a highly conductive path that can be annihilated during breakdown