The complement receptor C5aR controls acute inflammation and astrogliosis following spinal cord injury

This study investigated the role of the complement activation fragment C5a in secondary pathology following contusive spinal cord injury (SCI). C5ar(-/-) mice, which lack the signaling receptor for C5a, displayed signs of improved locomotor recovery and reduced inflammation during the first week of SCI compared with wild-type mice. Intriguingly, the early signs of improved recovery in C5ar(-/-) mice deteriorated from day 14 onward, with absence of C5aR ultimately leading to poorer functional outcomes, larger lesion volumes, reduced myelin content, and more widespread inflammation at 35 d SCI. Pharmacological blockade of C5aR with a selective antagonist (C5aR-A) during the first 7 d after SCI improved recovery compared with vehicle-treated mice, and this phenotype was sustained up to 35 d after injury. Consistent with observations made in C5ar(-/-) mice, these improvements were, however, lost if C5aR-A administration was continued into the more chronic phase of SCI. Signaling through the C5a-C5aR axis thus appears injurious in the acute period but serves a protective and/or reparative role in the post-acute phase of SCI. Further experiments in bone marrow chimeric mice suggested that the dual and opposing roles of C5aR on SCI outcomes primarily relate to its expression on CNS-resident cells and not infiltrating leukocytes. Additional in vivo and in vitro studies provided direct evidence that C5aR signaling is required during the postacute phase for astrocyte hyperplasia, hypertrophy, and glial scar formation. Collectively, these findings highlight the complexity of the inflammatory response to SCI and emphasize the importance of optimizing the timing of therapeutic interventions

Education and articulation: Laclau and Mouffe’s radical democracy in school

This paper outlines a theory of radical democratic education by addressing a key concept in Laclau and Mouffe’s Hegemony and Socialist Strategy: articulation. Through their concept of articulation, Laclau and Mouffe attempt to liberate Gramsci’s theory of hegemony from Marxist economism, and adapt it to a political sphere inhabited by a plurality of struggles and agents none of which is predominant. However, while for Gramsci the political process of hegemony formation has an explicit educational dimension, Laclau and Mouffe ignore this dimension altogether. My discussion starts with elaborating the concept of articulation and analysing it in terms of three dimensions: performance, connection and transformation. I then address the role of education in Gramsci’s politics, in which the figure of the intellectual is central, and argue that radical democratic education requires renouncing that figure. In the final section, I offer a theory of such education, in which both teacher and students articulate their political differences and identities

The ferric leaching kinetics of arsenopyrite

Abstract In this investigation batch, ferric leaching experiments were carried out in a 100 m l l jacketed vessel maintained at 258C. The parameters varied during the course of the experimental program included the initial redox potential, the total iron concentration, the solids concentration and the pH of the leaching solution. The initial redox potential used ranged from 625 to 470 mV, the overall iron concentration ranged from 8 to 32 g. l l y1 , the mineral concentration ranged from 5 to 20 g. l l y1 and the initial pH used ranged from 1.10 to 1.45. The redox potential of the leach solution was monitored continuously using a redox probe connected to a computer. The leach rates were calculated from the measured change in the redox potential of the leaching solution. The variation in the ferric leaching rate of the arsenopyrite as a function of the solution redox potential displayed similar trends, irrespective of the conditions employed. The ferric leaching rate of the arsenopyrite decreased with decreasing redox potential of the leaching solution and could be accurately described using a modified Butler-Volmer equation; yr s r e y . High concentrations of ferric iron and protons, and a reduction in the solids Ž concentration were found to impede the leach rate. The 'rest potential' i.e., the redox potential at . which the dissolution of arsenopyrite stops of the arsenopyrite was found to be higher under these conditions. However, no occluding sulphur layer could be detected on the surface of mineral particles, hence the results suggest that the reactivity of the mineral decreases with an increase in the effective concentration of the ferric iron species. Therefore, although the results suggest the Ž . PII: S 0 3 0 4 -3 8 6 X 9 9 0 0 0 0 7 -9 ( ) R. Ruitenberg et al.r Hydrometallurgy 52 1999 37-53 38 likelihood of an electrochemical mechanism being operative, it is necessary to modify the Butler-Volmer-based model to account for the above observations in order to obtain a model capable of predicting the ferric leaching rate of arsenopyrite across a broad range of operating conditions.

Experimental loophole-free violation of a Bell inequality using entangled electron spins separated by 1.3 km

For more than 80 years, the counterintuitive predictions of quantum theory have stimulated debate about the nature of reality. In his seminal work, John Bell proved that no theory of nature that obeys locality and realism can reproduce all the predictions of quantum theory. Bell showed that in any local realist theory the correlations between distant measurements satisfy an inequality and, moreover, that this inequality can be violated according to quantum theory. This provided a recipe for experimental tests of the fundamental principles underlying the laws of nature. In the past decades, numerous ingenious Bell inequality tests have been reported. However, because of experimental limitations, all experiments to date required additional assumptions to obtain a contradiction with local realism, resulting in loopholes. Here we report on a Bell experiment that is free of any such additional assumption and thus directly tests the principles underlying Bell's inequality. We employ an event-ready scheme that enables the generation of high-fidelity entanglement between distant electron spins. Efficient spin readout avoids the fair sampling assumption (detection loophole), while the use of fast random basis selection and readout combined with a spatial separation of 1.3 km ensure the required locality conditions. We perform 245 trials testing the CHSH-Bell inequality $S \leq 2$ and find $S = 2.42 \pm 0.20$. A null hypothesis test yields a probability of $p = 0.039$ that a local-realist model for space-like separated sites produces data with a violation at least as large as observed, even when allowing for memory in the devices. This result rules out large classes of local realist theories, and paves the way for implementing device-independent quantum-secure communication and randomness certification.Comment: Raw data will be made available after publicatio

A fusion of minicircle DNA and nanoparticle delivery technologies facilitates therapeutic genetic engineering of autologous canine olfactory mucosal cells

Olfactory ensheathing cells (OECs) promote axonal regeneration and improve locomotor function when transplanted into the injured spinal cord. A recent clinical trial demonstrated improved motor function in domestic dogs with spinal injury following autologous OEC transplantation. Their utility in canines offers promise for human translation, as dogs are comparable to humans in terms of clinical management and genetic/environmental variation. Moreover, the autologous, minimally invasive derivation of OECs makes them viable for human spinal injury investigation. Genetic engineering of transplant populations may augment their therapeutic potential, but relies heavily on viral methods which have several drawbacks for clinical translation. We present here the first proof that magnetic particles deployed with applied magnetic fields and advanced DNA minicircle vectors can safely bioengineer OECs to secrete a key neurotrophic factor, with an efficiency approaching that of viral vectors. We suggest that our alternative approach offers high translational potential for the delivery of augmented clinical cell therapies

The notion of contextual locking: Previously learnt items are not accessible as such when appearing in a less common context

We examined the effect of context on the learning of spatial coding in four experiments. Two partially overlapping sets of stimuli, which had the very same stimulus–response spatial coding, were presented in unique contexts. Results show contextual locking—that is, response times to the very same item in a more common context (80%) were significantly shorter than those in a less common context (20%). Contextual locking was obtained both when the context was more salient (Experiments 1 and 2) and less salient (Experiments 3 and 4). In addition, results were obtained even when contextualization seemed less necessary (Experiments 2 and 4). Binding of information to context is discussed in relation to chunking, transfer effects, and practical applications pertaining to professional training

Comparison of NITAG policies and working processes in selected developed countries

BACKGROUND: Vaccines are specific medicines characterized by two country-specific market access processes: (1) a recommendation by National Immunization Technical Advisory Group (NITAG), and (2) a funding policy decision. OBJECTIVES: The objective of this study was to compare and analyze NITAGs of 13 developed countries by describing vaccination committees' bodies and working processes. METHODS: Information about NITAGs bodies and working processes was searched from official sources from June 2011 to November 2012. Retrieved information was completed from relevant articles identified through a systematic literature review and by information provided by direct contact with NITAGs or parent organizations. An expert panel was also conducted to discuss, validate, and provide additional input on obtained results. RESULTS: While complete information, defined as 100%, was retrieved only for the UK, at least 80% of data was retrieved for 9 countries out of the 13 selected countries. Terms of references were identified in 7 countries, and the main mission for all NITAGs was to provide advice for National immunization programs. However, these terms of references did not fully encompass all the actual missions of the NITAGs. Decision analysis frameworks were identified for 10 out of the 13, and all NITAGs considered at least four criteria for decision-making: disease burden, efficacy/effectiveness, safety and cost-effectiveness. Advices were published by most NITAGs, but few NITAGs published meeting agendas and minutes. Only the United States had open meetings. CONCLUSIONS: This study supports previous findings about the disparities in NITAGs processes which could potentially explain the disparity in access to vaccinations and immunization programs across Europe. With NITAGs recommendations being used by policy decision makers for implementation and funding of vaccine programs, guidances should be well-informed and transparent to ensure National Immunization Programs' (NIP) credibility among the public and health care professionals

Transplantation of canine olfactory ensheathing cells producing chondroitinase ABC promotes chondroitin sulphate proteoglycan digestion and axonal sprouting following spinal cord injury

Olfactory ensheathing cell (OEC) transplantation is a promising strategy for treating spinal cord injury (SCI), as has been demonstrated in experimental SCI models and naturally occurring SCI in dogs. However, the presence of chondroitin sulphate proteoglycans within the extracellular matrix of the glial scar can inhibit efficient axonal repair and limit the therapeutic potential of OECs. Here we have used lentiviral vectors to genetically modify canine OECs to continuously deliver mammalian chondroitinase ABC at the lesion site in order to degrade the inhibitory chondroitin sulphate proteoglycans in a rodent model of spinal cord injury. We demonstrate that these chondroitinase producing canine OECs survived at 4 weeks following transplantation into the spinal cord lesion and effectively digested chondroitin sulphate proteoglycans at the site of injury. There was evidence of sprouting within the corticospinal tract rostral to the lesion and an increase in the number of corticospinal axons caudal to the lesion, suggestive of axonal regeneration. Our results indicate that delivery of the chondroitinase enzyme can be achieved with the genetically modified OECs to increase axon growth following SCI. The combination of these two promising approaches is a potential strategy for promoting neural regeneration following SCI in veterinary practice and human patients