Neutralizing Antibody Fails to Impact the Course of Ebola Virus Infection in Monkeys

Prophylaxis with high doses of neutralizing antibody typically offers protection against challenge with viruses producing acute infections. In this study, we have investigated the ability of the neutralizing human monoclonal antibody, KZ52, to protect against Ebola virus in rhesus macaques. This antibody was previously shown to fully protect guinea pigs from infection. Four rhesus macaques were given 50 mg/kg of neutralizing human monoclonal antibody KZ52 intravenously 1 d before challenge with 1,000 plaque-forming units of Ebola virus, followed by a second dose of 50 mg/kg antibody 4 d after challenge. A control animal was exposed to virus in the absence of antibody treatment. Passive transfer of the neutralizing human monoclonal antibody not only failed to protect macaques against challenge with Ebola virus but also had a minimal effect on the explosive viral replication following infection. We show that the inability of antibody to impact infection was not due to neutralization escape. It appears that Ebola virus has a mechanism of infection propagation in vivo in macaques that is uniquely insensitive even to high concentrations of neutralizing antibody

Translations of new public management: a decentred approach to school governance in four OECD countries

Despite the prevalence of corporate and performative models of school governance within and across different education systems, there are various cases of uneven, hybrid expressions of New Public Management (NPM) that reveal the contingency of global patterns of rule. Adopting a ‘decentred approach’ to governance (Bevir, M. 2010. “Rethinking Governmentality: Towards Genealogies of Governance.” European Journal of Social Theory 13 (4): 423–441), this paper compares the development of NPM in four OECD countries: Australia, England, Spain, and Switzerland. A focus of the paper is how certain policy instruments are created and sustained within highly differentiated geo-political settings and through different multi-scalar actors and authorities yet modified to reflect established traditions and practices

Natural IgE production in the absence of MHC Class II cognate help

IgE induction by parasites and allergens is antigen driven and cognate T cell help dependent. We demonstrate that spontaneously produced IgE in T cell-deficient and germ-free wild-type (wt) mice is composed of natural specificities and induced by a mechanism independent of MHC class II (MHC II) cognate help. This does not require secondary lymphoid structures or germinal center formation, although some bystander T cell-derived IL-4 is necessary. The pathway of spontaneous IgE production is not inhibited by regulatory T cells and increases with age to constitute significant serum concentrations, even in naive animals

Commissioning of the LHCb Silicon Tracker using data from the LHC injection tests

LHCb is a single-arm forward spectrometer dedicated to the study of the CP-violation and rare decays in the b-quark sector. An efficient and high precision tracking system is a key requirement of the experiment. The LHCb Silicon Tracker Project consists of two sub-detectors that make use of silicon micro-strip technology: the Tracker Turicensis located upstream of the spectrometer magnet and the Inner Tracker which covers the innermost part of the tracking stations after the magnet. In total an area of 12 m^2 is covered by silicon. In September 2008 and June 2009, injection tests from the SPS to the LHC were performed. Bunches of order 5x10^9 protons were dumped onto a beam stopper (TED) located upstream of LHCb. This produced a spray of ~10 GeV muons in the LHCb detector. Though the occupancy in this environment is relatively large, these TED runs have allowed a first space and time alignment of the tracking system. Results of these studies together and the overall detector performance obtained in the TED running will be discussed

Performance of the LHCb Silicon Tracker with first data

The LHCb Silicon Tracker consists of two sub-detectors the Tracker Turicensis and Inner Tracker that are constructed from silicon microstrip technology. Performance studies of both sub-detectors using data taken during the LHC synchronization tests are described

Ants, Cataglyphis cursor, Use Precisely Directed Rescue Behavior to Free Entrapped Relatives

Although helping behavior is ubiquitous throughout the animal kingdom, actual rescue activity is particularly rare. Nonetheless, here we report the first experimental evidence that ants, Cataglyphis cursor, use precisely directed rescue behavior to free entrapped victims; equally important, they carefully discriminate between individuals in distress, offering aid only to nestmates. Our experiments simulate a natural situation, which we often observed in the field when collecting Catagyphis ants, causing sand to collapse in the process. Using a novel experimental technique that binds victims experimentally, we observed the behavior of separate, randomly chosen groups of 5 C. cursor nestmates under one of six conditions. In five of these conditions, a test stimulus (the “victim”) was ensnared with nylon thread and held partially beneath the sand. The test stimulus was either (1) an individual from the same colony; (2) an individual from a different colony of C cursor; (3) an ant from a different ant species; (4) a common prey item; or, (5) a motionless (chilled) nestmate. In the final condition, the test stimulus (6) consisted of the empty snare apparatus. Our results demonstrate that ants are able to recognize what, exactly, holds their relative in place and direct their behavior to that object, the snare, in particular. They begin by excavating sand, which exposes the nylon snare, transporting sand away from it, and then biting at the snare itself. Snare biting, a behavior never before reported in the literature, demonstrates that rescue behavior is far more sophisticated, exact and complexly organized than the simple forms of helping behavior already known, namely limb pulling and sand digging. That is, limb pulling and sand digging could be released directly by a chemical call for help and thus result from a very simple mechanism. However, it's difficult to see how this same releasing mechanism could guide rescuers to the precise location of the nylon thread, and enable them to target their bites to the thread itself

First Operational Experience from the LHCb Silicon Tracker

The LHCb Silicon Tracker is a silicon micro-strip detector covering a sensitive area of 12 m2 with a total of 272k readout channels. The installation of the detector is complete and commissioning is making excellent progress. The detector has recorded first beam-induced events during LHC synchronization tests in August 2008 and in June 2009. These events have allowed the performance to be studied, and adjustments to the operational parameters to be made. In this contribution, we will draw first lessons from the in-situ commissioning of the Silicon Tracker, and present results from the reconstruction of data collected during the LHC synchronization tests

Production, Commissioning and First Data of the LHCb Silicon Tracker

We give here a short review of the LHCb Silicon Tracker, the main points of the module production and quality control, followed by the commissioning of the detector. Problems that were found during production or commissioning are described and the first performance assessment of the installed detector with “beam data” is given

Trail formation based on directed pheromone deposition

We propose an Individual-Based Model of ant-trail formation. The ants are modeled as self-propelled particles which deposit directed pheromones and interact with them through alignment interaction. The directed pheromones intend to model pieces of trails, while the alignment interaction translates the tendency for an ant to follow a trail when it meets it. Thanks to adequate quantitative descriptors of the trail patterns, the existence of a phase transition as the ant-pheromone interaction frequency is increased can be evidenced. Finally, we propose both kinetic and fluid descriptions of this model and analyze the capabilities of the fluid model to develop trail patterns. We observe that the development of patterns by fluid models require extra trail amplification mechanisms that are not needed at the Individual-Based Model level

Broadly Neutralizing Human Anti-HIV Antibody 2G12 Is Effective in Protection against Mucosal SHIV Challenge Even at Low Serum Neutralizing Titers

Developing an immunogen that elicits broadly neutralizing antibodies (bNAbs) is an elusive but important goal of HIV vaccine research, especially after the recent failure of the leading T cell based HIV vaccine in human efficacy trials. Even if such an immunogen can be developed, most animal model studies indicate that high serum neutralizing concentrations of bNAbs are required to provide significant benefit in typical protection experiments. One possible exception is provided by the anti-glycan bNAb 2G12, which has been reported to protect macaques against CXCR4-using SHIV challenge at relatively low serum neutralizing titers. Here, we investigated the ability of 2G12 administered intravenously (i.v.) to protect against vaginal challenge of rhesus macaques with the CCR5-using SHIVSF162P3. The results show that, at 2G12 serum neutralizing titers of the order of 1∶1 (IC90), 3/5 antibody-treated animals were protected with sterilizing immunity, i.e. no detectable virus replication following challenge; one animal showed a delayed and lowered primary viremia and the other animal showed a course of infection similar to 4 control animals. This result contrasts strongly with the typically high titers observed for protection by other neutralizing antibodies, including the bNAb b12. We compared b12 and 2G12 for characteristics that might explain the differences in protective ability relative to neutralizing activity. We found no evidence to suggest that 2G12 transudation to the vaginal surface was significantly superior to b12. We also observed that the ability of 2G12 to inhibit virus replication in target cells through antibody-mediated effector cell activity in vitro was equivalent or inferior to b12. The results raise the possibility that some epitopes on HIV may be better vaccine targets than others and support targeting the glycan shield of the envelope