In the absence of CD154, administration of interleukin-12 restores Th1 responses but not protective immunity to Schistosoma mansoni

The cytokine interplay during the development of protective immunity to the radiation-attenuated (RA) schistosome vaccine has been extensively characterized over recent years, yet the role of costimulatory molecules in the development of cell-mediated immunity is much less well understood. Here we demonstrate the importance of CD40/CD154 in vaccine-induced immunity, as CD154(-/-) mice exposed to RA schistosomes develop no protection to challenge infection. We showed that vaccinated CD154(-/-) mice have defective Th1-associated immune responses in the skin-draining lymph nodes and the lungs, with reduced or absent levels of interleukin-12p40 (IL-12p40), gamma interferon, and nitric oxide, but elevated levels of lung IL-4 and IL-5. The expression of major histocompatibility complex II (MHC-II) on antigen-presenting cells recovered from the lungs of vaccinated CD154(-/-) mice was also severely compromised. The administration of anti-CD40 monoclonal antibody (MAb) to CD154(-/-) mice did not reconstitute sustained Th1 responses in the lymph nodes or the lungs, nor did the MAb restore anti-parasite immunoglobulin G production or protective immunity. On the other hand, the administration of recombinant IL-12 (rIL-12) to CD154(-/-) mice shortly after vaccination caused elevated and sustained levels of Th1-associated cytokines, rescued MHC-II expression by lung CD11c(+) cells, and restored the appearance of inflammatory effector foci in the lungs. However, the treatment of CD154(-/-) mice with rIL-12 did not restore protection. We conclude that protective immunity to the RA schistosome vaccine is CD154 dependent but is independent of IL-12-orchestrated cellular immune mechanisms in the lungs

Using the null-stream of GEO600 to veto transient events in the detector output

A network of gravitational wave detectors is currently being commissioned around the world. Each of these detectors will search for gravitational waves from various astronomical sources. One of the main searches underway is for un-modelled, transient gravitational wave events. The nature of these signals is such that it will be difficult to distinguish them from bursts of instrumental noise that originate in or around the detector and which then couple to the main detector output. One way to deal with this is to look for events that are coincident in more than one gravitational wave detector. However, with very large event lists (potentially thousands of events per day per detector), the number of events that pass this test due to random chance can still be large. At each detector site, various methods are being developed to veto instrumental bursts from lists of candidate events from that particular detector. This reduces the size of the event lists of each detector, and hopefully the final coincident event list, to a more manageable level. This paper presents one such veto method that can be used to veto certain classes of transient events detected in the output data stream of GEO 600. The method uses events detected in the null-stream output of GEO 600 (which contains, in principle, no gravitational wave signal) with a threshold to veto events detected in the main strain output. We show that, for the certain types of signals tested, the method is very robust, delivering high efficiency for a very low false-veto rate. In particular, it is shown that when applied to real detector data, the method is able to strongly veto a certain type of events which appear around 370 Hz in the detector output

Null-stream veto for two co-located detectors: Implementation issues

Time-series data from multiple gravitational wave (GW) detectors can be linearly combined to form a null-stream, in which all GW information will be cancelled out. This null-stream can be used to distinguish between actual GW triggers and spurious noise transients in a search for GW bursts using a network of detectors. The biggest source of error in the null-stream analysis comes from the fact that the detector data are not perfectly calibrated. In this paper, we present an implementation of the null-stream veto in the simplest network of two co-located detectors. The detectors are assumed to have calibration uncertainties and correlated noise components. We estimate the effect of calibration uncertainties in the null-stream veto analysis and propose a new formulation to overcome this. This new formulation is demonstrated by doing software injections in Gaussian noise.Comment: Minor changes; To appear in Class. Quantum Grav. (Proc. GWDAW10

Myeloid Cell Phenotypes in Susceptibility and Resistance to Helminth Parasite Infections

Many major tropical diseases are caused by long-lived helminth parasites that are able to survive by modulation of the host immune system, including the innate compartment of myeloid cells. In particular, dendritic cells and macrophages show markedly altered phenotypes during parasite infections. In addition, many specialized subsets such as eosinophils and basophils expand dramatically in response to these pathogens. The changes in phenotype and function, and their effects on both immunity to infection and reactivity to bystander antigens such as allergens, are discussed

New LISA dynamics feedback control scheme: Common-mode isolation of test mass control and probes of test-mass acceleration

The Drag-Free and Attitude Control System is a central element of LISA technology, ensuring the very high dynamic stability of spacecraft and test masses required in order to reach the sensitivity that gravitational wave astronomy in space requires. Applying electrostatic forces on test-masses is unavoidable but should be restricted to the minimum necessary to keep the spacecraft-test masses system in place, while granting the optimal quality of test-mass free-fall. To realise this, we propose a new test-mass suspension scheme that applies forces and torques only in proportion to any differential test mass motion observed, and we demonstrate that the new scheme significantly mitigates the amount of suspension forces and torques needed to control the whole system. The mathematical method involved allows us to derive a new observable measuring the differential acceleration of test masses projected on the relevant sensitive axes, which will have important consequences for LISA data calibration, processing and analysis

Optimal time-domain combination of the two calibrated output quadratures of GEO 600

GEO 600 is an interferometric gravitational wave detector with a 600 m arm-length and which uses a dual-recycled optical configuration to give enhanced sensitivity over certain frequencies in the detection band. Due to the dual-recycling, GEO 600 has two main output signals, both of which potentially contain gravitational wave signals. These two outputs are calibrated to strain using a time-domain method. In order to simplify the analysis of the GEO 600 data set, it is desirable to combine these two calibrated outputs to form a single strain signal that has optimal signal-to-noise ratio across the detection band. This paper describes a time-domain method for doing this combination. The method presented is similar to one developed for optimally combining the outputs of two colocated gravitational wave detectors. In the scheme presented in this paper, some simplifications are made to allow its implementation using time-domain methods

Robust vetoes for gravitational-wave burst triggers using known instrumental couplings

The search for signatures of transient, unmodelled gravitational-wave (GW) bursts in the data of ground-based interferometric detectors typically uses `excess-power' search methods. One of the most challenging problems in the burst-data-analysis is to distinguish between actual GW bursts and spurious noise transients that trigger the detection algorithms. In this paper, we present a unique and robust strategy to `veto' the instrumental glitches. This method makes use of the phenomenological understanding of the coupling of different detector sub-systems to the main detector output. The main idea behind this method is that the noise at the detector output (channel H) can be projected into two orthogonal directions in the Fourier space -- along, and orthogonal to, the direction in which the noise in an instrumental channel X would couple into H. If a noise transient in the detector output originates from channel X, it leaves the statistics of the noise-component of H orthogonal to X unchanged, which can be verified by a statistical hypothesis testing. This strategy is demonstrated by doing software injections in simulated Gaussian noise. We also formulate a less-rigorous, but computationally inexpensive alternative to the above method. Here, the parameters of the triggers in channel X are compared to the parameters of the triggers in channel H to see whether a trigger in channel H can be `explained' by a trigger in channel X and the measured transfer function.Comment: 14 Pages, 8 Figures, To appear in Class. Quantum Gra

A statistical veto method employing an amplitude consistency check

Statistical veto methods are commonly used to reduce the list of candidate gravitational wave (GW) events which are detected as transient (burst) signals in the main output of GW detectors. If a burst event in the GW channel is coincident with an event in a veto channel (where the veto channel does not contain any GW signal), it is possible to veto the event from the GW channel with a low 'false-veto' rate. Unfortunately, many promising veto channels are interferometer channels which can, at some level, contain traces of any detected GW signal. In this case, the application of a 'standard statistical veto' could have a high false-veto rate. We will present an extension to the standard statistical veto method that includes an 'amplitude consistency check'. This method allows the application of statistical vetoes derived from interferometer channels containing GW information with a low false-veto rate. By applying a statistical veto with an amplitude consistency check to data from the GEO 600 detector, veto efficiencies between 5 and 20%, together with a use-percentage of up to 80%, were obtained. The robustness of this veto method was also confirmed by hardware injections. The burst triggers were generated using the mHACR detection algorithm

Novel O-linked methylated glycan antigens decorate secreted immunodominant glycoproteins from the intestinal nematode Heligmosomoides polygyrus

Glycan molecules from helminth parasites have been associated with diverse biological functions ranging from interactions with neighbouring host cell populations to down-modulation of specific host immunity. Glycoproteins secreted by the intestinal nematode Heligmosomoides polygyrus are of particular interest as the excretory-secretory products (termed HES) of this parasite contain both heat-labile and heat-stable components with immunomodulatory effects. We used MALDI-TOF-MS and LC-MS/MS to analyse the repertoire of N- and O-linked glycans released from Heligmosomoides polygyrus excretory-secretory products by PNGase A and F, β-elimination and hydrazinolysis revealing a broad range of structures including novel methylhexose- and methylfucose-containing glycans. Monoclonal antibodies to two immunodominant glycans of H. polygyrus, previously designated Glycans A and B, were found to react by glycan array analysis to a methyl-hexose-rich fraction and to a sulphated LacDiNAc (LDN; GalNAcβ1-4GlcNAc) structure, respectively. We also analysed the glycan repertoire of a major glycoprotein in Heligmosomoides polygyrus excretory-secretory products, VAL-2, which contains many glycan structures present in Heligmosomoides polygyrus excretory-secretory products including Glycan A. However, it was found that this set of glycans is not responsible for the heat-stable immunomodulatory properties of Heligmosomoides polygyrus excretory-secretory products, as revealed by the inability of VAL-2 to inhibit allergic lung inflammation. Taken together, these studies reveal that H. polygyrus secretes a diverse range of antigenic glycoconjugates, and provides a framework to explore the biological and immunomodulatory roles they may play within the mammalian host