Molecular characterisation of poliovirus inactivation with formaldehyde or other alternative chemical compounds

As the Global Polio Eradication Initiative progresses towards its conclusion inactivated poliovirus vaccine (IPV) is increasingly being used on a routine basis to ensure that any re-introduced viruses do not spread. However the current administration of conventional IPV (cIPV) includes a risk of wild seed viruses escaping from manufacturing facilities. To address this risk IPVs could instead be prepared from Sabin live attenuated strains. However Sabin IPV (sIPV) type 2 has been found to induce a lower level of antibodies than type 2 cIPV. The reason (s) for this difference is not clear as little is known about the molecular mechanisms that underpin the formaldehyde inactivation process. To investigate the process of inactivation and its consequences, this study has analysed the effect of inactivation on different aspects of poliovirus biology. As serotype 2 shows the greatest differences between sIPV and cIPV, a range of type 2 poliovirus strains with varied antigenic and biological properties have been inactivated using formaldehyde and alternative chemicals. The effect of inactivation on the viral antigenicity and immunogenicity of the poliovirus strains has been assessed using methods for the pre-release control of vaccine batches and various novel techniques including a biosensor-based technique and immunisation-challenge experiments in transgenic mice. Both the virus strain and inactivation chemical affected the potency of inactivated preparations. The effect of inactivation on the functionality of the viral RNA and the ability of inactivated virus to bind and undergo the conformational changes necessary to enter the target cell have been investigated using real-time RT-PCR and FACS flow cytometry. Inactivation modified the viral RNA and prevented poliovirus virions from undergoing necessary conformational changes. This research will contribute to better understanding the differences between sIPV and cIPV and will help to develop new/modified inactivation protocols to produce IPVs with improved immunogenicity

Geant4 based simulations for novel neutron detector development

A Geant4-based Python/C++ simulation and coding framework, which has been developed and used in order to aid the R&D efforts for thermal neutron detectors at neutron scattering facilities, is described. Built upon configurable geometry and generator modules, it integrates a general purpose object oriented output file format with meta-data, developed in order to facilitate a faster turn-around time when setting up and analysing simulations. Also discussed are the extensions to Geant4 which have been implemented in order to include the effects of low-energy phenomena such as Bragg diffraction in the polycrystalline support materials of the detector. Finally, an example application of the framework is briefly shown.Comment: Proceedings for the 20th International Conference on Computing in High Energy and Nuclear Physics (CHEP

Simulation Tools for Detector and Instrument Design

The high performance requirements at the European Spallation Source have been driving the technological advances on the neutron detector front. Now more than ever is it important to optimize the design of detectors and instruments, to fully exploit the ESS source brilliance. Most of the simulation tools the neutron scattering community has at their disposal target the instrument optimization until the sample position, with little focus on detectors. The ESS Detector Group has extended the capabilities of existing detector simulation tools to bridge this gap. An extensive software framework has been developed, enabling efficient and collaborative developments of required simulations and analyses -- based on the use of the Geant4 Monte Carlo toolkit, but with extended physics capabilities where relevant (like for Bragg diffraction of thermal neutrons in crystals). Furthermore, the MCPL (Monte Carlo Particle Lists) particle data exchange file format, currently supported for the primary Monte Carlo tools of the community (McStas, Geant4 and MCNP), facilitates the integration of detector simulations with existing simulations of instruments using these software packages. These means offer a powerful set of tools to tailor the detector and instrument design to the instrument application

Space-time Dimensional Organization the Obsolescent Man

This investigation contemplates man and the human organization in the temporal setting. It strives to erect a framework for the consideration of features of the social and economic environment which structure the architecture of organizational development, which mutate organizational form and substance. It focuses upon man in structured society and contrasts the organizational reality with the organizational ideal, sketched in terms of human and social aspirations and potentialities. The implications for cultural evolution of the ascension of organization in contemporary society and the pervasiveness of the economic foundations for organized life receive due emphasis. The materials utilized in the formulation of this investigation were chiefly library periodicals and books concerning aspects of business organization. The large corporate form appears increasingly to typify the organization of contemporary society. With the inertial tendency toward an authoritarian hierarchy of structured relationships in the conglomerate organization within which the significant countervailing forces are no longer those of the encompassing market structured economy, but what various loci of pluralistic power may be provided for in the system, the anonymous individual experiences increased vulnerability to the institutions he has erected. Awareness, however, by the individual of the implications of increased organization, elaboration, and complexity in modern living provides for man an instrument to effectuate social progress within the constructs of the contemporary organizational setting.Business Administratio

Ion Mobility-Mass Spectrometry with a Radial Opposed Migration Ion and Aerosol Classifier (ROMIAC)

The first application of a novel differential mobility analyzer, the radial opposed migration ion and aerosol classifier (ROMIAC), is demonstrated. The ROMIAC uses antiparallel forces from an electric field and a cross-flow gas to both scan ion mobilities and continuously transmit target mobility ions with 100% duty cycle. In the ROMIAC, diffusive losses are minimized, and resolution of ions, with collisional cross-sections of 200–2000 Å^2, is achieved near the nondispersive resolution of ~20. Higher resolution is theoretically possible with greater cross-flow rates. The ROMIAC was coupled to a linear trap quadrupole mass spectrometer and used to classify electrosprayed C2–C12 tetra-alkyl ammonium ions, bradykinin, angiotensin I, angiotensin II, bovine ubiquitin, and two pairs of model peptide isomers. Instrument and mobility calibrations of the ROMIAC show that it exhibits linear responses to changes in electrode potential, making the ROMIAC suitable for mobility and cross-section measurements. The high resolution of the ROMIAC facilitates separation of isobaric isomeric peptides. Monitoring distinct dissociation pathways associated with peptide isomers fully resolves overlapping peaks in the ion mobility data. The ability of the ROMIAC to operate at atmospheric pressure and serve as a front-end analyzer to continuously transmit ions with a particular mobility facilitates extensive studies of target molecules using a variety of mass spectrometric methods

Overcoming High Energy Backgrounds at Pulsed Spallation Sources

Instrument backgrounds at neutron scattering facilities directly affect the quality and the efficiency of the scientific measurements that users perform. Part of the background at pulsed spallation neutron sources is caused by, and time-correlated with, the emission of high energy particles when the proton beam strikes the spallation target. This prompt pulse ultimately produces a signal, which can be highly problematic for a subset of instruments and measurements due to the time-correlated properties, and different to that from reactor sources. Measurements of this background have been made at both SNS (ORNL, Oak Ridge, TN, USA) and SINQ (PSI, Villigen, Switzerland). The background levels were generally found to be low compared to natural background. However, very low intensities of high-energy particles have been found to be detrimental to instrument performance in some conditions. Given that instrument performance is typically characterised by S/N, improvements in backgrounds can both improve instrument performance whilst at the same time delivering significant cost savings. A systematic holistic approach is suggested in this contribution to increase the effectiveness of this. Instrument performance should subsequently benefit.Comment: 12 pages, 8 figures. Proceedings of ICANS XXI (International Collaboration on Advanced Neutron Sources), Mito, Japan. 201