A rhodanine agent active against non-replicating intracellular Mycobacterium avium subspecies paratuberculosis.

BACKGROUND: Antibiotic therapy targeting chronic mycobacterial disease is often ineffective due to problems with the emergence of drug resistance and non-replicating persistent intracellular antibiotic resistant phenotypes. Strategies which include agents able to enhance host cell killing mechanisms could represent an alternative to conventional methods with the potential for host clearance if active against dormant phenotypes. Investigations of agents with potential activity against non-replicating mycobacteria however are restricted due to a need for assays that can assess bacterial viability without having to culture. RESULTS: This study describes the development and use of a pre16S ribosomal gene RNA/DNA ratio viability assay which is independent of the need for culture, supported by a novel thin layer accelerated mycobacterial colony forming method for determining viability and culturability of MAP in intracellular environments. We describe the use of these tools to demonstrate intracellular killing activity of a novel rhodanine agent (D157070) against the intracellular pathogen Mycobacterium avium subspecies paratuberculosis (MAP) and show that the culturability of MAP decreases relative to its viability on intracellular entry suggesting the induction of a non-culturable phenotype. We further demonstrate that D157070, although having no direct activity against the culturability of extracellular MAP, can bind to cultured MAP cells and has significant influence on the MAP transcriptome, particularly with respect of delta(L )associated genes. D157070 is shown to be taken up by bovine and human cells and able to enhance host cell killing, as measured by significant decreases in both culturability and viability of intracellular MAP. CONCLUSIONS: This work suggests that pre16srRNA gene ratios represent a viable method for studying MAP viability. In addition, the rhodanine agent D157070 tested is non-toxic and enhances cell killing activity against both growing and latent MAP phenotypes

Development and flight test of a helicopter compact, portable, precision landing system concept

An airborne, radar-based, precision approach concept is being developed and flight tested as a part of NASA's Rotorcraft All-Weather Operations Research Program. A transponder-based beacon landing system (BLS) applying state-of-the-art X-band radar technology and digital processing techniques, was built and is being flight tested to demonstrate the concept feasibility. The BLS airborne hardware consists of an add-on microprocessor, installed in conjunction with the aircraft weather/mapping radar, which analyzes the radar beacon receiver returns and determines range, localizer deviation, and glide-slope deviation. The ground station is an inexpensive, portable unit which can be quickly deployed at a landing site. Results from the flight test program show that the BLS concept has a significant potential for providing rotorcraft with low-cost, precision instrument approach capability in remote areas

Fueling an investigative mindset: the importance of pre-interview planning in police interviews with suspects

Pre-interview planning is vital in interviews with suspects. Via a questionnaire administered to 596 police investigators in Singapore, the current study examined potential associations between pre-interview planning, interviewing behaviours and interview outcomes. Interviewing behaviours were hypothesised to mediate the relationship between pre-interview planning and interview outcomes. It is posited that pre-interview planning fosters an investigative mindset, which in turn, influences the nature of interviewing behaviours employed by investigators. The study also sought to provide insights into police interviews with suspects in Singapore, given the limited research from Singapore on the topic. Rapport-based interviewing behaviours were found to mediate the relationship between pre-interview planning and positive interview outcomes, contributing empirical support to the importance of pre-interview planning. In addition, accusatorial interviewing behaviours were associated with negative interview outcomes. This study also found that police investigators in Singapore reported frequent planning prior to their interviews and used rapport-based interviewing behaviours with suspects. These behaviours are in line with the interviewing model adopted in Singapore. Regression analyses showed that participants’ endorsement of rapport-based approaches was predicted by investigator experience, confidence, and interview length. Endorsement of pre-planning of interviews was also predicted by investigator confidence and interview length. Implications of these findings are discussed

Current status of MCNP6 as a simulation tool useful for space and accelerator applications

For the past several years, a major effort has been undertaken at Los Alamos National Laboratory (LANL) to develop the transport code MCNP6, the latest LANL Monte-Carlo transport code representing a merger and improvement of MCNP5 and MCNPX. We emphasize a description of the latest developments of MCNP6 at higher energies to improve its reliability in calculating rare-isotope production, high-energy cumulative particle production, and a gamut of reactions important for space-radiation shielding, cosmic-ray propagation, and accelerator applications. We present several examples of validation and verification of MCNP6 compared to a wide variety of intermediate- and high-energy experimental data on reactions induced by photons, mesons, nucleons, and nuclei at energies from tens of MeV to about 1 TeV/nucleon, and compare to results from other modern simulation tools.Comment: 4 pages, 3 figures, Proc. 11th Conference on the Intersections of Particle and Nuclear Physics (CIPANP 2012), St. Petersburg, FL, May 28 - June 3, 201

Virtual image out-the-window display system study. Volume 2 - Appendix

Virtual image out-the-window display system imaging techniques and simulation devices - appendices containing background materia

The relevance of the evolution of experimental studies for the interpretation and evaluation of some trace physical evidence

In order for trace evidence to have a high evidential value, experimental studies which mimic the forensic reality are of fundamental importance. Such primary level experimentation is crucial to establish a coherent body of theory concerning the generation, transfer and persistence of different forms of trace physical evidence. We contend that the forensic context, at whatever scale, will be specific to each individual forensic case and this context in which a crime takes place will influence the properties of trace evidence. it will, therefore, be necessary in many forensic cases to undertake secondary level experimental studies that incorporate specific variables pertinent to a particular case and supplement the established theory presented in the published literature. Such studies enable a better understanding of the specific forensic context and thus allow More accurate collection, analysis and interpretation of the trace physical evidence to be achieved. This paper presents two cases where the findings of secondary level experimental studies undertaken to address specific issues particular to two forensic investigations proved to be important. Specific pre-, syn- and post-forensic event factors were incorporated into the experimental design and proved to be invaluable in the recovery, analysis and in achieving accurate interpretations of both soil evidence from footwear and glass trace evidence from a broken window.These Studies demonstrate that a fuller understanding of the specific context within which trace physical evidence is generated and subsequently collected, as well as an understanding of the behaviour of certain forms of trace physical evidence under specific conditions, can add evidentiary weight to the analysis and interpretation of that evidence and thus help a court with greater certainty where resources (time and cost) permit