Targeting the proteolytic processing of the viral glycoprotein precursor is a promising novel antiviral strategy against arenaviruses.

A crucial step in the arenavirus life cycle is the biosynthesis of the viral envelope glycoprotein (GP) responsible for virus attachment and entry. Processing of the GP precursor (GPC) by the cellular proprotein convertase site 1 protease (S1P), also known as subtilisin-kexin-isozyme 1 (SKI-1), is crucial for cell-to-cell propagation of infection and production of infectious virus. Here, we sought to evaluate arenavirus GPC processing by S1P as a target for antiviral therapy using a recently developed peptide-based S1P inhibitor, decanoyl (dec)-RRLL-chloromethylketone (CMK), and the prototypic arenavirus lymphocytic choriomeningitis virus (LCMV). To control for off-target effects of dec-RRLL-CMK, we employed arenavirus reverse genetics to introduce a furin recognition site into the GPC of LCMV. The rescued mutant virus grew to normal titers, and the processing of its GPC critically depended on cellular furin, but not S1P. Treatment with the S1P inhibitor dec-RRLL-CMK resulted in specific blocking of viral spread and virus production of LCMV. Combination of the protease inhibitor with ribavirin, currently used clinically for treatment of human arenavirus infections, resulted in additive drug effects. In cells deficient in S1P, the furin-dependent LCMV variant established persistent infection, whereas wild-type LCMV underwent extinction without the emergence of S1P-independent escape variants. Together, the potent antiviral activity of an inhibitor of S1P-dependent GPC cleavage, the additive antiviral effect with ribavirin, and the low probability of emergence of S1P-independent viral escape variants make S1P-mediated GPC processing by peptide-derived inhibitors a promising strategy for the development of novel antiarenaviral drugs.

Comparison of Inoculation with the InoqulA and WASP Automated Systems with Manual Inoculation.

The quality of sample inoculation is critical for achieving an optimal yield of discrete colonies in both monomicrobial and polymicrobial samples to perform identification and antibiotic susceptibility testing. Consequently, we compared the performance between the InoqulA (BD Kiestra), the WASP (Copan), and manual inoculation methods. Defined mono- and polymicrobial samples of 4 bacterial species and cloudy urine specimens were inoculated on chromogenic agar by the InoqulA, the WASP, and manual methods. Images taken with ImagA (BD Kiestra) were analyzed with the VisionLab version 3.43 image analysis software to assess the quality of growth and to prevent subjective interpretation of the data. A 3- to 10-fold higher yield of discrete colonies was observed following automated inoculation with both the InoqulA and WASP systems than that with manual inoculation. The difference in performance between automated and manual inoculation was mainly observed at concentrations of >10(6) bacteria/ml. Inoculation with the InoqulA system allowed us to obtain significantly more discrete colonies than the WASP system at concentrations of >10(7) bacteria/ml. However, the level of difference observed was bacterial species dependent. Discrete colonies of bacteria present in 100- to 1,000-fold lower concentrations than the most concentrated populations in defined polymicrobial samples were not reproducibly recovered, even with the automated systems. The analysis of cloudy urine specimens showed that InoqulA inoculation provided a statistically significantly higher number of discrete colonies than that with WASP and manual inoculation. Consequently, the automated InoqulA inoculation greatly decreased the requirement for bacterial subculture and thus resulted in a significant reduction in the time to results, laboratory workload, and laboratory costs.

The First International Workshop on Warning Criteria for Active Slides: technical issues, problems and solutions for managing early warning systems

Early warning systems (EWSs) rely on the capacity to forecast a dangerous event with a certain amount of advance by defining warning criteria on which the safety of the population will depend. Monitoring of landslides is facilitated by new technologies, decreasing prices and easier data processing. At the same time, predicting the onset of a rapid failure or the sudden transition from slow to rapid failure and subsequent collapse, and its consequences is challenging for scientists that must deal with uncertainties and have limited tools to do so. Furthermore, EWS and warning criteria are becoming more and more a subject of concern between technical experts, researchers, stakeholders and decision makers responsible for the activation, enforcement and approval of civil protection actions. EWSs imply also a sharing of responsibilities which is often averted by technical staff, managers of technical offices and governing institutions. We organized the First International Workshop on Warning Criteria for Active Slides (IWWCAS) to promote sharing and networking among members from specialized institutions and relevant experts of EWS. In this paper, we summarize the event to stimulate discussion and collaboration between organizations dealing with the complex task of managing hazard and risk related to active slides.

Image processing of false identity documents for forensic intelligence

Forensic intelligence has recently gathered increasing attention as a potential expansion of forensic science that may contribute in a wider policing and security context. Whilst the new avenue is certainly promising, relatively few attempts to incorporate models, methods and techniques into practical projects are reported. This work reports a practical application of a generalised and transversal framework for developing forensic intelligence processes referred to here as the Transversal model adapted from previous work. Visual features present in the images of four datasets of false identity documents were systematically profiled and compared using image processing for the detection of a series of modus operandi (M.O.) actions. The nature of these series and their relation to the notion of common source was evaluated with respect to alternative known information and inferences drawn regarding respective crime systems. 439 documents seized by police and border guard authorities across 10 jurisdictions in Switzerland with known and unknown source level links formed the datasets for this study. Training sets were developed based on both known source level data, and visually supported relationships. Performance was evaluated through the use of intra-variability and inter-variability scores drawn from over 48,000 comparisons. The optimised method exhibited significant sensitivity combined with strong specificity and demonstrates its ability to support forensic intelligence efforts.