Towards automated verification of Splice in mu mu CRL

A considerable fragment of the coordination architecture {sc Splice, including Ethernet, is specified in the process-algebraic language{$mu${sc crl. This specification is used to generate transition systems for a number of simple{sc Splice applications which are verified by model checking using the{sc C{aesar/Ald'{ebaran tool set. For these cases the properties of deadlock freeness, soundness and weak completeness are proven. The primary result reported is a detailed formal model of{sc Splice that makes possible automated verification. In practice, however, it is only for very simple {sc Splice applications feasible to generate a transition system. Nevertheless, model checking applied to a large number of small applications, or scenarios, can be used to gather evidence for the validity of properties that is more general than testing in that it considers all possible system traces for a given scenario instead of just one trace. For applications with a high degree of non-determinism this can be an interesting advantage

High-Throughput Assay for the Identification of Compounds Regulating Osteogenic Differentiation of Human Mesenchymal Stromal Cells

Human mesenchymal stromal cells are regarded as the golden standard for cell-based therapies. They present multilineage differentiation potential and trophic and immunosuppressive abilities, making them the best candidate for clinical applications. Several molecules have been described to increase bone formation and were mainly discovered by candidate approaches towards known signaling pathways controlling osteogenesis. However, their bone forming potential is still limited, making the search for novel molecules a necessity. High-throughput screening (HTS) not only allows the screening of a large number of diverse chemical compounds, but also allows the discovery of unexpected signaling pathways and molecular mechanisms for a certain application, even without the prior knowledge of the full molecular pathway. Typically HTS is performed in cell lines, however, in this manuscript we have performed a phenotypical screen on more clinically relevant human mesenchymal stromal cells, as a proof of principle that HTS can be performed in those cells and can be used to find small molecules that impact stem cell fate. From a library of pharmacologically active small molecules, we were able to identify novel compounds with increased osteogenic activity. These compounds allowed achieving levels of bone-specific alkaline phosphatase higher than any other combination previously known. By combining biochemical techniques, we were able to demonstrate that a medium to high-throughput phenotypic assay can be performed in academic research laboratories allowing the discovery of novel molecules able to enhance stem cell differentiation

Technologies for Integration of small Unmanned Aerial Systems (s-UAS) in National Airspace System

SJN 135503Small Unmanned Air Systems (s-UAS) have generated a lot of interest in recent years due to their potential to revolutionize applications in civilian domains. For the widespread use of s-UAS to become a reality for civilian applications, s-UAS must safely and reliably integrated into the National Airspace System (NAS). Because the technology in this field is advancing rapidly, there has been no comprehensive study on the technologies involved. This study seeks to provide a comprehensive survey of the recent technological advances, identify potential issues, and propose solutions. Focus will be on the Sense and Avoid (SAA) and Unmanned Systems Traffic Management (UTM) aspects of s-UAS integration in NAS. This study surveyed available and developing technologies, performed a comparative study of existing solutions proposed by industry, academia, and the government, and formulated a UTM solution for urban package delivery

Intraoperative Defibrillation Testing of Subcutaneous Implantable Cardioverter‐Defibrillator Systems—A Simple Issue?

Background: The results of the recently published randomized SIMPLE trial question the role of routine intraoperative defibrillation testing. However, testing is still recommended during implantation of the entirely subcutaneous implantable cardioverter‐defibrillator (S‐ICD) system. To address the question of whether defibrillation testing in S‐ICD systems is still necessary, we analyzed the data of a large, standard‐of‐care prospective single‐center S‐ICD registry. // Methods and Results: In the present study, 102 consecutive patients received an S‐ICD for primary (n=50) or secondary prevention (n=52). Defibrillation testing was performed in all except 4 patients. In 74 (75%; 95% CI 0.66–0.83) of 98 patients, ventricular fibrillation was effectively terminated by the first programmed internal shock. In 24 (25%; 95% CI 0.22–0.44) of 98 patients, the first internal shock was ineffective and further internal or external shock deliveries were required. In these patients, programming to reversed shock polarity (n=14) or repositioning of the sensing lead (n=1) or the pulse generator (n=5) led to successful defibrillation. In 4 patients, a safety margin of <10 J was not attained. Nevertheless, in these 4 patients, ventricular arrhythmias were effectively terminated with an internal 80‐J shock. // Conclusions: Although it has been shown that defibrillation testing is not necessary in transvenous ICD systems, it seems particular important for S‐ICD systems, because in nearly 25% of the cases the primary intraoperative test was not successful. In most cases, a successful defibrillation could be achieved by changing shock polarity or by optimizing the shock vector caused by the pulse generator or lead repositioning.<br

An inter-laboratory comparison of standard membrane-feeding assays for evaluation of malaria transmission-blocking vaccines.

BACKGROUND: An effective malaria transmission-blocking vaccine may play an important role in malaria elimination efforts, and a robust biological assay is essential for its development. The standard membrane-feeding assay (SMFA) for Plasmodium falciparum infection of mosquitoes is considered a "gold standard" assay to measure transmission-blocking activity of test antibodies, and has been utilized widely in both non-clinical and clinical studies. While several studies have discussed the inherent variability of SMFA within a study group, there has been no assessment of inter-laboratory variation. Therefore, there is currently no assurance that SMFA results are comparable between different studies. METHODS: Mouse anti-Pfs25 monoclonal antibody (mAb, 4B7 mAb), rat anti-Pfs48/45 mAb (85RF45.1 mAb) and a human polyclonal antibody (pAb) collected from a malaria-exposed adult were tested at the same concentrations (6-94 μg/mL for 4B7, 1.2-31.3 μg/mL for 85RF45.1 and 23-630 μg/mL for human pAb) in two laboratories following their own standardized SMFA protocols. The mAbs and pAb, previously shown to have strong inhibition activities in the SMFA, were tested at three or four concentrations in two or three independent assays in each laboratory, and percent inhibition in mean oocyst intensity relative to a control in the same feed was determined in each feeding experiment. RESULTS: Both monoclonal and polyclonal antibodies dose-dependently reduced oocyst intensity in all experiments performed at the two test sites. In both laboratories, the inter-assay variability in percent inhibition in oocyst intensity decreased at higher levels of inhibition, regardless of which antibody was tested. At antibody concentrations that led to a >80 % reduction in oocyst numbers, the inter-laboratory variations were in the same range compared with the inter-assay variation observed within a single laboratory, and the differences in best estimates from multiple feeds between the two laboratories were <5 percentage points. CONCLUSIONS: This study confirms previous reports that the precision of the SMFA increases with increasing percent inhibition. Moreover, the variation between the two laboratories is not greater than the variation observed within a laboratory. The findings of this study provide guidance for comparison of SMFA data from different laboratories