Specification and Automated Verification of Real-Time Behaviour —A Case Study

In this paper we sketch a method for specification and automaticverification of real-time software properties. The method combinesthe IEC 848 norm and the recent specification techniques TCCS (TimedCalculus of Communicating Systems) and TML (Timed Modal Logic) - supported by an automatic verification tool, Epsilon. The methodis illustrated by modelling a small real-life steam generator example andsubsequent automated analysis of its properties.Keywords: Control system analysis; formal specification; formal verification; real-time systems; standards

A soil moisture and temperature network for SMOS validation in Western Denmark

The Soil Moisture and Ocean Salinity Mission (SMOS) acquires surface soil moisture data of global coverage every three days. Product validation for a range of climate and environmental conditions across continents is a crucial step. For this purpose, a soil moisture and soil temperature sensor network was established in the Skjern River Catchment, Denmark. The objectives of this article are to describe a method to implement a network suited for SMOS validation, and to present sample data collected by the network to verify the approach. The design phase included (1) selection of a single SMOS pixel (44 × 44 km), which is representative of the land surface conditions of the catchment and with minimal impact from open water (2) arrangement of three network clusters along the precipitation gradient, and (3) distribution of the stations according to respective fractions of classes representing the prevailing environmental conditions. Overall, measured moisture and temperature patterns could be related to the respective land cover and soil conditions. Texture-dependency of the 0–5 cm soil moisture measurements was demonstrated. Regional differences in 0–5 cm soil moisture, temperature and precipitation between the north-east and south-west were found to be small. A first comparison between the 0–5 cm network averages and the SMOS soil moisture (level 2) product is in range with worldwide validation results, showing comparable trends for SMOS retrieved soil moisture (<i>R</i><sup>2</sup> of 0.49) as well as initial soil moisture and temperature from ECMWF used in the retrieval algorithm (<i>R</i><sup>2</sup> of 0.67 and 0.97, respectively). While retrieved/initial SMOS soil moisture indicate significant under-/overestimation of the network data (biases of −0.092/0.057 m<sup>3</sup> m<sup>−3</sup>), the initial temperature is in good agreement (bias of −0.2 °C). Based on these findings, the network performs according to expectations and proves to be well-suited for its purpose. The discrepancies between network and SMOS soil moisture will be subject of subsequent studies

Alleviation of Murine Leukemia Virus Repression in Embryonic Carcinoma Cells by Genetically Engineered Primer Binding Sites and Artificial tRNA Primers

AbstractThe primer binding site (PBS) plays pivotal roles during reverse transcription of retroviruses and also is the target of a cellular host defense impeding the transcription of murine leukemia virus (MLV) harboring a proline (pro) PBS in embryonic cells. Both the PBS and the tRNA primer are copied during reverse transcription and anneal as complementary DNA sequences creating the PBS of the integrated provirus. The pro PBS of MLV can be exchanged by PBS sequences matching endogenous or engineered tRNAs to allow replication of Akv MLV-derived vectors in fibroblasts. Here we use the PBS escape mutant B2 to demonstrate the capacity of the synthetic tRNAB2 to function in reverse transcription in competition with endogenous tRNAs in fibroblasts and embryonic carcinoma (EC) cells. We further show symmetry between PBS and the primer by the ability of the synthetic tRNAB2 to confer escape from EC repression of a PBS-Pro vector. Of a panel of vectors with the repressed pro PBS substituted for other natural or artificial PBS sequences, all except one efficiently expressed the neo marker gene when transferred to NIH/3T3 and EC cells, hence avoiding PBS-mediated silencing in EC cells. A non-natural PBS matching an artificially designed tRNA molecule conferred no further relief from repression than that attained with the B2 escape mutant or the natural alternative PBSs. Interestingly, a vector harboring a PBS matching tRNALys1.2 suffered repression similar to the wild-type PBS-Pro but was partially rescued by a single point mutation of the PBS

Geostatistical inference using crosshole ground-penetrating radar

High-resolution tomographic images obtained from crosshole geophysical measurements have the potential to provide valuable information about the geostatistical properties of unsaturated-zone hydrologic-state va riables such as moisture content. Under drained or quasi-steady-state conditions, the moisture content will reflect the variation of the physical properties of the subsurface, which determine the flow patterns in the unsaturated zone. Deterministic least-squares inversion of crosshole groundpenetrating-radar GPR traveltimes result in smooth, minimumvariance estimates of the subsurface radar wave velocity structure, which may diminish the utility of these images for geostatistical inference. We have used a linearized stochastic inversion technique to infer the geostatistical properties of the subsurface radar wave velocity distribution using crosshole GPR traveltimes directly. Expanding on a previous study, we have determined that it is possible to obtain estimates of global variance and mean velocity values of the subsurface as well as the correlation lengths describing the subsurface velocity structures. Accurate estimation of the global variance is crucial if stochastic realizations of the subsurface are used to evaluate the uncertainty of the inversion estimate. We have explored the full potential of the geostatistical inference method using several synthetic models of varying correlation structures and have tested the influence of different assumptions concerning the choice of covariance function and data noise level. In addition, we have tested the methodology on traveltime data collected at a field site in Denmark. There, inferred correlation structures indicate that structural differences exist between two areas located approximately 10 m apart, an observation confirmed by a GPR reflection profile. Furthermore, the inferred values of the subsurface global variance and the mean velocity have been corroborated with moisturecontent measurements, obtained gravimetrically from samples collected at the field site

Impairment of alternative splice sites defining a novel gammaretroviral exon within gag modifies the oncogenic properties of Akv murine leukemia virus

<p>Abstract</p> <p>Background</p> <p>Mutations of an alternative splice donor site located within the <it>gag </it>region has previously been shown to broaden the pathogenic potential of the T-lymphomagenic gammaretrovirus Moloney murine leukemia virus, while the equivalent mutations in the erythroleukemia inducing Friend murine leukemia virus seem to have no influence on the disease-inducing potential of this virus. In the present study we investigate the splice pattern as well as the possible effects of mutating the alternative splice sites on the oncogenic properties of the B-lymphomagenic Akv murine leukemia virus.</p> <p>Results</p> <p>By exon-trapping procedures we have identified a novel gammaretroviral exon, resulting from usage of alternative splice acceptor (SA') and splice donor (SD') sites located in the capsid region of <it>gag </it>of the B-cell lymphomagenic Akv murine leukemia virus. To analyze possible effects <it>in vivo </it>of this novel exon, three different alternative splice site mutant viruses, mutated in either the SA', in the SD', or in both sites, respectively, were constructed and injected into newborn inbred NMRI mice. Most of the infected mice (about 90%) developed hematopoietic neoplasms within 250 days, and histological examination of the tumors showed that the introduced synonymous <it>gag </it>mutations have a significant influence on the phenotype of the induced tumors, changing the distribution of the different types as well as generating tumors of additional specificities such as <it>de novo </it>diffuse large B cell lymphoma (DLBCL) and histiocytic sarcoma. Interestingly, a broader spectrum of diagnoses was made from the two single splice-site mutants than from as well the wild-type as the double splice-site mutant. Both single- and double-spliced transcripts are produced <it>in vivo </it>using the SA' and/or the SD' sites, but the mechanisms underlying the observed effects on oncogenesis remain to be clarified. Likewise, analyses of provirus integration sites in tumor tissues, which identified 111 novel RISs (retroviral integration sites) and 35 novel CISs (common integration sites), did not clearly point to specific target genes or pathways to be associated with specific tumor diagnoses or individual viral mutants.</p> <p>Conclusion</p> <p>We present here the first example of a doubly spliced transcript within the group of gammaretroviruses, and we show that mutation of the alternative splice sites that define this novel RNA product change the oncogenic potential of Akv murine leukemia virus.</p

Breathing Exercises for Patients with Asthma in Specialist Care:A Multicenter Randomized Clinical Trial

RATIONALE: Moderate to severe asthma is associated with impaired asthma control and quality of life (QoL) despite access to specialist care and modern pharmacotherapy. Breathing exercises (BrEX) improve QoL in incompletely controlled mild asthma, but impact in moderate to severe asthma is unknown. OBJECTIVES: To investigate the effectiveness of BrEX as adjuvant treatment on QoL in patients with uncontrolled moderate to severe asthma. METHODS: Adult patients with incompletely controlled asthma attending respiratory specialist clinics were randomized to usual specialist care (UC) or UC and BrEX (UC + BrEX) with three individual physiotherapist-delivered sessions and home exercises. Primary outcome was asthma-related QoL (Mini-Asthma Quality of Life Questionnaire [Mini-AQLQ]) at 6 months on the basis of intention-to-treat analysis. Secondary outcomes: Mini-AQLQ at 12 months, lung function, 6-minute-walk test, physical activity level, Nijmegen Questionnaire, Hospital Anxiety and Depression Scale, and adverse events. Repeated-measures mixed-effects models were used to analyze data. Poisson regression models were used to analyze adverse event incidence rate ratio. RESULTS: A total of 193 participants were allocated to UC + BrEX (n = 94) or UC (n = 99). UC + BrEX was superior in the primary outcome (adjusted mean change difference, 0.35; 95% confidence interval [CI], 0.07 to 0.62). Superiority in Mini-AQLQ was sustained at 12 months (0.38; 95% CI, 0.12 to 0.65). A minor improvement in Hospital Anxiety and Depression Scale depression score at 6 months favoring UC + BrEX (−0.90; 95% CI, −1.67 to −0.14) was observed. Asthma-related adverse events occurred similarly in UC + BrEX and UC participants: 14.9% versus 18.1% (P = 0.38). CONCLUSIONS: BrEX as add-on to usual care improve asthma-related QoL in incompletely controlled asthma regardless of severity and with no evidence of harm. Clinical trial registered with www.clinicaltrials.gov (NCT 03127059)