Effortless Fault Localisation:Conformance Testing of Real-Time Systems in Ecdar

Model checking of real-time systems has evolved throughout the years. Recently, the model checker Ecdar, using timed I/O automata, was used to perform compositional verification. However, in order to fully integrate model checking of real-time systems into industrial development, we need a productive and reliable way to test if such a system conforms to its corresponding model. Hence, we present an extension of Ecdar that integrates conformance testing into a new IDE that now features modelling, verification, and testing. The new tool uses model-based mutation testing, requiring only the model and the system under test, to locate faults and to prove the absence of certain types of faults. It supports testing using either real-time or simulated time. It parallelises test-case generation and test execution to provide a significant speed-up. We also introduce new mutation operators that improve the ability to detect and locate faults. Finally, we conduct a case study with 140 faulty systems, where Ecdar detects all faults.Comment: In Proceedings GandALF 2018, arXiv:1809.0241

Adult rat retinal ganglion cells and glia can be printed by piezoelectric inkjet printing.

We have investigated whether inkjet printing technology can be extended to print cells of the adult rat central nervous system (CNS), retinal ganglion cells (RGC) and glia, and the effects on survival and growth of these cells in culture, which is an important step in the development of tissue grafts for regenerative medicine, and may aid in the cure of blindness. We observed that RGC and glia can be successfully printed using a piezoelectric printer. Whilst inkjet printing reduced the cell population due to sedimentation within the printing system, imaging of the printhead nozzle, which is the area where the cells experience the greatest shear stress and rate, confirmed that there was no evidence of destruction or even significant distortion of the cells during jet ejection and drop formation. Importantly, the viability of the cells was not affected by the printing process. When we cultured the same number of printed and non-printed RGC/glial cells, there was no significant difference in cell survival and RGC neurite outgrowth. In addition, use of a glial substrate significantly increased RGC neurite outgrowth, and this effect was retained when the cells had been printed. In conclusion, printing of RGC and glia using a piezoelectric printhead does not adversely affect viability and survival/growth of the cells in culture. Importantly, printed glial cells retain their growth-promoting properties when used as a substrate, opening new avenues for printed CNS grafts in regenerative medicine

Retinal ganglion cell survival and axon regeneration in WldS transgenic rats after optic nerve crush and lens injury.

BACKGROUND: We have previously shown that the slow Wallerian degeneration mutation, whilst delaying axonal degeneration after optic nerve crush, does not protect retinal ganglion cell (RGC) bodies in adult rats. To test the effects of a combination approach protecting both axons and cell bodies we performed combined optic nerve crush and lens injury, which results in both enhanced RGC survival as well as axon regeneration past the lesion site in wildtype animals. RESULTS: As previously reported we found that the Wld(S) mutation does not protect RGC bodies after optic nerve crush alone. Surprisingly, we found that Wld(S) transgenic rats did not exhibit the enhanced RGC survival response after combined optic nerve crush and lens injury that was observed in wildtype rats. RGC axon regeneration past the optic nerve lesion site was, however, similar in Wld(S) and wildtypes. Furthermore, activation of retinal glia, previously shown to be associated with enhanced RGC survival and axon regeneration after optic nerve crush and lens injury, was unaffected in Wld(S) transgenic rats. CONCLUSIONS: RGC axon regeneration is similar between Wld(S) transgenic and wildtype rats, but Wld(S) transgenic rats do not exhibit enhanced RGC survival after combined optic nerve crush and lens injury suggesting that the neuroprotective effects of lens injury on RGC survival may be limited by the Wld(S) protein.RIGHTS : This article is licensed under the BioMed Central licence at http://www.biomedcentral.com/about/license which is similar to the 'Creative Commons Attribution Licence'. In brief you may : copy, distribute, and display the work; make derivative works; or make commercial use of the work - under the following conditions: the original author must be given credit; for any reuse or distribution, it must be made clear to others what the license terms of this work are

Bioink properties before, during and after 3D bioprinting

Bioprinting is a process based on additive manufacturing from materials containing living cells. These materials, often referred to as bioink, are based on cytocompatible hydrogel precursor formulations, which gel in a manner compatible with different bioprinting approaches. The bioink properties before, during and after gelation are essential for its printability, comprising such features as achievable structural resolution, shape fidelity and cell survival. However, it is the final properties of the matured bioprinted tissue construct that are crucial for the end application. During tissue formation these properties are influenced by the amount of cells present in the construct, their proliferation, migration and interaction with the material. A calibrated computational framework is able to predict the tissue development and maturation and to optimize the bioprinting input parameters such as the starting material, the initial cell loading and the construct geometry. In this contribution relevant bioink properties are reviewed and discussed on the example of most popular bioprinting approaches. The effect of cells on hydrogel processing and vice versa is highlighted. Furthermore, numerical approaches were reviewed and implemented for depicting the cellular mechanics within the hydrogel as well as for prediction of mechanical properties to achieve the desired hydrogel construct considering cell density, distribution and material-cell interaction

Retinal glia promote dorsal root ganglion axon regeneration.

Axon regeneration in the adult central nervous system (CNS) is limited by several factors including a lack of neurotrophic support. Recent studies have shown that glia from the adult rat CNS, specifically retinal astrocytes and Müller glia, can promote regeneration of retinal ganglion cell axons. In the present study we investigated whether retinal glia also exert a growth promoting effect outside the visual system. We found that retinal glial conditioned medium significantly enhanced neurite growth and branching of adult rat dorsal root ganglion neurons (DRG) in culture. Furthermore, transplantation of retinal glia significantly enhanced regeneration of DRG axons past the dorsal root entry zone after root crush in adult rats. To identify the factors that mediate the growth promoting effects of retinal glia, mass spectrometric analysis of retinal glial conditioned medium was performed. Apolipoprotein E and secreted protein acidic and rich in cysteine (SPARC) were found to be present in high abundance, a finding further confirmed by western blotting. Inhibition of Apolipoprotein E and SPARC significantly reduced the neuritogenic effects of retinal glial conditioned medium on DRG in culture, suggesting that Apolipoprotein E and SPARC are the major mediators of this regenerative response.This work was supported by a van Geest Fight for Sight Early Career Investigator Award, grant number 1868 [BL].This is the final version of the article. It first appeared at http://journals.plos.org/plosone/article?id=10.1371/journal.pone.011599

Incidence of emergency department visits for electric rental scooters using detailed ridership data

INTRODUCTION: Electric scooter (e-scooter) rental usage has increased exponentially around the country, expanding to more than 120 cities by the end of 2018. Early attempts to capture the safety effects of widespread adoption of this technology have been hampered by lack of accurate ridership data. Here we describe a 17-month evolution of ridership characteristics in St. Louis, Missouri, and the frequency of e-scooter rental-related injuries serious enough to require an emergency department (ED) visit over this time frame; we also provide estimates of incidence rates of injuries based on company ridership data. METHODS: We performed a combination retrospective chart review and prospective questionnaire-based analysis of adult e-scooter rental-related ED visits in both downtown St. Louis Level 1 trauma centers during the first 17 months of e-scooter rental usage (August 2018-December 2019). The retrospective portion focused on demographics, alcohol use, helmet use, disposition, operative repair, and temporal and severity markers. The prospective portion focused on more detailed crash and rider data. Finally, we used ridership data from both e-scooter rental companies in St. Louis to estimate incidence and temporal trends. RESULTS: A total of 221 patients had e-scooter rental-related ED visits. The median age of our population was 31 years with 58.8% male and 53.8% White. There were no deaths. Ninety-two patients were found to have fractures with 38% requiring surgery. Of the 21 patients diagnosed with head injury, five had an intracranial bleed. Overall incidence of ED visits related to e-scooters was 2.1 per 10,000 trips and 2.2 per 10,000 miles with the number of ED visits by month closely correlated with the number of rides per month (Pearson correlation coefficient = 0.95). CONCLUSION: The number of e-scooter rental-related injuries seen in St. Louis trauma centers was relatively low and correlated closely with overall number of rides. The number of injuries decreased and were less severe from 2018 to 2019 with infrequent intracranial injuries and a large percentage of fractures requiring operative repair

Impact of ‘Black Race’ Coefficient in eGFR on Our Community and Medical Education

Introduction: The use of race in estimation of glomerular filtration rate (eGFR) started a critical national conversation on numerous areas of medicine touched by racism; with a call for removal of race from calculation of eGFR. We scrutinized use of ‘Black race’ coefficient in MDRD eGFR calculation and consequence of its use on our local community in SW Michigan. Methods: A cross-sectional analysis of de-identified electronic health record (EHR) data from routine outpatient primary care visits, from 1/1/2019 to 12/31/2019 included variables such as age, race, gender, serum creatinine levels and calculated eGFRs (if any), using Chi-square tests for association and Wald-approximation 95% confidence interval. During the data collection period in 2019, both hospital systems and the outpatient clinic site were all using MDRD. Results: eGFR and associated CKD stage were calculated for 131,863 patients. Chi-square tests found significant differences in rates of CKD stages 3,4 and 5 between ‘Black’ and ‘not Black’. And, the 95% confidence interval for the proportion of Black patients who would advance to the next stage of CKD upon ignoring ‘Black race’ (using Wald-approximated Confidence Interval for binomial proportion) is between 41.1% and 43.0%. Discussion: The eGFR calculations which place Black patients in lower CKD stages initially may deprive them of important treatment and referral early in their disease course. Removal of the Black race coefficient allows for referral to a nephrologist, Medicare coverage, and the potential need for transplant and/or dialysis. Conclusion: Our analysis demonstrates the impact removal of ‘black race’ coefficient from MDRD eGFR calculation could have on our community

Relative Reactivity of the Metal-Amido versus Metal-Imido Bond in Linked Cp-Amido and Half-Sandwich Complexes of Vanadium

Treatment of (η5-C5H4C2H4NR)V(N-t-Bu)Me (R = Me, i-Pr) and CpV(N-p-Tol)(N-i-Pr2)Me (Cp = η5-C5H5) with B(C6F5)3 or [Ph3C][B(C6F5)4] results in formation of the corresponding cations, [(η5-C5H4C2H4NR)V(N-t-Bu)]+ and [CpV(N-p-Tol)(N-i-Pr2)]+. The latter could also be generated as its N,N-dimethylaniline adduct by treatment of the methyl complex with [PhNMe2H][BAr4] (Ar = Ph, C6F5). Instead, the analogous reaction with the linked Cp-amido precursor results in protonation of the imido-nitrogen atom. Sequential cyclometalation of the amide substituents gave cationic imine complexes [(η5-C5H4C2H4NCR'2)V(NH-t-Bu)]+ (R' = H, Me) and methane. Reaction of cationic [(η5-C5H4C2H4NR)V(N-t-Bu)]+ with olefins affords the corresponding olefin adducts, whereas treatment with 1 or 2 equiv of 2-butyne results in insertion of the alkyne into the vanadium-nitrogen single bond, affording the mono- and bis-insertion products [(η5-C5H4C2H4N(i-Pr)C2Me2)V(N-t-Bu)]+ and [(η5-C5H4C2H4N(i-Pr)C4Me4)V(N-t-Bu)]+. The same reaction with the half-sandwich compound [CpV(N-p-Tol)(N-i-Pr2)]+ results in a paramagnetic compound that, upon alcoholysis, affords sec-butylidene-p-tolylamine, suggesting an initial [2+2] cycloaddition reaction. The difference in reactivity between the V-N bond versus the V=N bond was further studied using computational methods. Results were compared to the isoelectronic titanium system CpTi(NH)(NH2). These studies indicate that the kinetic product in each system is derived from a [2+2] cycloaddition reaction. For titanium, this was found as the thermodynamic product as well, whereas the insertion reaction was found to be thermodynamically more favorable in the case of vanadium.