Rule-based code generation in industrial automation Koziolek, Heiko; Burger, Andreas; Platenius-Mohr, Marie ...
2020 IEEE/ACM 42nd International Conference on Software Engineering: Software Engineering in Practice (ICSE-SEIP),
06/2020
Conference Proceeding
Software development for industrial automation applications is a growing market with high economic impact. Control engineers design and implement software for such systems using standardized ...programming languages (IEC 61131-3) and still require substantial manual work causing high engineering costs and potential quality issues. Methods for automatically generating control logic using knowledge extraction from formal requirements documents have been developed, but so far only been demonstrated in simplified lab settings. We have executed four case studies on large industrial plants with thousands of sensors and actuators for a rule-based control logic generation approach called CAYENNE to determine its practicability. We found that we can generate more than 70 percent of the required interlocking control logic with code generation rules that are applicable across different plants. This can lead to estimated overall development cost savings of up to 21 percent, which provides a promising outlook for methods in this class.
Glutathione transferase (GST) GSTT1-1 is involved in the biotransformation of several chemicals widely used in industry, such as butadiene and dichloro methane DCM. The polymorphic hGSTT1-1 may well ...play a role in the development of kidney tumours after high and long-term occupational exposure against trichloroethylene. Although several studies have investigated the association of this polymorphism with malignant diseases little is known about its enzyme activity in potential extrahepatic target tissues. The known theta-specific substrates methyl chloride (MC) dichloromethane and 1,2-epoxy-3-(p-nitrophenoxy)propane (EPNP) were used to assay GSTT1-1 activity in liver and kidney of rats, mice, hamsters and humans differentiating the three phenotypes (non-conjugators, low conjugators, high conjugators) seen in humans. In addition GSTT1-1 activity towards MC and DCM was determined in human erythrocytes. No GSTT1-1 activity was found in any tissue of non-conjugators (NC). In all organs high conjugators (HC) showed twofold higher activity towards MC and DCM than low conjugators (LC). The activity in human samples towards EPNP was too close to the detection limit to differentiate between the three conjugator phenotypes. GSTT1-1 activity towards MC was two to seven-times higher in liver cytosol than in kidney cytosol. The relation for MC between species was identical in both organs: mouse > HC > rat > LC > hamster > NC. In rats, mice and hamsters GSTT1-1 activity in liver cytosol towards DCM was also two to seven-times higher than in the kidney cytosol. In humans this activity was twice as high in kidney cytosol than in liver cytosol. The relation between species was mouse > rat > HC > LC > hamster > NC for liver, but mouse > HC > LC/rat > hamster/NC for kidney cytosol. The importance to heed the specific environment at potential target sites in risk assessment is emphasized by these results.
•The plasma facing Be tiles in ITER may detach from the supporting structure and overheat if the joint quality and performance were poor.•Nevertheless, when a heat flux is applied the temperature ...gradient causes a bending of the tile.•This bending can actually close the gap/crack so that the thermal conductivity is restored again.•Thermo-mechanical FEM simulations demonstrate this principle and its influence on the cool-down.•For practical reasons the use of an exponential fitting function is actually a good choice.
The design of the first wall in ITER foresees several hundred thousand beryllium tiles, which are bonded to the water-cooled CuCrZr supporting structure. Due to the nature of a Tokamak reactor this bonding is faced to thermal fatigue. Since the failure of a single tile might already have a major impact on the operability of ITER, comprehensive high heat flux tests are performed on prototypes prior to the acceptance of manufacturing procedures. For a deeper understanding of the temperature curves, which were and will be measured by IR devices of these first wall prototypes, thermo-mechanical FEM simulations shall demonstrate the possibilities of an early bonding failure detection. Hereby, the maximum temperatures for each cycle as well as the cool-down behaviour are the input data.
Abstract Background Up to now, plain radiographs are not well suited to assess spinal fusion. Radiostereometric analysis performed for two postures may deliver more reliable results. However, it is ...unknown, which postures are most suitable for this procedure. Methods In a finite element study, spinal fusion at the level L4–5 was simulated assuming a posterior approach and the implantation of two cages and a spinal fixation device. The change of the distance between markers in vertebrae adjacent to the cages was calculated for moving from one of the following postures standing, flexion, extension, axial rotation, lying, and extension in a lying position to another. The changes of marker distances were calculated for the intact model, as well as for the situations: directly after surgery before fusion started, in the early-fusion-phase and in the late-fusion-phase. Differences in the marker motion between two postoperative situations were also calculated. Findings The most anteriorly placed markers showed the greatest motion between two postures. The greatest differences in marker motions between the two situations before-fusion and early-fusion-phase (0.54 mm) as well as between early-fusion-phase and late-fusion-phase (0.34 mm) were found for the two postures flexion while standing and extension in a lying position. Interpretation Pairs of X-rays taken while standing with maximum flexed upper body and while lying with maximum extended trunk are most suited for the assessment of spinal fusion when using radiostereometric analysis.
Transforming a clone-and-own (i.e., new product variants are created by copying and modifying existing artifacts) code structure and development process to a Software Product Line Engineering (PLE) ...approach is a tedious and error-prone task. Holistic tool support for such a process is highly desirable, especially to lower efforts and to speed up the transformation. Unfortunately, such a holistic toolchain for reverse engineering of variability, supporting variant-centric and platform-centric extraction approaches is not available. In this paper, we present a toolchain covering the first steps for moving a clone-and-own product development to a PLE approach. We validate the first prototype of the toolchain on a case study consisting of industrial firmware for smart motor controllers and we show that even this early prototype reduces time and effort for moving to a configurable platform approach in the sense of PLE.
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Background: Continuous therapy with once-daily ibrutinib (Ibr) is associated with long-term PFS in pts with B-cell malignancies. Dose reduction is a potential AE management approach that may ...optimize treatment outcomes. We evaluated outcomes with dose reductions in Ibr-treated pts with cardiac AEs. Methods: Data were pooled for Ibr-treated pts from 10 studies of CLL (n=781), mantle cell lymphoma (MCL; n=250), marginal zone lymphoma (MZL; n=63) or Waldenström macroglobulinemia (WM; n=169). Cardiac AEs, initial and recurrent, were identified by preferred terms within the cardiac disorders system organ class. Recurrence was defined as an AE of same or worse grade, and was measured up to 30 days after last dose of ibrutinib or start of next-line therapy, whichever occurred earlier. Results: Overall, 234/1263 pts (19%) had cardiac AEs of any grade. Twelve pts were excluded from the analysis: 9 who had a dose reduction prior to a cardiac AE (0.7%) and 3 who had a fatal cardiac AE with no prior cardiac AE (0.2%). Of the remaining 222 pts with grade 1-4 cardiac AEs, 22 (10%) had Ibr dose reduction to 420 mg (n=3), 280 mg (n=10), or 140 mg (n=9) after a cardiac AE. These pts (n=22) tended to be older (≥75 y: 45% vs 29%), less heavily pretreated (≥1 prior therapy: 45% vs 73%), and with a lower Ibr discontinuation rate (23% vs 48%) than those without dose reduction (n=200). Recurrence of the same cardiac AEs at the same or worse severity was less frequent in pts with dose reductions, both overall (14% vs 18%) and as serious AEs (5% vs 10%). No pt died due to cardiac AE recurrence. Among pts with cardiac AEs who started with the 420 mg Ibr dose (177/222; excludes 45 patients with MCL or MZL who per label start with 560 mg dose), no cardiac AE recurred at same or worse severity in the subset with dose reductions (Table). PFS was not negatively impacted by dose reduction, both overall (n=22; median PFS not reached NR, 24-mo PFS: 91%), and in those who started with the 420 mg dose (n=18; median PFS NR; 24-mo PFS, 94%). Conclusions: Dose reduction for cardiac AEs may enable pts to continue to benefit from long-term Ibr and mitigate the risk of cardiac AE recurrence or worsening. Clinical trial information: NCT01105247 , NCT01236391 , NCT01578707 , NCT01722487 , NCT01611090 . Table: see text
Dynamic beam lasers are the latest tool to influence keyhole behaviour in laser welding. Civan's OPA6 laser can change spot position within the working field with a frequency up to MHz range 1, 2. ...During these time intervals, the laser beam interacts with the melt at different positions and with rapid position changes. The material surface heats up and cools down in dependence of shape frequency and number of shape points.
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Background: The addition of multi-kinase inhibitors of FLT3 such as midostaurin and sorafenib to chemotherapy have demonstrated improved outcomes in patients with newly diagnosed FLT3 mutated ...AML Gilteritinib (gilt) is a second generation FLT3 inhibitor approved for pts with relapsed/refractory (R/R) FLT3-mutated AML. We studied to the combination of gilt with the CLIA regimen in FLT3 mutated AML. Methods: Eligible pts were between 18-65 years (yrs) with FLT3-mutated AML. Induction was: Cladribine 5 mg/m2 IV on D1-5, Cytarabine 1.5-2.0 g/m2 IV on D1-5, Idarubicin 10 mg/m2 IV on D1-3 and gilt 120 mg on D1-14. Consolidation was cladribine 5 mg/m2 IV for 3d, Cytarabine 750 mg/m2 IV for 3 d, and idarubicin 8 mg/m2 IV for 2 d, with gilt 120 mg continuously during cycle two onward. A historical cohort combining sorafenib (400 mg PO BID) with idarubicin + cytarabine (1.5 g/m2) backbone was used as comparison. Results: Twenty-four pts were enrolled with a median age of 53 yrs (range, 28-63). 21 pts (88%) had FLT3-ITD, 6 pts (25%) had FLT3-D835, and 3 pts (13%) had both. Nineteen pts (79%) had diploid cytogenetics, and 4 pts (18%) had trisomy 8. The most commonly co-occurring mutations were: NPM1 (46%), ASXL1 (29%), DNMT3A (29%), TET2 (25%), and KDM6A (20%). 16 pts (67%) achieved complete remission (CR), 2 (8%) had CR with incomplete recovery (CRi), for a CR/CRi rate of 75%. 13 responding pts (54%) underwent to allogeneic SCT. The median overall survival for the entire cohort was not reached. We compared these outcomes to our historical cohort of 107 pts treated with sorafenib combined with high-dose cytarabine-based chemotherapy. Other than older age and greater anemia for the gilt, there was not significant difference in baseline characteristics between the two groups. The CR/CRi rate was similar (75% gilt vs. 71% sorafenib; P = > 0.999) between the 2 cohorts; while there was a trend, there was no significant difference in OS with CLIA + Gilt (median NR vs. 17.3 months for sorafenib; P = 0.533). Conclusions: The combination of the FLT3 inhibitor gilteritinib to CLIA produced high rates of complete remission in pts diagnosed with FLT3-mutated AML. These results were similar for Sorafenib when combined with intensive chemotherapy with OS rates favoring gilteritinib. Further study of intensive chemotherapy with different FLT3 inhibitors is warranted. Clinical trial information: NCT02115295.
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Background: Pts with newly diagnosed(ND) AML often present with abnormal organ function, poor performance status (PS), concurrent active malignancies, and active infections precluding them ...from enrolling on frontline clinical trials, since standard eligibility routinely exclude them. We designed a lower-intensity regimen of cladribine plus low-dose cytarabine (LDAC) alternating with decitabine with less stringent inclusion criteria in ND pts unfit or ineligible for existing clinical trials. Methods: Pts >18 years with untreated AML and ineligible for other frontline AML clinical trials were enrolled (NCT01515527). Eligibility criteria included either creatinine ≥2mg/dL; or total bilirubin ≥2 mg/dL; active concurrent cancer, infection, or ECOG PS of 3 or 4; or ineligible for participation in a higher priority protocol. Induction was cladribine 5 mg/m
2
IV on D1-5, Cytarabine 20 mg SQ twice daily on D 1-10, followed by consolidation with cladribine 5 mg/m
2
IV on D1-3, Cytarabine 20 mg SQ twice daily on D 1-10 alternating with decitabine 20 mg/m
2
IV, daily on D 1-5. Primary objective was 60-d survival rate. Results: 25 pts have been enrolled. The median age was 73 yrs (range, 52-82) with 76% aged ≥70 yo. 6 pts (24%) had concurrent active malignancy, 4 (16%) had baseline creatinine >2mg/dL, and 9 (36%) had PS ≥3. 76% were adverse risk per ELN 2017 (Table). Among 25 evaluable pts, 17 (68%) achieved a composite complete response (CRc) including 10 (40%) CR and 7 (28%) CR with incomplete count recovery (CRi). Among responders, 6 pts (35%) achieved MRD neg by flow. Of 7 pts with no response, all were ELN adverse risk. Median cycles to response was 1 (range: 1 - 4). 30- and 60 d mortality was 8% and 16%, respectively, including 2 pts (8%) who died due to pseudomonal sepsis on D8, and the other due to pneumonia on D11. At a median follow up of 9.4 months (range, 0.4- 19.9 m),median OS (6-mo OS% - 61 %), and EFS was 8.3 mo each (6-mo RFS% - 56 %) with a 60-d OS and EFS rate of 83% each, with a median RFS of 5.8 mo (2-mo RFS%-66%; 6-mo RFS% - 49 %). In this challenging patient population, this lower-intensity regimen was well tolerated, with an acceptable toxicity profile. Conclusions: In an unfit patient population of ND AML with high comorbidity burden, that were ineligible for other clinical trials, induction therapy with Cladribine plus LDAC was feasible and effective and can allow pts to achieve remission and move on to effective post-remission therapy. Clinical trial information: NCT01515527. Table: see text
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