The second edition of standard ISO 26262 (ed. 2018) for functional safety assessment in the automotive industry requires a hardware evaluation using the probabilistic metric for random hardware ...failures (PMHF). The standard for mentioned purpose highly recommends the fault tree analysis (FTA) utilization but does not give any specific calculation example. Therefore, this article describes computational procedures with derivation and explanation of mathematical formulas for various hardware architectures of electronic systems. Described formulas consider impact of multiple failures and impact of elf‐tests, but formulas are relatively simple. This simplicity allows them to be used in the early stages of hardware development when frequent hardware design changes can be expected. Thus, the article with attached case study is intended not only for scientists but also for developers of critical safety–related electronic systems in the automotive industry.
The aim of the article is to present the concept of an indirect diagnostic method using the assessment of the variability of the amount of released heat (mass fraction burn) and the heat release ...rate. The Wiebe function for the assessment of variability has been used. The Wiebe function parameters from the course of the high-pressure indication in the cylinder of internal combustion engine using linear regression have been calculated. From a sufficiently large number of measured samples, the upper and lower limits of the Wiebe function parameters have been statistically determined. Lower and upper limits characterize variability of the heat release process not only in terms of quantity but also in terms of heat release rate. The assessment of variability is thus more complicated than using one integral indicator, typically the mean value of amount of the released heat. The procedure enabling a more accurate estimation of heat generation beginning has been shown. For the combustion process variability assessment of the engine, statistical test of relative frequencies has been used.
Using a CFD simulation in the development of internal combustion engines, with 1-D approach, can significantly reduce the time and costs associated with experiments and prototyping. With commercial ...software we can use 1-D computational models to optimize the parameters of manufactured engines and observe hardly measurable values. This article describes the basic principle of creating and calibration of computational model.
The use of one-dimensional CFD engine simulation is an essential tool to the engine development process. Engine design through simulation can drastically reduce time needed to perform engine ...experiments and prototyping, as most engine experiments can be simulated within the software.
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•Toxicity of organochlorine effluent containing HCH and TCB to microalgae was studied.•Scenedesmus accumulated almost all HCH isomers dose-dependently and δ-HCH dominated.•Elevated ...activities of antioxidative enzymes may reflect toxicity of organochlorines.•Organochlorines stimulated thiols, ascorbate and Krebs cycle acids in both algae.•Fatty acids showed that SFAs or MUFAs increased in Coccomyxa but PUFAs in Scenedesmus.
Toxicity of mine dump effluent containing five hexachlorocyclohexane (α, β, γ, δ and ε-HCH, sum 159.4 μg/L) and two trichlorobenzene (TCB, sum 65.2 μg/L) isomers to two microalgae (Scenedesmus quadricauda and Coccomyxa subellipsoidea) was studied over 24 h exposure and also with 2- and 10-fold diluted stock solution (i.e. 1×, 0.5× and 0.1× strength). Individual isomers revealed rather dose-dependent accumulation typically higher in Scenedesmus than in Coccomyxa (max. sum of HCH 14.99 μg/g DW with bioaccumulation factor 94) and δ-HCH was dominant isomer. TCB isomers showed low accumulation in algae. 0.1× dose elevated chlorophylls and carotenoids in Coccomyxa while enzymatic activities (SOD, CAT, and APX), thiols (glutathione and phytochelatin 2) and ascorbic acid were rather elevated by 1× dose in both species. Malic acid, rather than citric acid, increased in response to 0.5× and 1× concentration. Sum of fatty acids was higher in Coccomyxa than in Scenedesmus with palmitic, oleic, linoleic and α-linolenic acids being dominant compounds in both species. Detailed profiling revealed that saturated and monounsaturated fatty acids increased in Coccomyxa while polyunsaturated fatty acids in Scenedesmus in response to increasing dose of organochlorines. Accumulation of organochlorines and metabolic responses in algae are reported here for the first time.
Breast cancer is the most common and molecularly relatively well characterized malignant disease in women, however, its progression to metastatic cancer remains lethal for 78% of patients 5years ...after diagnosis. Novel markers could identify the high risk patients and their verification using quantitative methods is essential to overcome genetic, inter-tumor and intra-tumor variability and translate novel findings into cancer diagnosis and treatment. We recently identified 13 proteins associated with estrogen receptor, tumor grade and lymph node status, the key factors of breast cancer aggressiveness, using untargeted proteomics. Here we verified these findings in the same set of 96 tumors using targeted proteomics based on selected reaction monitoring with mTRAQ labeling (mTRAQ-SRM), transcriptomics and immunohistochemistry and validated in 5 independent sets of 715 patients using transcriptomics. We confirmed: (i) positive association of anterior gradient protein 2 homolog (AGR2) and periostin (POSTN) and negative association of annexin A1 (ANXA1) with estrogen receptor status; (ii) positive association of stathmin (STMN1), cofilin-1 (COF1), plasminogen activator inhibitor 1 RNA-binding protein (PAIRBP1) and negative associations of thrombospondin-2 (TSP2) and POSTN levels with tumor grade; and (iii) positive association of POSTN, alpha-actinin-4 (ACTN4) and STMN1 with lymph node status. This study highlights a panel of gene products that can contribute to breast cancer aggressiveness and metastasis, the understanding of which is important for development of more precise breast cancer treatment.
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•The first application of mTRAQ-SRM in breast cancer tissue proteomics•SRM assays for 16 protein biomarker candidates were developed.•SRM, mRNA and IHC verification, mRNA validation•ER, tumor grade and lymph node status associated, validated gene products•These targets may contribute to mechanisms of tumor aggressiveness and metastasis.
Although smallpox has been known for centuries, the oldest available variola virus strains were isolated in the early 1940s. At that time, large regions of the world were already smallpox-free. ...Therefore, genetic information of these strains can represent only the very last fraction of a long evolutionary process. Based on the genomes of 48 strains, two clades are differentiated: Clade 1 includes variants of variola major, and clade 2 includes West African and variola minor (Alastrim) strains. Recently, the genome of an almost 400-year-old Lithuanian mummy was determined, which fell basal to all currently sequenced strains of variola virus on phylogenetic trees. Here, we determined two complete variola virus genomes from human tissues kept in a museum in Prague dating back 60 and 160 years, respectively. Moreover, mass spectrometry-based proteomic, chemical, and microscopic examinations were performed. The 60-year-old specimen was most likely an importation from India, a country with endemic smallpox at that time. The genome of the 160-year-old specimen is related to clade 2 West African and variola minor strains. This sequence likely represents a new endemic European variant of variola virus circulating in the midst of the 19th century in Europe.
Biśnik Cave is an important Palaeolithic site located in the Kraków-Częstochowa Upland. The cave fill is a complex well-stratified sequence composed of 35 layers/sublayers interrupted by number of ...hiatuses and ranging from Pliocene till modern times. Fifteen Middle Palaeolithic horizons, some of them among the oldest in Poland, represent the most important part of the sequence from an archaeological point of view. The sedimentary sequences in particular parts of the cave have been studied for more than 20 years to investigate the chronostratigraphy and palaeoenvironment. The recent multi-proxy study is based on the application of new methods for the site: analysis of sedimentary and post-sedimentary structures, and weathering stage of limestone rubble and fossil bones, pollen analysis, molecular biomarkers, palaeomagnetic analysis and radiometric dating. Results indicated a more intensive role of re-working and re-deposition in the cave. Older sediments were transported into some stratigraphic horizons from sources within the cave itself as well as from outside, including palaeontological and archaeological materials. Some the detected layers therefore represent a mix derived from different sources. A record of two interglacials (Eemian Interglacial, MIS 5e and Penultimate Interglacial, MIS 7) was established in layers Nos. 15–14–13a–13 and 19a–19, respectively. Middle–Upper Pleistocene sedimentary units were identified with MIS 3–MIS 7/8, instead of previous interpretation to MIS 4–MIS 9. The age of the basal vario-colored complex, previously interpreted mostly as pre-Pleistocene, was newly correlated with MIS 7/8 and Early Pleistocene/Pliocene.
Early detection of biohazardous bacteria that can be misused as biological weapons is one of the most important measures to prevent the spread and outbreak of biological warfare. For this reason, ...many instrument platforms need to be introduced into operation in the field of biological warfare detection. Therefore the purpose of this study is to establish a new detection panel for biothreat bacteria (
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spp.) and confirm it by collaborative validation by using a multiplex oligonucleotide ligation followed by polymerase chain reaction and hybridization to microspheres by MagPix detection platform (MOL-PCR). Appropriate specific sequences in bacterial DNA were selected and tested to assemble the detection panel, and MOLigo probes (short specific oligonucleotides) were designed to show no cross-reactivity when tested between bacteria and to decrease the background signal measurement on the MagPix platform. During testing, sensitivity was assessed for all target bacteria using serially diluted DNA and was determined to be at least 0.5 ng/µL. For use as a diagnostic kit and easier handling, the storage stability of ligation premixes (MOLigo probe mixes) was tested. This highly multiplex method can be used for rapid screening to prevent outbreaks arising from the use of bacterial strains for bioterrorism, because time of analysis take under 4 h.