Quantitative and Approximate Monitoring

In runtime verification, a monitor watches a trace of a system and, if possible, decides after observing each finite prefix whether or not the unknown infinite trace satisfies a given specification. We generalize the theory of runtime verification to monitors that attempt to estimate numerical values of quantitative trace properties (instead of attempting to conclude boolean values of trace specifications), such as maximal or average response time along a trace. Quantitative monitors are approximate: with every finite prefix, they can improve their estimate of the infinite trace's unknown property value. Consequently, quantitative monitors can be compared with regard to a precision-cost trade-off: better approximations of the property value require more monitor resources, such as states (in the case of finite-state monitors) or registers, and additional resources yield better approximations. We introduce a formal framework for quantitative and approximate monitoring, show how it conservatively generalizes the classical boolean setting for monitoring, and give several precision-cost trade-offs for monitors. For example, we prove that there are quantitative properties for which every additional register improves monitoring precision.Comment: To appear in LICS 2021; corrected a referenc

Safety and Liveness of Quantitative Automata

The safety-liveness dichotomy is a fundamental concept in formal languages which plays a key role in verification. Recently, this dichotomy has been lifted to quantitative properties, which are arbitrary functions from infinite words to partially-ordered domains. We look into harnessing the dichotomy for the specific classes of quantitative properties expressed by quantitative automata. These automata contain finitely many states and rational-valued transition weights, and their common value functions Inf, Sup, LimInf, LimSup, LimInfAvg, LimSupAvg, and DSum map infinite words into the totally-ordered domain of real numbers. In this automata-theoretic setting, we establish a connection between quantitative safety and topological continuity and provide an alternative characterization of quantitative safety and liveness in terms of their boolean counterparts. For all common value functions, we show how the safety closure of a quantitative automaton can be constructed in PTime, and we provide PSpace-complete checks of whether a given quantitative automaton is safe or live, with the exception of LimInfAvg and LimSupAvg automata, for which the safety check is in ExpSpace. Moreover, for deterministic Sup, LimInf, and LimSup automata, we give PTime decompositions into safe and live automata. These decompositions enable the separation of techniques for safety and liveness verification for quantitative specifications.Comment: Full version of the paper to appear in CONCUR 202

Investigation of mitophagy biomarkers in corneal epithelium of keratoconus patients

Purpose: The pathological mechanisms of keratoconus (KC) have not been elucidated yet. Mitophagy is an important mechanism that eliminates damaged mitochondria under oxidative stress, and it could be one of the leading pathological causes of KC. This study aimed to find out the role of mitophagy in the keratoconic corneal epithelium. Methods: The corneal epithelia were collected from the 103 progressive KC patients and the 46 control subjects. The real-time quantitative PCR was performed for PTEN-putative kinase-1 (PINK1), PARKIN, p62, and BNIP3 gene expressions in 31 KC and 9 control subjects. Western blot analyses were performed to investigate the protein expressions of PINK1, PARKIN, LC3B, ATG5, and BECLIN in the remaining 109 corneal epithelium samples from 72 patients and 37 control subjects. Results: mRNA and protein expressions of PINK1 decreased significantly in the corneal epithelium of KC patients compared to the control subjects. No significant change was found in mRNA levels of PARKIN, p62, and BNIP3 in KC patients. The protein expression of PARKIN, LC3B, ATG5, and Beclin did not significantly differ between KC patients and control subjects. Gene expression levels of mitophagy biomarkers were not affected by the KC grade. Conclusions: PINK1/PARKIN-dependent mitophagy is affected in the keratoconic corneal epithelium. We found significant decreases in both mRNA and protein expressions of PINK1 in the keratoconic corneal epithelium. However, we did not observe any other significant change in mitophagy markers. Mitochondrial stress-related mitophagy pathways could be interrupted by the decreased levels of PINK1 in the keratoconic corneal epithelium, but solely PINK1 dysregulation is not likely to induce KC pathogenesis

Focused Screening Identifies Different Sensitivities of Human TET Oxygenases to the Oncometabolite 2-Hydroxyglutarate

Ten-eleven translocation enzymes (TETs) are Fe(II)/2-oxoglutarate (2OG) oxygenases that catalyze the sequential oxidation of 5-methylcytosine to 5-hydroxymethylcytosine, 5-formylcytosine, and 5-carboxylcytosine in eukaryotic DNA. Despite their roles in epigenetic regulation, there is a lack of reported TET inhibitors. The extent to which 2OG oxygenase inhibitors, including clinically used inhibitors and oncometabolites, modulate DNA modifications via TETs has been unclear. Here, we report studies on human TET1–3 inhibition by a set of 2OG oxygenase-focused inhibitors, employing both enzyme-based and cellular assays. Most inhibitors manifested similar potencies for TET1–3 and caused increases in cellular 5hmC levels. (R)-2-Hydroxyglutarate, an oncometabolite elevated in isocitrate dehydrogenase mutant cancer cells, showed different degrees of inhibition, with TET1 being less potently inhibited than TET3 and TET2, potentially reflecting the proposed role of TET2 mutations in tumorigenesis. The results highlight the tractability of TETs as drug targets and provide starting points for selective inhibitor design

Reconciling the stratigraphy and depositional history of the Lycian orogen-top basins, SW Anatolia

Terrestrial fossil records from the SWAnatolian basins are crucial both for regional correlations and palaeoenvironmental reconstructions. By reassessing biostratigraphic constraints and incorporating new fossil data, we calibrated and reconstructed the late Neogene andQuaternary palaeoenvironments within a regional palaeogeographical framework. The culmination of the Taurides inSWAnatolia was followed by a regional crustal extension from the late Tortonian onwards that created a broad array of NE-trending orogen-top basins with synchronic associations of alluvial fan, fluvial and lacustrine deposits. The terrestrial basins are superimposed on the upper Burdigalian marine units with a c. 7 myr of hiatus that corresponds to a shift from regional shortening to extension. The initial infill of these basins is documented by a transition from marginal alluvial fans and axial fluvial systems into central shallow-perennial lakes coinciding with a climatic shift from warm/humid to arid conditions. The basal alluvial fan deposits abound in fossil macro-mammals of an early Turolian (MN11–12; late Tortonian) age. The Pliocene epoch in the region was punctuated by subhumid/humid conditions resulting in a rise of local base levels and expansion of lakes as evidenced by marsh-swamp deposits containing diverse fossilmammal assemblages indicating late Ruscinian (lateMN15; late Zanclean) ageWe are grateful for the support of the international bilateral project between The Scientific and Technological Research Council of Turkey (TUBITAK) and The Russian Scientific Foundation (RFBR) with grant a number of 111Y192. M.C.A. is grateful to the Turkish Academy of Sciences (TUBA) for a GEBIP (Young Scientist Award) grant. T.K. and S.M. are grateful to the Ege University Scientific Research Center for the TTM/002/2016 and TTM/001/2016 projects. M.C.A., H.A., S.M. and M.B. have obtained Martin and Temmick Fellowships at Naturalis Biodiversity Center (Leiden). F.A.D. is supported by a Mehmet Akif Ersoy University Scientific Research Grant. T.A.N. is supported by an Alexander-von-Humboldt Scholarship. L.H.O. received support from TUBITAK under the 2221 program for visiting scientists

Determination of the dispersion curve of the refractive index by the Stockwell transform

The determination of dispersion curves by the Stockwell transform (ST) is proposed. The required numerical data for dispersion curves are produced from the transmittance signal by the ST. The obtained data are then used to estimate the unknown dispersion parameters in Cauchy's formula using the genetic algorithm method through the minimisation problem based on the least-squares curve fitting. The results have shown that the dispersion curve obtained from the ST produced more improved outcomes than those obtained from the continuous wavelet transform. © 2009 The Institution of Engineering and Technology

Calcium, vitamin D supplements with or without alendronate and supragingival calculus formation in osteoporotic women: A preliminary study

PubMed ID: 18671457Objectives: Long-term calcium intake is related to the formation of urinary sotones. Structure and composition of kidney and gallstones are similar to dental calculus. Saliva is the source of calcium for supragingival dental calculus formation. The aim of this preliminary study was to evaluate the possible effects of long-term calcium and vitamin D supplementation with or without alendronate administration on salivary electrolyte concentrations and supragingival calculus formation in osteoporotic women. Methods: Thirty-one female patients with osteoporosis for at least 3 years participated in this study. Eighteen women were taking calcium plus vitamin D plus alendronate, while 13 women were taking only calcium plus vitamin D supplements. Eleven systemically healthy women volunteered for the control group. Whole saliva samples were collected from all women before initiation of any periodontal intervention. Plaque index, probing depth, clinical attachment level, bleeding on probing, and calculus index were recorded at six sites/tooth. Salivary concentrations of ionic calcium, potassium, magnesium and sodium were determined by atomic absorption spectrophotometer. Results were evaluated statistically by non-parametric tests. Results: No significant differences were found in clinical parameters or results of saliva analysis between the study groups (p > 0.05). Conclusion: Within the limits of this preliminary study, it is suggested that long-term calcium and vitamin D supplementation with or without alendronate does not appear to have a significant effect on supragingival calculus formation or saliva total calcium, potassium, magnesium and sodium concentrations. Larger-scale studies investigating the possible effects of various treatment modalities of osteoporosis on supragingival calculus formation are required to better clarify this issue. © 2008 Informa UK Ltd