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Industrial control systems (ICS) are required to be operated safely under cyberattacks. Fallback control is necessary for the safe operation of ICS. As one of fallback control systems, we develop a resilient third-party monitoring system. This system consists of Programmable Logic Controllers (PLCs) for normal control and for fallback control. The normal PLC controls field devices, and the fallback PLC takes over the control after the normal PLC is attacked. The fallback control of this paper is the control takeover of a robot arm control system. To quickly transition to this fallback control, it is necessary to incorporate a supervisor function to manage each PLC function in an integrated manner. This paper aims to propose a modeling method of ICS functions and its analysis method to ensure that the supervisor can work properly under cyberattacks. For modeling, we use UPPAAL, specializing in formal verification by timed automata. We implement the models of each PLC and supervisor on UPPAAL. To quantitatively analyze whether the supervisor can really realize the incident response during cyberattacks, we give the specifications necessary for fallback control to the supervisor model using Timed Computation Tree Logic (TCTL) and verify its feasibility. [ABSTRACT FROM AUTHOR]

A homeobox gene, PRESSED FLOWER (PRS), has been found to be very likely to regulate lateral axis-dependent development of Arabidopsis flowers. A flower mutant of Arabidopsis, pressed flower (prs), has been isolated and analyzed. The phenotype of prs has been found and the molecular identification of PRS has been carried out. This is the first report of a gene involved in the lateral axis-dependent development of lateral organs and floral meristems of Arabidopsis.

The maintenance and reformation of gene expression domains are the basis for the morphogenic processes of multicellular systems. In a leaf primordium of Arabidopsis thaliana, the expression of FILAMENTOUS FLOWER (FIL) and the activity of the microRNA miR165/166 are specific to the abaxial side. This miR165/166 activity restricts the target gene expression to the adaxial side. The adaxial and abaxial specific gene expressions are crucial for the wide expansion of leaf lamina. The FIL-expression and the miR165/166-free domains are almost mutually exclusive, and they have been considered to be maintained during leaf development. However, we found here that the position of the boundary between the two domains gradually shifts from the adaxial side to the abaxial side. The cell lineage analysis revealed that this boundary shifting was associated with a sequential gene expression switch from the FIL-expressing (miR165/166 active) to the miR165/166-free (non-FIL-expressing) states. Our genetic analyses using the enlarged fil expression domain2 (enf2) mutant and chemical treatment experiments revealed that impairment in the plastid (chloroplast) gene expression machinery retards this boundary shifting and inhibits the lamina expansion. Furthermore, these developmental effects caused by the abnormal plastids were not observed in the genomes uncoupled1 (gun1) mutant background. This study characterizes the dynamic nature of the adaxial-abaxial specification process in leaf primordia and reveals that the dynamic process is affected by the GUN1-dependent retrograde signal in response to the failure of plastid gene expression. These findings advance our understanding on the molecular mechanism linking the plastid function to the leaf morphogenic processes. [ABSTRACT FROM AUTHOR]

Floral organs usually initiate at fixed positions in concentric whorls within a flower. Although it is understood that floral homeotic genes determine the identity of floral organs, the mechanisms of position determination and the development of each organ have not been clearly explained. We isolated a novel mutant, rabbit ears (rbe), with defects in petal development. In rbe, under-developed petals are formed at the correct position in a flower, and the initiation of petal primordia is altered. The rbe mutation affects the second whorl organ shapes independently of the organ identity. RBE encodes a SUPERMAN-like protein and is located in the nucleus, and thus may be a transcription factor. RBE transcripts are expressed in petal primordia and their precursor cells, and disappeared at later stages. When cells that express RBE are ablated genetically, no petal primordia arise. RBE is not expressed in ap1-1 and ptl-1 mutants, indicating that RBE acts downstream of AP1 and PTL genes. These characteristics suggest that RBE is required for the early development of the organ primordia of the second whorl. [ABSTRACT FROM AUTHOR]

Aim: Lenvatinib mesylate (LEN) is an oral tyrosine kinase inhibitor used to treat various cancers, including hepatocellular carcinoma (HCC). HCC treatment with LEN is associated with a very high incidence of adverse events. This study was aimed at investigating the incidence of LEN‐induced palmar‐planter erythrodysesthesia syndrome (PPES) and its relationship with patient demographics by analyzing clinical laboratory data of LEN‐treated patients with HCC. Methods: This was a single‐centre, retrospective study of patients with HCC who received LEN between April 19, 2018, and September 30, 2020. The observation period was from 1 week before the start of LEN administration to 1 month after the end of administration. Results: Overall, 75 patients with HCC were enrolled. LEN‐induced PPES was found in 48.0% (36/75 patients). In these patients, alkaline phosphatase (ALP), γ‐Glutamyl transpeptidase (γ‐GTP) and monocytes (MONO) were significantly high (ALP: p = 1.32 × 10−3, γ‐GTP: p = 4.25 × 10−3 and MONO: p = 0.013). The cut off values of ALP, γ‐GTP and MONO for LEN‐induced PPES were estimated at 573 U/L, 89 U/L, and 310 counts/μL, respectively. In the multivariate analysis, γ‐GTP and MONO were independent risk factors for LEN‐induced PPES. Conclusions: High γ‐GTP and high MONO were risk factors for LEN‐induced PPES. [ABSTRACT FROM AUTHOR]

Abstract: The midbrain locomotor region including the nucleus of the medial longitudinal fasciculus (Nflm) was electrically stimulated in free-moving goldfish. Stimulation of sites on the midline induced forward movement, whereas that of sites off midline induced turning toward the stimulated side. The closer the site of stimulation to Nflm, the lower the threshold stimulus intensity required to evoke locomotor movement. Using a wirelessly controlled two-channel microstimulator, the locomotion of goldfish in the horizontal plane could be controlled directly by stimulating Nflm for movements involving the trunk and tail. Forward and turning movements could be arbitrarily induced in goldfish equipped with the stimulation device and electrodes implanted in or near the right and left Nflm. Together with previous observations, these findings confirm the role of Nflm in driving spinal segmental rhythm generators initiating swimming, which involves rhythmic contractions of the trunk musculature. [Copyright &y& Elsevier]

DNA polymerase κ (Pol κ) is a specialized DNA polymerase involved in translesion DNA synthesis. Although its bypass activities across lesions are well characterized in biochemistry, its cellular protective roles against genotoxic insults are still elusive. To better understand the in vivo protective roles, we have established a human cell line deficient in the expression of Pol κ (KO) and another expressing catalytically dead Pol κ (CD), to examine the cytotoxic sensitivity to 11 genotoxins including ultraviolet C light (UV). These cell lines were established in a genetic background of Nalm-6-MSH+, a human lymphoblastic cell line that has high efficiency for gene targeting, and functional p53 and mismatch repair activities. We classified the genotoxins into four groups. Group 1 includes benzo[ a]pyrene diolepoxide, mitomycin C, and bleomycin, where the sensitivity was equally higher in KO and CD than in the cell line expressing wild-type Pol κ (WT). Group 2 includes hydrogen peroxide and menadione, where hypersensitivity was observed only in KO. Group 3 includes methyl methanesulfonate and ethyl methanesulfonate, where hypersensitivity was observed only in CD. Group 4 includes UV and three chemicals, where the chemicals exhibited similar cytotoxicity to all three cell lines. The results suggest that Pol κ not only protects cells from genotoxic DNA lesions via DNA polymerase activities, but also contributes to genome integrity by acting as a non-catalytic protein against oxidative damage caused by hydrogen peroxide and menadione. The non-catalytic roles of Pol κ in protection against oxidative damage by hydrogen peroxide are discussed. Environ. Mol. Mutagen. 56:650-662, 2015. © 2015 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Presents several abstracts of papers on developmental biology, presented at the International Congress of Developmental Biology on July 8-12, 2001 in Kyoto, Japan. 'Molecular basis of eye development,' by Peter Gruss; 'Wiring up the brain: molecular mechanisms that control growth cone guidance,' by Corey S. Goodman; 'Regulation of cell assembly patterns,' by Masatoshi Takeichi.