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PML, a multifunctional protein, is crucial for forming PML-nuclear bodies involved in stress responses. Under specific conditions, PML associates with nucleolar caps formed after RNA polymerase I (RNAPI) inhibition, leading to PML-nucleolar associations (PNAs). This study investigates PNAs-inducing stimuli by exposing cells to various genotoxic stresses. We found that the most potent inducers of PNAs introduced topological stress and inhibited RNAPI. Doxorubicin, the most effective compound, induced double-strand breaks (DSBs) in the rDNA locus. PNAs co-localized with damaged rDNA, segregating it from active nucleoli. Cleaving the rDNA locus with I-PpoI confirmed rDNA damage as a genuine stimulus for PNAs. Inhibition of ATM, ATR kinases, and RAD51 reduced I-PpoI-induced PNAs, highlighting the importance of ATM/ATR-dependent nucleolar cap formation and homologous recombination (HR) in their triggering. I-PpoI-induced PNAs co-localized with rDNA DSBs positive for RPA32-pS33 but deficient in RAD51, indicating resected DNA unable to complete HR repair. Our findings suggest that PNAs form in response to persistent rDNA damage within the nucleolar cap, highlighting the interplay between PML/PNAs and rDNA alterations due to topological stress, RNAPI inhibition, and rDNA DSBs destined for HR. Cells with persistent PNAs undergo senescence, suggesting PNAs help avoid rDNA instability, with implications for tumorigenesis and aging.

PML, a multifunctional protein, is crucial for forming PML- nuclear bodies involved in stress responses. Under specific conditions, PML associates with nucleolar caps formed after RNA polymerase I (RNAPI) inhibition, leading to PML- nucleolar associations (PNAs). This study investigates PNAs- inducing stimuli by exposing cells to various genotoxic stresses. We found that the most potent inducers of PNAs introduced topological stress and inhibited RNAPI. Doxorubicin, the most effective compound, induced double- strand breaks (DSBs) in the rDNA locus. PNAs co- localized with damaged rDNA, segregating it from active nucleoli. Cleaving the rDNA locus with I- PpoI confirmed rDNA damage as a genuine stimulus for PNAs. Inhibition of ATM, ATR kinases, and RAD51 reduced I- PpoI- induced PNAs, highlighting the importance of ATM/ATR- dependent nucleolar cap formation and homologous recombination (HR) in their triggering. I- PpoI- induced PNAs co- localized with rDNA DSBs positive for RPA32- pS33 but deficient in RAD51, indicating resected DNA unable to complete HR repair. Our findings suggest that PNAs form in response to persistent rDNA damage within the nucleolar cap, highlighting the interplay between PML/PNAs and rDNA alterations due to topological stress, RNAPI inhibition, and rDNA DSBs destined for HR. Cells with persistent PNAs undergo senescence, suggesting PNAs help avoid rDNA instability, with implications for tumorigenesis and aging. [ABSTRACT FROM AUTHOR]

Currently, electromagnetic interference constitutes one of the major complications for a function of electronic or electrical devices. Because these devices are constantly exposed to effects of electromagnetic radiation, it is desirable to increase the electromagnetic immunity of device. One of the possibilities is to applicate the suitable shielding materials which can protect the device against the radiated electromagnetic emissions. This paper devotes to finding suitable materials for shielding security devices.

One of the major types of electromagnetic interference, which affect electronic devices in their normal operation, is the interference with radio-frequency electromagnetic fields. This interference is generated by the mainly radio and television transmitters, industrial equipment and other transmitters and receivers in general use for communication. Testing of electromagnetic susceptibility of electronic devices on radiated radio-frequency electromagnetic field is governed by the basic standard IEC 61000-4-3 and the equipment under test are exposed to test electromagnetic fields with an intensity from 1 V/m to 30 V/m, the most often in the frequency range from 80 MHz to 2 GHz. The aim of this paper is to explain the issue of electromagnetic susceptibility and to present sample the electromagnetic immunity tests of the basic set of the intrusion and hold-up alarm system against the radio-frequency electromagnetic field according to the relevant electromagnetic compatibility standards.

The popularity of e-commerce is increasing day-by-day. In order to provide a seamless experience and tailored offer for the customers, the knowledge of their preferences and behavior is required. The demography of customers is one of the important information used for, e.g., segmentation. To provide optimal service, machine learning is often used for various tasks. However, the amount of data generated by customers and also large and changing product catalogs result in poorly performing models. In this paper we aim at introducing behavior-based abstraction, which includes item and event abstractions also. Our method reduces the number of unique items in the e-commerce catalog and in the next step encodes the user behavior. We performed extensive evaluation over the real-world dataset. The results suggest the usefulness of proposed abstraction and also resulted in the improvement of the demography prediction performance both from model complexity and performance point of view. [ABSTRACT FROM AUTHOR]

Due to the increasing susceptibility of electronic device, the importance of electromagnetic immunity to interference also increasing. The basic task of testing the electromagnetic susceptibility of electronic device on the harmful interference is comparison of the data obtained by testing with data which are required by the relevant standards for the device. When the electronic device does not have a sufficient immunity can occur a deterioration of its functionality, temporary failure or even a permanent damage to the device. The aim of this paper is perform the test of electromagnetic susceptibility for the electrostatic discharge at the keyboard of the alarm system. Immunity test will be performed according to instructions in the standards of electromagnetic compatibility. [ABSTRACT FROM AUTHOR]

6-Nitrobenzo[ b ]thiophene 1,1-dioxide (Stattic) is a potent signal transducer and activator of the transcription 3 (STAT3) inhibitor developed originally for anticancer therapy. However, Stattic harbors several STAT3 inhibition-independent biological effects. To improve the properties of Stattic, we prepared a series of analogues derived from 6-aminobenzo[ b ]thiophene 1,1-dioxide, a compound directly obtained from the reduction of Stattic, that includes a methoxybenzylamino derivative (K2071) with optimized physicochemical characteristics, including the ability to cross the blood-brain barrier. Besides inhibiting the interleukin-6-stimulated activity of STAT3 mediated by tyrosine 705 phosphorylation, K2071 also showed cytotoxicity against a set of human glioblastoma-derived cell lines. In contrast to the core compound, a part of K2071 cytotoxicity reflected a STAT3 inhibition-independent block of mitotic progression in the prophase, affecting mitotic spindle formation, indicating that K2071 also acts as a mitotic poison. Compared to Stattic, K2071 was significantly less thiol-reactive. In addition, K2071 affected cell migration, suppressed cell proliferation in tumor spheroids, exerted cytotoxicity for glioblastoma temozolomide-induced senescent cells, and inhibited the secretion of the proinflammatory cytokine monocyte chemoattractant protein 1 (MCP-1) in senescent cells. Importantly, K2071 was well tolerated in mice, lacking manifestations of acute toxicity. The structure-activity relationship analysis of the K2071 molecule revealed the necessity of the para -substituted methoxyphenyl motif for antimitotic but not overall cytotoxic activity of its derivatives. Altogether, these results indicate that compound K2071 is a novel Stattic-derived STAT3 inhibitor and a mitotic poison with anticancer and senotherapeutic properties that is effective on glioblastoma cells and may be further developed as an agent for glioblastoma therapy., Competing Interests: The authors declare no competing financial interest., (© 2024 The Authors. Published by American Chemical Society.)