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41 result(s) for "Adamowicz, Marek"
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XRCC1 protects transcription from toxic PARP1 activity during DNA base excision repair
Genetic defects in the repair of DNA single-strand breaks (SSBs) can result in neurological disease triggered by toxic activity of the single-strand-break sensor protein PARP1. However, the mechanism(s) by which this toxic PARP1 activity triggers cellular dysfunction are unclear. Here we show that human cells lacking XRCC1 fail to rapidly recover transcription following DNA base damage, a phenotype also observed in patient-derived fibroblasts with XRCC1 mutations and Xrcc1 −/− mouse neurons. This defect is caused by excessive/aberrant PARP1 activity during DNA base excision repair, resulting from the loss of PARP1 regulation by XRCC1. We show that aberrant PARP1 activity suppresses transcriptional recovery during base excision repair by promoting excessive recruitment and activity of the ubiquitin protease USP3, which as a result reduces the level of monoubiquitinated histones important for normal transcriptional regulation. Importantly, inhibition and/or deletion of PARP1 or USP3 restores transcriptional recovery in XRCC1 −/− cells, highlighting PARP1 and USP3 as possible therapeutic targets in neurological disease. Adamowicz et al. report that toxic PARP1 activity, induced by ataxia-associated mutations in XRCC1, impairs the recovery of global transcription during DNA base excision repair by promoting aberrant recruitment and activity of the histone ubiquitin protease USP3.
SiC-Based Power Electronic Traction Transformer (PETT) for 3 kV DC Rail Traction
The design of rolling stock plays a key role in the attractiveness of the rail transport. Train design must strictly meet the requirements of rail operators to ensure high quality and cost-effective services. Semiconductor power devices made from silicon carbide (SiC) have reached a level of technology enabling their widespread use in traction power converters. SiC transistors offering energy savings, quieter operation, improved reliability and reduced maintenance costs have become the choice for the next-generation railway power converters and are quickly replacing the IGBT technology which has been used for decades. The paper describes the design and development of a novel SiC-based DC power electronic traction transformer (PETT) intended for electric multiple units (EMUs) operated in 3 kV DC rail traction. The details related to the 0.5 MVA peak power medium voltage prototype, including the electrical design of the main building blocks are presented in the first part of the paper. The second part deals with the implementation of the developed SiC-based DC PETT into a regional train operating on a 3 kV DC traction system. The experimental results obtained during the testing are presented to demonstrate the performance of the developed 3 kV DC PETT prototype.
BRCA2 controls DNA:RNA hybrid level at DSBs by mediating RNase H2 recruitment
DNA double-strand breaks (DSBs) are toxic DNA lesions, which, if not properly repaired, may lead to genomic instability, cell death and senescence. Damage-induced long non-coding RNAs (dilncRNAs) are transcribed from broken DNA ends and contribute to DNA damage response (DDR) signaling. Here we show that dilncRNAs play a role in DSB repair by homologous recombination (HR) by contributing to the recruitment of the HR proteins BRCA1, BRCA2, and RAD51, without affecting DNA-end resection. In S/G2-phase cells, dilncRNAs pair to the resected DNA ends and form DNA:RNA hybrids, which are recognized by BRCA1. We also show that BRCA2 directly interacts with RNase H2, mediates its localization to DSBs in the S/G2 cell-cycle phase, and controls DNA:RNA hybrid levels at DSBs. These results demonstrate that regulated DNA:RNA hybrid levels at DSBs contribute to HR-mediated repair. Long non-coding RNAs transcribed at DNA damaged sites can play part in DNA damage response. Here the authors reveal that damaged induced lncRNAs can form DNA:RNA hybrids at resected DNA-ends. These hybrids are involved in recruiting HR-mediated repair machinery which, in turn, controls their level at DSBs.
A Comprehensive System for Protection of Photovoltaic Installations in Normal and Emergency Conditions
The rapid growth of the photovoltaic industry necessitates the development of innovative solutions to ensure the safe operation of these systems. One of the most critical challenges in photovoltaic installations is ensuring protection against electric shock under both operational and emergency conditions, as well as minimizing the risk of fire spread in case of an installation fire. Existing safety measures do not provide a sufficient level of protection, particularly in terms of fire safety. To address these shortcomings, a comprehensive safety system has been developed. This system includes a photovoltaic panel shutter and a safety switch device, which enables the short-circuiting of individual panel outputs while also providing a break in the DC circuit. The proposed solution can be classified as part of the Balance of System (BoS). The effectiveness of this safety system has been validated through both numerical simulations and experimental investigations. Furthermore, an economic analysis indicates that implementing this system will not significantly impact the overall cost of a photovoltaic system.
Notch is a direct negative regulator of the DNA-damage response
Assays in both C. elegans and human cells show that Notch interacts with ATM kinase to inhibit the DNA-damage response and that Notch activity is inversely correlated with ATM activation in breast cancer cells. The DNA-damage response (DDR) ensures genome stability and proper inheritance of genetic information, both of which are essential to survival. It is presently unclear to what extent other signaling pathways modulate DDR function. Here we show that Notch receptor binds and inactivates ATM kinase and that this mechanism is evolutionarily conserved in Caenorhabditis elegans , Xenopus laevis and humans. In C. elegans, the Notch pathway impairs DDR signaling in gonad germ cells. In mammalian cells, activation of human Notch1 leads to reduced ATM signaling in a manner independent of Notch1 transcriptional activity. Notch1 binds directly to the regulatory FATC domain of ATM and inhibits ATM kinase activity. Notch1 and ATM activation are inversely correlated in human breast cancers, and inactivation of ATM by Notch1 contributes to the survival of Notch1-driven leukemia cells upon DNA damage.
Dual Active Bridge (DAB) DC-DC converter for multilevel propulsion converters for electrical multiple units (EMU)
Semiconductor power devices made from silicon carbide (SiC) reached a level of technology enabling their widespread use in power converters. Two different approaches to implementation of modern traction converters in electric multiple units (EMU) have been presented in recent years: (i) 3.3-kV SiC MOSFET-based three-level PWM inverter with regenerative braking and (ii) 6.5-kV IGBT-based fourquadrant power electronic traction transformer (PETT). The former has successfully reached optimized dimensions and efficiency but still requires a bulky line frequency transformer for multisystem applications. The latter characterizes inherent galvanic isolation from AC traction, which is realized by cascaded system of power electronic cells containing medium frequency transformers (MFT). The downsizing of the 6.5-kV IGBT-based cells is, however, problematic. The present paper proposes a different approach, that involves the use of a fast switching 1.2-kV SiC MOSFETS. The SiC-based PETT proposed in the paper is dedicated first for the DC traction. For multi-system application the input voltage of the proposed PETT can be adjusted using weight-optimized adjusting autotransformer. Thanks to utilization of fast-switching SiCbased power modules the weight and size of the power electronic cells can be optimized in a convenient way.
Operations & Maintenance of the Aircraft Arresting Gear Systems in the Polish Air Force. Part 1
In the article, the authors reviewed the arresting gears used in military aviation. The second part of this part describes the operation concept that is used in the Polish Air Force, in relation to the two types of gears, namely the post-Soviet ones that are still in service, and the second one: of U.S. production obtained due to the purchase of F-16 aircraft. The authors emphasize that in the case of an appropriate operation system, it is possible to extend the service life of devices and maintain safety of the air operations.
A role for RNA and DNA:RNA hybrids in the modulation of DNA repair by homologous recombination
DNA double-strand breaks (DSBs) are toxic DNA lesions which, if not properly repaired, may lead to genomic instability, cell death and senescence. Damage-induced long non-coding RNAs (dilncRNAs) are transcribed from broken DNA ends and contribute to DNA damage response (DDR) signaling. Here we show that dilncRNAs play a role in DSB repair by homologous recombination (HR) by contributing to the recruitment of the HR proteins BRCA1, BRCA2, and RAD51, without affecting DNA-end resection. In S/G2-phase cells, dilncRNAs pair to the resected DNA ends and form DNA:RNA hybrids, which are recognized by BRCA1 and promote its recruitment to DSBs. We also show that RNase H2 is in a complex with the HR proteins BRCA1, PALB2, BRCA2, and RAD51, and that it localizes to DSBs in the S/G2 cell-cycle phase. BRCA2 controls DNA:RNA hybrid levels at DSBs by mediating RNase H2 recruitment and, therefore, hybrids degradation. These results demonstrate that regulated DNA:RNA hybrid levels at DSBs contribute to HR-mediated repair.
The Impact of Selected Market Factors on the Prices of Wood Industry By-Products in Poland in the Context of Climate Policy Changes
The objective of this study was to analyze price variability and the factors influencing the formation of monthly prices of by-products of the wood industry in Poland between October 2017 and January 2025. The analysis considered the impact of economic variables, including energy commodity prices (natural gas and coal) and industrial wood prices, on the pricing of wood industry by-products. The adopted approach enabled the identification of key determinants shaping the prices of these by-products. The effectiveness of two tree-based regression models—Random Forest (RF) and CatBoost (CB)—was compared in the analysis. Although RF offers greater interpretability and lower computational requirements, CB proved more effective in modeling dynamic, time-dependent phenomena. The results indicate that industrial wood prices exerted a weaker influence on by-product prices than natural gas prices, suggesting that the energy sector plays a leading role in shaping biomass prices. Coal prices had only a marginal impact on the biomass market, implying that changes in coal availability and pricing did not directly translate into changes in the prices of wood industry by-products. The growing role of renewable energy sources derived from natural gas and wood biomass is contributing to the emergence of a distinct market, increasingly independent of the traditional coal market. In Poland, due to limited access to alternative energy sources, biomass plays a critical role in the decarbonization of the energy sector.
Wood Biomass Resources in Poland Depending on Forest Structure and Industrial Processing of Wood Raw Material
(1) Wood is a widely available raw material on the market, which satisfies the industrial demand and which is used both as a source of biomass for the wood materials industry in a broad sense and for energy-supplying purposes. These areas prove the functional values and the possibilities of the directional use of low-quality wood products. One of the factors influencing the overall balance of the wood biomass is the form and quality of the wood material that cannot be further processed mechanically. This study was conducted to determine the influence of this material by presenting the dependence between the level of wood biomass resources and the conditions of wood acquisition and processing in Poland. (2) The basic directions of biomass acquisition were verified in correlation with the level of its acquisition from forest areas and with the form of by-products generated by sawmills. The research was based on the data from reference publications and analysis of the processing of raw wood in sawmills. The research was conducted on raw hardwood and softwood from coniferous and deciduous forests in Poland. (3) The research confirmed the influence of the processing method on the form and share of by-products. It also showed that the form of the wood biomass obtained was influenced by the region of Poland. (4) The research showed that the regionalisation and wood processing directions were correlated with the structure of the wood biomass acquired.