61 research outputs found
A ubiquitin-dependent signalling axis specific for ALKBH-mediated DNA dealkylation repair
No full textDNA repair is essential to prevent the cytotoxic or mutagenic effects of various types of DNA lesions, which are sensed by distinct pathways to recruit repair factors specific to the damage type. Although biochemical mechanisms for repairing several forms of genomic insults are well understood, the upstream signalling pathways that trigger repair are established for only certain types of damage, such as double-stranded breaks and interstrand crosslinks. Understanding the upstream signalling events that mediate recognition and repair of DNA alkylation damage is particularly important, since alkylation chemotherapy is one of the most widely used systemic modalities for cancer treatment and because environmental chemicals may trigger DNA alkylation. Here we demonstrate that human cells have a previously unrecognized signalling mechanism for sensing damage induced by alkylation. We find that the alkylation repair complex ASCC (activating signal cointegrator complex) relocalizes to distinct nuclear foci specifically upon exposure of cells to alkylating agents. These foci associate with alkylated nucleotides, and coincide spatially with elongating RNA polymerase II and splicing components. Proper recruitment of the repair complex requires recognition of K63-linked polyubiquitin by the CUE (coupling of ubiquitin conjugation to ER degradation) domain of the subunit ASCC2. Loss of this subunit impedes alkylation adduct repair kinetics and increases sensitivity to alkylating agents, but not other forms of DNA damage. We identify RING finger protein 113A (RNF113A) as the E3 ligase responsible for upstream ubiquitin signalling in the ASCC pathway. Cells from patients with X-linked trichothiodystrophy, which harbour a mutation in RNF113A, are defective in ASCC foci formation and are hypersensitive to alkylating agents. Together, our work reveals a previously unrecognized ubiquitin-dependent pathway induced specifically to repair alkylation damage, shedding light on the molecular mechanism of X-linked trichothiodystrophy.Joshua R. Brickner, Jennifer M. Soll, Patrick M. Lombardi, Cathrine B. Vågbø, Miranda C. Mudge, Clement Oyeniran, Renana Rabe, Jessica Jackson, Meagan E. Sullender, Elyse Blazosky, Andrea K. Byrum, Yu Zhao, Mark A. Corbett, Jozef Gécz, Michael Field, Alessandro Vindigni, Geir Slupphaug, Cynthia Wolberger and Nima Mosammaparas
Development of court procedures for identifying problem drinkers. Interim - phase I
No full textNational Highway Traffic Safety Administration, Washington, D.C.http://deepblue.lib.umich.edu/bitstream/2027.42/1203/2/17646.0001.001.pd
Author Correction: Microbial Metagenomes Across a Complete Phytoplankton Bloom Cycle: High-Resolution Sampling Every 4 Hours Over 22 Days
No full textCorrection to: Scientific Datahttps://doi.org/10.1038/s41597-024-04013-5, published online 22 November 2024 In the version of this article initially published, two errors in authorship were made. First, Tatiana Rynearson of the School of Oceanography, University of Rhode Island was mistakenly omitted from the final author list. Second, Kurt LaButti of the Joint Genome Institute was mistakenly omitted from the final author list and replaces Alicia Clum due to a staffing change at the Joint Genome Institute. These authorship omissions were not identified until after the work had been published. We are updating the authorship to appropriately recognize the contributions of these authors. The error has been corrected in the PDF and HTML versions of the article
Author Correction: Transcript expression-aware annotation improves rare variant interpretation
No full textIn this Article, author Marquis P. Vawter was missing from the Genome Aggregation Database Consortium list. They are associated with the affiliation: ‘Department of Psychiatry & Human Behavior, University of California Irvine, Irvine, CA, USA’, and contributed to the generation of the primary data incorporated into the gnomAD resource. The original Article has been corrected online
Timing Measurement Platform for Arbitrary Black-Box Circuits Based on Transition Probability
No full text03.06.13 KB. Ok to add the author version to Spira
RNA ligase-like domain in activating signal cointegrator 1 complex subunit 1 (ASCC1) regulates ASCC complex function during alkylation damage
No full textFuzzy logic arbiters for multiple-bus multiprocessor systems
No full textThis paper describes and evaluates the use of fuzzy logic arbiters for multiple-bus shared memory multiprocessor system. Multiple-bus systems allow multiple and simultaneous bus transfer in addition to a high degree of fault tolerance. In such systems, arbiters are used to resolve conflicts to system resources, which are the shared memory modules and the buses. Typically, these conflicts are resolved by using two-stage arbitration schemes that employ policies such as random choice, daisy chaining, round-robin, etc. A new way of implementing these arbiters is the use of fuzzy logic to resolve resource request conflicts based on the system state and performance variables. This paper describes a new technique for implementation of fuzzy logic in the system arbiters and presents a simulation program that evaluates the system performance. The program is coded in such a way as to accommodate any arbitration scheme, from which the fixed priority and fuzzy priority have been implemented. Parameters affecting multiple-bus system performance are considered and used as inputs to the fuzzy arbiters. The inputs are fuzzified by using appropriate membership functions, and rules have been defined in such a way as to increase and distribute evenly the acceptance probability of each processor in the system. Results from the simulation program using a prioritized arbitration scheme are compared against other published results and show very close agreement. Furthermore, results show an increase in the acceptance probability of the processors using fuzzy arbiters. © 2004 IEEE.BHUYAN LN, 1985, IEEE T COMPUT, V34, P279; HIROTA K, 1989, IEEE T SYST MAN CYB, V19, P980, DOI 10.1109-21.44013; HOLLIDAY MA, 1984, IEEET COMPUT C, V33, P76; HWANG K, 1985, COMPUTER ARCH PARALL; John LK, 1996, IEEE T COMPUT, V45, P580, DOI 10.1109-12.509909; Klir G., 1988, FUZZY SETS UNCERTAIN; LIU YC, 1989, J PARALLEL DISTR COM, V7, P321, DOI 10.1016-0743-7315(89)90023-3; MAHMUD SM, 1994, IEEE T COMPUT, V43, P789, DOI 10.1109-12.293258; MARSAN MA, 1983, IEEE T COMPUT, V32, P60; Mudge T. N., 1984, Proceedings of the 1984 International Conference on Parallel Processing (Cat. No. 84CH2045-3); Qiao WZ, 1996, FUZZY SET SYST, V78, P23; UCHINO E, 1993, FUZZY SET SYST, V59, P259, DOI 10.1016-0165-0114(93)90471-S; ZADEH LA, 1965, INFORM CONTROL, V8, P338, DOI 10.1016-S0019-9958(65)90241-X11
Dynamic reconfiguration technologies based on FPGA in software defined radio system
No full textPartial Reconfiguration (PR) is a method for Field Programmable Gate Array (FPGA) designs which allows multiple applications to time-share a portion of an FPGA while the rest of the device continues to operate unaffected. Using this strategy, the physical layer processing architecture in Software Defined Radio (SDR) systems can benefit from reduced complexity and increased design flexibility, as different waveform applications can be grouped into one part of a single FPGA. Waveform switching often means not only changing functionality, but also changing the FPGA clock frequency. However, that is beyond the current functionality of PR processes as the clock components (such as Digital Clock Managers (DCMs)) are excluded from the process of partial reconfiguration. In this paper, we present a novel architecture that combines another reconfigurable technology, Dynamic Reconfigurable Port (DRP), with PR based on a single FPGA in order to dynamically change both functionality and also the clock frequency. The architecture is demonstrated to reduce hardware utilization significantly compared with standard, static FPGA design
Zinc Oxide Nanoparticle-Poly I:C RNA Complexes: Implication as Therapeutics against Experimental Melanoma
No full textThere is current interest in harnessing the combined anticancer and immunological effect of nanoparticles (NPs) and RNA. Here, we evaluate the bioactivity of poly I:C (pIC) RNA, bound to anticancer zinc oxide NP (ZnO-NP) against melanoma. Direct RNA association to unfunctionalized ZnO-NP is shown by observing change in size, zeta potential, and absorption/fluorescence spectra upon complexation. RNA corona was visualized by transmission electron microscopy (TEM) for the first time. Binding constant (Kb = 1.6-2.8 g-1 L) was determined by modified Stern-Volmer, absorption, and biological surface activity index analysis. The pIC-ZnO-NP complex increased cell death for both human (A375) and mouse (B16F10) cell lines and suppressed tumor cell growth in BALB/C-B16F10 mouse melanoma model. Ex vivo tumor analysis indicated significant molecular activity such as changes in the level of phosphoproteins JNK, Akt, and inflammation markers IL-6 and IFN-γ. High throughput proteomics analysis revealed zinc oxide and poly I:C-specific and combinational patterns that suggested possible utility as an anticancer and immunotherapeutic strategy against melanoma
DEFINITIONS, SOLVED AND U SOLVED PROBLEMS, CONJECTURES, AND THEOREMS IN NUMBER THEORY AND GEOMETRY
No full textFlorentin Smarandache, an American mathematician of Romanian descent, has generated a vast variety of mathematical problems. Some problems are easy, others medium, but many are interesting or unsolved and this is the reason why the present book appears. Here, of course, there are problems from various types. Solving these problems is addictive like eating pumpkin seed: having once started, one cannot help doing it over and over again
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