Forget the fact that the song itself is a tinnitus-inducing combination of brass parps, military drumming and discordant whistles.
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The drug treats recurrent ovarian cancer by inhibiting the production of proteins called PARPs, a highly sought after function for their potential in developing breakthrough cancer treatments.
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Thus cancers that have mutations in the BRCA213 and BRCA22015 genes rely heavily on a backup DNA repair mechanism which uses proteins called poly-ADP-ribose polymerases (PARPs).
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Niraparib kills cancer cells by inhibiting the production of proteins called PARPs, which help repair damaged DNA strands, thereby hastening the death of some types of cancer cells.
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Its drug Niraparib kills cancer cells by inhibiting the production of proteins called PARPs, which help repair damaged DNA strands, thereby hastening the death of some types of cancer cells.
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Poly [ADP-ribose] polymerase 10 is an enzyme that in humans is encoded by the PARP10 gene. Poly(ADP-ribose) polymerases (PARPs), such as PARP10, regulate gene transcription by altering chromatin organization by adding ADP-ribose to histones. PARPs can also function as transcriptional cofactors (Yu et al., 2005).
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PARPs are enzymes that are activated by DNA strand breaks and play a role in DNA base excision repair. Burkle et al. reviewed evidence that PARPs, and especially PARP-1, are involved in maintaining mammalian longevity. The life span of 13 mammalian species correlated with poly(ADP ribosyl)ation capability measured in mononuclear cells.
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Overactivation of PARPs has led to a necrotic cell death regulated by the tumor necrosis factor protein. Though the mechanism is not yet understood, PARP inhibitors have been shown to affect necroptosis.
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In packet based data communication services, the communication is bursty and the traffic load rapidly changing. For high system spectrum efficiency, DCA should be performed on a packet-by-packet basis. Examples of algorithms for packet-by-packet DCA are Dynamic Packet Assignment (DPA), Dynamic Single Frequency Networks (DSFN) and Packet and resource plan scheduling (PARPS).
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Histones are another protein target of the PARPs. All core histones and linker histone H1 are ADP-ribosylated following DNA damage. The function of these modifications is still unknown, but it has been proposed that ADP-ribosylation modulates higher-order chromatin structure in efforts to facilitate more accessible sites for repair factors to migrate to the DNA damage.
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This is important in carcinogenesis because it could lead to the selection of PARP1 deficient cells (but not depleted) due to their survival advantage during cancer growth. Susceptibility to carcinogenesis under PARP1 deficiency depends significantly on the type of DNA damage incurred. There are many implications that various PARPs are involved in preventing carcinogenesis. As stated previously, PARP1 and PARP2 are involved in BER and chromosomal stability.
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Poly-(ADP-ribose) polymerases (PARPs) are found mostly in eukaryotes and catalyze the transfer of multiple ADP-ribose molecules to target proteins. As with mono-ADP ribosylation, the source of ADP-ribose is NAD+. PARPs use a catalytic triad of His-Tyr-Glu to facilitate binding of NAD+ and positioning of the end of the existing poly-ADP ribose chain on the target protein; the Glu facilitates catalysis and formation of a (1->2) O-glycosidic linkage between two ribose molecules. There are several other enzymes that recognize poly-ADP ribose chains, hydrolyse them or form branches; over 800 proteins have been annotated to contain the loosely defined poly ADP-ribose binding motif; therefore, in addition to this modification altering target protein conformation and structure, it may also be used as a tag to recruit other proteins or for regulation of the target protein.
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If PARP3 is lost, this results in single-strand breaks, and thus the recruitment of PARP1. A second hypothesis suggests that the two enzyme work together; PARP3 catalyzes mono-ADP ribosylation and short poly-ADP ribosylation and serves to activate PARP1. The PARPs have many protein targets at the site of DNA damage. KU protein and DNA-PKcs are both double-stranded break repair components with unknown sites of ADP- ribosylation.
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PDB: 4AV1 PARPs have been shown to affect transcription factor structure and cause recruitment of many transcription factors to form complexes at DNA and elicit transcription. Mono ADP-ribosyltransferases are also shown to affect transcription factor binding at promoters. For example, PARP14, a mono ADP- ribosyltransferase, has been shown to affect STAT transcription factor binding. Other ADP-ribosyltransferases have been shown to modify proteins that bind mRNA, which can cause silencing of that gene transcript.
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Poly-ADP-ribose polymerases (PARPs) can function in DNA repair of single strand breaks as well as double strand breaks. In single-strand break repair (base excision repair) the PARP can either facilitate removal of an oxidized sugar or strand cleavage. PARP1 binds the single-strand breaks and pulls any nearby base excision repair intermediates close. These intermediates include XRCC1 and APLF and they can be recruited directly or through the PBZ domain of the APLF.
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Macro domain proteins can be found in eukaryotes, in (mostly pathogenic) bacteria, in archaea and in ssRNA viruses, such as coronaviruses, Rubella and Hepatitis E viruses. In vertebrates the domain occurs in e.g. histone macroH2A, predicted poly-ADP- ribose polymerases (PARPs) and B aggressive lymphoma (BAL) protein. ADP- ribosylation of proteins is an important post-translational modification that occurs in a variety of biological processes, including DNA repair, regulation of transcription, chromatin biology, maintenance of genomic stability, telomere dynamics, cell differentiation and proliferation, necrosis and apoptosis, and long-term memory formation.
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During DNA damage or cellular stress PARPs are activated, leading to an increase in the amount of poly-ADP-ribose and a decrease in the amount of NAD+. For over a decade it was thought that PARP1 was the only poly-ADP-ribose polymerase in mammalian cells, therefore this enzyme has been the most studied. Caspases are a family of cysteine proteases that are known to play an essential role in programmed cell death. This protease cleaves PARP-1 into two fragments, leaving it completely inactive, to limit poly-ADP-ribose production.
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One of its fragments migrates from the nucleus to the cytoplasm and is thought to become a target of autoimmunity. During caspase-independent apoptosis, also called parthanatos, poly-ADP-ribose accumulation can occur due to activation of PARPs or inactivation of poly(ADP-ribose) glycohydrolase, an enzyme that hydrolyses poly(ADP-ribose) to produce free ADP-ribose. Studies have shown poly-ADP- ribose drives the translocation of the apoptosis inducing factor protein to the nucleus where it will mediate DNA fragmentation. It has been suggested that if a failure of caspase activation under stress conditions were to occur, necroptosis would take place.
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Interactive multicast implies that TV programs are sent only over transmitters where there are viewers and that only the most popular programs are transmitted. It relies on an additional interaction channel (a back-channel or return channel), where user equipment may send join and leave messages when the user changes TV channel. Interactive multicast has been suggested as an efficient transmission scheme in DVB-H and DVB-T2 terrestrial digital television systems,M. Eriksson, S.M. Hasibur Rahman, F. Fraille, M. Sjöström, ”Efficient Interactive Multicast over DVB-T2 - Utilizing Dynamic SFNs and PARPS”, 2013 IEEE International Conference on Computer and Information Technology (BMSB’13), London, UK, June 2013.
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This correlation was striking and stimulated a series of 11 additional experiments in different laboratories over succeeding years on the relationship of nucleotide excision repair and life span in mammalian species (reviewed by Bernstein and Bernstein). In general, the findings of these studies indicated a good correlation between nucleotide excision repair capacity and life span. The association between nucleotide excision repair capability and longevity is strengthened by the evidence that defects in nucleotide excision repair proteins in humans and rodents cause features of premature aging, as reviewed by Diderich. Further support for the theory that DNA damage is the primary cause of aging comes from study of Poly ADP ribose polymerases (PARPs).
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The same relationship occurs in many other rankings of human created systems, such as the ranks of mathematical expressions or ranks of notes in music, and even in uncontrolled environments, such as the population ranks of cities in various countries, corporation sizes, income rankings, ranks of number of people watching the same TV channel,M. Eriksson, S.M. Hasibur Rahman, F. Fraille, M. Sjöström, Efficient Interactive Multicast over DVB-T2 - Utilizing Dynamic SFNs and PARPS , 2013 IEEE International Conference on Computer and Information Technology (BMSB'13), London, UK, June 2013. Suggests a heterogeneous Zipf-law TV channel-selection model and so on. The appearance of the distribution in rankings of cities by population was first noticed by Felix Auerbach in 1913.
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Musically, "Triumph of a Heart" is a song with pop, dance, and hip-hop elements. According to Michael Hubbard from MusicOMH, the song begins with "balloons being blown up" and goes on to feature a sequenced cacophany of "meaows, mmmmms, parps, waaayaas and other side-splitting human voice noises all strung together like so many deranged pixies letting out their tensions in pixie disco land". "Triumph of a Heart" also features orchestral arrangements by the Icelandic and London Choirs, as well as hooks coming from a "human trombone", the singer Gregory Purnhagen, and beatboxers Rahzel and Dokaka. Sal Cinquemani from Slant Magazine said the track "could be described as "future disco", with human voices subbing for bass kick, horns, house snare, and oscillating synthesizers".
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