The Complementary Role of Dominant Designs and Industry Standards

Poly (ADP-ribose) polymerases (PARP) 1-3 are well-known multi-domain enzymes, catalysing the covalent modification of proteins, DNA, and themselves. They attach mono- or poly-ADP-ribose to targets using NAD+ as a substrate. Poly-ADP-ribosylation (PARylation) is central to the important functions of PARP enzymes in the DNA damage response and nucleosome remodelling. Activation of PARP happens through DNA binding via zinc fingers and/or the WGR domain. Modulation of their activity using PARP inhibitors occupying the NAD+ binding site has proven successful in cancer therapies. For decades, studies set out to elucidate their full-length molecular structure and activation mechanism. In the last five years, significant advances have progressed the structural and functional understanding of PARP1-3, such as understanding allosteric activation via inter-domain contacts, how PARP senses damaged DNA in the crowded nucleus, and the complementary role of histone PARylation factor 1 in modulating the active site of PARP. Here, we review these advances together with the versatility of PARP domains involved in DNA binding, the targets and shape of PARylation and the role of PARPs in nucleosome remodelling.

Download Full-text

Calibrating the CreditRisk+ Model at Different Time Scales and in Presence of Temporal Autocorrelation †

Mathematics ◽

10.3390/math9141679 ◽

2021 ◽

Vol 9 (14) ◽

pp. 1679

Author(s):

Jacopo Giacomelli ◽

Luca Passalacqua

Keyword(s):

Time Series ◽

Default Risk ◽

Real Life ◽

Statistical Error ◽

Real Data ◽

Sampling Period ◽

Calibration Procedure ◽

Industry Standards ◽

Default Rate

The CreditRisk+ model is one of the industry standards for the valuation of default risk in credit loans portfolios. The calibration of CreditRisk+ requires, inter alia, the specification of the parameters describing the structure of dependence among default events. This work addresses the calibration of these parameters. In particular, we study the dependence of the calibration procedure on the sampling period of the default rate time series, that might be different from the time horizon onto which the model is used for forecasting, as it is often the case in real life applications. The case of autocorrelated time series and the role of the statistical error as a function of the time series period are also discussed. The findings of the proposed calibration technique are illustrated with the support of an application to real data.

Download Full-text

Changing paradigm for treatment of heavily calcified coronary artery disease. A complementary role of rotational atherectomy and intravascular lithotripsy with shockwave balloon: a case report

European Heart Journal - Case Reports ◽

10.1093/ehjcr/ytaa456 ◽

2020 ◽

Author(s):

Shana Tehrani ◽

Sudhir Rathore ◽

Vinod Achan

Keyword(s):

Coronary Artery ◽

Interventional Cardiology ◽

Rotational Atherectomy ◽

Stent Restenosis ◽

Case Summary ◽

Stent Expansion ◽

Complementary Role ◽

Artery Disease ◽

Stenotic Lesions

Abstract Background Management of heavily calcified coronary arteries is still a major challenge in interventional cardiology. Inadequate stent expansion in calcific lesions is the single most important predictor of stent thrombosis and in-stent restenosis. Rotational atherectomy (RA) is an important tool to modify the calcium burden but is associated with limitations and requires specific skills. Intravascular lithotripsy (IVL) is a novel technique to treat calcified stenotic lesions and has been proposed as an alternative to RA with promising results. Case summary We report a case of a patient with severely calcified right coronary artery stenosis successfully treated with combination of RA and IVL. Discussion In this case, we demonstrate that the RA and IVL are complementary strategies, not sufficient on their own and not alternative to each other.

Download Full-text