The Spanish Pension System: Overview and Long-Term Projections

In the middle of the so-called pension crisis, the ageing of population and the sharp decrease in affiliations to Social Security are threatening the well-functioning of the Spanish public pension system. The purpose of this paper is to present the main challenges to be faced by the Spanish pension system, as well as to shed light on the main determinants that will condition the evolution of pension expenditure over GDP along the following decades. This quantitative analysis, which considers the 2011 and 2013 pension reforms, uses the latest data on the Spanish demographic, labor market and institutional factors in order to project the evolution of the system from the expenditure side up to 2060. For the purpose of analyzing the dynamics and the underlying drivers of pension expenditure, the so-called aggregate accounting approach will be utilized. The alternative scenarios proposed allow for exploring the robustness of the results within the baseline scenario, which constitutes the reference point of projections in the exercise. The analysis concludes that, by the end of the projected period, Spain will count on a similar public pension expenditure ratio as the current one.

An update of the J48Consolidated WEKA’s class: CTC algorithm enhanced with the notion of coverage

This document aims to describe an update of the implementation of the J48Consolidated class within WEKA platform. The J48Consolidated class implements the CTC algorithm [2][3] which builds a unique decision tree based on a set of samples. The J48Consolidated class extends WEKA’s J48 class which implements the well-known C4.5 algorithm. This implementation was described in the technical report "J48Consolidated: An implementation of CTC algorithm for WEKA". The main, but not only, change in this update is the integration of the notion of coverage in order to determine the number of samples to be generated to build a consolidated tree. We define coverage as the percentage of examples of the training sample present in –or covered by– the set of generated subsamples. So, depending on the type of samples that we use, we will need more or less samples in order to achieve a specific value of coverage.

Structure-function analysis of USP1: insights into the role of Ser313 phosphorylation site and the effect of cancer-associated mutations on autocleavage

Background: In complex with its cofactor UAF1, the USP1 deubiquitinase plays an important role in cellular processes related to cancer, including the response to DNA damage. The USP1/UAF1 complex is emerging as a novel target in cancer therapy, but several aspects of its function and regulation remain to be further clarified. These include the role of the serine 313 phosphorylation site, the relative contribution of different USP1 sequence motifs to UAF1 binding, and the potential effect of cancer-associated mutations on USP1 regulation by autocleavage. Methods: We have generated a large set of USP1 structural variants, including a catalytically inactive form (C90S), non-phosphorylatable (S313A) and phosphomimetic (S313D) mutants, deletion mutants lacking potential UAF1 binding sites, a mutant (GG/AA) unable to undergo autocleavage at the well-characterized G670/G671 diglycine motif, and four USP1 mutants identified in tumor samples that cluster around this cleavage site (G667A, L669P, K673T and A676T). Using cell-based assays, we have determined the ability of these mutants to bind UAF1, to reverse DNA damage-induced monoubiquitination of PCNA, and to undergo autocleavage. Results: A non-phosphorylatable S313A mutant of USP1 retained the ability to bind UAF1 and to reverse PCNA ubiquitination in cell-based assays. Regardless of the presence of a phosphomimetic S313D mutation, deletion of USP1 fragment 420-520 disrupted UAF1 binding, as determined using a nuclear relocation assay. The UAF1 binding site in a second UAF1-interacting DUB, USP46, was mapped to a region homologous to USP1(420-520). Regarding USP1 autocleavage, co-expression of the C90S and GG/AA mutants did not result in cleavage, while the cancer-associated mutation L669P was found to reduce cleavage efficiency. Conclusions: USP1 phosphorylation at S313 is not critical for PCNA deubiquitination, neither for binding to UAF1 in a cellular environment. In this context, USP1 amino acid motif 420-520 is necessary and sufficient for UAF1 binding. This motif, and a homologous amino acid segment that mediates USP46 binding to UAF1, map to the Fingers sub-domain of these DUBs. On the other hand, our results support the view that USP1 autocleavage may occur in cis, and can be altered by a cancer-associated mutation.