Forecasting Longevity Gains Using a Seemingly Unrelated Time Series Model

In this paper a multivariate time series model using the seemingly unrelated time series equation (SUTSE) framework is proposed to forecast longevity gains. The proposed model is represented in state space form and uses Kalman filtering to estimate the unobservable components and fixed parameters. We apply the model both to male mortality rates in Portugal and the USA. Our results compare favorably, in terms of mean absolute percentage error, in‐sample and out‐of‐sample, to those obtained by the Lee–Carter method and some of its extensions. Copyright © 2015 John Wiley & Sons, Ltd.     

A decision rule to minimize daily capital charges in forecasting value‐at‐risk

Under the Basel II Accord, banks and other authorized deposit‐taking institutions (ADIs) have to communicate their daily risk estimates to the monetary authorities at the beginning of the trading day, using a variety of value‐at‐risk (VaR) models to measure risk. Sometimes the risk estimates communicated using these models are too high, thereby leading to large capital requirements and high capital costs. At other times, the risk estimates are too low, leading to excessive violations, so that realized losses are above the estimated risk. In this paper we analyze the profit‐maximizing problem of an ADI subject to capital requirements under the Basel II Accord as ADIs have to choose an optimal VaR reporting strategy that minimizes daily capital charges. Accordingly, we suggest a dynamic communication and forecasting strategy that responds to violations in a discrete and instantaneous manner, while adapting more slowly in periods of no violations. We apply the proposed strategy to Standard & Poor's 500 Index and show there can be substantial savings in daily capital charges, while restricting the number of violations to within the Basel II penalty limits. Copyright © 2009 John Wiley & Sons, Ltd.     

Natural variation at Strubbelig Receptor Kinase 3 drives immune-triggered incompatibilities between Arabidopsis thaliana accessions

Accumulation of genetic incompatibilities within species can lead to reproductive isolation and, potentially, speciation. In this study, we show that allelic variation at SRF3 (Strubbelig Receptor Family 3), encoding a receptor-like kinase, conditions the occurrence of incompatibility between Arabidopsis thaliana accessions. The geographical distribution of SRF3 alleles reveals that allelic forms causing epistatic incompatibility with a Landsberg erecta allele at the RPP1 resistance locus are present in A. thaliana accessions in central Asia. Incompatible SRF3 alleles condition for an enhanced early immune response to pathogens as compared to the resistance-dampening effect of compatible SRF3 forms in isogenic backgrounds. Variation in disease susceptibility suggests a basis for the molecular patterns of a recent selective sweep detected at the SRF3 locus in central Asian populations.     

Common variants at TRAF3IP2 are associated with susceptibility to psoriatic arthritis and psoriasis

Psoriatic arthritis (PsA) is an inflammatory joint disease that is distinct from other chronic arthritides and which is frequently accompanied by psoriasis vulgaris (PsV) and seronegativity for rheumatoid factor. We conducted a genome-wide association study in 609 German individuals with PsA (cases) and 990 controls with replication in 6 European cohorts including a total of 5,488 individuals. We replicated PsA associations at HLA-C and IL12B and identified a new association at TRAF3IP2 (rs13190932, P = 8.56 × 10?1?). TRAF3IP2 was also associated with PsV in a German cohort including 2,040 individuals (rs13190932, P = 1.95 × 10?3). Sequencing of the exons of TRAF3IP2 identified a coding variant (p.Asp10Asn, rs33980500) as the most significantly associated SNP (P = 1.13 × 10?2?, odds ratio = 1.95). Functional assays showed reduced binding of this TRAF3IP2 variant to TRAF6, suggesting altered modulation of immunoregulatory signals through altered TRAF interactions as a new and shared pathway for PsA and PsV.     

Potassium and sodium transport in non-animal cells: the Trk/Ktr/HKT transporter family

Bacterial Trk and Ktr, fungal Trk and plant HKT form a family of membrane transporters permeable to K⁺ and/or Na⁺ and characterized by a common structure probably derived from an ancestral K⁺ channel subunit. This transporter family, specific of non-animal cells, displays a large diversity in terms of ionic permeability, affinity and energetic coupling (H⁺–K⁺ or Na⁺–K⁺ symport, K⁺ or Na⁺ uniport), which might reflect a high need for adaptation in organisms living in fluctuating or dilute environments. Trk/Ktr/HKT transporters are involved in diverse functions, from K⁺ or Na⁺ uptake to membrane potential control, adaptation to osmotic or salt stress, or Na⁺ recirculation from shoots to roots in plants. Structural analyses of bacterial Ktr point to multimeric structures physically interacting with regulatory subunits. Elucidation of Trk/Ktr/HKT protein structures along with characterization of mutated transporters could highlight functional and evolutionary relationships between ion channels and transporters displaying channel-like features.     

L’émergence contrariée du chronographe imprimant dans les observatoires français (fin 19e – début 20e s.)

Les observatoires occidentaux se transforment en véritable usine scientifique à partir du milieu du 19^e siècle. L'astrométrie symbolise ce passage à une économie industrieuse des pratiques scientifiques. Le chronographe imprimant, qui permet de réduire les équations personnelles des observateurs, s'impose, d'abord aux Etats-Unis, puis en Angleterre, en instrument-emblème de cette transformation profonde. En France, les initiatives de l'astronome Liais restent prototypiques. Ce n'est qu'au début du 20^e siècle, par les voies détournées de l'observatoire d'Hendaye et de l'abbé Verschaffel, que le chronographe imprimant fait son retour et conquiert les espaces savants. La centralisation excessive de l'astronomie française, l'autoritarisme du directeur de l'Observatoire de Paris Urbain Le Verrier, et la faiblesse du marché des instruments expliquent pourquoi le chronographe imprimant n'a fait souche que très tardivement en France.     

Extensive characterization of sphere models established from colorectal cancer cell lines

Links between cancer and stem cells have been proposed for many years. As the cancer stem cell (CSC) theory became widely studied, new methods were developed to culture and expand cancer cells with conserved determinants of “stemness”. These cells show increased ability to grow in suspension as spheres in serum-free medium supplemented with growth factors and chemicals. The physiological relevance of this phenomenon in established cancer cell lines remains unclear. Cell lines have traditionally been used to explore tumor biology and serve as preclinical models for the screening of potential therapeutic agents. Here, we grew cell-forming spheres (CFS) from 25 established colorectal cancer cell lines. The molecular and cellular characteristics of CFS were compared to the bulk of tumor cells. CFS could be isolated from 72 % of the cell lines. Both CFS and their parental CRC cell lines were highly tumorigenic. Compared to their parental cells, they showed similar expression of putative CSC markers. The ability of CRC cells to grow as CFS was greatly enhanced by prior treatment with 5-fluorouracil. At the molecular level, CFS and parental CRC cells showed identical gene mutations and very similar genomic profiles, although microarray analysis revealed changes in CFS gene expression that were independent of DNA copy-number. We identified a CFS gene expression signature common to CFS from all CRC cell lines, which was predictive of disease relapse in CRC patients. In conclusion, CFS models derived from CRC cell lines possess interesting phenotypic features that may have clinical relevance for drug resistance and disease relapse.     

The LRRK2 G2019S mutant exacerbates basal autophagy through activation of the MEK/ERK pathway

Mutations in leucine-rich repeat kinase 2 (LRRK2) are a major cause of familial Parkinsonism, and the G2019S mutation of LRRK2 is one of the most prevalent mutations. The deregulation of autophagic processes in nerve cells is thought to be a possible cause of Parkinson’s disease (PD). In this study, we observed that G2019S mutant fibroblasts exhibited higher autophagic activity levels than control fibroblasts. Elevated levels of autophagic activity can trigger cell death, and in our study, G2019S mutant cells exhibited increased apoptosis hallmarks compared to control cells. LRRK2 is able to induce the phosphorylation of MAPK/ERK kinases (MEK). The use of 1,4-diamino-2,3-dicyano-1,4-bis[2-aminophenylthio]butadiene (U0126), a highly selective inhibitor of MEK1/2, reduced the enhanced autophagy and sensibility observed in G2019S LRRK2 mutation cells. These data suggest that the G2019S mutation induces autophagy via MEK/ERK pathway and that the inhibition of this exacerbated autophagy reduces the sensitivity observed in G2019S mutant cells.