Model‐based forecast adjustment: With an illustration to inflation

This paper introduces the idea of adjusting forecasts from a linear time series model where the adjustment relies on the assumption that this linear model is an approximation of a nonlinear time series model. This way of creating forecasts could be convenient when inference for a nonlinear model is impossible, complicated or unreliable in small samples. The size of the forecast adjustment can be based on the estimation results for the linear model and on other data properties such as the first few moments or autocorrelations. An illustration is given for a first‐order diagonal bilinear time series model, which in certain properties can be approximated by a linear ARMA(1, 1) model. For this case, the forecast adjustment is easy to derive, which is convenient as the particular bilinear model is indeed cumbersome to analyze in practice. An application to a range of inflation series for low‐income countries shows that such adjustment can lead to some improved forecasts, although the gain is small for this particular bilinear time series model.     

Evaluating Forecasts of a Vector of Variables: A German Forecasting Competition

In this paper we explore methodologies appropriate for evaluating a forecasting competition when the participants predict a number of variables that may be related to each other and are judged for a single period. Typically, forecasting competitions are judged on a variable‐by‐variable basis, but a multivariate analysis is required to determine how each competitor performed overall. We use three different multivariate tests to determine an overall winner for a forecasting competition for the German economy across 25 different institutions for a single time period using a vector of eight key economic variables. We find that neglecting the cross‐variable relationships greatly alters the outcome of the forecasting competition. Copyright © 2016 John Wiley & Sons, Ltd.     

A Bayesian analysis of periodic integration

Recent empirical research into the seasonal and trend properties of macroeconomic time series using periodic models has resulted in strong evidence in favour of periodic integration (PI). PI implies that the differencing filter necessary to remove a stochastic trend varies across seasons and, hence, that seasonal fluctuations are related to the stochastic trend. Previous studies finding evidence of PI have used classical econometric techniques. In this paper, we investigate the possible sensitivity of this empirical result by using Bayesian techniques. An application of posterior odds analysis and highest posterior density interval tests to several quarterly UK macroeconomic series suggests strong evidence for PI, even when we allow for structural breaks in the deterministic seasonals. A predictive exercise indicates that PI usually outperforms other competing models in terms of out-of-sample forecasting. © 1997 John Wiley & Sons, Ltd.     

Forecasting stock market volatility using (non-linear) Garch models

In this paper we study the performance of the GARCH model and two of its non-linear modifications to forecast weekly stock market volatility. The models are the Quadratic GARCH (Engle and Ng, 1993) and the Glosten, Jagannathan and Runkle (1992) models which have been proposed to describe, for example, the often observed negative skewness in stock market indices. We find that the QGARCH model is best when the estimation sample does not contain extreme observations such as the 1987 stock market crash and that the GJR model cannot be recommended for forecasting.     

SLX4, a coordinator of structure-specific endonucleases, is mutated in a new Fanconi anemia subtype

DNA interstrand crosslink repair requires several classes of proteins, including structure-specific endonucleases and Fanconi anemia proteins. SLX4, which coordinates three separate endonucleases, was recently recognized as an important regulator of DNA repair. Here we report the first human individuals found to have biallelic mutations in SLX4. These individuals, who were previously diagnosed as having Fanconi anemia, add SLX4 as an essential component to the FA-BRCA genome maintenance pathway.     

A degradation-sensitive anionic trypsinogen (PRSS2) variant protects against chronic pancreatitis

Chronic pancreatitis is a common inflammatory disease of the pancreas. Mutations in the genes encoding cationic trypsinogen (PRSS1) and the pancreatic secretory trypsin inhibitor (SPINK1) are associated with chronic pancreatitis. Because increased proteolytic activity owing to mutated PRSS1 enhances the risk for chronic pancreatitis, mutations in the gene encoding anionic trypsinogen (PRSS2) may also predispose to disease. Here we analyzed PRSS2 in individuals with chronic pancreatitis and controls and found, to our surprise, that a variant of codon 191 (G191R) is overrepresented in control subjects: G191R was present in 220/6,459 (3.4%) controls but in only 32/2,466 (1.3%) affected individuals (odds ratio 0.37; P = 1.1 x 10(-8)). Upon activation by enterokinase or trypsin, purified recombinant G191R protein showed a complete loss of trypsin activity owing to the introduction of a new tryptic cleavage site that renders the enzyme hypersensitive to autocatalytic proteolysis. In conclusion, the G191R variant of PRSS2 mitigates intrapancreatic trypsin activity and thereby protects against chronic pancreatitis.     

Mutations in the gene encoding the 3'-5' DNA exonuclease TREX1 cause Aicardi-Goutières syndrome at the AGS1 locus

Aicardi-Goutières syndrome (AGS) presents as a severe neurological brain disease and is a genetic mimic of the sequelae of transplacentally acquired viral infection. Evidence exists for a perturbation of innate immunity as a primary pathogenic event in the disease phenotype. Here, we show that TREX1, encoding the major mammalian 3' --> 5' DNA exonuclease, is the AGS1 gene, and AGS-causing mutations result in abrogation of TREX1 enzyme activity. Similar loss of function in the Trex1(-/-) mouse leads to an inflammatory phenotype. Our findings suggest an unanticipated role for TREX1 in processing or clearing anomalous DNA structures, failure of which results in the triggering of an abnormal innate immune response.     

Mutations in the colony stimulating factor 1 receptor (CSF1R) gene cause hereditary diffuse leukoencephalopathy with spheroids

Hereditary diffuse leukoencephalopathy with spheroids (HDLS) is an autosomal-dominant central nervous system white-matter disease with variable clinical presentations, including personality and behavioral changes, dementia, depression, parkinsonism, seizures and other phenotypes. We combined genome-wide linkage analysis with exome sequencing and identified 14 different mutations affecting the tyrosine kinase domain of the colony stimulating factor 1 receptor (encoded by CSF1R) in 14 families with HDLS. In one kindred, we confirmed the de novo occurrence of the mutation. Follow-up sequencing identified an additional CSF1R mutation in an individual diagnosed with corticobasal syndrome. In vitro, CSF-1 stimulation resulted in rapid autophosphorylation of selected tyrosine residues in the kinase domain of wild-type but not mutant CSF1R, suggesting that HDLS may result from partial loss of CSF1R function. As CSF1R is a crucial mediator of microglial proliferation and differentiation in the brain, our findings suggest an important role for microglial dysfunction in HDLS pathogenesis.     

A new species of Exitomelita (Amphipoda: Melitidae) from a deep-water wood fall in the northern Norwegian Sea

The recently erected amphipod genus Exitomelita (Tandberg et al., 2012) has so far been found only associated with the deep-water hydrothermal vent field “Loki's Castle” in the Norwegian-Greenland Sea. There it was found on the black smoker chimney walls as well as within fields of the tubeworm Sclerolinum contortum in sulphide- and methane-rich sediments surrounding the vent field. A new species has now been found in a large wood fall of pine at 2800 m depth close to this vent field. This group of amphipods is apparently confined to reduced habitats, and our data support the theory that the vent fauna in this area is closely related to fauna found on cold seeps and wood falls in the northernmost Atlantic and Arctic Oceans. Here we present morphological and molecular data and a short discussion of the habitat of the new species, in addition to a comparison with the previously described species of Exitomelita.http://www.zoobank.org/urn:lsid:zoobank.org:pub:2B0B3CC2-AB6A-4006-83BB-182280CB22B8     

Lgr5 marks cycling, yet long-lived, hair follicle stem cells

In mouse hair follicles, a group of quiescent cells in the bulge is believed to have stem cell activity. Lgr5, a marker of intestinal stem cells, is expressed in actively cycling cells in the bulge and secondary germ of telogen hair follicles and in the lower outer root sheath of anagen hair follicles. Here we show that Lgr5(+) cells comprise an actively proliferating and multipotent stem cell population able to give rise to new hair follicles and maintain all cell lineages of the hair follicle over long periods of time. Lgr5(+) progeny repopulate other stem cell compartments in the hair follicle, supporting the existence of a stem or progenitor cell hierarchy. By marking Lgr5(+) cells during trafficking through the lower outer root sheath, we show that these cells retain stem cell properties and contribute to hair follicle growth during the next anagen. Expression analysis suggests involvement of autocrine Hedgehog signaling in maintaining the Lgr5(+) stem cell population.