Combining expert‐adjusted forecasts

It is well known that a combination of model‐based forecasts can improve upon each of the individual constituent forecasts. Most forecasts available in practice are, however, not purely based on econometric models but entail adjustments, where experts with domain‐specific knowledge modify the original model forecasts. There is much evidence that expert‐adjusted forecasts do not necessarily improve the pure model‐based forecasts. In this paper we show, however, that combined expert‐adjusted model forecasts can improve on combined model forecasts, in the case when the individual expert‐adjusted forecasts are not better than their associated model‐based forecasts. We discuss various implications of this finding.     

Exploiting Spillovers to Forecast Crashes

We develop Hawkes models in which events are triggered through self‐excitation as well as cross‐excitation. We examine whether incorporating cross‐excitation improves the forecasts of extremes in asset returns compared to only self‐excitation. The models are applied to US stocks, bonds and dollar exchange rates. We predict the probability of crashes in the series and the value at risk (VaR) over a period that includes the financial crisis of 2008 using a moving window. A Lagrange multiplier test suggests the presence of cross‐excitation for these series. Out‐of‐sample, we find that the models that include spillover effects forecast crashes and the VaR significantly more accurately than the models without these effects. Copyright © 2016 John Wiley & Sons, Ltd.     

Chymotrypsin C (CTRC) variants that diminish activity or secretion are associated with chronic pancreatitis

Chronic pancreatitis is a persistent inflammatory disease of the pancreas, in which the digestive protease trypsin has a fundamental pathogenetic role. Here we have analyzed the gene encoding the trypsin-degrading enzyme chymotrypsin C (CTRC) in German subjects with idiopathic or hereditary chronic pancreatitis. Two alterations in this gene, p.R254W and p.K247_R254del, were significantly overrepresented in the pancreatitis group, being present in 30 of 901 (3.3%) affected individuals but only 21 of 2,804 (0.7%) controls (odds ratio (OR) = 4.6; confidence interval (CI) = 2.6-8.0; P = 1.3 x 10(-7)). A replication study identified these two variants in 10 of 348 (2.9%) individuals with alcoholic chronic pancreatitis but only 3 of 432 (0.7%) subjects with alcoholic liver disease (OR = 4.2; CI = 1.2-15.5; P = 0.02). CTRC variants were also found in 10 of 71 (14.1%) Indian subjects with tropical pancreatitis but only 1 of 84 (1.2%) healthy controls (OR = 13.6; CI = 1.7-109.2; P = 0.0028). Functional analysis of the CTRC variants showed impaired activity and/or reduced secretion. The results indicate that loss-of-function alterations in CTRC predispose to pancreatitis by diminishing its protective trypsin-degrading activity.     

Mutations in different components of FGF signaling in LADD syndrome

Lacrimo-auriculo-dento-digital (LADD) syndrome is characterized by lacrimal duct aplasia, malformed ears and deafness, small teeth and digital anomalies. We identified heterozygous mutations in the tyrosine kinase domains of the genes encoding fibroblast growth factor receptors 2 and 3 (FGFR2, FGFR3) in LADD families, and in one further LADD family, we detected a mutation in the gene encoding fibroblast growth factor 10 (FGF10), a known FGFR ligand. These findings increase the spectrum of anomalies associated with abnormal FGF signaling.     

Mutation of RRM2B, encoding p53-controlled ribonucleotide reductase (p53R2), causes severe mitochondrial DNA depletion

Mitochondrial DNA (mtDNA) depletion syndrome (MDS; MIM 251880) is a prevalent cause of oxidative phosphorylation disorders characterized by a reduction in mtDNA copy number. The hitherto recognized disease mechanisms alter either mtDNA replication (POLG (ref. 1)) or the salvage pathway of mitochondrial deoxyribonucleosides 5'-triphosphates (dNTPs) for mtDNA synthesis (DGUOK (ref. 2), TK2 (ref. 3) and SUCLA2 (ref. 4)). A last gene, MPV17 (ref. 5), has no known function. Yet the majority of cases remain unexplained. Studying seven cases of profound mtDNA depletion (1-2% residual mtDNA in muscle) in four unrelated families, we have found nonsense, missense and splice-site mutations and in-frame deletions of the RRM2B gene, encoding the cytosolic p53-inducible ribonucleotide reductase small subunit. Accordingly, severe mtDNA depletion was found in various tissues of the Rrm2b-/- mouse. The mtDNA depletion triggered by p53R2 alterations in both human and mouse implies that p53R2 has a crucial role in dNTP supply for mtDNA synthesis.     

Ein Sensibilisator der therapeutischen Digitaliswirkung

Summary Complexes of bivalent tin with polyoxybenzene-polysulfonic acids have a diuretic effect, when injected subcutaneously in dogs or rabbits. The same compounds also sensibilize the cardiotonic effect of digitalis-substances on the isolated heart or on fragments of the isolated heart as usually employed for testing digitalis-substances.In a small number of patients suffering from heart disease, a rapid increase of their till then lowered diuresis was induced through subcutaneous injections of a solution of the above mentioned tin complex.     

Hydrodynamisches Ähnlichkeitsprinzip zur Bestimmung von Gelstrukturen aus Durchströmungsversuchen

Summary The permeability of jellies of known structure can be determined by experiments on models by application of a principle of hydrodynamical similarity.     

Jun Ishiwaras Text über Albert Einsteins Gastvortrag an der Universität zu Kyoto am 14. Dezember 1922

Ohne Zusammenfassung Vorgelegt von B. L. van der Waerden     

The mode of formation of intracytoplasmic structures in tumours induced by viruses of the avian sarcoma leucosis group

Zusammenfassung Die durch Viren der Vögel-Sarkom-Leukose-Gruppe hervorgerufenen intrazytoplasmatischen Strukturen sind sehr wahrscheinlich Immunpräzipitate.

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This paper is dedicated to Prof.H. Lettré on the occasion of his 60th birthday.     

Genetics: relatedness among east African coelacanths

Coelacanths were discovered in the Comoros archipelago to the northwest of Madagascar in 1952. Since then, these rare, ancient fish have been found to the south off Mozambique, Madagascar and South Africa, and to the north off Kenya and Tanzania -- but it was unclear whether these are separate populations or even subspecies. Here we show that the genetic variation between individuals from these different locations is unexpectedly low. Combined with earlier results from submersible and oceanographic observations, our findings indicate that a separate African metapopulation is unlikely to have existed and that locations distant from the Comoros were probably inhabited relatively recently by either dead-end drifters or founders that originated in the Comoros.