The accuracy of extrapolation methods; an automatic box–jenkins package sift

Hill and Woodworth (1980) proposed an algorithm suitable for identifying Box–Jenkins models automatically without reliance on the investigator. This paper first reviews the method. It is then used on the 111 series analysed by Anderson in the Makridakis forecasting competition. The results show that the automatic method of Hill and Woodworth is comparable in terms of accuracy to the full Box–Jenkins identification procedure.     

Rauwolfia alkaloids XXXV. potent,fast-acting sedatives derived from methyl reserpate

Zusammenfassung Durch Umsetzung des Methyl-Reserpates (Ic) mit Diazomethan in Gegenwart von Fluoborsäure wird 18-O-Methylreserpsäure-methylester (Id) gewonnen. Reaktion des 18-O-p-Brombenzolsulfonylreserpsäure-methylesters (Ie) mit Methanol und Triäthylamin führt dagegen zum isomeren 18-epi-Methyläther (IIa). Diese Produkte, und besonders ihre wasserlöslichen Hydrochloride, besitzen ausgeprägte sedative Eigenschaften mit schnellem Wirkungseintritt; sie sind aber nicht hypotensiv wirksam.     

AGPAT2 is mutated in congenital generalized lipodystrophy linked to chromosome 9q34

Congenital generalized lipodystrophy is an autosomal recessive disorder characterized by marked paucity of adipose tissue, extreme insulin resistance, hypertriglyceridemia, hepatic steatosis and early onset of diabetes. We report several different mutations of the gene (AGPAT2) encoding 1-acylglycerol-3-phosphate O-acyltransferase 2 in 20 affected individuals from 11 pedigrees of diverse ethnicities showing linkage to chromosome 9q34. The AGPAT2 enzyme catalyzes the acylation of lysophosphatidic acid to form phosphatidic acid, a key intermediate in the biosynthesis of triacylglycerol and glycerophospholipids. AGPAT2 mRNA is highly expressed in adipose tissue. We conclude that mutations in AGPAT2 may cause congenital generalized lipodystrophy by inhibiting triacylglycerol synthesis and storage in adipocytes.     

Segregation at three loci explains familial and population risk in Hirschsprung disease

Hirschsprung disease (HSCR), the most common hereditary cause of intestinal obstruction, shows considerable variation and complex inheritance. Coding sequence mutations in RET, GDNF, EDNRB, EDN3 and SOX10 lead to long-segment (L-HSCR) and syndromic HSCR but fail to explain the transmission of the much more common short-segment form (S-HSCR). We conducted a genome scan in families with S-HSCR and identified susceptibility loci at 3p21, 10q11 and 19q12 that seem to be necessary and sufficient to explain recurrence risk and population incidence. The gene at 10q11 is probably RET, supporting its crucial role in all forms of HSCR; however, coding sequence mutations are present in only 40% of linked families, suggesting the importance of noncoding variation. Here we show oligogenic inheritance of S-HSCR, the 3p21 and 19q12 loci as RET-dependent modifiers, and a parent-of-origin effect at RET. This study demonstrates by a complete genetic dissection why the inheritance pattern of S-HSCR is nonmendelian.