A novel viral oncogene with structural similarity to phospholipase C

Numerous oncogenes have been isolated from acutely transforming retroviruses. To date, the products of these viral oncogenes have been protein kinases, nuclear proteins, growth factors, or GTP-binding proteins. We have cloned the previously uncharacterized avian sarcoma virus CT10 and sequenced its genome. This virus encodes a protein, p47gag-crk, that has blocks of sequence similarity to the amino-terminal, non-catalytic region of the non-receptor class of tyrosine kinases. In addition, the structure of p47gag-crk has striking similarity to a 180-amino acid region of bovine brain phospholipase C. Biochemical data suggest that p47gag-crk activates one or several endogenous tyrosine kinases.     

Retinoids,a new class of compounds with prophylactic and therapeutic activities in oncology and dermatology

Summary A review of recent investigations in the retinoid field is presented. Retinoic acid exerts a prophylactic and a therapeutic effect on chemically induced benign and malignant epithelial tumors in mice. In clinical studies positive therapeutic results have been obtained in patients with preneoplastic and neoplastic epithelial lesions. However, treatment with retinoic acid is limited by serious side effects (hypervitaminosis A syndrome). Therefore, the synthesis of analogs of retinoic acid (retinoids) possessing a more favorable therapeutic ratio has been initiated. Among a large series of synthesized compounds, certain aromatic analogs proved to have a particularly favorable therapeutic ratio. The structure-activity relationship of the most active retinoids is discussed including some biological data concerning prophylaxis and therapy of epithelial tumors. The total synthesis of retinoids according to various building schemes is discussed in detail. Methods for the synthesis of the cyclic end group, of the polyene chain component, and of the full retinoid skeleton are described. Metabolic studies of retinoic acid and of the most active retinoid, as well as the synthesis of some isolated metabolites are outlined. Suggestions concerning the mechanism of action of retinoids are made. Some clinical results on the treatment of acne, psoriasis and precancerous conditions are reported.Based on a lecture presented at the Symposium on Horizons in Medicinal Chemistry, Centennial ACS Meeting, New York, 6 April, 1976.     

Effect of 2-Br-α-ergokryptine (CB 154) on lactation in the bitch

Zusammenfassung Es wurde gezeigt, dass bei Hündinnen die Lactation durch den Prolactin-Sekretionshemmer 2-Br--Ergokryptin-methanesulfonat (CB 154, Sandoz) gehemmt wird. Gemessen über 24 Stunden beträgt die ED₅₀ i.m. 6 g/kg.     

均匀细圆环和均匀薄圆盘对任意轴线的转动惯量

分别运用一般方法和投影法计算了均匀细圆环和均匀薄圆盘对任意轴线的转动惯量,在验证投影法计算结果正确性的基础上,对计算结果进行了讨论,可以用于对实际问题的分析研究.     

Glutamate receptors at atomic resolution

At synapses throughout the brain and spinal cord, the amino-acid glutamate is the major excitatory neurotransmitter. During evolution, a family of glutamate-receptor ion channels seems to have been assembled from a kit consisting of discrete ligand-binding, ion-channel, modulatory and cytoplasmic domains. Crystallographic studies that exploit this unique architecture have greatly aided structural analysis of the ligand-binding core, but the results also pose a formidable challenge, namely that of resolving the allosteric mechanisms by which individual domains communicate and function in an intact receptor.     

Impact of corrections for dynamic selection bias on forecasts of retention behavior

We investigate the impact of corrections for dynamic selection bias on forecasting accuracy in a multi‐period stay/leave model. While corrections for selection bias are needed for consistent coefficient estimates, they do not necessarily produce more accurate forecasts than uncorrected techniques. Theorem 1 shows that, apart from estimation errors, a shrinkage principle applies: the heterogeneity restriction imposed by uncorrected and combination techniques improves accuracy for forecasting individuals that leave, and hurts accuracy for forecasting individuals that stay. This has important implications for decision making because of the potential for asymmetric losses. We also present an illustrative empirical application and results from Monte Carlo experiments. We find that differences in relative accuracy vary directly with the degree of selection bias and inversely with the percentage of the initial population that stays. Copyright © 2007 John Wiley & Sons, Ltd.