Oscillatory responses in cat visual cortex exhibit inter-columnar synchronization which reflects global stimulus properties

A fundamental step in visual pattern recognition is the establishment of relations between spatially separate features. Recently, we have shown that neurons in the cat visual cortex have oscillatory responses in the range 40-60 Hz (refs 1, 2) which occur in synchrony for cells in a functional column and are tightly correlated with a local oscillatory field potential. This led us to hypothesize that the synchronization of oscillatory responses of spatially distributed, feature selective cells might be a way to establish relations between features in different parts of the visual field. In support of this hypothesis, we demonstrate here that neurons in spatially separate columns can synchronize their oscillatory responses. The synchronization has, on average, no phase difference, depends on the spatial separation and the orientation preference of the cells and is influenced by global stimulus properties.     

Selective effects of cyclosporin A on colony-forming lymphoid and myeloid cells in man

THE properties of the fungus metabolite, cyclosporin A, have suggested its potential as a clinically valuable immunosup-pressive agent(1,2). Experiments in animals have demonstrated that its suppressive action against cell-mediated and humoral immunity is not accompanied by any appreciable myelotoxicity(3,4). In this respect, cyclosporin A contrasts with other immunosuppressants in current use, such as antilymphocyte globulin and azathioprine. There are, however, few data to substantiate a selective toxicity of cyclosporin A against human lymphocytes. Here, we have compared its effects against human lymphoid and myeloid cells, using colony formation by the different cell types as the end point. We found that the compound exhibited far greater toxicity towards a sub-population of T cells than towards either B lymphocytes or haematopoietic precursor cells.     

Postzygotic HRAS and KRAS mutations cause nevus sebaceous and Schimmelpenning syndrome

Nevus sebaceous is a common congenital cutaneous malformation. Affected individuals may develop benign and malignant secondary tumors in the nevi during life. Schimmelpenning syndrome is characterized by the association of nevus sebaceous with extracutaneous abnormalities. We report that of 65 sebaceous nevi studied, 62 (95%) had mutations in the HRAS gene and 3 (5%) had mutations in the KRAS gene. The HRAS c.37G>C mutation, which results in a p.Gly13Arg substitution, was present in 91% of lesions. Nonlesional tissues from 18 individuals had a wild-type sequence, confirming genetic mosaicism. The HRAS c.37G>C mutation was also found in 8 of 8 associated secondary tumors. Mosaicism for HRAS c.37G>C and KRAS c.35G>A mutations was found in two individuals with Schimmelpenning syndrome. Functional analysis of HRAS c.37G>C mutant cells showed constitutive activation of the MAPK and PI3K-Akt signaling pathways. Our results indicate that nevus sebaceous and Schimmelpenning syndrome are caused by postzygotic HRAS and KRAS mutations. These mutations may predispose individuals to the development of secondary tumors in nevus sebaceous.     

Membrane-traversing mechanism of thyroid hormone transport by monocarboxylate transporter 8

Monocarboxylate transporter 8 (MCT8) mediates thyroid hormone (TH) transport across the plasma membrane in many cell types. In order to better understand its mechanism, we have generated three new MCT8 homology models based on sugar transporters XylE in the intracellular opened (PDB ID: 4aj4) and the extracellular partly occluded (PDB ID: 4gby) conformations as well as FucP (PDB ID: 3o7q) and GLUT3 (PDB ID: 4zwc) in the fully extracellular opened conformation. T₃-docking studies from both sides revealed interactions with His192, His415, Arg445 and Asp498 as previously identified. Selected mutations revealed further transport-sensitive positions mainly at the discontinuous transmembrane helices TMH7 and 10. Lys418 is potentially involved in neutralising the charge of the TH substrate because it can be replaced by charged, but not by uncharged, amino acids. The side chain of Thr503 was hypothesised to stabilise a helix break at TMH10 that undergoes a prominent local shift during the transport cycle. A T503V mutation accordingly affected transport. The aromatic Tyr419, the polar Ser313 and Ser314 as well as the charged Glu422 and Glu423 lining the transport channel have been studied. Based on related sugar transporters, we suggest an alternating access mechanism for MCT8 involving a series of amino acid positions previously and newly identified as critical for transport.     

Variable selection and oversampling in the use of smooth support vector machines for predicting the default risk of companies

In the era of Basel II a powerful tool for bankruptcy prognosis is vital for banks. The tool must be precise but also easily adaptable to the bank's objectives regarding the relation of false acceptances (Type I error) and false rejections (Type II error). We explore the suitability of smooth support vector machines (SSVM), and investigate how important factors such as the selection of appropriate accounting ratios (predictors), length of training period and structure of the training sample influence the precision of prediction. Moreover, we show that oversampling can be employed to control the trade‐off between error types, and we compare SSVM with both logistic and discriminant analysis. Finally, we illustrate graphically how different models can be used jointly to support the decision‐making process of loan officers. Copyright © 2008 John Wiley & Sons, Ltd.     

Blood pressure lowering effect of eicosapentaenoic acid-rich diet in normotensive,hypertensive and hyperlipemic subjects

Summary A mackerel diet or a herring diet in which two cans of fish fillet were consumed daily over 2 weeks within a prescribed regimen, in a crossover design, were given to 15 normotensive volunteers, 14 patients with mild essential hypertension and eight patients with type IV and V hyperlipoproteinemia (HLP). In normotensives a markedly lower systolic and diastolic blood pressure at the end of the period on the mackerel diet could be observed, whereas in hypertensive and hyperlipemic subjects only systolic blood pressure was significantly decreased. After the herring diet, which served as control, changes in blood pressure were of a minor degree.