Stimulation of tyrosine-specific phosphorylation in vitro by insulin-like growth factor I

Several mitogens elicit tyrosine-specific protein kinase activities. Although the physiological significance of this is unclear, the generality of these reactions implies that this may be an inherent feature of growth factor-growth factor receptor interactions. The observed mitogenic properties of the polypeptide insulin-like growth factor I (IGF-I) indicated that it might also stimulate such activity. We report here that IGF-I stimulates a tyrosine-specific protein kinase in a time- and dose-dependent fashion. The close correspondence between an approximate 50% effective dose (ED50) of phosphorylation and an approximate Kd for IGF-I binding leads us to conclude that a high-affinity IGF-I receptor, not the structurally similar insulin receptor, is the mediator of IGF-I stimulated kinase activity. Immunoprecipitation indicates that both the beta-subunit of the IGF-I receptor and the beta-subunit of the insulin receptor are targets for the IGF-I-stimulated protein kinase.     

Tenascin-X deficiency mimics Ehlers-Danlos syndrome in mice through alteration of collagen deposition

Tenascin-X is a large extracellular matrix protein of unknown function. Tenascin-X deficiency in humans is associated with Ehlers-Danlos syndrome, a generalized connective tissue disorder resulting from altered metabolism of the fibrillar collagens. Because TNXB is the first Ehlers-Danlos syndrome gene that does not encode a fibrillar collagen or collagen-modifying enzyme, we suggested that tenascin-X might regulate collagen synthesis or deposition. To test this hypothesis, we inactivated Tnxb in mice. Tnxb-/- mice showed progressive skin hyperextensibility, similar to individuals with Ehlers-Danlos syndrome. Biomechanical testing confirmed increased deformability and reduced tensile strength of their skin. The skin of Tnxb-/- mice was histologically normal, but its collagen content was significantly reduced. At the ultrastructural level, collagen fibrils of Tnxb-/- mice were of normal size and shape, but the density of fibrils in their skin was reduced, commensurate with the reduction in collagen content. Studies of cultured dermal fibroblasts showed that although synthesis of collagen I by Tnxb-/- and wildtype cells was similar, Tnxb-/- fibroblasts failed to deposit collagen I into cell-associated matrix. This study confirms a causative role for TNXB in human Ehlers-Danlos syndrome and suggests that tenascin-X is an essential regulator of collagen deposition by dermal fibroblasts.     

Delineation of prognostic biomarkers in prostate cancer

Prostate cancer is the most frequently diagnosed cancer in American men. Screening for prostate-specific antigen (PSA) has led to earlier detection of prostate cancer, but elevated serum PSA levels may be present in non-malignant conditions such as benign prostatic hyperlasia (BPH). Characterization of gene-expression profiles that molecularly distinguish prostatic neoplasms may identify genes involved in prostate carcinogenesis, elucidate clinical biomarkers, and lead to an improved classification of prostate cancer. Using microarrays of complementary DNA, we examined gene-expression profiles of more than 50 normal and neoplastic prostate specimens and three common prostate-cancer cell lines. Signature expression profiles of normal adjacent prostate (NAP), BPH, localized prostate cancer, and metastatic, hormone-refractory prostate cancer were determined. Here we establish many associations between genes and prostate cancer. We assessed two of these genes-hepsin, a transmembrane serine protease, and pim-1, a serine/threonine kinase-at the protein level using tissue microarrays consisting of over 700 clinically stratified prostate-cancer specimens. Expression of hepsin and pim-1 proteins was significantly correlated with measures of clinical outcome. Thus, the integration of cDNA microarray, high-density tissue microarray, and linked clinical and pathology data is a powerful approach to molecular profiling of human cancer.     

一个广义凸规划强稳定性定理

对凸规划问题 ( Pt)的强稳定性定理作了相应的改进 ,将原定理中充分性条件“f( x,t)是关于 x的可微凸函数”减弱成条件“f( x,t)是关于 x的严格伪凸函数”。在其它条件不变的情形下 ,其强稳定性结论仍然成立。     

模拟文物铸铁的阴极保护

在模拟的文物铸铁上，研究已生成较厚锈层的带锈铸铁在３．５％ＮａＣｌ溶液中阴极保护的可能性和可行性，并确定最佳保护参数。结果表明，带锈铸铁的阴极保护是可行的；在本体系中最佳保护电位范围是－９００～－１０００ｍＶ（ＳＣＥ）；当保护电位比－１１００ｍＶ（ＳＣＥ）更负时，保护效率将显著降低。     

High-frequency precise excision of the Drosophila foldback transposable element

Precise excision of transposable elements in prokaryotes is a rare event which occurs at a significantly lower rate than transposition and other element-mediated events. Thus, we were intrigued by a eukaryotic transposable element which seemed capable of precise excision at high frequencies. The white-crimson (wc) mutation in Drosophila, a highly unstable allele of the X-linked eye colour locus, white, resulted from the insertion of a member of the foldback (FB) transposable element family. This mutation reverts to its parental phenotype at a frequency of greater than 1 in 10(3) X chromosomes. Characterization of these revertants by Southern blots of genomic DNA indicated that they resulted from loss of the wc insertion. Here we report the nucleotide sequence of the excision point in these revertants, and conclude that the FB element responsible for the wc mutation is capable of precise excision at high frequencies.     

Isoelectric focusing of neuraminidase

Zusammenfassung Die isoelektrischen Punkte der Neuraminidasen vonVibrio cholerae (pH 4.80) undClostridium perfringens (pH 4.95) wurden mittels isoelektrischer Fokusierung bestimmt. Neuraminidasen zwei verschiedener Influenzaviren (A₂/Aichi/68 und B/Mass/66) wurden entsprechend analysiert. Die Virus-Neuraminidasen waren Heterogen und hatten wesentlich höhere isoelektrische Punkte als die bakteriellen Enzyme.     

Oscillation Heuristics for the Two-group Classification Problem

We propose a new nonparametric family of oscillation heuristics for improving linear classifiers in the two-group discriminant problem. The heuristics are motivated by the intuition that the classification accuracy of a separating hyperplane can be improved through small perturbations to its slope and position, accomplished by substituting training observations near the hyperplane for those used to generate it. In an extensive simulation study, using data generated from multivariate normal distributions under a variety of conditions, the oscillation heuristics consistently improve upon the classical linear and logistic discriminant functions, as well as two published linear programming-based heuristics and a linear Support Vector Machine. Added to any of the methods above, they approach, and frequently attain, the best possible accuracy on the training samples, as determined by a mixed-integer programming (MIP) model, at a much smaller computational cost. They also improve expected accuracy on the overall populations when the populations overlap significantly and the heuristics are trained with large samples, at least in situations where the data conditions do not explicitly favor a particular classifier.