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101.
A translationally silent single nucleotide mutation in exon 44 (E44) of the von Willebrand factor (VWF) gene is associated with inefficient removal of intron 44 in a von Willebrand disease (VWD) patient. This intron retention (IR) event was previously attributed to reordered E44 secondary structure that sequesters the normal splice donor site. We propose an alternative mechanism: the mutation introduces a cryptic splice donor site that interferes with the function of the annotated site to favor IR. We evaluated both models using minigene splicing reporters engineered to vary in secondary structure and/or cryptic splice site content. Analysis of splicing efficiency in transfected K562 cells suggested that the mutation-generated cryptic splice site in E44 was sufficient to induce substantial IR. Mutations predicted to vary secondary structure at the annotated site also had modest effects on IR and shifted the balance of residual splicing between the cryptic site and annotated site, supporting competition among the sites. Further studies demonstrated that introduction of cryptic splice donor motifs at other positions in E44 did not promote IR, indicating that interference with the annotated site is context dependent. We conclude that mutant deep exon splice sites can interfere with proper splicing by inducing IR. 相似文献
102.
An indeterministic cycle can be represented as an infinite moving-average process and has a smooth peak in its spectrum. A deterministic cycle can be formulated in such a way that it is still stationary but its cyclical behaviour is characterized by a sudden jump in the spectral distribution function. This paper shows how both processes can be nested within the same model and how, when the cycle is buried in noise, the null hypothesis of a deterministic cycle can be tested. The preferred tests are based on the residuals from regressing the observations on sine and cosine functions of the frequency of interest. They are derived as point optimal and locally best invariant tests and can be extended to regression models which include other explanatory variables. The asymptotic distribution of the locally best invariant test, which is a one-sided score test, is shown to be Cramer–von Mises with two degrees of freedom. Modifications for dealing with serially correlated noise are discussed and the methods are illustrated with real data. 相似文献
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Özkan Öz 《Journal of Adhesion Science and Technology》2013,27(21):2133-2153
Bi-adhesive joints are an alternative stress-reduction technique for adhesively bonded joints. The joints have two types of adhesives in the overlap region. The stiff adhesive should be located in the middle and the flexible adhesive at the ends. This study is the extension of our previous paper to the von Mises stress evaluation and discusses the values and importance of the von Mises stresses in the bi-adhesive single-lap joint. Both analytical and numerical analyses were performed using three different bi-adhesive bondline configurations. The Zhao’s closed form (analytic) solution used includes the bending moment effect. In the finite element models, overlap surfaces of the adherends and the adhesives were modeled using surface-to-surface contact elements. The contribution levels of the peel and shear stresses for producing a peak von Mises stress are also studied. It is concluded that the contribution level of the shear stress at where von Mises stress becomes peak is more than that of the peel stress. Joint strength analyses were performed based on the peak elastic von Mises stresses. It is seen that joint strength can be increased using bi-adhesive bondline. The analytical and numerical results show that the appropriate bond-length ratio must be used to obtain high joint strength. 相似文献
110.
Application of a vector-analytic model for metrological analysis of an infrared Fourier spectrometer
The use of a vector-analytic method of computational estimation of the error of a measuring device is demonstrated using an
infrared Fourier spectrometer as an example. The results of such an estimate are compared with experiment and results obtained
by two other methods.
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Translated from Izmeritel’naya Tekhnika, No. 2, pp. 28–32, February, 2008. 相似文献