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We describe a novel, easy and efficient combinatorial phage display peptide substrate-mining method to map the substrate specificity of proteases. The peptide library is displayed on the pVII capsid of the M13 bacteriophage, which renders pIII necessary for infectivity and efficient retrieval, in an unmodified state. As capture module, the 3XFLAG was chosen due to its very high binding efficiency to anti-FLAG mAbs and its independency of any post-translational modification. This library was tested with Factor-VII activating protease (WT-FSAP) and its single-nucleotide polymorphism variant Marburg-I (MI)-FSAP. The WT-FSAP results confirmed the previously reported Arg/Lys centered FSAP cleavage site consensus as dominant, as well as reinforcing MI-FSAP as a loss-of-function mutant. Surprisingly, rare substrate clones devoid of basic amino acids were also identified. Indeed one of these peptides was cleaved as free peptide, thus suggesting a broader range of WT-FSAP substrates than previously anticipated.  相似文献   
3.
This paper explores the linkage between the entrepreneurial orientation of established firms and the development of radical innovation. Through five case studies in firms involved in radical innovation, three propositions are developed, suggesting that proactiveness, risk‐taking and autonomy stimulate the development of radical innovation, whereas competitive aggressiveness does not necessarily do so, as radical innovations are directed towards the creation of entirely new arenas of business, where existing competitors are not present.  相似文献   
4.
An 8-bit, 200 MSPS Folding and Interpolating ADC   总被引:1,自引:0,他引:1  
An 8-bit, 200 MSPS folding and interpolating analog-to-digitalconverter, ADC, has been implemented in a 1.2 µmBiCMOS-process. It achieves 7.5 effective bits with a power dissipationof 575mW. The active area is 4mm2. The implementationand measured results are presented. A simple analytical modelfor the interpolation-induced nonlinearity in a folding and interpolatingADC using sinusoidal folding is presented. The bowing of thereference ladder due to interaction with the input stages isanalyzed, and analytical models are derived.  相似文献   
5.
To find the exact probability distribution of the global maximum or minimum of a random field within a bounded domain is a pending problem even for Gaussian fields. Except for very special examples of fields, recourse must be taken to approximate reasoning or asymptotic considerations to be judged with respect to accuracy by simulations. In this paper, the problem is addressed through a functional equation that leads to the definition of a class of distribution functions that depend solely on process or field characteristics and domain quantities that can be calculated explicitly. This distribution function class is studied for Gaussian processes in earlier works by the author and it has been obtained explicitly for Gaussian fields on rectangular domains in the plane. Simulation studies show that rather good predictions are obtained for sufficiently smooth wide band Gaussian processes and fields. In this paper, the distribution function is obtained in general for Gaussian fields over arbitrary bounded domains with piecewise continuous and differentiable boundaries, and as in earlier works the distribution function is tested against empirical distribution functions obtained by simulation of sample functions of a smooth approximately Gaussian field, herein called a broken line Hino field. For completeness this particular field type is defined in appendix a and appendix b. The paper concludes with a statistical application on data for plain concrete tensile strength.  相似文献   
6.
The object of study is a stationary Gaussian white noise excited multi-degree-of-freedom (MDOF) linear elastic, ideal plastic, linearly damped, statically determinate oscillator with several potential elements of ideal plastic yielding. Specifically the study is exemplified for a plane multistory shear frame with rigid traverses where all the connecting columns except the columns in one or more of the bottom floors have finite symmetrical yield limits. The white noise excitation acts on the mass of the first floor making the movement of the elastic bottom floors simulate a ground motion that interacts with the structure above the bottom floors. The method of study is so-called Slepian model simulation and is in principle the same for other statically determinate MDOF elasto-plastic oscillators of the considered type. The method is fast as compared to direct simulation and provides results that give good insight in the behavior of the plastic displacement response process.  相似文献   
7.
The solubility of TiO2 in cryolite-alumina melts at 1020 °C was measured; it decreased with increasing alumina concentration up to ∼3.5 wt pct total oxide and then increased at higher alumina concentrations. The solubility was found to be 3.1 wt pct Ti in cryolite, and 2.7 wt pct Ti in an alumina-saturated melt. Modeling indicated that the most probable titanium species are TiOF2 and Na2TiO3, which coexist in the solution; the former dominates at low alumina concentrations and the latter at high alumina concentrations. Additional unknown amounts of fluoride may also be associated with these species. Determination of the solubility of TiO2 in alumina-saturated melts as a function of temperature showed that the solubility increased from 1.9 wt pct Ti at 975 °C to 2.8 wt pct Ti at 1035 °C, the apparent partial molar enthalpy of dissolution of TiO2 being 88±4 kJ mol−1.  相似文献   
8.
The distribution of the sum of a finite number of identically distributed random variables is in many cases easily determined given that the variables are independent. The moments of any order of the sum can always be expressed by the moments of the single term without computational problems. However, in the case of dependency between the terms even calculation of a few of the first moments of the sum presents serious computational problems.By use of computerized symbol manipulations it is practicable to obtain exact moments of partial sums of stationary sequences of mutually dependent lognormal variables or polynomials of standard Gaussian variables. The dependency structure is induced by specifying the autocorrelation structure of the sequence of standard Gaussian variables. Particularly useful polynomials are the Winterstein approximations that distributionally fit with non-Gaussian variables up to the moments of the fourth order [Winterstein, S. R. Nonlinear vibration models for extremes and fatigue. J. Engng Mech. ASCE 114 (1988) 1772–1790]1. A method to obtain the Winterstein approximation to a partial sum of a sequence of Winterstein approximations is explained and results are given for different autocorrelation functions of the generic Gaussian sequence.The primary purpose of the investigation is to provide a tool for judging the validity of the central limit theorem argument in specific applicational situations occurring in stochastic mechanics, that is, to judge the speed of convergence of the distribution of a sum (or an integral) of mutually dependent random variables to the Gaussian distribution. The paper is closely related to the work in Ditlevsen et al. [Ditlevsen, O., Mohr, G. & Hoffmeyer, P. Integration of non-Gaussian fields. Prob. Engng Mech 11 (1996) 15–23]2.  相似文献   
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10.
We have tested three methods for estimating 2003-2008 elevation changes of Svalbard glaciers from multi-temporal ICESat laser altimetry: (a) linear interpolation of crossover points between ascending and descending tracks, (b) projection of near repeat-tracks onto common locations using Digital Elevation Models (DEMs), and (c) least-squares fitting of rigid planes to segments of repeat-track data assuming a constant elevation change rate. The two repeat-track methods yield similar results and compare well to the more accurate, but sparsely sampled, crossover points. Most glacier regions in Svalbard have experienced low-elevation thinning combined with high-elevation balance or thickening during 2003-2008. The geodetic mass balance (excluding calving front retreat or advance) of Svalbard's 34,600 km2 glaciers is estimated to be −4.3 ± 1.4 Gt y1, corresponding to an area-averaged water equivalent (w.e.) balance of −0.12 ± 0.04 m w.e. y1. The largest ice losses have occurred in the west and south, while northeastern Spitsbergen and the Austfonna ice cap have gained mass. Winter and summer elevation changes derived from the same methods indicate that the spatial gradient in mass balance is mainly due to a larger summer season thinning in the west and the south than in the northeast. Our findings are consistent with in-situ mass balance measurements from the same period, confirming that repeat-track satellite altimetry can be a valuable tool for monitoring short term elevation changes of Arctic glaciers.  相似文献   
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