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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.
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   
4.
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   
5.
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   
6.
It is argued that Kirton's theory of styles of creativity is conceptually and methodologically unsound. A solution to the conceptual and methodological dilemmas is offered by way of making a clear‐cut distinction between novelty on the stimulus and novelty on the response side. This distinction is used as a platform for the development of a new taxonomy of different kinds of creativity and intelligent behaviour. A major feature of this new model is the distinction made between proactive and reactive creativity. The implications of this distinction for opening new avenues for a more differentiated assessment of creativity, as well as for the development of a conceptually firmer and more differentiated platform for developing new practical training programmes in creativity are suggested.  相似文献   
7.
A simple method, based in the frequency domain, was developed for calculating the dynamic response of a stall‐regulated wind turbine. Emphasis is placed on two aspects of the method, which are necessary in order to obtain a reasonable linearization of behavior when the blades are stalled. First, the tangential (in‐plane) component of turbulence is included, in addition to the axial component. Second, the linearized relationship between lift coefficient and angle‐of‐attack is adjusted to account for the effects of dynamic stall: separate linearizations are used for excitation and damping of vibration. A thorough comparison is made between linear and non‐linear dynamic‐stall methods, with the conclusion that the accuracy of the linear method depends upon the frequency and amplitude of oscillation. The linear dynamic‐stall method is accurate at blade vibrational frequencies, but it can be inaccurate at frequencies in the vicinity of 1P or below, when the angle‐of‐attack oscillates with an amplitude of 3° or more. Load spectra of a Nordtank 500 turbine, calculated using the frequency‐domain method, are compared with measurements. The frequency‐domain method provides estimates of load spectra and aerodynamic damping (stability) that are useful for preliminary design and optimization, but the method lacks sufficient accuracy and generality to be used for certification. Copyright © 2011 John Wiley & Sons, Ltd.  相似文献   
8.
Patient-centered care encourages active involvement of patients in their own treatment and a collaborative perspective on the relationship between patient and practitioner. However, to achieve constructive patient–practitioner collaboration in medical consultations the partakers need to successfully interact across conceptual boundaries that can impede intersubjectivity, i.e., the construction of shared meanings and understandings in communicative activities. We present a synthesis of a user-centered approach to designing interactive technology supporting collaboration in face-to-face consultations related to audiological (hearing) rehabilitation. Specifically, we focus on the case of hearing aid tuning, and on the design and utility assessment of a prototype sound environment simulator intended to support the process by helping the patient and the practitioner build a joint understanding of the individual patient’s hearing problem and perceived effects of treatment actions. We describe an empirical and qualitative investigation that calls specific attention to the multi-dimensional boundaries involved in collocated patient–practitioner interactions, and to the explorative and situated nature of the consultation as a collaborative problem-solving process. Here, various micro-practices play a key role in gradually forming a better understanding of the problem at hand and in identifying appropriate treatment steps. Our findings suggest that patient–practitioner collaboration can benefit from interactive technology, which is sufficiently flexible or open-ended in terms of use to accommodate, or be appropriated, to the immediate needs of the situation. We argue that designing technology with the aim of enhancing existing practices of intersubjectivity, rather than doing away with them, improves the chances of enriching collocated patient–practitioner interaction and reduces risk of obstructing it. The main research contribution is an increased understanding of the medical consultation as an instance of collocated collaborative work and learning, and the challenges and opportunities that lie in co-designing interactive solutions that can help the patient take an active and contributing part in the situation.  相似文献   
9.
Tryptophan (Trp) is an amino acid and an essential component of the human diet. It plays a crucial role in many metabolic functions. Clinicians can use Trp levels in the course of diagnosing various metabolic disorders and the symptoms associated with those diseases. Furthermore, supplementation with this amino acid is considered in the treatment of depression and sleep disorders, mainly due to the Trp relationship with the synthesis of serotonin (5-HT) and melatonin. It is also used in helping to resolve cognitive disorders, anxiety, or neurodegenerative diseases. Reduced secretion of serotonin is associated with autism spectrum disorder, obesity, anorexia and bulimia nervosa, and other diseases presenting peripherals symptoms. The literature strongly suggests that Trp has a significant role in the correct functionality of the brain-gut axis and immunology. This information leads to the consideration of Trp as an essential dietary component due to its role in the serotonin pathway. A reduced availability of Trp in diet and nutraceutical supplementation should be considered with greater concern than one might expect. This paper constitutes a review of the more salient aspects gleaned from the current knowledge base about the role of Trp in diseases, associated nutritional disorders, and food science, in general.  相似文献   
10.
This paper describes industrial aspects of combined inventory management and routing in maritime and road-based transportation, and gives a classification and comprehensive literature review of the current state of the research.The literature is contrasted with aspects of industrial applications from a constructive, but critical, viewpoint. Based on the status and trends within the field, future research is suggested with regard to both further development of the research area and industrial needs. By highlighting the industrial aspects, practitioners will hopefully see the benefit of using advanced decision support systems in complex situations related to combined inventory management and routing in their business. In addition, a classification and presentation of the research should help and motivate researchers to further focus on inventory management and routing challenges.  相似文献   
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