245,060 research outputs found
Higher nucleoporin-Importinβ affinity at the nuclear basket increases nucleocytoplasmic import.
Several in vitro studies have shown the presence of an affinity gradient in nuclear pore complex proteins for the import receptor Importinβ, at least partially contributing to nucleocytoplasmic transport, while others have historically argued against the presence of such a gradient. Nonetheless, the existence of an affinity gradient has remained an uncharacterized contributing factor. To shed light on the affinity gradient theory and better characterize how the existence of such an affinity gradient between the nuclear pore and the import receptor may influence the nucleocytoplasmic traffic, we have developed a general-purpose agent based modeling (ABM) framework that features a new method for relating rate constants to molecular binding and unbinding probabilities, and used our ABM approach to quantify the effects of a wide range of forward and reverse nucleoporin-Importinβ affinity gradients. Our results indicate that transport through the nuclear pore complex is maximized with an effective macroscopic affinity gradient of 2000 µM, 200 µM and 10 µM in the cytoplasmic, central channel and nuclear basket respectively. The transport rate at this gradient is approximately 10% higher than the transport rate for a comparable pore lacking any affinity gradient, which has a peak transport rate when all nucleoporins have an affinity of 200 µM for Importinβ. Furthermore, this optimal ratio of affinity gradients is representative of the ratio of affinities reported for the yeast nuclear pore complex--suggesting that the affinity gradient seen in vitro is highly optimized
Determining the basic principles in managing project schedule for construction.
The application of the scheduling software has been quite popular in Malaysia recently. Planning software like Microsoft Project and Primavera had been used to develop the schedule for construction project for the purpose or project monitoring and control. Many clients organization have made the task to submit computer generated schedule as mandatory. However in real practice the schedule submitted has not been very useful for the client. In some instances the schedule has been ignored once submitted to the client. There are many problems associated to this situation. Among them is due to the absent of the standard guideline that can be used to manage the schedule itself. The contractor. Contractor has been prepared the schedule based on their own assumption and without much consideration for actual application for the project later. Therefore this short term research has been conducted with the main aim to develop such guideline. The methodology adopted for the study includes the interviews with panel of professional in construction and questionnaire survey. The development of the guideline is based on the feedback by the respondents of the questionnaires survey conducted. Prior to that, the research has also investigated the current state of arts of the scheduling practice in Malaysia and its limitation. The major finding of the research is the development of the guideline for managing the scheduling process. This guideline can be used by the major client to regulate the process of preparing, submission and updating the project progress. It is expected that this schedule can be improve further by improving its level of comprehensiveness
- …