Molecular Network Control Through Boolean Canalization

Boolean networks are an important class of computational models for molecular interaction networks. Boolean canalization, a type of hierarchical clustering of the inputs of a Boolean function, has been extensively studied in the context of network modeling where each layer of canalization adds a degree of stability in the dynamics of the network. Recently, dynamic network control approaches have been used for the design of new therapeutic interventions and for other applications such as stem cell reprogramming. This work studies the role of canalization in the control of Boolean molecular networks. It provides a method for identifying the potential edges to control in the wiring diagram of a network for avoiding undesirable state transitions. The method is based on identifying appropriate input-output combinations on undesirable transitions that can be modified using the edges in the wiring diagram of the network. Moreover, a method for estimating the number of changed transitions in the state space of the system as a result of an edge deletion in the wiring diagram is presented. The control methods of this paper were applied to a mutated cell-cycle model and to a p53-mdm2 model to identify potential control targets

Modelling the joint distribution of competing risks survival times using copula functions

The problem of modelling the joint distribution of survival times in a competing risks model, using copula functions is considered. In order to evaluate this joint distribution and the related overall survival function, a system of non-linear differential equations is solved, which relates the crude and net survival functions of the modelled competing risks, through the copula. A similar approach to modelling dependent multiple decrements was applied by Carriere (1994) who used a Gaussian copula applied to an incomplete double decrement model which makes it difficult to calculate any actuarial functions and draw relevant conclusions. Here, we extend this methodology by studying the effect of complete and partial elimination of up to four competing risks on the overall survival function, the life expectancy and life annuity values. We further investigate how different choices of the copula function affect the resulting joint distribution of survival times and in particular the actuarial functions which are of importance in pricing life insurance and annuity products. For illustrative purposes, we have used a real data set and used extrapolation to prepare a complete multiple decrement model up to age 120. Extensive numerical results illustrate the sensitivity of the model with respect to the choice ofcopula and its parameter(s)

The Density Matrix Renormalization Group in Nuclear Physics: A Status Report

We report on the current status of recent efforts to develop the Density Matrix Renormalization Group method for use in large-scale nuclear shell-model calculations.Comment: 6 pages, 8 figures, $^*$ Talk presented at the XXVI$^{th}$ Symposium on Nuclear Physics, 6 pages, 8 figures, Talk presented at the XXVIth Symposium on Nuclear Physics,6-9 January 2003, Taxco, Mexic

Automatic, computer aided geometric design of free-knot, regression splines

A new algorithm for Computer Aided Geometric Design of least squares (LS) splines with variable knots, named GeDS, is presented. It is based on interpreting functional spline regression as a parametric B-spline curve, and on using the shape preserving property of its control polygon. The GeDS algorithm includes two major stages. For the first stage, an automatic adaptive, knot location algorithm is developed. By adding knots, one at a time, it sequentially "breaks" a straight line segment into pieces in order to construct a linear LS B-spline fit, which captures the "shape" of the data. A stopping rule is applied which avoids both over and under fitting and selects the number of knots for the second stage of GeDS, in which smoother, higher order (quadratic, cubic, etc.) fits are generated. The knots appropriate for the second stage are determined, according to a new knot location method, called the averaging method. It approximately preserves the linear precision property of B-spline curves and allows the attachment of smooth higher order LS B-spline fits to a control polygon, so that the shape of the linear polygon of stage one is followed. The GeDS method produces simultaneously linear, quadratic, cubic (and possibly higher order) spline fits with one and the same number of B-spline regression functions. The GeDS algorithm is very fast, since no deterministic or stochastic knot insertion/deletion and relocation search strategies are involved, neither in the first nor the second stage. Extensive numerical examples are provided, illustrating the performance of GeDS and the quality of the resulting LS spline fits. The GeDS procedure is compared with other existing variable knot spline methods and smoothing techniques, such as SARS, HAS, MDL, AGS methods and is shown to produce models with fewer parameters but with similar goodness of fit characteristics, and visual quality

Two-Body Density Matrix for Closed s-d Shell Nuclei

The two-body density matrix for $^{4}He,^{16}O$ and $^{40}Ca$ within the Low-order approximation of the Jastrow correlation method is considered. Closed analytical expressions for the two-body density matrix, the center of mass and relative local densities and momentum distributions are presented. The effects of the short-range correlations on the two-body nuclear characteristics are investigated.Comment: 13 pages(LaTeX), 4 figures (ps

Geotechnique, Physico-chemical Behaviour and a New Erosion Model for Mine Tailings under Environmental Loading

Comprehensive geotechnical characterisation of mine tailings is required for the design, construction and safe operation of mine waste management facilities against the large number of potential failure risks. It is important that the characterization is carried out under the stress range and drainage conditions relevant to those encountered in the field. The present research utilized mine tailings samples from a copper/nickel base-metal mine. Kaolinite and bentonite clays were added to the mine tailings in order to study the effect of clay percentage and clay mineralogy on the behaviour of saturated tailings/clay systems with varying composition. Slurries with moderate or high concentration of solids were prepared in the laboratory by mixing distilled water with mine tailings or artificial tailings/clay soils. Beds with different composition, thickness and age were sedimented from these slurries and tested under a stress range below 1 kPa, and under different degrees of drainage ranging from undrained to fully drained. The primary consolidation of the pure tailings beds was complete in approximately one hour and negligible volume changes occurred in the beds during secondary compression. The effect of adding kaolinite or bentonite to the tailings was to increase the time for primary consolidation of the mixed beds, but the rate of increase was greater when bentonite was used. The undrained shear strength of the beds was measured using an automated fall cone device at a depth interval of 1 cm below bed surface. It was found that the undrained strength increased, whereas the water content and void ratio decreased with depth within the beds. The factor controlling the undrained strength of the beds was the vertical effective stress, with the water content also having some secondary effect. A specially built Tilting Tank was used to measure the shear strength of the beds under drained and partially drained conditions that were simulated by varying the loading rate. Bed failure within the Tank always occurred at a plane parallel to the surface of the bed and at a depth of 0.4 to 2.5 cm. Linear drained and partially drained shear strength envelopes with zero cohesion intercept were defined, with the partially drained (total) friction angle always remaining lower than the drained (effective) friction angle. The latter varied from 35.2° for the tailings/bentonite mixtures to 40.4° for the pure tailings, depending on the percentage and mineralogy of the clay fraction. It was found that adding clay to the mine tailings generally caused a decrease in the frictional resistance of the mixtures, with the effect being more pronounced for the bentonite additive. Time for consolidation did not influence the shear strength of the tailings and tailings/kaolinite mixtures, but produced an increase of 2.1° in the frictional resistance of the tailings/bentonite mixtures. A critical stress for erosion as a function of depth was estimated for each bed using existing formulations for cohesive and noncohesive sediments and mixtures of both. A linear correlation between the undrained shear strength and the critical stress for erosion, with parameters dependent on the composition of the mixtures was proposed

Adaptive notifications to support knowledge sharing in virtual communities

Social web-groups where people with common interests and goals communicate, share resources, and construct knowledge, are becoming a major part of today’s organisational practice. Research has shown that appropriate support for effective knowledge sharing tailored to the needs of the community is paramount. This brings a new challenge to user modelling and adaptation, which requires new techniques for gaining sufficient understanding of a virtual community (VC) and identifying areas where the community may need support. The research presented here addresses this challenge presenting a novel computational approach for community-tailored support underpinned by organisational psychology and aimed at facilitating the functioning of the community as a whole (i.e. as an entity). A framework describing how key community processes—transactive memory (TM), shared mental models (SMMs), and cognitive centrality (CCen)—can be utilised to derive knowledge sharing patterns from community log data is described. The framework includes two parts: (i) extraction of a community model that represents the community based on the key processes identified and (ii) identification of knowledge sharing behaviour patterns that are used to generate adaptive notifications. Although the notifications target individual members, they aim to influence individuals’ behaviour in a way that can benefit the functioning of the community as a whole. A validation study has been performed to examine the effect of community-adapted notifications on individual members and on the community as a whole using a close-knit community of researchers sharing references. The study shows that notification messages can improve members’ awareness and perception of how they relate to other members in the community. Interesting observations have been made about the linking between the physical and the VC, and how this may influence members’ awareness and knowledge sharing behaviour. Broader implications for using log data to derive community models based on key community processes and generating community-adapted notifications are discussed