Distinct routes to metastasis: plasticity-dependent and plasticity-independent pathways.

The cascade that culminates in macrometastases is thought to be mediated by phenotypic plasticity, including epithelial-mesenchymal and mesenchymal-epithelial transitions (EMT and MET). Although there is substantial support for the role of EMT in driving cancer cell invasion and dissemination, much less is known about the importance of MET in the later steps of metastatic colonization. We created novel reporters, which integrate transcriptional and post-transcriptional regulation, to test whether MET is required for metastasis in multiple in vivo cancer models. In a model of carcinosarcoma, metastasis occurred via an MET-dependent pathway; however, in two prostate carcinoma models, metastatic colonization was MET independent. Our results provide evidence for both MET-dependent and MET-independent metastatic pathways.

Methylation-dependent T cell immunity to Mycobacterium tuberculosis heparin-binding hemagglutinin.

Although post-translational modifications of protein antigens may be important componenets of some B cell epitopes, the determinants of T cell immunity are generally nonmodified peptides. Here we show that methylation of the Mycobacterium tuberculosis heparin-binding hemagglutinin (HBHA) by the bacterium is essential for effective T cell immunity to this antigen in infected healthy humans and in mice. Methylated HBHA provides high levels of protection against M. tuberculosis challenge in mice, whereas nonmethylated HBHA does not. Protective immunity induced by methylated HBHA is comparable to that afforded by vaccination with bacille Calmette et Guérin, the only available anti-tuberculosis vaccine. Thus, post-translational modifications of proteins may be crucial for their ability to induce protective T cell-mediated immunity against infectious diseases such as tuberculosis.

A 3/2 algorithm for two-machine open shop with route-dependent processing times

This paper considers the problem of minimizing the schedule length of a two-machine shop in which not only can a job be assigned any of the two possible routes, but also the processing times depend on the chosen route. This problem is known to be NP-hard. We describe a simple approximation algorithm that guarantees a worst-case performance ratio of 2. We also present some modifications to this algorithm that improve its performance and guarantee a worst-case performance ratio of 3=2.

Birth-death processes with mass annihilation and state-dependent immigration

A birth-death process is subject to mass annihilation at rate β with subsequent mass immigration occurring into state j at rateα j . This structure enables the process to jump from one sector of state space to another one (via state 0) with transition rate independent of population size. First, we highlight the difficulties encountered when using standard techniques to construct both time-dependent and equilibrium probabilities. Then we show how to overcome such analytic difficulties by means of a tool developed in Chen and Renshaw (1990, 1993b); this approach is applicable to many processes whose underlying generator on E\{0} has known probability structure. Here we demonstrate the technique through application to the linear birth-death generator on which is superimposed an annihilation/immigration process.

Markovian bulk-arriving queues with state-dependent control at idle time

This paper considers a Markovian bulk-arriving queue modified to allow both mass arrivals when the queue is idle and mass departures which allow for the possibility of removing the entire workload. Properties of queues which terminate when the server becomes idle are developed first, since these play a key role in later developments. Results for the case of mass arrivals, but no mass annihilation, are then constructed with specific attention being paid to recurrence properties, equilibrium queue-size structure, and waiting-time distribution. A closed-form expression for the expected queue size and its Laplace transform are also established. All of these results are then generalised to allow for the removal of the entire workload, with closed-form expressions being developed for the equilibrium size and waiting-time distributions.

Time dependent electric, magnetic and hydrodynamic interaction in aluminium electrolysis cells

The waves in commercial cells for electrolytic aluminium production originate at the interface between the liquid aluminium and electrolyte, but their effect can spread into the surrounding busbar network as electric current perturbation, and the total magnetic field acquires a time dependent component. The presented model for the wave development accounts for the nonuniform electric current distribution at the cathode and the whole network of the surrounding busbars. The magnetic field is computed for the continuous current in the fluid zones, all busbars and the ferromagnetic construction elements. When the electric current and the associated magnetic field are computed according to the actual electrical circuit and updated for all times, the instability growth rate is significantly affected. The presented numerical model for the wave and electromagnetic interaction demonstrates how different physical coupling factors are affecting the wave development in the electrolysis cells. These small amplitude self-sustained interface oscillations are damped in the presence of intense turbulent viscosity created by the horizontal circulation velocity field. Additionally, the horizontal circulation vortices create a pressure gradient contributing to the deformation of the interface. Instructive examples for the 500 kA demonstration cell are presented.

Vacuum arc remelting time dependent modelling

Vacuum arc remelting (VAR) aims at production of high quality, segregation-free alloys. The quality of the produced ingots depends on the operating conditions which could be monitored and analyzed using numerical modelling. The remelting process uniformity is controlled by critical medium scale time variations of the order 1-100 s, which are physically initiated by the droplet detachment and the large scale arc motion at the top of liquid pool [1,2]. The newly developed numerical modelling tools are addressing the 3-dimensional magnetohydrodynamic and thermal behaviour in the liquid zone and the adjacent ingot, electrode and crucible.

Schedules with due-date assignment and position-dependent processing times

Single machine scheduling problems are considered, in which the processing of jobs depend on positions of the jobs in a schedule and the due-dates are assigned either according to the CON rule (a due-date common to all jobs is chosen) or according to the SLK rule (the due-dates are computed by increasing the actual processing times of each job by a slack, common to all jobs). Polynomial-time dynamic programming algorithms are proposed for the problems with the objective functions that include the cost of assigning the due-dates, the total cost of disgarded jobs (which are not scheduled) and, possibly, the total earliness of the scheduled jobs.

Single machine scheduling and due date assignment with positionally dependent processing times

We consider single machine scheduling and due date assignment problems in which the processing time of a job depends on its position in a processing sequence. The objective functions include the cost of changing the due dates, the total cost of discarded jobs that cannot be completed by their due dates and, possibly, the total earliness of the scheduled jobs. We present polynomial-time dynamic programming algorithms in the case of two popular due date assignment methods: CON and SLK. The considered problems are related to mathematical models of cooperation between the manufacturer and the customer in supply chain scheduling.

Time-dependent modelling and experimental validation of the metal/flux interface in a continuous casting mould

A finite volume computer model of the continuous casting process for steel flat products has been developed. In this first stage, the model concentrates on the hydrodynamic aspects of the process and in particular the dynamic behavior of the metal/slag interface. The model was validated against experimental measurements obtained in a water model apparatus.

Modelling the time-dependent behaviour of solder pastes used in the electronics assembly applications

Solder paste is the most widely used bonding material in the assembly of surface mount devices in electronic industries. It generally has a flocculated structure (show aggregation of solder particles), and hence are known to exhibit a thixotropic behavior. This is recognized by the decrease in apparent viscosity of paste material with time when subjected to a constant shear rate. The proper characterisation of this timedependent rheological behaviour of solder pastes is crucial for establishing the relationships between the pastes’ structure and flow behaviour; and for correlating the physical parameters with paste printing performance. In this paper, we present a novel method which has been developed for characterising the timedependent and non-Newtonian rheological behaviour of solder pastes as a function of shear rates. The objective of the study reported in this paper is to investigate the thixotropic build-up behaviour of solder pastes. The stretched exponential model(SEM) has been used to model the structural changes during the build-up process and to correlate model parameters with the paste printing process.

Vacuum arc remelting time dependent modelling

Newly developed numerical modelling tools are described, which address the 3-dimensional (3D) time-dependent magnetohydrodynamic and thermal behaviour in the liquid pool zone in the adjacent ingot, electrode and crucible. The melting electrode film flow and the droplet detachment initiation are simulated separately by an axisymmetric transient model.

Prooxidant action of knipholone anthrone: Copper dependent reactive oxygen species generation and DNA damage

Knipholone (KP) and knipholone anthrone (KA) are natural 4-phenylanthraquinone structural analogues with established differential biological activities including in vitro antioxidant and cytotoxic properties. By using DNA damage as an experimental model, the comparative Cu(II)-dependent prooxidant action of these two compounds were studied. In the presence of Cu(II) ions, the antioxidant KA (3.1-200 [mu]M) but not KP (6-384 [mu]M) caused a concentration-dependent pBR322 plasmid DNA strand scission. The DNA damage induced by KA could be abolished by reactive oxygen species scavengers, glutathione and catalase as well as EDTA and a specific Cu(I) chelator bathocuproine disulfonic acid. In addition to Cu(II) chelating activity, KA readily reduces Cu(II) to Cu(I). Copper-dependent generation of reactive oxygen species and the subsequent macromolecular damage may be involved in the antimicrobial and cytotoxic activity of KA.