Full deflection profile calculation and Young's modulus optimisation for engineered high performance materials.

New engineered materials have critical applications in different fields in medicine, engineering and technology but their enhanced mechanical performances are significantly affected by the microstructural design and the sintering process used in their manufacture. This work introduces (i) a methodology for the calculation of the full deflection profile from video recordings of bending tests, (ii) an optimisation algorithm for the characterisation of Young's modulus, (iii) a quantification of the effects of optical distortions and (iv) a comparison with other standard tests. The results presented in this paper show the capabilities of this procedure to evaluate the Young's modulus of highly stiff materials with greater accuracy than previously possible with bending tests, by employing all the available information from the video recording of the tests. This methodology extends to this class of materials the possibility to evaluate both the elastic modulus and the tensile strength with a single mechanical test, without the need for other experimental tools.

Some computational and algorithmic developments in computational mechanics of discontinua.

Discontinua simulations are becoming an important part of computational mechanics to the extent that computational mechanics of discontinua is becoming a separate sub-discipline of computational mechanics. Among the most widely used methods of computational mechanics of discontinua are discrete-element methods, combined finite-discrete-element methods and discontinuum deformation analysis methods. A range of key algorithmic procedures is common to most of these methods. These include contact detection, explicit solvers, fracture and fragmentation models, handling of complex geometric considerations when processing interaction in three dimensions (contact kinematics) and fluid coupling. In recent years, there have been major breakthroughs in almost all of these key algorithmic aspects. These include linear contact-detection procedures (NBS, C-grid), discretized contact solutions, fracture and fragmentation solutions, together with fluid pressure driven fracture process and three-dimensional explicit solvers incorporating finite rotations. Many of these breakthroughs have not yet been applied across the full range of relevant discontinuum problems. The major reason for this is that discrete-element method, discontinuum deformation analysis and combined finite-discrete-element method publications are spread over a wide range of specialist journals and conferences. Thus in this paper, the main features of a selection of algorithmic breakthroughs are reviewed for the first time, enabling researchers in different fields to apply these compatible developments to their specific applications.

The modelling of particle systems with real shapes.

The numerical modelling of particulate processes in environmental science increasingly requires an ability to represent the properties of individual natural particles. Considerable advances have been made in discontinuum modelling using spheres to represent particles. In this paper, we discuss recent developments that illustrate a way forward for tackling the complexity of realistically shaped bodies such as those exhibited by rock fragments. To address the validation of such approaches, we present a comparison of cube-packing experiments and their equivalent numerical simulation. Sensitivity to initial conditions, highlighted for non-spherical bodies, enters the discussion of problems with validation of numerical simulation. The algorithmic details behind these advances in modelling large systems of realistically shaped particles are summarized in our companion paper in this volume.

Prostate-specific antigen promoter/enhancer driven gene therapy for prostate cancer: construction and testing of a tissue-specific adenovirus vector.

A range of luciferase reporter vectors was constructed, incorporating 5'-flanking sequences from the prostate-specific antigen (PSA), human glandular kallikrein 2 (hKLK2), and cytomegalovirus (CMV) promoters for expression control. Tissue specificity was evaluated in the PSA-positive line LNCaP and PSA-negative cells from different tissues of origin (CoLo320, DG75, EJ, A2780, and Jurkat). The minimal 628-bp PSA and hKLK2 promoters showed only low-level expression in either PSA-positive or PSA-negative cells and showed no increase with the addition of androgen. Tandem duplication of the PSA promoter slightly increased expression in PSA-positive LNCaP cells. The addition of CMV enhancer sequences upstream of a single PSA or hKLK2 promoter substantially but nonspecifically increased luciferase expression in all cell lines tested. However, placing a 1455-bp PSA enhancer sequence upstream of either the PSA or hKLK2 promoters increased expression 20-fold in the PSA-positive cell line LNCaP but not in the PSA-negative lines. Tandem duplication of the PSA enhancer increased expression to approximately 50-fold higher than either promoter alone while retaining tissue-specific control. The level of expression was reduced by the addition of a third copy of the PSA enhancer. Expression from all enhancer constructs was increased 100-fold above basal levels when induced with the androgen dihydrotestosterone, with the PSA-based constructs consistently exhibiting roughly twice the level of expression of the hKLK2-based constructs at all androgen concentrations. Adenovirus vectors were produced in which either enhanced green fluorescent protein or nitroreductase could be expressed from the optimized PSA double enhancer-promoter construct and evaluated in LNCaP cells and the bladder-derived line EJ. Control vectors with the CMV promoter gave good levels of expression in both cell lines, whereas the PSA constructs only produced detectable levels of protein in the LNCaP cells as assessed by fluorescence of enhanced green fluorescent protein or by Western blotting of nitroreductase. LNCaP but not EJ cells were selectively sensitized to the prodrug CB1954 following infection with Ad-PSA(EEP)-NR. The PSA-based nitroreductase virus produced comparable amounts of nitroreductase and sensitization to CB1954 approaching that of the CMV-driven virus. Plasmid and adenovirus constructs combining PSA enhancer and promoter sequences demonstrate selective expression of linked genes in PSA-positive cells. The expression is induced by androgen and gives therapeutically relevant levels of effector proteins.