Pancreatic ductal adenocarcinoma (PDAC) has the worst prognosis among solid malignancies and improved therapeutic strategies are needed to improve outcomes. Patient-derived xenografts (PDX) and patient-derived organoids (PDO) serve as promising tools to identify new drugs with therapeutic potential in PDAC. For these preclinical disease models to be effective, they should both recapitulate the molecular heterogeneity of PDAC and validate patient-specific therapeutic sensitivities. To date however, deep characterization of the molecular heterogeneity of PDAC PDX and PDO models and comparison with matched human tumour remains largely unaddressed at the whole genome level. We conducted a comprehensive assessment of the genetic landscape of 16 whole-genome pairs of tumours and matched PDX, from primary PDAC and liver metastasis, including a unique cohort of 5 'trios' of matched primary tumour, PDX, and PDO. We developed a pipeline to score concordance between PDAC models and their paired human tumours for genomic events, including mutations, structural variations, and copy number variations. Tumour-model comparisons of mutations displayed single-gene concordance across major PDAC driver genes, but relatively poor agreement across the greater mutational load. Genome-wide and chromosome-centric analysis of structural variation (SV) events highlights previously unrecognized concordance across chromosomes that demonstrate clustered SV events. We found that polyploidy presented a major challenge when assessing copy number changes; however, ploidy-corrected copy number states suggest good agreement between donor-model pairs. Collectively, our investigations highlight that while PDXs and PDOs may serve as tractable and transplantable systems for probing the molecular properties of PDAC, these models may best serve selective analyses across different levels of genomic complexity.

Shadows are of great importance to computer graphics, especially for interactive animation due to the visual cues which they provide. Most research in the field of dynamic shadowing has focussed on shadows from point light sources, since they are much easier to compute than those from area light sources. This means that such shadows have sharp boundaries, and so often appear to be unrealistic. We present an algorithm which enables the interactive animation of shadows due to area light sources which have been computed using discontinuity meshing. The results in the paper show that it can be used interactively, and more importantly that it has good scalability characteristics with more complex scenes.

There are a number of practical difficulties in performing a path testing strategy for computer programs. One problem is in deciding which paths, out of a possible infinity, to use as test cases. A hierarchy of structural test metrics is suggested to direct the choide and to monitor the coverge of test paths. Another problem is that many of the chosen paths may be infeasible in the sense that no test data can ever execute them. Experience with the use of "allegations" to circumvent this problem and prevent the static generation of many infeasible paths is reported.

In this paper we describe the extension of an existing FORTRAN IV numerical software testbed (Hennell, 1978) to enable ALGOL 68 programs to be investigated. The extensions necessary were two-fold; firstly, a complete rewrite of the first phase, a static analysis in which the source text is reformatted (for reasons stated within this paper), analysed for all possible control jumps and statistics on language constructs are collected. The second major extension was to incorporate into the second phase an existing ALGOL 68 compiler which after some modification enables dynamic execution histories to be collected in a data base. These modifications to the compiler represent extensions to the language definition which enable user programs to trace themselves. The utilisation of this compiler restricts source code programs to be written in ALGOL 68s, an official ALGOL 68 subset (Hibbard, 1974). The third, analysis, phase is essentially identical in both the FORTRAN and ALGOL 68 systems.

This paper discusses the need for measures of complexity and unstructuredness of programs. A simple language independent concept is put forward as a measure of control flow complexity in program text and is then developed for use as a measure of unstructuredness. The proposed metric is compared with other metrics, the most notable of which is the cyclomatic complexity measure. Some experience with automatic tools for obtaining these metrics is reported.