A lisp-based occam interpreter

technical reportThe OCCAM programming language is an implementation of Communicating Sequential Processes and is used in a number of different areas. These areas usually require explicitly describing small-grain paralleslism. OCCAM programs formed by such descriptions can be tested for correctness by executing them on commercially availabe transputers. Unfortunately, this environment requires that all components be written in OCCUM instead of being able to describe parts of the program with behavioural models written in a more powerful language. The interpreter described here solves this problem. It allows programs to be written in OCCAM with behavioural descriptions in Lisp. A number of large programs which take advantage of this powerful environment have been implemented and tested

C-RISC A C language reduced instruction set computer

Journal ArticleThis project is the implementation of a Reduced Instruction Set Computer (RISC) on a tiny chip. RISC technology is based on the idea that a small number of simple instructions can be used to create a fast, flexible computer. Our RISC uses this principle while staying within the confines of the tiny chip. Size limitations directly affect the complexity in the number of possible instructions. Since the tiny chip is limited in size, a decision was required as to the set of instructions to include. Due to the implementers' knowledge of the C language, it was decided that the direction of the RISC instructions would follow the C language instruction set, hence the name C-RISC. The decision to direct the instruction set to the C language instructions does not restrict the flexibility of the C-RISC since many high level languages (HLLs) can be converted or cross-compiled into C code. The adoption of a given language direction allows easier comparison of quantitative results when deciding on instructions to be included in or discarded from the instruction set. A number of ingenious ideas were incorporated into the design of the C-RISC. These were necessitated by the small chip size as well as the desired power of the processor. The final C-RISC chip was implemented in Path Programmable Logic (PPL) [1] using 2 micron CMOS technology

Transforming disfigured and disoriented areas into routable switchboxes

Journal ArticleRouting an entire circuit requires partitioning the circuit (routing area) into smaller, localized routing areas. Using non-rectangular, rotated switchbox shapes (and therefore non-manhattan routing layout) has the potential to simplify the partitioning of the circuit into routable areas and to use "dead space" on a chip for routing. The method described in this paper for generating non-rectangular, rotated switchboxes borrows ideas from computer graphics

Switchbox routing by pattern matching

Journal ArticleMany good algorithms have been designed that provide good solutions to the wire routing problem in VLSI. Unfortunately, many of these algorithms only consider a small subset of different parameters such as number of layers, routability of layers and technology. We believe that these algorithms can be applied generally to any set of parameters by implementing the algorithms as a description that allows them to take advantage of this flexibility. We propose that routing algorithms either use patterns directly or can be converted to use patterns. We present a powerful formalism for describing these patterns

Strategy and narrative in higher education

In this paper we apply the idea of narrative to strategy and to the development of strategy in the higher education context. We explore how strategy is formed as an intertextual narrative in a comparative study of higher education (HE) in the UK context. Existing research suggests that competition between narratives, such as that in HE, should be problematic in strategy terms. We show that this is not necessarily the case. Unlike in other settings where new strategy narratives tend to drive out previous narratives, in HE it is the ongoing interaction between historical and new narratives that gives the content of strategy its essential voice. We show how apparently competing narratives are accommodated though appeals to emotion and values. The maintenance of strategic direction requires hope and a synthesis of societal values that maintains access to the past, the future, and multiple narrators. This approach helps us understand how universities perform the complex task of adapting the strengths of the university’s past to the challenges of external policy developments in strategy formation

Prebiotic and Probiotic Influence on Beef Calves Immunity

Objective: Evaluate whether prebiotic and probiotic feed additives influenced the immune response during the weaning period in beef calves. Hypothesis: Addition of both prebiotic and probiotic feed additives provided in a post weaning ration will enhance immune response and minimize morbidity. Furthermore, it is expected this will provide elevated IgG serum concentrations as compared to the control ration

Genome-Wide Analyses for Osteosarcoma in Leonberger Dogs Reveal the CDKN2A/B Gene Locus as a Major Risk Locus

Dogs represent a unique spontaneous cancer model. Osteosarcoma (OSA) is the most common primary bone tumor in dogs (OMIA 001441-9615), and strongly resembles human forms of OSA. Several large- to giant-sized dog breeds, including the Leonberger, have a greatly increased risk of developing OSA. We performed genome-wide association analysis with high-density imputed SNP genotype data from 273 Leonberger cases with a median age of 8.1 [3.1–13.5] years and 365 controls older than eight years. This analysis revealed significant associations at the CDKN2A/B gene locus on canine chromosome 11, mirroring previous findings in other dog breeds, such as the greyhound, that also show an elevated risk for OSA. Heritability (h2SNP) was determined to be 20.6% (SE = 0.08; p-value = 5.7 × 10−4) based on a breed prevalence of 20%. The 2563 SNPs across the genome accounted for nearly all the h2SNP of OSA, with 2183 SNPs of small effect, 316 SNPs of moderate effect, and 64 SNPs of large effect. As with many other cancers it is likely that regulatory, non-coding variants underlie the increased risk for cancer development. Our findings confirm a complex genetic basis of OSA, moderate heritability, and the crucial role of the CDKN2A/B locus leading to strong cancer predisposition in dogs. It will ultimately be interesting to study and compare the known genetic loci associated with canine OSA in human OSA

A synonymous germline variant in a gene encoding a cell adhesion molecule is associated with cutaneous mast cell tumour development in Labrador and Golden Retrievers

Mast cell tumours are the most common type of skin cancer in dogs, representing a significant concern in canine health. The molecular pathogenesis is largely unknown, but breed-predisposition for mast cell tumour development suggests the involvement of inherited genetic risk factors in some breeds. In this study, we aimed to identify germline risk factors associated with the development of mast cell tumours in Labrador Retrievers, a breed with an elevated risk of mast cell tumour development. Using a methodological approach that combined a genome-wide association study, targeted next generation sequencing, and TaqMan genotyping, we identified a synonymous variant in the DSCAM gene on canine chromosome 31 that is associated with mast cell tumours in Labrador Retrievers. DSCAM encodes a cell-adhesion molecule. We showed that the variant has no effect on the DSCAM mRNA level but is associated with a significant reduction in the level of the DSCAM protein, suggesting that the variant affects the dynamics of DSCAM mRNA translation. Furthermore, we showed that the variant is also associated with mast cell tumours in Golden Retrievers, a breed that is closely related to Labrador Retrievers and that also has a predilection for mast cell tumour development. The variant is common in both Labradors and Golden Retrievers and consequently is likely to be a significant genetic contributor to the increased susceptibility of both breeds to develop mast cell tumours. The results presented here not only represent an important contribution to the understanding of mast cell tumour development in dogs, as they highlight the role of cell adhesion in mast cell tumour tumourigenesis, but they also emphasise the potential importance of the effects of synonymous variants in complex diseases such as cancer. Author summary The combination of various genetic and environmental risk factors makes the understanding of the molecular circuitry behind complex diseases, like cancer, a major challenge. The homogeneous nature of pedigree dog breed genomes makes these dogs ideal for the identification of both simple disease-causing genetic variants and genetic risk factors for complex diseases. Mast cell tumours are the most common type of canine skin cancer, and one of the most common cancers affecting dogs of most breeds. Several breeds, including Labrador Retrievers (which represent one of the most popular dog breeds), have an elevated risk of mast cell tumour development. Here, by using a methodological approach that combined different techniques, we identified a common inherited synonymous variant, that predisposes Labrador Retrievers to mast cell tumour development. Interestingly, we showed that this variant, despite its synonymous nature, appears to have an effect on translation dynamics as it is associated with reduced levels of DSCAM, a cell adhesion molecule. The results presented here reveal dysregulation of cell adhesion to be an important factor in mast cell tumour pathogenesis, and also highlight the important role that synonymous variants can play in complex diseases

Genome-wide analysis of canine oral malignant melanoma metastasis-associated gene expression

Abstract Oral malignant melanoma (OMM) is the most common canine melanocytic neoplasm. Overlap between the somatic mutation profiles of canine OMM and human mucosal melanomas suggest a shared UV-independent molecular aetiology. In common with human mucosal melanomas, most canine OMM metastasise. There is no reliable means of predicting canine OMM metastasis, and systemic therapies for metastatic disease are largely palliative. Herein, we employed exon microarrays for comparative expression profiling of FFPE biopsies of 18 primary canine OMM that metastasised and 10 primary OMM that did not metastasise. Genes displaying metastasis-associated expression may be targets for anti-metastasis treatments, and biomarkers of OMM metastasis. Reduced expression of CXCL12 in the metastasising OMMs implies that the CXCR4/CXCL12 axis may be involved in OMM metastasis. Increased expression of APOBEC3A in the metastasising OMMs may indicate APOBEC3A-induced double-strand DNA breaks and pro-metastatic hypermutation. DNA double strand breakage triggers the DNA damage response network and two Fanconi anaemia DNA repair pathway members showed elevated expression in the metastasising OMMs. Cross-validation was employed to test a Linear Discriminant Analysis classifier based upon the RT-qPCR-measured expression levels of CXCL12, APOBEC3A and RPL29. Classification accuracies of 94% (metastasising OMMs) and 86% (non-metastasising OMMs) were estimated

Genome-wide analyses implicate 33 loci in heritable dog osteosarcoma, including regulatory variants near CDKN2A/B

Background: Canine osteosarcoma is clinically nearly identical to the human disease, but is common and highly heritable, making genetic dissection feasible. Results: Through genome-wide association analyses in three breeds (greyhounds, Rottweilers, and Irish wolfhounds), we identify 33 inherited risk loci explaining 55% to 85% of phenotype variance in each breed. The greyhound locus exhibiting the strongest association, located 150 kilobases upstream of the genes CDKN2A/B, is also the most rearranged locus in canine osteosarcoma tumors. The top germline candidate variant is found at a >90% frequency in Rottweilers and Irish wolfhounds, and alters an evolutionarily constrained element that we show has strong enhancer activity in human osteosarcoma cells. In all three breeds, osteosarcoma-associated loci and regions of reduced heterozygosity are enriched for genes in pathways connected to bone differentiation and growth. Several pathways, including one of genes regulated by miR124, are also enriched for somatic copy-number changes in tumors. Conclusions: Mapping a complex cancer in multiple dog breeds reveals a polygenic spectrum of germline risk factors pointing to specific pathways as drivers of disease