Virtual reality and program comprehension: application using spreadsheet visualisation

Program comprehension is an important function undertaken in the process of software maintenance. Compared to other research subjects, program comprehension has received little attention even though it is one of the biggest influences on a programmer's output. Research into aiding program comprehension has led to software visualisations, but these are mainly two-dimensional views and overload the viewer with information. With the advent of more powerful computers, virtual reality can be used to create three dimensional visualisations, in which the viewer is able to navigate freely. Spreadsheets were studied in this work on visualisation because programming languages are extremely complex and a model employing spreadsheets was developed. Spreadsheets offer many similarities to programming languages, for example, cell referencing and formulas in spreadsheets are similar to procedure calls, variable referencing and data manipulation in conventional programming languages. Common mistakes made in spreadsheets have been shown to be very difficult to locate, mainly because the spreadsheet user has a reduced ability to make hypotheses about the computational domain of a spreadsheet. Therefore, in order to address this shortcoming a visualisation model was developed to allow a spreadsheet user to be able to view both the problem domain (the what) and the computational domain (the how) simultaneously. A spreadsheet, a spreadsheet description language and a virtual reality system were the objects in the model, and a generator and translator were the links between those objects. Implementing the model indicated that spreadsheets could be visualised in virtual reality, and this technique was shown to improve the process of spreadsheet comprehension

Tumor-Infiltrating T Cells Correlate with NY-ESO-1-Specific Autoantibodies in Ovarian Cancer

BACKGROUND: Tumor-infiltrating CD8+ T cells are correlated with prolonged progression-free and overall survival in epithelial ovarian cancer (EOC). A significant fraction of EOC patients mount autoantibody responses to various tumor antigens, however the relationship between autoantibodies and tumor-infiltrating T cells has not been investigated in EOC or any other human cancer. We hypothesized that autoantibody and T cell responses may be correlated in EOC and directed toward the same antigens. METHODOLOGY AND PRINCIPAL FINDINGS: We obtained matched serum and tumor tissue from 35 patients with high-grade serous ovarian cancer. Serum samples were assessed by ELISA for autoantibodies to the common tumor antigen NY-ESO-1. Tumor tissue was examined by immunohistochemistry for expression of NY-ESO-1, various T cell markers (CD3, CD4, CD8, CD25, FoxP3, TIA-1 and Granzyme B) and other immunological markers (CD20, MHC class I and MHC class II). Lymphocytic infiltrates varied widely among tumors and included cells positive for CD3, CD8, TIA-1, CD25, FoxP3 and CD4. Twenty-six percent (9/35) of patients demonstrated serum IgG autoantibodies to NY-ESO-1, which were positively correlated with expression of NY-ESO-1 antigen by tumor cells (r = 0.57, p = 0.0004). Autoantibodies to NY-ESO-1 were associated with increased tumor-infiltrating CD8+, CD4+ and FoxP3+ cells. In an individual HLA-A2+ patient with autoantibodies to NY-ESO-1, CD8+ T cells isolated from solid tumor and ascites were reactive to NY-ESO-1 by IFN-gamma ELISPOT and MHC class I pentamer staining. CONCLUSION AND SIGNIFICANCE: We demonstrate that tumor-specific autoantibodies and tumor-infiltrating T cells are correlated in human cancer and can be directed against the same target antigen. This implies that autoantibodies may collaborate with tumor-infiltrating T cells to influence clinical outcomes in EOC. Furthermore, serological screening methods may prove useful for identifying clinically relevant T cell antigens for immunotherapy

Gênero e insegurança no trabalho no Reino Unido Gender and employment insecurity in the UK

O objetivo deste artigo é explorar a dimensão de gênero da insegurança do emprego no Reino Unido, focalizando, para tanto, as recentes tendências do trabalho temporário, que incluem o de prazo fixo, o sazonal, o sem vínculo empregatício, o contratado através de agência, o ocasional e outros tipos de trabalho temporário. Essas formas de trabalho são, inequivocamente, inseguras, sejam elas livremente escolhidas ou não. A primeira seção do artigo trata das pressões e resistências que têm, cumulativamente, levado à atual participação de mulheres no trabalho remunerado. Examinam-se, em seguida, as recentes tendências nos padrões de emprego no Reino Unido, com especial referência às diferenças entre mulheres em idade de trabalho, bem como à incidência e distribuição do trabalho de meio período. As tendências recentes e as diferenças de gênero no trabalho temporário são, assim, consideradas à luz desse contexto mais amplo. Finalmente, esses achados são confrontados com os argumentos no sentido de que o emprego atípico fornece oportunidades para um aumento da participação de mulheres na força de trabalho e para uma conciliação prática entre o emprego e os papéis e relacionamentos familiares.<br>The objective of this article is to explore how far employment insecurity is gendered in the UK, focusing on recent trends in temporary employment, covering fixed term, seasonal, agency, casual and other temporary work. The first section of this paper considers the pressures and resistances that have cumulatively led to women's current participation in paid work. This is followed by an examination of recent trends in UK employment patterns, with particular reference to differences within the female population of working age and the incidence and distribution of part-time employment. Recent trends and gender differences in temporary employment are then considered against this broader background. Finally, this evidence is considered in relation to arguments that atypical employment provides opportunities for women's increased labour force participation and the practical reconciliation of employment and family roles and relationships

A large-scale whole genome sequence-based analysis discovered novel genetic variants influencing bone mineral density: Results from the GEFOS and UK10K Consortia

International audienc

Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture.

The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF ≤ 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants, as well as rare, population-specific, coding variants. Here we identify novel non-coding genetic variants with large effects on BMD (ntotal = 53,236) and fracture (ntotal = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n = 2,882 from UK10K (ref. 10); a population-based genome sequencing consortium), whole-exome sequencing (n = 3,549), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (n = 26,534), and de novo replication genotyping (n = 20,271). We identified a low-frequency non-coding variant near a novel locus, EN1, with an effect size fourfold larger than the mean of previously reported common variants for lumbar spine BMD (rs11692564(T), MAF = 1.6%, replication effect size = +0.20 s.d., Pmeta = 2 × 10(-14)), which was also associated with a decreased risk of fracture (odds ratio = 0.85; P = 2 × 10(-11); ncases = 98,742 and ncontrols = 409,511). Using an En1(cre/flox) mouse model, we observed that conditional loss of En1 results in low bone mass, probably as a consequence of high bone turnover. We also identified a novel low-frequency non-coding variant with large effects on BMD near WNT16 (rs148771817(T), MAF = 1.2%, replication effect size = +0.41 s.d., Pmeta = 1 × 10(-11)). In general, there was an excess of association signals arising from deleterious coding and conserved non-coding variants. These findings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture, thereby providing rationale for whole-genome sequencing and improved imputation reference panels to study the genetic architecture of complex traits and disease in the general population