Shape description and matching using integral invariants on eccentricity transformed images

Matching occluded and noisy shapes is a problem frequently encountered in medical image analysis and more generally in computer vision. To keep track of changes inside the breast, for example, it is important for a computer aided detection system to establish correspondences between regions of interest. Shape transformations, computed both with integral invariants (II) and with geodesic distance, yield signatures that are invariant to isometric deformations, such as bending and articulations. Integral invariants describe the boundaries of planar shapes. However, they provide no information about where a particular feature lies on the boundary with regard to the overall shape structure. Conversely, eccentricity transforms (Ecc) can match shapes by signatures of geodesic distance histograms based on information from inside the shape; but they ignore the boundary information. We describe a method that combines the boundary signature of a shape obtained from II and structural information from the Ecc to yield results that improve on them separately

Transcriptional Regulation by CHIP/LDB Complexes

It is increasingly clear that transcription factors play versatile roles in turning genes “on” or “off” depending on cellular context via the various transcription complexes they form. This poses a major challenge in unraveling combinatorial transcription complex codes. Here we use the powerful genetics of Drosophila combined with microarray and bioinformatics analyses to tackle this challenge. The nuclear adaptor CHIP/LDB is a major developmental regulator capable of forming tissue-specific transcription complexes with various types of transcription factors and cofactors, making it a valuable model to study the intricacies of gene regulation. To date only few CHIP/LDB complexes target genes have been identified, and possible tissue-dependent crosstalk between these complexes has not been rigorously explored. SSDP proteins protect CHIP/LDB complexes from proteasome dependent degradation and are rate-limiting cofactors for these complexes. By using mutations in SSDP, we identified 189 down-stream targets of CHIP/LDB and show that these genes are enriched for the binding sites of APTEROUS (AP) and PANNIER (PNR), two well studied transcription factors associated with CHIP/LDB complexes. We performed extensive genetic screens and identified target genes that genetically interact with components of CHIP/LDB complexes in directing the development of the wings (28 genes) and thoracic bristles (23 genes). Moreover, by in vivo RNAi silencing we uncovered novel roles for two of the target genes, xbp1 and Gs-alpha, in early development of these structures. Taken together, our results suggest that loss of SSDP disrupts the normal balance between the CHIP-AP and the CHIP-PNR transcription complexes, resulting in down-regulation of CHIP-AP target genes and the concomitant up-regulation of CHIP-PNR target genes. Understanding the combinatorial nature of transcription complexes as presented here is crucial to the study of transcription regulation of gene batteries required for development

Influence of O6-benzylguanine on the anti-tumour activity and normal tissue toxicity of 1,3-bis(2-chloroethyl)-1-nitrosourea and molecular combinations of 5-fluorouracil and 2-chloroethyl-1-nitrosourea in mice

Previous studies have demonstrated that novel molecular combinations of 5-fluorouracil (5FU) and 2-chloroethyl-1-nitrosourea (CNU) have good preclinical activity and may exert less myelotoxicity than the clinically used nitrosoureas such as 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). This study examined the effect of O6-alkylguanine-DNA-alkyltransferase (ATase) depletion by the pseudosubstrate O6-benzylguanine (BG) on the anti-tumour activity and normal tissue toxicity in mice of three such molecular combinations, in comparison with BCNU. When used as single agents at their maximum tolerated dose, all three novel compounds produced a significant growth retardation of BCNU-resistant murine colon and human breast xenografts. This in vivo anti-tumour effect was potentiated by BG, but was accompanied by severe myelotoxicity as judged by spleen colony forming assays. However, while tumour resistance to BCNU was overcome using BG, this was at the expense of enhanced bone marrow, gut and liver toxicity. Therefore, although this ATase-depletion approach resulted in improved anti-tumour activity for all three 5-FU:CNU molecular combinations, the potentiated toxicities in already dose-limiting tissues indicate that these types of agents offer no therapeutic advantage over BCNU when they are used together with BG. © 1999 Cancer Research Campaig

Breaking Functional Connectivity into Components: A Novel Approach Using an Individual-Based Model, and First Outcomes

Landscape connectivity is a key factor determining the viability of populations in fragmented landscapes. Predicting ‘functional connectivity’, namely whether a patch or a landscape functions as connected from the perspective of a focal species, poses various challenges. First, empirical data on the movement behaviour of species is often scarce. Second, animal-landscape interactions are bound to yield complex patterns. Lastly, functional connectivity involves various components that are rarely assessed separately. We introduce the spatially explicit, individual-based model FunCon as means to distinguish between components of functional connectivity and to assess how each of them affects the sensitivity of species and communities to landscape structures. We then present the results of exploratory simulations over six landscapes of different fragmentation levels and across a range of hypothetical bird species that differ in their response to habitat edges. i) Our results demonstrate that estimations of functional connectivity depend not only on the response of species to edges (avoidance versus penetration into the matrix), the movement mode investigated (home range movements versus dispersal), and the way in which the matrix is being crossed (random walk versus gap crossing), but also on the choice of connectivity measure (in this case, the model output examined). ii) We further show a strong effect of the mortality scenario applied, indicating that movement decisions that do not fully match the mortality risks are likely to reduce connectivity and enhance sensitivity to fragmentation. iii) Despite these complexities, some consistent patterns emerged. For instance, the ranking order of landscapes in terms of functional connectivity was mostly consistent across the entire range of hypothetical species, indicating that simple landscape indices can potentially serve as valuable surrogates for functional connectivity. Yet such simplifications must be carefully evaluated in terms of the components of functional connectivity they actually predict

Using social and behavioural science to support COVID-19 pandemic response

The COVID-19 pandemic represents a massive global health crisis. Because the crisis requires large-scale behaviour change and places significant psychological burdens on individuals, insights from the social and behavioural sciences can be used to help align human behavior with the recommendations of epidemiologists and public health experts. Here we discuss evidence from a selection of research topics relevant to pandemics, including work on navigating threats, social and cultural influences on behaviour, science communication, moral decision-making, leadership, and stress and coping. In each section, we note the nature and quality of prior research, including uncertainty and unsettled issues. We identify several insights for effective response to the COVID-19 pandemic, and also highlight important gaps researchers should move quickly to fill in the coming weeks and months