Recovering the Imperfect: Cell Segmentation in the Presence of Dynamically Localized Proteins

Deploying off-the-shelf segmentation networks on biomedical data has become common practice, yet if structures of interest in an image sequence are visible only temporarily, existing frame-by-frame methods fail. In this paper, we provide a solution to segmentation of imperfect data through time based on temporal propagation and uncertainty estimation. We integrate uncertainty estimation into Mask R-CNN network and propagate motion-corrected segmentation masks from frames with low uncertainty to those frames with high uncertainty to handle temporary loss of signal for segmentation. We demonstrate the value of this approach over frame-by-frame segmentation and regular temporal propagation on data from human embryonic kidney (HEK293T) cells transiently transfected with a fluorescent protein that moves in and out of the nucleus over time. The method presented here will empower microscopic experiments aimed at understanding molecular and cellular function.Comment: Accepted at MICCAI Workshop on Medical Image Learning with Less Labels and Imperfect Data, 202

The number of metastable states in the generalized random orthogonal model

We calculate the number of metastable states in the generalized random orthogonal model. The results obtained are verified by exact numerical enumeration for small systems sizes but taking into account finite size effects. These results are compared with those for Hopfield model in order to examine the effect of strict orthonormality of neural network patterns on the number of metastable states.Comment: 12 pages, 4 EPS figure

The Computer Science Ontology: A Large-Scale Taxonomy of Research Areas

Ontologies of research areas are important tools for characterising, exploring, and analysing the research landscape. Some fields of research are comprehensively described by large-scale taxonomies, e.g., MeSH in Biology and PhySH in Physics. Conversely, current Computer Science taxonomies are coarse-grained and tend to evolve slowly. For instance, the ACM classification scheme contains only about 2K research topics and the last version dates back to 2012. In this paper, we introduce the Computer Science Ontology (CSO), a large-scale, automatically generated ontology of research areas, which includes about 26K topics and 226K semantic relationships. It was created by applying the Klink-2 algorithm on a very large dataset of 16M scientific articles. CSO presents two main advantages over the alternatives: i) it includes a very large number of topics that do not appear in other classifications, and ii) it can be updated automatically by running Klink-2 on recent corpora of publications. CSO powers several tools adopted by the editorial team at Springer Nature and has been used to enable a variety of solutions, such as classifying research publications, detecting research communities, and predicting research trends. To facilitate the uptake of CSO we have developed the CSO Portal, a web application that enables users to download, explore, and provide granular feedback on CSO at different levels. Users can use the portal to rate topics and relationships, suggest missing relationships, and visualise sections of the ontology. The portal will support the publication of and access to regular new releases of CSO, with the aim of providing a comprehensive resource to the various communities engaged with scholarly data

Structural Studies of West Nile Virus in Complex with Neutralizing Antibodies.

West Nile virus (WNV) is a positive strand RNA virus in the family Flaviviridae, which includes members such as dengue, Japanese encephalitis, tick-borne encephalitis, yellow fever and Hepatitis C. As with other members of the genus, it is arthropod transmitted and has recently established itself as an endemic virus in the United States. Although most infections are asymptomatic, clinical manifestations of WNV include encephalitis and death. We have been interested in investigating the nature of the immune response with particular emphasis on the role of antibodies in reducing the level of infection. We have used a combination of techniques, but primarily structure, as a tool to probe the nature of antibody-mediated virus neutralization. Our results suggest that neutralization of virus particles is more complex than originally envisioned, with multiple mechanisms utilized. Using a combination of X-ray crystallography and cryo-electron microscopy, several virus-antibody complexes have been determined at pseudo-atomic resolution. These studies suggest the following: 1) flavivirus particles exhibit dynamic motions or breathing that transiently expose cryptic epitopes; 2) although there are 180 potential binding sites for each monoclonal antibody the quasi-equivalent nature of the virion usually permits only a subset of sites to be utilized; 3) the availability of these sites, the epitope itself, and the avidity of antibody directly influence the mechanism of neutralization; and 4) particles thought to be incapable of infecting cells, so-called immature viruses, may play a critical role in immune surveillance and reactivity. The structure of the flavivirus virion and complexes of monoclonal antibodies will be presented along with data to support mechanisms antibody-mediated flavivirus neutralizatio

A compactness theorem for scalar-flat metrics on manifolds with boundary

Let (M,g) be a compact Riemannian manifold with boundary. This paper is concerned with the set of scalar-flat metrics which are in the conformal class of g and have the boundary as a constant mean curvature hypersurface. We prove that this set is compact for dimensions greater than or equal to 7 under the generic condition that the trace-free 2nd fundamental form of the boundary is nonzero everywhere.Comment: 49 pages. Final version, to appear in Calc. Var. Partial Differential Equation

An Exploratory Study into the Factors Impeding Ethical Consumption

Although consumers are increasingly engaged with ethical factors when forming opinions about products and making purchase decisions, recent studies have highlighted significant differences between consumers’ intentions to consume ethically, and their actual purchase behaviour. This article contributes to an understanding of this “ethical purchasing gap” through a review of existing literature, and the inductive analysis of focus group discussions. A model is suggested which includes exogenous variables such as moral maturity and age which have been well covered in the literature, together with further impeding factors identified from the focus group discussions. For some consumers, inertia in purchasing behaviour was such that the decision-making process was devoid of ethical considerations. Several manifested their ethical views through post-purchase dissonance and retrospective feelings of guilt. Others displayed a reluctance to consume ethically due to personal constraints, a perceived negative impact on image or quality, or an outright negation of responsibility. Those who expressed a desire to consume ethically often seemed deterred by cynicism, which caused them to question the impact they, as an individual, could achieve. These findings enhance the understanding of ethical consumption decisions and provide a platform for future research in this area

A phosphatase cascade by which rewarding stimuli control nucleosomal response

ArticleInternational audienceDopamine orchestrates motor behaviour and reward-driven learning. Perturbations of dopamine signalling have been implicated in several neurological and psychiatric disorders, and in drug addiction. The actions of dopamine are mediated in part by the regulation of gene expression in the striatum, through mechanisms that are not fully understood. Here we show that drugs of abuse, as well as food reinforcement learning, promote the nuclear accumulation of 32-kDa dopamine-regulated and cyclic-AMP-regulated phosphoprotein (DARPP-32). This accumulation is mediated through a signalling cascade involving dopamine D1 receptors, cAMP-dependent activation of protein phosphatase-2A, dephosphorylation of DARPP-32 at Ser 97 and inhibition of its nuclear export. The nuclear accumulation of DARPP-32, a potent inhibitor of protein phosphatase-1, increases the phosphorylation of histone H3, an important component of nucleosomal response. Mutation of Ser 97 profoundly alters behavioural effects of drugs of abuse and decreases motivation for food, underlining the functional importance of this signalling cascad

Establishment of a new human osteosarcoma cell line, UTOS-1: cytogenetic characterization by array comparative genomic hybridization

The cytogenetic characteristics of osteosarcoma (OS) remain controversial. The establishment of a new human OS cell line may improve the characterization. We report the establishment of a new human osteosarcoma cell line, UTOS-1, from a typical osteoblastic OS of an 18-year-old man. Cultured UTOS-1 cells are spindle-shaped, and have been maintained in vitro for over 50 passages in more than 2 years. Xenografted UTOS-1 cells exhibit features typical of OS, such as production of osteoid or immature bone matrix, and proliferation potency in vivo. UTOS-1 also exhibit morphological and immunohistochemical characteristics typical of osteoblastic OS. Chromosomal analysis by G-band show 73~85 chromosomes with complicated translocations. Array CGH show frequent gains at locus DAB2 at chromosome 5q13, CCND2 at 12p13, MDM2 at 12q14.3-q15, FLI and TOP3A at 17p11.2-p12 and OCRL1 at Xq25, and show frequent losses at HTR1B at 6q13, D6S268 at 6q16.3-q21, SHGC17327 at 18ptel, and STK6 at 20q13.2-q13.3. The UTOS-1 cell line may prove useful for biologic and molecular pathogenetic investigations of human OS