Representation of the Consumer Interest in the Federal Government

We describe a method for eye pupil localization based on an ensemble of randomized regression trees and use several publicly available datasets for its quantitative and qualitative evaluation. The method compares well with reported state-of-the-art and runs in real-time on hardware with limited processing power, such as mobile devices

A logic of defeasible argumentation: Constructing arguments in justification logic

In the 1980s, Pollock’s work on default reasons started the quest in the AI community for a formal system of defeasible argumentation. The main goal of this paper is to provide a logic of structured defeasible arguments using the language of justification logic. In this logic, we introduce defeasible justification assertions of the type t:F that read as “t is a defeasible reason that justifies F”. Such formulas are then interpreted as arguments and their acceptance semantics is given in analogy to Dung’s abstract argumentation framework semantics. We show that a large subclass of Dung’s frameworks that we call “warranted” frameworks is a special case of our logic in the sense that (1) Dung’s frameworks can be obtained from justification logic-based theories by focusing on a single aspect of attacks among justification logic arguments and (2) Dung’s warranted frameworks always have multiple justification logic instantiations called “realizations”. We first define a new justification logic that relies on operational semantics for default logic. One of the key features that is absent in standard justification logics is the possibility to weigh different epistemic reasons or pieces of evidence that might conflict with one another. To amend this, we develop a semantics for “defeaters”: conflicting reasons forming a basis to doubt the original conclusion or to believe an opposite statement. This enables us to formalize non-monotonic justifications that prompt extension revision already for normal default theories. Then we present our logic as a system for abstract argumentation with structured arguments. The format of conflicting reasons overlaps with the idea of attacks between arguments to the extent that it is possible to define all the standard notions of argumentation framework extensions. Using the definitions of extensions, we establish formal correspondence between Dung’s original argumentation semantics and our operational semantics for default theories. One of the results shows that the notorious attack cycles from abstract argumentation cannot always be realized as justification logic default theories

Nonverbal communication interface for collaborative virtual environments

Nonverbal communication is an important aspect of real-life face-to-face interaction and one of the most efficient ways to convey emotions, therefore users should be provided the means to replicate it in the virtual world. Because articulated embodiments are well suited to provide body communication in virtual environments, this paper first reviews some of the advantages and disadvantages of complex embodiments. After a brief introduction to nonverbal communication theories, we present our solution, taking into account the practical limitations of input devices and social science aspects. We introduce our sample of actions and implementation using our VLNET (Virtual Life Network) networked virtual environment and discuss the results of an informal evaluation experimen

Whole-exome sequencing in relapsing chronic lymphocytic leukemia: clinical impact of recurrent RPS15 mutations

Fludarabine, cyclophosphamide and rituximab (FCR) is first-line treatment for medically fit chronic lymphocytic leukemia (CLL) patients, however despite good response rates many patients eventually relapse. Whilst recent high-throughput studies have identified novel recurrent genetic lesions in adverse-prognostic CLL, the mechanisms leading to relapse after FCR therapy are not completely understood. To gain insight into this issue, we performed whole-exome sequencing of sequential samples from 41 CLL patients who were uniformly treated with FCR but relapsed after a median of 2 years. In addition to mutations with known adverse-prognostic impact (TP53, NOTCH1, ATM, SF3B1, NFKBIE, BIRC3) a large proportion of cases (19.5%) harbored mutations in RPS15, a gene encoding a component of the 40S ribosomal subunit. Extended screening, totaling 1119 patients, supported a role for RPS15 mutations in aggressive CLL, with one-third of RPS15-mutant cases also carrying TP53 aberrations. In most cases selection of dominant, relapse-specific subclones was observed over time. However, RPS15 mutations were clonal prior to treatment and remained stable at relapse. Notably, all RPS15 mutations represented somatic missense variants and resided within a 7 amino-acid evolutionarily conserved region. We confirmed the recently postulated direct interaction between RPS15 and MDM2/MDMX and transient expression of mutant RPS15 revealed defective regulation of endogenous p53 compared to wildtype RPS15. In summary, we provide novel insights into the heterogeneous genetic landscape of CLL relapsing after FCR treatment and highlight a novel mechanism underlying clinical aggressiveness involving a mutated ribosomal protein, potentially representing an early genetic lesion in CLL pathobiology

Nonverbal communication interface for collaborative virtual environments

Nonverbal communication is an important aspect of real-life face-to-face interaction and one of the most efficient ways to convey emotions, therefore users should be provided the means to replicate it in the virtual world. Because articulated embodiments are well suited to provide body communication in virtual environments, this paper first reviews some of the advantages and disadvantages of complex embodiments. After a brief introduction to nonverbal communication theories, we present our solution, taking into account the practical limitations of input devices and social science aspects. We introduce our sample of actions and implementation using our VLNET (Virtual Life Network) networked virtual environment and discuss the results of an informal evaluation experimen

Simulating virtual humans in networked virtual environments

In the past decade, networked virtual environments (NVEs) have been an increasingly active area of research, with the first commercial systems emerging recently. Graphical and behavioral representation of users within such systems is a particularly important issue that has lagged in development behind other issues such as network architectures and space structuring. We expose the importance of using virtual humans within these systems and provide a brief overview of several virtual human technologies used in particular for simulation of crowds. As the main technical contribution, the paper presents the integration of these technologies with the COVEN-DIVE platform, the extension of the DIVE system developed within the COVEN project. In conjunction with this, we present our contributions through the COVEN project to the MPEG-4 standard concerning the representation of virtual human

Actomyosin-dependent dynamic spatial patterns of cytoskeletal components drive mesoscale podosome organization

Podosomes are cytoskeletal structures crucial for cell protrusion and matrix remodelling in osteoclasts, activated endothelial cells, macrophages and dendritic cells. In these cells, hundreds of podosomes are spatially organized in diversely shaped clusters. Although we and others established individual podosomes as micron-sized mechanosensing protrusive units, the exact scope and spatiotemporal organization of podosome clustering remain elusive. By integrating a newly developed extension of Spatiotemporal Image Correlation Spectroscopy with novel image analysis, we demonstrate that F-actin, vinculin and talin exhibit directional and correlated flow patterns throughout podosome clusters. Pattern formation and magnitude depend on the cluster actomyosin machinery. Indeed, nanoscopy reveals myosin IIA-decorated actin filaments interconnecting multiple proximal podosomes. Extending well-beyond podosome nearest neighbours, the actomyosin-dependent dynamic spatial patterns reveal a previously unappreciated mesoscale connectivity throughout the podosome clusters. This directional transport and continuous redistribution of podosome components provides a mechanistic explanation of how podosome clusters function as coordinated mechanosensory area

Defined Microenvironments Trigger In Vitro Gastrulation in Human Pluripotent Stem Cells

Gastrulation is a stage in embryo development where three germ layers arise to dictate the human body plan. In vitro models of gastrulation have been demonstrated by treating pluripotent stem cells with soluble morphogens to trigger differentiation. However, in vivo gastrulation is a multistage process coordinated through feedback between soluble gradients and biophysical forces, with the multipotent epiblast transforming to the primitive streak followed by germ layer segregation. Here, the authors show how constraining pluripotent stem cells to hydrogel islands triggers morphogenesis that mirrors the stages preceding in vivo gastrulation, without the need for exogenous supplements. Within hours of initial seeding, cells display a contractile phenotype at the boundary, which leads to enhanced proliferation, yes-associated protein (YAP) translocation, epithelial to mesenchymal transition, and emergence of SRY-box transcription factor 17 (SOX17)+ T/BRACHYURY+ cells. Molecular profiling and pathway analysis reveals a role for mechanotransduction-coupled wingless-type (WNT) signaling in orchestrating differentiation, which bears similarities to processes observed in whole organism models of development. After two days, the colonies form multilayered aggregates, which can be removed for further growth and differentiation. This approach demonstrates how materials alone can initiate gastrulation, thereby providing in vitro models of development and a tool to support organoid bioengineering efforts.Pallavi Srivastava, Sara Romanazzo, Chantal Kopecky, Stephanie Nemec, Jake Ireland, Thomas G. Molley, Kang Lin, Pavithra B. Jayathilaka, Elvis Pandzic, Avani Yeola, Vashe Chandrakanthan, John Pimanda, and Kristopher Kilia

Ex vivo culture of intact human patient derived pancreatic tumour tissue

The poor prognosis of pancreatic ductal adenocarcinoma (PDAC) is attributed to the highly fibrotic stroma and complex multi-cellular microenvironment that is difficult to fully recapitulate in pre-clinical models. To fast-track translation of therapies and to inform personalised medicine, we aimed to develop a whole-tissue ex vivo explant model that maintains viability, 3D multicellular architecture, and microenvironmental cues of human pancreatic tumours. Patient-derived surgically-resected PDAC tissue was cut into 1-2 mm explants and cultured on gelatin sponges for 12 days. Immunohistochemistry revealed that human PDAC explants were viable for 12 days and maintained their original tumour, stromal and extracellular matrix architecture. As proof-of-principle, human PDAC explants were treated with Abraxane and we observed different levels of response between patients. PDAC explants were also transfected with polymeric nanoparticles + Cy5-siRNA and we observed abundant cytoplasmic distribution of Cy5-siRNA throughout the PDAC explants. Overall, our novel model retains the 3D architecture of human PDAC and has advantages over standard organoids: presence of functional multi-cellular stroma and fibrosis, and no tissue manipulation, digestion, or artificial propagation of organoids. This provides unprecedented opportunity to study PDAC biology including tumour-stromal interactions and rapidly assess therapeutic response to drive personalised treatment.John Kokkinos, George Sharbeen, Koroush S. Haghighi, Rosa Mistica C. Ignacio, Chantal Kopecky, Estrella Gonzales-Aloy ... et al