Deep Interactive Region Segmentation and Captioning

With recent innovations in dense image captioning, it is now possible to describe every object of the scene with a caption while objects are determined by bounding boxes. However, interpretation of such an output is not trivial due to the existence of many overlapping bounding boxes. Furthermore, in current captioning frameworks, the user is not able to involve personal preferences to exclude out of interest areas. In this paper, we propose a novel hybrid deep learning architecture for interactive region segmentation and captioning where the user is able to specify an arbitrary region of the image that should be processed. To this end, a dedicated Fully Convolutional Network (FCN) named Lyncean FCN (LFCN) is trained using our special training data to isolate the User Intention Region (UIR) as the output of an efficient segmentation. In parallel, a dense image captioning model is utilized to provide a wide variety of captions for that region. Then, the UIR will be explained with the caption of the best match bounding box. To the best of our knowledge, this is the first work that provides such a comprehensive output. Our experiments show the superiority of the proposed approach over state-of-the-art interactive segmentation methods on several well-known datasets. In addition, replacement of the bounding boxes with the result of the interactive segmentation leads to a better understanding of the dense image captioning output as well as accuracy enhancement for the object detection in terms of Intersection over Union (IoU).Comment: 17, pages, 9 figure

Structural funds, EU enlargement, and the redistribution of FDI in Europe

The EU enlargements of 2004 led to a redirection of Structural and Cohesion Funds expenditures from EU-15 to new EU members as did those of 2007. This redistribution of funds makes the accession countries even more attractive as a location of FDI. Using a logistic regressions approach, this paper shows that a reallocation of structural funds as outlined in Agenda (For a stronger and wider union, COM(97) 2000 final, 2000) and successive revisions of the financial perspectives for an enlarged union leads to a redistribution of FDI by approximately 4−8 percentage points from the current EU members to the accession countries (2004 scenario) and 7−10 percentage points (2007 scenario), respectivel

Vascular Morphogenesis in the Context of Inflammation: Self-Organization in a Fibrin-Based 3D Culture System

Introduction: New vessel formation requires a continuous and tightly regulated interplay between endothelial cells with cells of the perivascular microenvironment supported by mechanic-physical and chemical cues from the extracellular matrix.Aim: Here we investigated the potential of small fragments of synovial tissue to form de novo vascular structures in the context of inflammation within three dimensional (3D) fibrin-based matrices in vitro, and assessed the contribution of mesenchymal stromal cell (MSC)-immune cell cross-talk to neovascularization considering paracrine signals in a fibrin-based co-culture model.Material and Methods: Synovial tissue fragments from patients with rheumatoid arthritis (RA) and inflammatory osteoarthritis (OA) were cultivated within 3D fibrin matrices for up to 4 weeks. Cellular and structural re-arrangement of the initially acellular matrix were documented by phase contrast microscopy and characterized by confocal laser-scanning microscopy of topographically intact 3D cultures and by immunohistochemistry. MSC-peripheral blood mononuclear cell (PBMC) co-cultures in the 3D fibrin system specifically addressed the influence of perivascular cell interactions to neo-vessel formation in a pro-inflammatory microenvironment. Cytokine levels in the supernatants of cultured explant tissues and co-cultures were evaluated by the Bio-Plex cytokine assay and ELISA.Results: Vascular outgrowth from the embedded tissue into the fibrin matrix was preceded by leukocyte egress from the tissue fragments. Neo-vessels originating from both the embedded sample and from clusters locally formed by emigrated mononuclear cells were consistently associated with CD45(+) leukocytes. MSC and PBMC in co-culture formed vasculogenic clusters. Clusters and cells with endothelial phenotype emerging from them, were surrounded by a collagen IV scaffold. No vascular structures were observed in control 3D monocultures of PBMC or MSC. Paracrine signals released by cultured OA tissue fragments corresponded with elevated levels of granulocyte-colony stimulating factor, vascular endothelial growth factor and interleukin-6 secreted by MSC-PBMC co-cultures.Conclusion: Our results show that synovial tissue fragments with immune cell infiltrates have the potential to form new vessels in initially avascular 3D fibrin-based matrices. Cross-talk and cluster formation of MSC with immune cells within the 3D fibrin environment through self-organization and secretion of pro-angiogenic paracrine factors can support neo-vessel growth

De novo Vessel Formation Through Cross-Talk of Blood-Derived Cells and Mesenchymal Stromal Cells in the Absence of Pre-existing Vascular Structures

Background: The generation of functional blood vessels remains a key challenge for regenerative medicine. Optimized in vitro culture set-ups mimicking the in vivo perivascular niche environment during tissue repair may provide information about the biological function and contribution of progenitor cells to postnatal vasculogenesis, thereby enhancing their therapeutic potential. Aim: We established a fibrin-based xeno-free human 3D in vitro vascular niche model to study the interaction of mesenchymal stromal cells (MSC) with peripheral blood mononuclear cells (PBMC) including circulating progenitor cells in the absence of endothelial cells (EC), and to investigate the contribution of this cross-talk to neo-vessel formation. Materials and Methods: Bone marrow-derived MSC were co-cultured with whole PBMC, enriched monocytes (Mo), enriched T cells, and Mo together with T cells, respectively, obtained from leukocyte reduction chambers generated during the process of single-donor platelet apheresis. Cells were embedded in 3D fibrin matrices, using exclusively human-derived culture components without external growth factors. Cytokine secretion was analyzed in supernatants of 3D cultures by cytokine array, vascular endothelial growth factor (VEGF) secretion was quantified by ELISA. Cellular and structural re-arrangements were characterized by immunofluorescence and confocal laser-scanning microscopy of topographically intact 3D fibrin gels. Results: 3D co-cultures of MSC with PBMC, and enriched Mo together with enriched T cells, respectively, generated, within 2 weeks, complex CD31C /CD34C vascular structures, surrounded by basement membrane collagen type-IVC cells and matrix, in association with increased VEGF secretion. PBMC contained CD31C CD34CCD45dimCD14 progenitor-type cells, and EC of neo-vessels were PBMC-derived. Vascular structures showed intraluminal CD45C cells that underwent apoptosis thereby creating a lumen. Cross-talk of MSC with enriched Mo provided a proangiogenic paracrine environment. MSC co-cultured with enriched T cells formed "cellin-cell" structures generated through internalization of T cells by CD31C CD45dim = cells. No vascular structures were detected in co-cultures of MSC with either Mo or T cells. Conclusion: Our xeno-free 3D in vitro vascular niche model demonstrates that a complex synergistic network of cellular, extracellular and paracrine cross-talk can contribute to de novo vascular development through self-organization via co-operation of immune cells with blood-derived progenitor cells and MSC, and thereby may open a new perspective for advanced vascular tissue engineering in regenerative medicine

Exome-wide Rare Variant Analysis Identifies TUBA4A Mutations Associated with Familial ALS

Exome sequencing is an effective strategy for identifying human disease genes. However, this methodology is difficult in late-onset diseases where limited availability of DNA from informative family members prohibits comprehensive segregation analysis. To overcome this limitation, we performed an exome-wide rare variant burden analysis of 363 index cases with familial ALS (FALS). The results revealed an excess of patient variants within TUBA4A, the gene encoding the Tubulin, Alpha 4A protein. Analysis of a further 272 FALS cases and 5,510 internal controls confirmed the overrepresentation as statistically significant and replicable. Functional analyses revealed that TUBA4A mutants destabilize the microtubule network, diminishing its repolymerization capability. These results further emphasize the role of cytoskeletal defects in ALS and demonstrate the power of gene-based rare variant analyses in situations where causal genes cannot be identified through traditional segregation analysis

Targeting of alpha(v) integrin identifies a core molecular pathway that regulates fibrosis in several organs

Myofibroblasts are the major source of extracellular matrix components that accumulate during tissue fibrosis, and hepatic stellate cells (HSCs) are the major source of myofibroblasts in the liver. To date, robust systems to genetically manipulate these cells have not existed. We report that Pdgfrb-Cre inactivates genes in murine HSCs with high efficiency. We used this system to delete the αv integrin subunit because of the suggested role of multiple αv integrins as central mediators of fibrosis in multiple organs. Depletion of the αv integrin subunit in HSCs protected mice from CCl(4)-induced hepatic fibrosis, whereas global loss of αvβ3, αvβ5 or αvβ6 or conditional loss of αvβ8 on HSCs did not. Pdgfrb-Cre effectively targeted myofibroblasts in multiple organs, and depletion of αv integrins using this system was also protective in models of pulmonary and renal fibrosis. Critically, pharmacological blockade of αv integrins by a novel small molecule (CWHM 12) attenuated both liver and lung fibrosis, even when administered after fibrosis was established. These data identify a core pathway that regulates fibrosis, and suggest that pharmacological targeting of all αv integrins may have clinical utility in the treatment of patients with a broad range of fibrotic diseases

An analysis of the influence of data extrema on some first and second order central approximations of hyperbolic conservation laws

We discuss the occurrence of oscillations when using central schemes of the Lax-Friedrichs type (LFt), Rusanov's method and the staggered and non-staggered second order Nessyahu-Tadmor (NT) schemes. Although these schemes are monotone or TVD, respectively, oscillations may be introduced at local data extrema. The dependence of oscillatory properties on the numerical viscosity coefficient is investigated rigorously for the LFt schemes, illuminating also the properties of Rusanov's method. It turns out, that schemes with a large viscosity coefficient are prone to oscillations at data extrema. For all LFt schemes except for the classical Lax-Friedrichs method, occurring oscillations are damped in the course of a computation. This damping effect also holds for Rusanov's method. Concerning the NT schemes, the non-staggered version may yield oscillatory results, while it can be shown rigorously that the staggered NT scheme does not produce oscillations when using the classical minmod-limiter under a restriction on the time step size. Note that this restriction is not the same as the condition ensuring the TVD property. Numerical investigations of one-dimensional scalar problems and of the system of shallow water equations in two dimensions with respect to the phenomenon complete the paper

ESAIM: Mathematical Modelling and Numerical Analysis AN ANALYSIS OF THE INFLUENCE OF DATA EXTREMA ON SOME FIRST AND SECOND ORDER CENTRAL APPROXIMATIONS OF HYPERBOLIC CONSERVATION LAWS

Abstract. We discuss the occurrence of oscillations when using central schemes of the Lax-Friedrichs type (LFt), Rusanov’s method and the staggered and non-staggered second order Nessyahu-Tadmor (NT) schemes. Although these schemes are monotone or TVD, respectively, oscillations may be introduced at local data extrema. The dependence of oscillatory properties on the numerical viscosity coefficient is investigated rigorously for the LFt schemes, illuminating also the properties of Rusanov’s method. It turns out, that schemes with a large viscosity coefficient are prone to oscillations at data extrema. For all LFt schemes except for the classical Lax-Friedrichs method, occurring oscillations are damped in the course of a computation. This damping effect also holds for Rusanov’s method. Concerning the NT schemes, the non-staggered version may yield oscillatory results, while it can be shown rigorously that the staggered NT scheme does not produce oscillations when using the classical minmod-limiter under a restriction on the time step size. Note that this restriction is not the same as the condition ensuring the TVD property. Numerical investigations of one-dimensional scalar problems and of the system of shallow water equations in two dimensions with respect to the phenomenon complete the paper