Cross-reactivity between HLA-A2-restricted FLU-M1:58–66 and HIV p17 GAG:77–85 epitopes in HIV-infected and uninfected individuals

BACKGROUND: The matrix protein of the influenza A virus and the matrix and capsid proteins of the human immunodeficiency virus (HIV) share striking structural similarities which may have evolutionary and biological significance. These similarities led us to hypothesize the existence of cross-reactivity between HLA-A2-restricted FLU-M1:58–66 and HIV-1 p17 GAG:77–85 epitopes. METHODS: The hypothesis that these two epitopes are cross-reactive was tested by determining the presence and extent of FLU/GAG immune cross-reactivity in lymphocytes from HIV-seropositive and seronegative HLA-A2(+ )donors by cytotoxicity assays and tetramer analyses. Moreover, the molecular basis for FLU/GAG cross-reactivity in HIV-seropositive and seronegative donors was studied by comparing lymphocyte-derived cDNA sequences corresponding to the TCR-β variable regions, in order to determine whether stimulation of lymphocytes with either peptide results in the expansion of identical T-cell clonotypes. RESULTS: Here, we report evidence of cross-reactivity between FLU-M1:58–66 and HIV-1 p17 GAG:77–85 epitopes following in vitro stimulation of PBMC derived from either HIV-seropositive or seronegative HLA-A2(+ )donors as determined by cytotoxicity assays, tetramer analyses, and molecular clonotyping. CONCLUSION: These results suggest that immunity to the matrix protein of the influenza virus may drive a specific immune response to an HLA-A2-restricted HIV gag epitope in HIV-infected and uninfected donors vaccinated against influenza

From Multiview Image Curves to 3D Drawings

Reconstructing 3D scenes from multiple views has made impressive strides in recent years, chiefly by correlating isolated feature points, intensity patterns, or curvilinear structures. In the general setting - without controlled acquisition, abundant texture, curves and surfaces following specific models or limiting scene complexity - most methods produce unorganized point clouds, meshes, or voxel representations, with some exceptions producing unorganized clouds of 3D curve fragments. Ideally, many applications require structured representations of curves, surfaces and their spatial relationships. This paper presents a step in this direction by formulating an approach that combines 2D image curves into a collection of 3D curves, with topological connectivity between them represented as a 3D graph. This results in a 3D drawing, which is complementary to surface representations in the same sense as a 3D scaffold complements a tent taut over it. We evaluate our results against truth on synthetic and real datasets.Comment: Expanded ECCV 2016 version with tweaked figures and including an overview of the supplementary material available at multiview-3d-drawing.sourceforge.ne

MFGE8 does not influence chorio-retinal homeostasis or choroidal neovascularization in vivo

Purpose: Milk fat globule-epidermal growth factor-factor VIII (MFGE8) is necessary for diurnal outer segment phagocytosis and promotes VEGF-dependent neovascularization. The prevalence of two single nucleotide polymorphisms (SNP) in MFGE8 was studied in two exsudative or “wet” Age-related Macular Degeneration (AMD) groups and two corresponding control groups. We studied the effect of MFGE8 deficiency on retinal homeostasis with age and on choroidal neovascularization (CNV) in mice. Methods: The distribution of the SNP (rs4945 and rs1878326) of MFGE8 was analyzed in two groups of patients with “wet” AMD and their age-matched controls from Germany and France. MFGE8-expressing cells were identified in Mfge8+/− mice expressing ß-galactosidase. Aged Mfge8+/− and Mfge8−/− mice were studied by funduscopy, histology, electron microscopy, scanning electron microscopy of vascular corrosion casts of the choroid, and after laser-induced CNV. Results: rs1878326 was associated with AMD in the French and German group. The Mfge8 promoter is highly active in photoreceptors but not in retinal pigment epithelium cells. Mfge8−/− mice did not differ from controls in terms of fundus appearance, photoreceptor cell layers, choroidal architecture or laser-induced CNV. In contrast, the Bruch's membrane (BM) was slightly but significantly thicker in Mfge8−/− mice as compared to controls. Conclusions: Despite a reproducible minor increase of rs1878326 in AMD patients and a very modest increase in BM in Mfge8−/− mice, our data suggests that MFGE8 dysfunction does not play a critical role in the pathogenesis of AMD

Albumin Microspheres as “Trans-ferry-beads” for Easy Cell Passaging in Cell Culture Technology

Protein hydrogels represent ideal materials for advanced cell culture applications, including 3D-cultivation of even fastidious cells. Key properties of fully functional and, at the same time, economically successful cell culture materials are excellent biocompatibility and advanced fabrication processes allowing their easy production even on a large scale based on affordable compounds. Chemical crosslinking of bovine serum albumin (BSA) with N-(3-dimethylaminopropyl)-N’-ethylcarbodiimide hydrochloride (EDC) in a water-in-oil emulsion with isoparaffinic oil as the continuous phase and sorbitan monooleate as surfactant generates micro-meter-scale spherical particles. They allow a significant simplification of an indispensable and laborious step in traditional cell culture workflows. This cell passaging (or splitting) to fresh culture vessels/flasks conventionally requires harsh trypsinization, which can be omitted by using the “trans-ferry-beads” presented here. When added to different pre-cultivated adherent cell lines, the beads are efficiently boarded by cells as passengers and can be easily transferred afterward for the embarkment of novel flasks. After this procedure, cells are perfectly viable and show normal growth behavior. Thus, the trans-ferry-beads not only may become extremely affordable as a final product but also may generally replace trypsinization in conventional cell culture, thereby opening new routes for the establishment of optimized and resource-efficient workflows in biological and medical cell culture laboratories

Amplifying Signals and avoiding surprises: Potential synergies between ICOS and eLTER at the Water-Climate-Greenhouse Gas nexus

Environmental thresholds. tipping points and subsequent regime shifts associated with the water/climate/greenhouse gas nexus pose a genuine threat to sustainability. Both the ongoing forest dieback in Central Europe caused by the extreme droughts of the last years and the effect of global warming on ecosystem functioning have the potential to cause ecological surprise (sensu Lindenmayer et al. 2010) where ecosystems are pushed into new, unexpected and usually undesirable states. Formulating appropriate scientific and societal responses to such regime shifts requires breadth, depth, intensity and duration of environmental, ecological and socio-ecological monitoring. Broad geographic coverage to encompass relevant biophysical and societal gradients, consideration of all appropriate parameters, adequate measurement frequency and long-term, standardized observations are all needed to provide reliable early warnings of severe environmental change, test ecosystem models, avoid double counting in carbon accounting and to reduce the likelihood of undesirable ecological outcomes. This is especially true of events driven by simultaneous changes in climate, the water cycle and human activities. Well-supported, site-based research infrastructures (RIs; e.g., eLTER and ICOS) are essential tools with the necessary breadth, depth, intensity and duration for early detection and attribution of environmental change. Individually, the eLTER and ICOS RIs generate a wealth of data supporting the ecosystem and carbon research communities. Achieving synergies between the two RIs can add value to both communities and potentially offer meaningful insight into the European water-climate-greenhouse gas nexus. The unique insights into processes and mechanisms of ecosystem dynamics and functioning obtained from high intensity monitoring conducted by the ICOS RI greatly increase the likelihood of detecting signals of environmental change. These signals must be placed into the context of their long-term trajectory and potential societal and environmental drivers. The spatially extensive, long-term, multi-disciplinary monitoring conducted at LTER sites and LTSER platforms under the umbrella of the eLTER programme can provide this context. Here, we outline one potential roadmap for achieving synergies between the ICOS and eLTER RIs focussing on the value of co-location for improved understanding of the water/climate/greenhouse gas nexus. Based on data and experiences from intensively studied research sites, we highlight some of the possibilities for reducing the likelihood of ecological surprise that could result from such synergies.Peer reviewe

A supervised hierarchical segmentation of remote-sensing images using a committee of multi-scale convolutional neural networks

This paper presents a supervised, hierarchical remote-sensing image segmentation technique using a committee of multi-scale convolutional neural networks. With existing techniques, segmentation is achieved through fine-tuning a set of predefined feature detectors. However, such a solution is not robust since the introduction of new sensors or applications would require novel features and techniques to be developed. Conversely, the proposed method achieves segmentation through a set of learnt feature detectors. In order to learn feature detectors, the proposed method exploits a committee of convolutional neural networks that perform multi-scale analysis on each band in order to derive individual confidence maps on region boundaries. Confidence maps are then inter-fused in order to produce a fused confidence map. Furthermore, the fused map is intra-fused using a morphological scheme into a hierarchical segmentation map. The proposed method is quantitatively compared to baseline techniques on a publicly available data set. The results presented in this paper highlight the improved accuracy of the proposed method

Reanalysis in Earth System Science: Towards Terrestrial Ecosystem Reanalysis

A reanalysis is a physically consistent set of optimally merged simulated model states and historical observational data, using data assimilation. High computational costs for modelled processes and assimilation algorithms has led to Earth system specific reanalysis products for the atmosphere, the ocean and the land separately. Recent developments include the advanced uncertainty quantification and the generation of biogeochemical reanalysis for land and ocean. Here, we review atmospheric and oceanic reanalyses, and more in detail biogeochemical ocean and terrestrial reanalyses. In particular, we identify land surface, hydrologic and carbon cycle reanalyses which are nowadays produced in targeted projects for very specific purposes. Although a future joint reanalysis of land surface, hydrologic and carbon processes represents an analysis of important ecosystem variables, biotic ecosystem variables are assimilated only to a very limited extent. Continuous data sets of ecosystem variables are needed to explore biotic-abiotic interactions and the response of ecosystems to global change. Based on the review of existing achievements, we identify five major steps required to develop terrestrial ecosystem reanalysis to deliver continuous data streams on ecosystem dynamics

Semi-automatic identification of punching areas for tissue microarray building: the tubular breast cancer pilot study

Background: Tissue MicroArray technology aims to perform immunohistochemical staining on hundreds of different tissue samples simultaneously. It allows faster analysis, considerably reducing costs incurred in staining. A time consuming phase of the methodology is the selection of tissue areas within paraffin blocks: no utilities have been developed for the identification of areas to be punched from the donor block and assembled in the recipient block.Results: The presented work supports, in the specific case of a primary subtype of breast cancer (tubular breast cancer), the semi-automatic discrimination and localization between normal and pathological regions within the tissues. The diagnosis is performed by analysing specific morphological features of the sample such as the absence of a double layer of cells around the lumen and the decay of a regular glands-and-lobules structure. These features are analysed using an algorithm which performs the extraction of morphological parameters from images and compares them to experimentally validated threshold values. Results are satisfactory since in most of the cases the automatic diagnosis matches the response of the pathologists. In particular, on a total of 1296 sub-images showing normal and pathological areas of breast specimens, algorithm accuracy, sensitivity and specificity are respectively 89%, 84% and 94%.Conclusions: The proposed work is a first attempt to demonstrate that automation in the Tissue MicroArray field is feasible and it can represent an important tool for scientists to cope with this high-throughput technique

Steering Operational Synergies in Terrestrial Observation Networks: Opportunity for Advancing Earth System Dynamics Modelling

Advancing our understanding of Earth system dynamics (ESD) depends on the development of models and other analytical tools that apply physical, biological, and chemical data. This ambition to increase understanding and develop models of ESD based on site observations was the stimulus for creating the networks of Long-Term Ecological Research (LTER), Critical Zone Observatories (CZOs), and others. We organized a survey, the results of which identified pressing gaps in data availability from these networks, in particular for the future development and evaluation of models that represent ESD processes, and provide insights for improvement in both data collection and model integration. From this survey overview of data applications in the context of LTER and CZO research, we identified three challenges: (1) widen application of terrestrial observation network data in Earth system modelling, (2) develop integrated Earth system models that incorporate process representation and data of multiple disciplines, and (3) identify complementarity in measured variables and spatial extent, and promoting synergies in the existing observational networks. These challenges lead to perspectives and recommendations for an improved dialogue between the observation networks and the ESD modelling community, including co-location of sites in the existing networks and further formalizing these recommendations among these communities. Developing these synergies will enable cross-site and cross-network comparison and synthesis studies, which will help produce insights around organizing principles, classifications, and general rules of coupling processes with environmental conditions