Segmentation fusion for connectomics

We address the problem of automatic 3D segmentation of a stack of electron microscopy sections of brain tissue. Unlike previous efforts, where the reconstruction is usually done on a section-to-section basis, or by the agglomerative clustering of 2D segments, we leverage information from the entire volume to obtain a globally optimal 3D segmentation. To do this, we formulate the segmentation as the solution to a fusion problem. We first enumerate multiple possible 2D segmentations for each section in the stack, and a set of 3D links that may connect segments across consecutive sections. We then identify the fusion of segments and links that provide the most globally consistent segmentation of the stack. We show that this two-step approach of pre-enumeration and posterior fusion yields significant advantages and provides state-of-the-art reconstruction results. Finally, as part of this method, we also introduce a robust rotationally-invariant set of features that we use to learn and enumerate the above 2D segmentations. Our features outperform previous connectomic-specific descriptors without relying on a large set of heuristics or manually designed filter banks.Engineering and Applied Science

Ebola research funding: a systematic analysis, 1997–2015

Background: The latest outbreak of Ebola in West Africa overwhelmed the affected countries, with the impact on health extending far beyond Ebola–related deaths that have exceeded 11?000. The need to promptly mobilise resources to control emerging infections is widely recognized. Yet, data on research funding for emerging infections remains inadequately documented.Methods: We defined research investment as all funding flows for Ebola and/or Marburg virus from 1997 to April 2015 whose primary purpose was to advance knowledge and new technologies to prevent or cure disease. We sourced data directly from funding organizations and estimated the investment in 2015 US dollars (US$).Results: Funding for Ebola and Marburg virus research in 1997 to 2015 amounted to US$ 1.035 billion, including US$435.4 million (42.0$ 758.8 million (73.1%), philanthropic sources US$65.1 million (6.3$ 213.8 million (20.6%). Prior to the Ebola outbreak in 2014, pre–clinical research dominated research with US$443.6 million (73.9$ 399.1 million, with 61.3% awarded for vaccine research, 29.2% for novel therapeutics research such as antivirals and convalescent blood products, and 9.5% for diagnostics research. Research funding and bibliometric output were moderately associated (Spearman's ??=?0.5232, P?=?0.0259), however number of Ebola cases in previous outbreaks and research funding (??=?0.1706, P?=?0.4985) and Ebola cases in previous outbreaks and research output (??=?0.3020, P?=?0.0616) were poorly correlated.Conclusion: Significant public and philanthropic funds have been invested in Ebola and Marburg virus research in 2014 and 2015, following the outbreak in West Africa. Long term, strategic vision and leadership are needed to invest in infections with pandemic potential early, including innovative financing measures and open access investment data to promote the development of new therapies and technologies

Segmentation fusion for connectomics

We address the problem of automatic 3D segmentation of a stack of electron microscopy sections of brain tissue. Unlike previous efforts, where the reconstruction is usually done on a section-to-section basis, or by the agglomerative clustering of 2D segments, we leverage information from the entire volume to obtain a globally optimal 3D segmen-tation. To do this, we formulate the segmentation as the so-lution to a fusion problem. We first enumerate multiple pos-sible 2D segmentations for each section in the stack, and a set of 3D links that may connect segments across con-secutive sections. We then identify the fusion of segments and links that provide the most globally consistent segmen-tation of the stack. We show that this two-step approach of pre-enumeration and posterior fusion yields significant advantages and provides state-of-the-art reconstruction re-sults. Finally, as part of this method, we also introduce a robust rotationally-invariant set of features that we use to learn and enumerate the above 2D segmentations. Our fea-tures outperform previous connectomic-specific descriptors without relying on a large set of heuristics or manually de-signed filter banks. 1

A National Network of Neurotechnology Centers for the BRAIN Initiative

We propose the creation of a national network of neurotechnology centers to enhance and accelerate the BRAIN Initiative and optimally leverage the effort and creativity of individual laboratories involved in it. As ‘‘brain observatories,’’ these centers could provide the critical interdisciplinary environment both for realizing ambitious and complex technologies and for providing individual investigators with access to them

CD8+-T Cells With Specificity for a Model Antigen in Cardiomyocytes Can Become Activated After Transverse Aortic Constriction but Do Not Accelerate Progression to Heart Failure

Heart failure due to pressure overload is frequently associated with inflammation. In addition to inflammatory responses of the innate immune system, autoimmune reactions of the adaptive immune system appear to be triggered in subgroups of patients with heart failure as demonstrated by the presence of autoantibodies against myocardial antigens. Moreover, T cell-deficient and T cell-depleted mice have been reported to be protected from heart failure induced by transverse aortic constriction (TAC) and we have shown recently that CD4+-helper T cells with specificity for an antigen in cardiomyocytes accelerate TAC-induced heart failure. In this study, we set out to investigate the potential contribution of CD8+-cytotoxic T cells with specificity to a model antigen (ovalbumin, OVA) in cardiomyocytes to pressure overload-induced heart failure. In 78% of cMy-mOVA mice with cardiomyocyte-specific OVA expression, a low-grade OVA-specific cellular cytotoxicity was detected after TAC. Adoptive transfer of OVA-specific CD8+-T cells from T cell receptor transgenic OT-I mice before TAC did not increase the risk of OVA-specific autoimmunity in cMy-mOVA mice. After TAC, again 78% of the mice displayed an OVA-specific cytotoxicity with on average only a three-fold higher killing of OVA-expressing target cells. More CD8+ cells were present after TAC in the myocardium of cMy-mOVA mice with OT-I T cells (on average 17.5/mm2) than in mice that did not receive OVA-specific CD8+-T cells (3.6/mm2). However, the extent of fibrosis was similar in both groups. Functionally, as determined by echocardiography, the adoptive transfer of OVA-specific CD8+-T cells did not significantly accelerate the progression from hypertrophy to heart failure in cMy-mOVA mice. These findings argue therefore against a major impact of cytotoxic T cells with specificity for autoantigens of cardiomyocytes in pressure overload-induced heart failure