The laboratory rat (Rattus norvegicus) is an indispensable tool in experimental medicine and drug development, having made inestimable contributions to human health. We report here the genome sequence of the Brown Norway (BN) rat strain. The sequence represents a high-quality 'draft' covering over 90% of the genome. The BN rat sequence is the third complete mammalian genome to be deciphered, and three-way comparisons with the human and mouse genomes resolve details of mammalian evolution. This first comprehensive analysis includes genes and proteins and their relation to human disease, repeated sequences, comparative genome-wide studies of mammalian orthologous chromosomal regions and rearrangement breakpoints, reconstruction of ancestral karyotypes and the events leading to existing species, rates of variation, and lineage-specific and lineage-independent evolutionary events such as expansion of gene families, orthology relations and protein evolution.

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WirelessHART

Neural networks are typically designed to deal with data in tensor forms. In this paper, we propose a novel neural network architecture accepting graphs of arbitrary structure. Given a dataset containing graphs in the form of (G,y) where G is a graph and y is its class, we aim to develop neural networks that read the graphs directly and learn a classification function. There are two main challenges: 1) how to extract useful features characterizing the rich information encoded in a graph for classification purpose, and 2) how to sequentially read a graph in a meaningful and consistent order. To address the first challenge, we design a localized graph convolution model and show its connection with two graph kernels. To address the second challenge, we design a novel SortPooling layer which sorts graph vertices in a consistent order so that traditional neural networks can be trained on the graphs. Experiments on benchmark graph classification datasets demonstrate that the proposed architecture achieves highly competitive performance with state-of-the-art graph kernels and other graph neural network methods. Moreover, the architecture allows end-to-end gradient-based training with original graphs, without the need to first transform graphs into vectors.

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Hemophilia is a rare congenital bleeding disorder that is due to the deficiency of blood coagulation factor VIII or IX. Recurrent musculoskeletal bleeding is common and bleeding into joints results in a chronic inflammatory condition termed hemophilic synovitis. This destructive process is characterized by hemosiderin deposition in the superficial and deeper layers of the synovial membrane as well as a proliferation of synovial fibroblasts and vascular cells. The hyperplastic synovium and neovascular changes are reminiscent of the histopathologic appearance observed in malignant tissues. Indeed, the benign hyperplastic synovium in patients with hemophilia displays similar invasive and destructive behaviors suggesting the possibility of analogous disturbances in growth control and locally invasive mechanisms. Iron plays a role in malignant cell growth, local invasion, and tumor progression, possibly due to changes in the expression of the proto-oncogene, c-myc. We hypothesized that iron plays a similar role in hemophilic synovitis. To explore this hypothesis, we investigated the in vitro effects of iron on the proliferation of a primary, human synovial fibroblast cell (HSFC) line and the involvement of c-myc in this process. We also examined the role of ceramide, a sphingolipid capable of inducing apoptosis in this model system. HSFC proliferation was increased in a dose-dependent fashion and c-myc expression was enhanced by ferric citrate compared to sodium citrate control. Ceramide prevented both the iron-induced increases in HSFC proliferation and c-myc expression. These results indicate that iron probably plays a role in the proliferative changes observed in hemophilic joint disease and that aberrant expression of c-myc may underlie the iron effects. Furthermore, these results suggest that there may be a therapeutic role for ceramide in reversing these changes. IntroductionRecurrent musculoskeletal bleeding is the most frequent manifestation of severe hemophilia. Bleeding into a joint results in a complex arthritis known as "hemophilic arthropathy" that in time evolves into a chronic, persistent inflammatory disorder termed "hemophilic synovitis." It has been speculated that the persistent presence of blood in the joint space is involved in the pathogenesis of this disorder. 1 Iron deposition in synovial tissues is one of the hallmarks of hemophilic arthropathy. [2][3][4] In vitro, DNA synthesis by synovial fibroblast cells exposed to ferric citrate at concentrations up to 1 mM for 72 hours is increased compared to cells cultured with sodium citrate. 5 Iron, in combination with interleukin-1␤ (IL-␤), IL-7, tumor necrosis factor ␣ (TNF-␣), or interferon ␥ (IFN-␥) exerts an additive effect on DNA synthesis suggesting that iron increases cell proliferation by a mechanism distinct from inflammatory cytokines. 5 In vitro, cells isolated from hemophilic synovial tissue produce more IL-1␤, IL-6, and TNF-␣ compared to cells from normal synovial tissue. 4 Monocytes and synovial fibroblasts are capable of generating m...