Simultaneous non-negative matrix factorization for multiple large scale gene expression datasets in toxicology

Non-negative matrix factorization is a useful tool for reducing the dimension of large datasets. This work considers simultaneous non-negative matrix factorization of multiple sources of data. In particular, we perform the first study that involves more than two datasets. We discuss the algorithmic issues required to convert the approach into a practical computational tool and apply the technique to new gene expression data quantifying the molecular changes in four tissue types due to different dosages of an experimental panPPAR agonist in mouse. This study is of interest in toxicology because, whilst PPARs form potential therapeutic targets for diabetes, it is known that they can induce serious side-effects. Our results show that the practical simultaneous non-negative matrix factorization developed here can add value to the data analysis. In particular, we find that factorizing the data as a single object allows us to distinguish between the four tissue types, but does not correctly reproduce the known dosage level groups. Applying our new approach, which treats the four tissue types as providing distinct, but related, datasets, we find that the dosage level groups are respected. The new algorithm then provides separate gene list orderings that can be studied for each tissue type, and compared with the ordering arising from the single factorization. We find that many of our conclusions can be corroborated with known biological behaviour, and others offer new insights into the toxicological effects. Overall, the algorithm shows promise for early detection of toxicity in the drug discovery process

Social Gerontology- Integrative and Territorial Aspects: A Citation Analysis of Subject Scatter and Database Coverage

To determine the mix of resources used in social gerontology research, a citation analysis was conducted. A representative sample of citations was selected from three prominent gerontology journals and information was added to determine subject scatter and database coverage for the cited materials. Results indicate that a significant portion of gerontology research, even from a social science perspective, relies roughly equally on medical resources as it does social science resources. Furthermore, there is a small but defined core of literature constituting scholarly “territory” unique to gerontology. Analysis of database indexing indicated that broad, interdisciplinary databases provide more comprehensive coverage of the cited materials than do subject-specific databases

The physical structure of urban economies -- comparative assessment

Urban metabolism provides a characterization of anthropogenic material flows in urban systemsand should contribute to identify the economic activities that were involved on their supply andtransformation. Typically, its quantification requires data that is not easily available in differentgeographies. This paper makes use of a methodology based on monetary input–output tables andinternational trade statistics that might be easily replicable to many metropolitan areas in theworld, and which is intended to provide a first rough estimation of urban material flows.The paper discusses the results obtained for four metropolitan areas (Lisbon, Paris, Seoul–Incheonand Shanghai), assessing the material requirements of these economies. The urban areas arecompared in terms of the quantity and the type of material input, destination of materials withinthe economy and their distribution among economic activities. The results showed that whileLisbon is the most diverse urban area in terms of the consumption of material types, it is also theurban area with the least diversified manufacturing sector.The application of this methodology to several urban areas and across multiple years enables theassessment of the technological and economic evolution of those regionsIndustrial Ecolog

HIV-1 remission following CCR5Δ32/Δ32 haematopoietic stem-cell transplantation

HIV-1 cure remains elusive with only one reported case a decade ago1,2. Termed the 'Berlin patient', the individual underwent two allogeneic haematopoietic stem-cell transplantation (allo-HSCT) procedures using a donor with a homozygous mutation in the HIV coreceptor CCR5 (CCR5Δ32/Δ32) to treat his acute myeloid leukaemia. Total body irradiation was given with each HSCT. Critically, it is unclear which treatment or patient parameters contributed to this only documented case of long-term HIV remission. Here we show that HIV-1 remission may be possible with a less aggressive and toxic approach. An HIV-1-infected adult underwent allo-HSCT for Hodgkin's lymphoma using cells from a CCR5Δ32/Δ32 donor. He experienced mild gut graft versus host disease. Antiretroviral therapy was interrupted 16 months after transplantation. HIV-1 remission has been maintained through a further 18 months. Plasma HIV-1 RNA has been undetectable at less than 1 copy per millilitre along with undetectable HIV-1 DNA in peripheral CD4 T lymphocytes. Quantitative viral outgrowth assay from peripheral CD4 T lymphocytes shows no reactivatable virus using a total of 24 million resting CD4 T cells. CCR5-tropic, but not CXCR4-tropic viruses were identified in HIV-1 DNA from CD4 T cells of the patient prior to transplant. CD4 T cells isolated from peripheral blood post-transplant did not express CCR5 and were only susceptible to CXCR4-tropic virus ex vivo. HIV-1 Gag-specific CD4 and CD8 T cell responses were lost after transplantation, whereas cytomegalovirus (CMV)-specific responses were detectable. Likewise, HIV-1-specific antibodies and avidities fell to levels comparable to those in the Berlin patient following transplantation. Although at 18 months post-treatment interruption it is premature to conclude that this patient has been cured, these data suggest that single allo-HSCT with homozygous CCR5Δ32 donor cells may be sufficient to achieve HIV-1 remission with reduced intensity conditioning and no irradiation, and the findings further support the development of HIV remission strategies based on preventing CCR5 expression