153 research outputs found

    Assessing the value of the housing schemes through the sustainable return of investments : a path towards sustainability-led evaluations?

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    The New 2016 UN Urban Agenda clearly reaffirms the concept that sustainable cities require intertwined environmental and social sustainability. The United Nations Sustainable Development Goal 11 - Make cities inclusive, safe, resilient and sustainable - sets as primary target the provision of sufficient affordable housing. Despite the central role played by housing in ensuring sustainability and the importance of both environmental and social pillars in ensuring sustainable development, still current evaluative methods that support decision making on social housing interventions fail in capturing all the socio-environmental spillovers. The paper addresses this issue by demonstrating how Sustainable Return Of Investment allows successfully capturing a range of externalities, related to the broader concept of sustainability also in social housing regeneration schemes. To achieve this goal, a single case study strategy has been chosen. Two extant projects - a high rise housing scheme and an environmental-led program developed by the City West Housing Trust - a nonprofit housing association based in the Manchester area - have been assessed in order to monetise their externalities through different methods. Findings show that the environmental and social spillovers are largely disregarded because of a gap in the evaluation methods and that room for significant improvements exists

    Outcomes of donor evaluation in adult-to-adult living donor liver transplantation

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    The purpose of donor evaluation for adult-to-adult living donor liver transplantation (LDLT) is to discover medical conditions that could increase the donor postoperative risk of complications and to determine whether the donor can yield a suitable graft for the recipient. We report the outcomes of LDLT donor candidates evaluated in a large multicenter study of LDLT. The records of all donor candidates and their respective recipients between 1998 and 2003 were reviewed as part of the Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL). The outcomes of the evaluation were recorded along with demographic data on the donors and recipients. Of the 1011 donor candidates evaluated, 405 (40%) were accepted for donation. The donor characteristics associated with acceptance (P < 0.05) were younger age, lower body mass index, and biological or spousal relationship to the recipient. Recipient characteristics associated with donor acceptance were younger age, lower Model for End-stage Liver Disease score, and shorter time from listing to first donor evaluation. Other predictors of donor acceptance included earlier year of evaluation and transplant center

    Donor Morbidity After Living Donation for Liver Transplantation

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    Reports of complications among adult right hepatic lobe donors have been limited to single centers. The rate and severity of complications in living donors were investigated in the 9-center Adult-to-Adult Living Donor Liver Transplantation Cohort Study (A2ALL)

    Reprogramming of Escherichia coli K-12 Metabolism during the Initial Phase of Transition from an Anaerobic to a Micro-Aerobic Environment

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    Background: Many bacteria undergo transitions between environments with differing O2 availabilities as part of their natural lifestyles and during biotechnological processes. However, the dynamics of adaptation when bacteria experience changes in O2 availability are understudied. The model bacterium and facultative anaerobe Escherichia coli K-12 provides an ideal system for exploring this process. Methods and Findings: Time-resolved transcript profiles of E. coli K-12 during the initial phase of transition from anaerobic to micro-aerobic conditions revealed a reprogramming of gene expression consistent with a switch from fermentative to respiratory metabolism. The changes in transcript abundance were matched by changes in the abundances of selected central metabolic proteins. A probabilistic state space model was used to infer the activities of two key regulators, FNR (O2 sensing) and PdhR (pyruvate sensing). The model implied that both regulators were rapidly inactivated during the transition from an anaerobic to a micro-aerobic environment. Analysis of the external metabolome and protein levels suggested that the cultures transit through different physiological states during the process of adaptation, characterized by the rapid inactivation of pyruvate formate-lyase (PFL), a slower induction of pyruvate dehydrogenase complex (PDHC) activity and transient excretion of pyruvate, consistent with the predicted inactivation of PdhR and FNR. Conclusion: Perturbation of anaerobic steady-state cultures by introduction of a limited supply of O2 combined with time-resolved transcript, protein and metabolite profiling, and probabilistic modeling has revealed that pyruvate (sensed by PdhR) is a key metabolic signal in coordinating the reprogramming of E. coli K-12 gene expression by working alongside the O2 sensor FNR during transition from anaerobic to micro-aerobic conditions

    Inhibition of phosphodiesterase-4 promotes oligodendrocyte precursor cell differentiation and enhances CNS remyelination

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    The increasing effectiveness of new disease-modifying drugs that suppress disease activity in multiple sclerosis has opened up opportunities for regenerative medicines that enhance remyelination and potentially slow disease progression. Although several new targets for therapeutic enhancement of remyelination have emerged, few lend themselves readily to conventional drug development. Here, we used transcription profiling to identify mitogen-activated protein kinase (Mapk) signalling as an important regulator involved in the differentiation of oligodendrocyte progenitor cells (OPCs) into oligodendrocytes. We show in tissue culture that activation of Mapk signalling by elevation of intracellular levels of cyclic adenosine monophosphate (cAMP) using administration of either dibutyryl-cAMP or inhibitors of the cAMP-hydrolysing enzyme phosphodiesterase-4 (Pde4) enhances OPC differentiation. Finally, we demonstrate that systemic delivery of a Pde4 inhibitor leads to enhanced differentiation of OPCs within focal areas of toxin-induced demyelination and a consequent acceleration of remyelination. These data reveal a novel approach to therapeutic enhancement of remyelination amenable to pharmacological intervention and hence with significant potential for translation

    Improvement in Survival Associated With Adult-to-Adult Living Donor Liver Transplantation

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    More than 2000 adult-to-adult living donor liver transplants (LDLT) have been performed in the U.S., yet the potential benefit to liver transplant candidates of undergoing LDLT compared to waiting for deceased donor liver transplant (DDLT) is unknown. The aim of this study was to determine if there is a survival benefit of adult LDL

    Calculation of the relative metastabilities of proteins in subcellular compartments of Saccharomyces cerevisiae

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    [abridged] Background: The distribution of chemical species in an open system at metastable equilibrium can be expressed as a function of environmental variables which can include temperature, oxidation-reduction potential and others. Calculations of metastable equilibrium for various model systems were used to characterize chemical transformations among proteins and groups of proteins found in different compartments of yeast cells. Results: With increasing oxygen fugacity, the relative metastability fields of model proteins for major subcellular compartments go as mitochondrion, endoplasmic reticulum, cytoplasm, nucleus. In a metastable equilibrium setting at relatively high oxygen fugacity, proteins making up actin are predominant, but those constituting the microtubule occur with a low chemical activity. A reaction sequence involving the microtubule and spindle pole proteins was predicted by combining the known intercompartmental interactions with a hypothetical program of oxygen fugacity changes in the local environment. In further calculations, the most-abundant proteins within compartments generally occur in relative abundances that only weakly correspond to a metastable equilibrium distribution. However, physiological populations of proteins that form complexes often show an overall positive or negative correlation with the relative abundances of proteins in metastable assemblages. Conclusions: This study explored the outlines of a thermodynamic description of chemical transformations among interacting proteins in yeast cells. The results suggest that these methods can be used to measure the degree of departure of a natural biochemical process or population from a local minimum in Gibbs energy.Comment: 32 pages, 7 figures; supporting information is available at http://www.chnosz.net/yeas

    Inhibition of phosphodiesterase‐4 promotes oligodendrocyte precursor cell differentiation and enhances CNS

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    The increasing effectiveness of new disease-modifying drugs that suppress disease activity in multiple sclerosis has opened up opportunities for regenerative medicines that enhance remyelination and potentially slow disease progression. Although several new targets for therapeutic enhancement of remyelination have emerged, few lend themselves readily to conventional drug development. Here, we used transcription profiling to identify mitogen-activated protein kinase (Mapk) signalling as an important regulator involved in the differentiation of oligodendrocyte progenitor cells (OPCs) into oligodendrocytes. We show in tissue culture that activation of Mapk signalling by elevation of intracellular levels of cyclic adenosine monophosphate (cAMP) using administration of either dibutyryl-cAMP or inhibitors of the cAMP-hydrolysing enzyme phosphodiesterase-4 (Pde4) enhances OPC differentiation. Finally, we demonstrate that systemic delivery of a Pde4 inhibitor leads to enhanced differentiation of OPCs within focal areas of toxin-induced demyelination and a consequent acceleration of remyelination. These data reveal a novel approach to therapeutic enhancement of remyelination amenable to pharmacological intervention and hence with significant potential for translation
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