Improved thermal isolation of silicon suspended platforms for an all-silicon thermoelectric microgenerator based on large scale integration of Si nanowires as thermoelectric material

Special suspended micro-platforms have been designed as a part of silicon compatible planar thermoelectric microgenerators. Bottom-up grown silicon nanowires are going to bridge in the future such platforms to the surrounding silicon bulk rim. They will act as thermoelectric material thus configuring an all-silicon thermoelectric device. In the new platform design other additional bridging elements (usually auxiliary support silicon beams) are substituted by low conductance thin film dielectric membranes in order to maximize the temperature difference developed between both areas. These membranes follow a sieve-like design that allows fabricating them with a short additional wet anisotropic etch step. © Published under licence by IOP Publishing Ltd.Peer ReviewedPostprint (published version

Critical Behavior of Three-Dimensional Disordered Potts Models with Many States

We study the 3D Disordered Potts Model with p=5 and p=6. Our numerical simulations (that severely slow down for increasing p) detect a very clear spin glass phase transition. We evaluate the critical exponents and the critical value of the temperature, and we use known results at lower $p$ values to discuss how they evolve for increasing p. We do not find any sign of the presence of a transition to a ferromagnetic regime.Comment: 9 pages and 9 Postscript figures. Final version published in J. Stat. Mec

Respiratory Immunization With a Whole Cell Inactivated Vaccine Induces Functional Mucosal Immunoglobulins Against Tuberculosis in Mice and Non-human Primates

Vaccination through the natural route of infection represents an attractive immunization strategy in vaccinology. In the case of tuberculosis, vaccine delivery by the respiratory route has regained interest in recent years, showing efficacy in different animal models. In this context, respiratory vaccination triggers lung immunological mechanisms which are omitted when vaccines are administered by parenteral route. However, contribution of mucosal antibodies to vaccine- induced protection has been poorly studied. In the present study, we evaluated in mice and non-human primates (NHP) a novel whole cell inactivated vaccine (MTBVAC HK), by mucosal administration. MTBVAC HK given by intranasal route to BCG-primed mice substantially improved the protective efficacy conferred by subcutaneous BCG only. Interestingly, this improved protection was absent in mice lacking polymeric Ig receptor (pIgR), suggesting a crucial role of mucosal secretory immunoglobulins in protective immunity. Our study in NHP confirmed the ability of MTBVAC HK to trigger mucosal immunoglobulins. Importantly, in vitro assays demonstrated the functionality of these immunoglobulins to induce M. tuberculosis opsonization in the presence of human macrophages. Altogether, our results suggest that mucosal immunoglobulins can be induced by vaccination to improve protection against tuberculosis and therefore, they represent a promising target for next generation tuberculosis vaccines

IEA EBC Annex 57 ‘Evaluation of Embodied Energy and CO_2eq for Building Construction'

The current regulations to reduce energy consumption and greenhouse gas emissions (GHG) from buildings have focused on operational energy consumption. Thus legislation excludes measurement and reduction of the embodied energy and embodied GHG emissions over the building life cycle. Embodied impacts are a significant and growing proportion and it is increasingly recognized that the focus on reducing operational energy consumption needs to be accompanied by a parallel focus on reducing embodied impacts. Over the last six years the Annex 57 has addressed this issue, with researchers from 15 countries working together to develop a detailed understanding of the multiple calculation methods and the interpretation of their results. Based on an analysis of 80 case studies, Annex 57 showed various inconsistencies in current methodological approaches, which inhibit comparisons of results and difficult development of robust reduction strategies. Reinterpreting the studies through an understanding of the methodological differences enabled the cases to be used to demonstrate a number of important strategies for the reduction of embodied impacts. Annex 57 has also produced clear recommendations for uniform definitions and templates which improve the description of system boundaries, completeness of inventory and quality of data, and consequently the transparency of embodied impact assessments

DOR/Tp53inp2 and Tp53inp1 Constitute a Metazoan Gene Family Encoding Dual Regulators of Autophagy and Transcription

Human DOR/TP53INP2 displays a unique bifunctional role as a modulator of autophagy and gene transcription. However, the domains or regions of DOR that participate in those functions have not been identified. Here we have performed structure/function analyses of DOR guided by identification of conserved regions in the DOR gene family by phylogenetic reconstructions. We show that DOR is present in metazoan species. Invertebrates harbor only one gene, DOR/Tp53inp2, and in the common ancestor of vertebrates Tp53inp1 may have arisen by gene duplication. In keeping with these data, we show that human TP53INP1 regulates autophagy and that different DOR/TP53INP2 and TP53INP1 proteins display transcriptional activity. The use of molecular evolutionary information has been instrumental to determine the regions that participate in DOR functions. DOR and TP53INP1 proteins share two highly conserved regions (region 1, aa residues 28–42; region 2, 66–112 in human DOR). Mutation of conserved hydrophobic residues in region 1 of DOR (that are part of a nuclear export signal, NES) reduces transcriptional activity, and blocks nuclear exit and autophagic activity under autophagy-activated conditions. We also identify a functional and conserved LC3-interacting motif (LIR) in region 1 of DOR and TP53INP1 proteins. Mutation of conserved acidic residues in region 2 of DOR reduces transcriptional activity, impairs nuclear exit in response to autophagy activation, and disrupts autophagy. Taken together, our data reveal DOR and TP53INP1 as dual regulators of transcription and autophagy, and identify two conserved regions in the DOR family that concentrate multiple functions crucial for autophagy and transcription

Implication for Functions of the Ectopic Adipocyte Copper Amine Oxidase (AOC3) from Purified Enzyme and Cell-Based Kinetic Studies

AOC3 is highly expressed in adipocytes and smooth muscle cells, but its function in these cells is currently unknown. The in vivo substrate(s) of AOC3 is/are also unknown, but could provide an invaluable clue to the enzyme's function. Expression of untagged, soluble human AOC3 in insect cells provides a relatively simple means of obtaining pure enzyme. Characterization of enzyme indicates a 6% titer for the active site 2,4,5-trihydroxyphenylalanine quinone (TPQ) cofactor and corrected kcat values as high as 7 s−1. Substrate kinetic profiling shows that the enzyme accepts a variety of primary amines with different chemical features, including nonphysiological branched-chain and aliphatic amines, with measured kcat/Km values between 102 and 104 M−1 s−1. Km(O2) approximates the partial pressure of oxygen found in the interstitial space. Comparison of the properties of purified murine to human enzyme indicates kcat/Km values that are within 3 to 4-fold, with the exception of methylamine and aminoacetone that are ca. 10-fold more active with human AOC3. With drug development efforts investigating AOC3 as an anti-inflammatory target, these studies suggest that caution is called for when screening the efficacy of inhibitors designed against human enzymes in non-transgenic mouse models. Differentiated murine 3T3-L1 adipocytes show a uniform distribution of AOC3 on the cell surface and whole cell Km values that are reasonably close to values measured using purified enzymes. The latter studies support a relevance of the kinetic parameters measured with isolated AOC3 variants to adipocyte function. From our studies, a number of possible substrates with relatively high kcat/Km have been discovered, including dopamine and cysteamine, which may implicate a role for adipocyte AOC3 in insulin-signaling and fatty acid metabolism, respectively. Finally, the demonstrated AOC3 turnover of primary amines that are non-native to human tissue suggests possible roles for the adipocyte enzyme in subcutaneous bacterial infiltration and obesity

Vascular adhesion protein-1 promotes liver inflammation and drives hepatic fibrosis

Nonalcoholic fatty liver disease (NAFLD) encompasses a range of manifestations, including steatosis and cirrhosis. Progressive disease is characterized by hepatic leukocyte accumulation in the form of steatohepatitis. The adhesion molecule vascular adhesion protein-1 (VAP-1) is a membrane-bound amine oxidase that promotes leukocyte recruitment to the liver, and the soluble form (sVAP-1) accounts for most circulating monoamine oxidase activity, has insulin-like effects, and can initiate oxidative stress. Here, we determined that hepatic VAP-1 expression is increased in patients with chronic liver disease and that serum sVAP-1 levels are elevated in patients with NAFLD compared with those in control individuals. In 4 murine hepatic injury models, an absence or blockade of functional VAP-1 reduced inflammatory cell recruitment to the liver and attenuated fibrosis. Moreover, disease was reduced in animals expressing a catalytically inactive form of VAP-1, implicating enzyme activity in the disease pathogenesis. Within the liver, hepatic stromal cells expressed functional VAP-1, and evaluation of cultured cells revealed that sVAP-1 promotes leukocyte migration through catalytic generation of ROS, which depended on VAP-1 enzyme activity. VAP-1 enhanced stromal cell spreading and wound closure and modulated expression of profibrotic genes. Together, these results link the amine oxidase activity of VAP-1 with hepatic inflammation and fibrosis and suggest that targeting VAP-1 has therapeutic potential for NAFLD and other chronic fibrotic liver diseases

Improved thermal isolation of silicon suspended platforms for an all-silicon thermoelectric microgenerator based on large scale integration of Si nanowires as thermoelectric material

Special suspended micro-platforms have been designed as a part of silicon compatible planar thermoelectric microgenerators. Bottom-up grown silicon nanowires are going to bridge in the future such platforms to the surrounding silicon bulk rim. They will act as thermoelectric material thus configuring an all-silicon thermoelectric device. In the new platform design other additional bridging elements (usually auxiliary support silicon beams) are substituted by low conductance thin film dielectric membranes in order to maximize the temperature difference developed between both areas. These membranes follow a sieve-like design that allows fabricating them with a short additional wet anisotropic etch step. © Published under licence by IOP Publishing Ltd.Peer Reviewe