A review of existing building benchmarks and the development of a set of reference office buildings for England and Wales

The modern built environment has become more complex in terms of building types, environmental systems and use profiles. This complexity causes difficulties in terms of optimising buildings energy design. In this circumstance, introducing a set of prototype reference buildings, or so called benchmark buildings, that are able to represent all or majority parts of the UK building stock may be useful for the examination of the impact of national energy policies on building energy consumption. This study proposes a set of reference office buildings for England and Wales based on the information collected from the Non-Domestic Building Stock (NDBS) project and an intensive review of the existing building benchmarks. The proposed building benchmark comprises 10 prototypical reference buildings, which in relation to built form and size, represent 95% of office buildings in England and Wales. This building benchmark provides a platform for those involved in building energy simulations to evaluate energy-efficiency measures and for policy-makers to assess the influence of different building energy policies.

Clonal expansion of early to mid-life mitochondrial DNA point mutations drives mitochondrial dysfunction during human ageing

Age-related decline in the integrity of mitochondria is an important contributor to the human ageing process. In a number of ageing stem cell populations, this decline in mitochondrial function is due to clonal expansion of individual mitochondrial DNA (mtDNA) point mutations within single cells. However the dynamics of this process and when these mtDNA mutations occur initially are poorly understood. Using human colorectal epithelium as an exemplar tissue with a well-defined stem cell population, we analysed samples from 207 healthy participants aged 17-78 years using a combination of techniques (Random Mutation Capture, Next Generation Sequencing and mitochondrial enzyme histochemistry), and show that: 1) non-pathogenic mtDNA mutations are present from early embryogenesis or may be transmitted through the germline, whereas pathogenic mtDNA mutations are detected in the somatic cells, providing evidence for purifying selection in humans, 2) pathogenic mtDNA mutations are present from early adulthood (<20 years of age), at both low levels and as clonal expansions, 3) low level mtDNA mutation frequency does not change significantly with age, suggesting that mtDNA mutation rate does not increase significantly with age, and 4) clonally expanded mtDNA mutations increase dramatically with age. These data confirm that clonal expansion of mtDNA mutations, some of which are generated very early in life, is the major driving force behind the mitochondrial dysfunction associated with ageing of the human colorectal epithelium.

RE1 silencing transcription factor/neuron-restrictive silencing factor regulates expansion of adult mouse subventricular zone-derived neural stem/progenitor cells in vitro

Adult neural stem cell (aNSC) activity is tuned by external stimuli through the recruitment of transcription factors. This study examines the RE1 silencing transcription factor (REST) in neural stem/progenitor cells isolated from the subventricular zone of adult mouse brain and provides the first extensive characterization of REST-mediated control of the cellular and molecular properties. This study shows that REST knockdown affects the capacity of progenitor cells to generate neurospheres, reduces cell proliferation, and triggers cell differentiation despite the presence of growth factors. Genome- and transcriptome-wide analyses show that REST binding sites are significantly enriched in genes associated with synaptic transmission and nervous system development and function. Seeking candidate regulators of aNSC function, this study identifies a member of the bone morphogenetic protein (BMP) family, BMP6, the mRNA and protein of which increased after REST knockdown. The results of this study extend previous findings, demonstrating a reciprocal control of REST expression by BMPs. Administration of exogenous BMP6 inhibits aNSC proliferation and induces the expression of the astrocytic marker glial fibrillary acidic protein, highlighting its antimitogenic and prodifferentiative effects. This study suggests that BMP6 produced in a REST-regulated manner together with other signals can contribute to regulation of NSC maintenance and fate. © 2015 Wiley Periodicals, Inc.

Climate-driven expansion of blanket bogs in Britain during the Holocene

Blanket bog occupies approximately 6 % of the area of the UK today. The Holocene expansion of this hyperoceanic biome has previously been explained as a consequence of Neolithic forest clearance. However, the present distribution of blanket bog in Great Britain can be predicted accurately with a simple model (PeatStash) based on summer temperature and moisture index thresholds, and the same model correctly predicts the highly disjunct distribution of blanket bog worldwide. This finding suggests that climate, rather than land-use history, controls blanket-bog distribution in the UK and everywhere else. We set out to test this hypothesis for blanket bogs in the UK using bioclimate envelope modelling compared with a database of peat initiation age estimates. We used both pollen-based reconstructions and climate model simulations of climate changes between the mid-Holocene (6000 yr BP, 6 ka) and modern climate to drive PeatStash and predict areas of blanket bog. We compiled data on the timing of blanket-bog initiation, based on 228 age determinations at sites where peat directly overlies mineral soil. The model predicts large areas of northern Britain would have had blanket bog by 6000 yr BP, and the area suitable for peat growth extended to the south after this time. A similar pattern is shown by the basal peat ages and new blanket bog appeared over a larger area during the late Holocene, the greatest expansion being in Ireland, Wales and southwest England, as the model predicts. The expansion was driven by a summer cooling of about 2 °C, shown by both pollen-based reconstructions and climate models. The data show early Holocene (pre-Neolithic) blanket-bog initiation at over half of the sites in the core areas of Scotland, and northern England. The temporal patterns and concurrence of the bioclimate model predictions and initiation data suggest that climate change provides a parsimonious explanation for the early Holocene distribution and later expansion of blanket bogs in the UK, and it is not necessary to invoke anthropogenic activity as a driver of this major landscape change.

Climate-driven expansion of blanket bogs in Britain during the Holocene

Blanket bog occupies approximately 6% of the area of the UK today. The Holocene expansion of this hyperoceanic biome has previously been explained as a consequence of Neolithic forest clearance. However, the present distribution of blanket bog in Great Britain can be predicted accurately with a simple model (PeatStash) based on summer temperature and moisture index thresholds, and the same model correctly predicts the highly disjunct distribution of blanket bog worldwide. This finding suggests that climate, rather than land-use history, controls blanket-bog distribution in the UK and everywhere else. We set out to test this hypothesis for blanket bogs in the UK using bioclimate envelope modelling compared with a database of peat initiation age estimates. We used both pollen-based reconstructions and climate model simulations of climate changes between the mid-Holocene (6000 yr BP, 6 ka) and modern climate to drive PeatStash and predict areas of blanket bog. We compiled data on the timing of blanketbog initiation, based on 228 age determinations at sites where peat directly overlies mineral soil. The model predicts that large areas of northern Britain would have had blanket bog by 6000 yr BP, and the area suitable for peat growth extended to the south after this time. A similar pattern is shown by the basal peat ages and new blanket bog appeared over a larger area during the late Holocene, the greatest expansion being in Ireland,Wales, and southwest England, as the model predicts. The expansion was driven by a summer cooling of about 2 °C, shown by both pollen-based reconstructions and climate models. The data show early Holocene (pre- Neolithic) blanket-bog initiation at over half of the sites in the core areas of Scotland and northern England. The temporal patterns and concurrence of the bioclimate model predictions and initiation data suggest that climate change provides a parsimonious explanation for the early Holocene distribution and later expansion of blanket bogs in the UK, and it is not necessary to invoke anthropogenic activity as a driver of this major landscape change.

Study on the application of cool paintings for the passive cooling of existing buildings in Mediterranean climates

Building roofs play a very important role in the energy balance of buildings, especially in summer, when they are hit by a rather high solar irradiance. Depending on the type of finishing layer, roofs can absorb a great amount of heat and reach quite high temperatures on their outermost surface, which determines significant room overheating. However, the use of highly reflective cool materials can help to maintain low outer surface temperatures; this practice may improve indoor thermal comfort and reduce the cooling energy need during the hot season.This technology is currently well known and widely used in the USA, while receiving increasing attention in Europe. In order to investigate the effectiveness of cool roofs as a passive strategy for passive cooling in moderately hot climates, this paper presents the numerical results of a case study based on the dynamic thermal analysis of an existing office building in Catania (southern Italy, Mediterranean area). The results show how the application of a cool paint on the roof can enhance the thermal comfort of the occupants by reducing the operative temperatures of the rooms and to reduce the overall energy needs of the building for space heating and cooling.

Toll-Like Receptor 4 Signaling Leads to Severe Fungal Infection Associated with Enhanced Proinflammatory Immunity and Impaired Expansion of Regulatory T Cells

Toll-like receptors (TLRs) present in innate immune cells recognize pathogen molecular patterns and influence immunity to control the host-parasite interaction. The objective of this study was to characterize the involvement of TLR4 in the innate and adaptive immunity to Paracoccidioides brasiliensis, the most important primary fungal pathogen of Latin America. We compared the responses of C3H/HeJ mice, which are naturally defective in TLR4 signaling, with those of C3H/HePas mice, which express functional receptors, after in vitro and in vivo infection with P. brasiliensis. Unexpectedly, we verified that TLR4-defective macrophages infected in vitro with P. brasiliensis presented decreased fungal loads associated with impaired synthesis of nitric oxide, interleukin-12 (IL-12), and macrophage chemotactic protein 1 (MCP-1). After intratracheal infection with 1 million yeasts, TLR4-defective mice developed reduced fungal burdens and decreased levels of pulmonary nitric oxide, proinflammatory cytokines, and antibodies. TLR4-competent mice produced elevated levels of IL-12 and tumor necrosis factor alpha (TNF-alpha), besides cytokines of the Th17 pattern, indicating a proinflammatory role for TLR4 signaling. The more severe infection of TLR4-normal mice resulted in increased influx of activated macrophages and T cells to the lungs and progressive control of fungal burdens but impaired expansion of regulatory T cells (Treg cells). In contrast, TLR4-defective mice were not able to clear their diminished fungal burdens totally, a defect associated with deficient activation of T-cell immunity and enhanced development of Treg cells. These divergent patterns of immunity, however, resulted in equivalent mortality rates, indicating that control of elevated fungal growth mediated by vigorous inflammatory reactions is as deleterious to the hosts as low fungal loads inefficiently controlled by limited inflammatory reactions.

Expansion of CD4(+) CD25(+) Foxp3(+) T cells by bone marrow-derived dendritic cells

Dendritic cells (DCs) are the most important antigen-presenting cells of the immune system and have a crucial role in T-lymphocyte activation and adaptive immunity initiation. However, DCs have also been implicated in maintaining immunological tolerance. In this study, we evaluated changes in the CD4(+) CD25(+) Foxp3(+) T-cell population after co-culture of lymph node cells from BALB/c mice with syngeneic bone marrow-derived DCs. Our results showed an increase in CD4(+) CD25(+) Foxp3(+) T cells after co-culture which occurred regardless of the activation state of DCs and the presence of allogeneic apoptotic cells; however, it was greater when DCs were immature and were pulsed with the alloantigen. Interestingly, syngeneic apoptotic thymocytes were not as efficient as allogeneic apoptotic cells in expanding the CD4(+) CD25(+) Foxp3(+) T-cell population. In all experimental settings, DCs produced high amounts of transforming growth factor (TGF)-beta. The presence of allogeneic apoptotic cells induced interleukin (IL)-2 production in immature and mature DC cultures. This cytokine was also detected in the supernatants under all experimental conditions and enhanced when immature DCs were pulsed with the alloantigen. CD4(+) CD25(+) Foxp3(+) T-cell expansion during co-culture of lymph node cells with DCs strongly suggested that the presence of alloantigen enhanced the number of regulatory T cells (Tregs) in vitro. Our data also suggest a role for both TGF-beta and IL-2 in the augmentation of the CD4(+) CD25(+) Foxp3(+) population.

Iodine(III)-promoted ring expansion of 1-vinylcycloalkanol derivatives: A metal-free approach toward seven-membered rings

A versatile and metal-free approach for the synthesis of molecules bearing seven- and eight-membered rings is described. The strategy is based on the ring expansion of 1-vinylcycloalkanols (or the corresponding silyl or methyl ether) mediated by the hypervalent iodine reagent HTIB (Phl(OH)OTs). The reaction condition can be easily adjusted to give seven-membered rings bearing different functional groups. A route to medium-ring lactones was also developed.

Growing research where economies grow: essays on strategy and international expansion of companies from emerging countries

In recent years, emerging countries have assumed an increasingly prominent position in the world economy, as growth has picked up in these countries and slowed in developed economies. Two related phenomena, among others, can be associated with this growth: emerging countries were less affected by the 2008-2009 global economic recession; and they increased their participation in foreign direct investment, both inflows and outflows. This doctoral dissertation contributes to research on firms from emerging countries through four independent papers. The first group of two papers examines firm strategy in recessionary moments and uses Brazil, one of the largest emerging countries, as setting for the investigation. Data were collected through a survey on Brazilian firms referring to the 2008-2009 global recession, and 17 hypotheses were tested using structural equation modeling based on partial least squares. Paper 1 offered an integrative model linking RBV to literatures on entrepreneurship, improvisation, and flexibility to indicate the characteristics and capabilities that allow a firm to have superior performance in recessions. We found that firms that pre-recession have a propensity to recognize opportunities and improvisation capabilities for fast and creative actions have superior performance in recessions. We also found that entrepreneurial orientation and flexibility have indirect effects. Paper 2 built on business cycle literature to study which strategies - pro-cyclical or counter-cyclical – enable superior performance in recessions. We found that while most firms pro-cyclically reduce costs and investments during recessions, a counter-cyclical strategy of investing in opportunities created by changes in the environment enables superior performance. Most successful are firms with a propensity to recognize opportunities, entrepreneurial orientation to invest, and flexibility to efficiently implement these investments. The second group of two papers investigated international expansion of multinational enterprises, particularly the use of distance for their location decisions. Paper 3 proposed a conceptual framework to examine circumstances under which distance is less important for international location decisions, taking the new perspective of economic institutional distance as theoretical foundation. The framework indicated that the general preference for low-distance countries is lower: (1) when the company is state owned, rather than private owned; (2) when its internationalization motives are asset, resource, or efficiency seeking, as opposed to market seeking; and (3) when internationalization occurred after globalization and the advent of new technologies. Paper 4 compared five concurrent perspectives of distance and indicated their suitability to the study of various issues based on industry, ownership, and type, motive, and timing of internationalization. The paper also proposed that distance represents the disadvantages of host countries for international location decisions; as such, it should be used in conjunction with factors that represent host country attractiveness, or advantages as international locations. In conjunction, papers 3 and 4 provided additional, alternative explanations for the mixed empirical results of current research on distance. Moreover, the studies shed light into the discussion of differences between multinational enterprises from emerging countries versus those from advanced countries.

Multistage and coordinated planning of the expansion of transmission systems

In this paper, an efficient genetic algorithm (GA) is presented to solve the problem of multistage and coordinated transmission expansion planning. This is a mixed integer nonlinear programming problem, difficult for systems of medium and large size and high complexity. The GA presented has a set of specialized genetic operators and an efficient form of generation of the initial population that finds high quality suboptimal topologies for large size and high complexity systems. In these systems, multistage and coordinated planning present a lower investment than static planning. Tests results are shown in one medium complexity system and one large size high complexity system.

Setting time and thermal expansion of two endodontic cements

The purpose of this study was to evaluate the setting time and the thermal expansion coefficient of 2 endodontic cements, MTA-Angelus and a novel cement called CER. The setting time was determined in accordance to ANSI/ADA specifications no. 57. Three samples of 10 mm diameter and 2 mm thickness were prepared for each cement. The thermal expansion measurements were performed by strain gauge technique. Four samples of each cement were prepared using silicone rings of 5 mm diameter and 2 mm thickness. The data were analyzed statistically using the Student t test. The setting time obtained for the MTA-Angelus and CER cements was 15 (SD 1) min and 7 (SD 1) min, respectively. The linear coefficient of thermal expansion was 8.86 (SD 0.28) mu strain/degrees C for MTA-Angelus and 11.76 (SD 1.20) mu strain/degrees C for CER. The statistical analysis showed significant difference (P < .05) in the setting time and linear coefficient of thermal expansion between the 2 cements. The CER cement has a coefficient of expansion similar to dentin, which could contribute to a decrease of microleakage degree.