853 resultados para Weinberg, Steven: Unelmia viimeisestä teoriasta


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Purpose – Price indices for commercial real estate markets are difficult to construct because assets are heterogeneous, they are spatially dispersed and they are infrequently traded. Appraisal-based indices are one response to these problems, but may understate volatility or fail to capture turning points in a timely manner. This paper estimates “transaction linked indices” for major European markets to see whether these offer a different perspective on market performance. The paper aims to discuss these issues. Design/methodology/approach – The assessed value method is used to construct the indices. This has been recently applied to commercial real estate datasets in the USA and UK. The underlying data comprise appraisals and sale prices for assets monitored by Investment Property Databank (IPD). The indices are compared to appraisal-based series for the countries concerned for Q4 2001 to Q4 2012. Findings – Transaction linked indices show stronger growth and sharper declines over the course of the cycle, but they do not notably lead their appraisal-based counterparts. They are typically two to four times more volatile. Research limitations/implications – Only country-level indicators can be constructed in many cases owing to low trading volumes in the period studied, and this same issue prevented sample selection bias from being analysed in depth. Originality/value – Discussion of the utility of transaction-based price indicators is extended to European commercial real estate markets. The indicators offer alternative estimates of real estate market volatility that may be useful in asset allocation and risk modelling, including in a regulatory context.

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Much UK research and market practice on portfolio strategy and performance benchmarking relies on a sector‐geography subdivision of properties. Prior tests of the appropriateness of such divisions have generally relied on aggregated or hypothetical return data. However, the results found in aggregate may not hold when individual buildings are considered. This paper makes use of a dataset of individual UK property returns. A series of multivariate exploratory statistical techniques are utilised to test whether the return behaviour of individual properties conforms to their a priori grouping. The results suggest strongly that neither standard sector nor regional classifications provide a clear demarcation of individual building performance. This has important implications for both portfolio strategy and performance measurement and benchmarking. However, there do appear to be size and yield effects that help explain return behaviour at the property level.

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A global climatology (1979–2012) from the Modern-Era Retrospective Analysis for Research and Applications (MERRA) shows distributions and seasonal evolution of upper tropospheric jets and their relationships to the stratospheric subvortex and multiple tropopauses. The overall climatological patterns of upper tropospheric jets confirm those seen in previous studies, indicating accurate representation of jet stream dynamics in MERRA. The analysis shows a Northern Hemisphere (NH) upper tropospheric jet stretching nearly zonally from the mid-Atlantic across Africa and Asia. In winter–spring, this jet splits over the eastern Pacific, merges again over eastern North America, and then shifts poleward over the North Atlantic. The jets associated with tropical circulations are also captured, with upper tropospheric westerlies demarking cyclonic flow downstream from the Australian and Asian monsoon anticyclones and associated easterly jets. Multiple tropopauses associated with the thermal tropopause “break” commonly extend poleward from the subtropical upper tropospheric jet. In Southern Hemisphere (SH) summer, the tropopause break, along with a poleward-stretching secondary tropopause, often occurs across the tropical westerly jet downstream of the Australian monsoon region. SH high-latitude multiple tropopauses, nearly ubiquitous in June–July, are associated with the unique polar winter thermal structure. High-latitude multiple tropopauses in NH fall–winter are, however, sometimes associated with poleward-shifted upper tropospheric jets. The SH subvortex jet extends down near the level of the subtropical jet core in winter and spring. Most SH subvortex jets merge with an upper tropospheric jet between May and December; although much less persistent than in the SH, merged NH subvortex jets are common between November and April.

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The incidence and severity of light leaf spot epidemics caused by the ascomycete fungus Pyrenopeziza brassicae on UK oilseed rape crops is increasing. The disease is currently controlled by a combination of host resistance, cultural practices and fungicide applications. We report decreases in sensitivities of modern UK P. brassicae isolates to the azole (imidazole and triazole) class of fungicides. By cloning and sequencing the P. brassicae CYP51 (PbCYP51) gene, encoding the azole target sterol 14α-demethylase, we identified two non-synonymous mutations encoding substitutions G460S and S508T associated with reduced azole sensitivity. We confirmed the impact of the encoded PbCYP51 changes on azole sensitivity and protein activity by heterologous expression in a Saccharomyces cerevisiae mutant YUG37::erg11 carrying a controllable promoter of native CYP51 expression. In addition, we identified insertions in the predicted regulatory regions of PbCYP51 in isolates with reduced azole sensitivity. The presence of these insertions was associated with enhanced transcription of PbCYP51 in response to sub-inhibitory concentrations of the azole fungicide tebuconazole. Genetic analysis of in vitro crosses of sensitive and resistant isolates confirmed the impact of PbCYP51 alterations in coding and regulatory sequences on a reduced sensitivity phenotype, as well as identifying a second major gene at another locus contributing to resistance in some isolates. The least sensitive field isolates carry combinations of upstream insertions and non-synonymous mutations, suggesting PbCYP51 evolution is on-going and the progressive decline in azole sensitivity of UK P. brassicae populations will continue. The implications for the future control of light leaf spot are discussed.

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Evolution of resistance to drugs and pesticides poses a serious threat to human health and agricultural production. CYP51 encodes the target site of azole fungicides, widely used clinically and in agriculture. Azole resistance can evolve due to point mutations or overexpression of CYP51, and previous studies have shown that fungicide-resistant alleles have arisen by de novo mutation. Paralogs CYP51A and CYP51B are found in filamentous ascomycetes, but CYP51A has been lost from multiple lineages. Here, we show that in the barley pathogen Rhynchosporium commune, re-emergence of CYP51A constitutes a novel mechanism for the evolution of resistance to azoles. Pyrosequencing analysis of historical barley leaf samples from a unique long-term experiment from 1892 to 2008 indicates that the majority of the R. commune population lacked CYP51A until 1985, after which the frequency of CYP51A rapidly increased. Functional analysis demonstrates that CYP51A retains the same substrate as CYP51B, but with different transcriptional regulation. Phylogenetic analyses show that the origin of CYP51A far predates azole use, and newly sequenced Rhynchosporium genomes show CYP51A persisting in the R. commune lineage rather than being regained by horizontal gene transfer; therefore, CYP51A re-emergence provides an example of adaptation to novel compounds by selection from standing genetic variation.

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Here we describe general flow processes for the synthesis of alkyl and aryl azides, and the development of a new monolithic triphenylphosphine reagent, which provides a convenient format for the use of this versatile reagent in flow. The utility of these new tools was demonstrated by their application to a flow Staudinger aza-Wittig reaction sequence. Finally, a multistep aza-Wittig, reduction and purification flow process was designed, allowing access to amine products in an automated fashion.

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Recently, the original benchmarking methodology of the Sustainable Value approach became subjected to serious debate. While Kuosmanen and Kuosmanen (2009b) critically question its validity introducing productive efficiency theory, Figge and Hahn (2009) put forward that the implementation of productive efficiency theory severely conflicts with the original financial economics perspective of the Sustainable Value approach. We argue that the debate is very confusing because the original Sustainable Value approach presents two largely incompatible objectives. Nevertheless, we maintain that both ways of benchmarking could provide useful and moreover complementary insights. If one intends to present the overall resource efficiency of the firm from the investor's viewpoint, we recommend the original benchmarking methodology. If one on the other hand aspires to create a prescriptive tool setting up some sort of reallocation scheme, we advocate implementation of the productive efficiency theory. Although the discussion on benchmark application is certainly substantial, we should avoid the debate to become accordingly narrowed. Next to the benchmark concern, we see several other challenges considering the development of the Sustainable Value approach: (1) a more systematic resource selection, (2) the inclusion of the value chain and (3) additional analyses related to policy in order to increase interpretative power.

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Blends of PEEK with macrocyclic thioether-ketones show initial melt-viscosities reduced by more than an order of magnitude relative to the polymer itself, enabling more facile processing and fabrication. On raising the temperature of the melt, however, the macrocycle undergoes spontaneous, entropically-driven ring-opening polymerization (ED-ROP), so that the properties of the final polymer should not, in principle, be compromised by the presence of low-MW macrocyclic material.

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Amyloid fibrils are formed by a model surfactant-like peptide (Ala)10-(His)6 containing a hexahistidine tag. This peptide undergoes a remarkable two-step self-assembly process with two distinct critical aggregation concentrations (cac’s), probed by fluorescence techniques. A micromolar range cac is ascribed to the formation of prefibrillar structures, whereas a millimolar range cac is associated with the formation of well-defined but more compact fibrils. We examine the labeling of these model tagged amyloid fibrils using Ni-NTA functionalized gold nanoparticles (Nanogold). Successful labeling is demonstrated via electron microscopy imaging. The specificity of tagging does not disrupt the β-sheet structure of the peptide fibrils. Binding of fibrils and Nanogold is found to influence the circular dichroism associated with the gold nanoparticle plasmon absorption band. These results highlight a new approach to the fabrication of functionalized amyloid fibrils and the creation of peptide/nanoparticle hybrid materials.

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A framework for understanding the complexity of cancer development was established by Hanahan and Weinberg in their definition of the hallmarks of cancer. In this review, we consider the evidence that parabens can enable development in human breast epithelial cells of 4/6 of the basic hallmarks, 1/2 of the emerging hallmarks and 1/2 of the enabling characteristics. Hallmark 1: parabens have been measured as present in 99% of human breast tissue samples, possess oestrogenic activity and can stimulate sustained proliferation of human breast cancer cells at concentrations measurable in the breast. Hallmark 2: parabens can inhibit the suppression of breast cancer cell growth by hydroxytamoxifen, and through binding to the oestrogen-related receptor gamma (ERR) may prevent its deactivation by growth inhibitors. Hallmark 3: in the 10nM to 1M range, parabens give a dose-dependent evasion of apoptosis in high-risk donor breast epithelial cells. Hallmark 4: long-term exposure (>20weeks) to parabens leads to increased migratory and invasive activity in human breast cancer cells, properties which are linked to the metastatic process. Emerging hallmark: methylparaben has been shown in human breast epithelial cells to increase mTOR, a key regulator of energy metabolism. Enabling characteristic: parabens can cause DNA damage at high concentrations in the short term but more work is needed to investigate long-term low-doses of mixtures. The ability of parabens to enable multiple cancer hallmarks in human breast epithelial cells provides grounds for regulatory review of the implications of the presence of parabens in human breast tissue.

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Cities have developed into the hotspots of human economic activity. From the appearance of the first cities in the Neolithic to 21st century metropolis their impact on the environment has always been apparent. With more people living in cities than in rural environments now it becomes crucial to understand these environmental impacts. With the immergence of megacities in the 20th century and their continued growth in both, population and economic power, the environmental impact has reached the global scale. In this paper we examine megacity impacts on atmospheric composition and climate. We present basic concepts, discuss various definitions of footprints, summarize research on megacity impacts and assess the impact of megacity emissions on air quality and on the climate at the regional to global scale. The intention and ambition of this paper is to give a comprehensive but brief overview of the science with regard to megacities and the environment.