Generation of time delays: simplified models of intracellular signalling in cerebellar Purkinje cells

In many neuronal systems, information is encoded in temporal spike patterns. The recognition and storage of temporal patterns requires the generation and modulation of time delays between inputs and outputs. In cerebellar Purkinje cells, stimulation of metabotropic glutamate receptors (mGluRs) results in a delayed calcium and voltage response that has been implicated in classical conditioning and temporal pattern recognition. Here, we analyse and simplify a complex model of the intracellular signalling network that has been proposed as a substrate for this delayed response. We systematically simplify the original model, present a minimal model of time delay generation, and show that a delayed response can be produced by the combination of negative feedback and autocatalysis, without any intervening signalling steps that would contribute additive delays. The minimal model is analysed using phase plane methods, and classified as an excitable system. We discuss the implication of excitability for computations performed by intracellular signalling networks in general.     

Corporate Water Footprint Accounting and Impact Assessment: The Case of the Water Footprint of a Sugar-Containing Carbonated Beverage

All water use in the world is ultimately linked to final consumption by consumers. It is therefore interesting to know the specific water requirements of various consumer goods, particularly the water-intensive ones. This information is relevant not only for consumers, but also for food processors, retailers, and traders. The objective of this paper is to carry out a pilot study on water footprint accounting and impact assessment for a hypothetical sugar-containing carbonated beverage in a 0.5 l PET-bottle produced in a hypothetical factory that takes its sugar alternatively from sugar beet, sugar cane and high fructose maize syrup and from different countries. The composition of the beverage and the characteristics of the factory are hypothetical but realistic. The data assumed have been inspired by a real case. This paper does not only look at the water footprint of the ingredients of the beverage, but also at the water footprint of the bottle, other packaging materials and construction materials, paper and energy used in the factory. Although most companies focus on their own operational performance, this paper shows that it is important to consider freshwater usage along the supply chain. The water footprint of the beverage studied has a water footprint of 150 to 300 l of water per 0.5 l bottle, of which 99.7–99.8% refers to the supply chain. The study also shows that agricultural ingredients that constitute only a small fraction in weight of the final product have the biggest share at the total water footprint of a product.     

Do economic instruments matter? Wind turbine investments in the EU(15)

This paper analyses how governments in the EU(15) countries have succeeded in stimulating investments in wind turbines between 1985 and 2005. I use four different evaluation criteria (Tobin's Q, Euler equation estimation, investment accelerator model, and the effective marginal tax rate) to describe the observed investment patterns. After a period of rapid growth in capital stock (1985–2000), a period of modest growth (2001–2005) can be observed even though the economic attractiveness of investing increases modestly. This pattern cannot be explained by the evaluation criteria unless we accept economic attractiveness is a necessary condition and not a necessary and sufficient condition. When analysing which policy has worked best, the policies of Germany, Denmark and Spain stand out. Their early and consistent support has been based on feed-in tariffs combined with subsidies.     

Demonstration projects and sustainable housing

Because of the complicated structure of the built environment, it is frequently difficult to obtain good results on sustainable development projects. In The Netherlands, the Dutch government have used a range of new steering instruments which have cleverly enabled innovation to take place within a market economy. This imaginative governmental process uses covenants, network management and above all, demonstration projects to assess the feasibility of innovation. The authors describe the process and consider examples from energy efficient and sustainable housing, highlighting the importance of clear targets.     

High-temperature liquid chromatography coupled on-line to a continuous-flow biochemical screening assay with electrospray ionization mass spectrometric detection

The potential of high-temperature liquid chromatography (HTLC) was investigated in an on-line combination with a screening system for bioactive compounds against the enzyme cathepsin B. Samples were separated by HTLC and subsequently analyzed by an on-line continuous-flow enzymatic assay. Detection was performed by electrospray ionization mass spectrometry, revealing both the bioactivity and the molecular mass of the bioactive compounds. Compared to conventional reversed-phase liquid chromatography, the amount of methanol necessary for separation could be decreased to only 10%, which improved the compatibility of LC with a biochemical assay. Sufficient preheating of the mobile phase prior to the separation and postcolumn cooling to prevent deactivation of the enzyme, even at column temperatures as high as 208 degrees C, was achieved as indicated by the reliable peak shapes obtained. The sensitivity was comparable with previously described systems operating at ambient temperatures as similar IC50 values were obtained. Exposing the inhibitors to high temperatures did not lead to thermal decomposition. The separation of inhibitors and the subsequent biochemical assay was performed either isothermally at various temperatures or by applying various temperature gradients as well as at various flow rates. The results obtained clearly show the compatibility of HTLC with an enzymatic screening assay.     

浪漫茅屋记

坐落在荷兰海利近郊zoetermeer,覆盖了一层厚厚稻草的这座现代住宅,让我不禁想起了旧时的茅草屋。在那个建造技术有限、物质匮乏的年代,由夯土、木头、麦秆建成的房子,是当时人们赖以生     

Social learning for adaptive delta management: Tidal River Management in the Bangladesh Delta

ABSTRACT

The article analyzes Tidal River Management in Bangladesh from a social learning perspective. Four cases were investigated using participatory assessment. Knowledge acquisition through transformations in the Tidal River Management process was explored as an intended learning outcome. The study finds that social learning occurred more prominently at the individual stakeholder level and less at the collective level. For Tidal River Management to be responsive and sustainable, especially in times of increased uncertainty and climate vulnerability, more attention needs to be paid to coordination and facilitation of multi-level learning that includes all stakeholders.     

Domain-domain interactions in hybrids of tissue-type plasminogen activator and urokinase-type plasminogen activator

Fibrin-dependent plasminogen activation by tissue-type plasminogenactivator (t-PA) is in part associated with the presence ofthe kringle 2 domain in t-PA. Within this kringle 2 domain alysyl-binding site has been described. The plasminogen to plasminconversion by urokinase-type plasminogen activator (u-PA), incontrast to that of t-PA, is not enhanced in the presence offibrin. Within the u-PA kringle domain no lysyl-binding siteis found. To study whether introduction of a lysyl-binding sitein the u-PA kringle domain will make u-PA a fibrin-dependentplasminogen activator, three stretches of amino acid residuesof the u-PA kringle domain (A²⁸-Q³³, D⁵⁵-N⁵⁷ and G⁶⁷-V⁷²) weresubstituted by three stretches of amino acids from the correspondingpositions of the kringle 2 domain of t-PA (M²⁸-K³³, D⁵⁵-D⁵⁷and N⁶⁷-W⁷²). These changes resulted in the creation of thelysyl-binding site consensus of the kringle 2 domain (K³³, D⁵⁵,D⁵⁷, W⁶² and W⁷²) in the u-PA kringle. However, the resultingu-PA mutant did not interact with lysyl-Sepharose, nor did itdisplay fibrin-enhanced plasminogen activation in the presenceof soluble fibrin mimic. When the kringle domain of u-PA wasreplaced by the kringle 2 domain of t-PA, similar results wereobtained. The hybrid protein hardly interacted with lysyl-Sepharoseand the plasminogen activation was not enhanced in the presenceof fibrin mimic However, the N-terminal fragment isolated fromthis hybrid molecule (consisting of growth factor domain andkringle 2 domain) did interact with lysyl-Sepharose, suggestingthat in the hybrid molecule a functional lysyl-binding siteis present but not operational. Indeed, lysine analogue (e-amino-caproicacid) sensitive binding of isolated t-PA kringle 2 domain tou-PA could be observed. The modified u-PA kringle, the wildtype u-PA kringle and the kringle 2 of the u-PA hybrid werealso placed N-terminal of the protease domain of t-PA. As expected,the t-PA mutant consisting of the kringle 2 domain and the proteasedomain bound to lysyl-Sepharose and showed fibrin-dependentplasminogen activation. Further, the hybrid molecule consistingof the u-PA kringle placed N-terminal of the t-PA protease domaindid not display these features. Introduction of the modifiedu-PA kringle N-terminal of the t-PA protease domain resultedin a very weak interaction with lysyl-Sepharose. Despite thehigh overall similarity in primary structure of the modifiedu-PA kringle and t-PA kringle 2 (68%), no fibrin-dependent plasminogenactivation of this hybrid molecule was observed. The above-mentionedresults question the concept that the structural auto-nomousdomains within hybrid plasminogen activators t-PA and u-PA functionas autonomous domains and suggest that interactions betweenthe kringle and the protease domain in hybrid molecules stronglyinfluences their functional features     

Performance gaps in energy consumption: household groups and building characteristics

ABSTRACT

The difference between actual and calculated energy is called the ‘energy-performance gap’. Possible explanations for this gap are construction mistakes, improper adjusting of equipment, excessive simplification in simulation models and occupant behaviour. Many researchers and governmental institutions think the occupant is the main cause of this gap. However, only limited evidence exists for this. Therefore, an analysis is presented of actual and theoretical energy consumption based on specific household types and building characteristics. Using a large dataset (1.4 million social housing households), the average actual and theoretical energy consumptions (gas and electricity) of different household types and characteristics (income level, type of income, number of occupants and their age) were compared for each energy label. Additionally, the 10% highest and lowest energy-consuming groups were analysed. The use of combinations of occupant characteristics instead of individual occupant characteristics provides new insights into the influence of the occupant on energy demand. For example, in contrast to previous studies, low-income households consume more gas per m² (space heating and hot water) than households with a high income for all types of housing. Furthermore, the performance gap is caused not only by the occupant but also by the assumed building characteristics.     

Phase behavior and extended phase scheme of static cocoa butter investigated with real-time X-ray powder diffraction

A complete isothermal phase-transition scheme of cocoa butter under static conditions is presented, based on time-resolved X-ray powder diffraction experiments. In contrast to what is known from literature, not only β V, but also β VI can be obtained directly through transformation from β′. Another remarkable result is that β′ exists as a phase range rather than as two separate phases. Within this β′ phase range no isothermal phase transitions have been observed. More detailed information concerning the observed cocoa butter polymorphs was obtained by determination of melting ranges, using time-resolved X-ray powder diffraction. Also standard X-ray powder diffraction patterns of the γ, the α, and the two β phases and parts of the β′ phase range have been recorded. The observed phase behavior of cocoa butter has been explained based on the concept of individual crystallite phase behavior of cocoa butter