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Assessing the uncertainties of simulation results of ecological models is becoming increasingly important, specifically if these models are used to estimate greenhouse gas emissions on site to regional/national levels. Four general sources of uncertainty effect the outcome of process-based models: (i) uncertainty of information used to initialise and drive the model, (ii) uncertainty of model parameters describing specific ecosystem processes, (iii) uncertainty of the model structure, and (iv) accurateness of measurements (e.g., soil-atmosphere greenhouse gas exchange) which are used for model testing and development.
The aim of our study was to assess the simulation uncertainty of the process-based biogeochemical model LandscapeDNDC. For this we set up a Bayesian framework using a Markov Chain Monte Carlo (MCMC) method, to estimate the joint model parameter distribution. Data for model testing, parameter estimation and uncertainty assessment were taken from observations of soil fluxes of nitrous oxide (N2O), nitric oxide (NO) and carbon dioxide (CO2) as observed over a 10 yr period at the spruce site of the Höglwald Forest, Germany. By running four independent Markov Chains in parallel with identical properties (except for the parameter start values), an objective criteria for chain convergence developed by Gelman et al. (2003) could be used.
Our approach shows that by means of the joint parameter distribution, we were able not only to limit the parameter space and specify the probability of parameter values, but also to assess the complex dependencies among model parameters used for simulating soil C and N trace gas emissions. This helped to improve the understanding of the behaviour of the complex LandscapeDNDC model while simulating soil C and N turnover processes and associated C and N soil-atmosphere exchange. In a final step the parameter distribution of the most sensitive parameters determining soil-atmosphere C and N exchange were used to obtain the parameter-induced uncertainty of simulated N2O, NO and CO2 emissions. These were compared to observational data of an calibration set (6 yr) and an independent validation set of 4 yr. The comparison showed that most of the annual observed trace gas emissions were in the range of simulated values and were predicted with a high certainty (Root-mean-squared error (RMSE) NO: 2.4 to 18.95 g N ha−1 d−1, N2O: 0.14 to 21.12 g N ha−1 d−1, CO2: 5.4 to 11.9 kg C ha−1 d−1). However, LandscapeDNDC simulations were sometimes still limited to accurately predict observed seasonal variations in fluxes.
We show how Sestoft’s abstract machine for lazy evaluation of purely functional programs can be extended to evaluate expressions of the calculus CHF – a process calculus that models Concurrent Haskell extended by imperative and implicit futures. The abstract machine is modularly constructed by first adding monadic IO-actions to the machine and then in a second step we add concurrency. Our main result is that the abstract machine coincides with the original operational semantics of CHF, w.r.t. may- and should-convergence.
In the title molecule, C18H17N5O2, the dihedral angle between the benzene plane and the benzimidazole plane is 19.8 (1)° and the angle between the benzene plane and the triazole plane is 16.7 (1)°. In the crystal, molecules are connected by O—H[cdots, three dots, centered]N hydrogen bonds, forming zigzag chains along the c-axis direction. The chains are connected by bifurcated N—H[cdots, three dots, centered](N,N) hydrogen bonds into layers parallel to (100). These layers are connected along the a-axis direction by weak C—H[cdots, three dots, centered]O contacts, forming a three-dimensional network.
Hepatitis C virus (HCV) assembly and production is closely linked to lipid metabolism. Indeed, lipid droplets (LD) have been shown to serve as a platform for HCV assembly. To investigate the effect of HCV on the host cell proteome, 2D-gelelectrophoresis with subsequent MALDI-TOF mass spectrometry of HCV replicating and the corresponding control cells were done. Based on this analysis, it was found out that HCV-replicating Huh7.5 cells revealed lower amounts of TIP47 (tail interacting protein of 47kD) compared to HCV-negative cells. TIP47, a cytoplasmic sorting factor, has been shown to be associated with lipid droplets. As it is known that HCV-replication and assembly takes place at the so called ”membranous web” that is composed of LDs and rearranged ER-derived membranes, it was tempting to investigate the role of TIP47 in HCV life-cycle. Western blot analysis did reveal that overexpression of TIP47 in HCV replicating Huh7.5 cells leads to decreased amounts of the HCV core protein while the levels of non-structural protein (NS)5A and intracellular HCVgenomes are increased. Moreover, in TIP47 overproducing cells higher amounts of infectious HCV particles are secreted. Vice versa, inhibition of TIP47 expression by siRNA results in a decreased level of intracellular NS5A, increased amounts of intracellular core and less infectious viral particles in the supernatant. In addition, complete silencing of TIP47 by lentiviral transduction abolishes HCV replication that can be restored by transfection of these cells with a TIP47 expression construct. It has been shown recently that apoE binds to NS5A and that this interaction plays an important role for the HCV life cycle (Benga et al., 2010). The C-terminal part of TIP47 harbours a 4 helix bundle motif and displays high homology to the N-terminus of apoE. Therefore, we investigated the interaction of NS5A and TIP47. Confocal double immunofluorescence microscopy revealed that a fraction of NS5A colocalizes with TIP47. Coimmunoprecipitation experiments and a yeast-two-hybrid screening confirmed the interaction between NS5A and TIP47 and deletion of the N-terminal-TIP47-PAT domain abolishes this interaction. From this we conclude that the TIP47-NS5A interaction is required for virus morphogenesis. Moreover, TIP47 can bind to Rab9 and this is relevant for targeting the viral particle out of the cell. In accordance to this, TIP47 was identified to be associated to the viral particle. Mutants of TIP47 that fail to bind Rab9 reveal lower amounts and a changed distribution of the HCV core protein. Furthermore, we could see that the core staining colocalizes with subcellular structures that were identified as autophagosomes using a p62-specific antibody which is a specific autophagosome-marker. Based on this, we hypothized that destruction of the Rab9 binding domain misdirects the viral particle towards the lysosomal compartment.
For the first time it could be shown that TIP47 interacts with NS5A and is associated to the viral particle, therefore plays a crucial role for the virus morphogenesis and secretion of the viral article.
Taken together, these results indicate that TIP47 is an essential cellular factor for the life cycle of HCV Abstract and might be used as target for antiviral treatment, e.g. by targeting the NS5A-TIP47 interaction, based on small molecules that mimic the NS5A-specific sequence that binds to TIP47 which might result in a competition of the TIP47/NS5A interaction.
Modelling protein structure seems a challenging enterprise because the number of structure parameters required ordinarily exceeds the amount of independent data points available from experimental observations. Expressing the predominant conformation of a protein in terms of a geometry model, a polypeptide chain consisting of N atoms would command 3N – 6 Cartesian coordinates be fixed. Even for small proteins, this becomes a daunting number. Fortunately, so-called holonomic constraints limit the number of variables, leaving substantially fewer, truly relevant parameters for folding the polypeptide chain into its native tertiary structure. For example, adjusting bond lengths and the many angles between the covalent bonds connecting the atoms is of little concern and appropriate standard values can be inserted from tableworks (Pople & Gordon, 1967; Engh & Huber, 1991, 2006). Table 1 exemplifies for the 147-residue protein Desulfovibrio vulgaris flavodoxin how the number of truly independent internal rotational degrees of freedom amounts to less than one-tenth of the Cartesian coordinate set size...
Visual perception is highly variable and can be influenced by the surrounding world. Previous research has revealed that body perception can be biased due to adaptation to thin or fat body shapes. The aim of the present study was to show that adaptation to certain body shapes and the resulting perceptual biases transfer across different identities of adaptation and test stimuli. We designed two similar adaptation experiments in which healthy female participants adapted to pictures of either thin or fat bodies and subsequently compared more or less distorted pictures of their own body to their actual body shape. In the first experiment (n = 16) the same identity was used as adaptation and test stimuli (i.e. pictures of the participant’s own body) while in the second experiment (n = 16) we used pictures of unfamiliar thin or fat bodies as adaptation stimuli. We found comparable adaptation effects in both experiments: After adaptation to a thin body, participants rated a thinner than actual body picture to be the most realistic and vice versa. We therefore assume that adaptation to certain body shapes transfers across different identities. These results raise the questions of whether some type of natural adaptation occurs in everyday life. Natural and predominant exposure to certain bodily features like body shape – especially the thin ideal in Western societies – could bias perception for these features. In this regard, further research might shed light on aspects of body dissatisfaction and the development of body image disturbances in terms of eating disorders.
In Germany, as in almost all industrial countries, active pharmaceutical substances can now be found in virtually all water bodies and occasionally also in drinking water. Even though the concentrations in question tend to be very low, there are initial signs of their impact on aquatic life. There is no evidence as yet of any acute consequences for human health. It is, however, impossible to rule out long-term consequences from these minimal concentrations or unexpected effects from the interaction between various active ingredients (cocktail effect). At special risk here are sensitive segments of the population such as children and the chronically ill. There is thus a need for action on precautionary grounds.
The main actors in the health system are largely unaware of the problem posed by drug residues in water. Although knowledge cannot be equated with awareness – given the existence of the ‘not wanting to know' phenomenon – the first step is to generate a consolidated knowledge base. Only by creating awareness of the problem can further strategies be implemented to ultimately enlighten and bring about behavioural change. At stake here is the overall everyday handling of medications, including prescription, compliance, and drug-free disease prevention down to the doctor-patient relationship. The latter, namely, is often characterised by misunderstandings and a lack of communication about the – supposed – need to prescribe drugs.
The first part of the strategy for the general public involves using various channels and media to address three different target groups. These were identified by ISOE in an empirical survey as reacting differently to the problem under review:
· ‘The Deniers/Relativists'
· ‘The Truth-Seekers'
· ‘The Hypersensitives'
The intention is to address each target group in the right tone and using the most suitable line of reasoning via specific media and with the proper degree of differentiation. The ‘Truth-Seekers' play an opinion-leading role here. They can be provided with highly differentiated information through sophisticated media which they then pass on to their dialogue partners in an appropriate form.
The second part of the strategy for the general public relates to the communication of proper disposal routes for expired drugs. The goal is to confine disposal to pharmacies so that on no account are they flushed down the sink or toilet. Based on an analysis of typical errors in existing communications media on this topic, ISOE prepared recommendations for drafting proper information materials.
In addressing pharmacists, the first priority is to convey hard facts: to this end we propose a PR campaign to place articles in the main specialist media. At the same time, the subject should feature in training and continuing education programmes. Another aim is to strengthen the advisory function of the pharmacies. The environmentally sensitive target group would indeed react positively to having their attention drawn to the issue of drug residues in water. For all other customers, the pharmacists can and should act as consultants: they emphasise how important it is to take medication as instructed (compliance) and use suitable pack sizes, and warn older customers in particular about the potential hazards of improper drug intake.
The first stage of the communications strategy for doctors likewise revolves around knowledge. Here, however, it is important to take into account their self-image as scientists while in fact having little grasp of this specific area. The line to take is that of ‘discursive selfenlightenment'. This means that the issue of drug residues in water cannot be conveyed to doctors by laymen but must be taken up and imparted via the major media of the medical profession and by medical association officials (top-down).
The second stage, namely that of raising doctors’ awareness of the problem, is likely to encounter strong resistance from some of the medical profession. They may fear a threat of interference in treatment plans from an environmental perspective and feel the need to emphasise that doctors are not responsible for environmental issues. As shown in empirical surveys by ISOE, such a defensive reaction is ultimately down to an underlying taboo: people are loath to discuss the over-prescription taking place in countless doctors' surgeries. And it is a fact that this problem cannot be tackled from the environmental perspective, although the goals of water protection are indeed consistent with the economic objectives of restraint in the deployment of drugs. Any communications measure for this target group has to bear in mind that doctors feel restricted by what they see as a ‘perpetual health reform' no matter which government is in power. On no account are they prepared to tolerate any new form of regulation, in this case for environmental reasons.
An entirely different view of the problem is taken by ‘critical doctors' such as specialists in environmental health and those with a naturopathic focus. They are interested in the problem because they see a connection between the quality of our environment and our health. What is more, they have patients keen to be prescribed as few drugs as possible and who are instead interested in ‘talking medicine'. So, any communication strategy intent on tackling the difficult problem of oversubscribing drugs needs to look carefully at the experiences of these medical professionals and also at a ‘bottom-up strategy'.
Implementation of strategic communications should be entrusted to an agency with experience in ‘issue management'. Knowledge of social marketing and the influencing of behaviour are further prerequisites. All important decisions should be taken by a consensus committee (‘MeriWa'1 round table), in which the medical profession, pharmacists and consumers are represented.
This paper examines data on financial sophistication among the U.S. older population, using a special-purpose module implemented in the Health and Retirement Study. We show that financial sophistication is deficient for older respondents (aged 55+). Specifically, many in this group lack a basic grasp of asset pricing, risk diversification, portfolio choice, and investment fees. Subpopulations with particular deficits include women, the least educated, persons over the age of 75, and non-Whites. In view of the fact that people are increasingly being asked to take on responsibility for their own retirement security, such lack of knowledge can have serious implications.