Simulation vs. Reality: A Comparison of In Silico Distance Predictions with DEER and FRET Measurements

Site specific incorporation of molecular probes such as fluorescent- and nitroxide spin-labels into biomolecules, and subsequent analysis by Förster resonance energy transfer (FRET) and double electron-electron resonance (DEER) can elucidate the distance and distance-changes between the probes. However, the probes have an intrinsic conformational flexibility due to the linker by which they are conjugated to the biomolecule. This property minimizes the influence of the label side chain on the structure of the target molecule, but complicates the direct correlation of the experimental inter-label distances with the macromolecular structure or changes thereof. Simulation methods that account for the conformational flexibility and orientation of the probe(s) can be helpful in overcoming this problem. We performed distance measurements using FRET and DEER and explored different simulation techniques to predict inter-label distances using the Rpo4/7 stalk module of the M. jannaschii RNA polymerase. This is a suitable model system because it is rigid and a high-resolution X-ray structure is available. The conformations of the fluorescent labels and nitroxide spin labels on Rpo4/7 were modeled using in vacuo molecular dynamics simulations (MD) and a stochastic Monte Carlo sampling approach. For the nitroxide probes we also performed MD simulations with explicit water and carried out a rotamer library analysis. Our results show that the Monte Carlo simulations are in better agreement with experiments than the MD simulations and the rotamer library approach results in plausible distance predictions. Because the latter is the least computationally demanding of the methods we have explored, and is readily available to many researchers, it prevails as the method of choice for the interpretation of DEER distance distributions

Termination of the leprosy isolation policy in the US and Japan : Science, policy changes, and the garbage can model

BACKGROUND: In both the US and Japan, the patient isolation policy for leprosy /Hansen's disease (HD) was preserved along with the isolation facilities, long after it had been proven to be scientifically unnecessary. This delayed policy termination caused a deprivation of civil liberties of the involuntarily confined patients, the fostering of social stigmas attached to the disease, and an inefficient use of health resources. This article seeks to elucidate the political process which hindered timely policy changes congruent with scientific advances. METHODS: Examination of historical materials, supplemented by personal interviews. The role that science played in the process of policy making was scrutinized with particular reference to the Garbage Can model. RESULTS: From the vantage of history, science remained instrumental in all period in the sense that it was not the primary objective for which policy change was discussed or intended, nor was it the principal driving force for policy change. When the argument arose, scientific arguments were employed to justify the patient isolation policy. However, in the early post-WWII period, issues were foregrounded and agendas were set as the inadvertent result of administrative reforms. Subsequently, scientific developments were more or less ignored due to concern about adverse policy outcomes. Finally, in the 1980s and 1990s, scientific arguments were used instrumentally to argue against isolation and for the termination of residential care. CONCLUSION: Contrary to public expectations, health policy is not always rational and scientifically justified. In the process of policy making, the role of science can be limited and instrumental. Policy change may require the opening of policy windows, as a result of convergence of the problem, policy, and political streams, by effective exercise of leadership. Scientists and policymakers should be attentive enough to the political context of policies

The relationship between ownership and possession: observations from the context of digital virtual goods

This theoretical article highlights limitations in the current trend towards dichotomizing full ownership and access-based consumption by recognizing a broader, more complex array of ‘fragmented’ ownership configurations in the context of digital virtual goods 10 (DVGs). In challenging this dichotomy, we recognise that the relationship between ownership and possession becomes particularly significant. We therefore consider how prominent DVG ownership configurations may shape the way in which possession is assembled, potentially reducing consumers’ scope of action rela- 15 tive to DVGs and leaving possession susceptible to disruption. Conversely, we acknowledge ways in which consumers’ continued attempts at possession may impinge upon the agency of ownership mechanisms within the market. Our analysis ultimately builds upon existing understandings of both ownership and possession, 20 theorizing their often overlooked relation in consumptio

Ownership by Design

Ownership is central to the successful design of many offerings. This is made more evident with large contextual shifts in terms of immaterial ownership, ownership by multiple users, and time dependent ownership. Psychological ownership theory links naturally to existing experience design models and is thus useful in approaching how to design for ownership. Designers should consider the motives and routes to ownership described by psychological ownership theory but also the paths to ownership formed through interaction with an object. The result is a new frame for design in which the objective is to create a possession, not simply an object. Designing an object, which is owned, means focusing on the interactions between a user and the object through the entire lifecycle including consideration of when an object enters and exits a person’s possessions. Within this new frame, there are at least four main ways in which designers can create intentional ownership experiences. Specifically, they can help: give meaning to the ownership deprived experiences increasingly prevalent in modern digital and shared contexts; structure the ownership experience; reduce redundant effort made once an object is taken into a person's possession; and mitigate contaminated interaction, which is likely to prevent ownership from occurring