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One of the most salient explanations for the distinctive path of economic and political development of the United States is captured by the 'Frontier (or Turner) thesis'. Turner argued that it was the presence of the open frontier which explained why the United States became democratic and, at least implicitly, prosperous. In this paper we provide a simple test of this idea. We begin with the contradictory observation that almost every Latin American country had a frontier in the 19th century as well. We show that while the data does not support the Frontier thesis, it is consistent with a more complex 'conditional Frontier thesis.' In this view, the effect of the frontier is conditional on the way that the frontier was allocated and this in turn depends on political institutions at the time of frontier expansion. We show that for countries with the worst political institutions, there is a negative correlation between the historical extent of the frontier and contemporary income per-capita. For countries with better political institutions this correlation is positive. Though the effect of the frontier on democracy is positive irrespective of initial political institutions, it is larger the better were these institutions. In essence, Turner saw the frontier as having positive effects on development because he already lived in a country with good institutions.
However, some of plant sources are just hypothesized by observing the foraging behaviors of bees and not comparing the chemical composition of secondary metabolites in propolis and in the plant source. So, there is a strong need to compare the chemical composition of propolis and of plants to confirm the exact botanical origin .
We then consider the average number of mechanisms of action per drug, by starting year of the project (Fig. 4a), observing a clear positive trend with a pronounced increase after 2010. This trend is confirmed also for the individual ATC1 classes, as shown in Additional file 1: Fig. S2. Between 1990 and 2017, the average number of mechanisms of action per drug has nearly tripled. This result may reflect a general improvement of drug efficacy, as they act on multiple targets, while it also reflects the increasing difficulty of drug design .
How much of the improvement in R&D productivity that we documented is structural and how much is transient is an important question for future research. The duration of drug development remains a concern, even though the intensification of the collaboration between firms and regulatory agencies can provide guidance and contribute to positively impact development times (e.g. in Breakthrough Therapy Designation procedures ). If the evidences of an increasing productivity will be confirmed, several cohorts of novel therapeutic compounds will reach the market, targeting specific indications and patient groups. A new landscape is emerging, which will be shaped by the coevolution between the progress of the research frontier and the strategies that regulators will implement to deal with new, possible, trade-offs between innovation, access and sustainability.
Fukui realized that a good approximation for reactivity could be found by looking at the frontier orbitals (HOMO/LUMO). This was based on three main observations of molecular orbital theory as two molecules interact:
These results can be predicted with FMO theory by observing the interaction between the HOMO and LUMO of the species. To use FMO theory, the reaction should be considered as two separate ideas: (1) whether or not the reaction is allowed, and (2) which mechanism the reaction proceeds through. In the case of a [1,5] shift on pentadiene, the HOMO of the sigma bond (i.e. a constructive bond) and the LUMO of butadiene on the remaining 4 carbons is observed. Assuming the reaction happens suprafacially, the shift results with the HOMO of butadiene on the 4 carbons that are not involved in the sigma bond of the product. Since the pi system changed from the LUMO to the HOMO, this reaction is allowed (though it would not be allowed if the pi system went from LUMO to LUMO). 2b1af7f3a8