240 research outputs found
Dynamics of polymer ejection from capsid
Polymer ejection from a capsid through a nanoscale pore is an important
biological process with relevance to modern biotechnology. Here, we study
generic capsid ejection using Langevin dynamics. We show that even when the
ejection takes place within the drift-dominated region there is a very high
probability for the ejection process not to be completed. Introducing a small
aligning force at the pore entrance enhances ejection dramatically. Such a pore
asymmetry is a candidate for a mechanism by which a viral ejection is
completed. By detailed high-resolution simulations we show that such capsid
ejection is an out-of-equilibrium process that shares many common features with
the much studied driven polymer translocation through a pore in a wall or a
membrane. We find that the escape times scale with polymer length, . We show that for the pore without the asymmetry the previous
predictions corroborated by Monte Carlo simulations do not hold. For the pore
with the asymmetry the scaling exponent varies with the initial monomer density
(monomers per capsid volume) inside the capsid. For very low densities
the polymer is only weakly confined by the capsid, and we
measure , which is close to obtained for polymer
translocation. At intermediate densities the scaling exponents
and for and , respectively. These scalings are in
accord with a crude derivation for the lower limit . For the
asymmetrical pore precise scaling breaks down, when the density exceeds the
value for complete confinement by the capsid, . The
high-resolution data show that the capsid ejection for both pores, analogously
to polymer translocation, can be characterized as a multiplicative stochastic
process that is dominated by small-scale transitions.Comment: 10 pages, 6 figure
Consultocracy and its discontents : A critical typology and a call for a research agenda
Peer reviewe
Multiple Deprivation, Severity and Latent Sub-Groups:Advantages of Factor Mixture Modelling for Analysing Material Deprivation
Material deprivation is represented in different forms and manifestations. Two individuals with the same deprivation score (i.e. number of deprivations), for instance, are likely to be unable to afford or access entirely or partially different sets of goods and services, while one individual may fail to purchase clothes and consumer durables and another one may lack access to healthcare and be deprived of adequate housing . As such, the number of possible patterns or combinations of multiple deprivation become increasingly complex for a higher number of indicators. Given this difficulty, there is interest in poverty research in understanding multiple deprivation, as this analysis might lead to the identification of meaningful population sub-groups that could be the subjects of specific policies. This article applies a factor mixture model (FMM) to a real dataset and discusses its conceptual and empirical advantages and disadvantages with respect to other methods that have been used in poverty research . The exercise suggests that FMM is based on more sensible assumptions (i.e. deprivation covary within each class), provides valuable information with which to understand multiple deprivation and is useful to understand severity of deprivation and the additive properties of deprivation indicators
Radiosynthesis and preclinical evaluation of [68Ga]Ga-NOTA-folate for PET imaging of folate receptor ÎČ-positive macrophages
Folate receptor ÎČ (FR-ÎČ), a marker expressed on macrophages, is a promising target for imaging of inflammation. Here, we report the radiosynthesis and preclinical evaluation of [68Ga]Ga-NOTA-folate (68Ga-FOL). After determining the affinity of 68Ga-FOL using cells expressing FR-ÎČ, we studied atherosclerotic mice with 68Ga-FOL and 18F-FDG PET/CT. In addition, we studied tracer distribution and co-localization with macrophages in aorta cryosections using autoradiography, histology, and immunostaining. The specificity of 68Ga-FOL was assessed in a blocking study with folate glucosamine. As a final step, human radiation doses were extrapolated from rat PET data. We were able to produce 68Ga-FOL with high radiochemical purity and moderate molar activity. Cell binding studies revealed that 68Ga-FOL had 5.1 nM affinity for FR-ÎČ. Myocardial uptake of 68Ga-FOL was 20-fold lower than that of 18F-FDG. Autoradiography and immunohistochemistry of the aorta revealed that 68Ga-FOL radioactivity co-localized with Mac-3âpositive macrophage-rich atherosclerotic plaques. The plaque-to-healthy vessel wall ratio of 68Ga-FOL was significantly higher than that of 18F-FDG. Blocking studies verified that 68Ga-FOL was specific for FR. Based on estimations from rat data, the human effective dose was 0.0105 mSv/MBq. Together, these findings show that 68Ga-FOL represents a promising new FR-ÎČâtargeted tracer for imaging macrophage-associated inflammation.</p
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