Size distribution curves of senile plaques in patients with Alzheimer’s disease: do plaques grow according to the log-normal model?

The size frequency distributions of diffuse, primitive and cored senile plaques (SP) were studied in single sections of the temporal lobe from 10 patients with Alzheimer’s disease (AD). The size distribution curves were unimodal and positively skewed. The size distribution curve of the diffuse plaques was shifted towards larger plaques while those of the neuritic and cored plaques were shifted towards smaller plaques. The neuritic/diffuse plaque ratio was maximal in the 11 – 30 micron size class and the cored/ diffuse plaque ratio in the 21 – 30 micron size class. The size distribution curves of the three types of plaque deviated significantly from a log-normal distribution. Distributions expressed on a logarithmic scale were ‘leptokurtic’, i.e. with excess of observations near the mean. These results suggest that SP in AD grow to within a more restricted size range than predicted from a log-normal model. In addition, there appear to be differences in the patterns of growth of diffuse, primitive and cored plaques. If neuritic and cored plaques develop from earlier diffuse plaques, then smaller diffuse plaques are more likely to be converted to mature plaques.

Pd/C catalysts based on synthetic carbons with bi- and tri-modal pore-size distribution:applications in flow chemistry

Two new types of phenolic resin-derived synthetic carbons with bi-modal and tri-modal pore-size distributions were used as supports for Pd catalysts. The catalysts were tested in chemoselective hydrogenation and hydrodehalogenation reactions in a compact multichannel flow reactor. Bi-modal and tri-modal micro-mesoporous structures of the synthetic carbons were characterised by N2 adsorption. HR-TEM, PXRD and XPS analyses were performed for characterising the synthesised catalysts. N2 adsorption revealed that tri-modal synthetic carbon possesses a well-developed hierarchical mesoporous structure (with 6.5 nm and 42 nm pores), contributing to a larger mesopore volume than the bi-modal carbon (1.57 cm3 g-1versus 1.23 cm3 g-1). It was found that the tri-modal carbon promotes a better size distribution of Pd nanoparticles than the bi-modal carbon due to presence of hierarchical mesopore limitting the growth of Pd nanoparticles. For all the model reactions investigated, the Pd catalyst based on tri-modal synthetic carbon (Pd/triC) show high activity as well as high stability and reproducibility. The trend in reactivities of different functional groups over the Pd/triC catalyst follows a general order alkyne ≫ nitro > bromo ≫ aldehyde.

Mass transfer characteristics of two-aqueous-phase liquid-liquid mixtures

Mass transfer rates were studied using the falling drop method. Cibacron Blue 3 GA dye was the transferring solute from the salt phase to the PEG phase. Measurements were undertaken for several concentrations of the dye and the phase-forming solutes and with a range of different drop sizes, e.g. 2.8, 3.0 and 3.7 mm. The dye was observed to be present in the salt phase as finely dispersed solids but a model confirmed that the mass transfer process could still be described by an equation based upon the Whitman two-film model. The overall mass transfer coefficient increased with increasing concentration of the dye. The apparent mass transfer coefficient ranged from 1 x 10-5 to 2 x 10 -4 m/s. Further experiments suggested that mass transfer was enhanced at high concentration by several mechanisms. The dye was found to change the equilibrium composition of the two phases, leading to transfer of salt between the drop and continuous phases. It also lowered the interfacial tension (i.e. from 1.43 x 10-4 N/m for 0.01% w/w dye concentration to 1.07 x 10-4 N/m for 0.2% w/w dye concentration) between the two phases, which could have caused interfacial instabilities (Marangoni effects). The largest drops were deformable, which resulted in a significant increase in the mass transfer rate. Drop size distribution and Sauter mean drop diameter were studied on-line in a 1 litre agitated vessel using a laser diffraction technique. The effects of phase concentration, dispersed phase hold-up and impeller speed were investigated for the salt-PEG system. An increase in agitation speed in the range 300 rpm to 1000 rpm caused a decrease in mean drop diameter, e.g. from 50 m to 15 m. A characteristic bimodal drop size distribution was established within a very short time. An increase in agitation rate caused a shift of the larger drop size peak to a smaller size.

The size frequency distributions of beta-amyloid deposit subtypes in Alzheimer's disease

The size frequency distributions of diffuse, primitive and classic beta/A4 deposits was studied in single sections in the hippocampus, parahippocampal gyrus (PHG) and lateral occipitotemporal gyrus (LOT) in five cases of Alzheimer's disease. In most brain regions, the size distribution of the diffuse deposits was significantly different from that of the primitive and classic deposits. The data suggested that larger diffuse deposits appeared to be converted less often into primitive and classic deposits. Significant differences in the size distribution of primitive deposits were commonly observed between brain regions in which there was no difference in the size distribution of the diffuse deposits. Hence, local brain factors may influence the size of diffuse deposit which can be converted into mature amyloid deposit.

Firm growth and firm size

This article analyses the growth rates of the complete population of UK-registered firms for the period 2001 to 2005. We estimate Gibrat's law – that growth rates are independent of firm size – by deciles of the firm size distribution. Whether we are able to reject Gibrat's law varies across deciles. We also show how estimates vary according to the measure of firm size, time period and sample selection.

Nonlinear signalling networks and cell-to-cell variability transform external signals into broadly distributed or bimodal responses

We show theoretically and experimentally a mechanismbehind the emergence of wide or bimodal protein distributions in biochemical networks with nonlinear input-output characteristics (the dose-response curve) and variability in protein abundance. Large cell-to-cell variation in the nonlinear dose-response characteristics can be beneficial to facilitate two distinct groups of response levels as opposed to a graded response. Under the circumstances that we quantify mathematically, the two distinct responses can coexist within a cellular population, leading to the emergence of a bimodal protein distribution. Using flow cytometry, we demonstrate the appearance of wide distributions in the hypoxia-inducible factor-mediated response network in HCT116 cells. With help of our theoretical framework, we perform a novel calculation of the magnitude of cell-to-cell heterogeneity in the dose-response obtained experimentally. © 2014 The Author(s) Published by the Royal Society. All rights reserved.

An international cohort comparison of size effects on job growth

The contribution of different-sized businesses to job creation continues to attract policymakers’ attention; however, it has recently been recognised that conclusions about size were confounded with the effect of age. We probe the role of size, controlling for age, by comparing the cohorts of firms born in 1998 over their first decade of life, using variation across half a dozen northern European countries Austria, Finland, Germany, Norway, Sweden and the UK to pin down size effects. We find that a very small proportion of the smallest firms play a crucial role in accounting for cross-country differences in job growth. A closer analysis reveals that the initial size distribution and survival rates do not seem to explain job growth differences between countries, rather it is a small number of rapidly growing firms that are driving this result.

Design of experiments to study the impact of process parameters on droplet size and development of non-invasive imaging techniques in tablet coating

Atomisation of an aqueous solution for tablet film coating is a complex process with multiple factors determining droplet formation and properties. The importance of droplet size for an efficient process and a high quality final product has been noted in the literature, with smaller droplets reported to produce smoother, more homogenous coatings whilst simultaneously avoiding the risk of damage through over-wetting of the tablet core. In this work the effect of droplet size on tablet film coat characteristics was investigated using X-ray microcomputed tomography (XμCT) and confocal laser scanning microscopy (CLSM). A quality by design approach utilising design of experiments (DOE) was used to optimise the conditions necessary for production of droplets at a small (20 μm) and large (70 μm) droplet size. Droplet size distribution was measured using real-time laser diffraction and the volume median diameter taken as a response. DOE yielded information on the relationship three critical process parameters: pump rate, atomisation pressure and coating-polymer concentration, had upon droplet size. The model generated was robust, scoring highly for model fit (R2 = 0.977), predictability (Q2 = 0.837), validity and reproducibility. Modelling confirmed that all parameters had either a linear or quadratic effect on droplet size and revealed an interaction between pump rate and atomisation pressure. Fluidised bed coating of tablet cores was performed with either small or large droplets followed by CLSM and XμCT imaging. Addition of commonly used contrast materials to the coating solution improved visualisation of the coating by XμCT, showing the coat as a discrete section of the overall tablet. Imaging provided qualitative and quantitative evidence revealing that smaller droplets formed thinner, more uniform and less porous film coats.