A guide to choosing and implementing reference models for social network analysis

Analysing social networks is challenging. Key features of relational data require the use of non-standard statistical methods such as developing system-specific null, or reference, models that randomize one or more components of the observed data. Here we review a variety of randomization procedures that generate reference models for social network analysis. Reference models provide an expectation for hypothesis testing when analysing network data. We outline the key stages in producing an effective reference model and detail four approaches for generating reference distributions: permutation, resampling, sampling from a distribution, and generative models. We highlight when each type of approach would be appropriate and note potential pitfalls for researchers to avoid. Throughout, we illustrate our points with examples from a simulated social system. Our aim is to provide social network researchers with a deeper understanding of analytical approaches to enhance their confidence when tailoring reference models to specific research questions.     

The AC conductivity of human sweat ducts as the dominant factor in the sub-THz reflection coefficient of skin

The helical nature of human sweat ducts, combined with the morphological and dielectric properties of skin, suggests electromagnetic activity in the sub-THz frequency band. A detailed electromagnetic simulation model of the skin, with embedded sweat ducts, was created. The model includes realistic dielectric properties based on the measured water content of each layer of skin, derived from Raman Spectroscopy. The model was verified by comparing it to measurements of the reflection coefficient of the palms of 13 volunteers in the frequency band 350–410 GHz. They were subjected to a measurement protocol intended to induce mental stress, thereby also activating the sweat glands. The Galvanic Skin Response was concurrently measured. Using the simulation model the optimal ac-conductivity for each measurement was found. The range of variation for all subjects was found to be from 100 S/m to a maximum value of 6000 S/m with averages of 1000 S/m. These are one order of magnitude increase from the accepted values for water at these frequencies (~100 s/m at 100 GHz). Considering the known biochemical mechanism for inducing perspiration, we conclude that these ac-conductivity levels are probably valid, even though the real time measurements of sweat ac-conductivity levels inside the duct are inaccessible.     

Hormone-dependent transformation and nuclear localisation of 1,25-dihydroxyvitamin D3 receptors from human breast cancer cell lines and chick duodenum

Recent studies on the 1,25-dihydroxyvitamin D3 (calcitriol) receptor have shown association of unoccupied receptor with isolated nuclei, thus suggesting that hormone is not required for transformation and nuclear localisation of this receptor. In the present work calcitriol receptors from cultured breast cancer cells were studied for evidence of hormone-dependent activation and compared to those from chick duodenum. Unlike other steroid receptors changes in receptor mobility on ion exchange and gel filtration were not found for occupied and unoccupied receptors. Furthermore no changes in affinity were observed on DNA-cellulose with both hormone-bound and unoccupied receptor having equally high affinity, eluting at 0.25 M KCI. However, a substantial hormone-dependent increase in receptor affinity for nuclei was seen. Thus calcitriol receptors do appear to undergo hormone-dependent transformation which is detected by their increased affinity for nuclei, without any accompanying gross changes in charge density, size or affinity for DNA-cellulose. Previously, we have reported that fractionation of T-47D cells in a low salt buffer resulted in recovery of unoccupied receptors in the cytosol, whereas occupied receptors were associated with purified nuclei. The data presented in this paper and our previous work suggest that calcitriol receptors do undergo a hormone-dependent increase in their affinity for nuclei. Furthermore in all this work calcitriol receptors from cultured human breast cancer cells displayed identical physicochemical characteristics to those of chick duodenal receptors.     

In vitro enzyme evolution: the screening challenge of isolating the one in a million

The generation of large mutant libraries for in vitro enzyme evolution presents the challenge of effectively screening libraries of 10⁴–10⁷ mutants on the basis of simultaneously assaying their biocatalytic activity. In this review, we highlight the main steps involved in this process, describe the alternative approaches to address this challenge, survey the state-of-the-art technology and assess achievements already made. It is anticipated that, as a result of the expected accomplishment of further improvements in high-throughput screening that will allow routine screening of whole libraries, the number of useful new and improved enzymes derived through in vitro enzyme evolution will expand rapidly in the near future.