A graph theoretical approach to data fusion.

The rapid development of high throughput experimental techniques has resulted in a growing diversity of genomic datasets being produced and requiring analysis. Therefore, it is increasingly being recognized that we can gain deeper understanding about underlying biology by combining the insights obtained from multiple, diverse datasets. Thus we propose a novel scalable computational approach to unsupervised data fusion. Our technique exploits network representations of the data to identify similarities among the datasets. We may work within the Bayesian formalism, using Bayesian nonparametric approaches to model each dataset; or (for fast, approximate, and massive scale data fusion) can naturally switch to more heuristic modeling techniques. An advantage of the proposed approach is that each dataset can initially be modeled independently (in parallel), before applying a fast post-processing step to perform data integration. This allows us to incorporate new experimental data in an online fashion, without having to rerun all of the analysis. We first demonstrate the applicability of our tool on artificial data, and then on examples from the literature, which include yeast cell cycle, breast cancer and sporadic inclusion body myositis datasets

Cellular population dynamics control the robustness of the stem cell niche.

Within populations of cells, fate decisions are controlled by an indeterminate combination of cell-intrinsic and cell-extrinsic factors. In the case of stem cells, the stem cell niche is believed to maintain 'stemness' through communication and interactions between the stem cells and one or more other cell-types that contribute to the niche conditions. To investigate the robustness of cell fate decisions in the stem cell hierarchy and the role that the niche plays, we introduce simple mathematical models of stem and progenitor cells, their progeny and their interplay in the niche. These models capture the fundamental processes of proliferation and differentiation and allow us to consider alternative possibilities regarding how niche-mediated signalling feedback regulates the niche dynamics. Generalised stability analysis of these stem cell niche systems enables us to describe the stability properties of each model. We find that although the number of feasible states depends on the model, their probabilities of stability in general do not: stem cell-niche models are stable across a wide range of parameters. We demonstrate that niche-mediated feedback increases the number of stable steady states, and show how distinct cell states have distinct branching characteristics. The ecological feedback and interactions mediated by the stem cell niche thus lend (surprisingly) high levels of robustness to the stem and progenitor cell population dynamics. Furthermore, cell-cell interactions are sufficient for populations of stem cells and their progeny to achieve stability and maintain homeostasis. We show that the robustness of the niche - and hence of the stem cell pool in the niche - depends only weakly, if at all, on the complexity of the niche make-up: simple as well as complicated niche systems are capable of supporting robust and stable stem cell dynamics

Lymphatic Filariasis Control in Tanzania: Effect of Six Rounds of Mass Drug Administration with Ivermectin and Albendazole on Infection and Transmission.

Control of lymphatic filariasis (LF) in most countries of sub-Saharan Africa is based on annual mass drug administration (MDA) with a combination of ivermectin and albendazole, in order to interrupt transmission. We present findings from a detailed study on the effect of six rounds of MDA with this drug combination as implemented by the National Lymphatic Filariasis Elimination Programme (NLFEP) in a highly endemic rural area of north-eastern Tanzania.\ud The effect of treatment on transmission and human infection was monitored in a community- and a school-based study during an 8-year period (one pre-intervention and 7 post-intervention years) from 2003 to 2011. Before intervention, 24.5% of the community population had microfilariae (mf) in the blood, 53.3% had circulating filarial antigens (CFA) and 78.9% had specific antibodies to the recombinant filarial antigen Bm14. One year after the sixth MDA, these values had decreased considerably to 2.7%, 19.6% and 27.5%, respectively. During the same period, the CFA prevalence among new intakes of Standard 1 pupils in 10 primary schools decreased from 25.2% to 5.6%. In line with this, transmission by the three vectors (Anopheles gambiae, An. funestus and Culex quinquefasciatus) as determined by dissection declined sharply (overall vector infectivity rate by 99.3% and mean monthly transmission potential by 99.2% between pre-intervention and fifth post-intervention period). A major shift in vector species composition, from predominantly anopheline to almost exclusively culicine was observed over the years. This may be largely unrelated to the MDAs but may have important implications for the epidemiology of LF in the area. Six MDAs caused considerable decrease in all the measured indices for transmission and human infection. In spite of this, indices were still relatively high in the late period of the study, and it may take a long time to reach the recommended cut-off levels for interruption of transmission unless extra efforts are made. These should include increased engagement of the target population in the control activities, to ensure higher treatment coverage. It is expected that the recent initiative to distribute insecticide impregnated bed nets to every household in the area will also contribute towards reaching the goal of successful LF elimination

What Determines M&A Legal and Financial Advisors’ Competitiveness in an International Financial Centre: Using China's Going Out Policy as a Natural Experiment

Roughly 60% of all publically announced advisors to China’s 'Going Out' M&A transactions from 2000 to 2014 were from international financial centres (representing over 70% of deal value). Why did advisors, located so far away from both acquirer and target, manage to dominate the M&A advisory market in the early stages of the 'Going Out' policy? What can we learn from the smaller advisors located outside of these financial centres who managed to capture a growing share of this business in 'Going Out’s' more recent stages? In this paper, we hypothesize the existence of a 'legal complexity externality' that had the effect of increasing a financial centre’s ability to attract international business. We look at the way Going Out advisors have responded to advisory opportunities using what management theorists call 'blue ocean strategy.' We show that relationships across geography changed, as large global advisors lost their share of advisory business to advisors outside of international financial centres due to the interplay of these legal complexity externalities and blue ocean strategies. As cities helps foster changes in the law governing Going Out transactions – and as financial and legal advisors adapted their strategies to compete – cities gained or lost Going Out business. We provide 5 recommendations to existing and aspiring international financial centres looking to capture a larger share of global M&A and other investment advisory business.postprin

Model selection in systems biology depends on experimental design.

Experimental design attempts to maximise the information available for modelling tasks. An optimal experiment allows the inferred models or parameters to be chosen with the highest expected degree of confidence. If the true system is faithfully reproduced by one of the models, the merit of this approach is clear - we simply wish to identify it and the true parameters with the most certainty. However, in the more realistic situation where all models are incorrect or incomplete, the interpretation of model selection outcomes and the role of experimental design needs to be examined more carefully. Using a novel experimental design and model selection framework for stochastic state-space models, we perform high-throughput in-silico analyses on families of gene regulatory cascade models, to show that the selected model can depend on the experiment performed. We observe that experimental design thus makes confidence a criterion for model choice, but that this does not necessarily correlate with a model's predictive power or correctness. Finally, in the special case of linear ordinary differential equation (ODE) models, we explore how wrong a model has to be before it influences the conclusions of a model selection analysis

Correlating photovoltaic properties of PTB7-Th:PC71BM blend to photophysics and microstructure as a function of thermal annealing

Selective optimisation of light harvesting materials and interface properties has brought breakthroughs in power conversion efficiency (11–12%) of organic photovoltaics (OPVs). However to translate this promising efficiency to economically viable applications, long term stability is a fundamental requirement. A number of degradation pathways, both extrinsic and intrinsic, reduce the long term stability of OPVs. Here, the photovoltaic properties of a highly efficient bulk heterojunction PTB7-Th:PC71BM blend were investigated as a function of ex situ thermal annealing. The changes in charge generation, separation, and transport due to thermal annealing were measured and related to changes in the microstructure and photovoltaic performance. A 30% drop in the power conversion efficiency of PTB7-Th:PC71BM blends upon thermal annealing at 150 °C was identified as mainly due to morphological instability induced by strong phase separation of donor and acceptor molecules of the blend films. Based on the insight gained from these investigations, enhanced thermal stability was demonstrated by replacing the PC71BM fullerene acceptor with a non-fullerene acceptor ITIC, for which power conversion efficiency dropped only by 9% upon thermal annealing at 150 °C

MEANS: python package for Moment Expansion Approximation, iNference and Simulation.

MOTIVATION: Many biochemical systems require stochastic descriptions. Unfortunately these can only be solved for the simplest cases and their direct simulation can become prohibitively expensive, precluding thorough analysis. As an alternative, moment closure approximation methods generate equations for the time-evolution of the system's moments and apply a closure ansatz to obtain a closed set of differential equations; that can become the basis for the deterministic analysis of the moments of the outputs of stochastic systems. RESULTS: We present a free, user-friendly tool implementing an efficient moment expansion approximation with parametric closures that integrates well with the IPython interactive environment. Our package enables the analysis of complex stochastic systems without any constraints on the number of species and moments studied and the type of rate laws in the system. In addition to the approximation method our package provides numerous tools to help non-expert users in stochastic analysis. AVAILABILITY AND IMPLEMENTATION: https://github.com/theosysbio/means CONTACTS: [email protected] or [email protected] SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online

Passive water control at the surface of a superhydrophobic lichen

Some lichens have a super-hydrophobic upper surface, which repels water drops, keeping the surface dry but probably preventing water uptake. Spore ejection requires water and is most efficient just after rainfall. This study was carried out to investigate how super-hydrophobic lichens manage water uptake and repellence at their fruiting bodies, or podetia. Drops of water were placed onto separate podetia of Cladonia chlorophaea and observed using optical microscopy and cryo-scanning-electron microscopy (cryo-SEM) techniques to determine the structure of podetia and to visualise their interaction with water droplets. SEM and optical microscopy studies revealed that the surface of the podetia was constructed in a three-level structural hierarchy. By cryo-SEM of water-glycerol droplets placed on the upper part of the podetium, pinning of the droplet to specific, hydrophilic spots (pycnidia/apothecia) was observed. The results suggest a mechanism for water uptake, which is highly sophisticated, using surface wettability to generate a passive response to different types of precipitation in a manner similar to the Namib Desert beetle. This mechanism is likely to be found in other organisms as it offers passive but selective water control