Artificial intelligence for drug response prediction in disease models

Non peer reviewe

Long-term determination of energetic electron precipitation into the atmosphere from AARDDVARK subionospheric VLF observations

We analyze observations of subionospherically propagating very low frequency (VLF) radio waves to determine outer radiation belt energetic electron precipitation (EEP) flux magnitudes. The radio wave receiver in Sodankylä, Finland (Sodankylä Geophysical Observatory) observes signals from the transmitter with call sign NAA (Cutler, Maine). The receiver is part of the Antarctic-Arctic Radiation-belt Dynamic Deposition VLF Atmospheric Research Konsortia (AARDDVARK). We use a near-continuous data set spanning November 2004 until December 2013 to determine the long time period EEP variations. We determine quiet day curves over the entire period and use these to identify propagation disturbances caused by EEP. Long Wave Propagation Code radio wave propagation modeling is used to estimate the precipitating electron flux magnitudes from the observed amplitude disturbances, allowing for solar cycle changes in the ambient D region and dynamic variations in the EEP energy spectra. Our method performs well during the summer months when the daylit ionosphere is most stable but fails during the winter. From the summer observations, we have obtained 693 days worth of hourly EEP flux magnitudes over the 2004–2013 period. These AARDDVARK-based fluxes agree well with independent satellite precipitation measurements during high-intensity events. However, our method of EEP detection is 10–50 times more sensitive to low flux levels than the satellite measurements. Our EEP variations also show good agreement with the variation in lower band chorus wave powers, providing some confidence that chorus is the primary driver for the outer belt precipitation we are monitoring

Resonant tunneling through a C60 molecular junction in liquid environment

We present electronic transport measurements through thiolated C$_{60}$ molecules in liquid environment. The molecules were placed within a mechanically controllable break junction using a single anchoring group per molecule. When varying the electrode separation of the C$_{60}$-modified junctions, we observed a peak in the conductance traces. The shape of the curves is strongly influenced by the environment of the junction as shown by measurements in two distinct solvents. In the framework of a simple resonant tunneling model, we can extract the electronic tunneling rates governing the transport properties of the junctions.Comment: 13 pages, 4 figures. To appear in Nanotechnolog

Deep Vascular Imaging in Wounds by Two-Photon Fluorescence Microscopy

Deep imaging within tissue (over 300 mu m) at micrometer resolution has become possible with the advent of two-photon fluorescence microscopy (2PFM). The advantages of 2PFM have been used to interrogate endogenous and exogenous fluorophores in the skin. Herein, we employed the integrin (cell-adhesion proteins expressed by invading angiogenic blood vessels) targeting characteristics of a two-photon absorbing fluorescent probe to image new vasculature and fibroblasts up to approximate to 1600 mu m within wound (neodermis)/granulation tissue in lesions made on the skin of mice. Reconstruction revealed three dimensional (3D) architecture of the vascular plexus forming at the regenerating wound tissue and the presence of a fibroblast bed surrounding the capillaries. Biologically crucial events, such as angiogenesis for wound healing, may be illustrated and analyzed in 3D on the whole organ level, providing novel tools for biomedical applications

When the path is never shortest: a reality check on shortest path biocomputation

Shortest path problems are a touchstone for evaluating the computing performance and functional range of novel computing substrates. Much has been published in recent years regarding the use of biocomputers to solve minimal path problems such as route optimisation and labyrinth navigation, but their outputs are typically difficult to reproduce and somewhat abstract in nature, suggesting that both experimental design and analysis in the field require standardising. This chapter details laboratory experimental data which probe the path finding process in two single-celled protistic model organisms, Physarum polycephalum and Paramecium caudatum, comprising a shortest path problem and labyrinth navigation, respectively. The results presented illustrate several of the key difficulties that are encountered in categorising biological behaviours in the language of computing, including biological variability, non-halting operations and adverse reactions to experimental stimuli. It is concluded that neither organism examined are able to efficiently or reproducibly solve shortest path problems in the specific experimental conditions that were tested. Data presented are contextualised with biological theory and design principles for maximising the usefulness of experimental biocomputer prototypes.Comment: To appear in: Adamatzky, A (Ed.) Shortest path solvers. From software to wetware. Springer, 201

A curated DNA barcode reference library for parasitoids of northern European cyclically outbreaking geometrid moths

Large areas of forests are annually damaged or destroyed by outbreaking insect pests. Understanding the factors that trigger and terminate such population eruptions has become crucially important, as plants, plant-feeding insects, and their natural enemies may respond differentially to the ongoing changes in the global climate. In northernmost Europe, climate-driven range expansions of the geometrid moths Epirrita autumnata and Operophtera brumata have resulted in overlapping and increasingly severe outbreaks. Delayed density-dependent responses of parasitoids are a plausible explanation for the 10-year population cycles of these moth species, but the impact of parasitoids on geometrid outbreak dynamics is unclear due to a lack of knowledge on the host ranges and prevalences of parasitoids attacking the moths in nature. To overcome these problems, we reviewed the literature on parasitism in the focal geometrid species in their outbreak range and then constructed a DNA barcode reference library for all relevant parasitoid species based on reared specimens and sequences obtained from public databases. The combined recorded parasitoid community of E. autumnata and O. brumata consists of 32 hymenopteran species, all of which can be reliably identified based on their barcode sequences. The curated barcode library presented here opens up new opportunities for estimating the abundance and community composition of parasitoids across populations and ecosystems based on mass barcoding and metabarcoding approaches. Such information can be used for elucidating the role of parasitoids in moth population control, possibly also for devising methods for reducing the extent, intensity, and duration of outbreaks.publishedVersio

Quantifying loopy network architectures

Biology presents many examples of planar distribution and structural networks having dense sets of closed loops. An archetype of this form of network organization is the vasculature of dicotyledonous leaves, which showcases a hierarchically-nested architecture containing closed loops at many different levels. Although a number of methods have been proposed to measure aspects of the structure of such networks, a robust metric to quantify their hierarchical organization is still lacking. We present an algorithmic framework, the hierarchical loop decomposition, that allows mapping loopy networks to binary trees, preserving in the connectivity of the trees the architecture of the original graph. We apply this framework to investigate computer generated graphs, such as artificial models and optimal distribution networks, as well as natural graphs extracted from digitized images of dicotyledonous leaves and vasculature of rat cerebral neocortex. We calculate various metrics based on the Asymmetry, the cumulative size distribution and the Strahler bifurcation ratios of the corresponding trees and discuss the relationship of these quantities to the architectural organization of the original graphs. This algorithmic framework decouples the geometric information (exact location of edges and nodes) from the metric topology (connectivity and edge weight) and it ultimately allows us to perform a quantitative statistical comparison between predictions of theoretical models and naturally occurring loopy graphs.Comment: 17 pages, 8 figures. During preparation of this manuscript the authors became aware of the work of Mileyko at al., concurrently submitted for publicatio

Longitudinal changes in plasma hemopexin and alpha-1-microglobulin concentrations in women with and without clinical risk factors for pre-eclampsia

Recent studies have shown increased concentration of fetal hemoglobin (HbF) in pre-eclamptic women. Plasma hemopexin (Hpx) and alpha-1-microglobulin (A1M) are hemoglobin scavenger proteins that protect against toxic effects of free heme released in the hemoglobin degradation process. We used an enzyme-linked immunosorbent assay to analyze maternal plasma Hpx and A1M concentrations at 12–14, 18–20 and 26–28 weeks of gestation in three groups: 1) 51 women with a low risk for pre-eclampsia (LRW), 2) 49 women with a high risk for pre-eclampsia (PE) who did not develop PE (HRW) and 3) 42 women with a high risk for PE who developed PE (HRPE). The study had three aims: 1) to investigate whether longitudinal differences exist between study groups, 2) to examine if Hpx and A1M concentrations develop differently in pre-eclamptic women with small for gestational age (SGA) fetuses vs. pre-eclamptic women with appropriate for gestational age fetuses, and 3) to examine if longitudinal Hpx and A1M profiles differ by PE subtype (early-onset vs. late-onset and severe vs. non-severe PE). Repeated measures analysis of variance was used to analyze differences in Hpx and A1M concentrations between the groups. We found that the differences in longitudinal plasma Hpx and A1M concentrations in HRW compared to HRPE and to LRW may be associated with reduced risk of PE regardless of clinical risk factors. In women who developed PE, a high A1M concentration from midgestation to late second trimester was associated with SGA. There were no differences in longitudinal Hpx and A1M concentrations from first to late second trimester in high-risk women who developed early-onset or. late-onset PE or in women who developed severe or. non-severe PE.Peer reviewe

A healthy dietary pattern with a low inflammatory potential reduces the risk of gestational diabetes mellitus

Purpose An optimal diet for lowering the risk of gestational diabetes mellitus (GDM) is still to be defined, but may comprise of nutrient intakes, dietary patterns, diet quality, and eating frequency. This study was designed to investigate the contribution of diet in developing GDM in a comprehensive way. Methods The dietary intake of overweight or obese women, a risk group for GDM (n = 351), was assessed using 3-day food diaries and diet quality questionnaires in early pregnancy. Eating frequency and nutrient intakes were calculated, and dietary patterns identified using principal component analysis. The inflammatory potential of the diet was determined by calculating the dietary inflammatory index (DII(R)) and energy-adjusted DII (E-DII (TM)). GDM was diagnosed with an oral glucose tolerance test at 24-28 gestational weeks. Results Higher adherence to 'healthier dietary pattern' characterized by consumptions of vegetables and rye bread associated with a reduced risk of GDM (adjusted OR 0.27, 95% CI 0.11-0.70). Higher E-DII score, indicating pro-inflammatory diet, was associated with a 27% higher risk of GDM (adjusted OR 1.27; 95% CI 1.08-1.49) for each E-DII point. In the evaluation of nutrient intakes, total fat, saturated fatty acids (SFAs), and trans fatty acids were higher and fiber lower in women developing GDM compared to women not developing GDM (all p < 0.05). Intakes of total fat, SFAs, and trans fatty acids were also significant predictors for GDM (all p < 0.05). Conclusions The results emphasize the importance of an overall healthy diet and limitation of foods with SFAs, and other nutrients with a high inflammatory potential in reducing the risk of GDM.Peer reviewe

Electron precipitation from EMIC waves: a case study from 31 May 2013

On 31 May 2013 several rising-tone electromagnetic ion-cyclotron (EMIC) waves with intervals of pulsations of diminishing periods (IPDP) were observed in the magnetic local time afternoon and evening sectors during the onset of a moderate/large geomagnetic storm. The waves were sequentially observed in Finland, Antarctica, and western Canada. Co-incident electron precipitation by a network of ground-based Antarctic Arctic Radiation-belt Dynamic Deposition VLF Atmospheric Research Konsortia (AARDDVARK) and riometer instruments, as well as the Polar-orbiting Operational Environmental Satellite (POES) electron telescopes, was also observed. At the same time POES detected 30-80 keV proton precipitation drifting westwards at locations that were consistent with the ground-based observations, indicating substorm injection. Through detailed modelling of the combination of ground and satellite observations the characteristics of the EMIC-induced electron precipitation were identified as: latitudinal width of 2-3° or ΔL=1 Re, longitudinal width ~50° or 3 hours MLT, lower cut off energy 280 keV, typical flux 1×104 el. cm-2 sr-1 s-1 >300 keV. The lower cutoff energy of the most clearly defined EMIC rising tone in this study confirms the identification of a class of EMIC-induced precipitation events with unexpectedly low energy cutoffs of <400 keV