The silicon trypanosome

African trypanosomes have emerged as promising unicellular model organisms for the next generation of systems biology. They offer unique advantages, due to their relative simplicity, the availability of all standard genomics techniques and a long history of quantitative research. Reproducible cultivation methods exist for morphologically and physiologically distinct life-cycle stages. The genome has been sequenced, and microarrays, RNA-interference and high-accuracy metabolomics are available. Furthermore, the availability of extensive kinetic data on all glycolytic enzymes has led to the early development of a complete, experiment-based dynamic model of an important biochemical pathway. Here we describe the achievements of trypanosome systems biology so far and outline the necessary steps towards the ambitious aim of creating a , a comprehensive, experiment-based, multi-scale mathematical model of trypanosome physiology. We expect that, in the long run, the quantitative modelling enabled by the Silicon Trypanosome will play a key role in selecting the most suitable targets for developing new anti-parasite drugs

A neural network-based estimate of the seasonal to inter-annual variability of the Atlantic Ocean carbon sink

The Atlantic Ocean is one of the most important sinks for atmospheric carbon dioxide (CO2), but this sink has been shown to vary substantially in time. Here we use surface ocean CO2 observations to estimate this sink and the temporal variability from 1998 through 2007 in the Atlantic Ocean. We benefit from (i) a continuous improvement of the observations, i.e. the Surface Ocean CO2 Atlas (SOCAT) v1.5 database and (ii) a newly developed technique to interpolate the observations in space and time. In particular, we use a two-step neural network approach to reconstruct basin-wide monthly maps of the sea surface partial pressure of CO2 (pCO2) at a resolution of 1° × 1°. From those, we compute the air–sea CO2 flux maps using a standard gas exchange parameterization and high-resolution wind speeds. The neural networks fit the observed pCO2 data with a root mean square error (RMSE) of about 10 μatm and with almost no bias. A check against independent time-series data and new data from SOCAT v2 reveals a larger RMSE of 22.8 μatm for the entire Atlantic Ocean, which decreases to 16.3 μatm for data south of 40° N. We estimate a decadal mean uptake flux of −0.45 ± 0.15 Pg C yr−1 for the Atlantic between 44° S and 79° N, representing the sum of a strong uptake north of 18° N (−0.39 ± 0.10 Pg C yr−1), outgassing in the tropics (18° S–18° N, 0.11 ± 0.07 Pg C yr−1), and uptake in the subtropical/temperate South Atlantic south of 18° S (−0.16 ± 0.06 Pg C yr−1), consistent with recent studies. The strongest seasonal variability of the CO2 flux occurs in the temperature-driven subtropical North Atlantic, with uptake in winter and outgassing in summer. The seasonal cycle is antiphased in the subpolar latitudes relative to the subtropics largely as a result of the biologically driven winter-to-summer drawdown of CO2. Over the 10 yr analysis period (1998 through 2007), sea surface pCO2 increased faster than that of the atmosphere in large areas poleward of 40° N, while in other regions of the North Atlantic the sea surface pCO2 increased at a slower rate, resulting in a barely changing Atlantic carbon sink north of the Equator (−0.01 ± 0.02 Pg C yr−1 decade−1). Surface ocean pCO2 increased at a slower rate relative to atmospheric CO2 over most of the Atlantic south of the Equator, leading to a substantial trend toward a stronger CO2 sink for the entire South Atlantic (−0.14 ± 0.02 Pg C yr−1 decade−1). In contrast to the 10 yr trends, the Atlantic Ocean carbon sink varies relatively little on inter-annual timescales (±0.04 Pg C yr−1; 1 σ)

Environmental drivers of coccolithophore abundance and calcification across Drake Passage (Southern Ocean)

Although coccolithophores are not as numerically common or as diverse in the Southern Ocean as they are in subpolar waters of the North Atlantic, a few species, such as Emiliania huxleyi, are found during the summer months. Little is actually known about the calcite production (CP) of these communities or how their distribution and physiology relate to environmental variables in this region. In February 2009, we made observations across Drake Passage (between South America and the Antarctic Peninsula) of coccolithophore distribution, CP, primary production, chlorophyll a and macronutrient concentrations, irradiance and carbonate chemistry. Although CP represented less than 1% of total carbon fixation, coccolithophores were widespread across Drake Passage. The B/C morphotype of E. huxleyi was the dominant coccolithophore, with low estimates of coccolith calcite ( 0.01 pmol C coccolith-/ from biometric measurements. Both cell-normalised calcification (0.01–0.16 pmol C cell-1 d-1/ and total CP (< 20 μmol C m-1 d-1/were much lower than those observed in the subpolar North Atlantic where E. huxleyi morphotype A is dominant. However, estimates of coccolith production rates were similar (0.1–1.2 coccoliths cell-1 h-1/ to previous measurements made in the subpolar North Atlantic. A multivariate statistical approach found that temperature and irradiance together were best able to explain the observed variation in species distribution and abundance (Spearman’s rank correlation D0.4, p < 0.01). Rates of calcification per cell and coccolith production, as well as community CP and E. huxleyi abundance, were all positively correlated (p < 0.05) to the strong latitudinal gradient in temperature, irradiance and calcite saturation states across Drake Passage. Broadly, our results lend support to recent suggestions that coccolithophores, especially E. huxleyi, are advancing polewards. However, our in situ observations indicate that this may owe more to sea-surface warming and increasing irradiance rather than increasing CO2 concentrations

Random Surfaces and Lattice Gravity

In this talk I review some of the recent developments in the field of random surfaces and the Dynamical Triangulation approach to simplicial quantum gravity. In two dimensions I focus on the c=1 barrier and the fractal dimension of two-dimensional quantum gravity coupled to matter with emphasis on the comparison of analytic predictions and numerical simulations. Next is a survey of the current understanding in 3 and 4 dimensions. This is followed by a discussion of some problems in the statistical mechanics of membranes. Finally I conclude with a list of problems for the future.Comment: 12 pages, LaTeX with espcrc2.sty, 9 eps/ps figs. Some references added. Color figs. available at http://suhep.phy.syr.edu/research/computational/pics.html Plenary talk given at Lattice 97 (Edinburgh

Urinary excretion kinetics of [¹⁷⁷Lu]Lu-PSMA-617

Introduction: For the implementation of suitable radiation safety measures in [177Lu]Lu-PSMA-617 therapy, additional insight into excretion kinetics is important. This study evaluates this kinetics in prostate cancer patients via direct urine measurements. Methods: Both the short-term (up to 24 h, n = 28 cycles) and long-term kinetics (up to 7 weeks, n = 35 samples) were evaluated by collection of urine samples. Samples were measured on a scintillation counter to determine excretion kinetics. Results: The mean excretion half-time during the first 20 h was 4.9 h. Kinetics was significantly different for patients with kidney function below or above eGFR 65 ml/min. Calculated skin equivalent dose in case of urinary contamination was between 50 and 145 mSv when it was caused between 0 and 8 h p.i. Measurable amounts of 177Lu were found in urine samples up to 18 days p.i. Conclusion: Excretion kinetics of [177Lu]Lu-PSMA-617 is especially relevant during the first 24 h, when accurate radiation safety measures are important to prevent skin contamination. Measures for accurate waste management are relevant up to 18 days.</p