A unique Toxoplasma gondii haplotype under strong selection has accompanied domestic cats in their global expansion

ABSTRACTToxoplasma gondii is a cyst-forming apicomplexan parasite of virtually all warm-blooded species, with all true cats (Felidae) as definitive hosts. It is the etiologic agent of toxoplasmosis, a disease causing substantial public health burden worldwide. Its wide range of host species and its global occurrence probably complicate the study of its evolutionary history, and conflicting scenarios have been proposed to explain its current global distribution. In this study, we analyse a global set of 156 genomes (including 105 new genomes) and we provide the first direct estimate of T. gondii mutation rate and the first estimate of its generation time. We elucidate how the evolution of T. gondii populations is intimately linked to the major events that have punctuated the recent history of cats. We show that a unique haplotype —whose length represents only 0.16% of the whole T. gondii genome— is common to all domestic T. gondii strains worldwide and has accompanied wild cats (Felis silvestris) during their emergence from the wild to domestic settlements, their dispersal in the Old World and their recent expansion to the Americas in the last six centuries. By combining environmental and functional data to selection inference tools, we show that selection of this domestic haplotype is most parsimoniously explained by its role in initiation of sexual reproduction of T. gondii in domestic cats.

Comparing Evapotranspiration Estimates from the GEOframe-Prospero Model with Penman–Monteith and Priestley-Taylor Approaches under Different Climate Conditions

Evapotranspiration (ET) is a key variable in the hydrological cycle and it directly impacts the surface balance and its accurate assessment is essential for a correct water management. ET is difficult to measure, since the existing methods for its direct estimate, such as the weighing lysimeter or the eddy-covariance system, are often expensive and require well-trained research personnel. To overcome this limit, different authors developed experimental models for indirect estimation of ET. However, since the accuracy of ET prediction is crucial from different points of view, the continuous search for more and more precise modeling approaches is encouraged. In light of this, the aim of the present work is to test the efficiency in predicting ET fluxes in a newly introduced physical-based model, named Prospero, which is based on the ability to compute the ET using a multi-layer canopy model, solving the energy balance both for the sunlight and shadow vegetation, extending the recently developed Schymanski and Or method to canopy level. Additionally, Prospero is able to compute the actual ET using a Jarvis-like model. The model is integrated as a component in the hydrological modelling system GEOframe. Its estimates were validated against observed data from five Eddy covariance (EC) sites with different climatic conditions and the same vegetation cover. Then, its performances were compared with those of two already consolidated models, the Priestley–Taylor model and Penman FAO model, using four goodness-of-fit indices. Subsequently a calibration of the three methods has been carried out using LUCA calibration within GEOframe, with the purpose of prediction errors. The results showed that Prospero is more accurate and precise with respect to the other two models, even if no calibrations were performed, with better performances in dry climatic conditions. In addition, Prospero model turned to be the least affected by the calibration procedure and, therefore, it can be effectively also used in a context of data scarcity.

Multi-year assessment of ocean surface currents from Copernicus Sentinel-1 and HF radar in the German Bight

<p>Direct estimate of ocean surface motion sensed by the Doppler shift of the surface includes ocean surface current and a wind-wave induced artefact surface velocity (WASV). The Sentinel-1 (S1) C-band SAR mission includes direct ocean surface motion estimates as an operational Level-2 Ocean (OCN) Radial VeLocity (RVL) product. The existing operational RVL products suffer from significant uncorrected platform and instrument effects that presently prevent exploitation of the data. This paper proposes a simple method to calibrate and correct for these effects and evaluate the benefit of these corrections over 2.5 years S1A acquisition against ground truth measurements. A specific geometry for S1 has been chosen for S1-A over the HF radar (HFR) instrumented site in the German Bight. The 78 S1A snapshots end in 56 match-ups within 20 minutes of HFR measurements. HFR velocity fields were projected in the same radial direction as S1A. Land calibration corrects for constant snapshot biases of the operational products up to 2 m/s. Besides these constant biases there is persistent relative biases within snapshots between up to 0.4 m/s in addition to the TOPSAR uncorrected scalloping effect with an amplitude of 0.1 m/s. After calibration, corrected RVL are compared against HFR with various WASV correction. Applying WASV correction with a reduced 70% C-Dop model, gives the best results with a precision of 0.25 m/s and correlation in time of 0.9. This might be due to C-Dop amplitude in up/downwind being too strong for a coastal environment as encountered in the German Bight. Quadratic mean of all 78 S1A snapshots after all corrections applied exhibits coastal current jets in good agreement with bathymetry channels and is promising as a cheap way to infer local bathymetry channels.</p>

Predictive modeling of clinical trial terminations using feature engineering and embedding learning

In this study, we propose to use machine learning to understand terminated clinical trials. Our goal is to answer two fundamental questions: (1) what are common factors/markers associated to terminated clinical trials? and (2) how to accurately predict whether a clinical trial may be terminated or not? The answer to the first question provides effective ways to understand characteristics of terminated trials for stakeholders to better plan their trials; and the answer to the second question can direct estimate the chance of success of a clinical trial in order to minimize costs. By using 311,260 trials to build a testbed with 68,999 samples, we use feature engineering to create 640 features, reflecting clinical trial administration, eligibility, study information, criteria etc. Using feature ranking, a handful of features, such as trial eligibility, trial inclusion/exclusion criteria, sponsor types etc., are found to be related to the clinical trial termination. By using sampling and ensemble learning, we achieve over 67% Balanced Accuracy and over 0.73 AUC (Area Under the Curve) scores to correctly predict clinical trial termination, indicating that machine learning can help achieve satisfactory prediction results for clinical trial study.

A new test suggests that balancing selection maintains hundreds of non-synonymous polymorphisms in the human genome

The role that balancing selection plays in the maintenance of genetic diversity remains unresolved. Here we introduce a new test, based on the McDonald-Kreitman test, in which the number of polymorphisms that are shared between populations is contrasted to those that are private at selected and neutral sites. We show that this simple test is robust to a variety of demographic changes, and that it can also give a direct estimate of the number of shared polymorphisms that are directly maintained by balancing selection. We apply our method to population genomic data from humans and conclude that more than a thousand non-synonymous polymorphisms are subject to balancing selection.

Nascent fusion pore opening monitored at single-SNAREpin resolution

Vesicle fusion with a target membrane is a key event in cellular trafficking and ensures cargo transport within the cell and between cells. The formation of a protein complex, called SNAREpin, provides the energy necessary for the fusion process. In a three-dimensional microfluidic chip, we monitored the fusion of small vesicles with a suspended asymmetric lipid bilayer. Adding ion channels into the vesicles, our setup allows the observation of a single fusion event by electrophysiology with 10-μs precision. Intriguingly, we identified that small transient fusion pores of discrete sizes reversibly opened with a characteristic lifetime of ∼350 ms. The distribution of their apparent diameters displayed two peaks, at 0.4 ± 0.1 nm and 0.8 ± 0.2 nm. Varying the number of SNAREpins, we demonstrated that the first peak corresponds to fusion pores induced by a single SNAREpin and the second peak is associated with pores involving two SNAREpins acting simultaneously. The pore size fluctuations provide a direct estimate of the energy landscape of the pore. By extrapolation, the energy landscape for three SNAREpins does not exhibit any thermally significant energy barrier, showing that pores larger than 1.5 nm are spontaneously produced by three or more SNAREpins acting simultaneously, and expand indefinitely. Our results quantitatively explain why one SNAREpin is sufficient to open a fusion pore and more than three SNAREpins are required for cargo release. Finally, they also explain why a machinery that synchronizes three SNAREpins, or more, is mandatory to ensure fast neurotransmitter release during synaptic transmission.

Validation and Refinement of a Steering Friction Increase Detection Algorithm Using Test Drive Data

The Electric Power Steering (EPS) System provides steering assist in conventional vehicle driving and is the main actuator for vehicle lateral control in active safety features. While the driver can sometimes compensate for reduced or loss of steering assist caused by EPS mechanical or electrical degradations, it may become very difficult to steer for larger vehicles. Furthermore, active safety functions cannot control the vehicle effectively for lateral motions without a healthy EPS system. Hence, comprehensive EPS system fault monitoring is essential for the next generation of vehicles. Previous works have utilized computer simulation and hardware-in-the-loop experiments to develop fault diagnosis and prognosis algorithms for electrical and mechanical failures in EPS systems. Using test drive data collected, this paper validates and refines a previously developed algorithm designed for detecting increases in EPS system internal mechanical friction. The data include 215 minutes of natural driving with different speeds and steering maneuvers. Noise factors such as tire type and level of friction introduced are also considered. The previous algorithm is refined to enhance performance addressing issues of time delays and parameter uncertainty specific to the previous model-based algorithm. Specifically, a Kalman filter-based joint state-parameter estimator that uses a simplified vehicle dynamic model is developed to provide a direct estimate of steering friction increase. Data collected from test drives indicate that the refined algorithm can robustly indicate a friction increase before an average human driver notices a difference in steering feel.

A Faster and More Accurate Algorithm for Calculating Population Genetics Statistics Requiring Sums of Stirling Numbers of the First Kind

Ewen’s sampling formula is a foundational theoretical result that connects probability and number theory with molecular genetics and molecular evolution; it was the analytical result required for testing the neutral theory of evolution, and has since been directly or indirectly utilized in a number of population genetics statistics. Ewen’s sampling formula, in turn, is deeply connected to Stirling numbers of the first kind. Here, we explore the cumulative distribution function of these Stirling numbers, which enables a single direct estimate of the sum, using representations in terms of the incomplete beta function. This estimator enables an improved method for calculating an asymptotic estimate for one useful statistic, Fu’s Fs. By reducing the calculation from a sum of terms involving Stirling numbers to a single estimate, we simultaneously improve accuracy and dramatically increase speed.

Measuring the balance between fisheries catch and fish production

Balanced harvesting has been proposed as a fisheries management strategy to mitigate the impacts of fisheries removal on ecosystem structure. One definition of balanced harvest is that all species should be harvested in proportion to their annual production. However, most marine ecosystems lack comprehensive production estimates necessary to empirically measure the degree of balance. We developed and tested 2 new methods for estimating fish biomass production at the species level with limited data requirements. Application of our techniques to 4 ecological production units in the northwest Atlantic (Mid-Atlantic Bight, Georges Bank, Gulf of Maine, and western Scotian Shelf) from 1991-2013 provided a direct estimate of 1.9 million t yr-1 of total fish production. The degree of balance between catch and production distributions at the species level, assessed using the proportional similarity index, ranged from 0.34 to 0.83 on a scale from near 0 to 1. Increased balance was positively associated with yield in the Gulf of Maine (Spearman’s, p = 0.04). Increased balance was negatively associated with an ecosystem impact indicator in the Gulf of Maine (Spearman’s, p = 0.03) and Mid-Atlantic Bight (Spearman’s, p = 0.02). These case studies provide some evidence of benefit to humans and reduced ecosystem harm from more balanced harvest. More importantly, we provide a unique empirical metric of balanced harvest at the species level, and develop potential indicators and methods for ecosystem-based fisheries management.