Inductive queries for a drug designing robot scientist

It is increasingly clear that machine learning algorithms need to be integrated in an iterative scientific discovery loop, in which data is queried repeatedly by means of inductive queries and where the computer provides guidance to the experiments that are being performed. In this chapter, we summarise several key challenges in achieving this integration of machine learning and data mining algorithms in methods for the discovery of Quantitative Structure Activity Relationships (QSARs). We introduce the concept of a robot scientist, in which all steps of the discovery process are automated; we discuss the representation of molecular data such that knowledge discovery tools can analyse it, and we discuss the adaptation of machine learning and data mining algorithms to guide QSAR experiments

Exploring novel ice-core proxies for paleoclimate reconstruction in the sub-Antarctic

New ice-core records are being developed from the sub-Antarctic, a region previously lacking in paleoclimate archives. These records capture marine-sourced organic compounds that act as proxies for sea-ice concentration, and wind-lofted diatoms that reflect westerly wind strength

Recollection-Related Increases in Functional Connectivity Predict Individual Differences in Memory Accuracy

Recollection involves retrieving specific contextual details about a prior event. Functional neuroimaging studies have identified several brain regions that are consistently more active during successful versus failed recollection—the “core recollection network.” In the present study, we investigated whether these regions demonstrate recollection-related increases not only in activity but also in functional connectivity in healthy human adults. We used fMRI to compare time-series correlations during successful versus unsuccessful recollection in three separate experiments, each using a different operational definition of recollection. Across experiments, a broadly distributed set of regions consistently exhibited recollection-related increases in connectivity with different members of the core recollection network. Regions that demonstrated this effect included both recollection-sensitive regions and areas where activity did not vary as a function of recollection success. In addition, in all three experiments the magnitude of connectivity increases correlated across individuals with recollection accuracy in areas diffusely distributed throughout the brain. These findings suggest that enhanced functional interactions between distributed brain regions are a signature of successful recollection. In addition, these findings demonstrate that examining dynamic modulations in functional connectivity during episodic retrieval will likely provide valuable insight into neural mechanisms underlying individual differences in memory performance

Cryptic loxP sites in mammalian genomes: genome-wide distribution and relevance for the efficiency of BAC/PAC recombineering techniques

Cre is widely used for DNA tailoring and, in combination with recombineering techniques, to modify BAC/PAC sequences for generating transgenic animals. However, mammalian genomes contain recombinase recognition sites (cryptic loxP sites) that can promote illegitimate DNA recombination and damage when cells express the Cre recombinase gene. We have created a new bioinformatic tool, FuzznucComparator, which searches for cryptic loxP sites and we have applied it to the analysis of the whole mouse genome. We found that cryptic loxP sites occur frequently and are homogeneously distributed in the genome. Given the mammalian nature of BAC/PAC genomic inserts, we hypothesised that the presence of cryptic loxP sites may affect the ability to grow and modify BAC and PAC clones in E. coli expressing Cre recombinase. We have observed a defect in bacterial growth when some BACs and PACs were transformed into EL350, a DH10B-derived bacterial strain that expresses Cre recombinase under the control of an arabinose-inducible promoter. In this study, we have demonstrated that Cre recombinase expression is leaky in un-induced EL350 cells and that some BAC/PAC sequences contain cryptic loxP sites, which are active and mediate the introduction of single-strand nicks in BAC/PAC genomic inserts

Pre-main-sequence Lithium Depletion

In this review I briefly discuss the theory of pre-main-sequence (PMS) Li depletion in low-mass (0.075<M<1.2 Msun) stars and highlight those uncertain parameters which lead to substantial differences in model predictions. I then summarise observations of PMS stars in very young open clusters, clusters that have just reached the ZAMS and briefly highlight recent developments in the observation of Li in very low-mass PMS stars.Comment: 8 pages, invited review at "Chemical abundances and mixing in stars in the Milky Way and its satellites", eds. L. Pasquini, S. Randich. ESO Astrophysics Symposium (Springer-Verlag

Quantifying the frequency and volume of urine deposition by grazing sheep using tri-axial accelerometers

Urine patches deposited in pasture by grazing animals are sites of reactive nitrogen (N) loss to the environment due to high concentrations of N exceeding pasture uptake requirements. In order to upscale N losses from the urine patch, several urination parameters are required, including where, when and how often urination events occur as well as the volume and chemical composition. There are limited data available in this respect, especially for sheep. Here, we seek to address this knowledge gap by using non-invasive sensor-based technology (accelerometers) on ewes grazing in situ, using a Boolean algorithm to detect urination events in the accelerometer signal. We conducted an initial study with penned Welsh Mountain ewes (n = 5), with accelerometers attached to the hind, to derive urine flow rate and to determine whether urine volume could be estimated from ewe squat time. Then accelerometers attached to the hind of Welsh Mountain ewes (n = 30 at each site) were used to investigate the frequency of sheep urination events (n = 35 946) whilst grazing two extensively managed upland pastures (semi-improved and unimproved) across two seasons (spring and autumn) at each site (35–40 days each). Sheep urinated at a frequency of 10.2 ± 0.2 and 8.1 ± 0.3 times per day in the spring and autumn, respectively, while grazing the semi-improved pasture. Urination frequency was greater (19.0 ± 0.4 and 15.3 ± 0.3 times per day in the spring and autumn, respectively) in the unimproved pasture. Ewe squat duration could be reliably used to predict the volume of urine deposited per event and was thus used to estimate mean daily urine production volumes. Sheep urinated at a rate of 16.6 mL/s and, across the entire dataset, sheep squatted for an average of 9.62 ± 0.03 s per squatting event, producing an estimated average individual urine event volume of 159 ± 1 mL (n = 35 946 events), ranging between 17 and 745 mL (for squat durations of 1 to 45 s). The estimated mean daily urine volume was 2.15 ± 0.04 L (n = 2 669 days) across the entire dataset. The data will be useful for modelling studies estimating N losses (e.g. ammonia (NH3) volatilisation, nitrous oxide (N2O) emission via nitrification and denitrification and nitrate (NO3−) leaching) from urine patches

The latitudes, attitudes, and platitudes of watershed phosphorus management in North America

Phosphorus (P) plays a crucial role in agriculture as a primary fertilizer nutrient—and as a cause of the eutrophication of surface waters. Despite decades of efforts to keep P on agricultural fields and reduce losses to waterways, frequent algal blooms persist, triggering not only ecological disruption but also economic, social, and political consequences. We investigate historical and persistent factors affecting agricultural P mitigation in a transect of major watersheds across North America: Lake Winnipeg, Lake Erie, the Chesapeake Bay, and Lake Okeechobee/Everglades. These water bodies span 26 degrees of latitude, from the cold climate of central Canada to the subtropics of the southeastern United States. These water bodies and their associated watersheds have tracked trajectories of P mitigation that manifest remarkable similarities, and all have faced challenges in the application of science to agricultural management that continue to this day. An evolution of knowledge and experience in watershed P mitigation calls into question uniform solutions as well as efforts to transfer strategies from other arenas. As a result, there is a need to admit to shortcomings of past approaches, plotting a future for watershed P mitigation that accepts the sometimes two-sided nature of Hennig Brandt’s “Devil’s Element.

Monitoring Cross-Linking, the Evolution of Refractive Index and the Glass Transition Temperature of an Epoxy Resin Using an Optical Fiber Sensor

Hyphenated analytical techniques enable the simultaneous measurement of relevant processing and materials parameters under identical environmental conditions. In the current study, a power-compensated differential scanning calorimeter (DSC) was custom-modified to enable the integration of an optical fibre sensor to monitor in situ the progression of the cross-linking reactions by inferring the evolution of the refractive index. A cleaved optical fibre was used and it served as a Fresnel reflection sensor (FRS). The DSC was calibrated with and without the integrated FRS and it was demonstrated that it did not influence the performance of the DSC. The FRS was calibrated using reference refractive index oils within the DSC. An epoxy/amine resin system was cross-linked at 70 ^oC and the enthalpy of cross-linking and the evolution of the refractive index were monitored simultaneously using the DSC and FRS respectively. After the cross-linking was completed, the DSC was programmed to perform a ramped heating schedule from ambient temperature to 150 ^oC. The FRS was capable of detecting glass transition temperature (Tg) of the cross-linked resin. An excellent correlation was observed for the Tg obtained by the FRS and DSC. The contribution of factors affecting the resolution of the data from the FRS are discussed.</p

Influence of uniaxial tensile stress on the mechanical and piezoelectric properties of short-period ferroelectric superlattice

Tetragonal ferroelectric/ferroelectric BaTiO3/PbTiO3 superlattice under uniaxial tensile stress along the c axis is investigated from first principles. We show that the calculated ideal tensile strength is 6.85 GPa and that the superlattice under the loading of uniaxial tensile stress becomes soft along the nonpolar axes. We also find that the appropriately applied uniaxial tensile stress can significantly enhance the piezoelectricity for the superlattice, with piezoelectric coefficient d33 increasing from the ground state value by a factor of about 8, reaching 678.42 pC/N. The underlying mechanism for the enhancement of piezoelectricity is discussed

Search for Exotic Mesons in pi- P Interactions at 18 GeV/c

The recent search for non $q \bar{q}$ mesons in $\pi^{-}p$ interactions at Brookhaven National Laboratory is summarized. Many final states such as $\eta \pi$, $\eta' \pi^{-}$, $a_{0} \pi$, $f_{1} \pi$, $a_{2} \pi$, $b_{1} \pi$, which are favored decay modes of exotics, are under investigation.Comment: 9 pages, PostScript, Presented at the International School of Nuclear Physics, Erice, Sicily, Italy, September 199