Domain is a Moving Target for Relational Learning

The domain for relational learning was manipulated by varying the training set size for pigeons that had learned the same/different (S/D) concept. Six pigeons that had learned a S/D task with pairs of pictures with a set size of 1,024 picture items had their training set size reduced to 8 items. Training on the reduced 8-item set was followed by transfer testing that was repeated four times. Transfer performance following reduction of the training set to 8 items was less than it had been when the pigeons were trained with the 1,024-item set, but 25.8% above chance. This partial abstract-concept learning remained constant over the four tests with novel stimuli. The results show that a broad domain established by a large expanding training set can once again become restricted by further training with a small training set

Aviation Bird Hazard in NEXRAD Dual Polarization Weather Radar Confirmed by Visual Observations

Birds represent a significant hazard to flying aircraft as illustrated by the “Miracle on the Hudson” encounter in 2009 between U.S. Airways Flight 1549 and a flock of Canada Geese, forcing the flight to ditch in the river. Birds are common in the skies over Florida during the spring migration season, and often appear in the National Weather Service’s (NWS) NEXRAD weather radar imagery as an easily recognizable signature known as a “roost ring.” This paper presents a NEXRAD roost ring case in central Florida in a rare instance where the signatures were confirmed by visual observations of the birds. In 2013 the NWS completed an upgrade of its NEXRAD systems to dual polarization, a technology designed to improve target classification. Use of new dual polarization weather radar variables to better discriminate birds from precipitation for the current case is demonstrated. It is shown that the dual polarization capability, and specifically, the correlation coefficient product, allows for greater confidence in identifying radar echoes due to birds, and therefore could lead to better situational awareness for aviation operations personnel able to recognize these signatures

Testing the limits of SMILES-based de novo molecular generation with curriculum and deep reinforcement learning

Deep reinforcement learning methods have been shown to be potentially powerful tools for de novo design. Recurrent-neural-network-based techniques are the most widely used methods in this space. In this work we examine the behaviour of recurrent-neural-network-based methods when there are few (or no) examples of molecules with the desired properties in the training data. We find that targeted molecular generation is usually possible, but the diversity of generated molecules is often reduced and it is not possible to control the composition of generated molecular sets. To help overcome these issues, we propose a new curriculum-learning-inspired recurrent iterative optimization procedure that enables the optimization of generated molecules for seen and unseen molecular profiles, and allows the user to control whether a molecular profile is explored or exploited. Using our method, we generate specific and diverse sets of molecules with up to 18 times more scaffolds than standard methods for the same sample size; however, our results also point to substantial limitations of one-dimensional molecular representations, as used in this space. We find that the success or failure of a given molecular optimization problem depends on the choice of simplified molecular-input line-entry system (SMILES)

Quantum fluctuations in one-dimensional arrays of condensates

The effects of quantum and thermal fluctuations upon the fringe structure predicted to be observable in the momentum distribution of coupled Bose-Einstein condensates are studied by the effective-potential method. For a double-well trap, the coherence factor recently introduced by Pitaevskii and Stringari [Phys. Rev. Lett. 87, 180402 (2001)] is calculated using the effective potential approach and is found in good agreement with their result. The calculations are extended to the case of a one-dimensional array of condensates, showing that quantum effects are essentially described through a simple renormalization of the energy scale in the classical analytical expression for the fringe structure. The consequences for the experimental observability are discussed.Comment: RevTeX, 4 pages, 5 eps figures (published version with updated references

Fragment Hotspot Mapping to Identify Selectivity-Determining Regions between Related Proteins.

Funder: ExscientiaFunder: Diamond Light SourceFunder: Kungliga Tekniska HoegskolanFunder: Chinese Center for Disease Control and PreventionFunder: European Federation of Pharmaceutical Industries and AssociationsFunder: European CommissionFunder: Kennedy Trust for Rheumatology ResearchFunder: Ontario Institute for Cancer ResearchFunder: Royal Institution for the Advancement of Learning McGill UniversityFunder: UCBSelectivity is a crucial property in small molecule development. Binding site comparisons within a protein family are a key piece of information when aiming to modulate the selectivity profile of a compound. Binding site differences can be exploited to confer selectivity for a specific target, while shared areas can provide insights into polypharmacology. As the quantity of structural data grows, automated methods are needed to process, summarize, and present these data to users. We present a computational method that provides quantitative and data-driven summaries of the available binding site information from an ensemble of structures of the same protein. The resulting ensemble maps identify the key interactions important for ligand binding in the ensemble. The comparison of ensemble maps of related proteins enables the identification of selectivity-determining regions within a protein family. We applied the method to three examples from the well-researched human bromodomain and kinase families, demonstrating that the method is able to identify selectivity-determining regions that have been used to introduce selectivity in past drug discovery campaigns. We then illustrate how the resulting maps can be used to automate comparisons across a target protein family

Systematic errors in cosmic microwave background polarization measurements

We investigate the impact of instrumental systematic errors on the potential of cosmic microwave background polarization experiments targeting primordial B-modes. To do so, we introduce spin-weighted Muller matrix-valued fields describing the linear response of the imperfect optical system and receiver, and give a careful discussion of the behaviour of the induced systematic effects under rotation of the instrument. We give the correspondence between the matrix components and known optical and receiver imperfections, and compare the likely performance of pseudo-correlation receivers and those that modulate the polarization with a half-wave plate. The latter is shown to have the significant advantage of not coupling the total intensity into polarization for perfect optics, but potential effects like optical distortions that may be introduced by the quasi-optical wave plate warrant further investigation. A fast method for tolerancing time-invariant systematic effects is presented, which propagates errors through to power spectra and cosmological parameters. The method extends previous studies to an arbitrary scan strategy, and eliminates the need for time-consuming Monte-Carlo simulations in the early phases of instrument and survey design. We illustrate the method with both simple parametrized forms for the systematics and with beams based on physical-optics simulations. Example results are given in the context of next-generation experiments targeting tensor-to-scalar ratios r ~ 0.01.Comment: 19 pages, 7 figures; Minor changes to match version accepted by MNRA

Effects of early marine diagenesis and site-specific depositional controls on carbonate-associated sulfate : insights from paired S and O isotopic analyses

Acknowledgment is made to the donors of the American Chemical Society Petroleum Research Fund (#57548-ND2) to D.F. for partial support of this research and from the Estonian Research Council (#PUT611, #PRG836) to O.H and A.L.Carbon, sulfur and oxygen isotope profiles in Silurian strata of the Baltoscandian Basin (Estonia), coincident with the Ireviken Bioevent, provide insights into basin-scale and platform-specific depositional processes. Paired carbon isotope records preserve a positive isotope excursion during the early Wenlock, coincident with faunal turnover, yet δ13C variability of this excursion compared to other locations within the paleobasin reflects local depositional influences superimposed on a global signal. In comparison, sulfur isotope records do not preserve a systematic isotopic excursion over the same interval. Instead, sulfur isotope records have high sample-to-sample stratigraphic variability, particularly in shallow-water carbonate rocks (scatter up to ~10‰ for δ34SCAS and ~ 25‰ for δ34Spyr). This pattern of isotopic variability is also found between sites from the same carbonate platform, where the magnitude and isotopic variability in δ34SCAS and δ34Spyr differ depending on relative local sea level (and therefore facies). Such facies-dependent variability reflects more closed- versus more open-system diagenetic conditions where pulses of increased sedimentation rate in the shallow water environments generates greater isotopic variability in both δ34SCAS and δ34Spyr. Increased reworking and proximity to the shoreline results in local sulfide oxidation, seen as a decrease in δ34SCAS in the most proximal settings. Platform-scale evolution of isotopically distilled pore-fluids associated with dolomitization results in increased δ34SCAS in deep water settings. Correlations in paired δ34SCAS-δ18OCAS data support these conclusions, demonstrating the local alteration of CAS during deposition and early marine diagenesis. We present a framework to assess the sequence of diagenetic and depositional environmental processes that have altered δ34SCAS and find that δ34S of ~27–28‰ approximates Silurian seawater sulfate. Our findings provide a mechanism to understand the elevated variability in many deep-time δ34SCAS records that cannot otherwise be reconciled with behavior of the marine sulfate reservoir.PostprintPeer reviewe

Dual PI3K and Wnt pathway inhibition is a synergistic combination against triple negative breast cancer

Triple negative breast cancer accounts for 15-20% of all breast cancer cases, but despite its lower incidence, contributes to a disproportionately higher rate of mortality. As there are currently no Food and Drug Administration-approved targeted agents for triple negative breast cancer, we embarked on a genomic-guided effort to identify novel targeted modalities. Analyses by our group and The Cancer Genome Atlas have identified activation of the PI3K-pathway in the majority of triple negative breast cancers. As single agent therapy is commonly subject to resistance, we investigated the use of combination therapy against compensatory pathways. Herein, we demonstrate that pan-PI3K inhibition in triple negative breast cancers results in marked activation of the Wnt-pathway. Using the combination of two inhibitors currently in clinical trial as single agents, buparlisib(pan-PI3K) and WNT974(WNT-pathway), we demonstrate significant in vitro and in vivo synergy against triple negative breast cancer cell lines and xenografts. Taken together, these observations provide a strong rationale for testing dual targeting of the PI3K and WNT-pathways in clinical trials

Macroscopic Quantum Tunneling of a Bose-Einstein Condensate with Attractive Interaction

A Bose-Einstein condensate with attractive interaction can be metastable if it is spatially confined and if the number of condensate bosons $N_0$ is below a certain critical value $N_{\rm c}$. By applying a variational method and the instanton techinique to the Gross-Pitaevskii energy functional, we find analytically the frequency of the collective excitation and the rate of macroscopic quantum tunneling (MQT). We show that near the critical point the tunneling exponent vanishes according to $(1-N_0/N_c)^\frac{5}{4}$ and that MQT can be a dominant decay mechanism of the condensate for $N_0$ very close to $N_{\rm c}$.Comment: RevTex 4 pages with 1 postscript figure. Accepted for publication in Physical Review Letter