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In 2015, the largest recorded harmful algal bloom (HAB) occurred in the Northeast Pacific, causing nearly 100 million dollars in damages to fisheries and killing many protected marine mammals. Dominated by the toxic diatom Pseudo-nitzschia australis, this bloom produced high levels of the neurotoxin domoic acid (DA). Through molecular and transcriptional characterization of 52 near-weekly phytoplankton net-tow samples collected at a bloom hotspot in Monterey Bay, California, we identified active transcription of known DA biosynthesis (dab) genes from the three identified toxigenic species, including P. australis as the primary origin of toxicity. Elevated expression of silicon transporters (sit1) during the bloom supports the previously hypothesized role of dissolved silica (Si) exhaustion in contributing to bloom physiology and toxicity. We find that coexpression of the dabA and sit1 genes serves as a robust predictor of DA one week in advance, potentially enabling the forecasting of DA-producing HABs. We additionally present evidence that low levels of iron could have colimited the diatom population along with low Si. Iron limitation represents an overlooked driver of both toxin production and ecological success of the low-iron-adapted Pseudo-nitzschia genus during the 2015 bloom, and increasing pervasiveness of iron limitation may fuel the escalating magnitude and frequency of toxic Pseudo-nitzschia blooms globally. Our results advance understanding of bloom physiology underlying toxin production, bloom prediction, and the impact of global change on toxic blooms.

Einsteins general theory of relativity from 19151 remains the most successful description of gravitation. From the 1919 solar eclipse2 to the observation of gravitational waves3, the theory has passed many crucial experimental tests. However, the evolving concepts of dark matter and dark energy illustrate that there is much to be learned about the gravitating content of the universe. Singularities in the general theory of relativity and the lack of a quantum theory of gravity suggest that our picture is incomplete. It is thus prudent to explore gravity in exotic physical systems. Antimatter was unknown to Einstein in 1915. Diracs theory4 appeared in 1928; the positron was observed5 in 1932. There has since been much speculation about gravity and antimatter. The theoretical consensus is that any laboratory mass must be attracted6 by the Earth, although some authors have considered the cosmological consequences if antimatter should be repelled by matter7-10. In the general theory of relativity, the weak equivalence principle (WEP) requires that all masses react identically to gravity, independent of their internal structure. Here we show that antihydrogen atoms, released from magnetic confinement in the ALPHA-g apparatus, behave in a way consistent with gravitational attraction to the Earth. Repulsive antigravity is ruled out in this case. This experiment paves the way for precision studies of the magnitude of the gravitational acceleration between anti-atoms and the Earth to test the WEP.

The Mu2e experiment at the Fermilab Muon Campus will search for the coherent neutrinoless conversion of a muon into an electron in the field of an aluminum nucleus with a sensitivity improvement by a factor of 10000 over existing limits. The Mu2e Trigger and Data Acquisition System (TDAQ) uses otsdaq as the online Data Acquisition System (DAQ) solution. Developed at Fermilab, otsdaq integrates both the artdaq DAQ and the art analysis frameworks for event transfer, filtering, and processing. otsdaq is an online DAQ software suite with a focus on flexibility and scalability and provides a multi-user, web-based, interface accessible through a web browser. The data stream from the detector subsystems is read by a software filter algorithm that selects events which are combined with the data flux coming from a cosmic ray veto system. The Detector Control System (DCS) has been developed using the Experimental Physics and Industrial Control System (EPICS) open source platform for monitoring, controlling, alarming, and archiving. The DCS system has been integrated into otsdaq. A prototype of the TDAQ and the DCS systems has been built at Fermilab's Feynman Computing Center. In this paper, we report on the progress of the integration of this prototype in the online otsdaq software.

Diverse microbial ecosystems underpin life in the sea. Among these microbes are many unicellular eukaryotes that span the diversity of the eukaryotic tree of life. However, genetic tractability has been limited to a few species, which do not represent eukaryotic diversity or environmentally relevant taxa. Here, we report on the development of genetic tools in a range of protists primarily from marine environments. We present evidence for foreign DNA delivery and expression in 13 species never before transformed and for advancement of tools for eight other species, as well as potential reasons for why transformation of yet another 17 species tested was not achieved. Our resource in genetic manipulation will provide insights into the ancestral eukaryotic lifeforms, general eukaryote cell biology, protein diversification and the evolution of cellular pathways.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Diverse microbial ecosystems underpin life in the sea. Among these microbes are many unicellular eukaryotes that span the diversity of the eukaryotic tree of life. However, genetic tractability has been limited to a few species, which do not represent eukaryotic diversity or environmentally relevant taxa. Here, we report on the development of genetic tools in a range of protists primarily from marine environments. We present evidence for foreign DNA delivery and expression in 13 species never before transformed and for advancement of tools for eight other species, as well as potential reasons for why transformation of yet another 17 species tested was not achieved. Our resource in genetic manipulation will provide insights into the ancestral eukaryotic lifeforms, general eukaryote cell biology, protein diversification and the evolution of cellular pathways.

BackgroundThe first Multi-center Medication Reconciliation Quality Improvement Study (MARQUIS1) demonstrated that implementation of a medication reconciliation best practices toolkit decreased total unintentional medication discrepancies in five hospitals. We sought to implement the MARQUIS toolkit in more diverse hospitals, incorporating lessons learned from MARQUIS1.MethodsMARQUIS2 is a pragmatic, mentored implementation QI study which collected clinical and implementation outcomes. Sites implemented a revised toolkit, which included interventions from these domains: 1) best possible medication history (BPMH)-taking; 2) discharge medication reconciliation and patient/caregiver counseling; 3) identifying and defining clinician roles and responsibilities; 4) risk stratification; 5) health information technology improvements; 6) improved access to medication sources; 7) identification and correction of real-time discrepancies; and, 8) stakeholder engagement. Eight hospitalists mentored the sites via one site visit and monthly phone calls over the 18-month intervention period. Each site's local QI team assessed opportunities to improve, implemented at least one of the 17 toolkit components, and accessed a variety of resources (e.g. implementation manual, webinars, and workshops). Outcomes to be assessed will include unintentional medication discrepancies per patient.DiscussionA mentored multi-center medication reconciliation QI initiative using a best practices toolkit was successfully implemented across 18 medical centers. The 18 participating sites varied in size, teaching status, location, and electronic health record (EHR) platform. We introduce barriers to implementation and lessons learned from MARQUIS1, such as the importance of utilizing dedicated, trained medication history takers, simple EHR solutions, clarifying roles and responsibilities, and the input of patients and families when improving medication reconciliation.

BackgroundThe first Multi-center Medication Reconciliation Quality Improvement Study (MARQUIS1) demonstrated that implementation of a medication reconciliation best practices toolkit decreased total unintentional medication discrepancies in five hospitals. We sought to implement the MARQUIS toolkit in more diverse hospitals, incorporating lessons learned from MARQUIS1.MethodsMARQUIS2 is a pragmatic, mentored implementation QI study which collected clinical and implementation outcomes. Sites implemented a revised toolkit, which included interventions from these domains: 1) best possible medication history (BPMH)-taking; 2) discharge medication reconciliation and patient/caregiver counseling; 3) identifying and defining clinician roles and responsibilities; 4) risk stratification; 5) health information technology improvements; 6) improved access to medication sources; 7) identification and correction of real-time discrepancies; and, 8) stakeholder engagement. Eight hospitalists mentored the sites via one site visit and monthly phone calls over the 18-month intervention period. Each site's local QI team assessed opportunities to improve, implemented at least one of the 17 toolkit components, and accessed a variety of resources (e.g. implementation manual, webinars, and workshops). Outcomes to be assessed will include unintentional medication discrepancies per patient.DiscussionA mentored multi-center medication reconciliation QI initiative using a best practices toolkit was successfully implemented across 18 medical centers. The 18 participating sites varied in size, teaching status, location, and electronic health record (EHR) platform. We introduce barriers to implementation and lessons learned from MARQUIS1, such as the importance of utilizing dedicated, trained medication history takers, simple EHR solutions, clarifying roles and responsibilities, and the input of patients and families when improving medication reconciliation.

The GEp-III and GEp-2γ experiments, carried out in Jefferson Lab's Hall C from 2007–2008, consisted of measurements of polarization transfer in elastic electron–proton scattering at momentum transfers of Q2=2.5,5.2,6.8, and 8.54 GeV 2. These measurements were carried out to improve knowledge of the proton electromagnetic form factor ratio R=μpGEp∕GMp at large values of Q2 and to search for effects beyond the Born approximation in polarization transfer observables at Q2=2.5GeV2. The final results of both experiments were reported in a recent archival publication. A full reanalysis of the data from both experiments was carried out in order to reduce the systematic and, for the GEp-2γ experiment, statistical uncertainties. This technical note provides additional details of the final analysis omitted from the main publication, including the final evaluation of the systematic uncertainties.

The GEp-III and GEp-2γ experiments, carried out in Jefferson Lab's Hall C from 2007–2008, consisted of measurements of polarization transfer in elastic electron–proton scattering at momentum transfers of Q2=2.5,5.2,6.8, and 8.54 GeV 2. These measurements were carried out to improve knowledge of the proton electromagnetic form factor ratio R=μpGEp∕GMp at large values of Q2 and to search for effects beyond the Born approximation in polarization transfer observables at Q2=2.5GeV2. The final results of both experiments were reported in a recent archival publication. A full reanalysis of the data from both experiments was carried out in order to reduce the systematic and, for the GEp-2γ experiment, statistical uncertainties. This technical note provides additional details of the final analysis omitted from the main publication, including the final evaluation of the systematic uncertainties.

Oceanic harmful algal blooms of Pseudo-nitzschia diatoms produce the potent mammalian neurotoxin domoic acid (DA). Despite decades of research, the molecular basis for its biosynthesis is not known. By using growth conditions known to induce DA production in Pseudo-nitzschia multiseries, we implemented transcriptome sequencing in order to identify DA biosynthesis genes that colocalize in a genomic four-gene cluster. We biochemically investigated the recombinant DA biosynthetic enzymes and linked their mechanisms to the construction of DA's diagnostic pyrrolidine skeleton, establishing a model for DA biosynthesis. Knowledge of the genetic basis for toxin production provides an orthogonal approach to bloom monitoring and enables study of environmental factors that drive oceanic DA production.

Subsequent to the release of our original paper, we discovered in the context of preparing our technical supplement [1] for journal publication that a typographical error had existed in the text file that the analysis program used to construct the beam polarization "database" for both the original analysis, published in Ref. [2], and our final analysis. The electron-beam polarization P e and the analyzing power A y cancel exactly in the ratio R , which is proportional to the ratio P t / P l of the transferred polarization components. On the other hand, the extraction of the relative e dependence of P l / P Born l relies on knowledge of the beam polarization. As such, data taking was interrupted roughly every two days during the GEp - 2 ? experiment to perform invasive measurements of the beam polarization using the Hall C Moller polarimeter [3]. The run range affected by the typographical error was entirely contained within the data collected at Q 2 = 2.5 GeV 2 with a beam energy of E e = 3.680 GeV during January 2008. The data from this configuration were combined with the data collected at E e = 3.548 GeV due to the nearly complete overlap of these two settings in terms of Q 2 and e acceptance. It is worth remarking that this typographical error went unnoticed for so long because it only affected a small fraction of the data (less than half of the combined data for ? e ? = 0.790 ) and the difference between the actually assigned beam polarization and the polarization that should have been assigned was comparable in magnitude to the point-to-point systematic uncertainty of the measurement itself. As such, its effect did not show up in various diagnostic plots and statistical tests, such as the time stability of the extracted P l / P Born l ratio. The data for both E e = 3.548 and E e = 3.680 GeV were reprocessed using the corrected beam polarizations to determine the effect of the typographical error on the combined physics results at ? e ? = 0.790 . Because the value of P e cancels in the ratio R , changes in the assumed beam polarization can only affect the results for R via statistical fluctuations due to changes in the relative weighting of different run ranges in the unbinned maximum-likelihood estimators for R . These effects are negligible on the scale of both the statistical and the systematic uncertainties of the data. More noticeable changes are expected in the ratio P l / P Born l since the extracted value of P l is inversely proportional to the assumed value of P e . Table I shows the effect of the corrected beam polarization database on the polarization transfer observables for the combined data for the ? e ? = 0.790 setting, the only measurement affected by the typographical error. The analyzing power did not need to be recalibrated since it was determined using the ? e ? = 0.153 data, which were not affected by the typographical error. As expected, the change in the ratio R is negligible. The value of P Born l , which is computed event by event from the global fit described in the Appendix of the original paper and does not depend on P e , is also unchanged. The magnitudes of P t , P l , and P l / P Born l are reduced by a common multiplicative factor, reflecting the fact that the beam polarization had been underestimated for the run range affected by the typographical error. The most important result of the corrected analysis is that the ratio P l / P Born l has decreased by 0.0024 from 1.0167 to 1.0143, a change comparable in magnitude to the statistical uncertainty but small compared to the total and point-to-point systematic uncertainties. The P l / P Born l result for the original publication [2] would be reduced by the same multiplicative factor as the final result. The physics conclusions of both publications are not materially changed by this correction. (Table Presented). (Figure Presented).

Subsequent to the release of our original paper, we discovered in the context of preparing our technical supplement [1] for journal publication that a typographical error had existed in the text file that the analysis program used to construct the beam polarization "database" for both the original analysis, published in Ref. [2], and our final analysis. The electron-beam polarization P e and the analyzing power A y cancel exactly in the ratio R , which is proportional to the ratio P t / P l of the transferred polarization components. On the other hand, the extraction of the relative e dependence of P l / P Born l relies on knowledge of the beam polarization. As such, data taking was interrupted roughly every two days during the GEp - 2 ? experiment to perform invasive measurements of the beam polarization using the Hall C Moller polarimeter [3]. The run range affected by the typographical error was entirely contained within the data collected at Q 2 = 2.5 GeV 2 with a beam energy of E e = 3.680 GeV during January 2008. The data from this configuration were combined with the data collected at E e = 3.548 GeV due to the nearly complete overlap of these two settings in terms of Q 2 and e acceptance. It is worth remarking that this typographical error went unnoticed for so long because it only affected a small fraction of the data (less than half of the combined data for ? e ? = 0.790 ) and the difference between the actually assigned beam polarization and the polarization that should have been assigned was comparable in magnitude to the point-to-point systematic uncertainty of the measurement itself. As such, its effect did not show up in various diagnostic plots and statistical tests, such as the time stability of the extracted P l / P Born l ratio. The data for both E e = 3.548 and E e = 3.680 GeV were reprocessed using the corrected beam polarizations to determine the effect of the typographical error on the combined physics results at ? e ? = 0.790 . Because the value of P e cancels in the ratio R , changes in the assumed beam polarization can only affect the results for R via statistical fluctuations due to changes in the relative weighting of different run ranges in the unbinned maximum-likelihood estimators for R . These effects are negligible on the scale of both the statistical and the systematic uncertainties of the data. More noticeable changes are expected in the ratio P l / P Born l since the extracted value of P l is inversely proportional to the assumed value of P e . Table I shows the effect of the corrected beam polarization database on the polarization transfer observables for the combined data for the ? e ? = 0.790 setting, the only measurement affected by the typographical error. The analyzing power did not need to be recalibrated since it was determined using the ? e ? = 0.153 data, which were not affected by the typographical error. As expected, the change in the ratio R is negligible. The value of P Born l , which is computed event by event from the global fit described in the Appendix of the original paper and does not depend on P e , is also unchanged. The magnitudes of P t , P l , and P l / P Born l are reduced by a common multiplicative factor, reflecting the fact that the beam polarization had been underestimated for the run range affected by the typographical error. The most important result of the corrected analysis is that the ratio P l / P Born l has decreased by 0.0024 from 1.0167 to 1.0143, a change comparable in magnitude to the statistical uncertainty but small compared to the total and point-to-point systematic uncertainties. The P l / P Born l result for the original publication [2] would be reduced by the same multiplicative factor as the final result. The physics conclusions of both publications are not materially changed by this correction. (Table Presented). (Figure Presented).

The development and operation of liquid-argon time-projection chambers for neutrino physics has created a need for new approaches to pattern recognition in order to fully exploit the imaging capabilities offered by this technology. Whereas the human brain can excel at identifying features in the recorded events, it is a significant challenge to develop an automated, algorithmic solution. The Pandora Software Development Kit provides functionality to aid the design and implementation of pattern-recognition algorithms. It promotes the use of a multi-algorithm approach to pattern recognition, in which individual algorithms each address a specific task in a particular topology. Many tens of algorithms then carefully build up a picture of the event and, together, provide a robust automated pattern-recognition solution. This paper describes details of the chain of over one hundred Pandora algorithms and tools used to reconstruct cosmic-ray muon and neutrino events in the MicroBooNE detector. Metrics that assess the current pattern-recognition performance are presented for simulated MicroBooNE events, using a selection of final-state event topologies.

Multi-omic approaches promise to supply the power to detect genes underlying disease and fitness-related phenotypes. Optimal use of the resulting profusion of data requires detailed investigation of individual candidate genes, a challenging proposition. Here, we combine transcriptomic and genomic data with molecular modelling of candidate enzymes to characterize the evolutionary history and function of the serine protease cocoonase. Heliconius butterflies possess the unique ability to feed on pollen; recent work has identified cocoonase as a candidate gene in pollen digestion. Cocoonase was first described in moths, where it aids in eclosure from the cocoon and is present as a single copy gene. In heliconiine butterflies it is duplicated and highly expressed in the mouthparts of adults. At least six copies of cocoonase are present in Heliconius melpomene and copy number varies across H. melpomene sub-populations. Most cocoonase genes are under purifying selection, however branch-site analyses suggest cocoonase 3 genes may have evolved under episodic diversifying selection. Molecular modelling of cocoonase proteins and examination of their predicted structures revealed that the active site region of each type has a similar structure to trypsin, with the same predicted substrate specificity across types. Variation among heliconiine cocoonases instead lies in the outward-facing residues involved in solvent interaction. Thus, the neofunctionalization of cocoonase duplicates appears to have resulted from the need for these serine proteases to operate in diverse biochemical environments. We suggest that cocoonase may have played a buffering role in feeding during the diversification of Heliconius across the neotropics by enabling these butterflies to digest protein from a range of biochemical milieux.

The development and operation of liquid-argon time-projection chambers for neutrino physics has created a need for new approaches to pattern recognition in order to fully exploit the imaging capabilities offered by this technology. Whereas the human brain can excel at identifying features in the recorded events, it is a significant challenge to develop an automated, algorithmic solution. The Pandora Software Development Kit provides functionality to aid the design and implementation of pattern-recognition algorithms. It promotes the use of a multi-algorithm approach to pattern recognition, in which individual algorithms each address a specific task in a particular topology. Many tens of algorithms then carefully build up a picture of the event and, together, provide a robust automated pattern-recognition solution. This paper describes details of the chain of over one hundred Pandora algorithms and tools used to reconstruct cosmic-ray muon and neutrino events in the MicroBooNE detector. Metrics that assess the current pattern-recognition performance are presented for simulated MicroBooNE events, using a selection of final-state event topologies.

The MicroBooNE detector is a liquid argon time projection chamber at Fermilab designed to study short-baseline neutrino oscillations and neutrino-argon interaction cross-section. Due to its location near the surface, a good understanding of cosmic muons as a source of backgrounds is of fundamental importance for the experiment. We present a method of using an external 0.5 m (L) × 0.5 m (W) muon counter stack, installed above the main detector, to determine the cosmic-ray reconstruction efficiency in MicroBooNE. Data are acquired with this external muon counter stack placed in three different positions, corresponding to cosmic rays intersecting different parts of the detector. The data reconstruction efficiency of tracks in the detector is found to be ϵdata=(97.1±0.1 (stat) ± 1.4 (sys))%, in good agreement with the Monte Carlo reconstruction efficiency ϵMC = (97.4±0.1)%. This analysis represents a small-scale demonstration of the method that can be used with future data coming from a recently installed cosmic-ray tagger system, which will be able to tag ≈80% of the cosmic rays passing through the MicroBooNE detector.

The MicroBooNE detector is a liquid argon time projection chamber at Fermilab designed to study short-baseline neutrino oscillations and neutrino-argon interaction cross-section. Due to its location near the surface, a good understanding of cosmic muons as a source of backgrounds is of fundamental importance for the experiment. We present a method of using an external 0.5 m (L) × 0.5 m (W) muon counter stack, installed above the main detector, to determine the cosmic-ray reconstruction efficiency in MicroBooNE. Data are acquired with this external muon counter stack placed in three different positions, corresponding to cosmic rays intersecting different parts of the detector. The data reconstruction efficiency of tracks in the detector is found to be ϵdata=(97.1±0.1 (stat) ± 1.4 (sys))%, in good agreement with the Monte Carlo reconstruction efficiency ϵMC = (97.4±0.1)%. This analysis represents a small-scale demonstration of the method that can be used with future data coming from a recently installed cosmic-ray tagger system, which will be able to tag ≈80% of the cosmic rays passing through the MicroBooNE detector.

Background: Interest in the behavior of nucleon electromagnetic form factors at large momentum transfers has steadily increased since the discovery, using polarization observables, of the rapid decrease of the ratio GEp/GMp of the proton's electric and magnetic form factors for momentum transfers Q21 GeV2, in strong disagreement with previous extractions of this ratio using the traditional Rosenbluth separation technique. Purpose: The GEp-III and GEp-2γ experiments were carried out in Jefferson Laboratory's (JLab's) Hall C from 2007 to 2008, to extend the knowledge of GEp/GMp to the highest practically achievable Q2 given the maximum beam energy of 6 GeV and to search for effects beyond the Born approximation in polarization transfer observables of elastic ∫ - p scattering. This article provides an expanded description of the common experimental apparatus and data analysis procedures, and reports the results of a final reanalysis of the data from both experiments, including the previously unpublished results of the full-acceptance dataset of the GEp-2γ experiment. Methods: Polarization transfer observables in elastic ∫ - p→∫ - scattering were measured at central Q2 values of 2.5, 5.2, 6.8, and 8.54 GeV2. At Q2=2.5GeV2, data were obtained for central values of the virtual photon polarization parameter ϵ of 0.149, 0.632, and 0.783. The Hall C High Momentum Spectrometer detected and measured the polarization of protons recoiling elastically from collisions of JLab's polarized electron beam with a liquid hydrogen target. A large-acceptance electromagnetic calorimeter detected the elastically scattered electrons in coincidence to suppress inelastic backgrounds. Results: The final GEp-III data are largely unchanged relative to the originally published results. The statistical uncertainties of the final GEp-2γ data are significantly reduced at ϵ=0.632 and 0.783 relative to the original publication. Conclusions: The final GEp-III results show that the decrease with Q2 of GEp/GMp continues to Q2=8.5GeV2, but at a slowing rate relative to the approximately linear decrease observed in earlier Hall A measurements. At Q2=8.5GeV2, GEp/GMp remains positive but is consistent with zero. At Q2=2.5GeV2, GEp/GMp derived from the polarization component ratio R-Pt/P shows no statistically significant ϵ dependence, as expected in the Born approximation. On the other hand, the ratio P""/P""Born of the longitudinal polarization transfer component to its Born value shows an enhancement of roughly 1.7% at ϵ=0.783 relative to ϵ=0.149, with ≈2.2σ significance based on the total uncertainty, implying a similar effect in the transverse component Pt that cancels in the ratio R.

Background: Interest in the behavior of nucleon electromagnetic form factors at large momentum transfers has steadily increased since the discovery, using polarization observables, of the rapid decrease of the ratio GEp/GMp of the proton's electric and magnetic form factors for momentum transfers Q21 GeV2, in strong disagreement with previous extractions of this ratio using the traditional Rosenbluth separation technique. Purpose: The GEp-III and GEp-2γ experiments were carried out in Jefferson Laboratory's (JLab's) Hall C from 2007 to 2008, to extend the knowledge of GEp/GMp to the highest practically achievable Q2 given the maximum beam energy of 6 GeV and to search for effects beyond the Born approximation in polarization transfer observables of elastic ∫ - p scattering. This article provides an expanded description of the common experimental apparatus and data analysis procedures, and reports the results of a final reanalysis of the data from both experiments, including the previously unpublished results of the full-acceptance dataset of the GEp-2γ experiment. Methods: Polarization transfer observables in elastic ∫ - p→∫ - scattering were measured at central Q2 values of 2.5, 5.2, 6.8, and 8.54 GeV2. At Q2=2.5GeV2, data were obtained for central values of the virtual photon polarization parameter ϵ of 0.149, 0.632, and 0.783. The Hall C High Momentum Spectrometer detected and measured the polarization of protons recoiling elastically from collisions of JLab's polarized electron beam with a liquid hydrogen target. A large-acceptance electromagnetic calorimeter detected the elastically scattered electrons in coincidence to suppress inelastic backgrounds. Results: The final GEp-III data are largely unchanged relative to the originally published results. The statistical uncertainties of the final GEp-2γ data are significantly reduced at ϵ=0.632 and 0.783 relative to the original publication. Conclusions: The final GEp-III results show that the decrease with Q2 of GEp/GMp continues to Q2=8.5GeV2, but at a slowing rate relative to the approximately linear decrease observed in earlier Hall A measurements. At Q2=8.5GeV2, GEp/GMp remains positive but is consistent with zero. At Q2=2.5GeV2, GEp/GMp derived from the polarization component ratio R-Pt/P shows no statistically significant ϵ dependence, as expected in the Born approximation. On the other hand, the ratio P""/P""Born of the longitudinal polarization transfer component to its Born value shows an enhancement of roughly 1.7% at ϵ=0.783 relative to ϵ=0.149, with ≈2.2σ significance based on the total uncertainty, implying a similar effect in the transverse component Pt that cancels in the ratio R.

We discuss a technique for measuring a charged particle's momentum by means of multiple Coulomb scattering (MCS) in the MicroBooNE liquid argon time projection chamber (LArTPC). This method does not require the full particle ionization track to be contained inside of the detector volume as other track momentum reconstruction methods do (range-based momentum reconstruction and calorimetric momentum reconstruction). We motivate use of this technique, describe a tuning of the underlying phenomenological formula, quantify its performance on fully contained beam-neutrino-induced muon tracks both in simulation and in data, and quantify its performance on exiting muon tracks in simulation. Using simulation, we have shown that the standard Highland formula should be re-tuned specifically for scattering in liquid argon, which significantly improves the bias and resolution of the momentum measurement. With the tuned formula, we find agreement between data and simulation for contained tracks, with a small bias in the momentum reconstruction and with resolutions that vary as a function of track length, improving from about 10% for the shortest (one meter long) tracks to 5% for longer (several meter) tracks. For simulated exiting muons with at least one meter of track contained, we find a similarly small bias, and a resolution which is less than 15% for muons with momentum below 2 GeV/c. Above 2 GeV/c, results are given as a first estimate of the MCS momentum measurement capabilities of MicroBooNE for high momentum exiting tracks.

We discuss a technique for measuring a charged particle's momentum by means of multiple Coulomb scattering (MCS) in the MicroBooNE liquid argon time projection chamber (LArTPC). This method does not require the full particle ionization track to be contained inside of the detector volume as other track momentum reconstruction methods do (range-based momentum reconstruction and calorimetric momentum reconstruction). We motivate use of this technique, describe a tuning of the underlying phenomenological formula, quantify its performance on fully contained beam-neutrino-induced muon tracks both in simulation and in data, and quantify its performance on exiting muon tracks in simulation. Using simulation, we have shown that the standard Highland formula should be re-tuned specifically for scattering in liquid argon, which significantly improves the bias and resolution of the momentum measurement. With the tuned formula, we find agreement between data and simulation for contained tracks, with a small bias in the momentum reconstruction and with resolutions that vary as a function of track length, improving from about 10% for the shortest (one meter long) tracks to 5% for longer (several meter) tracks. For simulated exiting muons with at least one meter of track contained, we find a similarly small bias, and a resolution which is less than 15% for muons with momentum below 2 GeV/c. Above 2 GeV/c, results are given as a first estimate of the MCS momentum measurement capabilities of MicroBooNE for high momentum exiting tracks.

The MicroBooNE liquid argon time projection chamber (LArTPC) has been taking data at Fermilab since 2015 collecting, in addition to neutrino beam, cosmic-ray muons. Results are presented on the reconstruction of Michel electrons produced by the decay at rest of cosmic-ray muons. Michel electrons are abundantly produced in the TPC, and given their well known energy spectrum can be used to study MicroBooNE's detector response to low-energy electrons (electrons with energies up to ∼ 50 MeV). We describe the fully-automated algorithm developed to reconstruct Michel electrons, with which a sample of ∼ 14,000 Michel electron candidates is obtained. Most of this article is dedicated to studying the impact of radiative photons produced by Michel electrons on the accuracy and resolution of their energy measurement. In this energy range, ionization and bremsstrahlung photon production contribute similarly to electron energy loss in argon, leading to a complex electron topology in the TPC. By profiling the performance of the reconstruction algorithm on simulation we show that the ability to identify and include energy deposited by radiative photons leads to a significant improvement in the energy measurement of low-energy electrons. The fractional energy resolution we measure improves from over 30% to ∼ 20% when we attempt to include radiative photons in the reconstruction. These studies are relevant to a large number of analyses which aim to study neutrinos by measuring electrons produced by νe interactions over a broad energy range.

The MicroBooNE liquid argon time projection chamber (LArTPC) has been taking data at Fermilab since 2015 collecting, in addition to neutrino beam, cosmic-ray muons. Results are presented on the reconstruction of Michel electrons produced by the decay at rest of cosmic-ray muons. Michel electrons are abundantly produced in the TPC, and given their well known energy spectrum can be used to study MicroBooNE's detector response to low-energy electrons (electrons with energies up to ∼ 50 MeV). We describe the fully-automated algorithm developed to reconstruct Michel electrons, with which a sample of ∼ 14,000 Michel electron candidates is obtained. Most of this article is dedicated to studying the impact of radiative photons produced by Michel electrons on the accuracy and resolution of their energy measurement. In this energy range, ionization and bremsstrahlung photon production contribute similarly to electron energy loss in argon, leading to a complex electron topology in the TPC. By profiling the performance of the reconstruction algorithm on simulation we show that the ability to identify and include energy deposited by radiative photons leads to a significant improvement in the energy measurement of low-energy electrons. The fractional energy resolution we measure improves from over 30% to ∼ 20% when we attempt to include radiative photons in the reconstruction. These studies are relevant to a large number of analyses which aim to study neutrinos by measuring electrons produced by νe interactions over a broad energy range.

The low-noise operation of readout electronics in a liquid argon time projection chamber (LArTPC) is critical to properly extract the distribution of ionization charge deposited on the wire planes of the TPC, especially for the induction planes. This paper describes the characteristics and mitigation of the observed noise in the MicroBooNE detector. The MicroBooNE's single-phase LArTPC comprises two induction planes and one collection sense wire plane with a total of 8256 wires. Current induced on each TPC wire is amplified and shaped by custom low-power, low-noise ASICs immersed in the liquid argon. The digitization of the signal waveform occurs outside the cryostat. Using data from the first year of MicroBooNE operations, several excess noise sources in the TPC were identified and mitigated. The residual equivalent noise charge (ENC) after noise filtering varies with wire length and is found to be below 400 electrons for the longest wires (4.7 m). The response is consistent with the cold electronics design expectations and is found to be stable with time and uniform over the functioning channels. This noise level is significantly lower than previous experiments utilizing warm front-end electronics.

The low-noise operation of readout electronics in a liquid argon time projection chamber (LArTPC) is critical to properly extract the distribution of ionization charge deposited on the wire planes of the TPC, especially for the induction planes. This paper describes the characteristics and mitigation of the observed noise in the MicroBooNE detector. The MicroBooNE's single-phase LArTPC comprises two induction planes and one collection sense wire plane with a total of 8256 wires. Current induced on each TPC wire is amplified and shaped by custom low-power, low-noise ASICs immersed in the liquid argon. The digitization of the signal waveform occurs outside the cryostat. Using data from the first year of MicroBooNE operations, several excess noise sources in the TPC were identified and mitigated. The residual equivalent noise charge (ENC) after noise filtering varies with wire length and is found to be below 400 electrons for the longest wires (4.7 m). The response is consistent with the cold electronics design expectations and is found to be stable with time and uniform over the functioning channels. This noise level is significantly lower than previous experiments utilizing warm front-end electronics.

We present several studies of convolutional neural networks applied to data coming from the MicroBooNE detector, a liquid argon time projection chamber (LArTPC). The algorithms studied include the classification of single particle images, the localization of single particle and neutrino interactions in an image, and the detection of a simulated neutrino event overlaid with cosmic ray backgrounds taken from real detector data. These studies demonstrate the potential of convolutional neural networks for particle identification or event detection on simulated neutrino interactions. We also address technical issues that arise when applying this technique to data from a large LArTPC at or near ground level.

We present several studies of convolutional neural networks applied to data coming from the MicroBooNE detector, a liquid argon time projection chamber (LArTPC). The algorithms studied include the classification of single particle images, the localization of single particle and neutrino interactions in an image, and the detection of a simulated neutrino event overlaid with cosmic ray backgrounds taken from real detector data. These studies demonstrate the potential of convolutional neural networks for particle identification or event detection on simulated neutrino interactions. We also address technical issues that arise when applying this technique to data from a large LArTPC at or near ground level.

This paper describes the design and construction of the MicroBooNE liquid argon time projection chamber and associated systems. MicroBooNE is the first phase of the Short Baseline Neutrino program, located at Fermilab, and will utilize the capabilities of liquid argon detectors to examine a rich assortment of physics topics. In this document details of design specifications, assembly procedures, and acceptance tests are reported.

This paper describes the design and construction of the MicroBooNE liquid argon time projection chamber and associated systems. MicroBooNE is the first phase of the Short Baseline Neutrino program, located at Fermilab, and will utilize the capabilities of liquid argon detectors to examine a rich assortment of physics topics. In this document details of design specifications, assembly procedures, and acceptance tests are reported.

CRAL_TRIO domain proteins are known to bind small lipophilic molecules such as retinal, inositol and Vitamin E and include such gene family members as PINTA, α-tocopherol transfer (ATT) proteins, retinoid binding proteins, and clavesins. In insects, very little is known about either the molecular evolution of this family of proteins or their ligand specificity. Here we characterize insect CRAL_TRIO domain proteins and present the first insect CRAL_TRIO protein phylogeny constructed by performing reciprocal BLAST searches of the reference genomes of Drosophila melanogaster, Anopheles gambiae, Apis mellifera, Tribolium castaneum, Bombyx mori, Manduca sexta and Danaus plexippus. We find several highly conserved amino acid residues in the CRAL_TRIO domain-containing genes across insects and a gene expansion resulting in more than twice as many gene family members in lepidopterans than in other surveyed insect species, but no lepidopteran homolog of the PINTA gene in Drosophila. In addition, we examined the expression pattern of CRAL_TRIO domain genes in Manduca sexta heads using RNA-Seq data. Of the 42 gene family members found in the M.sexta reference genome, we found 30 expressed in the head tissue with similar expression profiles between males and females. Our results suggest this gene family underwent a large expansion in lepidopteran, making the lepidopteran CRAL_TRIO domain family distinct from other holometabolous insect lineages.

CRAL_TRIO domain proteins are known to bind small lipophilic molecules such as retinal, inositol and Vitamin E and include such gene family members as PINTA, α-tocopherol transfer (ATT) proteins, retinoid binding proteins, and clavesins. In insects, very little is known about either the molecular evolution of this family of proteins or their ligand specificity. Here we characterize insect CRAL_TRIO domain proteins and present the first insect CRAL_TRIO protein phylogeny constructed by performing reciprocal BLAST searches of the reference genomes of Drosophila melanogaster, Anopheles gambiae, Apis mellifera, Tribolium castaneum, Bombyx mori, Manduca sexta and Danaus plexippus. We find several highly conserved amino acid residues in the CRAL_TRIO domain-containing genes across insects and a gene expansion resulting in more than twice as many gene family members in lepidopterans than in other surveyed insect species, but no lepidopteran homolog of the PINTA gene in Drosophila. In addition, we examined the expression pattern of CRAL_TRIO domain genes in Manduca sexta heads using RNA-Seq data. Of the 42 gene family members found in the M.sexta reference genome, we found 30 expressed in the head tissue with similar expression profiles between males and females. Our results suggest this gene family underwent a large expansion in lepidopteran, making the lepidopteran CRAL_TRIO domain family distinct from other holometabolous insect lineages.

Genetic studies have identified single nucleotide polymorphisms (SNPs) associated with the risk of prostate cancer (PC). It remains unclear whether such genetic variants are associated with disease aggressiveness. The NCI-SPORE Genetics Working Group retrospectively collected clinicopathologic information and genotype data for 36 SNPs which at the time had been validated to be associated with PC risk from 25,674 cases with PC. Cases were grouped according to race, Gleason score (Gleason ≤6, 7, ≥8) and aggressiveness (non-aggressive, intermediate, and aggressive disease). Statistical analyses were used to compare the frequency of the SNPs between different disease cohorts. After adjusting for multiple testing, only PC-risk SNP rs2735839 (G) was significantly and inversely associated with aggressive (OR = 0.77; 95 % CI 0.69–0.87) and high-grade disease (OR = 0.77; 95 % CI 0.68–0.86) in European men. Similar associations with aggressive (OR = 0.72; 95 % CI 0.58–0.89) and high-grade disease (OR = 0.69; 95 % CI 0.54–0.87) were documented in African-American subjects. The G allele of rs2735839 was associated with disease aggressiveness even at low PSA levels (

Genetic studies have identified single nucleotide polymorphisms (SNPs) associated with the risk of prostate cancer (PC). It remains unclear whether such genetic variants are associated with disease aggressiveness. The NCI-SPORE Genetics Working Group retrospectively collected clinicopathologic information and genotype data for 36 SNPs which at the time had been validated to be associated with PC risk from 25,674 cases with PC. Cases were grouped according to race, Gleason score (Gleason ≤6, 7, ≥8) and aggressiveness (non-aggressive, intermediate, and aggressive disease). Statistical analyses were used to compare the frequency of the SNPs between different disease cohorts. After adjusting for multiple testing, only PC-risk SNP rs2735839 (G) was significantly and inversely associated with aggressive (OR = 0.77; 95 % CI 0.69–0.87) and high-grade disease (OR = 0.77; 95 % CI 0.68–0.86) in European men. Similar associations with aggressive (OR = 0.72; 95 % CI 0.58–0.89) and high-grade disease (OR = 0.69; 95 % CI 0.54–0.87) were documented in African-American subjects. The G allele of rs2735839 was associated with disease aggressiveness even at low PSA levels (

Current sampling of genomic sequence data from eukaryotes is relatively poor, biased, and inadequate to address important questions about their biology, evolution, and ecology; this Community Page describes a resource of 700 transcriptomes from marine microbial eukaryotes to help understand their role in the world's oceans.

Written and verbal languages are neurobehavioral traits vital to the development of communication skills. Unfortunately, disorders involving these traits-specifically reading disability (RD) and language impairment (LI)-are common and prevent affected individuals from developing adequate communication skills, leaving them at risk for adverse academic, socioeconomic and psychiatric outcomes. Both RD and LI are complex traits that frequently co-occur, leading us to hypothesize that these disorders share genetic etiologies. To test this, we performed a genome-wide association study on individuals affected with both RD and LI in the Avon Longitudinal Study of Parents and Children. The strongest associations were seen with markers in ZNF385D (OR = 1.81, P = 5.45 × 10(-7) ) and COL4A2 (OR = 1.71, P = 7.59 × 10(-7) ). Markers within NDST4 showed the strongest associations with LI individually (OR = 1.827, P = 1.40 × 10(-7) ). We replicated association of ZNF385D using receptive vocabulary measures in the Pediatric Imaging Neurocognitive Genetics study (P = 0.00245). We then used diffusion tensor imaging fiber tract volume data on 16 fiber tracts to examine the implications of replicated markers. ZNF385D was a predictor of overall fiber tract volumes in both hemispheres, as well as global brain volume. Here, we present evidence for ZNF385D as a candidate gene for RD and LI. The implication of transcription factor ZNF385D in RD and LI underscores the importance of transcriptional regulation in the development of higher order neurocognitive traits. Further study is necessary to discern target genes of ZNF385D and how it functions within neural development of fluent language.