Experimental evaluation of depth-of-interaction correction in a small-animal positron emission tomography scanner.

PubMed

Green, Michael V; Ostrow, Harold G; Seidel, Jurgen; Pomper, Martin G

2010-12-01

Human and small-animal positron emission tomography (PET) scanners with cylindrical geometry and conventional detectors exhibit a progressive reduction in radial spatial resolution with increasing radial distance from the geometric axis of the scanner. This "depth-of-interaction" (DOI) effect is sufficiently deleterious that many laboratories have devised novel schemes to reduce the magnitude of this effect and thereby yield PET images of greater quantitative accuracy. Here we examine experimentally the effects of a particular DOI correction method (dual-scintillator phoswich detectors with pulse shape discrimination) implemented in a small-animal PET scanner by comparing the same phantom and same mouse images with and without DOI correction. The results suggest that even this relatively coarse, two-level estimate of radial gamma ray interaction position significantly reduces the DOI parallax error. This study also confirms two less appreciated advantages of DOI correction: a reduction in radial distortion and radial source displacement as a source is moved toward the edge of the field of view and a resolution improvement detectable in the central field of view likely owing to improved spatial sampling.

A machine learning method for fast and accurate characterization of depth-of-interaction gamma cameras

NASA Astrophysics Data System (ADS)

Pedemonte, Stefano; Pierce, Larry; Van Leemput, Koen

2017-11-01

Measuring the depth-of-interaction (DOI) of gamma photons enables increasing the resolution of emission imaging systems. Several design variants of DOI-sensitive detectors have been recently introduced to improve the performance of scanners for positron emission tomography (PET). However, the accurate characterization of the response of DOI detectors, necessary to accurately measure the DOI, remains an unsolved problem. Numerical simulations are, at the state of the art, imprecise, while measuring directly the characteristics of DOI detectors experimentally is hindered by the impossibility to impose the depth-of-interaction in an experimental set-up. In this article we introduce a machine learning approach for extracting accurate forward models of gamma imaging devices from simple pencil-beam measurements, using a nonlinear dimensionality reduction technique in combination with a finite mixture model. The method is purely data-driven, not requiring simulations, and is applicable to a wide range of detector types. The proposed method was evaluated both in a simulation study and with data acquired using a monolithic gamma camera designed for PET (the cMiCE detector), demonstrating the accurate recovery of the DOI characteristics. The combination of the proposed calibration technique with maximum- a posteriori estimation of the coordinates of interaction provided a depth resolution of  ≈1.14 mm for the simulated PET detector and  ≈1.74 mm for the cMiCE detector. The software and experimental data are made available at http://occiput.mgh.harvard.edu/depthembedding/.

Amae as metalanguage: a critique of Doi's theory of amae.

PubMed

Taketomo, Y

1986-10-01

For many years Doi's ideas on the links between amae and the satisfaction of dependency needs have influenced discussions of the so-called Japanese character. In reviewing Doi's theory, however, major problems emerge. Beginning with the very definition of amae, one finds that Doi has chosen to stress only one aspect of amae. When one returns to his lexical sources, one discovers that the common denominator in the various definitions of amae does not lie in a single, monolithic motivation, as Doi proposes. Instead, it is suggested, amae should be viewed as a metalanguage. To understand the metacommunicational significance of amae, one must consider the rules that govern the behavior of the interactants in amae. Three different situations of amae are delineated. In the childhood interaction, the child playfully mimicks the infant's attachment behavior. With the adult coquetry situation, one observes the female playfully behaving as if she were the child mimicking the infant-mother prototype. Finally, in the third context subset of amae, there is a "trespassing on" or "taking advantage of" another person, with the beneficent approval of the second interactant. The common factor thus appears to be a mutually agreed-upon suspension of certain ordinary restraints on behavior. A metalanguage theory of amae, as an alternative to Doi's proposal, places emphasis on the culture-specific message of the interaction itself rather than on a single, monolithic motivation or an object-language interpretation. Indeed, various motivations are suggested, depending on the specific context of amae as well as the individual case. In this way, it is hoped, a metacommunicational approach to the understanding of amae may broaden the consideration of motivational issues, extending far beyond Doi's insistence on dependency and the search for passive love.

Dynamic metabolic exchange governs a marine algal-bacterial interaction

PubMed Central

Segev, Einat; Wyche, Thomas P; Kim, Ki Hyun; Petersen, Jörn; Ellebrandt, Claire; Vlamakis, Hera; Barteneva, Natasha; Paulson, Joseph N; Chai, Liraz; Clardy, Jon; Kolter, Roberto

2016-01-01

Emiliania huxleyi is a model coccolithophore micro-alga that generates vast blooms in the ocean. Bacteria are not considered among the major factors influencing coccolithophore physiology. Here we show through a laboratory model system that the bacterium Phaeobacter inhibens, a well-studied member of the Roseobacter group, intimately interacts with E. huxleyi. While attached to the algal cell, bacteria initially promote algal growth but ultimately kill their algal host. Both algal growth enhancement and algal death are driven by the bacterially-produced phytohormone indole-3-acetic acid. Bacterial production of indole-3-acetic acid and attachment to algae are significantly increased by tryptophan, which is exuded from the algal cell. Algal death triggered by bacteria involves activation of pathways unique to oxidative stress response and programmed cell death. Our observations suggest that bacteria greatly influence the physiology and metabolism of E. huxleyi. Coccolithophore-bacteria interactions should be further studied in the environment to determine whether they impact micro-algal population dynamics on a global scale. DOI: http://dx.doi.org/10.7554/eLife.17473.001 PMID:27855786

Structural basis of transcription arrest by coliphage HK022 Nun in an Escherichia coli RNA polymerase elongation complex

PubMed Central

Kang, Jin Young; Olinares, Paul Dominic B; Chen, James; Campbell, Elizabeth A; Mustaev, Arkady; Chait, Brian T; Gottesman, Max E; Darst, Seth A

2017-01-01

Coliphage HK022 Nun blocks superinfection by coliphage λ by stalling RNA polymerase (RNAP) translocation specifically on λ DNA. To provide a structural framework to understand how Nun blocks RNAP translocation, we determined structures of Escherichia coli RNAP ternary elongation complexes (TECs) with and without Nun by single-particle cryo-electron microscopy. Nun fits tightly into the TEC by taking advantage of gaps between the RNAP and the nucleic acids. The C-terminal segment of Nun interacts with the RNAP β and β’ subunits inside the RNAP active site cleft as well as with nearly every element of the nucleic acid scaffold, essentially crosslinking the RNAP and the nucleic acids to prevent translocation, a mechanism supported by the effects of Nun amino acid substitutions. The nature of Nun interactions inside the RNAP active site cleft suggests that RNAP clamp opening is required for Nun to establish its interactions, explaining why Nun acts on paused TECs. DOI: http://dx.doi.org/10.7554/eLife.25478.001 PMID:28318486

The Glide/Gcm fate determinant controls initiation of collective cell migration by regulating Frazzled

PubMed Central

Gupta, Tripti; Kumar, Arun; Cattenoz, Pierre B.; VijayRaghavan, K; Giangrande, Angela

2016-01-01

Collective migration is a complex process that contributes to build precise tissue and organ architecture. Several molecules implicated in cell interactions also control collective migration, but their precise role and the finely tuned expression that orchestrates this complex developmental process are poorly understood. Here, we show that the timely and threshold expression of the Netrin receptor Frazzled triggers the initiation of glia migration in the developing Drosophila wing. Frazzled expression is induced by the transcription factor Glide/Gcm in a dose-dependent manner. Thus, the glial determinant also regulates the efficiency of collective migration. NetrinB but not NetrinA serves as a chemoattractant and Unc5 contributes as a repellant Netrin receptor for glia migration. Our model includes strict spatial localization of a ligand, a cell autonomously acting receptor and a fate determinant that act coordinately to direct glia toward their final destination. DOI: http://dx.doi.org/10.7554/eLife.15983.001 PMID:27740455

A flood map based DOI decoding method for block detector: a GATE simulation study.

PubMed

Shi, Han; Du, Dong; Su, Zhihong; Peng, Qiyu

2014-01-01

Positron Emission Tomography (PET) systems using detectors with Depth of Interaction (DOI) capabilities could achieve higher spatial resolution and better image quality than those without DOI. Up till now, most DOI methods developed are not cost-efficient for a whole body PET system. In this paper, we present a DOI decoding method based on flood map for low-cost conventional block detector with four-PMT readout. Using this method, the DOI information can be directly extracted from the DOI-related crystal spot deformation in the flood map. GATE simulations are then carried out to validate the method, confirming a DOI sorting accuracy of 85.27%. Therefore, we conclude that this method has the potential to be applied in conventional detectors to achieve a reasonable DOI measurement without dramatically increasing their complexity and cost of an entire PET system.

Domain–domain interactions determine the gating, permeation, pharmacology, and subunit modulation of the IKs ion channel

PubMed Central

Zaydman, Mark A; Kasimova, Marina A; McFarland, Kelli; Beller, Zachary; Hou, Panpan; Kinser, Holly E; Liang, Hongwu; Zhang, Guohui; Shi, Jingyi; Tarek, Mounir; Cui, Jianmin

2014-01-01

Voltage-gated ion channels generate electrical currents that control muscle contraction, encode neuronal information, and trigger hormonal release. Tissue-specific expression of accessory (β) subunits causes these channels to generate currents with distinct properties. In the heart, KCNQ1 voltage-gated potassium channels coassemble with KCNE1 β-subunits to generate the IKs current (Barhanin et al., 1996; Sanguinetti et al., 1996), an important current for maintenance of stable heart rhythms. KCNE1 significantly modulates the gating, permeation, and pharmacology of KCNQ1 (Wrobel et al., 2012; Sun et al., 2012; Abbott, 2014). These changes are essential for the physiological role of IKs (Silva and Rudy, 2005); however, after 18 years of study, no coherent mechanism explaining how KCNE1 affects KCNQ1 has emerged. Here we provide evidence of such a mechanism, whereby, KCNE1 alters the state-dependent interactions that functionally couple the voltage-sensing domains (VSDs) to the pore. DOI: http://dx.doi.org/10.7554/eLife.03606.001 PMID:25535795

Quantitative time-resolved analysis reveals intricate, differential regulation of standard- and immuno-proteasomes

PubMed Central

Liepe, Juliane; Holzhütter, Hermann-Georg; Bellavista, Elena; Kloetzel, Peter M; Stumpf, Michael PH; Mishto, Michele

2015-01-01

Proteasomal protein degradation is a key determinant of protein half-life and hence of cellular processes ranging from basic metabolism to a host of immunological processes. Despite its importance the mechanisms regulating proteasome activity are only incompletely understood. Here we use an iterative and tightly integrated experimental and modelling approach to develop, explore and validate mechanistic models of proteasomal peptide-hydrolysis dynamics. The 20S proteasome is a dynamic enzyme and its activity varies over time because of interactions between substrates and products and the proteolytic and regulatory sites; the locations of these sites and the interactions between them are predicted by the model, and experimentally supported. The analysis suggests that the rate-limiting step of hydrolysis is the transport of the substrates into the proteasome. The transport efficiency varies between human standard- and immuno-proteasomes thereby impinging upon total degradation rate and substrate cleavage-site usage. DOI: http://dx.doi.org/10.7554/eLife.07545.001 PMID:26393687

WE-C-217BCD-10: Development of High Performance PET for Animal Imaging and Therapy Applications.

PubMed

Shao, Y; Sun, X; Lan, K; Bircher, C

2012-06-01

A prototype small animal PET is developed with several novel technologies to measure 3D gamma-interaction positions and to substantially improve imaging performance. Each new detector has an 8×8 array of 1.95×1.95×30 mm̂3 LYSO scintillators, with each end optically connected to a solid-state photo multiplier (SSPM) array through a light guide. This dual-ended-readout enables the depth-of-interaction (DOI) measurement. Each SSPM array has 16 SSPMs arranged in a 4×4 matrix. Each SSPM has active area about 3×3 mm̂2, with its output read by an ASIC electronics that directly converts analog signals to digital timing pulses which encode the interaction information for energy, timing, crystal of interaction, and DOI calculations. These digital pulses are transferred to and decoded by FPGA-based TDC for coincident event selection and data acquisition. This independent readout of each SSPM and parallel signal process significantly improve signal-to-noise ratio and permit applying flexible data processing algorithms. The current prototype system consists of two rotating detector panels on a portable gantry, with 4 detectors linearly packed together in each panel to provide ∼16 mm axial and variable trans- axial FOV with adjustable panel-to-panel distance. List-mode OSEM-based image reconstruction with resolution modeling was implemented. Both Na- 22 point source and phantom were used to evaluate the system performance. The measured energy, timing, spatial and DOI resolutions for each crystal were around 16%, 2.6 ns, 2.0 mm and 5.0 mm, respectively. The measured spatial resolutions with DOI were ∼1.7 mm across the entire FOV in all direction, while those without DOI were much worse and non-uniform across the FOV, in the range predominately around 3.0 to 4.0 mm. In addition, images from a F-18 hot-rod phantom with DOI show significantly improved quality compared to those without DOI. DOI- measurable PET shows substantially improved image performance for a compact system. National Institute of Health. University of Texas MD Anderson Cancer Center. © 2012 American Association of Physicists in Medicine.

Optimization, evaluation and calibration of a cross-strip DOI detector

NASA Astrophysics Data System (ADS)

Schmidt, F. P.; Kolb, A.; Pichler, B. J.

2018-02-01

This study depicts the evaluation of a SiPM detector with depth of interaction (DOI) capability via a dual-sided readout that is suitable for high-resolution positron emission tomography and magnetic resonance (PET/MR) imaging. Two different 12  ×  12 pixelated LSO scintillator arrays with a crystal pitch of 1.60 mm are examined. One array is 20 mm-long with a crystal separation by the specular reflector Vikuiti enhanced specular reflector (ESR), and the other one is 18 mm-long and separated by the diffuse reflector Lumirror E60 (E60). An improvement in energy resolution from 22.6% to 15.5% for the scintillator array with the E60 reflector is achieved by taking a nonlinear light collection correction into account. The results are FWHM energy resolutions of 14.0% and 15.5%, average FWHM DOI resolutions of 2.96 mm and 1.83 mm, and FWHM coincidence resolving times of 1.09 ns and 1.48 ns for the scintillator array with the ESR and that with the E60 reflector, respectively. The measured DOI signal ratios need to be assigned to an interaction depth inside the scintillator crystal. A linear and a nonlinear method, using the intrinsic scintillator radiation from lutetium, are implemented for an easy to apply calibration and are compared to the conventional method, which exploits a setup with an externally collimated radiation beam. The deviation between the DOI functions of the linear or nonlinear method and the conventional method is determined. The resulting average of differences in DOI positions is 0.67 mm and 0.45 mm for the nonlinear calibration method for the scintillator array with the ESR and with the E60 reflector, respectively; Whereas the linear calibration method results in 0.51 mm and 0.32 mm for the scintillator array with the ESR and the E60 reflector, respectively; and is, due to its simplicity, also applicable in assembled detector systems.

Optimization, evaluation and calibration of a cross-strip DOI detector.

PubMed

Schmidt, F P; Kolb, A; Pichler, B J

2018-02-20

This study depicts the evaluation of a SiPM detector with depth of interaction (DOI) capability via a dual-sided readout that is suitable for high-resolution positron emission tomography and magnetic resonance (PET/MR) imaging. Two different 12  ×  12 pixelated LSO scintillator arrays with a crystal pitch of 1.60 mm are examined. One array is 20 mm-long with a crystal separation by the specular reflector Vikuiti enhanced specular reflector (ESR), and the other one is 18 mm-long and separated by the diffuse reflector Lumirror E60 (E60). An improvement in energy resolution from 22.6% to 15.5% for the scintillator array with the E60 reflector is achieved by taking a nonlinear light collection correction into account. The results are FWHM energy resolutions of 14.0% and 15.5%, average FWHM DOI resolutions of 2.96 mm and 1.83 mm, and FWHM coincidence resolving times of 1.09 ns and 1.48 ns for the scintillator array with the ESR and that with the E60 reflector, respectively. The measured DOI signal ratios need to be assigned to an interaction depth inside the scintillator crystal. A linear and a nonlinear method, using the intrinsic scintillator radiation from lutetium, are implemented for an easy to apply calibration and are compared to the conventional method, which exploits a setup with an externally collimated radiation beam. The deviation between the DOI functions of the linear or nonlinear method and the conventional method is determined. The resulting average of differences in DOI positions is 0.67 mm and 0.45 mm for the nonlinear calibration method for the scintillator array with the ESR and with the E60 reflector, respectively; Whereas the linear calibration method results in 0.51 mm and 0.32 mm for the scintillator array with the ESR and the E60 reflector, respectively; and is, due to its simplicity, also applicable in assembled detector systems.

Prototype pre-clinical PET scanner with depth-of-interaction measurements using single-layer crystal array and single-ended readout

NASA Astrophysics Data System (ADS)

Lee, Min Sun; Kim, Kyeong Yun; Ko, Guen Bae; Lee, Jae Sung

2017-05-01

In this study, we developed a proof-of-concept prototype PET system using a pair of depth-of-interaction (DOI) PET detectors based on the proposed DOI-encoding method and digital silicon photomultiplier (dSiPM). Our novel cost-effective DOI measurement method is based on a triangular-shaped reflector that requires only a single-layer pixelated crystal and single-ended signal readout. The DOI detector consisted of an 18  ×  18 array of unpolished LYSO crystal (1.47  ×  1.47  ×  15 mm3) wrapped with triangular-shaped reflectors. The DOI information was encoded by depth-dependent light distribution tailored by the reflector geometry and DOI correction was performed using four-step depth calibration data and maximum-likelihood (ML) estimation. The detector pair and the object were placed on two motorized rotation stages to demonstrate 12-block ring PET geometry with 11.15 cm diameter. Spatial resolution was measured and phantom and animal imaging studies were performed to investigate imaging performance. All images were reconstructed with and without the DOI correction to examine the impact of our DOI measurement. The pair of dSiPM-based DOI PET detectors showed good physical performances respectively: 2.82 and 3.09 peak-to-valley ratios, 14.30% and 18.95% energy resolution, and 4.28 and 4.24 mm DOI resolution averaged over all crystals and all depths. A sub-millimeter spatial resolution was achieved at the center of the field of view (FOV). After applying ML-based DOI correction, maximum 36.92% improvement was achieved in the radial spatial resolution and a uniform resolution was observed within 5 cm of transverse PET FOV. We successfully acquired phantom and animal images with improved spatial resolution and contrast by using the DOI measurement. The proposed DOI-encoding method was successfully demonstrated in the system level and exhibited good performance, showing its feasibility for animal PET applications with high spatial resolution and sensitivity.

An experimentally validated network of nine haematopoietic transcription factors reveals mechanisms of cell state stability

PubMed Central

Schütte, Judith; Wang, Huange; Antoniou, Stella; Jarratt, Andrew; Wilson, Nicola K; Riepsaame, Joey; Calero-Nieto, Fernando J; Moignard, Victoria; Basilico, Silvia; Kinston, Sarah J; Hannah, Rebecca L; Chan, Mun Chiang; Nürnberg, Sylvia T; Ouwehand, Willem H; Bonzanni, Nicola; de Bruijn, Marella FTR; Göttgens, Berthold

2016-01-01

Transcription factor (TF) networks determine cell-type identity by establishing and maintaining lineage-specific expression profiles, yet reconstruction of mammalian regulatory network models has been hampered by a lack of comprehensive functional validation of regulatory interactions. Here, we report comprehensive ChIP-Seq, transgenic and reporter gene experimental data that have allowed us to construct an experimentally validated regulatory network model for haematopoietic stem/progenitor cells (HSPCs). Model simulation coupled with subsequent experimental validation using single cell expression profiling revealed potential mechanisms for cell state stabilisation, and also how a leukaemogenic TF fusion protein perturbs key HSPC regulators. The approach presented here should help to improve our understanding of both normal physiological and disease processes. DOI: http://dx.doi.org/10.7554/eLife.11469.001 PMID:26901438

Experimental Evaluation of Depth-of-Interaction Correction in a Small-Animal Positron Emission Tomography Scanner

PubMed Central

Green, Michael V.; Ostrow, Harold G.; Seidel, Jurgen; Pomper, Martin G.

2013-01-01

Human and small-animal positron emission tomography (PET) scanners with cylindrical geometry and conventional detectors exhibit a progressive reduction in radial spatial resolution with increasing radial distance from the geometric axis of the scanner. This “depth-of-interaction” (DOI) effect is sufficiently deleterious that many laboratories have devised novel schemes to reduce the magnitude of this effect and thereby yield PET images of greater quantitative accuracy. Here we examine experimentally the effects of a particular DOI correction method (dual-scintillator phoswich detectors with pulse shape discrimination) implemented in a small-animal PET scanner by comparing the same phantom and same mouse images with and without DOI correction. The results suggest that even this relatively coarse, two-level estimate of radial gamma ray interaction position significantly reduces the DOI parallax error. This study also confirms two less appreciated advantages of DOI correction: a reduction in radial distortion and radial source displacement as a source is moved toward the edge of the field of view and a resolution improvement detectable in the central field of view likely owing to improved spatial sampling. PMID:21084028

Depth-of-interaction estimates in pixelated scintillator sensors using Monte Carlo techniques

NASA Astrophysics Data System (ADS)

Sharma, Diksha; Sze, Christina; Bhandari, Harish; Nagarkar, Vivek; Badano, Aldo

2017-01-01

Image quality in thick scintillator detectors can be improved by minimizing parallax errors through depth-of-interaction (DOI) estimation. A novel sensor for low-energy single photon imaging having a thick, transparent, crystalline pixelated micro-columnar CsI:Tl scintillator structure has been described, with possible future application in small-animal single photon emission computed tomography (SPECT) imaging when using thicker structures under development. In order to understand the fundamental limits of this new structure, we introduce cartesianDETECT2, an open-source optical transport package that uses Monte Carlo methods to obtain estimates of DOI for improving spatial resolution of nuclear imaging applications. Optical photon paths are calculated as a function of varying simulation parameters such as columnar surface roughness, bulk, and top-surface absorption. We use scanning electron microscope images to estimate appropriate surface roughness coefficients. Simulation results are analyzed to model and establish patterns between DOI and photon scattering. The effect of varying starting locations of optical photons on the spatial response is studied. Bulk and top-surface absorption fractions were varied to investigate their effect on spatial response as a function of DOI. We investigated the accuracy of our DOI estimation model for a particular screen with various training and testing sets, and for all cases the percent error between the estimated and actual DOI over the majority of the detector thickness was ±5% with a maximum error of up to ±10% at deeper DOIs. In addition, we found that cartesianDETECT2 is computationally five times more efficient than MANTIS. Findings indicate that DOI estimates can be extracted from a double-Gaussian model of the detector response. We observed that our model predicts DOI in pixelated scintillator detectors reasonably well.

General features of the retinal connectome determine the computation of motion anticipation

PubMed Central

Johnston, Jamie; Lagnado, Leon

2015-01-01

Motion anticipation allows the visual system to compensate for the slow speed of phototransduction so that a moving object can be accurately located. This correction is already present in the signal that ganglion cells send from the retina but the biophysical mechanisms underlying this computation are not known. Here we demonstrate that motion anticipation is computed autonomously within the dendritic tree of each ganglion cell and relies on feedforward inhibition. The passive and non-linear interaction of excitatory and inhibitory synapses enables the somatic voltage to encode the actual position of a moving object instead of its delayed representation. General rather than specific features of the retinal connectome govern this computation: an excess of inhibitory inputs over excitatory, with both being randomly distributed, allows tracking of all directions of motion, while the average distance between inputs determines the object velocities that can be compensated for. DOI: http://dx.doi.org/10.7554/eLife.06250.001 PMID:25786068

Physical determinants of vesicle mobility and supply at a central synapse

PubMed Central

Rothman, Jason Seth; Kocsis, Laszlo; Herzog, Etienne; Nusser, Zoltan; Silver, Robin Angus

2016-01-01

Encoding continuous sensory variables requires sustained synaptic signalling. At several sensory synapses, rapid vesicle supply is achieved via highly mobile vesicles and specialized ribbon structures, but how this is achieved at central synapses without ribbons is unclear. Here we examine vesicle mobility at excitatory cerebellar mossy fibre synapses which sustain transmission over a broad frequency bandwidth. Fluorescent recovery after photobleaching in slices from VGLUT1Venus knock-in mice reveal 75% of VGLUT1-containing vesicles have a high mobility, comparable to that at ribbon synapses. Experimentally constrained models establish hydrodynamic interactions and vesicle collisions are major determinants of vesicle mobility in crowded presynaptic terminals. Moreover, models incorporating 3D reconstructions of vesicle clouds near active zones (AZs) predict the measured releasable pool size and replenishment rate from the reserve pool. They also show that while vesicle reloading at AZs is not diffusion-limited at the onset of release, diffusion limits vesicle reloading during sustained high-frequency signalling. DOI: http://dx.doi.org/10.7554/eLife.15133.001 PMID:27542193

43 CFR 17.314 - Age distinctions contained in DOI regulations.

Code of Federal Regulations, 2011 CFR

2011-10-01

... 43 Public Lands: Interior 1 2011-10-01 2011-10-01 false Age distinctions contained in DOI... Age Standards for Determining Age Discrimination § 17.314 Age distinctions contained in DOI regulations. Any age distinctions contained in a rule or regulation issued by DOI shall be presumed to be...

43 CFR 17.314 - Age distinctions contained in DOI regulations.

Code of Federal Regulations, 2013 CFR

2013-10-01

... 43 Public Lands: Interior 1 2013-10-01 2013-10-01 false Age distinctions contained in DOI... Age Standards for Determining Age Discrimination § 17.314 Age distinctions contained in DOI regulations. Any age distinctions contained in a rule or regulation issued by DOI shall be presumed to be...

43 CFR 17.314 - Age distinctions contained in DOI regulations.

Code of Federal Regulations, 2014 CFR

2014-10-01

... 43 Public Lands: Interior 1 2014-10-01 2014-10-01 false Age distinctions contained in DOI... Age Standards for Determining Age Discrimination § 17.314 Age distinctions contained in DOI regulations. Any age distinctions contained in a rule or regulation issued by DOI shall be presumed to be...

43 CFR 17.314 - Age distinctions contained in DOI regulations.

Code of Federal Regulations, 2012 CFR

2012-10-01

... 43 Public Lands: Interior 1 2012-10-01 2011-10-01 true Age distinctions contained in DOI... Age Standards for Determining Age Discrimination § 17.314 Age distinctions contained in DOI regulations. Any age distinctions contained in a rule or regulation issued by DOI shall be presumed to be...

43 CFR 17.320 - General responsibilities.

Code of Federal Regulations, 2010 CFR

2010-10-01

... ASSISTED PROGRAMS OF THE DEPARTMENT OF THE INTERIOR Nondiscrimination on the Basis of Age Duties of Doi Recipients § 17.320 General responsibilities. Each DOI recipient has primary responsibility to ensure that... information, and to afford DOI access to its records to the extent DOI finds necessary to determine whether...

43 CFR 17.314 - Age distinctions contained in DOI regulations.

Code of Federal Regulations, 2010 CFR

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Age distinctions contained in DOI... Age Standards for Determining Age Discrimination § 17.314 Age distinctions contained in DOI regulations. Any age distinctions contained in a rule or regulation issued by DOI shall be presumed to be...

43 CFR 17.320 - General responsibilities.

Code of Federal Regulations, 2011 CFR

2011-10-01

... ASSISTED PROGRAMS OF THE DEPARTMENT OF THE INTERIOR Nondiscrimination on the Basis of Age Duties of Doi Recipients § 17.320 General responsibilities. Each DOI recipient has primary responsibility to ensure that... information, and to afford DOI access to its records to the extent DOI finds necessary to determine whether...

Protein arginine methylation facilitates KCNQ channel-PIP2 interaction leading to seizure suppression

PubMed Central

Kim, Hyun-Ji; Jeong, Myong-Ho; Kim, Kyung-Ran; Jung, Chang-Yun; Lee, Seul-Yi; Kim, Hanna; Koh, Jewoo; Vuong, Tuan Anh; Jung, Seungmoon; Yang, Hyunwoo; Park, Su-Kyung; Choi, Dahee; Kim, Sung Hun; Kang, KyeongJin; Sohn, Jong-Woo; Park, Joo Min; Jeon, Daejong; Koo, Seung-Hoi; Ho, Won-Kyung; Kang, Jong-Sun; Kim, Seong-Tae; Cho, Hana

2016-01-01

KCNQ channels are critical determinants of neuronal excitability, thus emerging as a novel target of anti-epileptic drugs. To date, the mechanisms of KCNQ channel modulation have been mostly characterized to be inhibitory via Gq-coupled receptors, Ca2+/CaM, and protein kinase C. Here we demonstrate that methylation of KCNQ by protein arginine methyltransferase 1 (Prmt1) positively regulates KCNQ channel activity, thereby preventing neuronal hyperexcitability. Prmt1+/- mice exhibit epileptic seizures. Methylation of KCNQ2 channels at 4 arginine residues by Prmt1 enhances PIP2 binding, and Prmt1 depletion lowers PIP2 affinity of KCNQ2 channels and thereby the channel activities. Consistently, exogenous PIP2 addition to Prmt1+/- neurons restores KCNQ currents and neuronal excitability to the WT level. Collectively, we propose that Prmt1-dependent facilitation of KCNQ-PIP2 interaction underlies the positive regulation of KCNQ activity by arginine methylation, which may serve as a key target for prevention of neuronal hyperexcitability and seizures. DOI: http://dx.doi.org/10.7554/eLife.17159.001 PMID:27466704

Promiscuous interactions and protein disaggregases determine the material state of stress-inducible RNP granules

PubMed Central

Kroschwald, Sonja; Maharana, Shovamayee; Mateju, Daniel; Malinovska, Liliana; Nüske, Elisabeth; Poser, Ina; Richter, Doris; Alberti, Simon

2015-01-01

RNA-protein (RNP) granules have been proposed to assemble by forming solid RNA/protein aggregates or through phase separation into a liquid RNA/protein phase. Which model describes RNP granules in living cells is still unclear. In this study, we analyze P bodies in budding yeast and find that they have liquid-like properties. Surprisingly, yeast stress granules adopt a different material state, which is reminiscent of solid protein aggregates and controlled by protein disaggregases. By using an assay to ectopically nucleate RNP granules, we further establish that RNP granule formation does not depend on amyloid-like aggregation but rather involves many promiscuous interactions. Finally, we show that stress granules have different properties in mammalian cells, where they show liquid-like behavior. Thus, we propose that the material state of RNP granules is flexible and that the solid state of yeast stress granules is an adaptation to extreme environments, made possible by the presence of a powerful disaggregation machine. DOI: http://dx.doi.org/10.7554/eLife.06807.001 PMID:26238190

A conserved MCM single-stranded DNA binding element is essential for replication initiation.

PubMed

Froelich, Clifford A; Kang, Sukhyun; Epling, Leslie B; Bell, Stephen P; Enemark, Eric J

2014-04-01

The ring-shaped MCM helicase is essential to all phases of DNA replication. The complex loads at replication origins as an inactive double-hexamer encircling duplex DNA. Helicase activation converts this species to two active single hexamers that encircle single-stranded DNA (ssDNA). The molecular details of MCM DNA interactions during these events are unknown. We determined the crystal structure of the Pyrococcus furiosus MCM N-terminal domain hexamer bound to ssDNA and define a conserved MCM-ssDNA binding motif (MSSB). Intriguingly, ssDNA binds the MCM ring interior perpendicular to the central channel with defined polarity. In eukaryotes, the MSSB is conserved in several Mcm2-7 subunits, and MSSB mutant combinations in S. cerevisiae Mcm2-7 are not viable. Mutant Mcm2-7 complexes assemble and are recruited to replication origins, but are defective in helicase loading and activation. Our findings identify an important MCM-ssDNA interaction and suggest it functions during helicase activation to select the strand for translocation. DOI: http://dx.doi.org/10.7554/eLife.01993.001.

A conserved MCM single-stranded DNA binding element is essential for replication initiation

PubMed Central

Froelich, Clifford A; Kang, Sukhyun; Epling, Leslie B; Bell, Stephen P; Enemark, Eric J

2014-01-01

The ring-shaped MCM helicase is essential to all phases of DNA replication. The complex loads at replication origins as an inactive double-hexamer encircling duplex DNA. Helicase activation converts this species to two active single hexamers that encircle single-stranded DNA (ssDNA). The molecular details of MCM DNA interactions during these events are unknown. We determined the crystal structure of the Pyrococcus furiosus MCM N-terminal domain hexamer bound to ssDNA and define a conserved MCM-ssDNA binding motif (MSSB). Intriguingly, ssDNA binds the MCM ring interior perpendicular to the central channel with defined polarity. In eukaryotes, the MSSB is conserved in several Mcm2-7 subunits, and MSSB mutant combinations in S. cerevisiae Mcm2-7 are not viable. Mutant Mcm2-7 complexes assemble and are recruited to replication origins, but are defective in helicase loading and activation. Our findings identify an important MCM-ssDNA interaction and suggest it functions during helicase activation to select the strand for translocation. DOI: http://dx.doi.org/10.7554/eLife.01993.001 PMID:24692448

Improving Depth, Energy and Timing Estimation in PET Detectors with Deconvolution and Maximum Likelihood Pulse Shape Discrimination

PubMed Central

Berg, Eric; Roncali, Emilie; Hutchcroft, Will; Qi, Jinyi; Cherry, Simon R.

2016-01-01

In a scintillation detector, the light generated in the scintillator by a gamma interaction is converted to photoelectrons by a photodetector and produces a time-dependent waveform, the shape of which depends on the scintillator properties and the photodetector response. Several depth-of-interaction (DOI) encoding strategies have been developed that manipulate the scintillator’s temporal response along the crystal length and therefore require pulse shape discrimination techniques to differentiate waveform shapes. In this work, we demonstrate how maximum likelihood (ML) estimation methods can be applied to pulse shape discrimination to better estimate deposited energy, DOI and interaction time (for time-of-flight (TOF) PET) of a gamma ray in a scintillation detector. We developed likelihood models based on either the estimated detection times of individual photoelectrons or the number of photoelectrons in discrete time bins, and applied to two phosphor-coated crystals (LFS and LYSO) used in a previously developed TOF-DOI detector concept. Compared with conventional analytical methods, ML pulse shape discrimination improved DOI encoding by 27% for both crystals. Using the ML DOI estimate, we were able to counter depth-dependent changes in light collection inherent to long scintillator crystals and recover the energy resolution measured with fixed depth irradiation (~11.5% for both crystals). Lastly, we demonstrated how the Richardson-Lucy algorithm, an iterative, ML-based deconvolution technique, can be applied to the digitized waveforms to deconvolve the photodetector’s single photoelectron response and produce waveforms with a faster rising edge. After deconvolution and applying DOI and time-walk corrections, we demonstrated a 13% improvement in coincidence timing resolution (from 290 to 254 ps) with the LFS crystal and an 8% improvement (323 to 297 ps) with the LYSO crystal. PMID:27295658

Improving Depth, Energy and Timing Estimation in PET Detectors with Deconvolution and Maximum Likelihood Pulse Shape Discrimination.

PubMed

Berg, Eric; Roncali, Emilie; Hutchcroft, Will; Qi, Jinyi; Cherry, Simon R

2016-11-01

In a scintillation detector, the light generated in the scintillator by a gamma interaction is converted to photoelectrons by a photodetector and produces a time-dependent waveform, the shape of which depends on the scintillator properties and the photodetector response. Several depth-of-interaction (DOI) encoding strategies have been developed that manipulate the scintillator's temporal response along the crystal length and therefore require pulse shape discrimination techniques to differentiate waveform shapes. In this work, we demonstrate how maximum likelihood (ML) estimation methods can be applied to pulse shape discrimination to better estimate deposited energy, DOI and interaction time (for time-of-flight (TOF) PET) of a gamma ray in a scintillation detector. We developed likelihood models based on either the estimated detection times of individual photoelectrons or the number of photoelectrons in discrete time bins, and applied to two phosphor-coated crystals (LFS and LYSO) used in a previously developed TOF-DOI detector concept. Compared with conventional analytical methods, ML pulse shape discrimination improved DOI encoding by 27% for both crystals. Using the ML DOI estimate, we were able to counter depth-dependent changes in light collection inherent to long scintillator crystals and recover the energy resolution measured with fixed depth irradiation (~11.5% for both crystals). Lastly, we demonstrated how the Richardson-Lucy algorithm, an iterative, ML-based deconvolution technique, can be applied to the digitized waveforms to deconvolve the photodetector's single photoelectron response and produce waveforms with a faster rising edge. After deconvolution and applying DOI and time-walk corrections, we demonstrated a 13% improvement in coincidence timing resolution (from 290 to 254 ps) with the LFS crystal and an 8% improvement (323 to 297 ps) with the LYSO crystal.

A depth-of-interaction PET detector using mutual gain-equalized silicon photomultiplier

DOE Office of Scientific and Technical Information (OSTI.GOV)

W. Xi, A.G, Weisenberger, H. Dong, Brian Kross, S. Lee, J. McKisson, Carl Zorn

We developed a prototype high resolution, high efficiency depth-encoding detector for PET applications based on dual-ended readout of LYSO array with two silicon photomultipliers (SiPMs). Flood images, energy resolution, and depth-of-interaction (DOI) resolution were measured for a LYSO array - 0.7 mm in crystal pitch and 10 mm in thickness - with four unpolished parallel sides. Flood images were obtained such that individual crystal element in the array is resolved. The energy resolution of the entire array was measured to be 33%, while individual crystal pixel elements utilizing the signal from both sides ranged from 23.3% to 27%. By applyingmore » a mutual-gain equalization method, a DOI resolution of 2 mm for the crystal array was obtained in the experiments while simulations indicate {approx}1 mm DOI resolution could possibly be achieved. The experimental DOI resolution can be further improved by obtaining revised detector supporting electronics with better energy resolutions. This study provides a detailed detector calibration and DOI response characterization of the dual-ended readout SiPM-based PET detectors, which will be important in the design and calibration of a PET scanner in the future.« less

Investigation of depth-of-interaction (DOI) effects in single- and dual-layer block detectors by the use of light sharing in scintillators.

PubMed

Yamamoto, Seiichi

2012-01-01

In block detectors for PET scanners that use different lengths of slits in scintillators to share light among photomultiplier tubes (PMTs), a position histogram is distorted when the depth of interaction (DOI) of the gamma photons is near the PMTs (DOI effect). However, it remains unclear whether a DOI effect is observed for block detectors that use light sharing in scintillators. To investigate the effect, I tested the effect for single- and dual-layer block detectors. In the single-layer block detector, Ce doped Gd₂SiO₅ (GSO) crystals of 1.9 × 1.9 × 15 mm³ (0.5 mol% Ce) were used. In the dual-layer block detector, GSO crystals of a 1.9 × 1.9 × 6 mm³ (1.5 mol% Ce) were used for the front layer and GSO crystals of 1.9 × 1.9 × 9 mm³ (0.5 mol% Ce) for the back layer. These scintillators were arranged to form an 8 × 8 matrix with multi-layer optical film inserted partly between the scintillators for obtaining an optimized position response with use of two dual-PMTs. Position histograms and energy responses were measured for these block detectors at three different DOI positions, and the flood histograms were obtained. The results indicated that DOI effects are observed in both block detectors, but the dual-layer block showed more severe distortion in the position histogram as well as larger energy variations. We conclude that, in the block detectors that use light sharing in the scintillators, the DOI effect is an important factor for the performance of the detectors, especially for DOI block detectors.

CHERENCUBE: concept definition and implementation challenges of a Cherenkov-based detector block for PET.

PubMed

Somlai-Schweiger, I; Ziegler, S I

2015-04-01

A new concept for a depth-of-interaction (DOI) capable time-of-flight (TOF) PET detector is defined, based only on the detection of Cherenkov photons. The proposed "CHERENCUBE" consists of a cubic Cherenkov radiator with position-sensitive photodetectors covering each crystal face. By means of the spatial distribution of the detected photons and their time of arrival, the point of interaction of the gamma-ray in the crystal can be determined. This study analyzes through theoretical calculations and Monte Carlo simulations the potential advantages of the concept toward reaching a Cherenkov-only detector for TOF-PET with DOI capability. Furthermore, an algorithm for the DOI estimation is presented and the requirements for a practical implementation of the proposed concept are defined. The Monte Carlo simulations consisted of a cubic crystal with one photodetector coupled to each one of the faces of the cube. The sensitive area of the detector matched exactly the crystal size, which was varied in 1 mm steps between 1 × 1 × 1 mm(3) and 10 × 10 × 10 mm(3). For each size, five independent simulations of ten thousand 511 keV gamma-rays were triggered at a fixed distance of 10 mm. The crystal chosen was PbWO4. Its scintillation properties were simulated, but only Cherenkov photons were analyzed. Photodetectors were simulated having perfect photodetection efficiency and infinite time resolution. For every generated particle, the analysis considered its creation process, parent and daughter particles, energy, origin coordinates, trajectory, and time and position of detection. The DOI determination is based on the distribution of the emission time of all photons per event. These values are calculated as a function of the coordinates of detection and origin for every photon. The common origin is estimated by finding the distribution with the most similar emission time-points. Detection efficiency increases with crystal size from 8.2% (1 × 1 × 1 mm(3)) to 58.6% (10 × 10 × 10 mm(3)) and decreases applying a photon detection threshold of 5/10/20 photons to 6.3%/4.3%/0.7% and 49.3%/30.4%/2.8%, respectively. The detection rate in the six photodetectors is uniform due to the nearly isotropic cone emission. Most cones originated after a photoelectric effect interaction, with two dominating peaks for the kinetic energy of the electron at 422.99 and 441.47 keV. The detection distance between same-event photons defines the spatial resolution of the detector required for individual photon recognition, with 20% of the detected photons having their closest neighbor within a distance of 5% of the length of the cube. Same-event photons are detected within a time window whose width is determined by the crystal size, with values of 30 and 150 ps for a 1 × 1 × 1 mm(3) and a 10 × 10 × 10 mm(3) cube, respectively. The DOI reconstruction has an accuracy of approximately 23% of the length of the cube, with an average value of 2.2 mm for a 10 × 10 × 10 mm(3) CHERENCUBE. The proposed concept requires a detector with high photodetection efficiency. The structure of the sensitive surface of the detector should be a two dimensional array of microcells, able to provide individual detection coordinates and time stamps. The microcell size determines the ability to recognize individual photons, influencing detection efficiency. The 3D DOI recognition relies on the accuracy of the time stamps and detection coordinates, without the need for a recognition of the projected patterns of photons. The refractive index of the material defines a detector intrinsic energy-based rejection of scattered PET events at the cost of reduced sensitivity.

CHERENCUBE: Concept definition and implementation challenges of a Cherenkov-based detector block for PET

DOE Office of Scientific and Technical Information (OSTI.GOV)

Somlai-Schweiger, I., E-mail: ian.somlai@tum.de; Ziegler, S. I.

Purpose: A new concept for a depth-of-interaction (DOI) capable time-of-flight (TOF) PET detector is defined, based only on the detection of Cherenkov photons. The proposed “CHERENCUBE” consists of a cubic Cherenkov radiator with position-sensitive photodetectors covering each crystal face. By means of the spatial distribution of the detected photons and their time of arrival, the point of interaction of the gamma-ray in the crystal can be determined. This study analyzes through theoretical calculations and Monte Carlo simulations the potential advantages of the concept toward reaching a Cherenkov-only detector for TOF-PET with DOI capability. Furthermore, an algorithm for the DOI estimationmore » is presented and the requirements for a practical implementation of the proposed concept are defined. Methods: The Monte Carlo simulations consisted of a cubic crystal with one photodetector coupled to each one of the faces of the cube. The sensitive area of the detector matched exactly the crystal size, which was varied in 1 mm steps between 1 × 1 × 1 mm{sup 3} and 10 × 10 × 10 mm{sup 3}. For each size, five independent simulations of ten thousand 511 keV gamma-rays were triggered at a fixed distance of 10 mm. The crystal chosen was PbWO{sub 4}. Its scintillation properties were simulated, but only Cherenkov photons were analyzed. Photodetectors were simulated having perfect photodetection efficiency and infinite time resolution. For every generated particle, the analysis considered its creation process, parent and daughter particles, energy, origin coordinates, trajectory, and time and position of detection. The DOI determination is based on the distribution of the emission time of all photons per event. These values are calculated as a function of the coordinates of detection and origin for every photon. The common origin is estimated by finding the distribution with the most similar emission time-points. Results: Detection efficiency increases with crystal size from 8.2% (1 × 1 × 1 mm{sup 3}) to 58.6% (10 × 10 × 10 mm{sup 3}) and decreases applying a photon detection threshold of 5/10/20 photons to 6.3%/4.3%/0.7% and 49.3%/30.4%/2.8%, respectively. The detection rate in the six photodetectors is uniform due to the nearly isotropic cone emission. Most cones originated after a photoelectric effect interaction, with two dominating peaks for the kinetic energy of the electron at 422.99 and 441.47 keV. The detection distance between same-event photons defines the spatial resolution of the detector required for individual photon recognition, with 20% of the detected photons having their closest neighbor within a distance of 5% of the length of the cube. Same-event photons are detected within a time window whose width is determined by the crystal size, with values of 30 and 150 ps for a 1 × 1 × 1 mm{sup 3} and a 10 × 10 × 10 mm{sup 3} cube, respectively. The DOI reconstruction has an accuracy of approximately 23% of the length of the cube, with an average value of 2.2 mm for a 10 × 10 × 10 mm{sup 3} CHERENCUBE. Conclusions: The proposed concept requires a detector with high photodetection efficiency. The structure of the sensitive surface of the detector should be a two dimensional array of microcells, able to provide individual detection coordinates and time stamps. The microcell size determines the ability to recognize individual photons, influencing detection efficiency. The 3D DOI recognition relies on the accuracy of the time stamps and detection coordinates, without the need for a recognition of the projected patterns of photons. The refractive index of the material defines a detector intrinsic energy-based rejection of scattered PET events at the cost of reduced sensitivity.« less

A combined time-of-flight and depth-of-interaction detector for total-body positron emission tomography.

PubMed

Berg, Eric; Roncali, Emilie; Kapusta, Maciej; Du, Junwei; Cherry, Simon R

2016-02-01

In support of a project to build a total-body PET scanner with an axial field-of-view of 2 m, the authors are developing simple, cost-effective block detectors with combined time-of-flight (TOF) and depth-of-interaction (DOI) capabilities. This work focuses on investigating the potential of phosphor-coated crystals with conventional PMT-based block detector readout to provide DOI information while preserving timing resolution. The authors explored a variety of phosphor-coating configurations with single crystals and crystal arrays. Several pulse shape discrimination techniques were investigated, including decay time, delayed charge integration (DCI), and average signal shapes. Pulse shape discrimination based on DCI provided the lowest DOI positioning error: 2 mm DOI positioning error was obtained with single phosphor-coated crystals while 3-3.5 mm DOI error was measured with the block detector module. Minimal timing resolution degradation was observed with single phosphor-coated crystals compared to uncoated crystals, and a timing resolution of 442 ps was obtained with phosphor-coated crystals in the block detector compared to 404 ps without phosphor coating. Flood maps showed a slight degradation in crystal resolvability with phosphor-coated crystals; however, all crystals could be resolved. Energy resolution was degraded by 3%-7% with phosphor-coated crystals compared to uncoated crystals. These results demonstrate the feasibility of obtaining TOF-DOI capabilities with simple block detector readout using phosphor-coated crystals.

Target Surface Area Effects on Hot Electron Dynamics from High Intensity Laser-Plasma Interactions

DTIC Science & Technology

2016-08-19

New J. Phys. 18 (2016) 063020 doi:10.1088/1367-2630/18/6/063020 PAPER Target surface area effects on hot electron dynamics from high intensity laser ...Science, University ofMichigan, AnnArbor,MI 48109-2099, USA E-mail: czulick@umich.edu Keywords: laser -plasma,mass-limited, fast electrons, sheath...field Abstract Reduced surface area targets were studied using an ultra-high intensity femtosecond laser in order to determine the effect of electron

Birth order dependent growth cone segregation determines synaptic layer identity in the Drosophila visual system

PubMed Central

Kulkarni, Abhishek; Ertekin, Deniz; Lee, Chi-Hon; Hummel, Thomas

2016-01-01

The precise recognition of appropriate synaptic partner neurons is a critical step during neural circuit assembly. However, little is known about the developmental context in which recognition specificity is important to establish synaptic contacts. We show that in the Drosophila visual system, sequential segregation of photoreceptor afferents, reflecting their birth order, lead to differential positioning of their growth cones in the early target region. By combining loss- and gain-of-function analyses we demonstrate that relative differences in the expression of the transcription factor Sequoia regulate R cell growth cone segregation. This initial growth cone positioning is consolidated via cell-adhesion molecule Capricious in R8 axons. Further, we show that the initial growth cone positioning determines synaptic layer selection through proximity-based axon-target interactions. Taken together, we demonstrate that birth order dependent pre-patterning of afferent growth cones is an essential pre-requisite for the identification of synaptic partner neurons during visual map formation in Drosophila. DOI: http://dx.doi.org/10.7554/eLife.13715.001 PMID:26987017

The structure of plant photosystem I super-complex at 2.8 Å resolution

PubMed Central

Mazor, Yuval; Borovikova, Anna; Nelson, Nathan

2015-01-01

Most life forms on Earth are supported by solar energy harnessed by oxygenic photosynthesis. In eukaryotes, photosynthesis is achieved by large membrane-embedded super-complexes, containing reaction centers and connected antennae. Here, we report the structure of the higher plant PSI-LHCI super-complex determined at 2.8 Å resolution. The structure includes 16 subunits and more than 200 prosthetic groups, which are mostly light harvesting pigments. The complete structures of the four LhcA subunits of LHCI include 52 chlorophyll a and 9 chlorophyll b molecules, as well as 10 carotenoids and 4 lipids. The structure of PSI-LHCI includes detailed protein pigments and pigment–pigment interactions, essential for the mechanism of excitation energy transfer and its modulation in one of nature's most efficient photochemical machines. DOI: http://dx.doi.org/10.7554/eLife.07433.001 PMID:26076232

Computationally designed high specificity inhibitors delineate the roles of BCL2 family proteins in cancer

PubMed Central

Berger, Stephanie; Procko, Erik; Margineantu, Daciana; Lee, Erinna F; Shen, Betty W; Zelter, Alex; Silva, Daniel-Adriano; Chawla, Kusum; Herold, Marco J; Garnier, Jean-Marc; Johnson, Richard; MacCoss, Michael J; Lessene, Guillaume; Davis, Trisha N; Stayton, Patrick S; Stoddard, Barry L; Fairlie, W Douglas; Hockenbery, David M; Baker, David

2016-01-01

Many cancers overexpress one or more of the six human pro-survival BCL2 family proteins to evade apoptosis. To determine which BCL2 protein or proteins block apoptosis in different cancers, we computationally designed three-helix bundle protein inhibitors specific for each BCL2 pro-survival protein. Following in vitro optimization, each inhibitor binds its target with high picomolar to low nanomolar affinity and at least 300-fold specificity. Expression of the designed inhibitors in human cancer cell lines revealed unique dependencies on BCL2 proteins for survival which could not be inferred from other BCL2 profiling methods. Our results show that designed inhibitors can be generated for each member of a closely-knit protein family to probe the importance of specific protein-protein interactions in complex biological processes. DOI: http://dx.doi.org/10.7554/eLife.20352.001 PMID:27805565

43 CFR 17.323 - Information collection requirements.

Code of Federal Regulations, 2010 CFR

2010-10-01

... of Doi Recipients § 17.323 Information collection requirements. Each recipient shall: (a) Keep records in a form and containing information which DOI determines may be necessary to ascertain whether the recipient is complying with the Act and these regulations. (b) Provide to DOI, upon request...

43 CFR 17.323 - Information collection requirements.

Code of Federal Regulations, 2011 CFR

2011-10-01

... of Doi Recipients § 17.323 Information collection requirements. Each recipient shall: (a) Keep records in a form and containing information which DOI determines may be necessary to ascertain whether the recipient is complying with the Act and these regulations. (b) Provide to DOI, upon request...

A combined time-of-flight and depth-of-interaction detector for total-body positron emission tomography

PubMed Central

Berg, Eric; Roncali, Emilie; Kapusta, Maciej; Du, Junwei; Cherry, Simon R.

2016-01-01

Purpose: In support of a project to build a total-body PET scanner with an axial field-of-view of 2 m, the authors are developing simple, cost-effective block detectors with combined time-of-flight (TOF) and depth-of-interaction (DOI) capabilities. Methods: This work focuses on investigating the potential of phosphor-coated crystals with conventional PMT-based block detector readout to provide DOI information while preserving timing resolution. The authors explored a variety of phosphor-coating configurations with single crystals and crystal arrays. Several pulse shape discrimination techniques were investigated, including decay time, delayed charge integration (DCI), and average signal shapes. Results: Pulse shape discrimination based on DCI provided the lowest DOI positioning error: 2 mm DOI positioning error was obtained with single phosphor-coated crystals while 3–3.5 mm DOI error was measured with the block detector module. Minimal timing resolution degradation was observed with single phosphor-coated crystals compared to uncoated crystals, and a timing resolution of 442 ps was obtained with phosphor-coated crystals in the block detector compared to 404 ps without phosphor coating. Flood maps showed a slight degradation in crystal resolvability with phosphor-coated crystals; however, all crystals could be resolved. Energy resolution was degraded by 3%–7% with phosphor-coated crystals compared to uncoated crystals. Conclusions: These results demonstrate the feasibility of obtaining TOF–DOI capabilities with simple block detector readout using phosphor-coated crystals. PMID:26843254

A combined time-of-flight and depth-of-interaction detector for total-body positron emission tomography

DOE Office of Scientific and Technical Information (OSTI.GOV)

Berg, Eric, E-mail: eberg@ucdavis.edu; Roncali, Emilie; Du, Junwei

Purpose: In support of a project to build a total-body PET scanner with an axial field-of-view of 2 m, the authors are developing simple, cost-effective block detectors with combined time-of-flight (TOF) and depth-of-interaction (DOI) capabilities. Methods: This work focuses on investigating the potential of phosphor-coated crystals with conventional PMT-based block detector readout to provide DOI information while preserving timing resolution. The authors explored a variety of phosphor-coating configurations with single crystals and crystal arrays. Several pulse shape discrimination techniques were investigated, including decay time, delayed charge integration (DCI), and average signal shapes. Results: Pulse shape discrimination based on DCI providedmore » the lowest DOI positioning error: 2 mm DOI positioning error was obtained with single phosphor-coated crystals while 3–3.5 mm DOI error was measured with the block detector module. Minimal timing resolution degradation was observed with single phosphor-coated crystals compared to uncoated crystals, and a timing resolution of 442 ps was obtained with phosphor-coated crystals in the block detector compared to 404 ps without phosphor coating. Flood maps showed a slight degradation in crystal resolvability with phosphor-coated crystals; however, all crystals could be resolved. Energy resolution was degraded by 3%–7% with phosphor-coated crystals compared to uncoated crystals. Conclusions: These results demonstrate the feasibility of obtaining TOF–DOI capabilities with simple block detector readout using phosphor-coated crystals.« less

Metabotropic glutamate mGlu2 receptor is necessary for the pharmacological and behavioral effects induced by hallucinogenic 5-HT2A receptor agonists.

PubMed

Moreno, José L; Holloway, Terrell; Albizu, Laura; Sealfon, Stuart C; González-Maeso, Javier

2011-04-15

Hallucinogenic drugs, including mescaline, psilocybin and lysergic acid diethylamide (LSD), act at serotonin 5-HT2A receptors (5-HT2ARs). Metabotropic glutamate receptor 2/3 (mGluR2/3) ligands show efficacy in modulating the responses induced by activation of 5-HT2ARs. The formation of a 5-HT2AR-mGluR2 complex suggests a functional interaction that affects the hallucinogen-regulated cellular signaling pathways. Here, we tested the cellular and behavioral effects of hallucinogenic 5-HT2AR agonists in mGluR2 knockout (mGluR2-KO) mice. Mice were intraperitoneally injected with the hallucinogens DOI (2 mg/kg) and LSD (0.24 mg/kg), or vehicle. Head-twitch behavioral response, expression of c-fos, which is induced by all 5-HT2AR agonists, and expression of egr-2, which is hallucinogen-specific, were determined in wild type and mGluR2-KO mice. [(3)H]Ketanserin binding displacement curves by DOI were performed in mouse frontal cortex membrane preparations. Head twitch behavior was abolished in mGluR2-KO mice. The high-affinity binding site of DOI was undetected in mGluR2-KO mice. The hallucinogen DOI induced c-fos in both wild type and mGluR2-KO mice. However, the induction of egr-2 by DOI was eliminated in mGlu2-KO mice. These findings suggest that the 5-HT2AR-mGluR2 complex is necessary for the neuropsychological responses induced by hallucinogens. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Metabotropic glutamate mGlu2 receptor is necessary for the pharmacological and behavioral effects induced by hallucinogenic 5-HT2A receptor agonists

PubMed Central

Moreno, José L.; Holloway, Terrell; Albizu, Laura; Sealfon, Stuart C.; González-Maeso, Javier

2011-01-01

Hallucinogenic drugs, including mescaline, psilocybin and lysergic acid diethylamide (LSD), act at serotonin 5-HT2A receptors (5-HT2ARs). Metabotropic glutamate receptor 2/3 (mGluR2/3) ligands show efficacy in modulating the responses induced by activation of 5-HT2ARs. The formation of a 5-HT2AR-mGluR2 complex suggests a functional interaction that affects the hallucinogen-regulated cellular signaling pathways. Here, we tested the cellular and behavioral effects of hallucinogenic 5-HT2AR agonists in mGluR2 knockout (mGluR2-KO) mice. Mice were intraperitoneally injected with the hallucinogens DOI (2 mg/kg) and LSD (0.24 mg/kg), or vehicle. Head-twitch behavioral response, expression of c-fos, which is induced by all 5-HT2AR agonists, and expression of egr-2, which is hallucinogen-specific, were determined in wild type and mGluR2-KO mice. [3H]Ketanserin binding displacement curves by DOI were performed in mouse frontal cortex membrane preparations. Head twitch behavior was abolished in mGluR2-KO mice. The high-affinity binding site of DOI was undetected in mGluR2-KO mice. The hallucinogen DOI induced c-fos in both wild type and mGluR2-KO mice. However, the induction of egr-2 by DOI was eliminated in mGlu2-KO mice. These findings suggest that the 5-HT2AR-mGluR2 complex is necessary for the neuropsychological responses induced by hallucinogens. PMID:21276828

Departures from Axisymmetric Balance Dynamics during Secondary Eyewall Formation

DTIC Science & Technology

2014-10-01

tensification of Hurricane Opal as diagnosed from a GFDL model forecast. Mon. Wea. Rev., 130, 1866–1881, doi:10.1175/ 1520-0493(2002)130,1866:BCTTIO...2002: Environ- mental interactions in the GFDL hurricane model for Hurri- cane Opal . Mon. Wea. Rev., 130, 298–317, doi:10.1175/ 1520-0493(2002

Impulsive behaviour in rats induced by intracortical DOI infusions is antagonized by co-administration of an mGlu2/3 receptor agonist.

PubMed

Wischhof, Lena; Hollensteiner, Karl J; Koch, Michael

2011-12-01

The orbitofrontal cortex (OFC) and the medial prefrontal cortex (mPFC) modulate impulsive behaviours. Serotonin [5-hydroxytryptamine (5-HT)] 2A receptors have also been implicated in impulsivity and govern antagonistic interactions with metabotropic glutamate (mGlu)2/3 receptors. This study examined the interactions between 5-HT2A and mGlu2/3 receptors in the OFC and mPFC with relevance to impulsive choice and impulsive action. Impulsive choice was assessed in Lister Hooded rats, trained in a delay-discounting T-maze task, after bilateral intra-OFC infusions of the 5-HT2A/C receptor agonist DOI [(+/-)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropan hydrochloride; 5 μg/0.5 μl] and the mGlu2/3 receptor agonist LY379268 (1 μg/0.5 μl). Impulsive action was assessed in a second group of rats trained in a five-choice serial reaction time task (5-CSRTT) and receiving bilateral intra-mPFC infusions of DOI (5 μg/0.5 μl) and LY379268 (1 μg/0.5 μl). Intra-OFC DOI increased impulsive choice, which was not seen when DOI was co-administered with LY379268. LY379268 itself had no effect on choice behaviour. Intra-mPFC DOI caused impulsive over-responding in the 5-CSRTT that was attenuated when DOI and LY379268 were co-injected. Local mPFC-infusions of LY379268 had no effect on 5-CSRTT performance. This study suggests a differential involvement of OFC and mPFC 5-HT2A receptors in impulsive choice and impulsive action. Moreover, compounds acting at mGlu2/3 receptors might have the potential to improve impulsivity-related impairments.

Evolving a NASA Digital Object Identifiers System with Community Engagement

NASA Technical Reports Server (NTRS)

Wanchoo, Lalit; James, Nathan

2016-01-01

To demonstrate how the ESDIS (Earth Science Data and Information System) DOI (Digital Object Identifier) system and its processes have evolved over these years based on the recommendations provided by the user community (whether the community members create and manage DOI information or use DOIs in the data citations). The user community is comprised of people with common interests and needs for data identifiers who are actively involved in the creation and usage process. Engagement describes the interactive context wherein the community provides information, evaluates the proposed processes, and provides guidance in the area of identifiers.

25 CFR 1000.232 - When must DOI respond to a request for reconsideration?

Code of Federal Regulations, 2011 CFR

2011-04-01

... 25 Indians 2 2011-04-01 2011-04-01 false When must DOI respond to a request for reconsideration? 1000.232 Section 1000.232 Indians OFFICE OF THE ASSISTANT SECRETARY, INDIAN AFFAIRS, DEPARTMENT OF THE...-DETERMINATION AND EDUCATION ACT Waiver of Regulations § 1000.232 When must DOI respond to a request for...

Color sensitive silicon photomultiplers with micro-cell level encoding for DOI PET detectors

NASA Astrophysics Data System (ADS)

Shimazoe, Kenji; Koyama, Akihiro; Takahashi, Hiroyuki; Ganka, Thomas; Iskra, Peter; Marquez Seco, Alicia; Schneider, Florian; Wiest, Florian

2017-11-01

There have been many studies on Depth Of Interaction (DOI) identification for high resolution Positron Emission Tomography (PET) systems, including those on phoswich detectors, double-sided readout, light sharing methods, and wavelength discrimination. The wavelength discrimination method utilizes the difference in wavelength of stacked scintillators and requires a color sensitive photodetector. Here, a new silicon photomultiplier (SiPM) coupled to a color filter (colorSiPM) was designed and fabricated for DOI detection. The fabricated colorSiPM has two anode readouts that are sensitive to blue and green color. The colorSiPM's response and DOI identification capability for stacked GAGG and LYSO crystals are characterized. The fabricated colorSiPM is sensitive enough to detect a peak of 662 keV from a 137 Cs source.

Continuous depth-of-interaction encoding using phosphor-coated scintillators.

PubMed

Du, Huini; Yang, Yongfeng; Glodo, Jarek; Wu, Yibao; Shah, Kanai; Cherry, Simon R

2009-03-21

We investigate a novel detector using a lutetium oxyorthosilicate (LSO) scintillator and YGG (yttrium-aluminum-gallium oxide:cerium, Y(3)(Al,Ga)(5)O(12):Ce) phosphor to construct a detector with continuous depth-of-interaction (DOI) information. The far end of the LSO scintillator is coated with a thin layer of YGG phosphor powder which absorbs some fraction of the LSO scintillation light and emits wavelength-shifted photons with a characteristic decay time of approximately 50 ns. The near end of the LSO scintillator is directly coupled to a photodetector. The photodetector detects a mixture of the LSO light and the light emitted by YGG. With appropriate placement of the coating, the ratio of the light converted from the YGG coating with respect to the unconverted LSO light can be made to depend on the interaction depth. DOI information can then be estimated by inspecting the overall light pulse decay time. Experiments were conducted to optimize the coating method. 19 ns decay time differences across the length of the detector were achieved experimentally when reading out a 1.5 x 1.5 x 20 mm(3) LSO crystal with unpolished surfaces and half-coated with YGG phosphor. The same coating scheme was applied to a 4 x 4 LSO array. Pulse shape discrimination (PSD) methods were studied to extract DOI information from the pulse shape changes. The DOI full-width-half-maximum (FWHM) resolution was found to be approximately 8 mm for this 2 cm thick array.

Continuous Depth-of-Interaction Encoding Using Phosphor-Coated Scintillators

PubMed Central

Du, Huini; Yang, Yongfeng; Glodo, Jarek; Wu, Yibao; Shah, Kanai; Cherry, Simon R.

2009-01-01

We investigate a novel detector using lutetium oxyorthosilicate (LSO) scintillator and YGG (yttrium aluminum gallium oxide:cerium, Y3(Al,Ga)5O12:Ce) phosphor to construct a detector with continuous depth-of-interaction (DOI) information. The far end of the LSO scintillator is coated with a thin layer of YGG phosphor powder which absorbs some fraction of the LSO scintillation light and emits wavelength-shifted photons with a characteristic decay time of ∼ 50 ns. The near end of the LSO scintillator is directly coupled to a photodetector. The photodetector detects a mixture of the LSO light and the light emitted by YGG. With appropriate placement of the coating, the ratio of the light converted from the YGG coating with respect to the unconverted LSO light can be made to depend on the interaction depth. DOI information can then be estimated by inspecting the overall light pulse decay time. Experiments were conducted to optimize the coating method. 19 ns decay time differences across the length of the detector were achieved experimentally when reading out a 1.5×1.5×20 mm3 LSO crystal with unpolished surfaces and half-coated with YGG phosphor. The same coating scheme was applied to a 4 by 4 LSO array. Pulse shape discrimination (PSD) methods were studied to extract DOI information from the pulse shape changes. The DOI full-width-half-maximum (FWHM) resolution was found to be ∼8 mm for this 2 cm thick array. PMID:19258685

Emergence and evolution of an interaction between intrinsically disordered proteins

PubMed Central

Hultqvist, Greta; Åberg, Emma; Camilloni, Carlo; Sundell, Gustav N; Andersson, Eva; Dogan, Jakob; Chi, Celestine N; Vendruscolo, Michele; Jemth, Per

2017-01-01

Protein-protein interactions involving intrinsically disordered proteins are important for cellular function and common in all organisms. However, it is not clear how such interactions emerge and evolve on a molecular level. We performed phylogenetic reconstruction, resurrection and biophysical characterization of two interacting disordered protein domains, CID and NCBD. CID appeared after the divergence of protostomes and deuterostomes 450–600 million years ago, while NCBD was present in the protostome/deuterostome ancestor. The most ancient CID/NCBD formed a relatively weak complex (Kd∼5 µM). At the time of the first vertebrate-specific whole genome duplication, the affinity had increased (Kd∼200 nM) and was maintained in further speciation. Experiments together with molecular modeling using NMR chemical shifts suggest that new interactions involving intrinsically disordered proteins may evolve via a low-affinity complex which is optimized by modulating direct interactions as well as dynamics, while tolerating several potentially disruptive mutations. DOI: http://dx.doi.org/10.7554/eLife.16059.001 PMID:28398197

Lotka-Volterra pairwise modeling fails to capture diverse pairwise microbial interactions

PubMed Central

Momeni, Babak; Xie, Li; Shou, Wenying

2017-01-01

Pairwise models are commonly used to describe many-species communities. In these models, an individual receives additive fitness effects from pairwise interactions with each species in the community ('additivity assumption'). All pairwise interactions are typically represented by a single equation where parameters reflect signs and strengths of fitness effects ('universality assumption'). Here, we show that a single equation fails to qualitatively capture diverse pairwise microbial interactions. We build mechanistic reference models for two microbial species engaging in commonly-found chemical-mediated interactions, and attempt to derive pairwise models. Different equations are appropriate depending on whether a mediator is consumable or reusable, whether an interaction is mediated by one or more mediators, and sometimes even on quantitative details of the community (e.g. relative fitness of the two species, initial conditions). Our results, combined with potential violation of the additivity assumption in many-species communities, suggest that pairwise modeling will often fail to predict microbial dynamics. DOI: http://dx.doi.org/10.7554/eLife.25051.001 PMID:28350295

75 FR 82061 - Notice To Amend an Existing System of Records; Privacy Act of 1974; as Amended

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-29

... amended, the Department of the Interior (DOI) is issuing public notice of its intent to amend the Bureau... would require a contrary determination. The DOI will publish a revised notice if changes are made based... primary uses of the records are: (1) To provide the BLM, the DOI or state, local and tribal governments...

Space Particle Hazard Measurement and Modeling

DTIC Science & Technology

2016-09-01

understand the interactions of the physical processes driving, then specify and ultimately predict the state of the energetic particle populations...Hudson, and B. T. Kress (2013), Direct observation of the CRAND proton radiation belt source, J. Geophys. Res. Space Physics , 118, doi:10.1002...anticritical temperature for spacecraft charging, J. Geophys Res.: Space Physics , 113, 2156-2202, doi: 10.1029/2008JA013161 2010 – Tested basic

Functional double dissociation within the entorhinal cortex for visual scene-dependent choice behavior

PubMed Central

Yoo, Seung-Woo; Lee, Inah

2017-01-01

How visual scene memory is processed differentially by the upstream structures of the hippocampus is largely unknown. We sought to dissociate functionally the lateral and medial subdivisions of the entorhinal cortex (LEC and MEC, respectively) in visual scene-dependent tasks by temporarily inactivating the LEC and MEC in the same rat. When the rat made spatial choices in a T-maze using visual scenes displayed on LCD screens, the inactivation of the MEC but not the LEC produced severe deficits in performance. However, when the task required the animal to push a jar or to dig in the sand in the jar using the same scene stimuli, the LEC but not the MEC became important. Our findings suggest that the entorhinal cortex is critical for scene-dependent mnemonic behavior, and the response modality may interact with a sensory modality to determine the involvement of the LEC and MEC in scene-based memory tasks. DOI: http://dx.doi.org/10.7554/eLife.21543.001 PMID:28169828

Identification of octopaminergic neurons that modulate sleep suppression by male sex drive

PubMed Central

Machado, Daniel R; Afonso, Dinis JS; Kenny, Alexandra R; Öztürk-Çolak, Arzu; Moscato, Emilia H; Mainwaring, Benjamin; Kayser, Matthew; Koh, Kyunghee

2017-01-01

Molecular and circuit mechanisms for balancing competing drives are not well understood. While circadian and homeostatic mechanisms generally ensure sufficient sleep at night, other pressing needs can overcome sleep drive. Here, we demonstrate that the balance between sleep and sex drives determines whether male flies sleep or court, and identify a subset of octopaminergic neurons (MS1) that regulate sleep specifically in males. When MS1 neurons are activated, isolated males sleep less, and when MS1 neurons are silenced, the normal male sleep suppression in female presence is attenuated and mating behavior is impaired. MS1 neurons do not express the sexually dimorphic FRUITLESS (FRU) transcription factor, but form male-specific contacts with FRU-expressing neurons; calcium imaging experiments reveal bidirectional functional connectivity between MS1 and FRU neurons. We propose octopaminergic MS1 neurons interact with the FRU network to mediate sleep suppression by male sex drive. DOI: http://dx.doi.org/10.7554/eLife.23130.001 PMID:28510528

A neural basis for the spatial suppression of visual motion perception

PubMed Central

Liu, Liu D; Haefner, Ralf M; Pack, Christopher C

2016-01-01

In theory, sensory perception should be more accurate when more neurons contribute to the representation of a stimulus. However, psychophysical experiments that use larger stimuli to activate larger pools of neurons sometimes report impoverished perceptual performance. To determine the neural mechanisms underlying these paradoxical findings, we trained monkeys to discriminate the direction of motion of visual stimuli that varied in size across trials, while simultaneously recording from populations of motion-sensitive neurons in cortical area MT. We used the resulting data to constrain a computational model that explained the behavioral data as an interaction of three main mechanisms: noise correlations, which prevented stimulus information from growing with stimulus size; neural surround suppression, which decreased sensitivity for large stimuli; and a read-out strategy that emphasized neurons with receptive fields near the stimulus center. These results suggest that paradoxical percepts reflect tradeoffs between sensitivity and noise in neuronal populations. DOI: http://dx.doi.org/10.7554/eLife.16167.001 PMID:27228283

A Novel Method for gamma - text{photons} Depth-of-Interaction Detection in Monolithic Scintillation Crystals

NASA Astrophysics Data System (ADS)

Pani, Roberto; Bettiol, Marco; Preziosi, Enrico; Borrazzo, Cristian; Pellegrini, Rosanna; González, Antonio J.; Conde, Pablo; Cinti, Maria Nerina; Fabbri, Andrea; Di Castro, Elisabetta; Majewski, Stan

2016-10-01

Achieved spatial resolution of the PET systems is often limited by the parallax error due to the lack of information about the Depth of Interaction (DoI) inside the crystal of the incoming 511 keV annihilation photons. The smaller the diameter of the PET ring and the thicker the scintillator are, the more this error affects imaging performance. In this work, a DoI calculator suitable for monolithic scintillation crystals and based on the shape of the scintillation light distribution at the photodetector surface has been proposed. To test the estimator performance, a test PET module with a 50 × 50 × 20 mm monolithic LYSO crystal coupled to a 12 × 12 SiPM array has been employed. In addition, for calibration and validation of the method, Geant4 simulations have been also used. The key result of the application of the proposed DoI estimator is obtaining a continuous DoI estimation with an average DoI resolution of about 5 mm in the 20 mm-thick crystal. Benefiting from the DoI estimation capabilities of the method, it has been also possible to achieve additional important goals, first of all reducing the parallax error. First, because the scintillation light collection varies as a function of the 3D position of the interaction of the annihilation photon inside the crystal, a method to correct this response variation via a proper 3D look-up-table is proposed. This has led to an improvement of about 35% in energy resolution. Moreover, a DoI-dependent position algorithm has been proposed, allowing an improvement of both planar (X-Y) position linearity and planar spatial resolution. This algorithm is specifically developed for the rows/columns multi-channel readout logic, that reduces the number of independent channels from N × N to N + N, where N is the number of SiPM photodetection elements (12 in our case) in each row and column. This development was performed in the framework of the MindView PET/MilI brain imaging project.

A depth-of-interaction PET detector using a stair-shaped reflector arrangement and a single-ended scintillation light readout.

PubMed

Son, Jeong-Whan; Lee, Min Sun; Lee, Jae Sung

2017-01-21

Positron emission tomography (PET) detectors with the ability to encode depth-of-interaction (DOI) information allow us to simultaneously improve the spatial resolution and sensitivity of PET scanners. In this study, we propose a DOI PET detector based on a stair-pattern reflector arrangement inserted between pixelated crystals and a single-ended scintillation light readout. The main advantage of the proposed method is its simplicity; DOI information is decoded from a flood map and the data can be simply acquired by using a single-ended readout system. Another potential advantage is that the two-step DOI detectors can provide the largest peak position distance in a flood map because two-dimensional peak positions can be evenly distributed. We conducted a Monte Carlo simulation and obtained flood maps. Then, we conducted experimental studies using two-step DOI arrays of 5  ×  5 Lu 1.9 Y 0.1 SiO 5 :Ce crystals with a cross-section of 1.7  ×  1.7 mm 2 and different detector configurations: an unpolished single-layer ( U S) array, a polished single-layer ( P S) array and a polished stacked two-layer ( P T) array. For each detector configuration, both air gaps and room-temperature vulcanization (RTV) silicone gaps were tested. Detectors U S and P T showed good peak separation in each scintillator with an average peak-to-valley ratio (PVR) and distance-to-width ratio (DWR) of 2.09 and 1.53, respectively. Detector P S RTV showed lower PVR and DWR (1.65 and 1.34, respectively). The configuration of detector P T Air is preferable for the construction of time-of-flight-DOI detectors because timing resolution was degraded by only about 40 ps compared with that of a non-DOI detector. The performance of detectors U S Air and P S RTV was lower than that of a non-DOI detector, and thus these designs are favorable when the manufacturing cost is more important than timing performance. The results demonstrate that the proposed DOI-encoding method is a promising candidate for PET scanners that require high resolution and sensitivity and operate with conventional acquisition systems.

Spatial resolution recovery utilizing multi-ray tracing and graphic processing unit in PET image reconstruction.

PubMed

Liang, Yicheng; Peng, Hao

2015-02-07

Depth-of-interaction (DOI) poses a major challenge for a PET system to achieve uniform spatial resolution across the field-of-view, particularly for small animal and organ-dedicated PET systems. In this work, we implemented an analytical method to model system matrix for resolution recovery, which was then incorporated in PET image reconstruction on a graphical processing unit platform, due to its parallel processing capacity. The method utilizes the concepts of virtual DOI layers and multi-ray tracing to calculate the coincidence detection response function for a given line-of-response. The accuracy of the proposed method was validated for a small-bore PET insert to be used for simultaneous PET/MR breast imaging. In addition, the performance comparisons were studied among the following three cases: 1) no physical DOI and no resolution modeling; 2) two physical DOI layers and no resolution modeling; and 3) no physical DOI design but with a different number of virtual DOI layers. The image quality was quantitatively evaluated in terms of spatial resolution (full-width-half-maximum and position offset), contrast recovery coefficient and noise. The results indicate that the proposed method has the potential to be used as an alternative to other physical DOI designs and achieve comparable imaging performances, while reducing detector/system design cost and complexity.

X-ray computed microtomography of sea ice - comment on "A review of air-ice chemical and physical interactions (AICI): liquids, quasi-liquids, and solids in snow" by Bartels-Rausch et al. (2014)

NASA Astrophysics Data System (ADS)

Obbard, R. W.

2015-07-01

This comment addresses a statement made in "A review of air-ice chemical and physical interactions (AICI): liquids, quasi-liquids, and solids in snow" by Bartels-Rausch et al. (Atmos. Chem. Phys., 14, 1587-1633, doi:10.5194/acp-14-1587-2014, 2014). Here we rebut the assertion that X-ray computed microtomography of sea ice fails to reveal liquid brine inclusions by discussing the phases present at the analysis temperature.

Effects of reflector and crystal surface on the performance of a depth-encoding PET detector with dual-ended readout

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ren, Silin; Yang, Yongfeng, E-mail: yfyang@ucdavis.edu; Cherry, Simon R.

Purpose: Depth encoding detectors are required to improve the spatial resolution and spatial resolution uniformity of small animal positron emission tomography (PET) scanners, as well as dedicated breast and brain scanners. Depth of interaction (DOI) can be measured by using dual-ended readout of lutetium oxyorthosilicate (LSO) scintillator arrays with position-sensitive avalanche photodiodes. Inter-crystal reflectors and crystal surface treatments play important roles in determining the performance of dual-ended detectors. In this paper, the authors evaluated five LSO arrays made with three different intercrystal reflectors and with either polished or unpolished crystal surfaces. Methods: The crystal size in all arrays was 1.5more » mm, which is typical of the detector size used in small animal and dedicated breast scanners. The LSO arrays were measured with dual-ended readout and were compared in terms of flood histogram, energy resolution, and DOI resolution performance. Results: The four arrays using enhanced specular reflector (ESR) and Toray reflector provided similar quality flood histograms and the array using Crystal Wrap reflector gave the worst flood histogram. The two arrays using ESR reflector provided the best energy resolution and the array using Crystal Wrap reflector yielded the worst energy resolution. All arrays except the polished ESR array provided good DOI resolution ranging from 1.9 mm to 2.9 mm. DOI resolution improved as the gradient in light collection efficiency with depth (GLCED) increased. The geometric mean energies were also calculated for these dual-ended readout detectors as an alternative to the conventional summed total energy. It was shown that the geometric mean energy is advantageous in that it provides more uniform photopeak amplitude at different depths for arrays with high GLCED, and is beneficial in event selection by allowing a fixed energy window independent of depth. A new method of DOI calculation that improved the linearity of DOI ratio vs depth and simplifies the DOI calibration procedure also was developed and tested. Conclusions: The results of these studies provide useful guidance in selecting the proper reflectors and crystal surface treatments when LSO arrays are used for high-resolution PET applications in small animal scanners or dedicated breast and brain scanners.« less

Female mice ultrasonically interact with males during courtship displays

PubMed Central

Neunuebel, Joshua P; Taylor, Adam L; Arthur, Ben J; Egnor, SE Roian

2015-01-01

During courtship males attract females with elaborate behaviors. In mice, these displays include ultrasonic vocalizations. Ultrasonic courtship vocalizations were previously attributed to the courting male, despite evidence that both sexes produce virtually indistinguishable vocalizations. Because of this similarity, and the difficulty of assigning vocalizations to individuals, the vocal contribution of each individual during courtship is unknown. To address this question, we developed a microphone array system to localize vocalizations from socially interacting, individual adult mice. With this system, we show that female mice vocally interact with males during courtship. Males and females jointly increased their vocalization rates during chases. Furthermore, a female's participation in these vocal interactions may function as a signal that indicates a state of increased receptivity. Our results reveal a novel form of vocal communication during mouse courtship, and lay the groundwork for a mechanistic dissection of communication during social behavior. DOI: http://dx.doi.org/10.7554/eLife.06203.001 PMID:26020291

Decoupling global biases and local interactions between cell biological variables

PubMed Central

Zaritsky, Assaf; Obolski, Uri; Gan, Zhuo; Reis, Carlos R; Kadlecova, Zuzana; Du, Yi; Schmid, Sandra L; Danuser, Gaudenz

2017-01-01

Analysis of coupled variables is a core concept of cell biological inference, with co-localization of two molecules as a proxy for protein interaction being a ubiquitous example. However, external effectors may influence the observed co-localization independently from the local interaction of two proteins. Such global bias, although biologically meaningful, is often neglected when interpreting co-localization. Here, we describe DeBias, a computational method to quantify and decouple global bias from local interactions between variables by modeling the observed co-localization as the cumulative contribution of a global and a local component. We showcase four applications of DeBias in different areas of cell biology, and demonstrate that the global bias encapsulates fundamental mechanistic insight into cellular behavior. The DeBias software package is freely accessible online via a web-server at https://debias.biohpc.swmed.edu. DOI: http://dx.doi.org/10.7554/eLife.22323.001 PMID:28287393

Influence of detector pixel size, TOF resolution and DOI on image quality in MR-compatible whole-body PET.

PubMed

Thoen, Hendrik; Keereman, Vincent; Mollet, Pieter; Van Holen, Roel; Vandenberghe, Stefaan

2013-09-21

The optimization of a whole-body PET system remains a challenging task, as the imaging performance is influenced by a complex interaction of different design parameters. However, it is not always clear which parameters have the largest impact on image quality and are most eligible for optimization. To determine this, we need to be able to assess their influence on image quality. We performed Monte-Carlo simulations of a whole-body PET scanner to predict the influence on image quality of three detector parameters: the TOF resolution, the transverse pixel size and depth-of-interaction (DOI)-correction. The inner diameter of the PET scanner was 65 cm, small enough to allow physical integration into a simultaneous PET-MR system. Point sources were used to evaluate the influence of transverse pixel size and DOI-correction on spatial resolution as function of radial distance. To evaluate the influence on contrast recovery and pixel noise a cylindrical phantom of 35 cm diameter was used, representing a large patient. The phantom contained multiple hot lesions with 5 mm diameter. These lesions were placed at radial distances of 50, 100 and 150 mm from the center of the field-of-view, to be able to study the effects at different radial positions. The non-prewhitening (NPW) observer was used for objective analysis of the detectability of the hot lesions in the cylindrical phantom. Based on this analysis the NPW-SNR was used to quantify the relative improvements in image quality due to changes of the variable detector parameters. The image quality of a whole-body PET scanner can be improved significantly by reducing the transverse pixel size from 4 to 2.6 mm and improving the TOF resolution from 600 to 400 ps and further from 400 to 200 ps. Compared to pixel size, the TOF resolution has the larger potential to increase image quality for the simulated phantom. The introduction of two layer DOI-correction only leads to a modest improvement for the spheres at radial distance of 150 mm from the center of the transaxial FOV.

Determining the Depth of Injury in Bioengineered Tissue Models of Cornea and Conjunctiva for the Prediction of All Three Ocular GHS Categories

PubMed Central

Zorn-Kruppa, Michaela; Houdek, Pia; Wladykowski, Ewa; Engelke, Maria; Bartok, Melinda; Mewes, Karsten R.; Moll, Ingrid; Brandner, Johanna M.

2014-01-01

The depth of injury (DOI) is a mechanistic correlate to the ocular irritation response. Attempts to quantitatively determine the DOI in alternative tests have been limited to ex vivo animal eyes by fluorescent staining for biomarkers of cell death and viability in histological cross sections. It was the purpose of this study to assess whether DOI could also be measured by means of cell viability detected by the MTT assay using 3-dimensional (3D) reconstructed models of cornea and conjunctiva. The formazan-free area of metabolically inactive cells in the tissue after topical substance application is used as the visible correlate of the DOI. Areas of metabolically active or inactive cells are quantitatively analyzed on cryosection images with ImageJ software analysis tools. By incorporating the total tissue thickness, the relative MTT-DOI (rMTT-DOI) was calculated. Using the rMTT-DOI and human reconstructed cornea equivalents, we developed a prediction model based on suitable viability cut-off values. We tested 25 chemicals that cover the whole range of eye irritation potential based on the globally harmonized system of classification and labelling of chemicals (GHS). Principally, the MTT-DOI test method allows distinguishing between the cytotoxic effects of the different chemicals in accordance with all 3 GHS categories for eye irritation. Although the prediction model is slightly over-predictive with respect to non-irritants, it promises to be highly valuable to discriminate between severe irritants (Cat. 1), and mild to moderate irritants (Cat. 2). We also tested 3D conjunctiva models with the aim to specifically address conjunctiva-damaging substances. Using the MTT-DOI method in this model delivers comparable results as the cornea model, but does not add additional information. However, the MTT-DOI method using reconstructed cornea models already provided good predictability that was superior to the already existing established in vitro/ex vivo methods. PMID:25494045

Erratum to: Adsorption energies of H and H2: a quantum-chemical study. Eur. Phys. J. D 71: 45 (2017), DOI: 10.1140/epjd/e2017-70610-4

NASA Astrophysics Data System (ADS)

Sil, Milan; Gorai, Prasanta; Das, Ankan; Sahu, Dipen; Chakrabarti, Sandip K.

2017-12-01

Contribution to the Topical Issue "Low-Energy Interactions related to Atmospheric and Extreme Conditions", edited by S. Ptasinska, M. Smialek-Telega, A. Milosavljevic and B. Sivaraman.The online version of the original article can be found at http://https://doi.org/10.1140/epjd/e2017-70610-4.

Reply to Comment by Nishimura Et Al.

NASA Astrophysics Data System (ADS)

Mozer, F. S.; Hull, A.; Lejosne, S.; Vasko, I. Y.

2018-03-01

Nishimura et al. (2010, https://doi.org/10.1126/science.1193186, 2011, https://doi.org/10.1029/2011JA016876, 2013, https://doi.org/10.1029/2012JA018242, and in their comment, hereafter called N18) have suggested that chorus waves interact with equatorial electrons to produce pulsating auroras. We agree that chorus can scatter electrons >10 keV, as do Time Domain Structures (TDSs). Lower-energy electrons occurring in pulsating auroras cannot be produced by chorus, but such electrons are scattered and accelerated by TDS. TDSs often occur with chorus and have power in their spectra at chorus frequencies. Thus, the absence of power at low frequencies is not evidence that TDSs are absent, as an example shows. Through examination of equatorial electric field waveforms and electron pitch angle distributions measured on the Time History of Events and Macroscale Interactions during Substorms satellites (in place of examining field and particle spectra, as done by Nishimura et al.), we show that chorus cannot produce the field-aligned electrons associated with pulsating auroras in the Nishimura et al. (2010, https://doi.org/10.1126/science.1193186) events, but TDSs can. Equatorial field-aligned electron distributions associated with pulsating auroras and created by TDS in the absence of chorus or any other wave at the equator are also shown.

Tsunami mitigation - redistribution of energy

NASA Astrophysics Data System (ADS)

Kadri, Usama

2017-04-01

Tsunamis are water waves caused by the displacement of a large volume of water, in the deep ocean or a large lake, following an earthquake, landslide, underwater explosion, meteorite impacts, or other violent geological events. On the coastline, the resulting waves evolve from unnoticeable to devastating, reaching heights of tens of meters and causing destruction of property and loss of life. Over 225,000 people were killed in the 2004 Indian Ocean tsunami alone. For many decades, scientists have been studying tsunami, and progress has been widely reported in connection with the causes (1), forecasting (2), and recovery (3). However, none of the studies ratifies the approach of a direct mitigation of tsunamis, with the exception of mitigation using submarine barriers (e.g. see Ref. (4)). In an attempt to open a discussion on direct mitigation, I examine the feasibility of redistributing the total energy of a very long surface ocean (gravity) wave over a larger space through nonlinear resonant interaction with two finely tuned acoustic-gravity waves (see Refs. (5-8)). Theoretically, while the energy input in the acoustic-gravity waves required for an effective interaction is comparable to that in a tsunami (i.e. impractically large), employing the proposed mitigation technique the initial tsunami amplitude could be reduced substantially resulting in a much milder impact at the coastline. Moreover, such a technique would allow for the harnessing of the tsunami's own energy. Practically, this mitigation technique requires the design of highly accurate acoustic-gravity wave frequency transmitters or modulators, which is a rather challenging ongoing engineering problem. References 1. E. Bryant, 2014. Tsunami: the underrated hazard. Springer, doi:10.1007/978-3-319- 06133-7. 2. V. V. Titov, F. I. Gonza`lez, E. N. Bernard, M. C. Eble, H. O. Mofjeld, J. C. Newman, A. J. Venturato, 2005. Real-Time Tsunami Forecasting: Challenges and Solutions. Nat. Hazards 35:41-58, doi:10.1007/1-4020-3607-8 3 3. E. Check, 2005. Natural disasters: Roots of recovery. Nature 438, 910-911, doi:10.1038/438910a. 4. A. M. Fridman, L. S. Alperovich, L. Shemer, L. Pustil'nik, D. Shtivelman, A. G. Marchuk, D. Liberzon, 2010. Tsunami wave suppression using submarine barriers. Phys. Usp. 53 809-816, doi:10.3367/UFNe.0180.201008d.0843. 5. U. Kadri, M. Stiassnie, 2013. Generation of an acoustic-gravity wave by two gravity waves, and their mutual interaction. J. Fluid Mech. 735, R6, doi:10.1017/jfm.2013.539. 6. U. Kadri, 2015. Wave motion in a heavy compressible fluid: revisited. European Journal of Mechanics - B/Fluids, 49(A), 50-57, doi:10.1016/j.euromechflu.2014.07.008 7. U. Kadri, T.R. Akylas, 2016. On resonant triad interactions of acoustic-gravity waves. J. Fluid Mech., 788, R1(12 pages), doi:10.1017/jfm.2015.721. 8. U. Kadri, 2016. Triad resonance between a surface-gravity wave and two high frequency hydro-acoustic waves. Eur. J. Mech. B/Fluid, 55(1), 157-161, doi:10.1016/j.euromechflu.2015.09.008.

Reaching 200-ps timing resolution in a time-of-flight and depth-of-interaction positron emission tomography detector using phosphor-coated crystals and high-density silicon photomultipliers

PubMed Central

Kwon, Sun Il; Ferri, Alessandro; Gola, Alberto; Berg, Eric; Piemonte, Claudio; Cherry, Simon R.; Roncali, Emilie

2016-01-01

Abstract. Current research in the field of positron emission tomography (PET) focuses on improving the sensitivity of the scanner with thicker detectors, extended axial field-of-view, and time-of-flight (TOF) capability. These create the need for depth-of-interaction (DOI) encoding to correct parallax errors. We have proposed a method to encode DOI using phosphor-coated crystals. Our initial work using photomultiplier tubes (PMTs) demonstrated the possibilities of the proposed method, however, a major limitation of PMTs for this application is poor quantum efficiency in yellow light, corresponding to the wavelengths of the converted light by the phosphor coating. In contrast, the red-green-blue-high-density (RGB-HD) silicon photomultipliers (SiPMs) have a high photon detection efficiency across the visible spectrum. Excellent coincidence resolving time (CRT; <210  ps) was obtained by coupling RGB-HD SiPMs and  3 × 3 × 20  mm3 lutetium fine silicate crystals coated on a third of one of their lateral sides. Events were classified in three DOI bins (∼6.7-mm width) with an average sensitivity of 83.1%. A CRT of ∼200  ps combined with robust DOI encoding is a marked improvement in the phosphor-coated approach that we pioneered. For the first time, we read out these crystals with SiPMs and clearly demonstrated the potential of the RGB-HD SiPMs for this TOF-DOI PET detector. PMID:27921069

Evolution of DOI Usage and Registration

NASA Astrophysics Data System (ADS)

James, N.; Wanchoo, L.

2017-12-01

NASA's Earth Science Data and Information System (ESDIS) Project has implemented an automated system for assigning Digital Object Identifiers (DOIs) to Earth Science data products being managed by its network of 12 distributed active archive centers (DAACs). Using the ESDIS DOI system, over 3000 DOIs have been assigned, registered, and made publicly accessible while over 1000 assigned DOIs are being held in reserve until ready for public use. The goal is to assign a DOI to each of the 8000+ data collections under ESDIS management. DOIs make it easier for researchers to discover and use earth science data and they enable users to provide valid citations for the data they use in research. Also for the researcher wishing to reproduce the results presented in science publications, the DOI can be used to locate the exact data or data products being cited. ESDIS DOIs also provide data "Provenance" which is information about the creation and history of the data in question. This would include when the data was collected, which instrument was used to collect the data, and the version of the product at the time the DOI was assigned. Over the past few years, requests for DOIs have increased significantly as DAACs assign DOIs to both legacy data from earlier missions and new data products from in-orbit missions. This study will evaluate the evolution of DOI registration and its usage over those years comparing data products as they are organized by mission, science discipline and data product level. It is hoped that the study results will help NASA determine how to prioritize future products for DOI assignment and inform future studies that would identify trends over time of increased use of data citations resulting in increased discovery and distribution of NASA Earth science data products.

Dual interaction of scaffold protein Tim44 of mitochondrial import motor with channel-forming translocase subunit Tim23

PubMed Central

Ting, See-Yeun; Yan, Nicholas L; Schilke, Brenda A; Craig, Elizabeth A

2017-01-01

Proteins destined for the mitochondrial matrix are targeted to the inner membrane Tim17/23 translocon by their presequences. Inward movement is driven by the matrix-localized, Hsp70-based motor. The scaffold Tim44, interacting with the matrix face of the translocon, recruits other motor subunits and binds incoming presequence. The basis of these interactions and their functional relationships remains unclear. Using site-specific in vivo crosslinking and genetic approaches in Saccharomyces cerevisiae, we found that both domains of Tim44 interact with the major matrix-exposed loop of Tim23, with the C-terminal domain (CTD) binding Tim17 as well. Results of in vitro experiments showed that the N-terminal domain (NTD) is intrinsically disordered and binds presequence near a region important for interaction with Hsp70 and Tim23. Our data suggest a model in which the CTD serves primarily to anchor Tim44 to the translocon, whereas the NTD is a dynamic arm, interacting with multiple components to drive efficient translocation. DOI: http://dx.doi.org/10.7554/eLife.23609.001 PMID:28440746

Viruses are a dominant driver of protein adaptation in mammals

PubMed Central

Enard, David; Cai, Le; Gwennap, Carina; Petrov, Dmitri A

2016-01-01

Viruses interact with hundreds to thousands of proteins in mammals, yet adaptation against viruses has only been studied in a few proteins specialized in antiviral defense. Whether adaptation to viruses typically involves only specialized antiviral proteins or affects a broad array of virus-interacting proteins is unknown. Here, we analyze adaptation in ~1300 virus-interacting proteins manually curated from a set of 9900 proteins conserved in all sequenced mammalian genomes. We show that viruses (i) use the more evolutionarily constrained proteins within the cellular functions they interact with and that (ii) despite this high constraint, virus-interacting proteins account for a high proportion of all protein adaptation in humans and other mammals. Adaptation is elevated in virus-interacting proteins across all functional categories, including both immune and non-immune functions. We conservatively estimate that viruses have driven close to 30% of all adaptive amino acid changes in the part of the human proteome conserved within mammals. Our results suggest that viruses are one of the most dominant drivers of evolutionary change across mammalian and human proteomes. DOI: http://dx.doi.org/10.7554/eLife.12469.001 PMID:27187613

25 CFR 1000.232 - When must DOI respond to a request for reconsideration?

Code of Federal Regulations, 2010 CFR

2010-04-01

... INTERIOR ANNUAL FUNDING AGREEMENTS UNDER THE TRIBAL SELF-GOVERNMENT ACT AMENDMENTS TO THE INDIAN SELF-DETERMINATION AND EDUCATION ACT Waiver of Regulations § 1000.232 When must DOI respond to a request for...

Characterization of stacked-crystal PET detector designs for measurement of both TOF and DOI.

PubMed

Schmall, Jeffrey P; Surti, Suleman; Karp, Joel S

2015-05-07

A PET detector with good timing resolution and two-level depth-of-interaction (DOI) discrimination can be constructed using a single-ended readout of scintillator stacks of Lanthanum Bromide (LaBr3), with various Cerium dopant concentrations, including pure Cerium Bromide (CeBr3). The stacked crystal geometry creates a unique signal shape for interactions occurring in each layer, which can be used to identify the DOI, while retaining the inherently good timing properties of LaBr3 and CeBr3. In this work, single pixel elements are used to optimize the choice of scintillator, coupling of layers, and type of photodetector, evaluating the performance using a fast, single-channel photomultiplier tube (PMT) and a single 4 × 4 mm(2) silicon photomultiplier (SiPM). We also introduce a method to quantify and evaluate the DOI discrimination accuracy. From signal shape measurements using fast waveform sampling, we found that in addition to differences in signal rise times, between crystal layers, there were also differences in the signal fall times. A DOI accuracy of 98% was achieved using our classification method for a stacked crystal pair, consisting of a 15 mm long LaBr3(Ce:20%) crystal on top of a 15 mm long CeBr3 crystal, readout using a PMT. A DOI accuracy of 95% was measured with a stack of two, identical, 12 mm long, CeBr3 crystals. The DOI accuracy of this crystal pair was reduced to 91% when using a SiPM for readout. For the stack of two, 12 mm long, CeBr3 crystals, a coincidence timing resolution (average of timing results from the top and bottom layer) of 199 ps was measured using a PMT, and this was improved to 153 ps when using a SiPM. These results show that with stacked LaBr3/CeBr3 scintillators and fast waveform sampling nearly perfect DOI accuracy can be achieved with excellent timing resolution-timing resolution that is only minimally degraded compared to results from a single CeBr3 crystal of comparable length to the stacked crystals. The interface in the stacked crystal geometry itself plays a major role in creating the differences in signal shape and this can be used to construct stacked DOI detectors using the same scintillator type, thereby simplifying and broadening the application of this technique.

Characterization of stacked-crystal PET detector designs for measurement of both TOF and DOI

PubMed Central

Schmall, Jeffrey P; Surti, Suleman; Karp, Joel S

2015-01-01

A PET detector with good timing resolution and two-level depth-of-interaction (DOI) discrimination can be constructed using a single-ended readout of scintillator stacks of Lanthanum Bromide (LaBr3), with various Cerium dopant concentrations, including pure Cerium Bromide (CeBr3). The stacked crystal geometry creates a unique signal shape for interactions occurring in each layer, which can be used to identify the DOI, while retaining the inherently good timing properties of LaBr3 and CeBr3. In this work, single pixel elements are used to optimize the choice of scintillator, coupling of layers, and type of photodetector, evaluating the performance using a fast, single-channel photomultiplier tube (PMT) and a single 4×4 mm2 silicon photomultiplier (SiPM). We also introduce a method to quantify and evaluate the DOI discrimination accuracy. From signal shape measurements using fast waveform sampling, we found that in addition to differences in signal rise times, between crystal layers, there were also differences in the signal fall times. A DOI accuracy of 98% was achieved using our classification method for a stacked crystal pair, consisting of a 15-mm long LaBr3(Ce:20%) crystal on top of a 15-mm long CeBr3 crystal, readout using a PMT. A DOI accuracy of 95% was measured with a stack of two, identical, 12-mm long, CeBr3 crystals. The DOI accuracy of this crystal pair was reduced to 91% when using a SiPM for readout. For the stack of two, 12-mm long, CeBr3 crystals, a coincidence timing resolution (average of timing results from the top and bottom layer) of 199 ps was measured using a PMT, and this was improved to 153 ps when using a SiPM. These results show that with stacked LaBr3/CeBr3 scintillators and fast waveform sampling nearly perfect DOI accuracy can be achieved with excellent timing resolution—timing resolution that is only minimally degraded compared to results from a single CeBr3 crystal of comparable length to the stacked crystals. The interface in the stacked crystal geometry itself plays a major role in creating the differences in signal shape and this can be used to construct stacked DOI detectors using the same scintillator type, thereby simplifying and broadening the application of this technique. PMID:25860172

Impact of river restoration on groundwater - surface water - interactions

NASA Astrophysics Data System (ADS)

Kurth, Anne-Marie; Schirmer, Mario

2014-05-01

Since the end of the 19th century, flood protection was increasingly based on the construction of impermeable dams and side walls (BWG, 2003). In spite of providing flood protection, these measures also limited the connectivity between the river and the land, restricted the area available for flooding, and hampered the natural flow dynamics of the river. Apart from the debilitating effect on riverine ecosystems due to loss of habitats, these measures also limited bank filtration, inhibited the infiltration of storm water, and affected groundwater-surface water-interactions. This in turn had a profound effect on ecosystem health, as a lack of groundwater-surface water interactions led to decreased cycling of pollutants and nutrients in the hyporheic zone and limited the moderation of the water temperature (EA, 2009). In recent decades, it has become apparent that further damages to riverine ecosystems must be prohibited, as the damages to ecology, economy and society surmount any benefits gained from exploiting them. Nowadays, the restoration of rivers is a globally accepted means to restore ecosystem functioning, protect water resources and amend flood protection (Andrea et al., 2012; Palmer et al., 2005; Wortley et al., 2013). In spite of huge efforts regarding the restoration of rivers over the last 30 years, the question of its effectiveness remains, as river restorations often reconstruct a naturally looking rather than a naturally functioning stream (EA, 2009). We therefore focussed our research on the effectiveness of river restorations, represented by the groundwater-surface water-interactions. Given a sufficiently high groundwater level, a lack of groundwater-surface water-interactions after restoration may indicate that the vertical connectivity in the stream was not fully restored. In order to investigate groundwater-surface water-interactions we determined the thermal signature on the stream bed and in +/- 40 cm depth by using Distributed Temperature Sensing (DTS), a fibre optical method for temperature determination over long distances (Selker et al., 2006). Thermal signatures were determined in a small urban stream before and after restoration and compared to streams in natural and near-natural settings. BWG BUNDESAMT FÜR WASSER UND GEOLOGIE, 2003. Die Geschichte des Hochwasserschutzes in der Schweiz. Bericht des BWG, Serie Wasser. Biel. 208 p. EA ENVIRONMENT AGENCY (UK), 2009. The Hyporheic Handbook: A handbook on the groundwater-surface water interface and hyporheic zone for environment managers. Bristol. 280 p. ANDREA, F., GSCHÖPF, C., BLASCHKE, A.P., WEIGELHOFER, G., AND RECKENDORFER, W., 2012. Ecological niche models for the evaluation of management options in urban floodplain - conservation vs. restoration purposes. Environ. Sci. Policy, http://dx.doi.org/10.1016/j.envsci.2012.08.011. PALMER, M.A., BERNHARDT, E.S., ALLAN, J.D., LAKE, P.S., ALEXANDER, G., BROOKS, S., CARR, J., CLAYTON, S., DAHM, C.N., FOLLSTAD SHAH, J., GALAT, D.L., LOSS, S.G., GOODWIN, P., HART, D.D., HASSETT, B., JENKINSON, R., KONDOLF, G.M., LAVE, R., MEYER, J.L., O`DONNELL, T.K., PAGANO, L. AND SUDDUTH, E., 2005. Standards for ecologically successful river restoration. Journal of Applied Ecology, 42, pp. 208 - 217. DOI 10.1111/j.1365-2664.2005.01004.x. WORTLEY, L., HERO, J-M., HOWES, M., 2013. Evaluating Ecological Restoration Success: A Review of the Literature. Restoration Ecology, 21 (5), pp. 537 - 543. DOI 10.1111/rec.12028. SELKER, J.S., THEVENAZ, L., HUWALD, H., MALLET, A., LUXEMBURG, W., VAN DE GIESEN, N., STEJSKAL, M., ZEMAN, J., WESTHOFF, M., AND PARLANGE, M.B., 2006. Distributed fibre-optic temperature sensing for hydrologic systems. Water Resources Research, 42(12), W12202.

DOI Use of AVIRIS Data in Natural Resources Management: A Technology Transfer Project Status Report

NASA Technical Reports Server (NTRS)

Getter, James R.; Wickland, Diane

1998-01-01

A meeting was held in December 1996, attended by representatives from Department of the Interior (DOI) and National Aeronautical and Space Administration (NASA) at the request of Department of the Interior Secretary, Bruce Babbitt and NASA, Administrator Director Dan Goldin, to discuss the use of hyperspectral systems and related remote sensing technologies in addressing environmental issues of environmental importance to the (DOI). It was determined that NASA/DOI Coordination be established, comprised of representatives from each agency, designated to address the environmental issues and resulting technologies. A steering committee was formed consisting of representatives from NASA Headquarters, NASA PI's from University California-Davis, University of Colorado-Boulder, University of New Hampshire and DOI Bureaus (Indian Affairs, Land Management, Reclamation, National Park Service, and US Geological Survey).

Use of internal scintillator radioactivity to calibrate DOI function of a PET detector with a dual-ended-scintillator readout

PubMed Central

Bircher, Chad; Shao, Yiping

2012-01-01

Purpose: Positron emission tomography (PET) detectors that use a dual-ended-scintillator readout to measure depth-of-interaction (DOI) must have an accurate DOI function to provide the relationship between DOI and signal ratios to be used for detector calibration and recalibration. In a previous study, the authors used a novel and simple method to accurately and quickly measure DOI function by irradiating the detector with an external uniform flood source; however, as a practical concern, implementing external uniform flood sources in an assembled PET system is technically challenging and expensive. In the current study, therefore, the authors investigated whether the same method could be used to acquire DOI function from scintillator-generated (i.e., internal) radiation. The authors also developed a method for calibrating the energy scale necessary to select the events within the desired energy window. Methods: The authors measured the DOI function of a PET detector with lutetium yttrium orthosilicate (LYSO) scintillators. Radiation events originating from the scintillators’ internal Lu-176 beta decay were used to measure DOI functions which were then compared with those measured from both an external uniform flood source and an electronically collimated external point source. The authors conducted these studies with several scintillators of differing geometries (1.5 × 1.5 and 2.0 × 2.0 mm2 cross-section area and 20, 30, and 40 mm length) and various surface finishes (mirror-finishing, saw-cut rough, and other finishes in between), and in a prototype array. Results: All measured results using internal and external radiation sources showed excellent agreement in DOI function measurement. The mean difference among DOI values for all scintillators measured from internal and external radiation sources was less than 1.0 mm for different scintillator geometries and various surface finishes. Conclusions: The internal radioactivity of LYSO scintillators can be used to accurately measure DOI function in PET detectors, regardless of scintillator geometry or surface finish. Because an external radiation source is not needed, this method of DOI function measurement can be practically applied to individual PET detectors as well as assembled systems. PMID:22320787

Use of internal scintillator radioactivity to calibrate DOI function of a PET detector with a dual-ended-scintillator readout.

PubMed

Bircher, Chad; Shao, Yiping

2012-02-01

Positron emission tomography (PET) detectors that use a dual-ended-scintillator readout to measure depth-of-interaction (DOI) must have an accurate DOI function to provide the relationship between DOI and signal ratios to be used for detector calibration and recalibration. In a previous study, the authors used a novel and simple method to accurately and quickly measure DOI function by irradiating the detector with an external uniform flood source; however, as a practical concern, implementing external uniform flood sources in an assembled PET system is technically challenging and expensive. In the current study, therefore, the authors investigated whether the same method could be used to acquire DOI function from scintillator-generated (i.e., internal) radiation. The authors also developed a method for calibrating the energy scale necessary to select the events within the desired energy window. The authors measured the DOI function of a PET detector with lutetium yttrium orthosilicate (LYSO) scintillators. Radiation events originating from the scintillators' internal Lu-176 beta decay were used to measure DOI functions which were then compared with those measured from both an external uniform flood source and an electronically collimated external point source. The authors conducted these studies with several scintillators of differing geometries (1.5 × 1.5 and 2.0 × 2.0 mm(2) cross-section area and 20, 30, and 40 mm length) and various surface finishes (mirror-finishing, saw-cut rough, and other finishes in between), and in a prototype array. All measured results using internal and external radiation sources showed excellent agreement in DOI function measurement. The mean difference among DOI values for all scintillators measured from internal and external radiation sources was less than 1.0 mm for different scintillator geometries and various surface finishes. The internal radioactivity of LYSO scintillators can be used to accurately measure DOI function in PET detectors, regardless of scintillator geometry or surface finish. Because an external radiation source is not needed, this method of DOI function measurement can be practically applied to individual PET detectors as well as assembled systems.

Use of internal scintillator radioactivity to calibrate DOI function of a PET detector with a dual-ended-scintillator readout

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bircher, Chad; Shao Yiping

Purpose: Positron emission tomography (PET) detectors that use a dual-ended-scintillator readout to measure depth-of-interaction (DOI) must have an accurate DOI function to provide the relationship between DOI and signal ratios to be used for detector calibration and recalibration. In a previous study, the authors used a novel and simple method to accurately and quickly measure DOI function by irradiating the detector with an external uniform flood source; however, as a practical concern, implementing external uniform flood sources in an assembled PET system is technically challenging and expensive. In the current study, therefore, the authors investigated whether the same method couldmore » be used to acquire DOI function from scintillator-generated (i.e., internal) radiation. The authors also developed a method for calibrating the energy scale necessary to select the events within the desired energy window. Methods: The authors measured the DOI function of a PET detector with lutetium yttrium orthosilicate (LYSO) scintillators. Radiation events originating from the scintillators' internal Lu-176 beta decay were used to measure DOI functions which were then compared with those measured from both an external uniform flood source and an electronically collimated external point source. The authors conducted these studies with several scintillators of differing geometries (1.5 x 1.5 and 2.0 x 2.0 mm{sup 2} cross-section area and 20, 30, and 40 mm length) and various surface finishes (mirror-finishing, saw-cut rough, and other finishes in between), and in a prototype array. Results: All measured results using internal and external radiation sources showed excellent agreement in DOI function measurement. The mean difference among DOI values for all scintillators measured from internal and external radiation sources was less than 1.0 mm for different scintillator geometries and various surface finishes. Conclusions: The internal radioactivity of LYSO scintillators can be used to accurately measure DOI function in PET detectors, regardless of scintillator geometry or surface finish. Because an external radiation source is not needed, this method of DOI function measurement can be practically applied to individual PET detectors as well as assembled systems.« less

Biomolecular interactions modulate macromolecular structure and dynamics in atomistic model of a bacterial cytoplasm

PubMed Central

Yu, Isseki; Mori, Takaharu; Ando, Tadashi; Harada, Ryuhei; Jung, Jaewoon; Sugita, Yuji; Feig, Michael

2016-01-01

Biological macromolecules function in highly crowded cellular environments. The structure and dynamics of proteins and nucleic acids are well characterized in vitro, but in vivo crowding effects remain unclear. Using molecular dynamics simulations of a comprehensive atomistic model cytoplasm we found that protein-protein interactions may destabilize native protein structures, whereas metabolite interactions may induce more compact states due to electrostatic screening. Protein-protein interactions also resulted in significant variations in reduced macromolecular diffusion under crowded conditions, while metabolites exhibited significant two-dimensional surface diffusion and altered protein-ligand binding that may reduce the effective concentration of metabolites and ligands in vivo. Metabolic enzymes showed weak non-specific association in cellular environments attributed to solvation and entropic effects. These effects are expected to have broad implications for the in vivo functioning of biomolecules. This work is a first step towards physically realistic in silico whole-cell models that connect molecular with cellular biology. DOI: http://dx.doi.org/10.7554/eLife.19274.001 PMID:27801646

A hierarchy of timescales explains distinct effects of local inhibition of primary visual cortex and frontal eye fields

PubMed Central

Cocchi, Luca; Sale, Martin V; L Gollo, Leonardo; Bell, Peter T; Nguyen, Vinh T; Zalesky, Andrew; Breakspear, Michael; Mattingley, Jason B

2016-01-01

Within the primate visual system, areas at lower levels of the cortical hierarchy process basic visual features, whereas those at higher levels, such as the frontal eye fields (FEF), are thought to modulate sensory processes via feedback connections. Despite these functional exchanges during perception, there is little shared activity between early and late visual regions at rest. How interactions emerge between regions encompassing distinct levels of the visual hierarchy remains unknown. Here we combined neuroimaging, non-invasive cortical stimulation and computational modelling to characterize changes in functional interactions across widespread neural networks before and after local inhibition of primary visual cortex or FEF. We found that stimulation of early visual cortex selectively increased feedforward interactions with FEF and extrastriate visual areas, whereas identical stimulation of the FEF decreased feedback interactions with early visual areas. Computational modelling suggests that these opposing effects reflect a fast-slow timescale hierarchy from sensory to association areas. DOI: http://dx.doi.org/10.7554/eLife.15252.001 PMID:27596931

The molecular mechanism of nuclear transport revealed by atomic-scale measurements

PubMed Central

Hough, Loren E; Dutta, Kaushik; Sparks, Samuel; Temel, Deniz B; Kamal, Alia; Tetenbaum-Novatt, Jaclyn; Rout, Michael P; Cowburn, David

2015-01-01

Nuclear pore complexes (NPCs) form a selective filter that allows the rapid passage of transport factors (TFs) and their cargoes across the nuclear envelope, while blocking the passage of other macromolecules. Intrinsically disordered proteins (IDPs) containing phenylalanyl-glycyl (FG)-rich repeats line the pore and interact with TFs. However, the reason that transport can be both fast and specific remains undetermined, through lack of atomic-scale information on the behavior of FGs and their interaction with TFs. We used nuclear magnetic resonance spectroscopy to address these issues. We show that FG repeats are highly dynamic IDPs, stabilized by the cellular environment. Fast transport of TFs is supported because the rapid motion of FG motifs allows them to exchange on and off TFs extremely quickly through transient interactions. Because TFs uniquely carry multiple pockets for FG repeats, only they can form the many frequent interactions needed for specific passage between FG repeats to cross the NPC. DOI: http://dx.doi.org/10.7554/eLife.10027.001 PMID:26371551

Tracking transcription factor mobility and interaction in Arabidopsis roots with fluorescence correlation spectroscopy

PubMed Central

Clark, Natalie M; Hinde, Elizabeth; Winter, Cara M; Fisher, Adam P; Crosti, Giuseppe; Blilou, Ikram; Gratton, Enrico; Benfey, Philip N; Sozzani, Rosangela

2016-01-01

To understand complex regulatory processes in multicellular organisms, it is critical to be able to quantitatively analyze protein movement and protein-protein interactions in time and space. During Arabidopsis development, the intercellular movement of SHORTROOT (SHR) and subsequent interaction with its downstream target SCARECROW (SCR) control root patterning and cell fate specification. However, quantitative information about the spatio-temporal dynamics of SHR movement and SHR-SCR interaction is currently unavailable. Here, we quantify parameters including SHR mobility, oligomeric state, and association with SCR using a combination of Fluorescent Correlation Spectroscopy (FCS) techniques. We then incorporate these parameters into a mathematical model of SHR and SCR, which shows that SHR reaches a steady state in minutes, while SCR and the SHR-SCR complex reach a steady-state between 18 and 24 hr. Our model reveals the timing of SHR and SCR dynamics and allows us to understand how protein movement and protein-protein stoichiometry contribute to development. DOI: http://dx.doi.org/10.7554/eLife.14770.001 PMID:27288545

An internal thioester in a pathogen surface protein mediates covalent host binding

PubMed Central

Walden, Miriam; Edwards, John M; Dziewulska, Aleksandra M; Bergmann, Rene; Saalbach, Gerhard; Kan, Su-Yin; Miller, Ona K; Weckener, Miriam; Jackson, Rosemary J; Shirran, Sally L; Botting, Catherine H; Florence, Gordon J; Rohde, Manfred; Banfield, Mark J; Schwarz-Linek, Ulrich

2015-01-01

To cause disease and persist in a host, pathogenic and commensal microbes must adhere to tissues. Colonization and infection depend on specific molecular interactions at the host-microbe interface that involve microbial surface proteins, or adhesins. To date, adhesins are only known to bind to host receptors non-covalently. Here we show that the streptococcal surface protein SfbI mediates covalent interaction with the host protein fibrinogen using an unusual internal thioester bond as a ‘chemical harpoon’. This cross-linking reaction allows bacterial attachment to fibrin and SfbI binding to human cells in a model of inflammation. Thioester-containing domains are unexpectedly prevalent in Gram-positive bacteria, including many clinically relevant pathogens. Our findings support bacterial-encoded covalent binding as a new molecular principle in host-microbe interactions. This represents an as yet unexploited target to treat bacterial infection and may also offer novel opportunities for engineering beneficial interactions. DOI: http://dx.doi.org/10.7554/eLife.06638.001 PMID:26032562

Measuring biogeochemical responses to pulses of water

NASA Astrophysics Data System (ADS)

Balcerak, Ernie

2012-05-01

Hydrologic pulses, temporary increases in water inputs such as bouts of precipitation, can affect biogeochemical processes in ecosystems by providing water and nutrient resources. However, ecosystem responses to the water vary. Harms and Grimm conducted experiments to determine how hydrologic pulses and existing moisture conditions interact to affect the biogeochemistry of desert floodplains. During dry and monsoon seasons at their study site in the floodplains of the San Pedro River in Arizona, the researchers experimentally added pulses of water and then measured emissions of several trace gases that are indicators of biological processes. They found that the size of the added hydrologic pulse strongly interacted with existing soil moisture conditions in determining emissions of some trace gases. For instance, following dry conditions, pulses of water stimulated carbon dioxide, methane, and nitric oxide emissions, with larger water pulses stimulating more emissions. However, when soil was already wet, the addition of water pulses had less effect on the emission of these gases. (Journal of Geophysical Research-Biogeosciences, doi:10.1029/2011JG001775, 2012)

Streptomyces exploration is triggered by fungal interactions and volatile signals

PubMed Central

Jones, Stephanie E; Ho, Louis; Rees, Christiaan A; Hill, Jane E; Nodwell, Justin R; Elliot, Marie A

2017-01-01

It has long been thought that the life cycle of Streptomyces bacteria encompasses three developmental stages: vegetative hyphae, aerial hyphae and spores. Here, we show interactions between Streptomyces and fungi trigger a previously unobserved mode of Streptomyces development. We term these Streptomyces cells ‘explorers’, for their ability to adopt a non-branching vegetative hyphal conformation and rapidly transverse solid surfaces. Fungi trigger Streptomyces exploratory growth in part by altering the composition of the growth medium, and Streptomyces explorer cells can communicate this exploratory behaviour to other physically separated streptomycetes using an airborne volatile organic compound (VOC). These results reveal that interkingdom interactions can trigger novel developmental behaviours in bacteria, here, causing Streptomyces to deviate from its classically-defined life cycle. Furthermore, this work provides evidence that VOCs can act as long-range communication signals capable of propagating microbial morphological switches. DOI: http://dx.doi.org/10.7554/eLife.21738.001 PMID:28044982

Sodium taurocholate cotransporting polypeptide is a functional receptor for human hepatitis B and D virus

PubMed Central

Yan, Huan; Zhong, Guocai; Xu, Guangwei; He, Wenhui; Jing, Zhiyi; Gao, Zhenchao; Huang, Yi; Qi, Yonghe; Peng, Bo; Wang, Haimin; Fu, Liran; Song, Mei; Chen, Pan; Gao, Wenqing; Ren, Bijie; Sun, Yinyan; Cai, Tao; Feng, Xiaofeng; Sui, Jianhua; Li, Wenhui

2012-01-01

Human hepatitis B virus (HBV) infection and HBV-related diseases remain a major public health problem. Individuals coinfected with its satellite hepatitis D virus (HDV) have more severe disease. Cellular entry of both viruses is mediated by HBV envelope proteins. The pre-S1 domain of the large envelope protein is a key determinant for receptor(s) binding. However, the identity of the receptor(s) is unknown. Here, by using near zero distance photo-cross-linking and tandem affinity purification, we revealed that the receptor-binding region of pre-S1 specifically interacts with sodium taurocholate cotransporting polypeptide (NTCP), a multiple transmembrane transporter predominantly expressed in the liver. Silencing NTCP inhibited HBV and HDV infection, while exogenous NTCP expression rendered nonsusceptible hepatocarcinoma cells susceptible to these viral infections. Moreover, replacing amino acids 157–165 of nonfunctional monkey NTCP with the human counterpart conferred its ability in supporting both viral infections. Our results demonstrate that NTCP is a functional receptor for HBV and HDV. DOI: http://dx.doi.org/10.7554/eLife.00049.001 PMID:23150796

Filovirus receptor NPC1 contributes to species-specific patterns of ebolavirus susceptibility in bats

PubMed Central

Ng, Melinda; Ndungo, Esther; Kaczmarek, Maria E; Herbert, Andrew S; Binger, Tabea; Kuehne, Ana I; Jangra, Rohit K; Hawkins, John A; Gifford, Robert J; Biswas, Rohan; Demogines, Ann; James, Rebekah M; Yu, Meng; Brummelkamp, Thijn R; Drosten, Christian; Wang, Lin-Fa; Kuhn, Jens H; Müller, Marcel A; Dye, John M; Sawyer, Sara L; Chandran, Kartik

2015-01-01

Biological factors that influence the host range and spillover of Ebola virus (EBOV) and other filoviruses remain enigmatic. While filoviruses infect diverse mammalian cell lines, we report that cells from African straw-colored fruit bats (Eidolon helvum) are refractory to EBOV infection. This could be explained by a single amino acid change in the filovirus receptor, NPC1, which greatly reduces the affinity of EBOV-NPC1 interaction. We found signatures of positive selection in bat NPC1 concentrated at the virus-receptor interface, with the strongest signal at the same residue that controls EBOV infection in Eidolon helvum cells. Our work identifies NPC1 as a genetic determinant of filovirus susceptibility in bats, and suggests that some NPC1 variations reflect host adaptations to reduce filovirus replication and virulence. A single viral mutation afforded escape from receptor control, revealing a pathway for compensatory viral evolution and a potential avenue for expansion of filovirus host range in nature. DOI: http://dx.doi.org/10.7554/eLife.11785.001 PMID:26698106

The C-terminal region of the motor protein MCAK controls its structure and activity through a conformational switch

PubMed Central

Talapatra, Sandeep K; Harker, Bethany; Welburn, Julie PI

2015-01-01

The precise regulation of microtubule dynamics is essential during cell division. The kinesin-13 motor protein MCAK is a potent microtubule depolymerase. The divergent non-motor regions flanking the ATPase domain are critical in regulating its targeting and activity. However, the molecular basis for the function of the non-motor regions within the context of full-length MCAK is unknown. Here, we determine the structure of MCAK motor domain bound to its regulatory C-terminus. Our analysis reveals that the MCAK C-terminus binds to two motor domains in solution and is displaced allosterically upon microtubule binding, which allows its robust accumulation at microtubule ends. These results demonstrate that MCAK undergoes long-range conformational changes involving its C-terminus during the soluble to microtubule-bound transition and that the C-terminus-motor interaction represents a structural intermediate in the MCAK catalytic cycle. Together, our work reveals intrinsic molecular mechanisms underlying the regulation of kinesin-13 activity. DOI: http://dx.doi.org/10.7554/eLife.06421.001 PMID:25915621

Secretion of protein disulphide isomerase AGR2 confers tumorigenic properties

PubMed Central

Fessart, Delphine; Domblides, Charlotte; Avril, Tony; Eriksson, Leif A; Begueret, Hugues; Pineau, Raphael; Malrieux, Camille; Dugot-Senant, Nathalie; Lucchesi, Carlo; Chevet, Eric; Delom, Frederic

2016-01-01

The extracellular matrix (ECM) plays an instrumental role in determining the spatial orientation of epithelial polarity and the formation of lumens in glandular tissues during morphogenesis. Here, we show that the Endoplasmic Reticulum (ER)-resident protein anterior gradient-2 (AGR2), a soluble protein-disulfide isomerase involved in ER protein folding and quality control, is secreted and interacts with the ECM. Extracellular AGR2 (eAGR2) is a microenvironmental regulator of epithelial tissue architecture, which plays a role in the preneoplastic phenotype and contributes to epithelial tumorigenicity. Indeed, eAGR2, is secreted as a functionally active protein independently of its thioredoxin-like domain (CXXS) and of its ER-retention domain (KTEL), and is sufficient, by itself, to promote the acquisition of invasive and metastatic features. Therefore, we conclude that eAGR2 plays an extracellular role independent of its ER function and we elucidate this gain-of-function as a novel and unexpected critical ECM microenvironmental pro-oncogenic regulator of epithelial morphogenesis and tumorigenesis. DOI: http://dx.doi.org/10.7554/eLife.13887.001 PMID:27240165

Improved UT1 Predictions through Low-Latency VLBI Observations

DTIC Science & Technology

2010-03-14

J Geod (2010) 84:399–402 DOI 10.1007/s00190-010-0372-8 SHORT NOTE Improved UT1 predictions through low-latency VLBI observations Brian Luzum · Axel...polar motion and nutation on UT1 determinations from VLBI Intensive obser- vations. J Geod 82(12):863. doi:10.1007/s00190-008-0212-2 Ray JR, Carter WE...Behrend D (2007) The International VLBI Service for Geodesy and Astrometry (IVS): current capabilities and future prospects. J Geod 81(6–8):479. doi

Societal Interactions in Ovarian Cancer Metastases: A Quorum Sensing Hypothesis

DTIC Science & Technology

2007-11-01

subsequent studies we found that the density of the cells in culture at the time of harvest for injection did have a significant effect on their...VJ (2003) From motility to virulence: sensing and responding to environmental signals in Vibrio chol- erae. Curr Opin Microbiol 6:186–190. doi:10.1016...of luminescence in Vibrio har- veyi: sequence and function of genes encoding a second sensory pathway. Mol Microbiol 13:273–286. doi:10.1111/j.1365

Basic performance evaluation of a Si-PM array-based LGSO phoswich DOI block detector for a high-resolution small animal PET system.

PubMed

Yamamoto, Seiichi

2013-07-01

The silicon photomultiplier (Si-PM) is a promising photodetector for PET. However, it remains unclear whether Si-PM can be used for a depth-of-interaction (DOI) detector based on the decay time differences of the scintillator where pulse shape analysis is used. For clarification, we tested the Hamamatsu 4 × 4 Si-PM array (S11065-025P) combined with scintillators that used different decay times to develop DOI block detectors using the pulse shape analysis. First, Ce-doped Gd(2)SiO(5) (GSO) scintillators of 0.5 mol% Ce were arranged in a 4 × 4 matrix and were optically coupled to the center of each pixel of the Si-PM array for measurement of the energy resolution as well as its gain variations according to the temperature. Then two types of Ce-doped Lu(1.9)Gd(0.1)Si0(5) (LGSO) scintillators, 0.025 mol% Ce (decay time: ~31 ns) and 0.75 mol% Ce (decay time: ~46 ns), were optically coupled in the DOI direction, arranged in a 11 × 7 matrix, and optically coupled to a Si-PM array for testing of the possibility of a high-resolution DOI detector. The energy resolution of the Si-PM array-based GSO block detector was 18 ± 4.4 % FWHM for a Cs-137 gamma source (662 keV). Less than 1 mm crystals were clearly resolved in the position map of the LGSO DOI block detector. The peak-to-valley ratio (P/V) derived from the pulse shape spectra of the LGSO DOI block detector was 2.2. These results confirmed that Si-PM array-based DOI block detectors are promising for high-resolution small animal PET systems.

Data publication and dissemination of interactive keys under the open access model

USDA-ARS?s Scientific Manuscript database

The concepts of publication, citation and dissemination of interactive keys and other online keys are discussed and illustrated by a sample paper published in the present issue (doi: 10.3897/zookeys.21.271). The present model is based on previous experience with several existing examples of publishi...

Publications - DDS 8 | Alaska Division of Geological & Geophysical Surveys

Science.gov Websites

DGGS DDS 8 Publication Details Title: Alaska Volcano Observatory geochemical database Authors: Cameron ., Snedigar, S.F., and Nye, C.J., 2014, Alaska Volcano Observatory geochemical database: Alaska Division of ://doi.org/10.14509/29120 Publication Products Interactive Interactive Database Alaska Volcano Observatory

Pharmacological modulation of abnormal involuntary DOI-induced head twitch response in male DBA/2J mice: I. Effects of D2/D3 and D2 dopamine receptor selective compounds.

PubMed

Rangel-Barajas, Claudia; Malik, Maninder; Vangveravong, Suwanna; Mach, Robert H; Luedtke, Robert R

2014-08-01

Because of the complexity and heterogeneity of human neuropsychiatric disorders, it has been difficult to identify animal models that mimic the symptoms of these neuropathologies and can be used to screen for antipsychotic agents. For this study we selected the murine 5HT2A/2C receptor agonist-induced head twitch response (HTR) induced by the administration of 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI), which has been proposed as an animal model of symptoms associated with a variety of behavioral and psychiatric conditions. We investigated the DOI-induced HTR in male DBA/2J mice using a panel of D2-like (D2, D3 and D4) and D2 dopamine receptor selective compounds. When DBA/2J mice were administered a daily dose of DOI (5 mg/kg), tolerance to the DOI occurs. However, administrations of the same dose of DOI every other day (48 h) or on a weekly basis did not lead to tolerance and the ability to induce tolerance after daily administration of DOI remains intact after repeated weekly administration of DOI. Subsequently, a panel of D2-like dopamine receptor antagonists was found to effectively inhibit the DOI-induced HTR in DBA/2J mice. However, the benzamide eticlopride, which is a high affinity D2-like antagonist, was a notable exception. SV 293, SV-III-130s and N-methylbenperidol, which exhibit a high affinity for D2 versus the D3 dopamine receptor subtypes (60- to 100-fold binding selectivity), were also found to inhibit the HTR in DBA/2J mice. This observation suggests a functional interaction between dopaminergic and serotonergic systems through D2 dopamine receptors and the 5-HT2A serotonin receptors in vivo. Copyright © 2014 Elsevier Ltd. All rights reserved.

An FPGA-Based Real-Time Maximum Likelihood 3D Position Estimation for a Continuous Crystal PET Detector

NASA Astrophysics Data System (ADS)

Wang, Yonggang; Xiao, Yong; Cheng, Xinyi; Li, Deng; Wang, Liwei

2016-02-01

For the continuous crystal-based positron emission tomography (PET) detector built in our lab, a maximum likelihood algorithm adapted for implementation on a field programmable gate array (FPGA) is proposed to estimate the three-dimensional (3D) coordinate of interaction position with the single-end detected scintillation light response. The row-sum and column-sum readout scheme organizes the 64 channels of photomultiplier (PMT) into eight row signals and eight column signals to be readout for X- and Y-coordinates estimation independently. By the reference events irradiated in a known oblique angle, the probability density function (PDF) for each depth-of-interaction (DOI) segment is generated, by which the reference events in perpendicular irradiation are assigned to DOI segments for generating the PDFs for X and Y estimation in each DOI layer. Evaluated by the experimental data, the algorithm achieves an average X resolution of 1.69 mm along the central X-axis, and DOI resolution of 3.70 mm over the whole thickness (0-10 mm) of crystal. The performance improvements from 2D estimation to the 3D algorithm are also presented. Benefiting from abundant resources of FPGA and a hierarchical storage arrangement, the whole algorithm can be implemented into a middle-scale FPGA. By a parallel structure in pipelines, the 3D position estimator on the FPGA can achieve a processing throughput of 15 M events/s, which is sufficient for the requirement of real-time PET imaging.

A model of mechanical interactions between heart and lungs.

PubMed

Fontecave Jallon, Julie; Abdulhay, Enas; Calabrese, Pascale; Baconnier, Pierre; Gumery, Pierre-Yves

2009-12-13

To study the mechanical interactions between heart, lungs and thorax, we propose a mathematical model combining a ventilatory neuromuscular model and a model of the cardiovascular system, as described by Smith et al. (Smith, Chase, Nokes, Shaw & Wake 2004 Med. Eng. Phys.26, 131-139. (doi:10.1016/j.medengphy.2003.10.001)). The respiratory model has been adapted from Thibault et al. (Thibault, Heyer, Benchetrit & Baconnier 2002 Acta Biotheor. 50, 269-279. (doi:10.1023/A:1022616701863)); using a Liénard oscillator, it allows the activity of the respiratory centres, the respiratory muscles and rib cage internal mechanics to be simulated. The minimal haemodynamic system model of Smith includes the heart, as well as the pulmonary and systemic circulation systems. These two modules interact mechanically by means of the pleural pressure, calculated in the mechanical respiratory system, and the intrathoracic blood volume, calculated in the cardiovascular model. The simulation by the proposed model provides results, first, close to experimental data, second, in agreement with the literature results and, finally, highlighting the presence of mechanical cardiorespiratory interactions.

Angiopoietin-like proteins stimulate HSPC development through interaction with notch receptor signaling

PubMed Central

Lin, Michelle I; Price, Emily N; Boatman, Sonja; Hagedorn, Elliott J; Trompouki, Eirini; Satishchandran, Sruthi; Carspecken, Charles W; Uong, Audrey; DiBiase, Anthony; Yang, Song; Canver, Matthew C; Dahlberg, Ann; Lu, Zhigang; Zhang, Cheng Cheng; Orkin, Stuart H; Bernstein, Irwin D; Aster, Jon C; White, Richard M; Zon, Leonard I

2015-01-01

Angiopoietin-like proteins (angptls) are capable of ex vivo expansion of mouse and human hematopoietic stem and progenitor cells (HSPCs). Despite this intriguing ability, their mechanism is unknown. In this study, we show that angptl2 overexpression is sufficient to expand definitive HSPCs in zebrafish embryos. Angptl1/2 are required for definitive hematopoiesis and vascular specification of the hemogenic endothelium. The loss-of-function phenotype is reminiscent of the notch mutant mindbomb (mib), and a strong genetic interaction occurs between angptls and notch. Overexpressing angptl2 rescues mib while overexpressing notch rescues angptl1/2 morphants. Gene expression studies in ANGPTL2-stimulated CD34+ cells showed a strong MYC activation signature and myc overexpression in angptl1/2 morphants or mib restored HSPCs formation. ANGPTL2 can increase NOTCH activation in cultured cells and ANGPTL receptor interacted with NOTCH to regulate NOTCH cleavage. Together our data provide insight to the angptl-mediated notch activation through receptor interaction and subsequent activation of myc targets. DOI: http://dx.doi.org/10.7554/eLife.05544.001 PMID:25714926

Pharmacological targeting of the transcription factor SOX18 delays breast cancer in mice

PubMed Central

Overman, Jeroen; Fontaine, Frank; Moustaqil, Mehdi; Mittal, Deepak; Sierecki, Emma; Sacilotto, Natalia; Zuegg, Johannes; Robertson, Avril AB; Holmes, Kelly; Salim, Angela A; Mamidyala, Sreeman; Butler, Mark S; Robinson, Ashley S; Lesieur, Emmanuelle; Johnston, Wayne; Alexandrov, Kirill; Black, Brian L; Hogan, Benjamin M; De Val, Sarah; Capon, Robert J; Carroll, Jason S; Bailey, Timothy L; Koopman, Peter; Jauch, Ralf; Smyth, Mark J; Cooper, Matthew A; Gambin, Yann; Francois, Mathias

2017-01-01

Pharmacological targeting of transcription factors holds great promise for the development of new therapeutics, but strategies based on blockade of DNA binding, nuclear shuttling, or individual protein partner recruitment have yielded limited success to date. Transcription factors typically engage in complex interaction networks, likely masking the effects of specifically inhibiting single protein-protein interactions. Here, we used a combination of genomic, proteomic and biophysical methods to discover a suite of protein-protein interactions involving the SOX18 transcription factor, a known regulator of vascular development and disease. We describe a small-molecule that is able to disrupt a discrete subset of SOX18-dependent interactions. This compound selectively suppressed SOX18 transcriptional outputs in vitro and interfered with vascular development in zebrafish larvae. In a mouse pre-clinical model of breast cancer, treatment with this inhibitor significantly improved survival by reducing tumour vascular density and metastatic spread. Our studies validate an interactome-based molecular strategy to interfere with transcription factor activity, for the development of novel disease therapeutics. DOI: http://dx.doi.org/10.7554/eLife.21221.001 PMID:28137359

Estrogen receptor coregulator binding modulators (ERXs) effectively target estrogen receptor positive human breast cancers

PubMed Central

Raj, Ganesh V; Sareddy, Gangadhara Reddy; Ma, Shihong; Lee, Tae-Kyung; Viswanadhapalli, Suryavathi; Li, Rui; Liu, Xihui; Murakami, Shino; Chen, Chien-Cheng; Lee, Wan-Ru; Mann, Monica; Krishnan, Samaya Rajeshwari; Manandhar, Bikash; Gonugunta, Vijay K; Strand, Douglas; Tekmal, Rajeshwar Rao; Ahn, Jung-Mo; Vadlamudi, Ratna K

2017-01-01

The majority of human breast cancer is estrogen receptor alpha (ER) positive. While anti-estrogens/aromatase inhibitors are initially effective, resistance to these drugs commonly develops. Therapy-resistant tumors often retain ER signaling, via interaction with critical oncogenic coregulator proteins. To address these mechanisms of resistance, we have developed a novel ER coregulator binding modulator, ERX-11. ERX-11 interacts directly with ER and blocks the interaction between a subset of coregulators with both native and mutant forms of ER. ERX-11 effectively blocks ER-mediated oncogenic signaling and has potent anti-proliferative activity against therapy-sensitive and therapy-resistant human breast cancer cells. ERX-11 is orally bioavailable, with no overt signs of toxicity and potent activity in both murine xenograft and patient-derived breast tumor explant models. This first-in-class agent, with its novel mechanism of action of disrupting critical protein-protein interactions, overcomes the limitations of current therapies and may be clinically translatable for patients with therapy-sensitive and therapy-resistant breast cancers. DOI: http://dx.doi.org/10.7554/eLife.26857.001 PMID:28786813

Dna2 nuclease-helicase structure, mechanism and regulation by Rpa

PubMed Central

Zhou, Chun; Pourmal, Sergei; Pavletich, Nikola P

2015-01-01

The Dna2 nuclease-helicase maintains genomic integrity by processing DNA double-strand breaks, Okazaki fragments and stalled replication forks. Dna2 requires ssDNA ends, and is dependent on the ssDNA-binding protein Rpa, which controls cleavage polarity. Here we present the 2.3 Å structure of intact mouse Dna2 bound to a 15-nucleotide ssDNA. The nuclease active site is embedded in a long, narrow tunnel through which the DNA has to thread. The helicase domain is required for DNA binding but not threading. We also present the structure of a flexibly-tethered Dna2-Rpa interaction that recruits Dna2 to Rpa-coated DNA. We establish that a second Dna2-Rpa interaction is mutually exclusive with Rpa-DNA interactions and mediates the displacement of Rpa from ssDNA. This interaction occurs at the nuclease tunnel entrance and the 5’ end of the Rpa-DNA complex. Hence, it only displaces Rpa from the 5’ but not 3’ end, explaining how Rpa regulates cleavage polarity. DOI: http://dx.doi.org/10.7554/eLife.09832.001 PMID:26491943

Effects of myosin variants on interacting-heads motif explain distinct hypertrophic and dilated cardiomyopathy phenotypes

PubMed Central

Alamo, Lorenzo; Ware, James S; Pinto, Antonio; Gillilan, Richard E; Seidman, Jonathan G; Seidman, Christine E; Padrón, Raúl

2017-01-01

Cardiac β-myosin variants cause hypertrophic (HCM) or dilated (DCM) cardiomyopathy by disrupting sarcomere contraction and relaxation. The locations of variants on isolated myosin head structures predict contractility effects but not the prominent relaxation and energetic deficits that characterize HCM. During relaxation, pairs of myosins form interacting-heads motif (IHM) structures that with other sarcomere proteins establish an energy-saving, super-relaxed (SRX) state. Using a human β-cardiac myosin IHM quasi-atomic model, we defined interactions sites between adjacent myosin heads and associated protein partners, and then analyzed rare variants from 6112 HCM and 1315 DCM patients and 33,370 ExAC controls. HCM variants, 72% that changed electrostatic charges, disproportionately altered IHM interaction residues (expected 23%; HCM 54%, p=2.6×10−19; DCM 26%, p=0.66; controls 20%, p=0.23). HCM variant locations predict impaired IHM formation and stability, and attenuation of the SRX state - accounting for altered contractility, reduced diastolic relaxation, and increased energy consumption, that fully characterizes HCM pathogenesis. DOI: http://dx.doi.org/10.7554/eLife.24634.001 PMID:28606303

Side readout of long scintillation crystal elements with digital SiPM for TOF-DOI PET.

PubMed

Yeom, Jung Yeol; Vinke, Ruud; Levin, Craig S

2014-12-01

Side readout of scintillation light from crystal elements in positron emission tomography (PET) is an alternative to conventional end-readout configurations, with the benefit of being able to provide accurate depth-of-interaction (DOI) information and good energy resolution while achieving excellent timing resolution required for time-of-flight PET. This paper explores different readout geometries of scintillation crystal elements with the goal of achieving a detector that simultaneously achieves excellent timing resolution, energy resolution, spatial resolution, and photon sensitivity. The performance of discrete LYSO scintillation elements of different lengths read out from the end/side with digital silicon photomultipliers (dSiPMs) has been assessed. Compared to 3 × 3 × 20 mm(3) LYSO crystals read out from their ends with a coincidence resolving time (CRT) of 162 ± 6 ps FWHM and saturated energy spectra, a side-readout configuration achieved an excellent CRT of 144 ± 2 ps FWHM after correcting for timing skews within the dSiPM and an energy resolution of 11.8% ± 0.2% without requiring energy saturation correction. Using a maximum likelihood estimation method on individual dSiPM pixel response that corresponds to different 511 keV photon interaction positions, the DOI resolution of this 3 × 3 × 20 mm(3) crystal side-readout configuration was computed to be 0.8 mm FWHM with negligible artifacts at the crystal ends. On the other hand, with smaller 3 × 3 × 5 mm(3) LYSO crystals that can also be tiled/stacked to provide DOI information, a timing resolution of 134 ± 6 ps was attained but produced highly saturated energy spectra. The energy, timing, and DOI resolution information extracted from the side of long scintillation crystal elements coupled to dSiPM have been acquired for the first time. The authors conclude in this proof of concept study that such detector configuration has the potential to enable outstanding detector performance in terms of timing, energy, and DOI resolution.

Timing properties of phosphor-coated polished LSO crystals.

PubMed

Schmall, Jeffrey P; Roncali, Emilie; Berg, Eric; Viswanath, Varsha; Du, Junwei; Cherry, Simon R

2014-08-07

This study investigates a time-of-flight (TOF)-depth-of-interaction (DOI) detector design for positron emission tomography (PET), based on phosphor-coated lutetium oxyorthosilicate (LSO) scintillator crystals coupled to fast single channel photomultiplier tubes. Interaction of the scintillation light with the phosphor coating changes the pulse shape in a depth-dependent manner. 3 × 3 × 10 mm(3) LSO scintillation crystals with polished surfaces were characterized, with and without phosphor coating, to assess DOI capability and timing properties. Two different phosphor coating geometries were studied: coating of the top surface of the crystal, and the top plus half of the crystal sides. There was negligible depth dependency in the decay time when coating only the top surface, however there was a ∼10 ns difference in end-to-end decay time when coating the top plus half of the crystal sides, sufficient to support the use of three DOI bins (3.3 mm DOI bin width). The rise time of the half-coated phosphor crystal was slightly faster at all depths, compared to uncoated crystals, however the signal amplitude was lower. Phosphor coating resulted in depth-dependent photopeak positions with an energy resolution of 13.7%, at a depth of 1 mm, and 15.3%, at a depth of 9 mm, for the half-coated crystal. Uncoated LSO crystals showed no change in photopeak position as a function of depth, with an energy resolution of 10.4%. The head-on coincidence timing resolution (CTR) of two uncoated LSO crystals was 287 ps using constant fraction discrimination for time pick-off. With phosphor coating, the CTR of the top-coated crystal was 314 ps, compared to 384 ps for the half-coated crystal. We demonstrate that the trade-off between timing resolution and DOI resolution can be controlled by the phosphor coating geometry. Here we present preliminary results demonstrating that good DOI resolution can be achieved with only a modest 26% degradation in CTR.

Side readout of long scintillation crystal elements with digital SiPM for TOF-DOI PET

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yeom, Jung Yeol, E-mail: yeomjy@kumoh.ac.kr, E-mail: cslevin@stanford.edu; Vinke, Ruud; Levin, Craig S., E-mail: yeomjy@kumoh.ac.kr, E-mail: cslevin@stanford.edu

Purpose: Side readout of scintillation light from crystal elements in positron emission tomography (PET) is an alternative to conventional end-readout configurations, with the benefit of being able to provide accurate depth-of-interaction (DOI) information and good energy resolution while achieving excellent timing resolution required for time-of-flight PET. This paper explores different readout geometries of scintillation crystal elements with the goal of achieving a detector that simultaneously achieves excellent timing resolution, energy resolution, spatial resolution, and photon sensitivity. Methods: The performance of discrete LYSO scintillation elements of different lengths read out from the end/side with digital silicon photomultipliers (dSiPMs) has been assessed.more » Results: Compared to 3 × 3 × 20 mm{sup 3} LYSO crystals read out from their ends with a coincidence resolving time (CRT) of 162 ± 6 ps FWHM and saturated energy spectra, a side-readout configuration achieved an excellent CRT of 144 ± 2 ps FWHM after correcting for timing skews within the dSiPM and an energy resolution of 11.8% ± 0.2% without requiring energy saturation correction. Using a maximum likelihood estimation method on individual dSiPM pixel response that corresponds to different 511 keV photon interaction positions, the DOI resolution of this 3 × 3 × 20 mm{sup 3} crystal side-readout configuration was computed to be 0.8 mm FWHM with negligible artifacts at the crystal ends. On the other hand, with smaller 3 × 3 × 5 mm{sup 3} LYSO crystals that can also be tiled/stacked to provide DOI information, a timing resolution of 134 ± 6 ps was attained but produced highly saturated energy spectra. Conclusions: The energy, timing, and DOI resolution information extracted from the side of long scintillation crystal elements coupled to dSiPM have been acquired for the first time. The authors conclude in this proof of concept study that such detector configuration has the potential to enable outstanding detector performance in terms of timing, energy, and DOI resolution.« less

Patterns of call communication between group-housed zebra finches change during the breeding cycle

PubMed Central

Gill, Lisa F; Goymann, Wolfgang; Ter Maat, Andries; Gahr, Manfred

2015-01-01

Vocal signals such as calls play a crucial role for survival and successful reproduction, especially in group-living animals. However, call interactions and call dynamics within groups remain largely unexplored because their relation to relevant contexts or life-history stages could not be studied with individual-level resolution. Using on-bird microphone transmitters, we recorded the vocalisations of individual zebra finches (Taeniopygia guttata) behaving freely in social groups, while females and males previously unknown to each other passed through different stages of the breeding cycle. As birds formed pairs and shifted their reproductive status, their call repertoire composition changed. The recordings revealed that calls occurred non-randomly in fine-tuned vocal interactions and decreased within groups while pair-specific patterns emerged. Call-type combinations of vocal interactions changed within pairs and were associated with successful egg-laying, highlighting a potential fitness relevance of calling dynamics in communication systems. DOI: http://dx.doi.org/10.7554/eLife.07770.001 PMID:26441403

A bacteriophage endolysin that eliminates intracellular streptococci

PubMed Central

Shen, Yang; Barros, Marilia; Vennemann, Tarek; Gallagher, D Travis; Yin, Yizhou; Linden, Sara B; Heselpoth, Ryan D; Spencer, Dennis J; Donovan, David M; Moult, John; Fischetti, Vincent A; Heinrich, Frank; Lösche, Mathias; Nelson, Daniel C

2016-01-01

PlyC, a bacteriophage-encoded endolysin, lyses Streptococcus pyogenes (Spy) on contact. Here, we demonstrate that PlyC is a potent agent for controlling intracellular Spy that often underlies refractory infections. We show that the PlyC holoenzyme, mediated by its PlyCB subunit, crosses epithelial cell membranes and clears intracellular Spy in a dose-dependent manner. Quantitative studies using model membranes establish that PlyCB interacts strongly with phosphatidylserine (PS), whereas its interaction with other lipids is weak, suggesting specificity for PS as its cellular receptor. Neutron reflection further substantiates that PlyC penetrates bilayers above a PS threshold concentration. Crystallography and docking studies identify key residues that mediate PlyCB–PS interactions, which are validated by site-directed mutagenesis. This is the first report that a native endolysin can traverse epithelial membranes, thus substantiating the potential of PlyC as an antimicrobial for Spy in the extracellular and intracellular milieu and as a scaffold for engineering other functionalities. DOI: http://dx.doi.org/10.7554/eLife.13152.001 PMID:26978792

Global reorganisation of cis-regulatory units upon lineage commitment of human embryonic stem cells

PubMed Central

Freire-Pritchett, Paula; Schoenfelder, Stefan; Várnai, Csilla; Wingett, Steven W; Cairns, Jonathan; Collier, Amanda J; García-Vílchez, Raquel; Furlan-Magaril, Mayra; Osborne, Cameron S; Fraser, Peter; Rugg-Gunn, Peter J; Spivakov, Mikhail

2017-01-01

Long-range cis-regulatory elements such as enhancers coordinate cell-specific transcriptional programmes by engaging in DNA looping interactions with target promoters. Deciphering the interplay between the promoter connectivity and activity of cis-regulatory elements during lineage commitment is crucial for understanding developmental transcriptional control. Here, we use Promoter Capture Hi-C to generate a high-resolution atlas of chromosomal interactions involving ~22,000 gene promoters in human pluripotent and lineage-committed cells, identifying putative target genes for known and predicted enhancer elements. We reveal extensive dynamics of cis-regulatory contacts upon lineage commitment, including the acquisition and loss of promoter interactions. This spatial rewiring occurs preferentially with predicted changes in the activity of cis-regulatory elements and is associated with changes in target gene expression. Our results provide a global and integrated view of promoter interactome dynamics during lineage commitment of human pluripotent cells. DOI: http://dx.doi.org/10.7554/eLife.21926.001 PMID:28332981

Bidirectional interactions between indomethacin and the murine intestinal microbiota

PubMed Central

Liang, Xue; Bittinger, Kyle; Li, Xuanwen; Abernethy, Darrell R; Bushman, Frederic D; FitzGerald, Garret A

2015-01-01

The vertebrate gut microbiota have been implicated in the metabolism of xenobiotic compounds, motivating studies of microbe-driven metabolism of clinically important drugs. Here, we studied interactions between the microbiota and indomethacin, a nonsteroidal anti-inflammatory drug (NSAID) that inhibits cyclooxygenases (COX) -1 and -2. Indomethacin was tested in both acute and chronic exposure models in mice at clinically relevant doses, which suppressed production of COX-1- and COX-2-derived prostaglandins and caused small intestinal (SI) damage. Deep sequencing analysis showed that indomethacin exposure was associated with alterations in the structure of the intestinal microbiota in both dosing models. Perturbation of the intestinal microbiome by antibiotic treatment altered indomethacin pharmacokinetics and pharmacodynamics, which is probably the result of reduced bacterial β-glucuronidase activity. Humans show considerable inter-individual differences in their microbiota and their responses to indomethacin — thus, the drug-microbe interactions described here provide candidate mediators of individualized drug responses. DOI: http://dx.doi.org/10.7554/eLife.08973.001 PMID:26701907

Attention operates uniformly throughout the classical receptive field and the surround

PubMed Central

Verhoef, Bram-Ernst; Maunsell, John HR

2016-01-01

Shifting attention among visual stimuli at different locations modulates neuronal responses in heterogeneous ways, depending on where those stimuli lie within the receptive fields of neurons. Yet how attention interacts with the receptive-field structure of cortical neurons remains unclear. We measured neuronal responses in area V4 while monkeys shifted their attention among stimuli placed in different locations within and around neuronal receptive fields. We found that attention interacts uniformly with the spatially-varying excitation and suppression associated with the receptive field. This interaction explained the large variability in attention modulation across neurons, and a non-additive relationship among stimulus selectivity, stimulus-induced suppression and attention modulation that has not been previously described. A spatially-tuned normalization model precisely accounted for all observed attention modulations and for the spatial summation properties of neurons. These results provide a unified account of spatial summation and attention-related modulation across both the classical receptive field and the surround. DOI: http://dx.doi.org/10.7554/eLife.17256.001 PMID:27547989

Spatial signals link exit from mitosis to spindle position

PubMed Central

Falk, Jill Elaine; Tsuchiya, Dai; Verdaasdonk, Jolien; Lacefield, Soni; Bloom, Kerry; Amon, Angelika

2016-01-01

In budding yeast, if the spindle becomes mispositioned, cells prevent exit from mitosis by inhibiting the mitotic exit network (MEN). The MEN is a signaling cascade that localizes to spindle pole bodies (SPBs) and activates the phosphatase Cdc14. There are two competing models that explain MEN regulation by spindle position. In the 'zone model', exit from mitosis occurs when a MEN-bearing SPB enters the bud. The 'cMT-bud neck model' posits that cytoplasmic microtubule (cMT)-bud neck interactions prevent MEN activity. Here we find that 1) eliminating cMT– bud neck interactions does not trigger exit from mitosis and 2) loss of these interactions does not precede Cdc14 activation. Furthermore, using binucleate cells, we show that exit from mitosis occurs when one SPB enters the bud despite the presence of a mispositioned spindle. We conclude that exit from mitosis is triggered by a correctly positioned spindle rather than inhibited by improper spindle position. DOI: http://dx.doi.org/10.7554/eLife.14036.001 PMID:27166637

A complete toolset for the study of Ustilago bromivora and Brachypodium sp. as a fungal-temperate grass pathosystem

PubMed Central

Rabe, Franziska; Bosch, Jason; Stirnberg, Alexandra; Guse, Tilo; Bauer, Lisa; Seitner, Denise; Rabanal, Fernando A; Czedik-Eysenberg, Angelika; Uhse, Simon; Bindics, Janos; Genenncher, Bianca; Navarrete, Fernando; Kellner, Ronny; Ekker, Heinz; Kumlehn, Jochen; Vogel, John P; Gordon, Sean P; Marcel, Thierry C; Münsterkötter, Martin; Walter, Mathias C; Sieber, Christian MK; Mannhaupt, Gertrud; Güldener, Ulrich; Kahmann, Regine; Djamei, Armin

2016-01-01

Due to their economic relevance, the study of plant pathogen interactions is of importance. However, elucidating these interactions and their underlying molecular mechanisms remains challenging since both host and pathogen need to be fully genetically accessible organisms. Here we present milestones in the establishment of a new biotrophic model pathosystem: Ustilago bromivora and Brachypodium sp. We provide a complete toolset, including an annotated fungal genome and methods for genetic manipulation of the fungus and its host plant. This toolset will enable researchers to easily study biotrophic interactions at the molecular level on both the pathogen and the host side. Moreover, our research on the fungal life cycle revealed a mating type bias phenomenon. U. bromivora harbors a haplo-lethal allele that is linked to one mating type region. As a result, the identified mating type bias strongly promotes inbreeding, which we consider to be a potential speciation driver. DOI: http://dx.doi.org/10.7554/eLife.20522.001 PMID:27835569

Highly improved operation of monolithic BGO-PET blocks

NASA Astrophysics Data System (ADS)

Gonzalez-Montoro, A.; Sanchez, F.; Majewski, S.; Zanettini, S.; Benlloch, J. M.; Gonzalez, A. J.

2017-11-01

In PET scanners both scintillation crystals and photosensors are key components defining the system's performance and cost. Original PET systems used BGO or NaI(Tl) scintillators but achieved limited performance due to its slow decay and relatively low light output. Moreover, NaI(Tl) has low stopping power for 511 keV annihilation photons. In this study we report the possibility to reintroduce BGO crystals, and in particular in the form of monolithic blocks, especially suitable for low-dose large-size PET scanners, offering significantly improved sensitivity at a highly reduced cost compared to LYSO type fast scintillators. We have studied the performance of a monolithic BGO block as large as 50 × 50 × 15 mm3 with black-painted lateral walls to reduce lights spread, enabling accurate photon depth of interaction (DOI) measurements. A directional optical layer, called retro-reflector, was coupled to the entrance face bouncing back the scintillation light in the direction of the emission source and, therefore, adding to the light signal while preserving the narrow light cone distribution. Four configurations namely 12 × 12 and 16 × 16 SiPM arrays (3 mm × 3 mm each) as photosensors, with or without a nanopattern treatment at the crystal exit face, have been studied. This structure consisted of a thin layer of a specific high refractive index material shaped with a periodic nanopattern, increasing the scintillation light extraction. The readout returned information for each SiPM row and column, characterizing the X-Y light distribution projections. We have studied the detector spatial resolution using collimated 22Na sources at normal incidence. The DOI resolution was evaluated using collimated gamma beams with lateral incidence. The overall best detector performance was obtained for the 16× 16 SiPM array offering higher readout granularity. We have determined the spatial resolution for 3 separated DOI layers, obtaining the best results for the DOI region near to the photosensor.

Cellular uptake and trafficking of polydiacetylene micelles

NASA Astrophysics Data System (ADS)

Gravel, Edmond; Thézé, Benoit; Jacques, Isabelle; Anilkumar, Parambath; Gombert, Karine; Ducongé, Frédéric; Doris, Eric

2013-02-01

Polydiacetylene (PDA) micelles coated with either carboxylate-, ammonium-, or methoxy-polyethyleneglycol (PEG) chains were assembled and loaded with a fluorescent dye (DiO). Their interaction with MCF-7 human breast tumor cells was investigated by epi-fluorescence microscopy and fluorescence-activated cell sorting (FACS) to determine their internalization pathway and intracellular fate. It was found that the ionic character of the micelles influenced their internalization kinetics through a caveolae-mediated pathway and that all micelle types behaved somewhat similarly inside cells.Polydiacetylene (PDA) micelles coated with either carboxylate-, ammonium-, or methoxy-polyethyleneglycol (PEG) chains were assembled and loaded with a fluorescent dye (DiO). Their interaction with MCF-7 human breast tumor cells was investigated by epi-fluorescence microscopy and fluorescence-activated cell sorting (FACS) to determine their internalization pathway and intracellular fate. It was found that the ionic character of the micelles influenced their internalization kinetics through a caveolae-mediated pathway and that all micelle types behaved somewhat similarly inside cells. Electronic supplementary information (ESI) available: Detailed synthetic procedures and supplementary figures. See DOI: 10.1039/c2nr34149b

Light-Sharing Interface for dMiCE Detectors Using Sub-Surface Laser Engraving

PubMed Central

Hunter, William C. J.; Miyaoka, Robert S.; MacDonald, Lawrence; McDougald, Wendy; Lewellen, Thomas K.

2015-01-01

We have previously reported on dMiCE, a method of resolving depth or interaction (DOI) in a pair of discrete crystals by encoding light sharing properties as a function of depth in the interface of a crystal-element pair. A challenge for this method is the cost and repeatability of interface treatment for each crystal pair. In this work, we report our preliminary results on using sub-surface laser engraving (SSLE) as a means of forming this depth-dependent interface in a dMiCE detector. A surplus first-generation SSLE system was used to create a partially reflective layer 100-microns thick at the boundary between two halves of a 1.4-by-2.9-by-20 mm3 LYSO crystal. The boundary of these paired crystal elements was positioned between two 3-mm wide Silicon photomultiplier arrays. The responses of these two photodetectors were acquired for an ensemble of 511-keV photons collimated to interact at a fixed depth in just one crystal element. Interaction position was then varied to measure detector response as a function of depth, which was then used to maximum-likelihood positions. Despite use of sub-optimal SSLE processing we found an average DOI resolution of 3.4 mm for front-sided readout and 3.9 mm for back-sided readout while obtaining energy resolutions on the order of 10%. We expect DOI resolution can be improved significantly by optimizing the SSLE process and pattern. PMID:25914421

Light-Sharing Interface for dMiCE Detectors using Sub-Surface Laser Engraving.

PubMed

Hunter, William C J; Miyaoka, Robert S; MacDonald, Lawrence; McDougald, Wendy; Lewellen, Thomas K

2013-10-01

We have previously reported on dMiCE, a method of resolving depth or interaction (DOI) in a pair of discrete crystals by encoding light sharing properties as a function of depth in the interface of this crystal-element pair. A challenge for this method is the cost and repeatability of interface treatment for a crystal pair. In this work, we report our preliminary results on using sub-surface laser engraving (SSLE) as a means of forming this depth-dependent interface in a dMiCE detector. A surplus first-generation SSLE system was used to create a partially reflective layer 100-microns thick at the boundary between two halves of a 1.4-by-2.9-by-20 mmˆ3 LYSO crystal. The boundary of these paired crystal elements was positioned between two 3-mm wide Geiger-Müller avalanche photodiodes from Hamamatsu. The responses of these two photodetectors were acquired for an ensemble of 511-keV photons collimated to interact at a fixed depth in just one crystal element. Interaction position was then varied to measure detector response as a function of depth, which was then used to maximum-likelihood positions events. Despite use of sub-optimal SSLE processing we found an average DOI resolution of 3.4 mm for front-sided readout and 3.9 mm for back-sided readout. We expect DOI resolution can be improved significantly by optimizing the SSLE process and pattern.

Light-Sharing Interface for dMiCE Detectors using Sub-Surface Laser Engraving

PubMed Central

Hunter, William C.J.; Miyaoka, Robert S.; MacDonald, Lawrence; McDougald, Wendy; Lewellen, Thomas K.

2014-01-01

We have previously reported on dMiCE, a method of resolving depth or interaction (DOI) in a pair of discrete crystals by encoding light sharing properties as a function of depth in the interface of this crystal-element pair. A challenge for this method is the cost and repeatability of interface treatment for a crystal pair. In this work, we report our preliminary results on using sub-surface laser engraving (SSLE) as a means of forming this depth-dependent interface in a dMiCE detector. A surplus first-generation SSLE system was used to create a partially reflective layer 100-microns thick at the boundary between two halves of a 1.4-by-2.9-by-20 mmˆ3 LYSO crystal. The boundary of these paired crystal elements was positioned between two 3-mm wide Geiger-Müller avalanche photodiodes from Hamamatsu. The responses of these two photodetectors were acquired for an ensemble of 511-keV photons collimated to interact at a fixed depth in just one crystal element. Interaction position was then varied to measure detector response as a function of depth, which was then used to maximum-likelihood positions events. Despite use of sub-optimal SSLE processing we found an average DOI resolution of 3.4 mm for front-sided readout and 3.9 mm for back-sided readout. We expect DOI resolution can be improved significantly by optimizing the SSLE process and pattern. PMID:25506194

Light-Sharing Interface for dMiCE Detectors Using Sub-Surface Laser Engraving.

PubMed

Hunter, William C J; Miyaoka, Robert S; MacDonald, Lawrence; McDougald, Wendy; Lewellen, Thomas K

2015-02-06

We have previously reported on dMiCE, a method of resolving depth or interaction (DOI) in a pair of discrete crystals by encoding light sharing properties as a function of depth in the interface of a crystal-element pair. A challenge for this method is the cost and repeatability of interface treatment for each crystal pair. In this work, we report our preliminary results on using sub-surface laser engraving (SSLE) as a means of forming this depth-dependent interface in a dMiCE detector. A surplus first-generation SSLE system was used to create a partially reflective layer 100-microns thick at the boundary between two halves of a 1.4-by-2.9-by-20 mm 3 LYSO crystal. The boundary of these paired crystal elements was positioned between two 3-mm wide Silicon photomultiplier arrays. The responses of these two photodetectors were acquired for an ensemble of 511-keV photons collimated to interact at a fixed depth in just one crystal element. Interaction position was then varied to measure detector response as a function of depth, which was then used to maximum-likelihood positions. Despite use of sub-optimal SSLE processing we found an average DOI resolution of 3.4 mm for front-sided readout and 3.9 mm for back-sided readout while obtaining energy resolutions on the order of 10%. We expect DOI resolution can be improved significantly by optimizing the SSLE process and pattern.

The interactome of the copper transporter ATP7A belongs to a network of neurodevelopmental and neurodegeneration factors

PubMed Central

Comstra, Heather S; McArthy, Jacob; Rudin-Rush, Samantha; Hartwig, Cortnie; Gokhale, Avanti; Zlatic, Stephanie A; Blackburn, Jessica B; Werner, Erica; Petris, Michael; D’Souza, Priya; Panuwet, Parinya; Barr, Dana Boyd; Lupashin, Vladimir; Vrailas-Mortimer, Alysia; Faundez, Victor

2017-01-01

Genetic and environmental factors, such as metals, interact to determine neurological traits. We reasoned that interactomes of molecules handling metals in neurons should include novel metal homeostasis pathways. We focused on copper and its transporter ATP7A because ATP7A null mutations cause neurodegeneration. We performed ATP7A immunoaffinity chromatography and identified 541 proteins co-isolating with ATP7A. The ATP7A interactome concentrated gene products implicated in neurodegeneration and neurodevelopmental disorders, including subunits of the Golgi-localized conserved oligomeric Golgi (COG) complex. COG null cells possess altered content and subcellular localization of ATP7A and CTR1 (SLC31A1), the transporter required for copper uptake, as well as decreased total cellular copper, and impaired copper-dependent metabolic responses. Changes in the expression of ATP7A and COG subunits in Drosophila neurons altered synapse development in larvae and copper-induced mortality of adult flies. We conclude that the ATP7A interactome encompasses a novel COG-dependent mechanism to specify neuronal development and survival. DOI: http://dx.doi.org/10.7554/eLife.24722.001 PMID:28355134

Structural basis for interdomain communication in SHIP2 providing high phosphatase activity

PubMed Central

Le Coq, Johanne; Camacho-Artacho, Marta; Velázquez, José Vicente; Santiveri, Clara M; Gallego, Luis Heredia; Campos-Olivas, Ramón; Dölker, Nicole; Lietha, Daniel

2017-01-01

SH2-containing-inositol-5-phosphatases (SHIPs) dephosphorylate the 5-phosphate of phosphatidylinositol-3,4,5-trisphosphate (PI(3,4,5)P3) and play important roles in regulating the PI3K/Akt pathway in physiology and disease. Aiming to uncover interdomain regulatory mechanisms in SHIP2, we determined crystal structures containing the 5-phosphatase and a proximal region adopting a C2 fold. This reveals an extensive interface between the two domains, which results in significant structural changes in the phosphatase domain. Both the phosphatase and C2 domains bind phosphatidylserine lipids, which likely helps to position the active site towards its substrate. Although located distant to the active site, the C2 domain greatly enhances catalytic turnover. Employing molecular dynamics, mutagenesis and cell biology, we identify two distinct allosteric signaling pathways, emanating from hydrophobic or polar interdomain interactions, differentially affecting lipid chain or headgroup moieties of PI(3,4,5)P3. Together, this study reveals details of multilayered C2-mediated effects important for SHIP2 activity and points towards interesting new possibilities for therapeutic interventions. DOI: http://dx.doi.org/10.7554/eLife.26640.001 PMID:28792888

Biophysical landscape interactions: Bridging disciplines and scale with connectivity

NASA Astrophysics Data System (ADS)

van der Ploeg, Martine; Baartman, Jantiene; Robinson, David

2017-04-01

The combination of climate change, population growth and soil threats, such as carbon loss, biodiversity decline or erosion amongst others , increasingly confront the global community [1]. One of the major challenges in studying processes involved in soil threats, landscape resilience, ecosystem stability, sustainable land management and the economic consequences, is that it is an interdisciplinary field [2], that needs less stringent scientific disciplinary boundaries [3]. As a result of disciplinary focus, ambiguity may arise on the understanding of landscape interactions, and this is especially true in the interaction between a landscape's physical and biological processes [4]. Another important aspect in biophysical landscape interactions are the differences in scale related to the various processes that play a role in these systems. While scaling of environmental processes is possible, as long as the phenomena at hand can be described by the same set of differential equations [5], biophysical landscape interactions pose problems for scaling approaches. Landscape position and land use impact the coupled processes in soil and vegetation. Differences in micro-behavior, driven by the interplay of heterogeneous soil and vegetation dynamics, impact emergent characteristics across a landscape. A complicating factor is the response of vegetation to changing environmental conditions, including a possible and often unknown time-lag. By altering soil conditions, plants may leave an imprint in the landscape that remains even after vegetation has disappeared due to e.g. drought, wildfire or overgrazing. Plants also respond biochemically to their environment, while the models used for hydrology are often based on physical interactions. Gene-expression and genotype adaptation may further complicate our modelling efforts in for example climate change impacts. What are we missing by not having more connectivity in our thinking, and what we can solve? We think that integrated concepts of biophysical landscape interactions are needed to evaluate soil water availability in relation to the stability of natural vegetation, especially in the perspective of soil threats, population growth, climate change, and global water scarcity. An integrated concept can only be established by bridging the gap between several disciplines, but needs to be appealing to those disciplines at the same time. As evidence suggests interdisciplinary work is more challenging to get funded [6]. The key aspect of the connectivity concept is that it can create pathways for feedbacks which are so often missing in soil and water models. Connectivity could thus play an important role in bridging disciplines and scales. [1] Schwilch G, Bernet L. Fleskens L, Giannakis E, Leventon J, Marañón T, Mills J, Short C, Stolte J, van Delden H, Verzandvoort S. 2016. Operationalizing ecosystem services for the mitigation of soil threats: A proposed framework. Ecological Indicators 67: 586-597,doi:10.1016/j.ecolind.2016.03.016 [2] Pelletier JD, DeLong SB, Orem CA, Becerra P, Compton K, Gressett K, Lyons-Baral J, McGuire LA, Molaro JL, Spinler JCCF. 2012. How do vegetation bands form in dry lands? Insights from numerical modeling and field studies in southern Nevada, USA. Journal of Geophysical Research: Earth Surface 117: F04026,doi:10.1029/2012JF002465 [3] Liu J, Dietz T, Carpenter SR, Alberti M, Folke C, Moran E, ..., Ostrom E. 2007. Complexity of coupled human and natural systems. Science 317.5844: 1513-1516,doi:10.1126/science.1144004 [4] Cook BJ, Hauer FR. 2007. Effects of hydrologic connectivity on water chemistry, soils, and vegetation structure and function in an intermontane depressional wetland landscape. Wetlands 27.3: 719-738,doi:10.1672/0277-5212(2007)27 [5] Roth K. 2008. Scaling of water flow through porous media and soils. European journal of soil science, 59(1), 125-130, doi: 10.1111/j.1365-2389.2007.00986.x [6] Bromham, L, Dinnage R, Hua X. 2016. Interdisciplinary research has consistently lower funding success. Nature 534: 684-687,doi:10.1038/nature18315

Tidal asymmetry in a funnel-shaped estuary with mixed semidiurnal tides

NASA Astrophysics Data System (ADS)

Gong, Wenping; Schuttelaars, Henk; Zhang, Heng

2016-05-01

Different types of tidal asymmetry (see review of de Swart and Zimmerman Annu Rev Fluid Mech 41: 203-229, 2009) are examined in this study. We distinguish three types of tidal asymmetry: duration and magnitude differences between flood and ebb tidal flow, duration difference between the rising and falling tides. For waterborne substance transport, the first two asymmetries are important while the last one is not. In this study, we take the Huangmaohai Estuary (HE), Pearl River Delta, China as an example to examine the spatio-temporal variations of the tidal asymmetry in a mixed semidiurnal tidal regime and to explain them by investigating the associated mechanisms. The methodology defining the tidal duration asymmetry and velocity skewness, proposed by Nidzieko (J Geophys Res 115: C08006. doi: 10.1029/2009JC005864 , 2010) and synthesized by Song et al. (J Geophys Res 116: C12007. doi: 10.1029/2011JC007270 , 2011), is utilized here and referred to as tidal duration asymmetry (TDA) and flow velocity asymmetry (FVA), respectively. The methodology is further used to quantify the flow duration asymmetry (FDA). A positive asymmetry means a shorter duration of low water slack for FDA, a shorter duration of the rising tide for TDA, and a flood dominance for FVA and vice versa. The Regional Ocean Modeling System (ROMS) model is used to provide relatively long-term water elevation and velocity data and to conduct diagnostic experiments. In the HE, the main tidal constituents are diurnal tides K 1, O 1 and semidiurnal tides M 2 and S 2. The interaction among the diurnal and semidiurnal tides generates a negative tidal asymmetry, while the interactions among semidiurnal tides and their overtides or compound tides result in a positive tidal asymmetry. The competition among the above interactions determines the FDA and TDA, whereas for the FVA, aside from the interaction among different tidal constituents, an extra component, the residual flow, plays an important role. The results show that the FDA exhibits a predominant tendency of shorter duration of low water slack, favoring the landward transport of fine sediment. The FVA demonstrates prevailing ebb dominance in the study period, favoring the seaward transport of coarse sediment. This ebb dominance is primarily induced by the interaction among the residual flow and the tidal constituents. The external TDA in the ocean experiences distinct cyclic variations with positive asymmetry when semidiurnal tides dominate and negative asymmetry during the periods when diurnal tides dominate. The funnel shape of the HE is advantageous for the development of positive tidal asymmetry as the semidiurnal tides are more amplified than the diurnal tides. The effect of river flow can enhance the ebb dominance, while the baroclinic effect is more complex. The existence of channel and shoals favors the development of residual pattern with seaward flow (ebb dominance) in the channel and landward flow (flood dominance) at the shoal when the tides are strong (semidiurnal tides dominate) and the residual pattern with landward flow (flood dominance) in the channel and seaward flow (ebb dominance) at the shoal when the baroclinic effect is dominant (diurnal tides dominate).

The role of ENSO in determining the emission, the speciation and the resulting fate of Hg from Biomass Burning, a lesson from the recent past

NASA Astrophysics Data System (ADS)

De Simone, F.; Hedgecock, I. M.; Cinnirella, S.; Carbone, F.; Sprovieri, F.; Pirrone, N.

2017-12-01

The burning of vegetation is an environmental process that impacts the chemical composition of troposphere on a global scale, and has significant consequences on atmospheric pollution and climate. ENSO influences the alternating patterns of drier and wetter periods in almost all continents, therefore causing a rise in, and varying the timing of, fire activity in numerous regions and ecosystems (Le Page et al). A large amount of legacy Hg is currently buffered in different environmental compartments, including soil and vegetation, due to past and current anthropogenic processes and activities. Biomass Burning (BB) is a major source of atmospheric Hg, and a main driver in recycling this legacy Hg which is eventually re-deposited over land and oceans. Hg from BB is emitted mainly as Hg(0)(g), but a large fraction (up to 30% and more) is released as Hg bound to particulate matter, Hg(p), which is more likely to be deposited close to the fire activity (De Simone et al). Thus, speciation is one of the most important factors in determining the redistribution of Hg, and of the subsequent geographical distribution of its atmospheric deposition. Although the drivers controlling speciation remain uncertain, there is evidence that it depends on burn characteristics and fuel moisture content, which depends on the climatological characteristics of the regions where BB occurs (Obrist et al). The areas where atmospheric Hg is deposited depends ultimately on atmospheric transport, transformation and precipitation patterns, hence the fate of Hg emitted from BB is determined by a complex series of interacting processes and mechanisms, which begin with the release of Hg and continue until deposition. Many of these processes are influenced by ENSO. This modeling study analyses the deposition of Hg from BB using different satellite imagery based products, spanning a number of years, characterized by different ENSO regimes, to evaluate how it impacts BB, the speciation of emitted Hg, and ultimately the fate of Hg. The aim is to identify the key mechanism(s) involved in determining the final receptors of Hg recycled by BB changing climate. Le Page et al., https://doi.org/10.5194/acp-8-1911-2008, 2008 De Simone et al., https://doi.org/10.5194/acp-17-1881-2017, 2017 Obrist et al., https://doi.org/10.1021/es071279n

Structure of catalase determined by MicroED

PubMed Central

Nannenga, Brent L; Shi, Dan; Hattne, Johan; Reyes, Francis E; Gonen, Tamir

2014-01-01

MicroED is a recently developed method that uses electron diffraction for structure determination from very small three-dimensional crystals of biological material. Previously we used a series of still diffraction patterns to determine the structure of lysozyme at 2.9 Å resolution with MicroED (Shi et al., 2013). Here we present the structure of bovine liver catalase determined from a single crystal at 3.2 Å resolution by MicroED. The data were collected by continuous rotation of the sample under constant exposure and were processed and refined using standard programs for X-ray crystallography. The ability of MicroED to determine the structure of bovine liver catalase, a protein that has long resisted atomic analysis by traditional electron crystallography, demonstrates the potential of this method for structure determination. DOI: http://dx.doi.org/10.7554/eLife.03600.001 PMID:25303172

Performance study of a PET scanner based on monolithic scintillators for different DoI-dependent methods

NASA Astrophysics Data System (ADS)

Preziosi, E.; Sánchez, S.; González, A. J.; Pani, R.; Borrazzo, C.; Bettiol, M.; Rodriguez-Alvarez, M. J.; González-Montoro, A.; Moliner, L.; Benlloch, J. M.

2016-12-01

One of the technical objectives of the MindView project is developing a brain-dedicated PET insert based on monolithic scintillation crystals. It will be inserted in MRI systems with the purpose to obtain simultaneous PET and MRI brain images. High sensitivity, high image quality performance and accurate detection of the Depth-of-Interaction (DoI) of the 511keV photons are required. We have developed a DoI estimation method, dedicated to monolithic scintillators, allowing continuous DoI estimation and a DoI-dependent algorithm for the estimation of the photon planar impact position, able to improve the single module imaging capabilities. In this work, through experimental measurements, the proposed methods have been used for the estimation of the impact positions within the monolithic crystal block. We have evaluated the PET system performance following the NEMA NU 4-2008 protocol by reconstructing the images using the STIR 3D platform. The results obtained with two different methods, providing discrete and continuous DoI information, are compared with those obtained from an algorithm without DoI capabilities and with the ideal response of the detector. The proposed DoI-dependent imaging methods show clear improvements in the spatial resolution (FWHM) of reconstructed images, allowing to obtain values from 2mm (at the center FoV) to 3mm (at the FoV edges).

π-π stacking tackled with density functional theory

PubMed Central

Swart, Marcel; van der Wijst, Tushar; Fonseca Guerra, Célia

2007-01-01

Through comparison with ab initio reference data, we have evaluated the performance of various density functionals for describing π-π interactions as a function of the geometry between two stacked benzenes or benzene analogs, between two stacked DNA bases, and between two stacked Watson–Crick pairs. Our main purpose is to find a robust and computationally efficient density functional to be used specifically and only for describing π-π stacking interactions in DNA and other biological molecules in the framework of our recently developed QM/QM approach "QUILD". In line with previous studies, most standard density functionals recover, at best, only part of the favorable stacking interactions. An exception is the new KT1 functional, which correctly yields bound π-stacked structures. Surprisingly, a similarly good performance is achieved with the computationally very robust and efficient local density approximation (LDA). Furthermore, we show that classical electrostatic interactions determine the shape and depth of the π-π stacking potential energy surface. Figure Additivity approximation for the π-π interaction between two stacked Watson–Crick base pairs in terms of pairwise interactions between individual bases Electronic supplementary material The online version of this article (doi:10.1007/s00894-007-0239-y) contains supplementary material, which is available to authorized users. PMID:17874150

A fitness trade-off between seasons causes multigenerational cycles in phenotype and population size

PubMed Central

Betini, Gustavo S; McAdam, Andrew G; Griswold, Cortland K; Norris, D Ryan

2017-01-01

Although seasonality is widespread and can cause fluctuations in the intensity and direction of natural selection, we have little information about the consequences of seasonal fitness trade-offs for population dynamics. Here we exposed populations of Drosophila melanogaster to repeated seasonal changes in resources across 58 generations and used experimental and mathematical approaches to investigate how viability selection on body size in the non-breeding season could affect demography. We show that opposing seasonal episodes of natural selection on body size interacted with both direct and delayed density dependence to cause populations to undergo predictable multigenerational density cycles. Our results provide evidence that seasonality can set the conditions for life-history trade-offs and density dependence, which can, in turn, interact to cause multigenerational population cycles. DOI: http://dx.doi.org/10.7554/eLife.18770.001 PMID:28164780

Experimental Evidence of Dipolar Interaction in Bilayer Nanocomposite Magnets

DTIC Science & Technology

2010-11-25

corporated to improve experimental systems. However, re- ported bulk nanocomposite magnets exhibit (BH)max val- ues that are far below the...Appl Phys A DOI 10.1007/s00339-010-6073-6 Experimental evidence of dipolar interaction in bilayer nanocomposite magnets A.J. Zambano · H. Oguchi · I...Abstract We use magnetic thin film hard/non/soft-mag- netic trilayer systems to probe the nature of the hard–soft phase interaction and the role

Investigation of the Hydantoin Monomer and its Interaction with Water Molecules

NASA Astrophysics Data System (ADS)

Gruet, Sébastien; Perez, Cristobal; Schnell, Melanie

2017-06-01

Hydantoin (Imidazolidine-2,4-dione, C_3H_4N_2O_2) is a five-membered heterocyclic compound of astrobiological interest. This molecule has been detected in carbonaceous chondrites [1], and its formation can rise from the presence of glycolic acid and urea, two prebiotic molecules [2]. The hydrolysis of hydantoin under acidic conditions can also produce glycine [3], an amino acid actively searched for in the interstellar medium. Spectroscopic data of hydantoin is very limited and mostly dedicated to the solid phase. The high resolution study in gas phase is restricted to the work recently published by Ozeki et al. reporting the pure rotational spectra of the ground state and two vibrational states of the molecule in the millimeter-wave region (90-370 GHz)[4]. Using chirped-pulse Fourier-transform microwave (CP-FTMW) spectroscopy, we recorded the jet-cooled rotational spectra of hydantoin with water between 2 to 8 GHz. We observed the ground state of hydantoin monomer and several water complexes with one or two water molecules. All the observed species exhibit a hyperfine structure due to the two nitrogen atoms present in the molecule, which were fully resolved and analyzed. Additional experiments with a ^{18}O enriched water sample were realized to determine the oxygen-atom positions of the water monomers. These experiments yielded accurate structural information on the preferred water binding sites. The observed complexes and the interactions that hold them together, mainly strong directional hydrogen bonds, will be presented and discussed. [1] Shimoyama, A. and Ogasawara, R., Orig. Life Evol. Biosph., 32, 165-179, 2002. DOI:10.1023/A:1016015319112. [2] Menor-Salván, C. and Marín-Yaseli, M.R., Chem. Soc. Rev., 41(16), 5404-5415, 2012. DOI:10.1039/c2cs35060b. [3] De Marcellus P., Bertrand M., Nuevo M., Westall F. and Le Sergeant d'Hendecourt L., Astrobiology. 11(9), 847-854, 2011. DOI:10.1089/ast.2011.0677. [4] Ozeki, H., Miyahara R., Ihara H., Todaka S., Kobayashi K., and Ohishi M., Astron. Astrophys., Forthcoming article (

A novel single-ended readout depth-of-interaction PET detector fabricated using sub-surface laser engraving.

PubMed

Uchida, H; Sakai, T; Yamauchi, H; Hakamata, K; Shimizu, K; Yamashita, T

2016-09-21

We propose a novel scintillation detector design for positron emission tomography (PET), which has depth of interaction (DOI) capability and uses a single-ended readout scheme. The DOI detector contains a pair of crystal bars segmented using sub-surface laser engraving (SSLE). The two crystal bars are optically coupled to each other at their top segments and are coupled to two photo-sensors at their bottom segments. Initially, we evaluated the performance of different designs of single crystal bars coupled to photomultiplier tubes at both ends. We found that segmentation by SSLE results in superior performance compared to the conventional method. As the next step, we constructed a crystal unit composed of a 3  ×  3  ×  20 mm 3 crystal bar pair, with each bar containing four layers segmented using the SSLE. We measured the DOI performance by changing the optical conditions for the crystal unit. Based on the experimental results, we then assessed the detector performance in terms of the DOI capability by evaluating the position error, energy resolution, and light collection efficiency for various crystal unit designs with different bar sizes and a different number of layers (four to seven layers). DOI encoding with small position error was achieved for crystal units composed of a 3  ×  3  ×  20 mm 3 LYSO bar pair having up to seven layers, and with those composed of a 2  ×  2  ×  20 mm 3 LYSO bar pair having up to six layers. The energy resolution of the segment in the seven-layer 3  ×  3  ×  20 mm 3 crystal bar pair was 9.3%-15.5% for 662 keV gamma-rays, where the segments closer to the photo-sensors provided better energy resolution. SSLE provides high geometrical accuracy at low production cost due to the simplicity of the crystal assembly. Therefore, the proposed DOI detector is expected to be an attractive choice for practical small-bore PET systems dedicated to imaging of the brain, breast, and small animals.

Metabolite exchange between microbiome members produces compounds that influence Drosophila behavior

PubMed Central

Fischer, Caleb N; Trautman, Eric P; Crawford, Jason M; Stabb, Eric V; Handelsman, Jo; Broderick, Nichole A

2017-01-01

Animals host multi-species microbial communities (microbiomes) whose properties may result from inter-species interactions; however, current understanding of host-microbiome interactions derives mostly from studies in which elucidation of microbe-microbe interactions is difficult. In exploring how Drosophila melanogaster acquires its microbiome, we found that a microbial community influences Drosophila olfactory and egg-laying behaviors differently than individual members. Drosophila prefers a Saccharomyces-Acetobacter co-culture to the same microorganisms grown individually and then mixed, a response mainly due to the conserved olfactory receptor, Or42b. Acetobacter metabolism of Saccharomyces-derived ethanol was necessary, and acetate and its metabolic derivatives were sufficient, for co-culture preference. Preference correlated with three emergent co-culture properties: ethanol catabolism, a distinct volatile profile, and yeast population decline. Egg-laying preference provided a context-dependent fitness benefit to larvae. We describe a molecular mechanism by which a microbial community affects animal behavior. Our results support a model whereby emergent metabolites signal a beneficial multispecies microbiome. DOI: http://dx.doi.org/10.7554/eLife.18855.001 PMID:28068220

SOX2 O-GlcNAcylation alters its protein-protein interactions and genomic occupancy to modulate gene expression in pluripotent cells

PubMed Central

Myers, Samuel A; Peddada, Sailaja; Chatterjee, Nilanjana; Friedrich, Tara; Tomoda, Kiichrio; Krings, Gregor; Thomas, Sean; Maynard, Jason; Broeker, Michael; Thomson, Matthew; Pollard, Katherine; Yamanaka, Shinya; Burlingame, Alma L; Panning, Barbara

2016-01-01

The transcription factor SOX2 is central in establishing and maintaining pluripotency. The processes that modulate SOX2 activity to promote pluripotency are not well understood. Here, we show SOX2 is O-GlcNAc modified in its transactivation domain during reprogramming and in mouse embryonic stem cells (mESCs). Upon induction of differentiation SOX2 O-GlcNAcylation at serine 248 is decreased. Replacing wild type with an O-GlcNAc-deficient SOX2 (S248A) increases reprogramming efficiency. ESCs with O-GlcNAc-deficient SOX2 exhibit alterations in gene expression. This change correlates with altered protein-protein interactions and genomic occupancy of the O-GlcNAc-deficient SOX2 compared to wild type. In addition, SOX2 O-GlcNAcylation impairs the SOX2-PARP1 interaction, which has been shown to regulate ESC self-renewal. These findings show that SOX2 activity is modulated by O-GlcNAc, and provide a novel regulatory mechanism for this crucial pluripotency transcription factor. DOI: http://dx.doi.org/10.7554/eLife.10647.001 PMID:26949256

Cyclophilin A-regulated ubiquitination is critical for RIG-I-mediated antiviral immune responses

PubMed Central

Liu, Wei; Li, Jing; Zheng, Weinan; Shang, Yingli; Zhao, Zhendong; Wang, Shanshan; Bi, Yuhai; Zhang, Shuang; Xu, Chongfeng; Duan, Ziyuan; Zhang, Lianfeng; Wang, Yue L; Jiang, Zhengfan; Liu, Wenjun; Sun, Lei

2017-01-01

RIG-I is a key cytosolic pattern recognition receptor that interacts with MAVS to induce type I interferons (IFNs) against RNA virus infection. In this study, we found that cyclophilin A (CypA), a peptidyl-prolyl cis/trans isomerase, functioned as a critical positive regulator of RIG-I-mediated antiviral immune responses. Deficiency of CypA impaired RIG-I-mediated type I IFN production and promoted viral replication in human cells and mice. Upon Sendai virus infection, CypA increased the interaction between RIG-I and its E3 ubiquitin ligase TRIM25, leading to enhanced TRIM25-mediated K63-linked ubiquitination of RIG-I that facilitated recruitment of RIG-I to MAVS. In addition, CypA and TRIM25 competitively interacted with MAVS, thereby inhibiting TRIM25-induced K48-linked ubiquitination of MAVS. Taken together, our findings reveal an essential role of CypA in boosting RIG-I-mediated antiviral immune responses by controlling the ubiquitination of RIG-I and MAVS. DOI: http://dx.doi.org/10.7554/eLife.24425.001 PMID:28594325

The E3 ligase Ubr3 regulates Usher syndrome and MYH9 disorder proteins in the auditory organs of Drosophila and mammals

PubMed Central

Li, Tongchao; Giagtzoglou, Nikolaos; Eberl, Daniel F; Jaiswal, Sonal Nagarkar; Cai, Tiantian; Godt, Dorothea; Groves, Andrew K; Bellen, Hugo J

2016-01-01

Myosins play essential roles in the development and function of auditory organs and multiple myosin genes are associated with hereditary forms of deafness. Using a forward genetic screen in Drosophila, we identified an E3 ligase, Ubr3, as an essential gene for auditory organ development. Ubr3 negatively regulates the mono-ubiquitination of non-muscle Myosin II, a protein associated with hearing loss in humans. The mono-ubiquitination of Myosin II promotes its physical interaction with Myosin VIIa, a protein responsible for Usher syndrome type IB. We show that ubr3 mutants phenocopy pathogenic variants of Myosin II and that Ubr3 interacts genetically and physically with three Usher syndrome proteins. The interactions between Myosin VIIa and Myosin IIa are conserved in the mammalian cochlea and in human retinal pigment epithelium cells. Our work reveals a novel mechanism that regulates protein complexes affected in two forms of syndromic deafness and suggests a molecular function for Myosin IIa in auditory organs. DOI: http://dx.doi.org/10.7554/eLife.15258.001 PMID:27331610

Sgol2 provides a regulatory platform that coordinates essential cell cycle processes during meiosis I in oocytes

PubMed Central

Rattani, Ahmed; Wolna, Magda; Ploquin, Mickael; Helmhart, Wolfgang; Morrone, Seamus; Mayer, Bernd; Godwin, Jonathan; Xu, Wenqing; Stemmann, Olaf; Pendas, Alberto; Nasmyth, Kim

2013-01-01

Accurate chromosome segregation depends on coordination between cohesion resolution and kinetochore-microtubule interactions (K-fibers), a process regulated by the spindle assembly checkpoint (SAC). How these diverse processes are coordinated remains unclear. We show that in mammalian oocytes Shugoshin-like protein 2 (Sgol2) in addition to protecting cohesin, plays an important role in turning off the SAC, in promoting the congression and bi-orientation of bivalents on meiosis I spindles, in facilitating formation of K-fibers and in limiting bivalent stretching. Sgol2’s ability to protect cohesin depends on its interaction with PP2A, as is its ability to silence the SAC, with the latter being mediated by direct binding to Mad2. In contrast, its effect on bivalent stretching and K-fiber formation is independent of PP2A and mediated by recruitment of MCAK and inhibition of Aurora C kinase activity respectively. By virtue of its multiple interactions, Sgol2 links many of the processes essential for faithful chromosome segregation. DOI: http://dx.doi.org/10.7554/eLife.01133.001 PMID:24192037

Integration of Tmc1/2 into the mechanotransduction complex in zebrafish hair cells is regulated by Transmembrane O-methyltransferase (Tomt)

PubMed Central

Erickson, Timothy; Morgan, Clive P; Olt, Jennifer; Hardy, Katherine; Busch-Nentwich, Elisabeth; Maeda, Reo; Clemens, Rachel; Krey, Jocelyn F; Nechiporuk, Alex; Barr-Gillespie, Peter G; Marcotti, Walter; Nicolson, Teresa

2017-01-01

Transmembrane O-methyltransferase (TOMT/LRTOMT) is responsible for non-syndromic deafness DFNB63. However, the specific defects that lead to hearing loss have not been described. Using a zebrafish model of DFNB63, we show that the auditory and vestibular phenotypes are due to a lack of mechanotransduction (MET) in Tomt-deficient hair cells. GFP-tagged Tomt is enriched in the Golgi of hair cells, suggesting that Tomt might regulate the trafficking of other MET components to the hair bundle. We found that Tmc1/2 proteins are specifically excluded from the hair bundle in tomt mutants, whereas other MET complex proteins can still localize to the bundle. Furthermore, mouse TOMT and TMC1 can directly interact in HEK 293 cells, and this interaction is modulated by His183 in TOMT. Thus, we propose a model of MET complex assembly where Tomt and the Tmcs interact within the secretory pathway to traffic Tmc proteins to the hair bundle. DOI: http://dx.doi.org/10.7554/eLife.28474.001 PMID:28534737

Dynamic NF-κB and E2F interactions control the priority and timing of inflammatory signalling and cell proliferation

PubMed Central

Ankers, John M; Awais, Raheela; Jones, Nicholas A; Boyd, James; Ryan, Sheila; Adamson, Antony D; Harper, Claire V; Bridge, Lloyd; Spiller, David G; Jackson, Dean A; Paszek, Pawel; Sée, Violaine; White, Michael RH

2016-01-01

Dynamic cellular systems reprogram gene expression to ensure appropriate cellular fate responses to specific extracellular cues. Here we demonstrate that the dynamics of Nuclear Factor kappa B (NF-κB) signalling and the cell cycle are prioritised differently depending on the timing of an inflammatory signal. Using iterative experimental and computational analyses, we show physical and functional interactions between NF-κB and the E2 Factor 1 (E2F-1) and E2 Factor 4 (E2F-4) cell cycle regulators. These interactions modulate the NF-κB response. In S-phase, the NF-κB response was delayed or repressed, while cell cycle progression was unimpeded. By contrast, activation of NF-κB at the G1/S boundary resulted in a longer cell cycle and more synchronous initial NF-κB responses between cells. These data identify new mechanisms by which the cellular response to stress is differentially controlled at different stages of the cell cycle. DOI: http://dx.doi.org/10.7554/eLife.10473.001 PMID:27185527

Trifunctional cross-linker for mapping protein-protein interaction networks and comparing protein conformational states

PubMed Central

Tan, Dan; Li, Qiang; Zhang, Mei-Jun; Liu, Chao; Ma, Chengying; Zhang, Pan; Ding, Yue-He; Fan, Sheng-Bo; Tao, Li; Yang, Bing; Li, Xiangke; Ma, Shoucai; Liu, Junjie; Feng, Boya; Liu, Xiaohui; Wang, Hong-Wei; He, Si-Min; Gao, Ning; Ye, Keqiong; Dong, Meng-Qiu; Lei, Xiaoguang

2016-01-01

To improve chemical cross-linking of proteins coupled with mass spectrometry (CXMS), we developed a lysine-targeted enrichable cross-linker containing a biotin tag for affinity purification, a chemical cleavage site to separate cross-linked peptides away from biotin after enrichment, and a spacer arm that can be labeled with stable isotopes for quantitation. By locating the flexible proteins on the surface of 70S ribosome, we show that this trifunctional cross-linker is effective at attaining structural information not easily attainable by crystallography and electron microscopy. From a crude Rrp46 immunoprecipitate, it helped identify two direct binding partners of Rrp46 and 15 protein-protein interactions (PPIs) among the co-immunoprecipitated exosome subunits. Applying it to E. coli and C. elegans lysates, we identified 3130 and 893 inter-linked lysine pairs, representing 677 and 121 PPIs. Using a quantitative CXMS workflow we demonstrate that it can reveal changes in the reactivity of lysine residues due to protein-nucleic acid interaction. DOI: http://dx.doi.org/10.7554/eLife.12509.001 PMID:26952210

Mechanism of allosteric regulation of β2-adrenergic receptor by cholesterol

PubMed Central

Manna, Moutusi; Niemelä, Miia; Tynkkynen, Joona; Javanainen, Matti; Kulig, Waldemar; Müller, Daniel J; Rog, Tomasz; Vattulainen, Ilpo

2016-01-01

There is evidence that lipids can be allosteric regulators of membrane protein structure and activation. However, there are no data showing how exactly the regulation emerges from specific lipid-protein interactions. Here we show in atomistic detail how the human β2-adrenergic receptor (β2AR) – a prototypical G protein-coupled receptor – is modulated by cholesterol in an allosteric fashion. Extensive atomistic simulations show that cholesterol regulates β2AR by limiting its conformational variability. The mechanism of action is based on the binding of cholesterol at specific high-affinity sites located near the transmembrane helices 5–7 of the receptor. The alternative mechanism, where the β2AR conformation would be modulated by membrane-mediated interactions, plays only a minor role. Cholesterol analogues also bind to cholesterol binding sites and impede the structural flexibility of β2AR, however cholesterol generates the strongest effect. The results highlight the capacity of lipids to regulate the conformation of membrane receptors through specific interactions. DOI: http://dx.doi.org/10.7554/eLife.18432.001 PMID:27897972

Development of high resolution phoswich depth-of-interaction block detectors utilizing Mg co-doped new scintillators

NASA Astrophysics Data System (ADS)

Kobayashi, Takahiro; Yamamoto, Seiichi; Yeom, Jung-Yeol; Kamada, Kei; Yoshikawa, Akira

2017-12-01

To correct for parallax error in positron emission tomography (PET), phoswich depth-of-interaction (DOI) detector using multiple scintillators with different decay times is a practical approach. However not many scintillator combinations suitable for phoswich DOI detector have been reported. Ce doped Gd3Ga3Al2O12 (GFAG) is a newly developed promising scintillator for PET detector, which has high density, high light output, appropriate light emission wavelength for silicon-photomultiplier (Si-PM) and faster decay time than that of Ce doped Gd3Al2Ga3O12 (GAGG). In this study, we developed a Si-PM based phoswich DOI block detector of GFAG with GAGG crystal arrays and evaluated its performance. We assembled a GFAG block and a GAGG block and they were optically coupled in depth direction to form a phoswich detector block. The phoswich block was optically coupled to a Si-PM array with a 1 mm thick light guide. The sizes of the GFAG and GAGG pixels were 0.9 mm x 0.9 mm x 7.5 mm and they were arranged into 24 x 24 matrix with 0.1 mm thick BaSO4 as reflector. We conducted the performance evaluation for two types of configurations; GFAG block arranged in upper layer (GFAG/GAGG) and GAGG arranged in upper layer (GAGG/GFAG). The measured two dimensional position histograms of these block detectors showed good separation and pulse shape spectra produced two distinct peaks for both configurations although some difference in energy spectra were observed. These results indicate phoswich block detectors composed of GFAG and GAGG are promising for high resolution DOI PET systems.

Predicting the timing properties of phosphor-coated scintillators using Monte Carlo light transport simulation

PubMed Central

Roncali, Emilie; Schmall, Jeffrey P.; Viswanath, Varsha; Berg, Eric; Cherry, Simon R.

2014-01-01

Current developments in positron emission tomography (PET) focus on improving timing performance for scanners with time-of-flight (TOF) capability, and incorporating depth-of-interaction (DOI) information. Recent studies have shown that incorporating DOI correction in TOF detectors can improve timing resolution, and that DOI also becomes more important in long axial field-of-view scanners. We have previously reported the development of DOI-encoding detectors using phosphor-coated scintillation crystals; here we study the timing properties of those crystals to assess the feasibility of providing some level of DOI information without significantly degrading the timing performance. We used Monte Carlo simulations to provide a detailed understanding of light transport in phosphor-coated crystals which cannot be fully characterized experimentally. Our simulations used a custom reflectance model based on 3D crystal surface measurements. Lutetium oxyorthosilicate (LSO) crystals were simulated with a phosphor coating in contact with the scintillator surfaces and an external diffuse reflector (teflon). Light output, energy resolution, and pulse shape showed excellent agreement with experimental data obtained on 3 × 3 × 10 mm3 crystals coupled to a photomultiplier tube (PMT). Scintillator intrinsic timing resolution was simulated with head-on and side-on configurations, confirming the trends observed experimentally. These results indicate that the model may be used to predict timing properties in phosphor-coated crystals and guide the coating for optimal DOI resolution/timing performance trade-off for a given crystal geometry. Simulation data suggested that a time stamp generated from early photoelectrons minimizes degradation of the timing resolution, thus making this method potentially more useful for TOF-DOI detectors than our initial experiments suggested. Finally, this approach could easily be extended to the study of timing properties in other scintillation crystals, with a range of treatments and materials attached to the surface. PMID:24694727

A depth-encoding PET detector that uses light sharing and single-ended readout with silicon photomultipliers

NASA Astrophysics Data System (ADS)

Kuang, Zhonghua; Yang, Qian; Wang, Xiaohui; Fu, Xin; Ren, Ning; Sang, Ziru; Wu, San; Zheng, Yunfei; Zhang, Xianming; Hu, Zhanli; Du, Junwei; Liang, Dong; Liu, Xin; Zheng, Hairong; Yang, Yongfeng

2018-02-01

Detectors with depth-encoding capability and good timing resolution are required to develop high-performance whole-body or total-body PET scanners. In this work, depth-encoding PET detectors that use light sharing between two discrete crystals and single-ended readout with silicon photomultipliers (SiPMs) were manufactured and evaluated. The detectors consisted of two unpolished 3  ×  3  ×  20 mm3 LYSO crystals with different coupling materials between them and were read out by Hamamatsu 3  ×  3 mm2 SiPMs with one-to-one coupling. The ratio of the energy of one SiPM to the total energy of two SiPMs was used to measure the depth of interaction (DOI). Detectors with different coupling materials in-between the crystals were measured in the singles mode in an effort to obtain detectors that can provide good DOI resolution. The DOI resolution and energy resolution of three types of detector were measured and the timing resolution was measured for the detector with the best DOI and energy resolution. The optimum detector, with 5 mm optical glue, a 9 mm triangular ESR and a 6 mm rectangular ESR in-between the unpolished crystals, provides a DOI resolution of 2.65 mm, an energy resolution of 10.0% and a timing resolution of 427 ps for events of E  >  400 keV. The detectors simultaneously provide good DOI and timing resolution, and show great promise for the development of high-performance whole-body and total-body PET scanners.

Effects of Detector Thickness on Geometric Sensitivity and Event Positioning Errors in the Rectangular PET/X Scanner

NASA Astrophysics Data System (ADS)

MacDonald, Lawrence R.; Hunter, William C. J.; Kinahan, Paul E.; Miyaoka, Robert S.

2013-10-01

We used simulations to investigate the relationship between sensitivity and spatial resolution as a function of crystal thickness in a rectangular PET scanner intended for quantitative assessment of breast cancers. The system had two 20 × 15-cm2 and two 10 × 15-cm2 flat detectors forming a box, with the larger detectors separated by 4 or 8 cm. Depth-of-interaction (DOI) resolution was modeled as a function of crystal thickness based on prior measurements. Spatial resolution was evaluated independent of image reconstruction by deriving and validating a surrogate metric from list-mode data ( dFWHM). When increasing crystal thickness from 5 to 40 mm, and without using DOI information, the dFWHM for a centered point source increased from 0.72 to 1.6 mm. Including DOI information improved dFWHM by 12% and 27% for 5- and 40-mm-thick crystals, respectively. For a point source in the corner of the FOV, use of DOI information improved dFWHM by 20% (5-mm crystal) and 44% (40-mm crystal). Sensitivity was 7.7% for 10-mm-thick crystals (8-cm object). Increasing crystal thickness on the smaller side detectors from 10 to 20 mm (keeping 10-mm crystals on the larger detectors) boosted sensitivity by 24% (relative) and degraded dFWHM by only 3%/8% with/without DOI information. The benefits of measuring DOI must be evaluated in terms of the intended clinical task of assessing tracer uptake in small lesions. Increasing crystal thickness on the smaller side detectors provides substantial sensitivity increase with minimal accompanying loss in resolution.

Serotonergic and dopaminergic distinctions in the behavioral pharmacology of (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and lysergic acid diethylamide (LSD).

PubMed

Schindler, Emmanuelle A D; Dave, Kuldip D; Smolock, Elaine M; Aloyo, Vincent J; Harvey, John A

2012-03-01

After decades of social stigma, hallucinogens have reappeared in the clinical literature demonstrating unique benefits in medicine. The precise behavioral pharmacology of these compounds remains unclear, however. Two commonly studied hallucinogens, (±)-1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI) and lysergic acid diethylamide (LSD), were investigated both in vivo and in vitro to determine the pharmacology of their behavioral effects in an animal model. Rabbits were administered DOI or LSD and observed for head bob behavior after chronic drug treatment or after pretreatment with antagonist ligands. The receptor binding characteristics of DOI and LSD were studied in vitro in frontocortical homogenates from naïve rabbits or ex vivo in animals receiving an acute drug injection. Both DOI- and LSD-elicited head bobs required serotonin(2A) (5-HT(2A)) and dopamine(1) (D(1)) receptor activation. Serotonin(2B/2C) receptors were not implicated in these behaviors. In vitro studies demonstrated that LSD and the 5-HT(2A/2C) receptor antagonist, ritanserin, bound frontocortical 5-HT(2A) receptors in a pseudo-irreversible manner. In contrast, DOI and the 5-HT(2A/2C) receptor antagonist, ketanserin, bound reversibly. These binding properties were reflected in ex vivo binding studies. The two hallucinogens also differed in that LSD showed modest D(1) receptor binding affinity whereas DOI had negligible binding affinity at this receptor. Although DOI and LSD differed in their receptor binding properties, activation of 5-HT(2A) and D(1) receptors was a common mechanism for eliciting head bob behavior. These findings implicate these two receptors in the mechanism of action of hallucinogens. Copyright © 2011 Elsevier Inc. All rights reserved.

P- T- t constraints on the development of the Doi Inthanon metamorphic core complex domain and implications for the evolution of the western gneiss belt, northern Thailand

NASA Astrophysics Data System (ADS)

Macdonald, A. S.; Barr, S. M.; Miller, B. V.; Reynolds, P. H.; Rhodes, B. P.; Yokart, B.

2010-01-01

The western gneiss belt in northern Thailand is exposed within two overlapping Cenozoic structural domains: the extensional Doi Inthanon metamorphic core complex domain located west of the Chiang Mai basin, and the Mae Ping strike-slip fault domain located west of the Tak batholith. New P- T estimates and U-Pb and 40Ar/ 39Ar age determinations from the Doi Inthanon domain show that the gneiss there records a complex multi-stage history that can be represented by a clockwise P- T- t path. U-Pb zircon and titanite dating of mylonitic calc-silicate gneiss from the Mae Wang area of the complex indicates that the paragneissic sequence experienced high-grade, medium-pressure metamorphism (M1) in the Late Triassic - Early Jurassic (ca. 210 Ma), in good agreement with previously determined zircon ages from the underlying core orthogneiss exposed on Doi Inthanon. Late Cretaceous monazite ages of 84 and 72 Ma reported previously from the core orthogneiss are attributed to a thermal overprint (M2) to upper-amphibolite facies in the sillimanite field. U-Pb zircon and monazite dating of granitic mylonite from the Doi Suthep area of the complex provides an upper age limit of 40 Ma (Late Eocene) for the early stage(s) of development of the actual core complex, by initially ductile, low-angle extensional shearing under lower amphibolite-facies conditions (M3), accompanied by near-isothermal diapiric rise and decompression melting. 40Ar/ 39Ar laserprobe dating of muscovite from both Doi Suthep and Doi Inthanon provided Miocene ages of ca. 26-15 Ma, representing cooling through the ca. 350 °C isotherm and marking late-stage development of the core complex by detachment faulting of the cover rocks and isostatic uplift of the sheared core zone and mantling gneisses in the footwall. Similarities in the thermochronology of high-grade gneisses exposed in the core complex and shear zone domains in the western gneiss belt of northern Thailand (and also in northern Vietnam, Laos, Yunnan, and central Myanmar) suggest a complex regional response to indentation of Southeast Asia by India.

Leadership emergence in a data-driven model of zebrafish shoals with speed modulation

NASA Astrophysics Data System (ADS)

Zienkiewicz, A.; Barton, D. A. W.; Porfiri, M.; Di Bernardo, M.

2015-11-01

Models of collective animal motion can greatly aid in the design and interpretation of behavioural experiments that seek to unravel, isolate, and manipulate the determinants of leader-follower relationships. Here, we develop an initial model of zebrafish social behaviour, which accounts for both speed and angular velocity regulatory interactions among conspecifics. Using this model, we analyse the macroscopic observables of small shoals influenced by an "informed" agent, showing that leaders which actively modulate their speed with respect to their neighbours can entrain and stabilise collective dynamics of the naïve shoal. Supplementary material in the form of two mp4 files available from the Journal web page at http://dx.doi.org/10.1140/epjst/e2015-50093-5

Brassinosteroids control root epidermal cell fate via direct regulation of a MYB-bHLH-WD40 complex by GSK3-like kinases

PubMed Central

Cheng, Yinwei; Zhu, Wenjiao; Chen, Yuxiao; Ito, Shinsaku; Asami, Tadao; Wang, Xuelu

2014-01-01

In Arabidopsis, root hair and non-hair cell fates are determined by a MYB-bHLH-WD40 transcriptional complex and are regulated by many internal and environmental cues. Brassinosteroids play important roles in regulating root hair specification by unknown mechanisms. Here, we systematically examined root hair phenotypes in brassinosteroid-related mutants, and found that brassinosteroid signaling inhibits root hair formation through GSK3-like kinases or upstream components. We found that with enhanced brassinosteroid signaling, GL2, a cell fate marker for non-hair cells, is ectopically expressed in hair cells, while its expression in non-hair cells is suppressed when brassinosteroid signaling is reduced. Genetic analysis demonstrated that brassinosteroid-regulated root epidermal cell patterning is dependent on the WER-GL3/EGL3-TTG1 transcriptional complex. One of the GSK3-like kinases, BIN2, interacted with and phosphorylated EGL3, and EGL3s mutated at phosphorylation sites were retained in hair cell nuclei. BIN2 phosphorylated TTG1 to inhibit the activity of the WER-GL3/EGL3-TTG1 complex. Thus, our study provides insights into the mechanism of brassinosteroid regulation of root hair patterning. DOI: http://dx.doi.org/10.7554/eLife.02525.001 PMID:24771765

Understanding Protein-Protein Interactions: Essential Players in (Patho)physiology (Part 1).

PubMed

Wilson, Andrew J; Gunning, Patrick T

2016-04-15

This is the first of a two-part Editorial by the Guest Editors of the ChemBioChem and ChemMedChem joint Special Issue on Protein-Protein Interactions. Part 2 can be accessed via http://dx.doi.org/10.1002/cmdc.201600158; the complete issue can be viewed here: bit.ly/cbcVIppi. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Multiresolution Algorithms for Processing Giga-Models: Real-time Visualization, Reasoning, and Interaction

DTIC Science & Technology

2012-04-23

Interactive Virtual Hair Salon , Presence, (05 2007): 237. doi: 2012/04/17 12:55:26 31 Theodore Kim, Jason Sewall, Avneesh Sud, Ming Lin. Fast...in Games , Utrecht, Netherlands, Nov. 2009. Keynote Speaker, IADIS International Conference on Computer Graphics and Visualization, Portugal, June 2009...Keynote Speaker, ACM Symposium on Virtual Reality Software and Technology, Bordeaux, France, October 2008. Invited Speaker, Motion in Games , Utrecht

Performance and field tests of a handheld Compton camera using 3-D position-sensitive scintillators coupled to multi-pixel photon counter arrays

NASA Astrophysics Data System (ADS)

Kishimoto, A.; Kataoka, J.; Nishiyama, T.; Fujita, T.; Takeuchi, K.; Okochi, H.; Ogata, H.; Kuroshima, H.; Ohsuka, S.; Nakamura, S.; Hirayanagi, M.; Adachi, S.; Uchiyama, T.; Suzuki, H.

2014-11-01

After the nuclear disaster in Fukushima, radiation decontamination has become particularly urgent. To help identify radiation hotspots and ensure effective decontamination operation, we have developed a novel Compton camera based on Ce-doped Gd3Al2Ga3O12 scintillators and multi-pixel photon counter (MPPC) arrays. Even though its sensitivity is several times better than that of other cameras being tested in Fukushima, we introduce a depth-of-interaction (DOI) method to further improve the angular resolution. For gamma rays, the DOI information, in addition to 2-D position, is obtained by measuring the pulse-height ratio of the MPPC arrays coupled to ends of the scintillator. We present the detailed performance and results of various field tests conducted in Fukushima with the prototype 2-D and DOI Compton cameras. Moreover, we demonstrate stereo measurement of gamma rays that enables measurement of not only direction but also approximate distance to radioactive hotspots.

Efficient system modeling for a small animal PET scanner with tapered DOI detectors.

PubMed

Zhang, Mengxi; Zhou, Jian; Yang, Yongfeng; Rodríguez-Villafuerte, Mercedes; Qi, Jinyi

2016-01-21

A prototype small animal positron emission tomography (PET) scanner for mouse brain imaging has been developed at UC Davis. The new scanner uses tapered detector arrays with depth of interaction (DOI) measurement. In this paper, we present an efficient system model for the tapered PET scanner using matrix factorization and a virtual scanner geometry. The factored system matrix mainly consists of two components: a sinogram blurring matrix and a geometrical matrix. The geometric matrix is based on a virtual scanner geometry. The sinogram blurring matrix is estimated by matrix factorization. We investigate the performance of different virtual scanner geometries. Both simulation study and real data experiments are performed in the fully 3D mode to study the image quality under different system models. The results indicate that the proposed matrix factorization can maintain image quality while substantially reduce the image reconstruction time and system matrix storage cost. The proposed method can be also applied to other PET scanners with DOI measurement.

Evaluation of the interaction between plant roots and preferential flow paths

NASA Astrophysics Data System (ADS)

Zhang, Yinghu; Niu, Jianzhi; Zhang, Mingxiang; Xiao, Zixing; Zhu, Weili

2017-04-01

Introduction Preferential flow causing environmental issues by carrying contaminants to the groundwater resources level, occurs throughout the world. Soil water flow and solute transportation via preferential flow paths with little resistance could bypass soil matrix quickly. It is necessary to characterize preferential flow phenomenon because of its understanding of ecological functions of soil, including the degradation of topsoil, the low activity of soil microorganisms, the loss of soil nutrients, and the serious source of pollution of groundwater resources (Brevik et al., 2015; Singh et al., 2015). Studies on the interaction between plant roots and soil water flow in response to preferential flow is promising increasingly. However, it is complicated to evaluate soil hydrology when plant roots are associated with the mechanisms of soil water flow and solute transportation, especially preferential flow (Ola et al., 2015). Root channels formed by living/decayed plant roots and root-soil interfaces affect soil hydrology (Tracy et al., 2011). For example, Jørgensen et al. (2002) stated that soil water flow was more obvious in soil profiles with plant roots than in soil profiles without plant roots. The present study was conducted to investigate the interaction between plant roots and soil water flow in response to preferential flow in stony soils. Materials and methods Field experiments: field dye tracing experiments centered on experimental plants (S. japonica Linn, P. orientalis (L.) Franco, and Q. dentata Thunb) were conducted to characterize the root length density, preferential flow paths (stained areas), and soil matrix (unstained areas). Brilliant Blue FCF (C.I. Food Blue 2) as dye solution (50 L) was applied to the experimental plots. Laboratory analyses: undisturbed soil columns (7-cm diameter, 10 cm high) obtained from soil depths of 0-20, 20-40, and 40-60 cm, respectively, were conducted with breakthrough curves experiments under different conditions maintaining (1) a constant hydraulic head of 1ṡ0 cm of water with various solution concentrations of 0ṡ5, 1ṡ0, and 1ṡ5 g L-1, and (2) a constant solution concentration of 1ṡ0 g L-1 with various hydraulic heads of 0ṡ5, 1ṡ0, and 1ṡ5 cm of water, and those columns were conducted under saturated and unsaturated soil conditions, respectively. The effluent samples were measured with an ultraviolet spectrometer subsystem to determine the relative concentration. The plant root-water interaction (PRWI) was recognized as an indicator of the influences of plant roots on soil water flow. Results Our study showed that (1) fine plant roots in preferential flow paths decreased with soil depth and was mostly recorded in the upper soil layers to a depth of 20 cm for all experimental plots. The root length density of preferential flow paths made up at least 50% of the total root length density at each soil depth; (2) preferential flow effects were most apparent on soil water flow at the 0-20-cm soil depth compared with the other depths (20-40 and 40-60 cm); (3) positive correlations between fine plant roots and the plant root-water interaction (PRWI) were observed. References Brevik EC, Cerdà A, Mataix-Solera J, Pereg L, Quinton JN, Six J, Van Oost K. 2015. The interdisciplinary nature of SOIL. SOIL 1: 117-129. DOI: 10.5194/soil-1-117-2015. Singh YP, Nayak AK, Sharma DK, Singh G, Mishra VK, Singh D. 2015. Evaluation of Jatropha curcas genotypes for rehabilitation of degraded sodic lands. Land Degradation & Development 26(5): 510-520. DOI: 10.1002/ldr.2398. Ola A, Dodd IC, Quinton JN. 2015. Can we manipulate root system architecture to control soil erosion? SOIL 1: 603-612. DOI: 10.5194/soild-2-265-2015. Tracy SR, Black CR, Roberts JA, Mooney SJ. 2011. Soil compaction: a review of past and present techniques for investigating effects on root growth. Journal of the Science of Food & Agriculture 91: 1528-1537. DOI: 10.1002/jsfa.4424. Jørgensen PR, Hoffmann M, Kistrup JP, Bryde C, Bossi R, Villholth KG. 2002. Preferential flow and pesticide transport in a clay-rich till: field, laboratory, and modeling analysis. Water Resources Research 38: 1246-1261. DOI: 10.1029/2001WR000494.

Mapping microbial ecosystems and spoilage-gene flow in breweries highlights patterns of contamination and resistance

PubMed Central

Bokulich, Nicholas A; Bergsveinson, Jordyn; Ziola, Barry; Mills, David A

2015-01-01

Distinct microbial ecosystems have evolved to meet the challenges of indoor environments, shaping the microbial communities that interact most with modern human activities. Microbial transmission in food-processing facilities has an enormous impact on the qualities and healthfulness of foods, beneficially or detrimentally interacting with food products. To explore modes of microbial transmission and spoilage-gene frequency in a commercial food-production scenario, we profiled hop-resistance gene frequencies and bacterial and fungal communities in a brewery. We employed a Bayesian approach for predicting routes of contamination, revealing critical control points for microbial management. Physically mapping microbial populations over time illustrates patterns of dispersal and identifies potential contaminant reservoirs within this environment. Habitual exposure to beer is associated with increased abundance of spoilage genes, predicting greater contamination risk. Elucidating the genetic landscapes of indoor environments poses important practical implications for food-production systems and these concepts are translatable to other built environments. DOI: http://dx.doi.org/10.7554/eLife.04634.001 PMID:25756611

Diabetes regulates fructose absorption through thioredoxin-interacting protein

PubMed Central

Dotimas, James R; Lee, Austin W; Schmider, Angela B; Carroll, Shannon H; Shah, Anu; Bilen, Julide; Elliott, Kayla R; Myers, Ronald B; Soberman, Roy J; Yoshioka, Jun; Lee, Richard T

2016-01-01

Metabolic studies suggest that the absorptive capacity of the small intestine for fructose is limited, though the molecular mechanisms controlling this process remain unknown. Here we demonstrate that thioredoxin-interacting protein (Txnip), which regulates glucose homeostasis in mammals, binds to fructose transporters and promotes fructose absorption by the small intestine. Deletion of Txnip in mice reduced fructose transport into the peripheral bloodstream and liver, as well as the severity of adverse metabolic outcomes resulting from long-term fructose consumption. We also demonstrate that fructose consumption induces expression of Txnip in the small intestine. Diabetic mice had increased expression of Txnip in the small intestine as well as enhanced fructose uptake and transport into the hepatic portal circulation. The deletion of Txnip in mice abolished the diabetes-induced increase in fructose absorption. Our results indicate that Txnip is a critical regulator of fructose metabolism and suggest that a diabetic state can promote fructose uptake. DOI: http://dx.doi.org/10.7554/eLife.18313.001 PMID:27725089

Extensive site-directed mutagenesis reveals interconnected functional units in the alkaline phosphatase active site

PubMed Central

Sunden, Fanny; Peck, Ariana; Salzman, Julia; Ressl, Susanne; Herschlag, Daniel

2015-01-01

Enzymes enable life by accelerating reaction rates to biological timescales. Conventional studies have focused on identifying the residues that have a direct involvement in an enzymatic reaction, but these so-called ‘catalytic residues’ are embedded in extensive interaction networks. Although fundamental to our understanding of enzyme function, evolution, and engineering, the properties of these networks have yet to be quantitatively and systematically explored. We dissected an interaction network of five residues in the active site of Escherichia coli alkaline phosphatase. Analysis of the complex catalytic interdependence of specific residues identified three energetically independent but structurally interconnected functional units with distinct modes of cooperativity. From an evolutionary perspective, this network is orders of magnitude more probable to arise than a fully cooperative network. From a functional perspective, new catalytic insights emerge. Further, such comprehensive energetic characterization will be necessary to benchmark the algorithms required to rationally engineer highly efficient enzymes. DOI: http://dx.doi.org/10.7554/eLife.06181.001 PMID:25902402

Protein translocation channel of mitochondrial inner membrane and matrix-exposed import motor communicate via two-domain coupling protein

PubMed Central

Banerjee, Rupa; Gladkova, Christina; Mapa, Koyeli; Witte, Gregor; Mokranjac, Dejana

2015-01-01

The majority of mitochondrial proteins are targeted to mitochondria by N-terminal presequences and use the TIM23 complex for their translocation across the mitochondrial inner membrane. During import, translocation through the channel in the inner membrane is coupled to the ATP-dependent action of an Hsp70-based import motor at the matrix face. How these two processes are coordinated remained unclear. We show here that the two domain structure of Tim44 plays a central role in this process. The N-terminal domain of Tim44 interacts with the components of the import motor, whereas its C-terminal domain interacts with the translocation channel and is in contact with translocating proteins. Our data suggest that the translocation channel and the import motor of the TIM23 complex communicate through rearrangements of the two domains of Tim44 that are stimulated by translocating proteins. DOI: http://dx.doi.org/10.7554/eLife.11897.001 PMID:26714107

Coordination of planar cell polarity pathways through Spiny-legs

PubMed Central

Ambegaonkar, Abhijit A; Irvine, Kenneth D

2015-01-01

Morphogenesis and physiology of tissues and organs requires planar cell polarity (PCP) systems that orient and coordinate cells and their behaviors, but the relationship between PCP systems has been controversial. We have characterized how the Frizzled and Dachsous-Fat PCP systems are connected through the Spiny-legs isoform of the Prickle-Spiny-legs locus. Two different components of the Dachsous-Fat system, Dachsous and Dachs, can each independently interact with Spiny-legs and direct its localization in vivo. Through characterization of the contributions of Prickle, Spiny-legs, Dachsous, Fat, and Dachs to PCP in the Drosophila wing, eye, and abdomen, we define where Dachs-Spiny-legs and Dachsous-Spiny-legs interactions contribute to PCP, and provide a new understanding of the orientation of polarity and the basis of PCP phenotypes. Our results support the direct linkage of PCP systems through Sple in specific locales, while emphasizing that cells can be subject to and must ultimately resolve distinct, competing PCP signals. DOI: http://dx.doi.org/10.7554/eLife.09946.001 PMID:26505959

Spatial self-organization favors heterotypic cooperation over cheating.

PubMed

Momeni, Babak; Waite, Adam James; Shou, Wenying

2013-11-12

Heterotypic cooperation-two populations exchanging distinct benefits that are costly to produce-is widespread. Cheaters, exploiting benefits while evading contribution, can undermine cooperation. Two mechanisms can stabilize heterotypic cooperation. In 'partner choice', cooperators recognize and choose cooperating over cheating partners; in 'partner fidelity feedback', fitness-feedback from repeated interactions ensures that aiding your partner helps yourself. How might a spatial environment, which facilitates repeated interactions, promote fitness-feedback? We examined this process through mathematical models and engineered Saccharomyces cerevisiae strains incapable of recognition. Here, cooperators and their heterotypic cooperative partners (partners) exchanged distinct essential metabolites. Cheaters exploited partner-produced metabolites without reciprocating, and were competitively superior to cooperators. Despite initially random spatial distributions, cooperators gained more partner neighbors than cheaters did. The less a cheater contributed, the more it was excluded and disfavored. This self-organization, driven by asymmetric fitness effects of cooperators and cheaters on partners during cell growth into open space, achieves assortment. DOI: http://dx.doi.org/10.7554/eLife.00960.001.

Spatial self-organization favors heterotypic cooperation over cheating

PubMed Central

Momeni, Babak; Waite, Adam James; Shou, Wenying

2013-01-01

Heterotypic cooperation—two populations exchanging distinct benefits that are costly to produce—is widespread. Cheaters, exploiting benefits while evading contribution, can undermine cooperation. Two mechanisms can stabilize heterotypic cooperation. In ‘partner choice’, cooperators recognize and choose cooperating over cheating partners; in ‘partner fidelity feedback’, fitness-feedback from repeated interactions ensures that aiding your partner helps yourself. How might a spatial environment, which facilitates repeated interactions, promote fitness-feedback? We examined this process through mathematical models and engineered Saccharomyces cerevisiae strains incapable of recognition. Here, cooperators and their heterotypic cooperative partners (partners) exchanged distinct essential metabolites. Cheaters exploited partner-produced metabolites without reciprocating, and were competitively superior to cooperators. Despite initially random spatial distributions, cooperators gained more partner neighbors than cheaters did. The less a cheater contributed, the more it was excluded and disfavored. This self-organization, driven by asymmetric fitness effects of cooperators and cheaters on partners during cell growth into open space, achieves assortment. DOI: http://dx.doi.org/10.7554/eLife.00960.001 PMID:24220506

A physical model describing the interaction of nuclear transport receptors with FG nucleoporin domain assemblies

PubMed Central

Zahn, Raphael; Osmanović, Dino; Ehret, Severin; Araya Callis, Carolina; Frey, Steffen; Stewart, Murray; You, Changjiang; Görlich, Dirk; Hoogenboom, Bart W; Richter, Ralf P

2016-01-01

The permeability barrier of nuclear pore complexes (NPCs) controls bulk nucleocytoplasmic exchange. It consists of nucleoporin domains rich in phenylalanine-glycine motifs (FG domains). As a bottom-up nanoscale model for the permeability barrier, we have used planar films produced with three different end-grafted FG domains, and quantitatively analyzed the binding of two different nuclear transport receptors (NTRs), NTF2 and Importin β, together with the concomitant film thickness changes. NTR binding caused only moderate changes in film thickness; the binding isotherms showed negative cooperativity and could all be mapped onto a single master curve. This universal NTR binding behavior – a key element for the transport selectivity of the NPC – was quantitatively reproduced by a physical model that treats FG domains as regular, flexible polymers, and NTRs as spherical colloids with a homogeneous surface, ignoring the detailed arrangement of interaction sites along FG domains and on the NTR surface. DOI: http://dx.doi.org/10.7554/eLife.14119.001 PMID:27058170

Real-time imaging of Huntingtin aggregates diverting target search and gene transcription

PubMed Central

Li, Li; Liu, Hui; Dong, Peng; Li, Dong; Legant, Wesley R; Grimm, Jonathan B; Lavis, Luke D; Betzig, Eric; Tjian, Robert; Liu, Zhe

2016-01-01

The presumptive altered dynamics of transient molecular interactions in vivo contributing to neurodegenerative diseases have remained elusive. Here, using single-molecule localization microscopy, we show that disease-inducing Huntingtin (mHtt) protein fragments display three distinct dynamic states in living cells – 1) fast diffusion, 2) dynamic clustering and 3) stable aggregation. Large, stable aggregates of mHtt exclude chromatin and form 'sticky' decoy traps that impede target search processes of key regulators involved in neurological disorders. Functional domain mapping based on super-resolution imaging reveals an unexpected role of aromatic amino acids in promoting protein-mHtt aggregate interactions. Genome-wide expression analysis and numerical simulation experiments suggest mHtt aggregates reduce transcription factor target site sampling frequency and impair critical gene expression programs in striatal neurons. Together, our results provide insights into how mHtt dynamically forms aggregates and disrupts the finely-balanced gene control mechanisms in neuronal cells. DOI: http://dx.doi.org/10.7554/eLife.17056.001 PMID:27484239

Molecular insights into the origin of the Hox-TALE patterning system

PubMed Central

Hudry, Bruno; Thomas-Chollier, Morgane; Volovik, Yael; Duffraisse, Marilyne; Dard, Amélie; Frank, Dale; Technau, Ulrich; Merabet, Samir

2014-01-01

Despite tremendous body form diversity in nature, bilaterian animals share common sets of developmental genes that display conserved expression patterns in the embryo. Among them are the Hox genes, which define different identities along the anterior–posterior axis. Hox proteins exert their function by interaction with TALE transcription factors. Hox and TALE members are also present in some but not all non-bilaterian phyla, raising the question of how Hox–TALE interactions evolved to provide positional information. By using proteins from unicellular and multicellular lineages, we showed that these networks emerged from an ancestral generic motif present in Hox and other related protein families. Interestingly, Hox-TALE networks experienced additional and extensive molecular innovations that were likely crucial for differentiating Hox functions along body plans. Together our results highlight how homeobox gene families evolved during eukaryote evolution to eventually constitute a major patterning system in Eumetazoans. DOI: http://dx.doi.org/10.7554/eLife.01939.001 PMID:24642410

Molecular insights into the origin of the Hox-TALE patterning system.

PubMed

Hudry, Bruno; Thomas-Chollier, Morgane; Volovik, Yael; Duffraisse, Marilyne; Dard, Amélie; Frank, Dale; Technau, Ulrich; Merabet, Samir

2014-03-18

Despite tremendous body form diversity in nature, bilaterian animals share common sets of developmental genes that display conserved expression patterns in the embryo. Among them are the Hox genes, which define different identities along the anterior-posterior axis. Hox proteins exert their function by interaction with TALE transcription factors. Hox and TALE members are also present in some but not all non-bilaterian phyla, raising the question of how Hox-TALE interactions evolved to provide positional information. By using proteins from unicellular and multicellular lineages, we showed that these networks emerged from an ancestral generic motif present in Hox and other related protein families. Interestingly, Hox-TALE networks experienced additional and extensive molecular innovations that were likely crucial for differentiating Hox functions along body plans. Together our results highlight how homeobox gene families evolved during eukaryote evolution to eventually constitute a major patterning system in Eumetazoans. DOI: http://dx.doi.org/10.7554/eLife.01939.001.

Reward modulates the effect of visual cortical microstimulation on perceptual decisions

PubMed Central

Cicmil, Nela; Cumming, Bruce G; Parker, Andrew J; Krug, Kristine

2015-01-01

Effective perceptual decisions rely upon combining sensory information with knowledge of the rewards available for different choices. However, it is not known where reward signals interact with the multiple stages of the perceptual decision-making pathway and by what mechanisms this may occur. We combined electrical microstimulation of functionally specific groups of neurons in visual area V5/MT with performance-contingent reward manipulation, while monkeys performed a visual discrimination task. Microstimulation was less effective in shifting perceptual choices towards the stimulus preferences of the stimulated neurons when available reward was larger. Psychophysical control experiments showed this result was not explained by a selective change in response strategy on microstimulated trials. A bounded accumulation decision model, applied to analyse behavioural performance, revealed that the interaction of expected reward with microstimulation can be explained if expected reward modulates a sensory representation stage of perceptual decision-making, in addition to the better-known effects at the integration stage. DOI: http://dx.doi.org/10.7554/eLife.07832.001 PMID:26402458

Homeostatic reinforcement learning for integrating reward collection and physiological stability

PubMed Central

Keramati, Mehdi; Gutkin, Boris

2014-01-01

Efficient regulation of internal homeostasis and defending it against perturbations requires adaptive behavioral strategies. However, the computational principles mediating the interaction between homeostatic and associative learning processes remain undefined. Here we use a definition of primary rewards, as outcomes fulfilling physiological needs, to build a normative theory showing how learning motivated behaviors may be modulated by internal states. Within this framework, we mathematically prove that seeking rewards is equivalent to the fundamental objective of physiological stability, defining the notion of physiological rationality of behavior. We further suggest a formal basis for temporal discounting of rewards by showing that discounting motivates animals to follow the shortest path in the space of physiological variables toward the desired setpoint. We also explain how animals learn to act predictively to preclude prospective homeostatic challenges, and several other behavioral patterns. Finally, we suggest a computational role for interaction between hypothalamus and the brain reward system. DOI: http://dx.doi.org/10.7554/eLife.04811.001 PMID:25457346

Unfair competition governs the interaction of pCPI-17 with myosin phosphatase (PP1-MYPT1)

PubMed Central

Filter, Joshua J; Williams, Byron C; Eto, Masumi; Shalloway, David; Goldberg, Michael L

2017-01-01

The small phosphoprotein pCPI-17 inhibits myosin light-chain phosphatase (MLCP). Current models postulate that during muscle relaxation, phosphatases other than MLCP dephosphorylate and inactivate pCPI-17 to restore MLCP activity. We show here that such hypotheses are insufficient to account for the observed rapidity of pCPI-17 inactivation in mammalian smooth muscles. Instead, MLCP itself is the critical enzyme for pCPI-17 dephosphorylation. We call the mutual sequestration mechanism through which pCPI-17 and MLCP interact inhibition by unfair competition: MLCP protects pCPI-17 from other phosphatases, while pCPI-17 blocks other substrates from MLCP’s active site. MLCP dephosphorylates pCPI-17 at a slow rate that is, nonetheless, both sufficient and necessary to explain the speed of pCPI-17 dephosphorylation and the consequent MLCP activation during muscle relaxation. DOI: http://dx.doi.org/10.7554/eLife.24665.001 PMID:28387646

Acknowledging selection at sub-organismal levels resolves controversy on pro-cooperation mechanisms

PubMed Central

Shou, Wenying

2015-01-01

Cooperators who pay a cost to produce publically-available benefits can be exploited by cheaters who do not contribute fairly. How might cooperation persist against cheaters? Two classes of mechanisms are known to promote cooperation: 'partner choice', where a cooperator preferentially interacts with cooperative over cheating partners; and 'partner fidelity feedback', where repeated interactions between individuals ensure that cheaters suffer as their cooperative partners languish (see, for example, Momeni et al., 2013). However when both mechanisms can act, differentiating them has generated controversy. Here, I resolve this controversy by noting that selection can operate on organismal and sub-organismal 'entities' such that partner fidelity feedback at sub-organismal level can appear as partner choice at organismal level. I also show that cooperation between multicellular eukaryotes and mitochondria is promoted by partner fidelity feedback and partner choice between sub-organismal entities, in addition to being promoted by partner fidelity feedback between hosts and symbionts, as was previously known. DOI: http://dx.doi.org/10.7554/eLife.10106.001 PMID:26714105

Development of a novel depth of interaction PET detector using highly multiplexed G-APD cross-strip encoding

DOE Office of Scientific and Technical Information (OSTI.GOV)

Kolb, A., E-mail: armin.kolb@med.uni-tuebingen.de; Parl, C.; Liu, C. C.

Purpose: The aim of this study was to develop a prototype PET detector module for a combined small animal positron emission tomography and magnetic resonance imaging (PET/MRI) system. The most important factor for small animal imaging applications is the detection sensitivity of the PET camera, which can be optimized by utilizing longer scintillation crystals. At the same time, small animal PET systems must yield a high spatial resolution. The measured object is very close to the PET detector because the bore diameter of a high field animal MR scanner is limited. When used in combination with long scintillation crystals, thesemore » small-bore PET systems generate parallax errors that ultimately lead to a decreased spatial resolution. Thus, we developed a depth of interaction (DoI) encoding PET detector module that has a uniform spatial resolution across the whole field of view (FOV), high detection sensitivity, compactness, and insensitivity to magnetic fields. Methods: The approach was based on Geiger mode avalanche photodiode (G-APD) detectors with cross-strip encoding. The number of readout channels was reduced by a factor of 36 for the chosen block elements. Two 12 × 2 G-APD strip arrays (25μm cells) were placed perpendicular on each face of a 12 × 12 lutetium oxyorthosilicate crystal block with a crystal size of 1.55 × 1.55 × 20 mm. The strip arrays were multiplexed into two channels and used to calculate the x, y coordinates for each array and the deposited energy. The DoI was measured in step sizes of 1.8 mm by a collimated {sup 18}F source. The coincident resolved time (CRT) was analyzed at all DoI positions by acquiring the waveform for each event and applying a digital leading edge discriminator. Results: All 144 crystals were well resolved in the crystal flood map. The average full width half maximum (FWHM) energy resolution of the detector was 12.8% ± 1.5% with a FWHM CRT of 1.14 ± 0.02 ns. The average FWHM DoI resolution over 12 crystals was 2.90 ± 0.15 mm. Conclusions: The novel DoI PET detector, which is based on strip G-APD arrays, yielded a DoI resolution of 2.9 mm and excellent timing and energy resolution. Its high multiplexing factor reduces the number of electronic channels. Thus, this cross-strip approach enables low-cost, high-performance PET detectors for dedicated small animal PET and PET/MRI and potentially clinical PET/MRI systems.« less

Mitogen-activated protein kinase-interacting kinase regulates mTOR/AKT signaling and controls the serine/arginine-rich protein kinase-responsive type 1 internal ribosome entry site-mediated translation and viral oncolysis.

PubMed

Brown, Michael C; Dobrikov, Mikhail I; Gromeier, Matthias

2014-11-01

Translation machinery is a major recipient of the principal mitogenic signaling networks involving Raf-ERK1/2 and phosphoinositol 3-kinase (PI3K)-mechanistic target of rapamycin (mTOR). Picornavirus internal ribosomal entry site (IRES)-mediated translation and cytopathogenic effects are susceptible to the status of such signaling cascades in host cells. We determined that tumor-specific cytotoxicity of the poliovirus/rhinovirus chimera PVSRIPO is facilitated by Raf-ERK1/2 signals to the mitogen-activated protein kinase (MAPK)-interacting kinase (MNK) and its effects on the partitioning/activity of the Ser/Arg (SR)-rich protein kinase (SRPK) (M. C. Brown, J. D. Bryant, E. Y. Dobrikova, M. Shveygert, S. S. Bradrick, V. Chandramohan, D. D. Bigner, and M, Gromeier, J. Virol. 22:13135-13148, 2014, doi:http://dx.doi.org/10.1128/JVI.01883-14). Here, we show that MNK regulates SRPK via mTOR and AKT. Our investigations revealed a MNK-controlled mechanism acting on mTORC2-AKT. The resulting suppression of AKT signaling attenuates SRPK activity to enhance picornavirus type 1 IRES translation and favor PVSRIPO tumor cell toxicity and killing. Oncolytic immunotherapy with PVSRIPO, the type 1 live-attenuated poliovirus (PV) (Sabin) vaccine containing a human rhinovirus type 2 (HRV2) IRES, is demonstrating early promise in clinical trials with intratumoral infusion in recurrent glioblastoma (GBM). Our investigations demonstrate that the core mechanistic principle of PVSRIPO, tumor-selective translation and cytotoxicity, relies on constitutive ERK1/2-MNK signals that counteract the deleterious effects of runaway AKT-SRPK activity in malignancy. Copyright © 2014, American Society for Microbiology. All Rights Reserved.

Mitogen-Activated Protein Kinase-Interacting Kinase Regulates mTOR/AKT Signaling and Controls the Serine/Arginine-Rich Protein Kinase-Responsive Type 1 Internal Ribosome Entry Site-Mediated Translation and Viral Oncolysis

PubMed Central

Brown, Michael C.; Dobrikov, Mikhail I.

2014-01-01

ABSTRACT Translation machinery is a major recipient of the principal mitogenic signaling networks involving Raf-ERK1/2 and phosphoinositol 3-kinase (PI3K)-mechanistic target of rapamycin (mTOR). Picornavirus internal ribosomal entry site (IRES)-mediated translation and cytopathogenic effects are susceptible to the status of such signaling cascades in host cells. We determined that tumor-specific cytotoxicity of the poliovirus/rhinovirus chimera PVSRIPO is facilitated by Raf-ERK1/2 signals to the mitogen-activated protein kinase (MAPK)-interacting kinase (MNK) and its effects on the partitioning/activity of the Ser/Arg (SR)-rich protein kinase (SRPK) (M. C. Brown, J. D. Bryant, E. Y. Dobrikova, M. Shveygert, S. S. Bradrick, V. Chandramohan, D. D. Bigner, and M, Gromeier, J. Virol. 22:13135–13148, 2014, doi:http://dx.doi.org/10.1128/JVI.01883-14). Here, we show that MNK regulates SRPK via mTOR and AKT. Our investigations revealed a MNK-controlled mechanism acting on mTORC2-AKT. The resulting suppression of AKT signaling attenuates SRPK activity to enhance picornavirus type 1 IRES translation and favor PVSRIPO tumor cell toxicity and killing. IMPORTANCE Oncolytic immunotherapy with PVSRIPO, the type 1 live-attenuated poliovirus (PV) (Sabin) vaccine containing a human rhinovirus type 2 (HRV2) IRES, is demonstrating early promise in clinical trials with intratumoral infusion in recurrent glioblastoma (GBM). Our investigations demonstrate that the core mechanistic principle of PVSRIPO, tumor-selective translation and cytotoxicity, relies on constitutive ERK1/2-MNK signals that counteract the deleterious effects of runaway AKT-SRPK activity in malignancy. PMID:25187540

Examining social identity and intrateam moral behaviours in competitive youth ice hockey using stimulated recall.

PubMed

Bruner, Mark W; Boardley, Ian D; Allan, Veronica; Root, Zach; Buckham, Sara; Forrest, Chris; Côté, Jean

2017-10-01

Social identity - identity formed through membership in groups - may play an important role in regulating intrateam moral behaviour in youth sport (Bruner, M. W., Boardley, I., & Côté, J. (2014). Social identity and prosocial and antisocial behavior in youth sport. Psychology of Sport and Exercise, 15(1), 56-64. doi:10.1016/j.psychsport.2013.09.003). The aim of this study was to qualitatively examine this potential role through stimulated recall interviews with competitive youth-ice-hockey players. Twenty-three players (M age  = 13.27 years, SD = 1.79) who reported engaging in high, median or low frequency of antisocial teammate behaviour (determined through pre-screening with the Prosocial and Antisocial Behaviour in Sport Scale [Kavussanu, M., & Boardley, I. D. (2009). The prosocial and antisocial behavior in sport scale. Journal of Sport and Exercise Psychology, 31(1), 97-117. doi:10.1123/jsep.31.1.97]) were recruited from eight youth-ice-hockey teams in Canada. Interviews involved participants recalling their thoughts during prosocial/antisocial interactions with teammates, prompted by previously recorded video sequences of such incidents. Thematic analysis of interview data revealed all athletes - regardless of reported frequency of intrateam antisocial behaviour - felt prosocial interactions with teammates enhanced social identity. In contrast, the perceived influence of antisocial teammate behaviour on social identity differed depending on athletes' reported frequency of intrateam antisocial behaviour; those reporting low and median frequencies described how such behaviour undermines social identity, whereas athletes reporting high frequency did not perceive this effect. The study findings highlight the potential importance of intrateam moral behaviour and social identity for youth-sport team functioning.

Centriolar satellites assemble centrosomal microcephaly proteins to recruit CDK2 and promote centriole duplication

PubMed Central

Kodani, Andrew; Yu, Timothy W; Johnson, Jeffrey R; Jayaraman, Divya; Johnson, Tasha L; Al-Gazali, Lihadh; Sztriha, Lāszló; Partlow, Jennifer N; Kim, Hanjun; Krup, Alexis L; Dammermann, Alexander; Krogan, Nevan J; Walsh, Christopher A; Reiter, Jeremy F

2015-01-01

Primary microcephaly (MCPH) associated proteins CDK5RAP2, CEP152, WDR62 and CEP63 colocalize at the centrosome. We found that they interact to promote centriole duplication and form a hierarchy in which each is required to localize another to the centrosome, with CDK5RAP2 at the apex, and CEP152, WDR62 and CEP63 at sequentially lower positions. MCPH proteins interact with distinct centriolar satellite proteins; CDK5RAP2 interacts with SPAG5 and CEP72, CEP152 with CEP131, WDR62 with MOONRAKER, and CEP63 with CEP90 and CCDC14. These satellite proteins localize their cognate MCPH interactors to centrosomes and also promote centriole duplication. Consistent with a role for satellites in microcephaly, homozygous mutations in one satellite gene, CEP90, may cause MCPH. The satellite proteins, with the exception of CCDC14, and MCPH proteins promote centriole duplication by recruiting CDK2 to the centrosome. Thus, centriolar satellites build a MCPH complex critical for human neurodevelopment that promotes CDK2 centrosomal localization and centriole duplication. DOI: http://dx.doi.org/10.7554/eLife.07519.001 PMID:26297806

PHF13 is a molecular reader and transcriptional co-regulator of H3K4me2/3

PubMed Central

Chung, Ho-Ryun; Xu, Chao; Fuchs, Alisa; Mund, Andreas; Lange, Martin; Staege, Hannah; Schubert, Tobias; Bian, Chuanbing; Dunkel, Ilona; Eberharter, Anton; Regnard, Catherine; Klinker, Henrike; Meierhofer, David; Cozzuto, Luca; Winterpacht, Andreas; Di Croce, Luciano; Min, Jinrong; Will, Hans; Kinkley, Sarah

2016-01-01

PHF13 is a chromatin affiliated protein with a functional role in differentiation, cell division, DNA damage response and higher chromatin order. To gain insight into PHF13's ability to modulate these processes, we elucidate the mechanisms targeting PHF13 to chromatin, its genome wide localization and its molecular chromatin context. Size exclusion chromatography, mass spectrometry, X-ray crystallography and ChIP sequencing demonstrate that PHF13 binds chromatin in a multivalent fashion via direct interactions with H3K4me2/3 and DNA, and indirectly via interactions with PRC2 and RNA PolII. Furthermore, PHF13 depletion disrupted the interactions between PRC2, RNA PolII S5P, H3K4me3 and H3K27me3 and resulted in the up and down regulation of genes functionally enriched in transcriptional regulation, DNA binding, cell cycle, differentiation and chromatin organization. Together our findings argue that PHF13 is an H3K4me2/3 molecular reader and transcriptional co-regulator, affording it the ability to impact different chromatin processes. DOI: http://dx.doi.org/10.7554/eLife.10607.001 PMID:27223324

Performance studies towards a TOF-PET sensor using Compton scattering at plastic scintillators

NASA Astrophysics Data System (ADS)

Kuramoto, M.; Nakamori, T.; Gunji, S.; Kamada, K.; Shoji, Y.; Yoshikawa, A.; Aoki, T.

2018-01-01

We have developed a sensor head for a time-of-flight (TOF) PET scanner using plastic scintillators that have a very fast timing property. Given the very small cross section of photoelectric absorption in plastic scintillators at 511 keV, we use Compton scattering in order to compensate for detection efficiency. The detector will consist of two layers of scatterers and absorbers which are made of plastic and inorganic scintillators such as GAGG:Ce, respectively. Signals are read by monolithic Multi Pixel Photon Counters, and with energy deposits and interaction time stamps are being acquired. The scintillators are built to be capable of resolving interaction position in three dimensions, so that our system has also a function of depth-of-interaction (DOI) PET scanners. TOF resolution of ~ 200 ps (FWHM) is achieved in both cases of using the leading-edge discriminator and time-walk correction and using a configuration sensitive to DOI. Both the position resolution and spectroscopy are demonstrated using the prototype data acquisition system, with Compton scattering events subsequently being obtained. We also demonstrated that the background rejection technique using the Compton cone constraint could be valid with our system.

Initial Orbit Determination Based on Propagation of Admissible Regions with Differential Algebra

DTIC Science & Technology

2017-01-19

Asteroid close encounter characterization using differential algebra: the case of aphophis. Celestial Mechanics and Dynamical Astronomy , 107(4), 2010...Mechanics and Dynamical Astronomy , 112 (3):331–352, 2012. ISSN 09232958. doi: 10.1007/s10569-012-9400-8. Roberto Armellin, Pierluigi Di Lizia, and Renato... Astronomy , 90(1-2):59–87, 2004. ISSN 09232958. doi: 10.1007/s10569-004-6593-5. 50 DISTRIBUTION A. Approved for public release: distribution unlimited

PPI layouts: BioJS components for the display of Protein-Protein Interactions.

PubMed

Salazar, Gustavo A; Meintjes, Ayton; Mulder, Nicola

2014-01-01

We present two web-based components for the display of Protein-Protein Interaction networks using different self-organizing layout methods: force-directed and circular. These components conform to the BioJS standard and can be rendered in an HTML5-compliant browser without the need for third-party plugins. We provide examples of interaction networks and how the components can be used to visualize them, and refer to a more complex tool that uses these components. http://github.com/biojs/biojs; http://dx.doi.org/10.5281/zenodo.7753.

Performance evaluation for 120 four-layer DOI block detectors of the jPET-D4.

PubMed

Inadama, Naoko; Murayama, Hideo; Ono, Yusuke; Tsuda, Tomoaki; Hamamoto, Manabu; Yamaya, Taiga; Yoshida, Eiji; Shibuya, Kengo; Nishikido, Fumihiko; Takahashi, Kei; Kawai, Hideyuki

2008-01-01

The jPET-D4 is a brain positron emission tomography (PET) scanner that we have developed to meet user demands for high sensitivity and high spatial resolution. For this scanner, we developed a four-layer depth-of-interaction (DOI) detector. The four-layer DOI detector is a key component for the jPET-D4, its performance has great influence on the overall system performance. Previously, we reported the original technique for encoding four-layer DOI. Here, we introduce the final design of the jPET-D4 detector and present the results of an investigation on uniformity in performance of the detector. The performance evaluation was done over the 120 DOI crystal blocks for the detectors, which are to be assembled into the jPET-D4 scanner. We also introduce the crystal assembly method, which is simple enough, even though each DOI crystal block is composed of 1,024 crystal elements. The jPET-D4 detector consists of four layers of 16 x 16 Gd(2)SiO(5) (GSO) crystals and a 256-channel flat-panel position-sensitive photomultiplier tube (256ch FP-PMT). To identify scintillated crystals in the four-layer DOI detector, we use pulse shape discrimination and position discrimination on the two-dimensional (2D) position histogram. For pulse shape discrimination, two kinds of GSO crystals that show different scintillation decay time constants are used in the upper two and lower two layers, respectively. Proper reflector arrangement in the crystal block then allows the scintillated crystals to be identified in these two-layer groupings with two 2D position histograms. We produced the 120 DOI crystal blocks for the jPET-D4 system, and measured their characteristics such as the accuracy of pulse shape discrimination, energy resolution, and the pulse height of the full energy peak. The results show a satisfactory and uniform performance of the four-layer DOI crystal blocks; for example, misidentification rate in each GSO layer is <5% based on pulse shape discrimination, the averaged energy resolutions for the central four crystals of the first (farthest from the FP-PMT), second, third, and 4th layers are 15.7 +/- 1.0, 15.8 +/- 0.6, 17.7 +/- 1.2, and 17.3 +/- 1.4%, respectively, and variation in pulse height of the full energy peak among the four layers is <5% on average.

The effect of the sigma-1 receptor selective compound LS-1-137 on the DOI-induced head twitch response in mice.

PubMed

Malik, Maninder; Rangel-Barajas, Claudia; Mach, Robert H; Luedtke, Robert R

2016-09-01

Several receptor mediated pathways have been shown to modulate the murine head twitch response (HTR). However, the role of sigma receptors in the murine (±)-2,5-dimethoxy-4-iodoamphetamine (DOI)-induced HTR has not been previously investigated. We examined the ability of LS-1-137, a novel sigma-1 vs. sigma-2 receptor selective phenylacetamide, to modulate the DOI-induced HTR in DBA/2J mice. We also assessed the in vivo efficacy of reference sigma-1 receptor antagonists and agonists PRE-084 and PPCC. The effect of the sigma-2 receptor selective antagonist RHM-1-86 was also examined. Rotarod analysis was performed to monitor motor coordination after LS-1-137 administration. Radioligand binding techniques were used to determine the affinity of LS-1-137 at 5-HT2A and 5-HT2C receptors. LS-1-137 and the sigma-1 receptor antagonists haloperidol and BD 1047 were able to attenuate a DOI-induced HTR, indicating that LS-1-137 was acting in vivo as a sigma-1 receptor antagonist. LS-1-137 did not compromise rotarod performance within a dose range capable of attenuating the effects of DOI. Radioligand binding studies indicate that LS-1-137 exhibits low affinity binding at both 5-HT2A and 5-HT2C receptors. Based upon the results from these and our previous studies, LS-1-137 is a neuroprotective agent that attenuates the murine DOI-induced HTR independent of activity at 5-HT2 receptor subtypes, D2-like dopamine receptors, sigma-2 receptors and NMDA receptors. LS-1-137 appears to act as a sigma-1 receptor antagonist to inhibit the DOI-induced HTR. Therefore, the DOI-induced HTR can be used to assess the in vivo efficacy of sigma-1 receptor selective compounds. Copyright © 2016. Published by Elsevier Inc.

A novel depth-of-interaction block detector for positron emission tomography using a dichotomous orthogonal symmetry decoding concept.

PubMed

Zhang, Yuxuan; Yan, Han; Baghaei, Hossain; Wong, Wai-Hoi

2016-02-21

Conventionally, a dual-end depth-of-interaction (DOI) block detector readout requires two two-dimensional silicon photomultiplier (SiPM) arrays, one on top and one on the bottom, to define the XYZ positions. However, because both the top and bottom SiPM arrays are reading the same pixels, this creates information redundancy. We propose a dichotomous orthogonal symmetric (DOS) dual-end readout block detector design, which removes this redundancy by reducing the number of SiPMs and still achieves XY and DOI (Z) decoding for positron emission tomography (PET) block detector. Reflecting films are used within the block detector to channel photons going to the top of the block to go only in the X direction, and photons going to the bottom are channeled along the Y direction. Despite the unidirectional channeling on each end, the top readout provides both X and Y information using two one-dimensional SiPM arrays instead of a two-dimensional SiPM array; similarly, the bottom readout also provides both X and Y information with just two one-dimensional SiPM arrays. Thus, a total of four one-dimensional SiPM arrays (4  ×  N SiPMs) are used to decode the XYZ positions of the firing pixels instead of two two-dimensional SiPM arrays (2  ×  N  ×  N SiPMs), reducing the number of SiPM arrays per block from 2N(2) to 4 N for PET/MR or PET/CT systems. Moreover, the SiPM arrays on one end can be replaced by two regular photomultiplier tubes (PMTs), so that a block needs only 2 N SiPMs  +  2 half-PMTs; this hybrid-DOS DOI block detector can be used in PET/CT systems. Monte Carlo simulations were carried out to study the performance of our DOS DOI block detector design, including the XY-decoding quality, energy resolution, and DOI resolution. Both BGO and LSO scintillators were studied. We found that 4 mm pixels were well decoded for 5  ×  5 BGO and 9  ×  9 LSO arrays with 4 to 5 mm DOI resolution and 16-20% energy resolution. By adding light-channel decoding, we modified the DOS design to a high-resolution design, which resolved scintillator pixels smaller than the SiPM dimensions. Detector pixels of 2.4 mm were decoded for 8  ×  8 BGO and 15  ×  15 LSO arrays with 5 mm DOI resolution and 20-23% energy resolution. Time performance was also studied for the 8  ×  8 BGO and 15  ×  15 LSO HR-DOS arrays. The timing resolution for the corner and central crystals is 986  ±  122 ps and 1.89  ±  0.17 μs respectively with BGO, 137  ±  42 ps and 458  ±  67 ps respectively with LSO. Monte Carlo simulations with GATE/Geant4 demonstrated the feasibility of our DOS DOI block detector design. In conclusion, our novel design achieved good performance except the time performance while using fewer SiPMs and supporting electronic channels than the current non-DOI PET detectors. This novel design can significantly reduce the cost, heat, and readout complexity of DOI block detectors for PET/MR/CT systems that don't require the time-of-flight capability.

Radiation Belt Transport Driven by Solar Wind Dynamic Pressure Fluctuations

NASA Astrophysics Data System (ADS)

Kress, B. T.; Hudson, M. K.; Ukhorskiy, A. Y.; Mueller, H.

2012-12-01

The creation of the Earth's outer zone radiation belts is attributed to earthward transport and adiabatic acceleration of electrons by drift-resonant interactions with electromagnetic fluctuations in the magnetosphere. Three types of radial transport driven by solar wind dynamic pressure fluctuations that have been identified are: (1) radial diffusion [Falthammer, 1965], (2) significant changes in the phase space density radial profile due to a single or few ULF drift-resonant interactions [Ukhorskiy et al., 2006; Degeling et al., 2008], and (3) shock associated injections of radiation belt electrons occurring in less than a drift period [Li et al., 1993]. A progress report will be given on work to fully characterize different forms of radial transport and their effect on the Earth's radiation belts. The work is being carried out by computing test-particle trajectories in electric and magnetic fields from a simple analytic ULF field model and from global MHD simulations of the magnetosphere. Degeling, A. W., L. G. Ozeke, R. Rankin, I. R. Mann, and K. Kabin (2008), Drift resonant generation of peaked relativistic electron distributions by Pc 5 ULF waves, textit{J. Geophys. Res., 113}, A02208, doi:10.1029/2007JA012411. Fälthammar, C.-G. (1965), Effects of Time-Dependent Electric Fields on Geomagnetically Trapped Radiation, J. Geophys. Res., 70(11), 2503-2516, doi:10.1029/JZ070i011p02503. Li, X., I. Roth, M. Temerin, J. R. Wygant, M. K. Hudson, and J. B. Blake (1993), Simulation of the prompt energization and transport of radiation belt particles during the March 24, 1991 SSC, textit{Geophys. Res. Lett., 20}(22), 2423-2426, doi:10.1029/93GL02701. Ukhorskiy, A. Y., B. J. Anderson, K. Takahashi, and N. A. Tsyganenko (2006), Impact of ULF oscillations in solar wind dynamic pressure on the outer radiation belt electrons, textit{Geophys. Res. Lett., 33}(6), L06111, doi:10.1029/2005GL024380.

Role of Autism Susceptibility Gene, CNTNAP2, in Neural Circuitry for Vocal Communication

DTIC Science & Technology

2013-10-01

Grimbert et al., 2003), and ATP2C2 is part of a pathway responsible for shuttling divalent ions to the Golgi apparatus (Faddy et al., 2008...L., & Wuytack, F. (2007). Calcium in the Golgi apparatus . Cell Calcium, 41(5), 405–416. doi:10.1016/j. ceca.2006.11.001 Mizutani, A., Matsuzaki, A...determination. Nature Structural & Molecular Biology, 16(4), 365–371. doi:10.1038/nsmb.1576 This is a contribution from New Perspectives on the Origins

A New In Vitro Model of Breast Cancer Metastasis to Bone

DTIC Science & Technology

2009-04-01

videomicroscopy [11, 12] have revealed that early stage, pre-angiogenic interactions between the cancer cells and the bone environment are crucial regulators of...1995) Steps in tumor metastasis: new concepts from intravital videomicroscopy . Cancer Metastasis Rev 14:279–301. doi:10.1007/BF00690599 12. Chambers AF

Data in support of the identification of neuronal and astrocyte proteins interacting with extracellularly applied oligomeric and fibrillar α-synuclein assemblies by mass spectrometry

PubMed Central

Shrivastava, Amulya Nidhi; Redeker, Virginie; Fritz, Nicolas; Pieri, Laura; Almeida, Leandro G.; Spolidoro, Maria; Liebmann, Thomas; Bousset, Luc; Renner, Marianne; Léna, Clément; Aperia, Anita; Melki, Ronald; Triller, Antoine

2016-01-01

α-Synuclein (α-syn) is the principal component of Lewy bodies, the pathophysiological hallmark of individuals affected by Parkinson disease (PD). This neuropathologic form of α-syn contributes to PD progression and propagation of α-syn assemblies between neurons. The data we present here support the proteomic analysis used to identify neuronal proteins that specifically interact with extracellularly applied oligomeric or fibrillar α-syn assemblies (conditions 1 and 2, respectively) (doi: 10.15252/embj.201591397[1]). α-syn assemblies and their cellular partner proteins were pulled down from neuronal cell lysed shortly after exposure to exogenous α-syn assemblies and the associated proteins were identified by mass spectrometry using a shotgun proteomic-based approach. We also performed experiments on pure cultures of astrocytes to identify astrocyte-specific proteins interacting with oligomeric or fibrillar α-syn (conditions 3 and 4, respectively). For each condition, proteins interacting selectively with α-syn assemblies were identified by comparison to proteins pulled-down from untreated cells used as controls. The mass spectrometry data, the database search and the peak lists have been deposited to the ProteomeXchange Consortium database via the PRIDE partner repository with the dataset identifiers PRIDE: PXD002256 to PRIDE: PXD002263 and doi: 10.6019/PXD002256 to 10.6019/PXD002263. PMID:26958642

Data in support of the identification of neuronal and astrocyte proteins interacting with extracellularly applied oligomeric and fibrillar α-synuclein assemblies by mass spectrometry.

PubMed

Shrivastava, Amulya Nidhi; Redeker, Virginie; Fritz, Nicolas; Pieri, Laura; Almeida, Leandro G; Spolidoro, Maria; Liebmann, Thomas; Bousset, Luc; Renner, Marianne; Léna, Clément; Aperia, Anita; Melki, Ronald; Triller, Antoine

2016-06-01

α-Synuclein (α-syn) is the principal component of Lewy bodies, the pathophysiological hallmark of individuals affected by Parkinson disease (PD). This neuropathologic form of α-syn contributes to PD progression and propagation of α-syn assemblies between neurons. The data we present here support the proteomic analysis used to identify neuronal proteins that specifically interact with extracellularly applied oligomeric or fibrillar α-syn assemblies (conditions 1 and 2, respectively) (doi: 10.15252/embj.201591397[1]). α-syn assemblies and their cellular partner proteins were pulled down from neuronal cell lysed shortly after exposure to exogenous α-syn assemblies and the associated proteins were identified by mass spectrometry using a shotgun proteomic-based approach. We also performed experiments on pure cultures of astrocytes to identify astrocyte-specific proteins interacting with oligomeric or fibrillar α-syn (conditions 3 and 4, respectively). For each condition, proteins interacting selectively with α-syn assemblies were identified by comparison to proteins pulled-down from untreated cells used as controls. The mass spectrometry data, the database search and the peak lists have been deposited to the ProteomeXchange Consortium database via the PRIDE partner repository with the dataset identifiers PRIDE: PXD002256 to PRIDE: PXD002263 and doi: 10.6019/PXD002256 to 10.6019/PXD002263.

Observing terrestrial water storage and land-atmosphere dynamics from space: Implications for forecasting and climate projections

NASA Astrophysics Data System (ADS)

Seneviratne, S. I.; Humphrey, V.; Nicolai-Shaw, N.; Gudmundsson, L.; Guillod, B.; Hirschi, M.; Michel, D.; Orth, R.; Zscheischler, J.

2016-12-01

In recent years, several new satellite products have been derived which allow an unprecendented assessment of terrestrial water storage and land-atmosphere dynamics. This presentation will review some of these new developments, with a focus on drought dynamics, plant-water interactions, and soil moisture-atmosphere feedbacks. Results derived based on the Gravity Recovery and Climate Experiment (GRACE, Humphrey et al. 2016) and the European Space Agency Climate Change Initiative (ESA CCI) Soil Moisture dataset (Nicolai-Shaw et al. 2015, 2016; Hirschi et al. 2014) will be highlighted, as well as assessments using satellite-based estimates of evapotranspiration (Mueller and Seneviratne 2014, Michel et al. 2016), vegetation activity (Zscheischler et al. 2015), and combined soil moisture and precipitation analyses (Guillod et al. 2015). These findings provide new insights on the development of prediction capabilities for droughts, precipitation events, and heat waves, and the reduction of uncertainties in climate model projections. References: Guillod, B.P., B. Orlowsky, D.G. Miralles, A.J. Teuling, and S.I. Seneviratne, 2015. Nature Communications, 6:6443, DOI: 10.1038/ncomms7443 Hirschi, M., B. Mueller, W. Dorigo, and S.I. Seneviratne, 2014. Remote Sensing of Environment, 154, 246-252. Humphrey, V., L. Gudmundsson, and S.I. Seneviratne, 2016. Surv. Geophysics, 37, 357-395, DOI 10.1007/s10712-016-9367-1. Michel, D., et al. 2016. Hydrol. Earth Syst. Sci. 20, 803-822, doi:10.5194/hess-20-803-2016. Mueller, M., and S.I. Seneviratne, 2014. Geophys. Res. Lett., 41, 1-7, doi:10.1002/2013GL058055. Nicolai-Shaw, N., L. Gudmundsson, M. Hirschi, and S.I. Seneviratne, 2016. Geophys. Res. Lett., in review. Nicolai-Shaw, N., M. Hirschi, H. Mittelbach, and S.I. Seneviratne, 2015. Journal of Geophysical Research, 120, doi:10.1002/2015JD023305. Zscheischler, J., R. Orth, and S.I. Seneviratne, 2015. Geophys. Res. Lett., 42, 9816-9824, doi:10.1002/2015GL066563.

Impact location of objects hitting the water surface

NASA Astrophysics Data System (ADS)

Kadri, Usama

2017-04-01

Analysis of data, recorded on March 8th 2014 at the Comprehensive Test ban Treaty Organisation's hydroacoustic station off Cape Leeuwin Western Australia, reveal pressure signatures of objects impacting at the sea surface which could be associated with falling meteorites as well as the missing Malaysian MH370 airplane. The location of the sources are identified analytically by an inverse solution based on acoustic-gravity wave theory (e.g. see references below) which have been developed and validated experimentally. Apart from the direct contribution to the search efforts after the missing airplane, the method we describe here is very efficient for identifying the location of sources that result in a sudden change in the water pressure in general. References 1. T.Yamamoto,1982.Gravity waves and acoustic waves generated by submarine earthquakes, Soil Dyn. Earthquake Eng., 1, 75-82. 2. M. Stiassnie, 2010. Tsunamis and acoustic-gravity waves from underwater earthquakes, J. Eng. Math., 67, 23-32, doi:10.1007/s10665-009-9323-x. 3. U. Kadri and M. Staissnie, 2012. Acoustic-gravity waves interacting with the shelf break. J. Geophys. Res., 117, C03035, doi: 10.1029/2011JC007674. 4. E. Eyov, A. Klar, U. Kadri and M. Stiassnie, 2013. Progressive waves in a compressible ocean with elastic bottom, Wave Motion 50, 929-939. doi: 10.1016/j.wavemoti.2013.03.003 5. G. Hendin and M. Stiassnie, 2013. Tsunami and acoustic-gravity waves in water of constant depth, Phys. Fluids 25, 086103, doi: 10.1063/1.481799. 6. U. Kadri, 2016. Acoustic-gravity waves from an oscillating ice-block in arctic zones. Advances in Acoustics and Vibration, 8076108, http://dx.doi.org/10.1155/2016/8076108 7. T.C.A. Oliveira, U. Kadri, 2016. Acoustic-gravity waves from the 2004 Indian Ocean earthquake and tsunami. Journal of Geophysical Research: Oceans. doi: 10.1002/2016JC011742

Development of 1.45-mm resolution four-layer DOI-PET detector for simultaneous measurement in 3T MRI.

PubMed

Nishikido, Fumihiko; Tachibana, Atsushi; Obata, Takayuki; Inadama, Naoko; Yoshida, Eiji; Suga, Mikio; Murayama, Hideo; Yamaya, Taiga

2015-01-01

Recently, various types of PET-MRI systems have been developed by a number of research groups. However, almost all of the PET detectors used in these PET-MRI systems have no depth-of-interaction (DOI) capability. The DOI detector can reduce the parallax error and lead to improvement of the performance. We are developing a new PET-MRI system which consists of four-layer DOI detectors positioned close to the measured object to achieve high spatial resolution and high scanner sensitivity. As a first step, we are investigating influences the PET detector and the MRI system have on each other using a prototype four-layer DOI-PET detector. This prototype detector consists of a lutetium yttrium orthosilicate crystal block and a 4 × 4 multi-pixel photon counter array. The size of each crystal element is 1.45 mm × 1.45 mm × 4.5 mm, and the crystals are arranged in 6 × 6 elements × 4 layers with reflectors. The detector and some electric components are packaged in an aluminum shielding box. Experiments were carried out with 3.0 T MRI (GE, Signa HDx) and a birdcage-type RF coil. We demonstrated that the DOI-PET detector was normally operated in simultaneous measurements with no influence of the MRI measurement. A slight influence of the PET detector on the static magnetic field of the MRI was observed near the PET detector. The signal-to-noise ratio was decreased by presence of the PET detector due to environmental noise entering the MRI room through the cables, even though the PET detector was not powered up. On the other hand, no influence of electric noise from the PET detector in the simultaneous measurement on the MRI images was observed, even though the PET detector was positioned near the RF coil.

Vortex, ULF wave and Aurora Observation after Solar Wind Dynamic Pressure Change

NASA Astrophysics Data System (ADS)

Shi, Q.

2017-12-01

Here we will summarize our recent study and show some new results on the Magnetosphere and Ionosphere Response to Dynamic Pressure Change/disturbances in the Solar Wind and foreshock regions. We study the step function type solar wind dynamic pressure change (increase/decrease) interaction with the magnetosphere using THEMIS satellites at both dayside and nightside in different geocentric distances. Vortices generated by the dynamic pressure change passing along the magnetopause are found and compared with model predictions. ULF waves and vortices are excited in the dayside and nightside plasma sheet when dynamic pressure change hit the magnetotail. The related ionospheric responses, such as aurora and TCVs, are also investigated. We compare Global MHD simulations with the observations. We will also show some new results that dayside magnetospheric FLRs might be caused by foreshock structures.Shi, Q. Q. et al. (2013), THEMIS observations of ULF wave excitation in the nightside plasma sheet during sudden impulse events, J. Geophys. Res. Space Physics, 118, doi:10.1029/2012JA017984. Shi, Q. Q. et al. (2014), Solar wind pressure pulse-driven magnetospheric vortices and their global consequences, J. Geophys. Res. Space Physics, 119, doi:10.1002/2013JA019551. Tian, A.M. et al.(2016), Dayside magnetospheric and ionospheric responses to solar wind pressure increase: Multispacecraft and ground observations, J. Geophys. Res., 121, doi:10.1002/2016JA022459. Shen, X.C. et al.(2015), Magnetospheric ULF waves with increasing amplitude related to solar wind dynamic pressure changes: THEMIS observations, J. Geophys. Res., 120, doi:10.1002/2014JA020913Zhao, H. Y. et al. (2016), Magnetospheric vortices and their global effect after a solar wind dynamic pressure decrease, J. Geophys. Res. Space Physics, 121, doi:10.1002/2015JA021646. Shen, X. C., et al. (2017), Dayside magnetospheric ULF wave frequency modulated by a solar wind dynamic pressure negative impulse, J. Geophys. Res., 122, doi:10.1002/2016JA023351.

Variation Process of Radiation Belt Electron Fluxes due to Interaction With Chorus and EMIC Rising-tone Emissions Localized in Longitude

NASA Astrophysics Data System (ADS)

Kubota, Y.; Omura, Y.

2017-12-01

Using results of test particle simulations of a large number of electrons interacting with a pair of chorus emissions, we create Green's functions to model the electron distribution function after all of the possible interactions with the waves [Omura et al., 2015]. Assuming that the waves are generated in a localized range of longitudes in the dawn side, we repeat taking the convolution integral of the Green's function with the distribution function of the electrons injected into the generation region of the localized waves. From numerical and theoretical analyses, we find that electron acceleration process only takes place efficiently below 4 MeV. Because extremely relativistic electrons go through the wave generation region rapidly due to grad-B0 and curvature drift, they don't have enough interaction time to be accelerated. In setting up the electrons after all interaction with chorus emissions as initial electron distribution function, we also compute the loss process of radiation belt electron fluxes due to interaction with EMIC rising-tone emissions generated in a localized range of longitudes in the dusk side [Kubota and Omura,2017]. References: (1) Omura, Y., Y. Miyashita, M. Yoshikawa, D. Summers, M. Hikishima, Y. Ebihara, and Y. Kubota (2015), Formation process of relativistic electron flux through interaction with chorus emissions in the Earth's inner magnetosphere, J. Geophys. Res. Space Physics, 120, 9545-9562, doi:10.1002/2015JA021563. (2) Kubota, Y., and Y. Omura (2017), Rapid precipitation of radiation belt electrons induced by EMIC rising tone emissions localized in longitude inside and outside the plasmapause, J. Geophys. Res. Space Physics, 122, 293-309, doi:10.1002/2016JA023267.

43 CFR Appendix B to Part 2 - Internet Addresses

Code of Federal Regulations, 2010 CFR

2010-10-01

... Page: http://www.doi.gov 2. DOI FOIA Home Page: http://www.doi.gov/foia/ 3. DOI Reference Guide for Obtaining Information: http://www.doi.gov/foia/foitabl.htm 4. List of DOI Public Affairs Offices: http://www.doi.gov/foia/list.html 5. DOI FOIA Contacts: http://www.doi.gov/foia/contacts.html 6. DOI FOIA...

43 CFR Appendix B to Part 2 - Internet Addresses

Code of Federal Regulations, 2012 CFR

2012-10-01

... Page: http://www.doi.gov 2. DOI FOIA Home Page: http://www.doi.gov/foia/ 3. DOI Reference Guide for Obtaining Information: http://www.doi.gov/foia/foitabl.htm 4. List of DOI Public Affairs Offices: http://www.doi.gov/foia/list.html 5. DOI FOIA Contacts: http://www.doi.gov/foia/contacts.html 6. DOI FOIA...

Anion dependent self-assembly of 56-metal Cd-Ln nanoclusters with enhanced near-infrared luminescence properties

NASA Astrophysics Data System (ADS)

Yang, Xiaoping; Schipper, Desmond; Zhang, Lijie; Yang, Keqin; Huang, Shaoming; Jiang, Jijun; Su, Chengyong; Jones, Richard A.

2014-08-01

Two series of Cd-Ln clusters: nano-drum [Ln8Cd24L12(OAc)48] and nano-double-drum [Ln12Cd44L20Cl30(OAc)54] (Ln = Nd and Yb) were prepared using a flexible Schiff base ligand bearing two aryl-Br groups. Chloride (Cl-) ions, together with the interactions of Br with other electronegative atoms, play a key role in the formation of the nano-double-drums. The structures were studied by TEM and photophysical properties were determined.Two series of Cd-Ln clusters: nano-drum [Ln8Cd24L12(OAc)48] and nano-double-drum [Ln12Cd44L20Cl30(OAc)54] (Ln = Nd and Yb) were prepared using a flexible Schiff base ligand bearing two aryl-Br groups. Chloride (Cl-) ions, together with the interactions of Br with other electronegative atoms, play a key role in the formation of the nano-double-drums. The structures were studied by TEM and photophysical properties were determined. Electronic supplementary information (ESI) available: Full experimental and characterization details for 1-4. CCDC 972369-972372. For ESI and crystallographic data in CIF or other electronic format see DOI: 10.1039/c4nr03075c

PPI layouts: BioJS components for the display of Protein-Protein Interactions

PubMed Central

Salazar, Gustavo A.; Meintjes, Ayton; Mulder, Nicola

2014-01-01

Summary: We present two web-based components for the display of Protein-Protein Interaction networks using different self-organizing layout methods: force-directed and circular. These components conform to the BioJS standard and can be rendered in an HTML5-compliant browser without the need for third-party plugins. We provide examples of interaction networks and how the components can be used to visualize them, and refer to a more complex tool that uses these components. Availability: http://github.com/biojs/biojs; http://dx.doi.org/10.5281/zenodo.7753 PMID:25075288

Direct observation of frequency modulated transcription in single cells using light activation

PubMed Central

Larson, Daniel R; Fritzsch, Christoph; Sun, Liang; Meng, Xiuhau; Lawrence, David S; Singer, Robert H

2013-01-01

Single-cell analysis has revealed that transcription is dynamic and stochastic, but tools are lacking that can determine the mechanism operating at a single gene. Here we utilize single-molecule observations of RNA in fixed and living cells to develop a single-cell model of steroid-receptor mediated gene activation. We determine that steroids drive mRNA synthesis by frequency modulation of transcription. This digital behavior in single cells gives rise to the well-known analog dose response across the population. To test this model, we developed a light-activation technology to turn on a single steroid-responsive gene and follow dynamic synthesis of RNA from the activated locus. DOI: http://dx.doi.org/10.7554/eLife.00750.001 PMID:24069527

Time-over-threshold for pulse shape discrimination in a time-of-flight phoswich PET detector.

PubMed

Chang, Chen-Ming; Cates, Joshua W; Levin, Craig S

2017-01-07

It is well known that a PET detector capable of measuring both photon time-of-flight (TOF) and depth-of-interaction (DOI) improves the image quality and accuracy. Phoswich designs have been realized in PET detectors to measure DOI for more than a decade. However, PET detectors based on phoswich designs put great demand on the readout circuits, which have to differentiate the pulse shape produced by different crystal layers. A simple pulse shape discrimination approach is required to realize the phoswich designs in a clinical PET scanner, which consists of thousands of scintillation crystal elements. In this work, we studied time-over-threshold (ToT) as a pulse shape parameter for DOI. The energy, timing and DOI performance were evaluated for a phoswich detector design comprising [Formula: see text] mm LYSO:Ce crystal optically coupled to [Formula: see text] mm calcium co-doped LSO:Ce,Ca(0.4%) crystal read out by a silicon photomultiplier (SiPM). A DOI accuracy of 97.2% has been achieved for photopeak events using the proposed time-over-threshold (ToT) processing. The energy resolution without correction for SiPM non-linearity was [Formula: see text]% and [Formula: see text]% FWHM at 511 keV for LYSO and LSO crystal layers, respectively. The coincidence time resolution for photopeak events ranges from 164.6 ps to 183.1 ps FWHM, depending on the layer combinations. The coincidence time resolution for inter-crystal scatter events ranges from 214.6 ps to 418.3 ps FWHM, depending on the energy windows applied. These results show great promises of using ToT for pulse shape discrimination in a TOF phoswich detector since a ToT measurement can be easily implemented in readout electronics.

An edge-readout, multilayer detector for positron emission tomography.

PubMed

Li, Xin; Ruiz-Gonzalez, Maria; Furenlid, Lars R

2018-06-01

We present a novel gamma-ray-detector design based on total internal reflection (TIR) of scintillation photons within a crystal that addresses many limitations of traditional PET detectors. Our approach has appealing features, including submillimeter lateral resolution, DOI positioning from layer thickness, and excellent energy resolution. The design places light sensors on the edges of a stack of scintillator slabs separated by small air gaps and exploits the phenomenon that more than 80% of scintillation light emitted during a gamma-ray event reaches the edges of a thin crystal with polished faces due to TIR. Gamma-ray stopping power is achieved by stacking multiple layers, and DOI is determined by which layer the gamma ray interacts in. The concept of edge readouts of a thin slab was verified by Monte Carlo simulation of scintillation light transport. An LYSO crystal of dimensions 50.8 mm × 50.8 mm × 3.0 mm was modeled with five rectangular SiPMs placed along each edge face. The mean-detector-response functions (MDRFs) were calculated by simulating signals from 511 keV gamma-ray interactions in a grid of locations. Simulations were carried out to study the influence of choice of scintillator material and dimensions, gamma-ray photon energies, introduction of laser or mechanically induced optical barriers (LIOBs, MIOBs), and refractive indices of optical-coupling media and SiPM windows. We also analyzed timing performance including influence of gamma-ray interaction position and presence of optical barriers. We also modeled and built a prototype detector, a 27.4 mm × 27.4 mm × 3.0 mm CsI(Tl) crystal with 4 SiPMs per edge to experimentally validate the results predicted by the simulations. The prototype detector used CsI(Tl) crystals from Proteus outfitted with 16 Hamamatsu model S13360-6050PE MPPCs read out by an AiT-16-channel readout. The MDRFs were measured by scanning the detector with a collimated beam of 662-keV photons from a 137 Cs source. The spatial resolution was experimentally determined by imaging a tungsten slit that created a beam of 0.44 mm (FWHM) width normal to the detector surface. The energy resolution was evaluated by analyzing list-mode data from flood illumination by the 137 Cs source. We find that in a block-detector-sized LYSO layer read out by five SiPMs per edge, illuminated by 511-keV photons, the average resolution is 1.49 mm (FWHM). With the introduction of optical barriers, average spatial resolution improves to 0.56 mm (FWHM). The DOI resolution is the layer thickness of 3.0 mm. We also find that optical-coupling media and SiPM-window materials have an impact on spatial resolution. The timing simulation with LYSO crystal yields a coincidence resolving time (CRT) of 200-400 ps, which is slightly position dependent. And the introduction of optical barriers has minimum influence. The prototype CsI(Tl) detector, with a smaller area and fewer SiPMs, was measured to have central-area spatial resolutions of 0.70 and 0.39 mm without and with optical barriers, respectively. These results match well with our simulations. An energy resolution of 6.4% was achieved at 662 keV. A detector design based on a stack of monolithic scintillator layers that uses edge readouts offers several advantages over current block detectors for PET. For example, there is no tradeoff between spatial resolution and detection sensitivity since no reflector material displaces scintillator crystal, and submillimeter resolution can be achieved. DOI information is readily available, and excellent timing and energy resolutions are possible. © 2018 The Authors. Medical Physics published by Wiley Periodicals, Inc. on behalf of American Association of Physicists in Medicine.

Controlling the Electronic Structure of Graphene Using Surface-adsorbate Interactions

DTIC Science & Technology

2015-07-21

substrate via n doping, with or without intercalation, suggests that the graphene-to-substrate interaction could be controlled dynamically. DOI : 10.1103...which form a Dirac cone and are degenerate at the Fermi level [1]. These states change in response to atoms adsorbed on top of graphene (doping) or when...coupling to the substrate is strong. In the case of graphene on metals, the energy of the Dirac cone can change as a result of interfacial doping, or

Resolving dual binding conformations of cellulosome cohesin-dockerin complexes using single-molecule force spectroscopy

PubMed Central

Jobst, Markus A; Milles, Lukas F; Schoeler, Constantin; Ott, Wolfgang; Fried, Daniel B; Bayer, Edward A; Gaub, Hermann E; Nash, Michael A

2015-01-01

Receptor-ligand pairs are ordinarily thought to interact through a lock and key mechanism, where a unique molecular conformation is formed upon binding. Contrary to this paradigm, cellulosomal cohesin-dockerin (Coh-Doc) pairs are believed to interact through redundant dual binding modes consisting of two distinct conformations. Here, we combined site-directed mutagenesis and single-molecule force spectroscopy (SMFS) to study the unbinding of Coh:Doc complexes under force. We designed Doc mutations to knock out each binding mode, and compared their single-molecule unfolding patterns as they were dissociated from Coh using an atomic force microscope (AFM) cantilever. Although average bulk measurements were unable to resolve the differences in Doc binding modes due to the similarity of the interactions, with a single-molecule method we were able to discriminate the two modes based on distinct differences in their mechanical properties. We conclude that under native conditions wild-type Doc from Clostridium thermocellum exocellulase Cel48S populates both binding modes with similar probabilities. Given the vast number of Doc domains with predicteddual binding modes across multiple bacterial species, our approach opens up newpossibilities for understanding assembly and catalytic properties of a broadrange of multi-enzyme complexes. DOI: http://dx.doi.org/10.7554/eLife.10319.001 PMID:26519733

Multiscale modeling and simulation of microtubule-motor-protein assemblies

NASA Astrophysics Data System (ADS)

Gao, Tong; Blackwell, Robert; Glaser, Matthew A.; Betterton, M. D.; Shelley, Michael J.

2015-12-01

Microtubules and motor proteins self-organize into biologically important assemblies including the mitotic spindle and the centrosomal microtubule array. Outside of cells, microtubule-motor mixtures can form novel active liquid-crystalline materials driven out of equilibrium by adenosine triphosphate-consuming motor proteins. Microscopic motor activity causes polarity-dependent interactions between motor proteins and microtubules, but how these interactions yield larger-scale dynamical behavior such as complex flows and defect dynamics is not well understood. We develop a multiscale theory for microtubule-motor systems in which Brownian dynamics simulations of polar microtubules driven by motors are used to study microscopic organization and stresses created by motor-mediated microtubule interactions. We identify polarity-sorting and crosslink tether relaxation as two polar-specific sources of active destabilizing stress. We then develop a continuum Doi-Onsager model that captures polarity sorting and the hydrodynamic flows generated by these polar-specific active stresses. In simulations of active nematic flows on immersed surfaces, the active stresses drive turbulent flow dynamics and continuous generation and annihilation of disclination defects. The dynamics follow from two instabilities, and accounting for the immersed nature of the experiment yields unambiguous characteristic length and time scales. When turning off the hydrodynamics in the Doi-Onsager model, we capture formation of polar lanes as observed in the Brownian dynamics simulation.

Multiscale modeling and simulation of microtubule-motor-protein assemblies.

PubMed

Gao, Tong; Blackwell, Robert; Glaser, Matthew A; Betterton, M D; Shelley, Michael J

2015-01-01

Microtubules and motor proteins self-organize into biologically important assemblies including the mitotic spindle and the centrosomal microtubule array. Outside of cells, microtubule-motor mixtures can form novel active liquid-crystalline materials driven out of equilibrium by adenosine triphosphate-consuming motor proteins. Microscopic motor activity causes polarity-dependent interactions between motor proteins and microtubules, but how these interactions yield larger-scale dynamical behavior such as complex flows and defect dynamics is not well understood. We develop a multiscale theory for microtubule-motor systems in which Brownian dynamics simulations of polar microtubules driven by motors are used to study microscopic organization and stresses created by motor-mediated microtubule interactions. We identify polarity-sorting and crosslink tether relaxation as two polar-specific sources of active destabilizing stress. We then develop a continuum Doi-Onsager model that captures polarity sorting and the hydrodynamic flows generated by these polar-specific active stresses. In simulations of active nematic flows on immersed surfaces, the active stresses drive turbulent flow dynamics and continuous generation and annihilation of disclination defects. The dynamics follow from two instabilities, and accounting for the immersed nature of the experiment yields unambiguous characteristic length and time scales. When turning off the hydrodynamics in the Doi-Onsager model, we capture formation of polar lanes as observed in the Brownian dynamics simulation.

NuMA-microtubule interactions are critical for spindle orientation and the morphogenesis of diverse epidermal structures

PubMed Central

Seldin, Lindsey; Muroyama, Andrew; Lechler, Terry

2016-01-01

Mitotic spindle orientation is used to generate cell fate diversity and drive proper tissue morphogenesis. A complex of NuMA and dynein/dynactin is required for robust spindle orientation in a number of cell types. Previous research proposed that cortical dynein/dynactin was sufficient to generate forces on astral microtubules (MTs) to orient the spindle, with NuMA acting as a passive tether. In this study, we demonstrate that dynein/dynactin is insufficient for spindle orientation establishment in keratinocytes and that NuMA’s MT-binding domain, which targets MT tips, is also required. Loss of NuMA-MT interactions in skin caused defects in spindle orientation and epidermal differentiation, leading to neonatal lethality. In addition, we show that NuMA-MT interactions are also required in adult mice for hair follicle morphogenesis and spindle orientation within the transit-amplifying cells of the matrix. Loss of spindle orientation in matrix cells results in defective differentiation of matrix-derived lineages. Our results reveal an additional and direct function of NuMA during mitotic spindle positioning, as well as a reiterative use of spindle orientation in the skin to build diverse structures. DOI: http://dx.doi.org/10.7554/eLife.12504.001 PMID:26765568

Interaction of serotonin and cholecystokinin in the lateral parabrachial nucleus to control sodium intake.

PubMed

Fratucci De Gobbi, J I; De Luca, L A; Johnson, A K; Menani, J V

2001-05-01

Serotonin [5-hydroxytryptamine (5-HT)] and CCK injected into the lateral parabrachial nucleus (LPBN) inhibit NaCl and water intake. In this study, we investigated interactions between 5-HT and CCK into the LPBN to control water and NaCl intake. Male Holtzman rats with cannulas implanted bilaterally in the LPBN were treated with furosemide + captopril to induce water and NaCl intake. Bilateral LPBN injections of high doses of the 5-HT antagonist methysergide (4 microg) or the CCK antagonist proglumide (50 microg), alone or combined, produced similar increases in water and 1.8% NaCl intake. Low doses of methysergide (0.5 microg) + proglumide (20 microg) produced greater increases in NaCl intake than when they were injected alone. The 5-HT(2a/2c) agonist 2,5-dimetoxy-4-iodoamphetamine hydrobromide (DOI; 5 microg) into the LPBN reduced water and NaCl intake. After proglumide (50 microg) + DOI treatment, the intake was not different from vehicle treatment. CCK-8 (1 microg) alone produced no effect. CCK-8 combined with methysergide (4 microg) reduced the effect of methysergide on NaCl intake. The data suggest that functional interactions between 5-HT and CCK in the LPBN may be important for exerting inhibitory control of NaCl intake.

Multiscale modeling and simulation of microtubule–motor-protein assemblies

PubMed Central

Gao, Tong; Blackwell, Robert; Glaser, Matthew A.; Betterton, M. D.; Shelley, Michael J.

2016-01-01

Microtubules and motor proteins self-organize into biologically important assemblies including the mitotic spindle and the centrosomal microtubule array. Outside of cells, microtubule-motor mixtures can form novel active liquid-crystalline materials driven out of equilibrium by adenosine triphosphate–consuming motor proteins. Microscopic motor activity causes polarity-dependent interactions between motor proteins and microtubules, but how these interactions yield larger-scale dynamical behavior such as complex flows and defect dynamics is not well understood. We develop a multiscale theory for microtubule-motor systems in which Brownian dynamics simulations of polar microtubules driven by motors are used to study microscopic organization and stresses created by motor-mediated microtubule interactions. We identify polarity-sorting and crosslink tether relaxation as two polar-specific sources of active destabilizing stress. We then develop a continuum Doi-Onsager model that captures polarity sorting and the hydrodynamic flows generated by these polar-specific active stresses. In simulations of active nematic flows on immersed surfaces, the active stresses drive turbulent flow dynamics and continuous generation and annihilation of disclination defects. The dynamics follow from two instabilities, and accounting for the immersed nature of the experiment yields unambiguous characteristic length and time scales. When turning off the hydrodynamics in the Doi-Onsager model, we capture formation of polar lanes as observed in the Brownian dynamics simulation. PMID:26764729

Cover Image, Volume 119, Number 1, January 2018.

PubMed

Rubio-Infante, Nestor; Ilhuicatzi-Alvarado, Damaris; Torres-Martínez, Marilu; Reyes-Grajeda, Juan Pablo; Nava-Acosta, Raúl; González-González, Edith; Moreno-Fierros, Leticia

2018-01-01

Cover: The cover image, by Nestor Rubio-Infante et al., is based on the Article The Macrophage Activation Induced by Bacillus thuringiensis Cry1Ac Protoxin Involves ERK1/2 and p38 Pathways and the Interaction with Cell-Surface-HSP70, DOI: 10.1002/jcb.26216. © 2017 Wiley Periodicals, Inc.

Nucleophosmin integrates within the nucleolus via multi-modal interactions with proteins displaying R-rich linear motifs and rRNA

PubMed Central

Mitrea, Diana M; Cika, Jaclyn A; Guy, Clifford S; Ban, David; Banerjee, Priya R; Stanley, Christopher B; Nourse, Amanda; Deniz, Ashok A; Kriwacki, Richard W

2016-01-01

The nucleolus is a membrane-less organelle formed through liquid-liquid phase separation of its components from the surrounding nucleoplasm. Here, we show that nucleophosmin (NPM1) integrates within the nucleolus via a multi-modal mechanism involving multivalent interactions with proteins containing arginine-rich linear motifs (R-motifs) and ribosomal RNA (rRNA). Importantly, these R-motifs are found in canonical nucleolar localization signals. Based on a novel combination of biophysical approaches, we propose a model for the molecular organization within liquid-like droplets formed by the N-terminal domain of NPM1 and R-motif peptides, thus providing insights into the structural organization of the nucleolus. We identify multivalency of acidic tracts and folded nucleic acid binding domains, mediated by N-terminal domain oligomerization, as structural features required for phase separation of NPM1 with other nucleolar components in vitro and for localization within mammalian nucleoli. We propose that one mechanism of nucleolar localization involves phase separation of proteins within the nucleolus. DOI: http://dx.doi.org/10.7554/eLife.13571.001 PMID:26836305

Response of radiation belt simulations to different radial diffusion coefficients for relativistic and ultra-relativistic electrons

NASA Astrophysics Data System (ADS)

Drozdov, Alexander; Mann, Ian; Baker, Daniel N.; Subbotin, Dmitriy; Ozeke, Louis; Shprits, Yuri; Kellerman, Adam

Two parameterizations of the resonant wave-particle interactions of electrons with ULF waves in the magnetosphere by Brautigam and Albert [2000] and Ozeke et al. [2012] are evaluated using the Versatile Electron Radiation Belt (VERB) diffusion code to estimate the effect of changing a diffusion coefficient on the radiation belt simulation. The period of investigation includes geomagnetically quiet and active time. The simulations take into account wave-particle interactions represented by radial diffusion transport, local acceleration, losses due to pitch-angle diffusion, and mixed diffusion. 1. Brautigam, D. H., and J. M. Albert (2000), Radial diffusion analysis of outer radiation belt electrons during the October 9, 1990, magnetic storm, J. Geophys. Res., 105(A1), 291-309, doi:10.1029/1999JA900344 2. Ozeke, L. G., I. R. Mann, K. R. Murphy, I. J. Rae, D. K. Milling, S. R. Elkington, A. A. Chan, and H. J. Singer (2012), ULF wave derived radiation belt radial diffusion coefficients, J. Geophys. Res., 117, A04222, doi:10.1029/2011JA017463.

The Ndc80 complex bridges two Dam1 complex rings

PubMed Central

Kim, Jae ook; Zelter, Alex; Umbreit, Neil T; Bollozos, Athena; Riffle, Michael; Johnson, Richard; MacCoss, Michael J; Asbury, Charles L; Davis, Trisha N

2017-01-01

Strong kinetochore-microtubule attachments are essential for faithful segregation of sister chromatids during mitosis. The Dam1 and Ndc80 complexes are the main microtubule binding components of the Saccharomyces cerevisiae kinetochore. Cooperation between these two complexes enhances kinetochore-microtubule coupling and is regulated by Aurora B kinase. We show that the Ndc80 complex can simultaneously bind and bridge across two Dam1 complex rings through a tripartite interaction, each component of which is regulated by Aurora B kinase. Mutations in any one of the Ndc80p interaction regions abrogates the Ndc80 complex’s ability to bind two Dam1 rings in vitro, and results in kinetochore biorientation and microtubule attachment defects in vivo. We also show that an extra-long Ndc80 complex, engineered to space the two Dam1 rings further apart, does not support growth. Taken together, our work suggests that each kinetochore in vivo contains two Dam1 rings and that proper spacing between the rings is vital. DOI: http://dx.doi.org/10.7554/eLife.21069.001 PMID:28191870

Na+/K+ pump interacts with the h-current to control bursting activity in central pattern generator neurons of leeches

PubMed Central

Kueh, Daniel; Barnett, William H; Cymbalyuk, Gennady S; Calabrese, Ronald L

2016-01-01

The dynamics of different ionic currents shape the bursting activity of neurons and networks that control motor output. Despite being ubiquitous in all animal cells, the contribution of the Na+/K+ pump current to such bursting activity has not been well studied. We used monensin, a Na+/H+ antiporter, to examine the role of the pump on the bursting activity of oscillator heart interneurons in leeches. When we stimulated the pump with monensin, the period of these neurons decreased significantly, an effect that was prevented or reversed when the h-current was blocked by Cs+. The decreased period could also occur if the pump was inhibited with strophanthidin or K+-free saline. Our monensin results were reproduced in model, which explains the pump’s contributions to bursting activity based on Na+ dynamics. Our results indicate that a dynamically oscillating pump current that interacts with the h-current can regulate the bursting activity of neurons and networks. DOI: http://dx.doi.org/10.7554/eLife.19322.001 PMID:27588351

A FYVE zinc finger domain protein specifically links mRNA transport to endosome trafficking

PubMed Central

Pohlmann, Thomas; Baumann, Sebastian; Haag, Carl; Albrecht, Mario; Feldbrügge, Michael

2015-01-01

An emerging theme in cellular logistics is the close connection between mRNA and membrane trafficking. A prominent example is the microtubule-dependent transport of mRNAs and associated ribosomes on endosomes. This coordinated process is crucial for correct septin filamentation and efficient growth of polarised cells, such as fungal hyphae. Despite detailed knowledge on the key RNA-binding protein and the molecular motors involved, it is unclear how mRNAs are connected to membranes during transport. Here, we identify a novel factor containing a FYVE zinc finger domain for interaction with endosomal lipids and a new PAM2-like domain required for interaction with the MLLE domain of the key RNA-binding protein. Consistently, loss of this FYVE domain protein leads to specific defects in mRNA, ribosome, and septin transport without affecting general functions of endosomes or their movement. Hence, this is the first endosomal component specific for mRNP trafficking uncovering a new mechanism to couple mRNPs to endosomes. DOI: http://dx.doi.org/10.7554/eLife.06041.001 PMID:25985087

Assembling the Tat protein translocase

PubMed Central

Alcock, Felicity; Stansfeld, Phillip J; Basit, Hajra; Habersetzer, Johann; Baker, Matthew AB; Palmer, Tracy; Wallace, Mark I; Berks, Ben C

2016-01-01

The twin-arginine protein translocation system (Tat) transports folded proteins across the bacterial cytoplasmic membrane and the thylakoid membranes of plant chloroplasts. The Tat transporter is assembled from multiple copies of the membrane proteins TatA, TatB, and TatC. We combine sequence co-evolution analysis, molecular simulations, and experimentation to define the interactions between the Tat proteins of Escherichia coli at molecular-level resolution. In the TatBC receptor complex the transmembrane helix of each TatB molecule is sandwiched between two TatC molecules, with one of the inter-subunit interfaces incorporating a functionally important cluster of interacting polar residues. Unexpectedly, we find that TatA also associates with TatC at the polar cluster site. Our data provide a structural model for assembly of the active Tat translocase in which substrate binding triggers replacement of TatB by TatA at the polar cluster site. Our work demonstrates the power of co-evolution analysis to predict protein interfaces in multi-subunit complexes. DOI: http://dx.doi.org/10.7554/eLife.20718.001 PMID:27914200

Monochromatic multicomponent fluorescence sedimentation velocity for the study of high-affinity protein interactions

PubMed Central

Zhao, Huaying; Fu, Yan; Glasser, Carla; Andrade Alba, Eric J; Mayer, Mark L; Patterson, George; Schuck, Peter

2016-01-01

The dynamic assembly of multi-protein complexes underlies fundamental processes in cell biology. A mechanistic understanding of assemblies requires accurate measurement of their stoichiometry, affinity and cooperativity, and frequently consideration of multiple co-existing complexes. Sedimentation velocity analytical ultracentrifugation equipped with fluorescence detection (FDS-SV) allows the characterization of protein complexes free in solution with high size resolution, at concentrations in the nanomolar and picomolar range. Here, we extend the capabilities of FDS-SV with a single excitation wavelength from single-component to multi-component detection using photoswitchable fluorescent proteins (psFPs). We exploit their characteristic quantum yield of photo-switching to imprint spatio-temporal modulations onto the sedimentation signal that reveal different psFP-tagged protein components in the mixture. This novel approach facilitates studies of heterogeneous multi-protein complexes at orders of magnitude lower concentrations and for higher-affinity systems than previously possible. Using this technique we studied high-affinity interactions between the amino-terminal domains of GluA2 and GluA3 AMPA receptors. DOI: http://dx.doi.org/10.7554/eLife.17812.001 PMID:27436096

Multi-functional roles for the polypeptide transport associated domains of Toc75 in chloroplast protein import

PubMed Central

Paila, Yamuna D; Richardson, Lynn GL; Inoue, Hitoshi; Parks, Elizabeth S; McMahon, James; Inoue, Kentaro; Schnell, Danny J

2016-01-01

Toc75 plays a central role in chloroplast biogenesis in plants as the membrane channel of the protein import translocon at the outer envelope of chloroplasts (TOC). Toc75 is a member of the Omp85 family of bacterial and organellar membrane insertases, characterized by N-terminal POTRA (polypeptide-transport associated) domains and C-terminal membrane-integrated β-barrels. We demonstrate that the Toc75 POTRA domains are essential for protein import and contribute to interactions with TOC receptors, thereby coupling preprotein recognition at the chloroplast surface with membrane translocation. The POTRA domains also interact with preproteins and mediate the recruitment of molecular chaperones in the intermembrane space to facilitate membrane transport. Our studies are consistent with the multi-functional roles of POTRA domains observed in other Omp85 family members and demonstrate that the domains of Toc75 have evolved unique properties specific to the acquisition of protein import during endosymbiotic evolution of the TOC system in plastids. DOI: http://dx.doi.org/10.7554/eLife.12631.001 PMID:26999824

A team of heterochromatin factors collaborates with small RNA pathways to combat repetitive elements and germline stress

PubMed Central

McMurchy, Alicia N; Stempor, Przemyslaw; Gaarenstroom, Tessa; Wysolmerski, Brian; Dong, Yan; Aussianikava, Darya; Appert, Alex; Huang, Ni; Kolasinska-Zwierz, Paulina; Sapetschnig, Alexandra; Miska, Eric A; Ahringer, Julie

2017-01-01

Repetitive sequences derived from transposons make up a large fraction of eukaryotic genomes and must be silenced to protect genome integrity. Repetitive elements are often found in heterochromatin; however, the roles and interactions of heterochromatin proteins in repeat regulation are poorly understood. Here we show that a diverse set of C. elegans heterochromatin proteins act together with the piRNA and nuclear RNAi pathways to silence repetitive elements and prevent genotoxic stress in the germ line. Mutants in genes encoding HPL-2/HP1, LIN-13, LIN-61, LET-418/Mi-2, and H3K9me2 histone methyltransferase MET-2/SETDB1 also show functionally redundant sterility, increased germline apoptosis, DNA repair defects, and interactions with small RNA pathways. Remarkably, fertility of heterochromatin mutants could be partially restored by inhibiting cep-1/p53, endogenous meiotic double strand breaks, or the expression of MIRAGE1 DNA transposons. Functional redundancy among factors and pathways underlies the importance of safeguarding the genome through multiple means. DOI: http://dx.doi.org/10.7554/eLife.21666.001 PMID:28294943

Axon tension regulates fasciculation/defasciculation through the control of axon shaft zippering

PubMed Central

Šmít, Daniel; Fouquet, Coralie; Pincet, Frédéric; Zapotocky, Martin; Trembleau, Alain

2017-01-01

While axon fasciculation plays a key role in the development of neural networks, very little is known about its dynamics and the underlying biophysical mechanisms. In a model system composed of neurons grown ex vivo from explants of embryonic mouse olfactory epithelia, we observed that axons dynamically interact with each other through their shafts, leading to zippering and unzippering behavior that regulates their fasciculation. Taking advantage of this new preparation suitable for studying such interactions, we carried out a detailed biophysical analysis of zippering, occurring either spontaneously or induced by micromanipulations and pharmacological treatments. We show that zippering arises from the competition of axon-axon adhesion and mechanical tension in the axons, and provide the first quantification of the force of axon-axon adhesion. Furthermore, we introduce a biophysical model of the zippering dynamics, and we quantitatively relate the individual zipper properties to global characteristics of the developing axon network. Our study uncovers a new role of mechanical tension in neural development: the regulation of axon fasciculation. DOI: http://dx.doi.org/10.7554/eLife.19907.001 PMID:28422009

Autophagy functions as an antiviral mechanism against geminiviruses in plants

PubMed Central

Haxim, Yakupjan; Ismayil, Asigul; Jia, Qi; Wang, Yan; Zheng, Xiyin; Chen, Tianyuan; Qian, Lichao; Liu, Na; Wang, Yunjing; Han, Shaojie; Cheng, Jiaxuan; Qi, Yijun; Hong, Yiguo; Liu, Yule

2017-01-01

Autophagy is an evolutionarily conserved process that recycles damaged or unwanted cellular components, and has been linked to plant immunity. However, how autophagy contributes to plant immunity is unknown. Here we reported that the plant autophagic machinery targets the virulence factor βC1 of Cotton leaf curl Multan virus (CLCuMuV) for degradation through its interaction with the key autophagy protein ATG8. A V32A mutation in βC1 abolished its interaction with NbATG8f, and virus carrying βC1V32A showed increased symptoms and viral DNA accumulation in plants. Furthermore, silencing of autophagy-related genes ATG5 and ATG7 reduced plant resistance to the DNA viruses CLCuMuV, Tomato yellow leaf curl virus, and Tomato yellow leaf curl China virus, whereas activating autophagy by silencing GAPC genes enhanced plant resistance to viral infection. Thus, autophagy represents a novel anti-pathogenic mechanism that plays an important role in antiviral immunity in plants. DOI: http://dx.doi.org/10.7554/eLife.23897.001 PMID:28244873

The dimerization equilibrium of a ClC Cl−/H+ antiporter in lipid bilayers

PubMed Central

Chadda, Rahul; Krishnamani, Venkatramanan; Mersch, Kacey; Wong, Jason; Brimberry, Marley; Chadda, Ankita; Kolmakova-Partensky, Ludmila; Friedman, Larry J; Gelles, Jeff; Robertson, Janice L

2016-01-01

Interactions between membrane protein interfaces in lipid bilayers play an important role in membrane protein folding but quantification of the strength of these interactions has been challenging. Studying dimerization of ClC-type transporters offers a new approach to the problem, as individual subunits adopt a stable and functionally verifiable fold that constrains the system to two states – monomer or dimer. Here, we use single-molecule photobleaching analysis to measure the probability of ClC-ec1 subunit capture into liposomes during extrusion of large, multilamellar membranes. The capture statistics describe a monomer to dimer transition that is dependent on the subunit/lipid mole fraction density and follows an equilibrium dimerization isotherm. This allows for the measurement of the free energy of ClC-ec1 dimerization in lipid bilayers, revealing that it is one of the strongest membrane protein complexes measured so far, and introduces it as new type of dimerization model to investigate the physical forces that drive membrane protein association in membranes. DOI: http://dx.doi.org/10.7554/eLife.17438.001 PMID:27484630

Viral dark matter and virus–host interactions resolved from publicly available microbial genomes

PubMed Central

Roux, Simon; Hallam, Steven J; Woyke, Tanja; Sullivan, Matthew B

2015-01-01

The ecological importance of viruses is now widely recognized, yet our limited knowledge of viral sequence space and virus–host interactions precludes accurate prediction of their roles and impacts. In this study, we mined publicly available bacterial and archaeal genomic data sets to identify 12,498 high-confidence viral genomes linked to their microbial hosts. These data augment public data sets 10-fold, provide first viral sequences for 13 new bacterial phyla including ecologically abundant phyla, and help taxonomically identify 7–38% of ‘unknown’ sequence space in viromes. Genome- and network-based classification was largely consistent with accepted viral taxonomy and suggested that (i) 264 new viral genera were identified (doubling known genera) and (ii) cross-taxon genomic recombination is limited. Further analyses provided empirical data on extrachromosomal prophages and coinfection prevalences, as well as evaluation of in silico virus–host linkage predictions. Together these findings illustrate the value of mining viral signal from microbial genomes. DOI: http://dx.doi.org/10.7554/eLife.08490.001 PMID:26200428

Impaired retrograde transport of axonal autophagosomes contributes to autophagic stress in Alzheimer’s disease neurons

PubMed Central

Tammineni, Prasad; Ye, Xuan; Feng, Tuancheng; Aikal, Daniyal; Cai, Qian

2017-01-01

Neurons face unique challenges of transporting nascent autophagic vacuoles (AVs) from distal axons toward the soma, where mature lysosomes are mainly located. Autophagy defects have been linked to Alzheimer’s disease (AD). However, the mechanisms underlying altered autophagy remain unknown. Here, we demonstrate that defective retrograde transport contributes to autophagic stress in AD axons. Amphisomes predominantly accumulate at axonal terminals of mutant hAPP mice and AD patient brains. Amyloid-β (Aβ) oligomers associate with AVs in AD axons and interact with dynein motors. This interaction impairs dynein recruitment to amphisomes through competitive interruption of dynein-Snapin motor-adaptor coupling, thus immobilizing them in distal axons. Consistently, deletion of Snapin in mice causes AD-like axonal autophagic stress, whereas overexpressing Snapin in hAPP neurons reduces autophagic accumulation at presynaptic terminals by enhancing AV retrograde transport. Altogether, our study provides new mechanistic insight into AD-associated autophagic stress, thus establishing a foundation for ameliorating axonal pathology in AD. DOI: http://dx.doi.org/10.7554/eLife.21776.001 PMID:28085665

Long-range population dynamics of anatomically defined neocortical networks

PubMed Central

Chen, Jerry L; Voigt, Fabian F; Javadzadeh, Mitra; Krueppel, Roland; Helmchen, Fritjof

2016-01-01

The coordination of activity across neocortical areas is essential for mammalian brain function. Understanding this process requires simultaneous functional measurements across the cortex. In order to dissociate direct cortico-cortical interactions from other sources of neuronal correlations, it is furthermore desirable to target cross-areal recordings to neuronal subpopulations that anatomically project between areas. Here, we combined anatomical tracers with a novel multi-area two-photon microscope to perform simultaneous calcium imaging across mouse primary (S1) and secondary (S2) somatosensory whisker cortex during texture discrimination behavior, specifically identifying feedforward and feedback neurons. We find that coordination of S1-S2 activity increases during motor behaviors such as goal-directed whisking and licking. This effect was not specific to identified feedforward and feedback neurons. However, these mutually projecting neurons especially participated in inter-areal coordination when motor behavior was paired with whisker-texture touches, suggesting that direct S1-S2 interactions are sensory-dependent. Our results demonstrate specific functional coordination of anatomically-identified projection neurons across sensory cortices. DOI: http://dx.doi.org/10.7554/eLife.14679.001 PMID:27218452

Gap junctions composed of connexins 41.8 and 39.4 are essential for colour pattern formation in zebrafish

PubMed Central

Irion, Uwe; Frohnhöfer, Hans Georg; Krauss, Jana; Çolak Champollion, Tuǧba; Maischein, Hans-Martin; Geiger-Rudolph, Silke; Weiler, Christian; Nüsslein-Volhard, Christiane

2014-01-01

Interactions between all three pigment cell types are required to form the stripe pattern of adult zebrafish (Danio rerio), but their molecular nature is poorly understood. Mutations in leopard (leo), encoding Connexin 41.8 (Cx41.8), a gap junction subunit, cause a phenotypic series of spotted patterns. A new dominant allele, leotK3, leads to a complete loss of the pattern, suggesting a dominant negative impact on another component of gap junctions. In a genetic screen, we identified this component as Cx39.4 (luchs). Loss-of-function alleles demonstrate that luchs is required for stripe formation in zebrafish; however, the fins are almost not affected. Double mutants and chimeras, which show that leo and luchs are only required in xanthophores and melanophores, but not in iridophores, suggest that both connexins form heteromeric gap junctions. The phenotypes indicate that these promote homotypic interactions between melanophores and xanthophores, respectively, and those cells instruct the patterning of the iridophores. DOI: http://dx.doi.org/10.7554/eLife.05125.001 PMID:25535837

The structure of SV40 large T hexameric helicase in complex with AT-rich origin DNA

PubMed Central

Gai, Dahai; Wang, Damian; Li, Shu-Xing; Chen, Xiaojiang S

2016-01-01

DNA replication is a fundamental biological process. The initial step in eukaryotic DNA replication is the assembly of the pre-initiation complex, including the formation of two head-to-head hexameric helicases around the replication origin. How these hexameric helicases interact with their origin dsDNA remains unknown. Here, we report the co-crystal structure of the SV40 Large-T Antigen (LT) hexameric helicase bound to its origin dsDNA. The structure shows that the six subunits form a near-planar ring that interacts with the origin, so that each subunit makes unique contacts with the DNA. The origin dsDNA inside the narrower AAA+ domain channel shows partial melting due to the compression of the two phosphate backbones, forcing Watson-Crick base-pairs within the duplex to flip outward. This structure provides the first snapshot of a hexameric helicase binding to origin dsDNA, and suggests a possible mechanism of origin melting by LT during SV40 replication in eukaryotic cells. DOI: http://dx.doi.org/10.7554/eLife.18129.001 PMID:27921994

Dopamine and opioid systems interact within the nucleus accumbens to maintain monogamous pair bonds

PubMed Central

Resendez, Shanna L; Keyes, Piper C; Day, Jeremy J; Hambro, Caely; Austin, Curtis J; Maina, Francis K; Eidson, Lori N; Porter-Stransky, Kirsten A; Nevárez, Natalie; McLean, J William; Kuhnmuench, Morgan A; Murphy, Anne Z; Mathews, Tiffany A; Aragona, Brandon J

2016-01-01

Prairie vole breeder pairs form monogamous pair bonds, which are maintained through the expression of selective aggression toward novel conspecifics. Here, we utilize behavioral and anatomical techniques to extend the current understanding of neural mechanisms that mediate pair bond maintenance. For both sexes, we show that pair bonding up-regulates mRNA expression for genes encoding D1-like dopamine (DA) receptors and dynorphin as well as enhances stimulated DA release within the nucleus accumbens (NAc). We next show that D1-like receptor regulation of selective aggression is mediated through downstream activation of kappa-opioid receptors (KORs) and that activation of these receptors mediates social avoidance. Finally, we also identified sex-specific alterations in KOR binding density within the NAc shell of paired males and demonstrate that this alteration contributes to the neuroprotective effect of pair bonding against drug reward. Together, these findings suggest motivational and valence processing systems interact to mediate the maintenance of social bonds. DOI: http://dx.doi.org/10.7554/eLife.15325.001 PMID:27371827

Interaction of plasticity and circuit organization during the acquisition of cerebellum-dependent motor learning

PubMed Central

Yang, Yan; Lisberger, Stephen G

2013-01-01

Motor learning occurs through interactions between the cerebellar circuit and cellular plasticity at different sites. Previous work has established plasticity in brain slices and suggested plausible sites of behavioral learning. We now reveal what actually happens in the cerebellum during short-term learning. We monitor the expression of plasticity in the simple-spike firing of cerebellar Purkinje cells during trial-over-trial learning in smooth pursuit eye movements of monkeys. Our findings imply that: 1) a single complex-spike response driven by one instruction for learning causes short-term plasticity in a Purkinje cell’s mossy fiber/parallel-fiber input pathways; 2) complex-spike responses and simple-spike firing rate are correlated across the Purkinje cell population; and 3) simple-spike firing rate at the time of an instruction for learning modulates the probability of a complex-spike response, possibly through a disynaptic feedback pathway to the inferior olive. These mechanisms may participate in long-term motor learning. DOI: http://dx.doi.org/10.7554/eLife.01574.001 PMID:24381248

MorphoGraphX: A platform for quantifying morphogenesis in 4D

PubMed Central

Barbier de Reuille, Pierre; Routier-Kierzkowska, Anne-Lise; Kierzkowski, Daniel; Bassel, George W; Schüpbach, Thierry; Tauriello, Gerardo; Bajpai, Namrata; Strauss, Sören; Weber, Alain; Kiss, Annamaria; Burian, Agata; Hofhuis, Hugo; Sapala, Aleksandra; Lipowczan, Marcin; Heimlicher, Maria B; Robinson, Sarah; Bayer, Emmanuelle M; Basler, Konrad; Koumoutsakos, Petros; Roeder, Adrienne HK; Aegerter-Wilmsen, Tinri; Nakayama, Naomi; Tsiantis, Miltos; Hay, Angela; Kwiatkowska, Dorota; Xenarios, Ioannis; Kuhlemeier, Cris; Smith, Richard S

2015-01-01

Morphogenesis emerges from complex multiscale interactions between genetic and mechanical processes. To understand these processes, the evolution of cell shape, proliferation and gene expression must be quantified. This quantification is usually performed either in full 3D, which is computationally expensive and technically challenging, or on 2D planar projections, which introduces geometrical artifacts on highly curved organs. Here we present MorphoGraphX (www.MorphoGraphX.org), a software that bridges this gap by working directly with curved surface images extracted from 3D data. In addition to traditional 3D image analysis, we have developed algorithms to operate on curved surfaces, such as cell segmentation, lineage tracking and fluorescence signal quantification. The software's modular design makes it easy to include existing libraries, or to implement new algorithms. Cell geometries extracted with MorphoGraphX can be exported and used as templates for simulation models, providing a powerful platform to investigate the interactions between shape, genes and growth. DOI: http://dx.doi.org/10.7554/eLife.05864.001 PMID:25946108

Structural analysis of autoinhibition in the Ras-specific exchange factor RasGRP1

PubMed Central

Iwig, Jeffrey S; Vercoulen, Yvonne; Das, Rahul; Barros, Tiago; Limnander, Andre; Che, Yan; Pelton, Jeffrey G; Wemmer, David E; Roose, Jeroen P; Kuriyan, John

2013-01-01

RasGRP1 and SOS are Ras-specific nucleotide exchange factors that have distinct roles in lymphocyte development. RasGRP1 is important in some cancers and autoimmune diseases but, in contrast to SOS, its regulatory mechanisms are poorly understood. Activating signals lead to the membrane recruitment of RasGRP1 and Ras engagement, but it is unclear how interactions between RasGRP1 and Ras are suppressed in the absence of such signals. We present a crystal structure of a fragment of RasGRP1 in which the Ras-binding site is blocked by an interdomain linker and the membrane-interaction surface of RasGRP1 is hidden within a dimerization interface that may be stabilized by the C-terminal oligomerization domain. NMR data demonstrate that calcium binding to the regulatory module generates substantial conformational changes that are incompatible with the inactive assembly. These features allow RasGRP1 to be maintained in an inactive state that is poised for activation by calcium and membrane-localization signals. DOI: http://dx.doi.org/10.7554/eLife.00813.001 PMID:23908768

Translation repression via modulation of the cytoplasmic poly(A)-binding protein in the inflammatory response

PubMed Central

Zhang, Xu; Chen, Xiaoli; Liu, Qiuying; Zhang, Shaojie; Hu, Wenqian

2017-01-01

Gene expression is precisely regulated during the inflammatory response to control infection and limit the detrimental effects of inflammation. Here, we profiled global mRNA translation dynamics in the mouse primary macrophage-mediated inflammatory response and identified hundreds of differentially translated mRNAs. These mRNAs’ 3’UTRs have enriched binding motifs for several RNA-binding proteins, which implies extensive translational regulatory networks. We characterized one such protein, Zfp36, as a translation repressor. Using primary macrophages from a Zfp36-V5 epitope tagged knock-in mouse generated by CRISPR/Cas9-mediated genome editing, we found that the endogenous Zfp36 directly interacts with the cytoplasmic poly(A)-binding protein. Importantly, this interaction is required for the translational repression of Zfp36’s target mRNAs in resolving inflammation. Altogether, these results uncovered critical roles of translational regulations in controlling appropriate gene expression during the inflammatory response and revealed a new biologically relevant molecular mechanism of translational repression via modulating the cytoplasmic poly(A)-binding protein. DOI: http://dx.doi.org/10.7554/eLife.27786.001 PMID:28635594

Spatio-temporal analysis of aftershock sequences in terms of Non Extensive Statistical Physics.

NASA Astrophysics Data System (ADS)

Chochlaki, Kalliopi; Vallianatos, Filippos

2017-04-01

Earth's seismicity is considered as an extremely complicated process where long-range interactions and fracturing exist (Vallianatos et al., 2016). For this reason, in order to analyze it, we use an innovative methodological approach, introduced by Tsallis (Tsallis, 1988; 2009), named Non Extensive Statistical Physics. This approach introduce a generalization of the Boltzmann-Gibbs statistical mechanics and it is based on the definition of Tsallis entropy Sq, which maximized leads the the so-called q-exponential function that expresses the probability distribution function that maximizes the Sq. In the present work, we utilize the concept of Non Extensive Statistical Physics in order to analyze the spatiotemporal properties of several aftershock series. Marekova (Marekova, 2014) suggested that the probability densities of the inter-event distances between successive aftershocks follow a beta distribution. Using the same data set we analyze the inter-event distance distribution of several aftershocks sequences in different geographic regions by calculating non extensive parameters that determine the behavior of the system and by fitting the q-exponential function, which expresses the degree of non-extentivity of the investigated system. Furthermore, the inter-event times distribution of the aftershocks as well as the frequency-magnitude distribution has been analyzed. The results supports the applicability of Non Extensive Statistical Physics ideas in aftershock sequences where a strong correlation exists along with memory effects. References C. Tsallis, Possible generalization of Boltzmann-Gibbs statistics, J. Stat. Phys. 52 (1988) 479-487. doi:10.1007/BF01016429 C. Tsallis, Introduction to nonextensive statistical mechanics: Approaching a complex world, 2009. doi:10.1007/978-0-387-85359-8. E. Marekova, Analysis of the spatial distribution between successive earthquakes in aftershocks series, Annals of Geophysics, 57, 5, doi:10.4401/ag-6556, 2014 F. Vallianatos, G. Papadakis, G. Michas, Generalized statistical mechanics approaches to earthquakes and tectonics. Proc. R. Soc. A, 472, 20160497, 2016.

Roles of Transpiration, Forest Bioproductivity and Fire on a Long-Term Dripwater Hydrochemistry Dataset from Golgotha Cave, SW Australia

NASA Astrophysics Data System (ADS)

Treble, P. C.; Baker, A.; Fairchild, I. J.; Bradley, C.; Mahmud, K.; Andersen, M. S.; Meredith, K.; Mariethoz, G.

2015-12-01

Golgotha Cave is located in a forested catchment in SW Australia where evapotranspiration losses from the vadose-zone are high and forest biomass has been disturbed by fire. The cave has been continuously monitored since 2005 and this extensive dataset has been used to quantify key processes determining dripwater hydrology and chemistry (Mahmud et al., 2015; Treble et al., 2013; 2015). In this paper we present a synthesis of these findings and derive a conceptual model to illustrate the main hydrochemical processes that will impact cave dripwater in similar environments. We applied mass-balance techniques to quantify sources (water/rock interactions and aerosol) and sinks (prior calcite precipitation and biomass uptake). Mass-balance results suggest that transpiration and elemental sequestration into biomass modifies dripwater ion concentrations. The vegetation uptake impacts dripwater Mg, K and SO4, with the largest impact on SO4, estimated to be up to 60% at some drip sites. Overall, our findings suggest that varying amounts of transpiration by deeply-rooted trees contribute significantly to spatial and temporal variability in dripwater solute concentrations. This is in addition to the partitioning of infiltrating water between characteristic flow pathways. Applying principal components analysis, we identify a common long-term rising trend in dripwater Cl, Mg, K, Ca, Sr and Si. We assess whether the long-term trends in dripwater solutes are driven by post-fire biomass recovery and/or the impacts of a drying climate in SW Australia.ReferencesMahmud et al. (2015), Terrestrial Lidar Survey and Morphological Analysis to Identify Infiltration Properties in the Tamala Limestone, Western Australia, doi:10.1109/JSTARS.2015.2451088. Treble et al. (2013), An isotopic and modelling study of flow paths and storage in Quaternary calcarenite, doi:10.1016/J.Quascirev.2012.12.015. Treble et al. (2015), Impacts of cave air ventilation and in-cave prior calcite precipitation on Golgotha Cave dripwater chemistry, doi:10.1016/J.Quascirev.2015.06.001.

Cellular resolution circuit mapping with temporal-focused excitation of soma-targeted channelrhodopsin

PubMed Central

Baker, Christopher A; Elyada, Yishai M; Parra, Andres; Bolton, M McLean

2016-01-01

We describe refinements in optogenetic methods for circuit mapping that enable measurements of functional synaptic connectivity with single-neuron resolution. By expanding a two-photon beam in the imaging plane using the temporal focusing method and restricting channelrhodopsin to the soma and proximal dendrites, we are able to reliably evoke action potentials in individual neurons, verify spike generation with GCaMP6s, and determine the presence or absence of synaptic connections with patch-clamp electrophysiological recording. DOI: http://dx.doi.org/10.7554/eLife.14193.001 PMID:27525487

44 CFR 206.349 - Consistency determinations.

Code of Federal Regulations, 2014 CFR

2014-10-01

... consistency determination is required, the FEMA Regional Administrator shall evaluate the action according to... with DOI. (a) Impact identification. FEMA shall identify impacts of the following types that would... evaluation must result in a finding of consistency with CBRA by the Regional Administrator before funding may...

44 CFR 206.349 - Consistency determinations.

Code of Federal Regulations, 2012 CFR

2012-10-01

... consistency determination is required, the FEMA Regional Administrator shall evaluate the action according to... with DOI. (a) Impact identification. FEMA shall identify impacts of the following types that would... evaluation must result in a finding of consistency with CBRA by the Regional Administrator before funding may...

Sleep deprivation suppresses aggression in Drosophila

PubMed Central

Kayser, Matthew S; Mainwaring, Benjamin; Yue, Zhifeng; Sehgal, Amita

2015-01-01

Sleep disturbances negatively impact numerous functions and have been linked to aggression and violence. However, a clear effect of sleep deprivation on aggressive behaviors remains unclear. We find that acute sleep deprivation profoundly suppresses aggressive behaviors in the fruit fly, while other social behaviors are unaffected. This suppression is recovered following post-deprivation sleep rebound, and occurs regardless of the approach to achieve sleep loss. Genetic and pharmacologic approaches suggest octopamine signaling transmits changes in aggression upon sleep deprivation, and reduced aggression places sleep-deprived flies at a competitive disadvantage for obtaining a reproductive partner. These findings demonstrate an interaction between two phylogenetically conserved behaviors, and suggest that previous sleep experiences strongly modulate aggression with consequences for reproductive fitness. DOI: http://dx.doi.org/10.7554/eLife.07643.001 PMID:26216041

Cannabinoids: clearing the smoke on pain, inflammation and neurodegeneration.

PubMed

Downer, E J; Finn, D P

2014-03-01

This article is part of a themed section on Cannabinoids 2013. To view the other articles in this section, see Fagan and Campbell (2014) DOI: 10.1111/bph.12492, Ignatowska-Jankowska et al. (2014) DOI: 10.1111/bph.12298, Ligresti et al. (2014) DOI: 10.1111/bph.12410, Lopez-Rodriguez et al. (2014) DOI: 10.1111/bph.12519, Murataeva et al. (2014) DOI: 10.1111/bph.12411, Okine et al. (2014) DOI: 10.1111/bph.12540, Rodríguez-Cueto et al. (2014) DOI: 10.1111/bph.12283, Stanley and O'Sullivan (2014) DOI: 10.1111/bph.12560, Toguri et al. (2014) DOI: 10.1111/bph.12545, Wu et al. (2014) DOI: 10.1111/bph.12500. Linked articles are: Avraham et al. (2014) DOI: 10.1111/bph.12478, Machado et al. (2014) DOI: 10.1111/bph.12488, Ward et al. (2014) DOI: 10.1111/bph.12439. © 2014 The British Pharmacological Society.

The integrated water balance and soil data set of the Rollesbroich hydrological observatory

NASA Astrophysics Data System (ADS)

Qu, Wei; Bogena, Heye R.; Huisman, Johan A.; Schmidt, Marius; Kunkel, Ralf; Weuthen, Ansgar; Schiedung, Henning; Schilling, Bernd; Sorg, Jürgen; Vereecken, Harry

2016-10-01

The Rollesbroich headwater catchment located in western Germany is a densely instrumented hydrological observatory and part of the TERENO (Terrestrial Environmental Observatories) initiative. The measurements acquired in this observatory present a comprehensive data set that contains key hydrological fluxes in addition to important hydrological states and properties. Meteorological data (i.e., precipitation, air temperature, air humidity, radiation components, and wind speed) are continuously recorded and actual evapotranspiration is measured using the eddy covariance technique. Runoff is measured at the catchment outlet with a gauging station. In addition, spatiotemporal variations in soil water content and temperature are measured at high resolution with a wireless sensor network (SoilNet). Soil physical properties were determined using standard laboratory procedures from samples taken at a large number of locations in the catchment. This comprehensive data set can be used to validate remote sensing retrievals and hydrological models, to improve the understanding of spatial temporal dynamics of soil water content, to optimize data assimilation and inverse techniques for hydrological models, and to develop upscaling and downscaling procedures of soil water content information. The complete data set is freely available online (http://www.tereno.net, doi:10.5880/TERENO.2016.001, doi:10.5880/TERENO.2016.004, doi:10.5880/TERENO.2016.003) and additionally referenced by three persistent identifiers securing the long-term data and metadata availability.

Pseudo-direct bandgap transitions in silicon nanocrystals: effects on optoelectronics and thermoelectrics

NASA Astrophysics Data System (ADS)

Singh, Vivek; Yu, Yixuan; Sun, Qi-C.; Korgel, Brian; Nagpal, Prashant

2014-11-01

While silicon nanostructures are extensively used in electronics, the indirect bandgap of silicon poses challenges for optoelectronic applications like photovoltaics and light emitting diodes (LEDs). Here, we show that size-dependent pseudo-direct bandgap transitions in silicon nanocrystals dominate the interactions between (photoexcited) charge carriers and phonons, and hence the optoelectronic properties of silicon nanocrystals. Direct measurements of the electronic density of states (DOS) for different sized silicon nanocrystals reveal that these pseudo-direct transitions, likely arising from the nanocrystal surface, can couple with the quantum-confined silicon states. Moreover, we demonstrate that since these transitions determine the interactions of charge carriers with phonons, they change the light emission, absorption, charge carrier diffusion and phonon drag (Seebeck coefficient) in nanoscaled silicon semiconductors. Therefore, these results can have important implications for the design of optoelectronics and thermoelectric devices based on nanostructured silicon.While silicon nanostructures are extensively used in electronics, the indirect bandgap of silicon poses challenges for optoelectronic applications like photovoltaics and light emitting diodes (LEDs). Here, we show that size-dependent pseudo-direct bandgap transitions in silicon nanocrystals dominate the interactions between (photoexcited) charge carriers and phonons, and hence the optoelectronic properties of silicon nanocrystals. Direct measurements of the electronic density of states (DOS) for different sized silicon nanocrystals reveal that these pseudo-direct transitions, likely arising from the nanocrystal surface, can couple with the quantum-confined silicon states. Moreover, we demonstrate that since these transitions determine the interactions of charge carriers with phonons, they change the light emission, absorption, charge carrier diffusion and phonon drag (Seebeck coefficient) in nanoscaled silicon semiconductors. Therefore, these results can have important implications for the design of optoelectronics and thermoelectric devices based on nanostructured silicon. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr04688a

25 CFR 1000.3 - Purpose and scope.

Code of Federal Regulations, 2011 CFR

2011-04-01

... UNDER THE TRIBAL SELF-GOVERNMENT ACT AMENDMENTS TO THE INDIAN SELF-DETERMINATION AND EDUCATION ACT... rules for the Department of the Interior (DOI) in implementing Title IV of the Indian Self-Determination... of Pub. L. 103-413, the Tribal Self-Governance Act of 1994 (108 Stat. 4250, October 25, 1994). (b...

Hallucinogenic 5-HT2AR agonists LSD and DOI enhance dopamine D2R protomer recognition and signaling of D2-5-HT2A heteroreceptor complexes.

PubMed

Borroto-Escuela, Dasiel O; Romero-Fernandez, Wilber; Narvaez, Manuel; Oflijan, Julia; Agnati, Luigi F; Fuxe, Kjell

2014-01-03

Dopamine D2LR-serotonin 5-HT2AR heteromers were demonstrated in HEK293 cells after cotransfection of the two receptors and shown to have bidirectional receptor-receptor interactions. In the current study the existence of D2L-5-HT2A heteroreceptor complexes was demonstrated also in discrete regions of the ventral and dorsal striatum with in situ proximity ligation assays (PLA). The hallucinogenic 5-HT2AR agonists LSD and DOI but not the standard 5-HT2AR agonist TCB2 and 5-HT significantly increased the density of D2like antagonist (3)H-raclopride binding sites and significantly reduced the pKiH values of the high affinity D2R agonist binding sites in (3)H-raclopride/DA competition experiments. Similar results were obtained in HEK293 cells and in ventral striatum. The effects of the hallucinogenic 5-HT2AR agonists on D2R density and affinity were blocked by the 5-HT2A antagonist ketanserin. In a forskolin-induced CRE-luciferase reporter gene assay using cotransfected but not D2R singly transfected HEK293 cells DOI and LSD but not TCB2 significantly enhanced the D2LR agonist quinpirole induced inhibition of CRE-luciferase activity. Haloperidol blocked the effects of both quinpirole alone and the enhancing actions of DOI and LSD while ketanserin only blocked the enhancing actions of DOI and LSD. The mechanism for the allosteric enhancement of the D2R protomer recognition and signalling observed is likely mediated by a biased agonist action of the hallucinogenic 5-HT2AR agonists at the orthosteric site of the 5-HT2AR protomer. This mechanism may contribute to the psychotic actions of LSD and DOI and the D2-5-HT2A heteroreceptor complex may thus be a target for the psychotic actions of hallunicogenic 5-HT2A agonists. Copyright © 2013 Elsevier Inc. All rights reserved.

Head-twitch response in rodents induced by the hallucinogen 2,5-dimethoxy-4-iodoamphetamine: a comprehensive history, a re-evaluation of mechanisms, and its utility as a model

PubMed Central

Canal, Clint E.; Morgan, Drake

2013-01-01

Two primary animal models persist for assessing hallucinogenic potential of novel compounds and for examining the pharmacological and neurobiological substrates underlying the actions of classical hallucinogens, the two-lever drug discrimination procedure and the drug-induced head-twitch response (HTR) in rodents. The substituted amphetamine hallucinogen, serotonin 2 (5-HT2) receptor agonist, 2,5-dimethoxy-4-iodoamphetamine (DOI) has emerged as the most popular pharmacological tool used in HTR studies of hallucinogens. Synthesizing classic, recent, and relatively overlooked findings, addressing ostensibly conflicting observations, and considering contemporary theories in receptor and behavioural pharmacology, this review provides an up-to-date and comprehensive synopsis of DOI and the HTR model, from neural mechanisms to utility for understanding psychiatric diseases. Also presented is support for the argument that, although both the two-lever drug discrimination and the HTR models in rodents are useful for uncovering receptors, interacting proteins, intracellular signalling pathways, and neurochemical processes affected by DOI and related classical hallucinogens, results from both models suggest they are not reporting hallucinogenic experiences in animals. PMID:22517680

Population-based Neisseria gonorrhoeae, Chlamydia trachomatis and Trichomonas vaginalis Prevalence Using Discarded, Deidentified Urine Specimens Previously Collected for Drug Testing (Open Access Publisher’s Version)

DTIC Science & Technology

2017-10-24

123van Houdt R, et al. Sex Transm Infect 2018;94:117–123. doi:10.1136/sextrans-2017-053133 Epidemiology letter Population-based Neisseria...trichomonas vaginalis testing, Melinda Balansay-ames, chris Myers and gary Brice for Pcr- based sex determination testing, and Kimberly De Vera for...dx. doi. org/ 10. 1136/ sextrans- 2017- 053355) To cite Harbertson J, Jamerson M, graf PcF, et al. Sex Transm Infect 2018;94:123. received 28 July

Carbon-free production of 2-deoxy-scyllo-inosose (DOI) in cyanobacterium Synechococcus elongatus PCC 7942.

PubMed

Watanabe, Satoru; Ozawa, Hiroaki; Kato, Hiroaki; Nimura-Matsune, Kaori; Hirayama, Toshifumi; Kudo, Fumitaka; Eguchi, Tadashi; Kakinuma, Katsumi; Yoshikawa, Hirofumi

2018-01-01

Owing to their photosynthetic capabilities, there is increasing interest in utilizing cyanobacteria to convert solar energy into biomass. 2-Deoxy-scyllo-inosose (DOI) is a valuable starting material for the benzene-free synthesis of catechol and other benzenoids. DOI synthase (DOIS) is responsible for the formation of DOI from d-glucose-6-phosphate (G6P) in the biosynthesis of 2-deoxystreptamine-containing aminoglycoside antibiotics such as neomycin and butirosin. DOI fermentation using a recombinant Escherichia coli strain has been reported, although a carbon source is necessary for high-yield DOI production. We constructed DOI-producing cyanobacteria toward carbon-free and sustainable DOI production. A DOIS gene derived from the butirosin producer strain Bacillus circulans (btrC) was introduced and expressed in the cyanobacterium Synechococcus elongatus PCC 7942. We ultimately succeeded in producing 400 mg/L of DOI in S. elongatus without using a carbon source. DOI production by cyanobacteria represents a novel and efficient approach for producing benzenoids from G6P synthesized by photosynthesis.

Structural characterization of framework–gas interactions in the metal–organic framework Co2(dobdc) by in situ single-crystal X-ray diffraction† †Electronic supplementary information (ESI) available: Supplementary figures, crystallographic information, adsorption isotherms and fits, CCDC 1530119–1530126. For ESI and crystallographic data in CIF or other electronic format. See DOI: 10.1039/c7sc00449d Click here for additional data file. Click here for additional data file.

PubMed Central

Gonzalez, Miguel I.; Mason, Jarad A.; Bloch, Eric D.; Teat, Simon J.; Gagnon, Kevin J.; Morrison, Gregory Y.; Queen, Wendy L.

2017-01-01

The crystallographic characterization of framework–guest interactions in metal–organic frameworks allows the location of guest binding sites and provides meaningful information on the nature of these interactions, enabling the correlation of structure with adsorption behavior. Here, techniques developed for in situ single-crystal X-ray diffraction experiments on porous crystals have enabled the direct observation of CO, CH4, N2, O2, Ar, and P4 adsorption in Co2(dobdc) (dobdc4– = 2,5-dioxido-1,4-benzenedicarboxylate), a metal–organic framework bearing coordinatively unsaturated cobalt(ii) sites. All these molecules exhibit such weak interactions with the high-spin cobalt(ii) sites in the framework that no analogous molecular structures exist, demonstrating the utility of metal–organic frameworks as crystalline matrices for the isolation and structural determination of unstable species. Notably, the Co–CH4 and Co–Ar interactions observed in Co2(dobdc) represent, to the best of our knowledge, the first single-crystal structure determination of a metal–CH4 interaction and the first crystallographically characterized metal–Ar interaction. Analysis of low-pressure gas adsorption isotherms confirms that these gases exhibit mainly physisorptive interactions with the cobalt(ii) sites in Co2(dobdc), with differential enthalpies of adsorption as weak as –17(1) kJ mol–1 (for Ar). Moreover, the structures of Co2(dobdc)·3.8N2, Co2(dobdc)·5.9O2, and Co2(dobdc)·2.0Ar reveal the location of secondary (N2, O2, and Ar) and tertiary (O2) binding sites in Co2(dobdc), while high-pressure CO2, CO, CH4, N2, and Ar adsorption isotherms show that these binding sites become more relevant at elevated pressures. PMID:28966783

Process Architecture for Managing Digital Object Identifiers

NASA Astrophysics Data System (ADS)

Wanchoo, L.; James, N.; Stolte, E.

2014-12-01

In 2010, NASA's Earth Science Data and Information System (ESDIS) Project implemented a process for registering Digital Object Identifiers (DOIs) for data products distributed by Earth Observing System Data and Information System (EOSDIS). For the first 3 years, ESDIS evolved the process involving the data provider community in the development of processes for creating and assigning DOIs, and guidelines for the landing page. To accomplish this, ESDIS established two DOI User Working Groups: one for reviewing the DOI process whose recommendations were submitted to ESDIS in February 2014; and the other recently tasked to review and further develop DOI landing page guidelines for ESDIS approval by end of 2014. ESDIS has recently upgraded the DOI system from a manually-driven system to one that largely automates the DOI process. The new automated feature include: a) reviewing the DOI metadata, b) assigning of opaque DOI name if data provider chooses, and c) reserving, registering, and updating the DOIs. The flexibility of reserving the DOI allows data providers to embed and test the DOI in the data product metadata before formally registering with EZID. The DOI update process allows the changing of any DOI metadata except the DOI name unless the name has not been registered. Currently, ESDIS has processed a total of 557 DOIs of which 379 DOIs are registered with EZID and 178 are reserved with ESDIS. The DOI incorporates several metadata elements that effectively identify the data product and the source of availability. Of these elements, the Uniform Resource Locator (URL) attribute has the very important function of identifying the landing page which describes the data product. ESDIS in consultation with data providers in the Earth Science community is currently developing landing page guidelines that specify the key data product descriptive elements to be included on each data product's landing page. This poster will describe in detail the unique automated process and underlying system implemented by ESDIS for registering DOIs, as well as some of the lessons learned from the development of the process. In addition, this paper will summarize the recommendations made by the DOI Process and DOI Landing Page User Working Groups, and the procedures developed for implementing those recommendations.

The antipsychotic-like effects of positive allosteric modulators of metabotropic glutamate mGlu4 receptors in rodents

PubMed Central

Sławińska, Anna; Wierońska, Joanna M; Stachowicz, Katarzyna; Marciniak, Marcin; Łasoń-Tyburkiewicz, Magdalena; Gruca, Piotr; Papp, Mariusz; Kusek, Magdalena; Tokarski, Krzysztof; Doller, Darío; Pilc, Andrzej

2013-01-01

Background and Purpose Because agonists at metabotropic glutamate receptors exert beneficial effects in schizophrenia, we have assessed the actions of Lu AF21934 and Lu AF32615, two chemically distinct, selective and brain-penetrant positive allosteric modulators (PAMs) of the mGlu4 receptor, in several tests reflecting positive, negative and cognitive symptoms of schizophrenia in rodents. Experimental Approach Hyperactivity induced by MK-801 or amphetamine and head twitches induced by 2,5-dimethoxy-4-iodoamphetamine (DOI) in mice were used as models for positive symptoms. Disruption of social interaction and spatial delayed alternation tests induced by MK-801 in rats were used as models for negative and cognitive symptoms of schizophrenia, respectively. Key Results Lu AF21934 (0.1–5 mg·kg−1) and Lu AF32615 (2–10 mg·kg−1) dose-dependently inhibited hyperactivity induced by MK-801 or amphetamine. They also antagonized head twitches and increased frequency of spontaneous excitatory postsynaptic currents (EPSCs) in brain slices, induced by DOI. In mice lacking the mGlu4 receptor (mGlu4−/−) mice, Lu AF21934 did not antagonize DOI-induced head twitches. MK-801-induced disruption in the social interaction test was decreased by Lu AF21934 at 0.5 mg·kg−1 and by Lu AF32615 at 10 mg·kg−1. In the delayed spatial alternation test, Lu AF21934 was active at 1 and 2 mg·kg−1, while Lu AF32615 was active at 10 mg·kg−1. Conclusions and Implications We propose that activation by PAMs of the mGlu4 receptor is a promising approach to the discovery of novel antipsychotic drugs. PMID:23714045

Digital pulse processing and electronic noise analysis for improving energy resolutions in planar TlBr detectors

NASA Astrophysics Data System (ADS)

Tada, Tsutomu; Hitomi, Keitaro; Tanaka, Tomonobu; Wu, Yan; Kim, Seong-Yun; Yamazaki, Hiromichi; Ishii, Keizo

2011-05-01

Digital pulse processing and electronic noise analysis are proposed for improving energy resolution in planar thallium bromide (TlBr) detectors. An energy resolution of 5.8% FWHM at 662 keV was obtained from a 0.5 mm thick planar TlBr detector at room temperature using a digitizer with a sampling rate of 100 MS/s and 8 bit resolution. The electronic noise in the detector-preamplifier system was measured as a function of pulse shaping time in order to investigate the optimum shaping time for the detector. The depth of interaction (DOI) in TlBr detectors for incident gamma-rays was determined by taking the ratio of pulse heights for fast-shaped to slow-shaped signals. FWHM energy resolution of the detector was improved from 5.8% to 4.2% by implementing depth correction and by using the obtained optimum shaping time.

Coordination and Collective Decision Making

DTIC Science & Technology

2015-08-21

Fisheries , (06 2014): 1. doi: 10.1111/faf.12084 L. Giuggioli, J. R. Potts, D. I. Rubenstein, S. A. Levin. Stigmergy, collective actions, and animal ...terrestrial and marine food webs, as well as enabling interspecies interactions such as reproduction. Eulerian models describe aggregations of animals in...achieved in decision-making. Animal groups frequently display highly coordinated movements, and provide an excellent vehicle by which to understand

The structure of the core NuRD repression complex provides insights into its interaction with chromatin

PubMed Central

Millard, Christopher J; Varma, Niranjan; Saleh, Almutasem; Morris, Kyle; Watson, Peter J; Bottrill, Andrew R; Fairall, Louise; Smith, Corinne J; Schwabe, John WR

2016-01-01

The NuRD complex is a multi-protein transcriptional corepressor that couples histone deacetylase and ATP-dependent chromatin remodelling activities. The complex regulates the higher-order structure of chromatin, and has important roles in the regulation of gene expression, DNA damage repair and cell differentiation. HDACs 1 and 2 are recruited by the MTA1 corepressor to form the catalytic core of the complex. The histone chaperone protein RBBP4, has previously been shown to bind to the carboxy-terminal tail of MTA1. We show that MTA1 recruits a second copy of RBBP4. The crystal structure reveals an extensive interface between MTA1 and RBBP4. An EM structure, supported by SAXS and crosslinking, reveals the architecture of the dimeric HDAC1:MTA1:RBBP4 assembly which forms the core of the NuRD complex. We find evidence that in this complex RBBP4 mediates interaction with histone H3 tails, but not histone H4, suggesting a mechanism for recruitment of the NuRD complex to chromatin. DOI: http://dx.doi.org/10.7554/eLife.13941.001 PMID:27098840

Folding behavior of a T-shaped, ribosome-binding translation enhancer implicated in a wide-spread conformational switch

PubMed Central

Le, My-Tra; Kasprzak, Wojciech K; Kim, Taejin; Gao, Feng; Young, Megan YL; Yuan, Xuefeng; Shapiro, Bruce A; Seog, Joonil; Simon, Anne E

2017-01-01

Turnip crinkle virus contains a T-shaped, ribosome-binding, translation enhancer (TSS) in its 3’UTR that serves as a hub for interactions throughout the region. The viral RNA-dependent RNA polymerase (RdRp) causes the TSS/surrounding region to undergo a conformational shift postulated to inhibit translation. Using optical tweezers (OT) and steered molecular dynamic simulations (SMD), we found that the unusual stability of pseudoknotted element H4a/Ψ3 required five upstream adenylates, and H4a/Ψ3 was necessary for cooperative association of two other hairpins (H5/H4b) in Mg2+. SMD recapitulated the TSS unfolding order in the absence of Mg2+, showed dependence of the resistance to pulling on the 3D orientation and gave structural insights into the measured contour lengths of the TSS structure elements. Adenylate mutations eliminated one-site RdRp binding to the 3’UTR, suggesting that RdRp binding to the adenylates disrupts H4a/Ψ3, leading to loss of H5/H4b interaction and promoting a conformational switch interrupting translation and promoting replication. DOI: http://dx.doi.org/10.7554/eLife.22883.001 PMID:28186489

Elucidation of the anti-autophagy mechanism of the Legionella effector RavZ using semisynthetic LC3 proteins

PubMed Central

Yang, Aimin; Pantoom, Supansa; Wu, Yao-Wen

2017-01-01

Autophagy is a conserved cellular process involved in the elimination of proteins and organelles. It is also used to combat infection with pathogenic microbes. The intracellular pathogen Legionella pneumophila manipulates autophagy by delivering the effector protein RavZ to deconjugate Atg8/LC3 proteins coupled to phosphatidylethanolamine (PE) on autophagosomal membranes. To understand how RavZ recognizes and deconjugates LC3-PE, we prepared semisynthetic LC3 proteins and elucidated the structures of the RavZ:LC3 interaction. Semisynthetic LC3 proteins allowed the analysis of structure-function relationships. RavZ extracts LC3-PE from the membrane before deconjugation. RavZ initially recognizes the LC3 molecule on membranes via its N-terminal LC3-interacting region (LIR) motif. The RavZ α3 helix is involved in extraction of the PE moiety and docking of the acyl chains into the lipid-binding site of RavZ that is related in structure to that of the phospholipid transfer protein Sec14. Thus, Legionella has evolved a novel mechanism to specifically evade host autophagy. DOI: http://dx.doi.org/10.7554/eLife.23905.001 PMID:28395732

Unipolar distributions of junctional Myosin II identify cell stripe boundaries that drive cell intercalation throughout Drosophila axis extension

PubMed Central

Tetley, Robert J; Blanchard, Guy B; Fletcher, Alexander G; Adams, Richard J; Sanson, Bénédicte

2016-01-01

Convergence and extension movements elongate tissues during development. Drosophila germ-band extension (GBE) is one example, which requires active cell rearrangements driven by Myosin II planar polarisation. Here, we develop novel computational methods to analyse the spatiotemporal dynamics of Myosin II during GBE, at the scale of the tissue. We show that initial Myosin II bipolar cell polarization gives way to unipolar enrichment at parasegmental boundaries and two further boundaries within each parasegment, concomitant with a doubling of cell number as the tissue elongates. These boundaries are the primary sites of cell intercalation, behaving as mechanical barriers and providing a mechanism for how cells remain ordered during GBE. Enrichment at parasegment boundaries during GBE is independent of Wingless signaling, suggesting pair-rule gene control. Our results are consistent with recent work showing that a combinatorial code of Toll-like receptors downstream of pair-rule genes contributes to Myosin II polarization via local cell-cell interactions. We propose an updated cell-cell interaction model for Myosin II polarization that we tested in a vertex-based simulation. DOI: http://dx.doi.org/10.7554/eLife.12094.001 PMID:27183005

A chloroplast retrograde signal, 3’-phosphoadenosine 5’-phosphate, acts as a secondary messenger in abscisic acid signaling in stomatal closure and germination

PubMed Central

Pornsiriwong, Wannarat; Estavillo, Gonzalo M; Chan, Kai Xun; Tee, Estee E; Ganguly, Diep; Crisp, Peter A; Phua, Su Yin; Zhao, Chenchen; Qiu, Jiaen; Park, Jiyoung; Yong, Miing Tiem; Nisar, Nazia; Yadav, Arun Kumar; Schwessinger, Benjamin; Rathjen, John; Cazzonelli, Christopher I; Wilson, Philippa B; Gilliham, Matthew; Chen, Zhong-Hua; Pogson, Barry J

2017-01-01

Organelle-nuclear retrograde signaling regulates gene expression, but its roles in specialized cells and integration with hormonal signaling remain enigmatic. Here we show that the SAL1-PAP (3′-phosphoadenosine 5′- phosphate) retrograde pathway interacts with abscisic acid (ABA) signaling to regulate stomatal closure and seed germination in Arabidopsis. Genetically or exogenously manipulating PAP bypasses the canonical signaling components ABA Insensitive 1 (ABI1) and Open Stomata 1 (OST1); priming an alternative pathway that restores ABA-responsive gene expression, ROS bursts, ion channel function, stomatal closure and drought tolerance in ost1-2. PAP also inhibits wild type and abi1-1 seed germination by enhancing ABA sensitivity. PAP-XRN signaling interacts with ABA, ROS and Ca2+; up-regulating multiple ABA signaling components, including lowly-expressed Calcium Dependent Protein Kinases (CDPKs) capable of activating the anion channel SLAC1. Thus, PAP exhibits many secondary messenger attributes and exemplifies how retrograde signals can have broader roles in hormone signaling, allowing chloroplasts to fine-tune physiological responses. DOI: http://dx.doi.org/10.7554/eLife.23361.001 PMID:28323614

A new topology of the HK97-like fold revealed in Bordetella bacteriophage by cryoEM at 3.5 Å resolution

PubMed Central

Zhang, Xing; Guo, Huatao; Jin, Lei; Czornyj, Elizabeth; Hodes, Asher; Hui, Wong H; Nieh, Angela W; Miller, Jeff F; Zhou, Z Hong

2013-01-01

Bacteriophage BPP-1 infects and kills Bordetella species that cause whooping cough. Its diversity-generating retroelement (DGR) provides a naturally occurring phage-display system, but engineering efforts are hampered without atomic structures. Here, we report a cryo electron microscopy structure of the BPP-1 head at 3.5 Å resolution. Our atomic model shows two of the three protein folds representing major viral lineages: jellyroll for its cement protein (CP) and HK97-like (‘Johnson’) for its major capsid protein (MCP). Strikingly, the fold topology of MCP is permuted non-circularly from the Johnson fold topology previously seen in viral and cellular proteins. We illustrate that the new topology is likely the only feasible alternative of the old topology. β-sheet augmentation and electrostatic interactions contribute to the formation of non-covalent chainmail in BPP-1, unlike covalent inter-protein linkages of the HK97 chainmail. Despite these complex interactions, the termini of both CP and MCP are ideally positioned for DGR-based phage-display engineering. DOI: http://dx.doi.org/10.7554/eLife.01299.001 PMID:24347545

A host basal transcription factor is a key component for infection of rice by TALE-carrying bacteria

PubMed Central

Yuan, Meng; Ke, Yinggen; Huang, Renyan; Ma, Ling; Yang, Zeyu; Chu, Zhaohui; Xiao, Jinghua; Li, Xianghua; Wang, Shiping

2016-01-01

Transcription activator-like effectors (TALEs) are sequence-specific DNA binding proteins found in a range of plant pathogenic bacteria, where they play important roles in host-pathogen interactions. However, it has been unclear how TALEs, after they have been injected into the host cells, activate transcription of host genes required for infection success. Here, we show that the basal transcription factor IIA gamma subunit TFIIAγ5 from rice is a key component for infection by the TALE-carrying bacterium Xanthomonas oryzae pv. oryzae, the causal agent for bacterial blight. Direct interaction of several TALEs with TFIIAγ5 is required for activation of disease susceptibility genes. Conversely, reduced expression of the TFIIAγ5 host gene limits the induction of susceptibility genes and thus decreases bacterial blight symptoms. Suppression or mutation of TFIIAγ5 can also reduce bacterial streak, another devastating disease of rice caused by TALE-carrying X. oryzae pv. oryzicola. These results have important implications for formulating a widely applicable strategy with which to improve resistance of plants to TALE-carrying pathogens. DOI: http://dx.doi.org/10.7554/eLife.19605.001 PMID:27472897

The RNF168 paralog RNF169 defines a new class of ubiquitylated histone reader involved in the response to DNA damage

PubMed Central

Kitevski-LeBlanc, Julianne; Fradet-Turcotte, Amélie; Portella, Guillem; Yuwen, Tairan; Panier, Stephanie; Duan, Shili; Canny, Marella D; van Ingen, Hugo; Arrowsmith, Cheryl H; Rubinstein, John L; Vendruscolo, Michele; Durocher, Daniel; Kay, Lewis E

2017-01-01

Site-specific histone ubiquitylation plays a central role in orchestrating the response to DNA double-strand breaks (DSBs). DSBs elicit a cascade of events controlled by the ubiquitin ligase RNF168, which promotes the accumulation of repair factors such as 53BP1 and BRCA1 on the chromatin flanking the break site. RNF168 also promotes its own accumulation, and that of its paralog RNF169, but how they recognize ubiquitylated chromatin is unknown. Using methyl-TROSY solution NMR spectroscopy and molecular dynamics simulations, we present an atomic resolution model of human RNF169 binding to a ubiquitylated nucleosome, and validate it by electron cryomicroscopy. We establish that RNF169 binds to ubiquitylated H2A-Lys13/Lys15 in a manner that involves its canonical ubiquitin-binding helix and a pair of arginine-rich motifs that interact with the nucleosome acidic patch. This three-pronged interaction mechanism is distinct from that by which 53BP1 binds to ubiquitylated H2A-Lys15 highlighting the diversity in site-specific recognition of ubiquitylated nucleosomes. DOI: http://dx.doi.org/10.7554/eLife.23872.001 PMID:28406400

Major satellite repeat RNA stabilize heterochromatin retention of Suv39h enzymes by RNA-nucleosome association and RNA:DNA hybrid formation

PubMed Central

Velazquez Camacho, Oscar; Galan, Carmen; Swist-Rosowska, Kalina; Ching, Reagan; Gamalinda, Michael; Karabiber, Fethullah; De La Rosa-Velazquez, Inti; Engist, Bettina; Koschorz, Birgit; Shukeir, Nicholas; Onishi-Seebacher, Megumi; van de Nobelen, Suzanne; Jenuwein, Thomas

2017-01-01

The Suv39h1 and Suv39h2 histone lysine methyltransferases are hallmark enzymes at mammalian heterochromatin. We show here that the mouse Suv39h2 enzyme differs from Suv39h1 by containing an N-terminal basic domain that facilitates retention at mitotic chromatin and provides an additional affinity for major satellite repeat RNA. To analyze an RNA-dependent interaction with chromatin, we purified native nucleosomes from mouse ES cells and detect that Suv39h1 and Suv39h2 exclusively associate with poly-nucleosomes. This association was attenuated upon RNaseH incubation and entirely lost upon RNaseA digestion of native chromatin. Major satellite repeat transcripts remain chromatin-associated and have a secondary structure that favors RNA:DNA hybrid formation. Together, these data reveal an RNA-mediated mechanism for the stable chromatin interaction of the Suv39h KMT and suggest a function for major satellite non-coding RNA in the organization of an RNA-nucleosome scaffold as the underlying structure of mouse heterochromatin. DOI: http://dx.doi.org/10.7554/eLife.25293.001 PMID:28760199

The E3 ubiquitin ligase ZNRF2 is a substrate of mTORC1 and regulates its activation by amino acids

PubMed Central

Hoxhaj, Gerta; Caddye, Edward; Najafov, Ayaz; Houde, Vanessa P; Johnson, Catherine; Dissanayake, Kumara; Toth, Rachel; Campbell, David G; Prescott, Alan R; MacKintosh, Carol

2016-01-01

The mechanistic Target of Rapamycin complex 1 (mTORC1) senses intracellular amino acid levels through an intricate machinery, which includes the Rag GTPases, Ragulator and vacuolar ATPase (V-ATPase). The membrane-associated E3 ubiquitin ligase ZNRF2 is released into the cytosol upon its phosphorylation by Akt. In this study, we show that ZNRF2 interacts with mTOR on membranes, promoting the amino acid-stimulated translocation of mTORC1 to lysosomes and its activation in human cells. ZNRF2 also interacts with the V-ATPase and preserves lysosomal acidity. Moreover, knockdown of ZNRF2 decreases cell size and cell proliferation. Upon growth factor and amino acid stimulation, mTORC1 phosphorylates ZNRF2 on Ser145, and this phosphosite is dephosphorylated by protein phosphatase 6. Ser145 phosphorylation stimulates vesicle-to-cytosol translocation of ZNRF2 and forms a novel negative feedback on mTORC1. Our findings uncover ZNRF2 as a component of the amino acid sensing machinery that acts upstream of Rag-GTPases and the V-ATPase to activate mTORC1. DOI: http://dx.doi.org/10.7554/eLife.12278.001 PMID:27244671

TAPBPR bridges UDP-glucose:glycoprotein glucosyltransferase 1 onto MHC class I to provide quality control in the antigen presentation pathway

PubMed Central

Neerincx, Andreas; Hermann, Clemens; Antrobus, Robin; van Hateren, Andy; Cao, Huan; Trautwein, Nico; Stevanović, Stefan; Elliott, Tim; Deane, Janet E; Boyle, Louise H

2017-01-01

Recently, we revealed that TAPBPR is a peptide exchange catalyst that is important for optimal peptide selection by MHC class I molecules. Here, we asked whether any other co-factors associate with TAPBPR, which would explain its effect on peptide selection. We identify an interaction between TAPBPR and UDP-glucose:glycoprotein glucosyltransferase 1 (UGT1), a folding sensor in the calnexin/calreticulin quality control cycle that is known to regenerate the Glc1Man9GlcNAc2 moiety on glycoproteins. Our results suggest the formation of a multimeric complex, dependent on a conserved cysteine at position 94 in TAPBPR, in which TAPBPR promotes the association of UGT1 with peptide-receptive MHC class I molecules. We reveal that the interaction between TAPBPR and UGT1 facilities the reglucosylation of the glycan on MHC class I molecules, promoting their recognition by calreticulin. Our results suggest that in addition to being a peptide editor, TAPBPR improves peptide optimisation by promoting peptide-receptive MHC class I molecules to associate with the peptide-loading complex. DOI: http://dx.doi.org/10.7554/eLife.23049.001 PMID:28425917

Soil erosion measurements by means of experimental plots to determine best land management strategies in vineyards and olive orchards

NASA Astrophysics Data System (ADS)

Cerdà, Artemi; Keesstra, Saskia; Jordan, Antonio; Brevik, Erik; Nova, Agata; Prosdocimi, Massimo; Azorín-Molina, César; Yazdanpanah, Najme; Mahmoodabadi, Majid; Pereira, Paulo; Burguet, María

2016-04-01

In order to design sustainable land management there is a need to have accurate information on the impact this land management strategies have on water and sediment dynamics. This is especially important when a proper management is designed to reduce the soil losses due to the complex interaction of mechanisms that interact within the soil erosion process. Soil erosion is an non-linear process, both spatially and temporally, and as a consequence of that only well-monitored and accurate measurements can give insights in the processes and how these processes can be influenced by management to reduce soil losses (Cerdà, 2007; Ligonja and Shrestha, 2015; Nanko et al., 2015; Seutloali and Beckedahl, 2015). This is necessary at different scales: pedon, slope, and watershed because the governing processes differ at different scale (Keesstra, 2007; Jordán and Martínez Zavala, 2008; Borrelli et al., 2015). Soil erosion plots can give information about the temporal and spatial variability of soil losses. We present here a strategy developed by the Soil Erosion and Degradation Research Group from the University of Valencia to assess the soil erosion rates in Eastern Spain. In 2002 the Soil Erosion Experimental Station in El Teularet-Sierra de Enguera was installed, to assess soil losses in rainfed agriculture orchards, and 73 plots of 1, 2, 4, 16 and 48 m2 were installed. In 2005 6 plots of 300 m2 were installed in the nearby Montesa soil erosion station to assess soil losses in citrus orchards. In 2011 16 plots of 2 m2 where installed in Les Alcusses to determine soil losses in olive orchards, and in 2015 8 plots in Celler del Roure vineyard to assess the impact of land management in vineyards and 8 plots in the El Teularet to study the impact of straw mulch on soil erosion rates. All erosion stations are located in several kilometres distance from each other. This research which we developed since 2002 is complementary to previous research where we used rainfall simulation experiments to assess soil properties under different management (Cerdà, 1997; Cerdà, 1998a; Cerdà 1998b; Cerdà, 2001). The results from the soil erosion plots monitoring demonstrate the positive impact of vegetation to reduce soil loss. In addition, we proved that the use of straw, chipped pruned branches and rock fragments as surface cover reduces soil losses (Cerdà et al., 2015, Pereira et al., 2015; Prosdocimi et al., 2016). Acknowledgements The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement n° 603498 (RECARE project) and by the Spanish Government with the research Project CGL2013- 47862-C2-1-R. References Borrelli, P., Märker, M., Schütt, B. 2015. Modelling Post-Tree-Harvesting soil erosion and sediment deposition potential in the turano river basin (Italian central apennine. Land Degradation and Development, 26, 356-366. DOI: 10.1002/ldr.2214 Cerdà, A. 1997.The effect of patchy distribution of Stipa tenacissima L. on runoff and erosion. Journal of Arid Environments, 36 (1), pp. 37-51.DOI: 10.1006/jare.1995.0198 Cerdà, A. 1998a. Changes in overland flow and infiltration after a rangeland fire in a Mediterranean scrubland. Hydrological Processes, 12 (7), pp. 1031-1042. Cerdà, A. 1998b Soil aggregate stability under different Mediterranean vegetation types. Catena, 32 (2), pp. 73-86. DOI: 10.1016/S0341-8162(98)00041-1 Cerdà, A. 2001. Effects of rock fragment cover on soil infiltration, interrill runoff and erosion. European Journal of Soil Science, 52 (1), pp. 59-68. DOI: 10.1046/j.1365-2389.2001.00354.x Cerdà, A. 2007. Soil water erosion on road embankments in eastern Spain. Science of the Total Environment, 378 (1-2), 151-155. DOI: 10.1016/j.scitotenv.2007.01.041 Cerdà, A., González-Pelayo, O., Giménez-Morera, A., Jordán, A., Pereira, P., Novara, A., Brevik, E.C., Prosdocimi, M., Mahmoodabadi, M., Keesstra, S., García Orenes, F., Ritsema, C., 2015. The use of barley straw residues to avoid high erosion and runoff rates on persimmon plantations in Eastern Spain under low frequency - high magnitude simulated rainfall events. Soil Res. (In press) Jordán, A., & Martínez-Zavala, L. 2008. Soil loss and runoff rates on unpaved forest roads in southern Spain after simulated rainfall. Forest Ecology and Management, 255(3), 913-919. Keesstra, S.D. 2007. Impact of natural reforestation on floodplain sedimentation in the Dragonja basin, SW Slovenia. Earth Surface Processes and Landforms, 32(1): 49-65. DOI: 10.1002/esp.1360 Ligonja, P.J., Shrestha, R.P. 2015. Soil erosion assessment in kondoa eroded area in Tanzania using universal soil loss equation, geographic information systems and socioeconomic approach (2015) Land Degradation and Development, 26 (4), pp. 367-379. DOI: 10.1002/ldr.2215 Nanko, K., Giambelluca, T.W., Sutherland, R.A., Mudd, R.G., Nullet, M.A., Ziegler, A.D. 2015.Erosion potential under miconia calvescens stands on the island of hawai'i. Land Degradation and Development, 26 (3), pp. 218-226. DOI: 10.1002/ldr.2200 Pereira, P., Giménez-Morera, A., Novara, A., Keesstra, S., Jordán, A., Masto, R. E., Brevik, E., Azorin-Molina, C. Cerdà, A. 2015. The impact of road and railway embankments on runoff and soil erosion in eastern Spain. Hydrology and Earth System Sciences Discussions, 12, 12947-12985. Prosdocimi,M., Jordán, A., Tarolli, P., Keesstra, S., Novara, A., Cerdà, A. 2016. The immediate effectiveness of barley straw mulch in reducing soil erodibility and surface runoff generation in Mediterranean vineyards. Science of The Total Environment, 547, 15 ,323-330, doi:10.1016/j.scitotenv.2015.12.076 Seutloali, K.E., Beckedahl, H.R. 2015. Understanding the factors influencing rill erosion on roadcuts in the south eastern region of South Africa. Solid Earth, 6 (2) 633-641. DOI: 10.5194/se-6-633-2015

Plant defense phenotypes determine the consequences of volatile emission for individuals and neighbors

PubMed Central

Schuman, Meredith C; Allmann, Silke; Baldwin, Ian T

2015-01-01

Plants are at the trophic base of terrestrial ecosystems, and the diversity of plant species in an ecosystem is a principle determinant of community structure. This may arise from diverse functional traits among species. In fact, genetic diversity within species can have similarly large effects. However, studies of intraspecific genetic diversity have used genotypes varying in several complex traits, obscuring the specific phenotypic variation responsible for community-level effects. Using lines of the wild tobacco Nicotiana attenuata genetically altered in specific well-characterized defense traits and planted into experimental populations in their native habitat, we investigated community-level effects of trait diversity in populations of otherwise isogenic plants. We conclude that the frequency of defense traits in a population can determine the outcomes of these traits for individuals. Furthermore, our results suggest that some ecosystem-level services afforded by genetically diverse plant populations could be recaptured in intensive monocultures engineered to be functionally diverse. DOI: http://dx.doi.org/10.7554/eLife.04490.001 PMID:25873033

Engineering of a synthetic quadrastable gene network to approach Waddington landscape and cell fate determination

PubMed Central

Wu, Fuqing; Su, Ri-Qi; Lai, Ying-Cheng; Wang, Xiao

2017-01-01

The process of cell fate determination has been depicted intuitively as cells travelling and resting on a rugged landscape, which has been probed by various theoretical studies. However, few studies have experimentally demonstrated how underlying gene regulatory networks shape the landscape and hence orchestrate cellular decision-making in the presence of both signal and noise. Here we tested different topologies and verified a synthetic gene circuit with mutual inhibition and auto-activations to be quadrastable, which enables direct study of quadruple cell fate determination on an engineered landscape. We show that cells indeed gravitate towards local minima and signal inductions dictate cell fates through modulating the shape of the multistable landscape. Experiments, guided by model predictions, reveal that sequential inductions generate distinct cell fates by changing landscape in sequence and hence navigating cells to different final states. This work provides a synthetic biology framework to approach cell fate determination and suggests a landscape-based explanation of fixed induction sequences for targeted differentiation. DOI: http://dx.doi.org/10.7554/eLife.23702.001 PMID:28397688

Intrahippocampal LSD accelerates learning and desensitizes the 5-HT(2A) receptor in the rabbit, Romano et al.

PubMed

Romano, Anthony G; Quinn, Jennifer L; Li, Luchuan; Dave, Kuldip D; Schindler, Emmanuelle A; Aloyo, Vincent J; Harvey, John A

2010-10-01

Parenteral injections of d-lysergic acid diethylamide (LSD), a serotonin 5-HT(2A) receptor agonist, enhance eyeblink conditioning. Another hallucinogen, (±)-1(2, 5-dimethoxy-4-iodophenyl)-2-aminopropane hydrochloride (DOI), was shown to elicit a 5-HT(2A)-mediated behavior (head bobs) after injection into the hippocampus, a structure known to mediate trace eyeblink conditioning. This study aims to determine if parenteral injections of the hallucinogens LSD, d,l-2,5-dimethoxy-4-methylamphetamine, and 5-methoxy-dimethyltryptamine elicit the 5-HT(2A)-mediated behavior of head bobs and whether intrahippocampal injections of LSD would produce head bobs and enhance trace eyeblink conditioning. LSD was infused into the dorsal hippocampus just prior to each of eight conditioning sessions. One day after the last infusion of LSD, DOI was infused into the hippocampus to determine whether there had been a desensitization of the 5-HT(2A) receptor as measured by a decrease in DOI-elicited head bobs. Acute parenteral or intrahippocampal LSD elicited a 5-HT(2A) but not a 5-HT(2C)-mediated behavior, and chronic administration enhanced conditioned responding relative to vehicle controls. Rabbits that had been chronically infused with 3 or 10 nmol per side of LSD during Pavlovian conditioning and then infused with DOI demonstrated a smaller increase in head bobs relative to controls. LSD produced its enhancement of Pavlovian conditioning through an effect on 5-HT(2A) receptors located in the dorsal hippocampus. The slight, short-lived enhancement of learning produced by LSD appears to be due to the development of desensitization of the 5-HT(2A) receptor within the hippocampus as a result of repeated administration of its agonist (LSD).

Basic performance of Mg co-doped new scintillator used for TOF-DOI-PET systems

NASA Astrophysics Data System (ADS)

Kobayashi, Takahiro; Yamamoto, Seiichi; Okumura, Satoshi; Yeom, Jung Yeol; Kamada, Kei; Yoshikawa, Akira

2017-01-01

Phoswich depth-of-interaction (DOI) detectors utilizing multiple scintillators with different decay time are a useful device for developing a high spatial resolution, high sensitivity PET scanner. However, in order to apply pulse shape discrimination (PSD), there are not many combinations of scintillators for which phoswich technique can be implemented. Ce doped Gd3Ga3Al2O12 (GFAG) is a recently developed scintillator with a fast decay time. This scintillator is similar to Ce doped Gd3Al2Ga3O12 (GAGG), which is a promising scintillator for PET detector with high light yield. By stacking these scintillators, it may be possible to realize a high spatial resolution and high timing resolution phoswich DOI detector. Such phoswich DOI detector may be applied to time-of-flight (TOF) systems with high timing performance. Therefore, in this study, we tested the basic performance of the new scintillator -GFAG for use in a TOF phoswich detector. The measured decay time of a GFAG element of 2.9 mmx2.9 mmx10 mm in dimension, which was optically coupled to a photomultiplier tube (PMT), was faster (66 ns) than that of same sized GAGG (103 ns). The energy resolution of the GFAG element was 5.7% FWHM which was slightly worse than that of GAGG with 4.9% FWHM for 662 keV gamma photons without saturation correction. Then we assembled the GFAG and the GAGG crystals in the depth direction to form a 20 mm long phoswich element (GFAG/GAGG). By pulse shape analysis, the two types of scintillators were clearly resolved. Measured timing resolution of a pair of opposing GFAG/GAGG phoswich scintillator coupled to Silicon Photomultipliers (Si-PM) was good with coincidence resolving time of 466 ps FWHM. These results indicate that the GFAG combined with GAGG can be a candidate for TOF-DOI-PET systems.

Time-over-threshold for pulse shape discrimination in a time-of-flight phoswich PET detector

PubMed Central

Chang, Chen-Ming; Cates, Joshua W.; Levin, Craig S.

2016-01-01

It is well known that a PET detector capable of measuring both photon time-of-flight (TOF) and depth-of-interaction (DOI) improves the image quality and accuracy. Phoswich designs have been realized in PET detectors to measure DOI for more than a decade. However, PET detectors based on phoswich designs put great demand on the readout circuits, which have to differentiate the pulse shape produced by different crystal layers. A simple pulse shape discrimination approach is required to realize the phoswich designs in a clinical PET scanner, which consists of thousands of scintillation crystal elements. In this work, we studied time-over-threshold (ToT) as a pulse shape parameter for DOI. The energy, timing and DOI performance were evaluated for a phoswich detector design comprising 3 mm × 3 mm × 10 mm LYSO:Ce crystal optically coupled to 3 mm × 3 mm × 10 mm calcium co-doped LSO:Ce,Ca(0.4%) crystal read out by a silicon photomultiplier (SiPM). A DOI accuracy of 97.2% has been achieved for photopeak events using the proposed time-over-threshold (ToT) processing. The energy resolution without correction for SiPM non-linearity was 9.7 ± 0.2% and 11.3 ± 0.2% FWHM at 511 keV for LYSO and LSO crystal layers, respectively. The coincidence time resolution for photopeak events ranges from 164.6 ps to 183.1 ps FWHM, depending on the layer combinations. The coincidence time resolution for inter-crystal scatter events ranges from 214.6 ps to 418.3 ps FWHM, depending on the energy windows applied. These results show great promises of using ToT for pulse shape discrimination in a TOF phoswich detector since a ToT measurement can be easily implemented in readout electronics. PMID:27991437

Evolution of Evaluation and Assessment in Diverse Audiences in the Digital Age

NASA Astrophysics Data System (ADS)

Eriksson, S. C.

2015-12-01

Over the past decades, researchers have learned more about how people think and act and about the social and political aspects of teaching and learning. This understanding has brought changes in researchers' and practitioners' interactions with diverse groups and individuals. This paper addresses evaluation, a process that measures the degree to which learning and project goals are met and factors contributing to or hindering outcomes. Parallels are drawn to learning assessment. The concepts of inclusion, participation, and constructivism (Mertens, 1999; Mertens and Hopson, 2006) now drive best evaluation practices for projects with persons with disabilities (AEA, 2011). This is also true in cases of other people who have been marginalized in STEM fields, e.g. women and underrepresented groups. Inclusion of these stakeholders has important implications for the validity of an evaluation, including the accuracy of results (Jacobson et al, 2012; Gill, 1999; Lee, 1999). The American Indian Higher Education Consortium's framework for indigenous groups incorporates their values and goals into evaluation design and implementation. It is feasible to include participant input in designing the questions and methods of obtaining data, ensuring that issues of access, opportunity, and power (Shuffelbeam, 2001) are taken into consideration. Geoscience projects with u-learning and m-learning provide opportunities to test these theoretical models in innovative programs such as: field work for students with physical disability; underrepresented minority, secondary students using mobile devices in contextualized learning in informal settings; and graduate students using digital maps to enhance traditional field work. This study compares program evaluation methodology of tradition learning with that of programs for diverse groups of students using digital technology. Ref: Mertens doi:10.1177/109821409902000102; Mertens and Hopson DOI: 10.1002/ev.177; AEA http://www.eval.org/p/cm/ld/fid=92; Jacobson et al DOI 10.1177/1098214012461558; Gill DOI:10.1016/S1098-2140(99)00018-1; Lee DOI: 10.1177/109821409902000210; Shuffelbeam ISBN: 978-0-7879-5755-1

A single-molecule force spectroscopy study of the interactions between lectins and carbohydrates on cancer and normal cells

NASA Astrophysics Data System (ADS)

Zhao, Weidong; Cai, Mingjun; Xu, Haijiao; Jiang, Junguang; Wang, Hongda

2013-03-01

The interaction forces between carbohydrates and lectins were investigated by single-molecule force spectroscopy on both cancer and normal cells. The binding kinetics was also studied, which shows that the carbohydrate-lectin complex on cancer cells is less stable than that on normal cells.The interaction forces between carbohydrates and lectins were investigated by single-molecule force spectroscopy on both cancer and normal cells. The binding kinetics was also studied, which shows that the carbohydrate-lectin complex on cancer cells is less stable than that on normal cells. Electronic supplementary information (ESI) available: Experimental details. See DOI: 10.1039/c3nr00553d

Brain activation and connectivity of social cognition using diffuse optical imaging

NASA Astrophysics Data System (ADS)

Zhu, Banghe; Godavarty, Anuradha

2009-02-01

In the current research, diffuse optical imaging (DOI) is used for the first time towards studies related to sociocommunication impairments, which is a characteristic feature of autism. DOI studies were performed on normal adult volunteers to determine the differences in the brain activation (cognitive regions) in terms of the changes in the cerebral blood oxygenation levels in response to joint and non-joint attention based stimulus (i.e. socio-communicative paradigms shown as video clips). Functional connectivity models are employed to assess the extent of synchronization between the left and right pre-frontal regions of the brain in response to the above stimuli.

panMetaDocs, eSciDoc, and DOIDB - an infrastructure for the curation and publication of file-based datasets for 'GFZ Data Services'

NASA Astrophysics Data System (ADS)

Ulbricht, Damian; Elger, Kirsten; Bertelmann, Roland; Klump, Jens

2016-04-01

With the foundation of DataCite in 2009 and the technical infrastructure installed in the last six years it has become very easy to create citable dataset DOIs. Nowadays, dataset DOIs are increasingly accepted and required by journals in reference lists of manuscripts. In addition, DataCite provides usage statistics [1] of assigned DOIs and offers a public search API to make research data count. By linking related information to the data, they become more useful for future generations of scientists. For this purpose, several identifier systems, as ISBN for books, ISSN for journals, DOI for articles or related data, Orcid for authors, and IGSN for physical samples can be attached to DOIs using the DataCite metadata schema [2]. While these are good preconditions to publish data, free and open solutions that help with the curation of data, the publication of research data, and the assignment of DOIs in one software seem to be rare. At GFZ Potsdam we built a modular software stack that is made of several free and open software solutions and we established 'GFZ Data Services'. 'GFZ Data Services' provides storage, a metadata editor for publication and a facility to moderate minted DOIs. All software solutions are connected through web APIs, which makes it possible to reuse and integrate established software. Core component of 'GFZ Data Services' is an eSciDoc [3] middleware that is used as central storage, and has been designed along the OAIS reference model for digital preservation. Thus, data are stored in self-contained packages that are made of binary file-based data and XML-based metadata. The eSciDoc infrastructure provides access control to data and it is able to handle half-open datasets, which is useful in embargo situations when a subset of the research data are released after an adequate period. The data exchange platform panMetaDocs [4] makes use of eSciDoc's REST API to upload file-based data into eSciDoc and uses a metadata editor [5] to annotate the files with metadata. The metadata editor has a user-friendly interface with nominal lists, extensive explanations, and an interactive mapping tool to provide assistance to scientists describing the data. It is possible to deposit metadata templates to fill certain fields with default values. The metadata editor generates metadata in the schemas ISO19139, NASA GCMD DIF, and DataCite and could be extended for other schemas. panMetaDocs is able to mint dataset DOIs through DOIDB, which is our component to moderate dataset DOIs issued through 'GFZ Data Services'. DOIDB accepts metadata in the schemas ISO19139, DIF, and DataCite. In addition, DOIDB provides an OAI-PMH interface to disseminate all deposited metadata to data portals. The presentation of datasets on DOI landing pages is done though XSLT stylesheet transformation of the XML-based metadata. The landing pages have been designed to meet needs of scientists. We are able to render the metadata to different layouts. Furthermore, additional information about datasets and publications is assembled into the webpage by querying public databases on the internet. The work presented here will focus on technical details of the software stack. [1] http://stats.datacite.org [2] http://www.dlib.org/dlib/january11/starr/01starr.html [3] http://www.escidoc.org [4] http://panmetadocs.sf.net [5] http://github.com/ulbricht

The contrasting phylodynamics of human influenza B viruses

PubMed Central

Vijaykrishna, Dhanasekaran; Holmes, Edward C; Joseph, Udayan; Fourment, Mathieu; Su, Yvonne CF; Halpin, Rebecca; Lee, Raphael TC; Deng, Yi-Mo; Gunalan, Vithiagaran; Lin, Xudong; Stockwell, Timothy B; Fedorova, Nadia B; Zhou, Bin; Spirason, Natalie; Kühnert, Denise; Bošková, Veronika; Stadler, Tanja; Costa, Anna-Maria; Dwyer, Dominic E; Huang, Q Sue; Jennings, Lance C; Rawlinson, William; Sullivan, Sheena G; Hurt, Aeron C; Maurer-Stroh, Sebastian; Wentworth, David E; Smith, Gavin JD; Barr, Ian G

2015-01-01

A complex interplay of viral, host, and ecological factors shapes the spatio-temporal incidence and evolution of human influenza viruses. Although considerable attention has been paid to influenza A viruses, a lack of equivalent data means that an integrated evolutionary and epidemiological framework has until now not been available for influenza B viruses, despite their significant disease burden. Through the analysis of over 900 full genomes from an epidemiological collection of more than 26,000 strains from Australia and New Zealand, we reveal fundamental differences in the phylodynamics of the two co-circulating lineages of influenza B virus (Victoria and Yamagata), showing that their individual dynamics are determined by a complex relationship between virus transmission, age of infection, and receptor binding preference. In sum, this work identifies new factors that are important determinants of influenza B evolution and epidemiology. DOI: http://dx.doi.org/10.7554/eLife.05055.001 PMID:25594904

Intramolecular interactions in the polar headgroup of sphingosine: serinol† †Electronic supplementary information (ESI) available: Ab initio parameters for serinol conformers within 1000 cm–1, measured transition frequencies, typical a-type transition for conformer aa1, interconversion barriers and possible tunnelling pathways. See DOI: 10.1039/c5cc09423b Click here for additional data file.

PubMed Central

Loru, Donatella; Peña, Isabel; Alonso, José L.

2016-01-01

The intramolecular interactions in the lipid sphingosine have been elucidated through the investigation of the amino alcohol serinol which mimics its polar headgroup. Intricate networks of intramolecular hydrogen bonds involving the hydroxyl groups and the amino group contribute to the stabilisation of five different conformations observed in the broadband rotational spectrum. PMID:26727395

Spatial correlated games

PubMed Central

2017-01-01

This article studies correlated two-person games constructed from games with independent players as proposed in Iqbal et al. (2016 R. Soc. open sci. 3, 150477. (doi:10.1098/rsos.150477)). The games are played in a collective manner, both in a two-dimensional lattice where the players interact with their neighbours, and with players interacting at random. Four game types are scrutinized in iterated games where the players are allowed to change their strategies, adopting that of their best paid mate neighbour. Particular attention is paid in the study to the effect of a variable degree of correlation on Nash equilibrium strategy pairs. PMID:29291120

Towards monolithic scintillator based TOF-PET systems: practical methods for detector calibration and operation.

PubMed

Borghi, Giacomo; Tabacchini, Valerio; Schaart, Dennis R

2016-07-07

Gamma-ray detectors based on thick monolithic scintillator crystals can achieve spatial resolutions  <2 mm full-width-at-half-maximum (FWHM) and coincidence resolving times (CRTs) better than 200 ps FWHM. Moreover, they provide high sensitivity and depth-of-interaction (DOI) information. While these are excellent characteristics for clinical time-of-flight (TOF) positron emission tomography (PET), the application of monolithic scintillators has so far been hampered by the lengthy and complex procedures needed for position- and time-of-interaction estimation. Here, the algorithms previously developed in our group are revised to make the calibration and operation of a large number of monolithic scintillator detectors in a TOF-PET system practical. In particular, the k-nearest neighbor (k-NN) classification method for x,y-position estimation is accelerated with an algorithm that quickly preselects only the most useful reference events, reducing the computation time for position estimation by a factor of ~200 compared to the previously published k-NN 1D method. Also, the procedures for estimating the DOI and time of interaction are revised to enable full detector calibration by means of fan-beam or flood irradiations only. Moreover, a new technique is presented to allow the use of events in which some of the photosensor pixel values and/or timestamps are missing (e.g. due to dead time), so as to further increase system sensitivity. The accelerated methods were tested on a monolithic scintillator detector specifically developed for clinical PET applications, consisting of a 32 mm  ×  32 mm  ×  22 mm LYSO : Ce crystal coupled to a digital photon counter (DPC) array. This resulted in a spatial resolution of 1.7 mm FWHM, an average DOI resolution of 3.7 mm FWHM, and a CRT of 214 ps. Moreover, the possibility of using events missing the information of up to 16 out of 64 photosensor pixels is shown. This results in only a small deterioration of the detector performance.

MO-F-CAMPUS-J-03: Development of a Human Brain PET for On-Line Proton Beam-Range Verification

DOE Office of Scientific and Technical Information (OSTI.GOV)

Shao, Yiping

Purpose: To develop a prototype PET for verifying proton beam-range before each fractionated therapy that will enable on-line re-planning proton therapy. Methods: Latest “edge-less” silicon photomultiplier arrays and customized ASIC readout electronics were used to develop PET detectors with depth-of-interaction (DOI) measurement capability. Each detector consists of one LYSO array with each end coupled to a SiPM array. Multiple detectors can be seamlessly tiled together to form a large detector panel. Detectors with 1.5×1.5 and 2.0×2.0 mm crystals at 20 or 30 mm lengths were studied. Readout of individual SiPM or signal multiplexing was used to transfer 3D interaction position-codedmore » analog signals through flexible-print-circuit cables or PCB board to dedicated ASIC front-end electronics to output digital timing pulses that encode interaction information. These digital pulses can be transferred to, through standard LVDS cables, and decoded by a FPGA-based data acquisition of coincidence events and data transfer. The modular detector and scalable electronics/data acquisition will enable flexible PET system configuration for different imaging geometry. Results: Initial detector performance measurement shows excellent crystal identification even with 30 mm long crystals, ∼18% and 2.8 ns energy and timing resolutions, and around 2–3 mm DOI resolution. A small prototype PET scanner with one detector ring has been built and evaluated, validating the technology and design. A large size detector panel has been fabricated by scaling up from modular detectors. Different designs of resistor and capacitor based signal multiplexing boards were tested and selected based on optimal crystal identification and timing performance. Stackable readout electronics boards and FPGA-based data acquisition boards were developed and tested. A brain PET is under construction. Conclusion: Technology of large-size DOI detector based on SiPM array and advanced readout has been developed. PET imaging performance and initial phantom studies of on-line proton beam-range measurement will be conducted and reported. NIH grant R21CA187717; Cancer Prevention and Research Institute of Texas grant RP120326.« less

Next generation PET data acquisition architectures

NASA Astrophysics Data System (ADS)

Jones, W. F.; Reed, J. H.; Everman, J. L.; Young, J. W.; Seese, R. D.

1997-06-01

New architectures for higher performance data acquisition in PET are proposed. Improvements are demanded primarily by three areas of advancing PET state of the art. First, larger detector arrays such as the Hammersmith ECAT/sup (R/) EXACT HR/sup ++/ exceed the addressing capacity of 32 bit coincidence event words. Second, better scintillators (LSO) make depth-of interaction (DOI) and time-of-flight (TOF) operation more practical. Third, fully optimized single photon attenuation correction requires higher rates of data collection. New technologies which enable the proposed third generation Real Time Sorter (RTS III) include: (1) 80 Mbyte/sec Fibre Channel RAID disk systems, (2) PowerPC on both VMEbus and PCI Local bus, and (3) quadruple interleaved DRAM controller designs. Data acquisition flexibility is enhanced through a wider 64 bit coincidence event word. PET methodology support includes DOI (6 bits), TOF (6 bits), multiple energy windows (6 bits), 512/spl times/512 sinogram indexes (18 bits), and 256 crystal rings (16 bits). Throughput of 10 M events/sec is expected for list-mode data collection as well as both on-line and replay histogramming. Fully efficient list-mode storage for each PET application is provided by real-time bit packing of only the active event word bits. Real-time circuits provide DOI rebinning.

X-ray Generation in Strongly Nonlinear Plasma Waves

NASA Astrophysics Data System (ADS)

Kiselev, S.; Pukhov, A.; Kostyukov, I.

2004-09-01

We show that a laser wake field in the “bubble” regime [

Epsin deficiency impairs endocytosis by stalling the actin-dependent invagination of endocytic clathrin-coated pits

PubMed Central

Messa, Mirko; Fernández-Busnadiego, Rubén; Sun, Elizabeth Wen; Chen, Hong; Czapla, Heather; Wrasman, Kristie; Wu, Yumei; Ko, Genevieve; Ross, Theodora; Wendland, Beverly; De Camilli, Pietro

2014-01-01

Epsin is an evolutionarily conserved endocytic clathrin adaptor whose most critical function(s) in clathrin coat dynamics remain(s) elusive. To elucidate such function(s), we generated embryonic fibroblasts from conditional epsin triple KO mice. Triple KO cells displayed a dramatic cell division defect. Additionally, a robust impairment in clathrin-mediated endocytosis was observed, with an accumulation of early and U-shaped pits. This defect correlated with a perturbation of the coupling between the clathrin coat and the actin cytoskeleton, which we confirmed in a cell-free assay of endocytosis. Our results indicate that a key evolutionary conserved function of epsin, in addition to other roles that include, as we show here, a low affinity interaction with SNAREs, is to help generate the force that leads to invagination and then fission of clathrin-coated pits. DOI: http://dx.doi.org/10.7554/eLife.03311.001 PMID:25122462

Preliminary evaluation of a monolithic detector module for integrated PET/MRI scanner with high spatial resolution

NASA Astrophysics Data System (ADS)

Pani, R.; Gonzalez, A. J.; Bettiol, M.; Fabbri, A.; Cinti, M. N.; Preziosi, E.; Borrazzo, C.; Conde, P.; Pellegrini, R.; Di Castro, E.; Majewski, S.

2015-06-01

The proposal of Mindview European Project concerns with the development of a very high resolution and high efficiency brain dedicated PET scanner simultaneously working with a Magnetic Resonance scanner, that expects to visualize neurotransmitter pathways and their disruptions in the quest to better diagnose schizophrenia. On behalf of this project, we propose a low cost PET module for the first prototype, based on monolithic crystals, suitable to be integrated with a head Radio Frequency (RF) coil. The aim of the suggested module is to achieve high performances in terms of efficiency, planar spatial resolution (expected about 1 mm) and discrimination of gamma Depth Of Interaction (DOI) in order to reduce the parallax error. Our preliminary results are very promising: a DOI resolution of about 3 mm, a spatial resolution ranging from about 1 to 1.5 mm and a good position linearity.

Vocal development in a Waddington landscape

PubMed Central

Teramoto, Yayoi; Takahashi, Daniel Y; Holmes, Philip; Ghazanfar, Asif A

2017-01-01

Vocal development is the adaptive coordination of the vocal apparatus, muscles, the nervous system, and social interaction. Here, we use a quantitative framework based on optimal control theory and Waddington’s landscape metaphor to provide an integrated view of this process. With a biomechanical model of the marmoset monkey vocal apparatus and behavioral developmental data, we show that only the combination of the developing vocal tract, vocal apparatus muscles and nervous system can fully account for the patterns of vocal development. Together, these elements influence the shape of the monkeys’ vocal developmental landscape, tilting, rotating or shifting it in different ways. We can thus use this framework to make quantitative predictions regarding how interfering factors or experimental perturbations can change the landscape within a species, or to explain comparative differences in vocal development across species DOI: http://dx.doi.org/10.7554/eLife.20782.001 PMID:28092262

Stacking the odds for Golgi cisternal maturation

PubMed Central

Mani, Somya; Thattai, Mukund

2016-01-01

What is the minimal set of cell-biological ingredients needed to generate a Golgi apparatus? The compositions of eukaryotic organelles arise through a process of molecular exchange via vesicle traffic. Here we statistically sample tens of thousands of homeostatic vesicle traffic networks generated by realistic molecular rules governing vesicle budding and fusion. Remarkably, the plurality of these networks contain chains of compartments that undergo creation, compositional maturation, and dissipation, coupled by molecular recycling along retrograde vesicles. This motif precisely matches the cisternal maturation model of the Golgi, which was developed to explain many observed aspects of the eukaryotic secretory pathway. In our analysis cisternal maturation is a robust consequence of vesicle traffic homeostasis, independent of the underlying details of molecular interactions or spatial stacking. This architecture may have been exapted rather than selected for its role in the secretion of large cargo. DOI: http://dx.doi.org/10.7554/eLife.16231.001 PMID:27542195

Perception as a closed-loop convergence process

PubMed Central

Ahissar, Ehud; Assa, Eldad

2016-01-01

Perception of external objects involves sensory acquisition via the relevant sensory organs. A widely-accepted assumption is that the sensory organ is the first station in a serial chain of processing circuits leading to an internal circuit in which a percept emerges. This open-loop scheme, in which the interaction between the sensory organ and the environment is not affected by its concurrent downstream neuronal processing, is strongly challenged by behavioral and anatomical data. We present here a hypothesis in which the perception of external objects is a closed-loop dynamical process encompassing loops that integrate the organism and its environment and converging towards organism-environment steady-states. We discuss the consistency of closed-loop perception (CLP) with empirical data and show that it can be synthesized in a robotic setup. Testable predictions are proposed for empirical distinction between open and closed loop schemes of perception. DOI: http://dx.doi.org/10.7554/eLife.12830.001 PMID:27159238

Tapered whiskers are required for active tactile sensation.

PubMed

Hires, Samuel Andrew; Pammer, Lorenz; Svoboda, Karel; Golomb, David

2013-11-19

Many mammals forage and burrow in dark constrained spaces. Touch through facial whiskers is important during these activities, but the close quarters makes whisker deployment challenging. The diverse shapes of facial whiskers reflect distinct ecological niches. Rodent whiskers are conical, often with a remarkably linear taper. Here we use theoretical and experimental methods to analyze interactions of mouse whiskers with objects. When pushed into objects, conical whiskers suddenly slip at a critical angle. In contrast, cylindrical whiskers do not slip for biologically plausible movements. Conical whiskers sweep across objects and textures in characteristic sequences of brief sticks and slips, which provide information about the tactile world. In contrast, cylindrical whiskers stick and remain stuck, even when sweeping across fine textures. Thus the conical whisker structure is adaptive for sensor mobility in constrained environments and in feature extraction during active haptic exploration of objects and surfaces. DOI: http://dx.doi.org/10.7554/eLife.01350.001.

Mapping the function of neuronal ion channels in model and experiment

PubMed Central

Podlaski, William F; Seeholzer, Alexander; Groschner, Lukas N; Miesenböck, Gero; Ranjan, Rajnish; Vogels, Tim P

2017-01-01

Ion channel models are the building blocks of computational neuron models. Their biological fidelity is therefore crucial for the interpretation of simulations. However, the number of published models, and the lack of standardization, make the comparison of ion channel models with one another and with experimental data difficult. Here, we present a framework for the automated large-scale classification of ion channel models. Using annotated metadata and responses to a set of voltage-clamp protocols, we assigned 2378 models of voltage- and calcium-gated ion channels coded in NEURON to 211 clusters. The IonChannelGenealogy (ICGenealogy) web interface provides an interactive resource for the categorization of new and existing models and experimental recordings. It enables quantitative comparisons of simulated and/or measured ion channel kinetics, and facilitates field-wide standardization of experimentally-constrained modeling. DOI: http://dx.doi.org/10.7554/eLife.22152.001 PMID:28267430

Finite Element Modeling of Non-linear Coupled Interacting Fault System

NASA Astrophysics Data System (ADS)

Xing, H. L.; Zhang, J.; Wyborn, D.

2009-04-01

PANDAS - Parallel Adaptive static/dynamic Nonlinear Deformation Analysis System - a novel supercomputer simulation tool is developed for simulating the highly non-linear coupled geomechanical-fluid flow-thermal systems involving heterogeneously fractured geomaterials. PANDAS includes the following key components: Pandas/Pre, ESyS_Crustal, Pandas/Thermo, Pandas/Fluid and Pandas/Post as detailed in the following: • Pandas/Pre is developed to visualise the microseismicity events recorded during the hydraulic stimulation process to further evaluate the fracture location and evolution and geological setting of a certain reservoir, and then generate the mesh by it and/or other commercial graphics software (such as Patran) for the further finite element analysis of various cases; The Delaunay algorithm is applied as a suitable method for mesh generation using such a point set; • ESyS_Crustal is a finite element code developed for the interacting fault system simulation, which employs the adaptive static/dynamic algorithm to simulate the dynamics and evolution of interacting fault systems and processes that are relevant on short to mediate time scales in which several dynamic phenomena related with stick-slip instability along the faults need to be taken into account, i.e. (a). slow quasi-static stress accumulation, (b) rapid dynamic rupture, (c) wave propagation and (d) corresponding stress redistribution due to the energy release along the multiple fault boundaries; those are needed to better describe ruputure/microseimicity/earthquake related phenomena with applications in earthquake forecasting, hazard quantification, exploration, and environmental problems. It has been verified with various available experimental results[1-3]; • Pandas/Thermo is a finite element method based module for the thermal analysis of the fractured porous media; the temperature distribution is calculated from the heat transfer induced by the thermal boundary conditions without/with the coupled fluid effects and the geomechanical energy conversion for the pure/coupled thermal analysis. • Pandas/Fluid is a finite element method based module for simulating the fluid flow in the fractured porous media; the fluid flow velocity and pressure are calculated from energy equilibrium equations without/together with the coupling effects of the thermal and solid rock deformation for an independent/coupled fluid flow analysis; • Pandas/Post is to visualise the simulation results through the integration of VTK and/or Patran. All the above modules can be used independently/together to simulate individual/coupled phenomena (such as interacting fault system dynamics, heat flow and fluid flow) without/with coupling effects. PANDAS has been applied to the following issues: • visualisation of the microseismic events to monitor and determine where/how the underground rupture proceeds during a hydraulic stimulation, to generate the mesh using the recorded data for determining the domain of the ruptured zone and to evaluate the material parameters (i.e. the permeability) for the further numerical analysis; • interacting fault system simulation to determine the relevant complicated dynamic rupture process. • geomechanical-fluid flow coupling analysis to investigate the interactions between fluid flow and deformation in the fractured porous media under different loading conditions. • thermo-fluid flow coupling analysis of a fractured geothermal reservoir system. PANDAS will be further developed for a multiscale simulation of multiphase dynamic behaviour for a certain fractured geothermal reservoir. More details and additional application examples will be given during the presentation. References [1] Xing, H. L., Makinouchi, A. and Mora, P. (2007). Finite element modeling of interacting fault system, Physics of the Earth and Planetary Interiors, 163, 106-121.doi:10.1016/j.pepi.2007.05.006 [2] Xing, H. L., Mora, P., Makinouchi, A. (2006). An unified friction description and its application to simulation of frictional instability using finite element method. Philosophy Magazine, 86, 3453-3475 [3] Xing, H. L., Mora, P.(2006). Construction of an intraplate fault system model of South Australia, and simulation tool for the iSERVO institute seed project.. Pure and Applied Geophysics. 163, 2297-2316. DOI 10.1007/s00024-006-0127-x

Structural Basis for DNA Recognition by the Two-Component Response Regulator RcsB.

PubMed

Filippova, Ekaterina V; Zemaitaitis, Bozena; Aung, Theint; Wolfe, Alan J; Anderson, Wayne F

2018-02-27

RcsB is a highly conserved transcription regulator of the Rcs phosphorelay system, a complex two-component signal transduction system (N. Majdalani and S. Gottesman, Annu Rev Microbiol 59:379-405, 2005; A. J. Wolfe, Curr Opin Microbiol 13:204-209, 2010, https://doi.org/10.1016/j.mib.2010.01.002; D. J. Clarke, Future Microbiol 5:1173-1184, 2010, https://doi.org/10.2217/fmb.10.83). RcsB plays an important role in virulence and pathogenicity in human hosts by regulating biofilm formation. RcsB can regulate transcription alone or together with its auxiliary transcription regulators by forming heterodimers. This complexity allows RcsB to regulate transcription of more than 600 bacterial genes in response to different stresses (D. Wang et al., Mol Plant Microbe Interact 25:6-17, 2012, https://doi.org/10.1094/MPMI-08-11-0207). Despite increasing knowledge of RcsB importance, molecular mechanisms that drive the ability of RcsB to control transcription of a large number of genes remain unclear. Here, we present crystal structures of unphosphorylated RcsB in complex with the consensus DNA-binding sequence of 22-mer (DNA22) and 18-mer (DNA18) of the flhDC operon from Escherichia coli determined at 3.15- and 3.37-Å resolution, respectively. The results of our structural analysis combined with the results of in vitro binding assays provide valuable insights to the protein regulatory mechanism, demonstrate how RcsB recognizes target DNA sequences, and reveal a unique oligomeric state that allows RcsB to form homo- and heterodimers. This information will help us understand the complex mechanisms of transcriptional regulation by RcsB in bacteria. IMPORTANCE RcsB is a well-studied two-component response regulator of the Rcs phosphorelay system, conserved within the family Enterobacteriaceae , which includes many pathogens. It is a global regulator, controlling more than 5% of bacterial genes associated with capsule biosynthesis, flagellar biogenesis, cell wall biosynthesis, antibiotic resistance, biofilm formation, and virulence in pathogens. Knowledge of RcsB structure represents a unique opportunity to explore mechanisms that regulate the Rcs phosphorelay system and its role in the family Enterobacteriaceae . Copyright © 2018 Filippova et al.

Modeling of Wave Spectrum and Wave Breaking Statistics Based on Balance Equation

NASA Astrophysics Data System (ADS)

Irisov, V.

2012-12-01

Surface roughness and foam coverage are the parameters determining microwave emissivity of sea surface in a wide range of wind. Existing empirical wave spectra are not associated with wave breaking statistics although physically they are closely related. We propose a model of sea surface based on the balance of three terms: wind input, dissipation, and nonlinear wave-wave interaction. It provides an insight on wave generation, interaction, and dissipation - very important parameters for understanding of wave development under changing oceanic and atmospheric conditions. The wind input term is the best known among all three. For our analysis we assume a wind input term as it was proposed by Plant [1982] and consider modification necessary to do to account for proper interaction of long fast waves with wind. For long gravity waves (longer than 15-30 cm) the dissipation term can be related to the wave breaking with whitecaps, as it was shown by Kudryavtsev et al. [2003], so we assume the cubic dependence of dissipation term on wind. It implies certain limitations on the spectrum shape. The most difficult is to estimate the term describing nonlinear wave-wave interaction. Hasselmann [1962] and Zakharov [1999] developed theory of 4-wave interaction, but the resulting equation requires at least 3-fold integration over wavenumbers at each time step of integration of balance equation, which makes it difficult for direct numerical modeling. It is desirable to use an approximation of wave-wave interaction term, which preserves wave action, energy, and momentum, and can be easily estimated during time integration of balance equation. Zakharov and Pushkarev [1999] proposed the diffusion approximation of the wave interaction term and showed that it can be used for estimate of wave spectrum. We believe their assumption that wave-wave interaction is the dominant factor in forming the wave spectrum does not agree with the observations made by Hwang and Sletten [2008]. Finally we consider modifications of the model equation, which can be done to describe gravity-capillary and capillary waves. An obvious correction is to add viscous dissipation. A little less obvious is a transition from 4-wave to 3-wave interaction. The model allows one to include easily generation of parasitic capillary waves as it was proposed by Kudryavtsev et al. [2003]. A modification of dissipation term can explain an "overshoot" phenomenon observed in JONSWAP spectrum. These examples demonstrate that the proposed model is quite flexible and can be used to account for various physical phenomena. The resulting balance equation is easy to integrate using a personal computer and necessity of its numerical solution is paid by the model flexibility and better physical background compared with empirical spectra. References Hasselmann, K., J. Fluid Mech., 12, pp.481-500, 1962. Hwang, P., and M. Sletten, J. Geophys. Res., 113, doi:10.1029/2007JC004277, 2008. Kudryavtsev, V., et al., J. Geophys. Res., 108 (C3), doi:10.1029/2001JC001003, 2003. Plant, W. J., J. Geophys. Res., vol. 87, pp. 1961-1967, 1982. Zakharov, V., and A. Pushkarev, Nonlinear Processes in Geophysics, 6, pp.1-10, 1999. Zakharov, V., Eur. J. Mech. B/Fluids, 18, pp.327-344, 1999.

Can we define an asymptotic value for the ice active surface site density for heterogeneous ice nucleation?

NASA Astrophysics Data System (ADS)

Niedermeier, Dennis; Augustin-Bauditz, Stefanie; Hartmann, Susan; Wex, Heike; Ignatius, Karoliina; Stratmann, Frank

2015-04-01

The formation of ice in atmospheric clouds has a substantial influence on the radiative properties of clouds as well as on the formation of precipitation. Therefore much effort has been made to understand and quantify the major ice formation processes in clouds. Immersion freezing has been suggested to be a dominant primary ice formation process in low and mid-level clouds (mixed-phase cloud conditions). It also has been shown that mineral dust particles are the most abundant ice nucleating particles in the atmosphere and thus may play an important role for atmospheric ice nucleation (Murray et al., 2012). Additionally, biological particles like bacteria and pollen are suggested to be potentially involved in atmospheric ice formation, at least on a regional scale (Murray et al., 2012). In recent studies for biological particles (SNOMAX and birch pollen), it has been demonstrated that freezing is induced by ice nucleating macromolecules and that an asymptotic value for the mass density of these ice nucleating macromolecules can be determined (Hartmann et al., 2013; Augustin et al., 2013, Wex et al., 2014). The question arises whether such an asymptotic value can also be determined for the ice active surface site density ns, a parameter which is commonly used to describe the ice nucleation activity of e.g., mineral dust. Such an asymptotic value for ns could be an important input parameter for atmospheric modeling applications. In the presented study, we therefore investigated the immersion freezing behavior of droplets containing size-segregated, monodisperse feldspar particles utilizing the Leipzig Aerosol Cloud Interaction Simulator (LACIS). For all particle sizes considered in the experiments, we observed a leveling off of the frozen droplet fraction reaching a plateau within the heterogeneous freezing temperature regime (T > -38°C) which was proportional to the particle surface area. Based on these findings, we could determine an asymptotic value for the ice active surface site density, which we named ns*, for the investigated feldspar sample. The comparison of these results with those of other studies elucidates the general feasibility of determining such an asymptotic value and also show that the value of ns* strongly depends on the method of the particle surface area determination. Acknowledgement This work is partly funded by the Federal Ministry of Education and Research (BMBF - project CLOUD 12) and by the German Research Foundation (DFG project WE 4722/1-1, part of the research unit INUIT, FOR 1525). D. Niedermeier acknowledges financial support from the Alexander von Humboldt-foundation. References Augustin et al.: Immersion freezing of birch pollen washing water, Atmos. Chem. Phys., 13, 10989-11003, doi:10.5194/acp-13-10989-2013, 2013. Hartmann et al.: Immersion freezing of ice nucleation active protein complexes, Atmos. Chem. Phys., 13, 5751-5766, doi:10.5194/acp-13-5751-2013, 2013. Murray et al.: Ice nucleation by particles immersed in supercooled cloud droplets, Chem. Soc. Rev., 41, 6519-6554, 2012. Wex et al.: Intercomparing different devices for the investigation of ice nucleating particles using Snomax® as test substance, Atmos. Chem. Phys. Discuss., 14, 22321-22384, doi:10.5194/acpd-14-22321-2014, 2014.

Design study of a high-resolution breast-dedicated PET system built from cadmium zinc telluride detectors

PubMed Central

Peng, Hao; Levin, Craig S

2013-01-01

We studied the performance of a dual-panel positron emission tomography (PET) camera dedicated to breast cancer imaging using Monte Carlo simulation. The proposed system consists of two 4 cm thick 12 × 15 cm2 area cadmium zinc telluride (CZT) panels with adjustable separation, which can be put in close proximity to the breast and/or axillary nodes. Unique characteristics distinguishing the proposed system from previous efforts in breast-dedicated PET instrumentation are the deployment of CZT detectors with superior spatial and energy resolution, using a cross-strip electrode readout scheme to enable 3D positioning of individual photon interaction coordinates in the CZT, which includes directly measured photon depth-of-interaction (DOI), and arranging the detector slabs edge-on with respect to incoming 511 keV photons for high photon sensitivity. The simulation results show that the proposed CZT dual-panel PET system is able to achieve superior performance in terms of photon sensitivity, noise equivalent count rate, spatial resolution and lesion visualization. The proposed system is expected to achieve ~32% photon sensitivity for a point source at the center and a 4 cm panel separation. For a simplified breast phantom adjacent to heart and torso compartments, the peak noise equivalent count (NEC) rate is predicted to be ~94.2 kcts s−1 (breast volume: 720 cm3 and activity concentration: 3.7 kBq cm−3) for a ~10% energy window around 511 keV and ~8 ns coincidence time window. The system achieves 1 mm intrinsic spatial resolution anywhere between the two panels with a 4 cm panel separation if the detectors have DOI resolution less than 2 mm. For a 3 mm DOI resolution, the system exhibits excellent sphere resolution uniformity (σrms/mean) ≤ 10%) across a 4 cm width FOV. Simulation results indicate that the system exhibits superior hot sphere visualization and is expected to visualize 2 mm diameter spheres with a 5:1 activity concentration ratio within roughly 7 min imaging time. Furthermore, we observe that the degree of spatial resolution degradation along the direction orthogonal to the two panels that is typical of a limited angle tomography configuration is mitigated by having high-resolution DOI capabilities that enable more accurate positioning of oblique response lines. PMID:20400807

Statistical microeconomics and commodity prices: theory and empirical results.

PubMed

Baaquie, Belal E

2016-01-13

A review is made of the statistical generalization of microeconomics by Baaquie (Baaquie 2013 Phys. A 392, 4400-4416. (doi:10.1016/j.physa.2013.05.008)), where the market price of every traded commodity, at each instant of time, is considered to be an independent random variable. The dynamics of commodity market prices is given by the unequal time correlation function and is modelled by the Feynman path integral based on an action functional. The correlation functions of the model are defined using the path integral. The existence of the action functional for commodity prices that was postulated to exist in Baaquie (Baaquie 2013 Phys. A 392, 4400-4416. (doi:10.1016/j.physa.2013.05.008)) has been empirically ascertained in Baaquie et al. (Baaquie et al. 2015 Phys. A 428, 19-37. (doi:10.1016/j.physa.2015.02.030)). The model's action functionals for different commodities has been empirically determined and calibrated using the unequal time correlation functions of the market commodity prices using a perturbation expansion (Baaquie et al. 2015 Phys. A 428, 19-37. (doi:10.1016/j.physa.2015.02.030)). Nine commodities drawn from the energy, metal and grain sectors are empirically studied and their auto-correlation for up to 300 days is described by the model to an accuracy of R(2)>0.90-using only six parameters. © 2015 The Author(s).

Maturation of a central brain flight circuit in Drosophila requires Fz2/Ca2+ signaling

PubMed Central

Agrawal, Tarjani; Hasan, Gaiti

2015-01-01

The final identity of a differentiated neuron is determined by multiple signaling events, including activity dependent calcium transients. Non-canonical Frizzled2 (Fz2) signaling generates calcium transients that determine neuronal polarity, neuronal migration, and synapse assembly in the developing vertebrate brain. Here, we demonstrate a requirement for Fz2/Ca2+ signaling in determining the final differentiated state of a set of central brain dopaminergic neurons in Drosophila, referred to as the protocerebral anterior medial (PAM) cluster. Knockdown or inhibition of Fz2/Ca2+ signaling during maturation of the flight circuit in pupae reduces Tyrosine Hydroxylase (TH) expression in the PAM neurons and affects maintenance of flight. Thus, we demonstrate that Fz2/Ca2+ transients during development serve as a pre-requisite for normal adult behavior. Our results support a neural mechanism where PAM neuron send projections to the α' and β' lobes of a higher brain centre, the mushroom body, and function in dopaminergic re-inforcement of flight. DOI: http://dx.doi.org/10.7554/eLife.07046.001 PMID:25955970

ACT-R/E: An Embodied Cognitive Architecture for Human-Robot Interaction

DTIC Science & Technology

2013-01-01

Threaded Cognition: An Integrated Theory of Concurrent Multitasking . Psychological Review, 115(1), 101–130, http://dx.doi.org/10.1037/0033-295X...Trafton, Naval Research Laboratory, Washington, DC, USA Email : greg.trafton@nrl.navy.mil Laura Hiatt, Naval Research Laboratory, Washington, DC, USA Email ...laura.hiatt@nrl.navy.mil Anthony Harrison, Naval Research Laboratory, Washington, DC, USA Email : anthony.harrison@nrl.navy.mil Frank Tamborello, Naval

Spin-Orbit Coupled Bose-Einstein Condensates

DTIC Science & Technology

2016-11-03

generalized the new concepts to interacting spin-1/2 bosons in optical lattices and described a superfluid-to-Mott insulator transition in spin-orbit...and quantum phase transitions in topological insulators , Physical Review B, (09 2010): 0. doi: 10.1103/PhysRevB.82.115125 Christopher Varney, Kai...109.235308 J. Radi?, A. Di Ciolo, K. Sun, V. Galitski. Exotic Quantum Spin Models in Spin-Orbit-Coupled Mott Insulators , Physical Review Letters

STS-87 Day 09 Highlights

NASA Technical Reports Server (NTRS)

1997-01-01

On this ninth day of the STS-87 mission, the flight crew, Cmdr. Kevin R. Kregel, Pilot Steven W. Lindsey, Mission Specialists Winston E. Scott, Kalpana Chawla, and Takao Doi, and Payload Specialist Leonid K. Kadenyuk continue work with the microgravity science investigations in a special glovebox facility on the middeck. The autonomous operations with the mission's prime payload continue in the payload bay of Columbia with no interaction by the crew required.

Novel Colloidal and Dynamic Interfacial Phenomena in Liquid Crystalline Systems

DTIC Science & Technology

2014-09-13

Pablo. Effects of anchoring strength on the diffusivity of nanoparticles in model liquid-crystalline fluids, Soft Matter, (03 2011): 6828. doi...10.1021/la103975s Santanu Kumar Pal, Claribel Acevedo-Ve?lez, Jacob T. Hunter, Nicholas L. Abbott. Effects of Divalent Ligand Interactions on Surface...peer-reviewed journals: (c) Presentations 7 Presentation #1 (a) Electrical double layer and specific ion effects at interfaces between thermotropic

Ultrafast Laser Interaction Processes for Libs and Other Sensing Technologies

DTIC Science & Technology

2013-04-05

Wang. Propagation of ultrashort pulses through water, Optics Express, (02 2007): . doi: 12/02/2009 8.00 Z. Chen, S. Mao. Femtosecond laser -induced...Richardson, "Nd:YAG-CO2 double- pulse laser -induced breakdown spectroscopy for explosive residues detection" SPIE Defense, Security, Sensing; Orlando, FL... Ultrashort Pulse Laser Workshop, Directed Energy Professional Society; Newton, MA, USA; 06/29,2009. 63. Martin C. Richardson, Michael Sigman

Ultrafast Laser Interaction Processes for LIBS and Other Sensing Technologies

DTIC Science & Technology

2013-04-05

Propagation of ultrashort pulses through water, Optics Express, (02 2007): . doi: 12/02/2009 8.00 Z. Chen, S. Mao. Femtosecond laser -induced electronic...CO2 double- pulse laser -induced breakdown spectroscopy for explosive residues detection" SPIE Defense, Security, Sensing; Orlando, FL, USA; 04/07...Matthieu Baudelet, Michael Sigman, Paul J Dagdigian, Martin C. Richardson, "Nd:YAG-CO2 Double- Pulse Laser Induced Breakdown Spectroscopy for Explosive

Eukaryotic translation initiation factor 3 plays distinct roles at the mRNA entry and exit channels of the ribosomal preinitiation complex

PubMed Central

Aitken, Colin Echeverría; Beznosková, Petra; Vlčkova, Vladislava; Chiu, Wen-Ling; Zhou, Fujun; Valášek, Leoš Shivaya; Hinnebusch, Alan G; Lorsch, Jon R

2016-01-01

Eukaryotic translation initiation factor 3 (eIF3) is a central player in recruitment of the pre-initiation complex (PIC) to mRNA. We probed the effects on mRNA recruitment of a library of S. cerevisiae eIF3 functional variants spanning its 5 essential subunits using an in vitro-reconstituted system. Mutations throughout eIF3 disrupt its interaction with the PIC and diminish its ability to accelerate recruitment to a native yeast mRNA. Alterations to the eIF3a CTD and eIF3b/i/g significantly slow mRNA recruitment, and mutations within eIF3b/i/g destabilize eIF2•GTP•Met-tRNAi binding to the PIC. Using model mRNAs lacking contacts with the 40S entry or exit channels, we uncovered a critical role for eIF3 requiring the eIF3a NTD, in stabilizing mRNA interactions at the exit channel, and an ancillary role at the entry channel requiring residues of the eIF3a CTD. These functions are redundant: defects at each channel can be rescued by filling the other channel with mRNA. DOI: http://dx.doi.org/10.7554/eLife.20934.001 PMID:27782884

Structural basis for recognition and remodeling of the TBP:DNA:NC2 complex by Mot1

PubMed Central

Butryn, Agata; Schuller, Jan M; Stoehr, Gabriele; Runge-Wollmann, Petra; Förster, Friedrich; Auble, David T; Hopfner, Karl-Peter

2015-01-01

Swi2/Snf2 ATPases remodel substrates such as nucleosomes and transcription complexes to control a wide range of DNA-associated processes, but detailed structural information on the ATP-dependent remodeling reactions is largely absent. The single subunit remodeler Mot1 (modifier of transcription 1) dissociates TATA box-binding protein (TBP):DNA complexes, offering a useful system to address the structural mechanisms of Swi2/Snf2 ATPases. Here, we report the crystal structure of the N-terminal domain of Mot1 in complex with TBP, DNA, and the transcription regulator negative cofactor 2 (NC2). Our data show that Mot1 reduces DNA:NC2 interactions and unbends DNA as compared to the TBP:DNA:NC2 state, suggesting that Mot1 primes TBP:NC2 displacement in an ATP-independent manner. Electron microscopy and cross-linking data suggest that the Swi2/Snf2 domain of Mot1 associates with the upstream DNA and the histone fold of NC2, thereby revealing parallels to some nucleosome remodelers. This study provides a structural framework for how a Swi2/Snf2 ATPase interacts with its substrate DNA:protein complex. DOI: http://dx.doi.org/10.7554/eLife.07432.001 PMID:26258880

The nucleolar protein NIFK promotes cancer progression via CK1α/β-catenin in metastasis and Ki-67-dependent cell proliferation

PubMed Central

Lin, Tsung-Chieh; Su, Chia-Yi; Wu, Pei-Yu; Lai, Tsung-Ching; Pan, Wen-An; Jan, Yi-Hua; Chang, Yu-Chang; Yeh, Chi-Tai; Chen, Chi-Long; Ger, Luo-Ping; Chang, Hong-Tai; Yang, Chih-Jen; Huang, Ming-Shyan; Liu, Yu-Peng; Lin, Yuan-Feng; Shyy, John Y-J; Tsai, Ming-Daw; Hsiao, Michael

2016-01-01

Nucleolar protein interacting with the FHA domain of pKi-67 (NIFK) is a Ki-67-interacting protein. However, its precise function in cancer remains largely uninvestigated. Here we show the clinical significance and metastatic mechanism of NIFK in lung cancer. NIFK expression is clinically associated with poor prognosis and metastasis. Furthermore, NIFK enhances Ki-67-dependent proliferation, and promotes migration, invasion in vitro and metastasis in vivo via downregulation of casein kinase 1α (CK1α), a suppressor of pro-metastatic TCF4/β-catenin signaling. Inversely, CK1α is upregulated upon NIFK knockdown. The silencing of CK1α expression in NIFK-silenced cells restores TCF4/β-catenin transcriptional activity, cell migration, and metastasis. Furthermore, RUNX1 is identified as a transcription factor of CSNK1A1 (CK1α) that is negatively regulated by NIFK. Our results demonstrate the prognostic value of NIFK, and suggest that NIFK is required for lung cancer progression via the RUNX1-dependent CK1α repression, which activates TCF4/β-catenin signaling in metastasis and the Ki-67-dependent regulation in cell proliferation. DOI: http://dx.doi.org/10.7554/eLife.11288.001 PMID:26984280

Isolation of 2-deoxy-scyllo-inosose (DOI)-assimilating yeasts and cloning and characterization of the DOI reductase gene of Cryptococcus podzolicus ND1.

PubMed

Ara, Satoshi; Yamazaki, Harutake; Takaku, Hiroaki

2018-04-01

2-Deoxy-scyllo-inosose (DOI) is the first intermediate in the 2-deoxystreptamine-containing aminoglycoside antibiotic biosynthesis pathway and has a six-membered carbocycle structure. DOI is a valuable material because it is easily converted to aromatic compounds and carbasugar derivatives. In this study, we isolated yeast strains capable of assimilating DOI as a carbon source. One of the strains, Cryptococcus podzolicus ND1, mainly converted DOI to scyllo-quercitol and (-)-vibo-quercitol, which is a valuable compound used as an antihypoglycemia agent and as a heat storage material. An NADH-dependent DOI reductase coding gene, DOIR, from C. podzolicus ND1 was cloned and successfully overexpressed in Escherichia coli. The purified protein catalyzed the irreversible reduction of DOI with NADH and converted DOI into (-)-vibo-quercitol. The enzyme had an optimal pH of 8.5 and optimal temperature of 35°C, respectively. The k cat of this enzyme was 9.98 s -1 , and the K m values for DOI and NADH were 4.38 and 0.24 mM, respectively. The enzyme showed a strong preference for NADH and showed no activity with NADPH. Multiple-alignment analysis of DOI reductase revealed that it belongs to the GFO_IDH_MocA protein family and is an inositol dehydrogenase homolog in other fungi, such as Cryptococcus gattii, and bacteria, such as Bacillus subtilis. This is the first identification of a DOI-assimilating yeast and a gene involved in DOI metabolism in fungi. Copyright © 2017 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

Novel Algorithms Enabling Rapid, Real-Time Earthquake Monitoring and Tsunami Early Warning Worldwide

NASA Astrophysics Data System (ADS)

Lomax, A.; Michelini, A.

2012-12-01

We have introduced recently new methods to determine rapidly the tsunami potential and magnitude of large earthquakes (e.g., Lomax and Michelini, 2009ab, 2011, 2012). To validate these methods we have implemented them along with other new algorithms within the Early-est earthquake monitor at INGV-Rome (http://early-est.rm.ingv.it, http://early-est.alomax.net). Early-est is a lightweight software package for real-time earthquake monitoring (including phase picking, phase association and event detection, location, magnitude determination, first-motion mechanism determination, ...), and for tsunami early warning based on discriminants for earthquake tsunami potential. In a simulation using archived broadband seismograms for the devastating M9, 2011 Tohoku earthquake and tsunami, Early-est determines: the epicenter within 3 min after the event origin time, discriminants showing very high tsunami potential within 5-7 min, and magnitude Mwpd(RT) 9.0-9.2 and a correct shallow-thrusting mechanism within 8 min. Real-time monitoring with Early-est givess similar results for most large earthquakes using currently available, real-time seismogram data. Here we summarize some of the key algorithms within Early-est that enable rapid, real-time earthquake monitoring and tsunami early warning worldwide: >>> FilterPicker - a general purpose, broad-band, phase detector and picker (http://alomax.net/FilterPicker); >>> Robust, simultaneous association and location using a probabilistic, global-search; >>> Period-duration discriminants TdT0 and TdT50Ex for tsunami potential available within 5 min; >>> Mwpd(RT) magnitude for very large earthquakes available within 10 min; >>> Waveform P polarities determined on broad-band displacement traces, focal mechanisms obtained with the HASH program (Hardebeck and Shearer, 2002); >>> SeisGramWeb - a portable-device ready seismogram viewer using web-services in a browser (http://alomax.net/webtools/sgweb/info.html). References (see also: http://alomax.net/pub_list.html): Lomax, A. and A. Michelini (2012), Tsunami early warning within 5 minutes, Pure and Applied Geophysics, 169, nnn-nnn, doi: 10.1007/s00024-012-0512-6. Lomax, A. and A. Michelini (2011), Tsunami early warning using earthquake rupture duration and P-wave dominant period: the importance of length and depth of faulting, Geophys. J. Int., 185, 283-291, doi: 10.1111/j.1365-246X.2010.04916.x. Lomax, A. and A. Michelini (2009b), Tsunami early warning using earthquake rupture duration, Geophys. Res. Lett., 36, L09306, doi:10.1029/2009GL037223. Lomax, A. and A. Michelini (2009a), Mwpd: A Duration-Amplitude Procedure for Rapid Determination of Earthquake Magnitude and Tsunamigenic Potential from P Waveforms, Geophys. J. Int.,176, 200-214, doi:10.1111/j.1365-246X.2008.03974.x

Regulation of Serotonin-Induced Trafficking and Migration of Eosinophils

PubMed Central

Kang, Bit Na; Ha, Sung Gil; Bahaie, Nooshin S.; Hosseinkhani, M. Reza; Ge, Xiao Na; Blumenthal, Malcolm N.; Rao, Savita P.; Sriramarao, P.

2013-01-01

Association of the neurotransmitter serotonin (5-HT) with the pathogenesis of allergic asthma is well recognized and its role as a chemoattractant for eosinophils (Eos) in vitro and in vivo has been previously demonstrated. Here we have examined the regulation of 5-HT-induced human and murine Eos trafficking and migration at a cellular and molecular level. Eos from allergic donors and bone marrow-derived murine Eos (BM-Eos) were found to predominantly express the 5-HT2A receptor. Exposure to 5-HT or 2,5-dimethoxy-4-iodoamphetamine (DOI), a 5-HT2A/C selective agonist, induced rolling of human Eos and AML14.3D10 human Eos-like cells on vascular cell adhesion molecule (VCAM)-1 under conditions of flow in vitro coupled with distinct cytoskeletal and cell shape changes as well as phosphorylation of MAPK. Blockade of 5-HT2A or of ROCK MAPK, PI3K, PKC and calmodulin, but not Gαi-proteins, with specific inhibitors inhibited DOI-induced rolling, actin polymerization and changes in morphology of VCAM-1-adherent AML14.3D10 cells. More extensive studies with murine BM-Eos demonstrated the role of 5-HT in promoting rolling in vivo within inflamed post-capillary venules of the mouse cremaster microcirculation and confirmed that down-stream signaling of 5-HT2A activation involves ROCK, MAPK, PI3K, PKC and calmodulin similar to AML14.3D10 cells. DOI-induced migration of BM-Eos is also dependent on these signaling molecules and requires Ca2+. Further, activation of 5-HT2A with DOI led to an increase in intracellular Ca2+ levels in murine BM-Eos. Overall, these data demonstrate that 5-HT (or DOI)/5-HT2A interaction regulates Eos trafficking and migration by promoting actin polymerization associated with changes in cell shape/morphology that favor cellular trafficking and recruitment via activation of specific intracellular signaling molecules (ROCK, MAPK, PI3K and the PKC-calmodulin pathway). PMID:23372779

The effect of plasma inhomogeneities on (i) radio emission generation by non-gyrotropic electron beams and (ii) particle acceleration by Langmuir waves

NASA Astrophysics Data System (ADS)

Tsiklauri, David

2015-04-01

Extensive particle-in-cell simulations of fast electron beams injected in a background magnetised plasma with a decreasing density profile were carried out. These simulations were intended to further shed light on a newly proposed mechanism for the generation of electromagnetic waves in type III solar radio bursts [1]. Here recent progress in an alternative to the plasma emission model using Particle-In-Cell, self-consistent electromagnetic wave emission simulations of solar type III radio bursts will be presented. In particular, (i) Fourier space drift (refraction) of non-gyrotropic electron beam-generated wave packets, caused by the density gradient [1,2], (ii) parameter space investigation of numerical runs [3], (iii) concurrent generation of whistler waves [4] and a separate problem of (iv) electron acceleration by Langmuir waves in a background magnetised plasma with an increasing density profile [5] will be discussed. In all considered cases the density inhomogeneity-induced wave refraction plays a crucial role. In the case of non-gyrotropic electron beam, the wave refraction transforms the generated wave packets from standing into freely escaping EM radiation. In the case of electron acceleration by Langmuir waves, a positive density gradient in the direction of wave propagation causes a decrease in the wavenumber, and hence a higher phase velocity vph = ω/k. The k-shifted wave is then subject to absorption by a faster electron by wave-particle interaction. The overall effect is an increased number of high energy electrons in the energy spectrum. [1] D. Tsiklauri, Phys. Plasmas 18, 052903 (2011); http://dx.doi.org/10.1063/1.3590928 [2] H. Schmitz, D. Tsiklauri, Phys. Plasmas 20, 062903 (2013); http://dx.doi.org/10.1063/1.4812453 [3] R. Pechhacker, D. Tsiklauri, Phys. Plasmas 19, 112903 (2012); http://dx.doi.org/10.1063/1.4768429 [4] M. Skender, D. Tsiklauri, Phys. Plasmas 21, 042904 (2014); http://dx.doi.org/10.1063/1.4871723 [5] R. Pechhacker, D. Tsiklauri, Phys. Plasmas 21, 012903 (2014); http://dx.doi.org/10.1063/1.4863494 This research is funded by the Leverhulme Trust Research Project Grant RPG-311

Improvement of crystal identification performance for a four-layer DOI detector composed of crystals segmented by laser processing

NASA Astrophysics Data System (ADS)

Mohammadi, Akram; Inadama, Naoko; Yoshida, Eiji; Nishikido, Fumihiko; Shimizu, Keiji; Yamaya, Taiga

2017-09-01

We have developed a four-layer depth of interaction (DOI) detector with single-side photon readout, in which segmented crystals with the patterned reflector insertion are separately identified by the Anger-type calculation. Optical conditions between segmented crystals, where there is no reflector, affect crystal identification ability. Our objective of this work was to improve crystal identification performance of the four-layer DOI detector that uses crystals segmented with a recently developed laser processing technique to include laser processed boundaries (LPBs). The detector consisted of 2 × 2 × 4mm3 LYSO crystals and a 4 × 4 array multianode photomultiplier tube (PMT) with 4.5 mm anode pitch. The 2D position map of the detector was calculated by the Anger calculation method. At first, influence of optical condition on crystal identification was evaluated for a one-layer detector consisting of a 2 × 2 crystal array with three different optical conditions between the crystals: crystals stuck together using room temperature vulcanized (RTV) rubber, crystals with air coupling and segmented crystals with LPBs. The crystal array with LPBs gave the shortest distance between crystal responses in the 2D position map compared with the crystal array coupled with RTV rubber or air due to the great amount of cross-talk between segmented crystals with LPBs. These results were used to find optical conditions offering the optimum distance between crystal responses in the 2D position map for the four-layer DOI detector. Crystal identification performance for the four-layer DOI detector consisting of an 8 × 8 array of crystals segmented with LPBs was examined and it was not acceptable for the crystals in the first layer. The crystal identification was improved for the first layer by changing the optical conditions between all 2 × 2 crystal arrays of the first layer to RTV coupling. More improvement was observed by combining different optical conditions between all crystals of the first layer and some crystals of the second and the third layers of the segmented array.

A hybrid parallel architecture for electrostatic interactions in the simulation of dissipative particle dynamics

NASA Astrophysics Data System (ADS)

Yang, Sheng-Chun; Lu, Zhong-Yuan; Qian, Hu-Jun; Wang, Yong-Lei; Han, Jie-Ping

2017-11-01

In this work, we upgraded the electrostatic interaction method of CU-ENUF (Yang, et al., 2016) which first applied CUNFFT (nonequispaced Fourier transforms based on CUDA) to the reciprocal-space electrostatic computation and made the computation of electrostatic interaction done thoroughly in GPU. The upgraded edition of CU-ENUF runs concurrently in a hybrid parallel way that enables the computation parallelizing on multiple computer nodes firstly, then further on the installed GPU in each computer. By this parallel strategy, the size of simulation system will be never restricted to the throughput of a single CPU or GPU. The most critical technical problem is how to parallelize a CUNFFT in the parallel strategy, which is conquered effectively by deep-seated research of basic principles and some algorithm skills. Furthermore, the upgraded method is capable of computing electrostatic interactions for both the atomistic molecular dynamics (MD) and the dissipative particle dynamics (DPD). Finally, the benchmarks conducted for validation and performance indicate that the upgraded method is able to not only present a good precision when setting suitable parameters, but also give an efficient way to compute electrostatic interactions for huge simulation systems. Program Files doi:http://dx.doi.org/10.17632/zncf24fhpv.1 Licensing provisions: GNU General Public License 3 (GPL) Programming language: C, C++, and CUDA C Supplementary material: The program is designed for effective electrostatic interactions of large-scale simulation systems, which runs on particular computers equipped with NVIDIA GPUs. It has been tested on (a) single computer node with Intel(R) Core(TM) i7-3770@ 3.40 GHz (CPU) and GTX 980 Ti (GPU), and (b) MPI parallel computer nodes with the same configurations. Nature of problem: For molecular dynamics simulation, the electrostatic interaction is the most time-consuming computation because of its long-range feature and slow convergence in simulation space, which approximately take up most of the total simulation time. Although the parallel method CU-ENUF (Yang et al., 2016) based on GPU has achieved a qualitative leap compared with previous methods in electrostatic interactions computation, the computation capability is limited to the throughput capacity of a single GPU for super-scale simulation system. Therefore, we should look for an effective method to handle the calculation of electrostatic interactions efficiently for a simulation system with super-scale size. Solution method: We constructed a hybrid parallel architecture, in which CPU and GPU are combined to accelerate the electrostatic computation effectively. Firstly, the simulation system is divided into many subtasks via domain-decomposition method. Then MPI (Message Passing Interface) is used to implement the CPU-parallel computation with each computer node corresponding to a particular subtask, and furthermore each subtask in one computer node will be executed in GPU in parallel efficiently. In this hybrid parallel method, the most critical technical problem is how to parallelize a CUNFFT (nonequispaced fast Fourier transform based on CUDA) in the parallel strategy, which is conquered effectively by deep-seated research of basic principles and some algorithm skills. Restrictions: The HP-ENUF is mainly oriented to super-scale system simulations, in which the performance superiority is shown adequately. However, for a small simulation system containing less than 106 particles, the mode of multiple computer nodes has no apparent efficiency advantage or even lower efficiency due to the serious network delay among computer nodes, than the mode of single computer node. References: (1) S.-C. Yang, H.-J. Qian, Z.-Y. Lu, Appl. Comput. Harmon. Anal. 2016, http://dx.doi.org/10.1016/j.acha.2016.04.009. (2) S.-C. Yang, Y.-L. Wang, G.-S. Jiao, H.-J. Qian, Z.-Y. Lu, J. Comput. Chem. 37 (2016) 378. (3) S.-C. Yang, Y.-L. Zhu, H.-J. Qian, Z.-Y. Lu, Appl. Chem. Res. Chin. Univ., 2017, http://dx.doi.org/10.1007/s40242-016-6354-5. (4) Y.-L. Zhu, H. Liu, Z.-W. Li, H.-J. Qian, G. Milano, Z.-Y. Lu, J. Comput. Chem. 34 (2013) 2197.

Erratum.

PubMed

2015-04-01

In issue 21.1 three of the DOIs were printed incorrectly, please see below for the correct information. Andrea Giorgianni, et al. Flow-diverter stenting of post-traumatic bilateral anterior cerebral artery pseudoaneurysm: A case report. Doi: 10.15274/INR-2014-10059 Correct: Doi: 10.1177/1591019915575441 Lee-Anne Slater, et al. Effect of flow diversion with silk on aneurysm size: A single center experience. Doi: 10.15274/INR-2014-10062 Correct DOI: 10.1177/1591019915576433 Robert J McDonald, et al. Periprocedural safety of Pipeline therapy for unruptured cerebral aneurysms: Analysis of 279 Patients in a multihospital database. Doi: 10.15274/INR-2014-10074 Correct DOI: 10.1177/1591019915576289. © The Author(s) 2015 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

Time since plantation is the most important determining factor for soil erosion rates in vineyards. A case study in the valley of Les Alcusses valley, Eastern Spain

NASA Astrophysics Data System (ADS)

Rodrígo Comino, Jesús; Keesstra, Saskia; Novara, Agata; García Díaz, Andrés; Jordán, Antonio; Brevik, Eric C.; Cerdà, Artemi

2017-04-01

Vineyards are known to suffer from soil erosion around the world (Novara et al., 2011; 2013; 2015; Rodrigo Comino et al., 2015; Prosdocimi et al., 2016; Rodrigo-Comino et al., 2016a; 2016b, 2016b). As in other crops in the Mediterranean such as citrus (Cerdà et al., 2009), olives (Taguas et al., 2015), persimmon (Cerdà et al., 2016) or apricot (Keesstra et al., 2016) plantations, there is a need to survey the spatial and temporal changes in soil erosion in vineyards. Soil redistribution in agricultural land is determined by human management due to the control it exerts on the vegetation cover and soil properties. This is why the time since plantation is important in soil erosion spatial and temporal distribution. Especially because during the plantation of the saplings, the soil is compacted and all other vegetation is removed. In our experiment we selected four paired plot research sites in the Les Alcusses valley, in Eastern Spain. We selected recently planted vineyards (1-year old) and 40-years old plantations. In total 80 rainfall simulations were performed with an intensity of 55 mm h-1 on small 0.25 m2 circular plots to determine the soil detachment by rainfall. The results show that soil erosion rates in the 40-year old vineyards were high (### a rate??), and in the recently planted ones were extremely high, on average six times higher. Acknowledgements The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement n 603498 (RECARE project) and the CGL2013- 47862-C2-1-R and CGL2016-75178-C2-2-R national research projects. References Cerdà, A., González-Pelayo, O., Giménez-Morera, A., Jordán, A., Pereira, P., Novara, A., Brevik, E.C., Prosdocimi, M., Mahmoodabadi, M., Keesstra, S., García Orenes, F., Ritsema, C., 2016. The use of barley straw residues to avoid high erosion and runoff rates on persimmon plantations in Eastern Spain under low frequency - high magnitude simulated rainfall events. Soil Res, 54, 2, 154-165 DOI: 10.1071/SR15092 Keesstra S, Pereira P, Novara A, Brevik EC, Azorin-Molina C, Parras-Alcántara L, Jordán A, Cerdà A. 2016. Effects of soil management techniques on soil water erosion in apricot orchards. Science of the Total Environment 551-552: 357-366. DOI: 10.1016/j.scitotenv.2016.01.182 Novara, A., A. Cerdà, D. Carmelo, L. P. Giuseppe, S. Antonino, and G. Luciano. 2015. Effectiveness of Carbon Isotopic Signature for Estimating Soil Erosion and Deposition Rates in Sicilian Vineyards. Soil and Tillage Research 152: 1-7. doi:10.1016/j.still.2015.03.010. Novara, A., L. Gristina, F. Guaitoli, A. Santoro, and A. Cerdà. 2013. Managing Soil Nitrate with Cover Crops and Buffer Strips in Sicilian Vineyards. Solid Earth 4 (2): 255-262. doi:10.5194/se-4-255-2013. Novara, A., L. Gristina, S. S. Saladino, A. Santoro, and A. Cerdà. 2011. Soil Erosion Assessment on Tillage and Alternative Soil Managements in a Sicilian Vineyard. Soil and Tillage Research 117: 140-147. doi:10.1016/j.still.2011.09.007. Prosdocimi, M., A. Cerdà, and P. Tarolli. 2016a. Soil Water Erosion on Mediterranean Vineyards: A Review. Catena 141: 1-21. doi:10.1016/j.catena.2016.02.010. Prosdocimi, M., A. Jordán, P. Tarolli, S. Keesstra, A. Novara, and A. Cerdà. 2016b. The Immediate Effectiveness of Barley Straw Mulch in Reducing Soil Erodibility and Surface Runoff Generation in Mediterranean Vineyards. Science of the Total Environment 547: 323-330. doi:10.1016/j.scitotenv.2015.12.076. Rodrigo Comino J, Iserloh T, Morvan X, Malam Issa O, Naisse C, Keesstra SD, Cerdà A, Prosdocimi M, Arnáez J, Lasanta T, Ramos MC, Marqués MJ, Ruiz Colmenero M, Bienes R, Ruiz Sinoga JD, Seeger M, Ries JB 2016a. Soil Erosion Processes in European Vineyards: A Qualitative Comparison of Rainfall Simulation Measurements in Germany, Spain and France. Hydrology, 3 (1), 6; doi:10.3390/hydrology3010006 Rodrigo Comino, J., Iserloh, T., Lassu, T., Cerdà, A., Keesstra, S.D., Prosdocimi, M., Brings, C., Marzen, M., Ramos, M.C., Senciales, J.M., Ruiz Sinoga, J.D., Seeger, M., Ries, J.B., 2016b. Quantitative comparison of initial soil erosion processes and runoff generation in Spanish and German vineyards. Sci. Total Environ. 565, 1165-1174. DOI:10.1016/j.scitotenv.2016.05.163 Rodrigo-Comino, J., Brings, C., Lassu, T., Iserloh, T., Senciales, J.M., Martínez Murillo, J.F., Ruiz Sinoga, J.D., Seeger, M., Ries, J.B. Rainfall and human activity impacts on soil losses and rill erosion in vineyards (Ruwer Valley, Germany). 2015. Solid Earth, 6 (3), pp. 823-837. DOI: http://dx.doi.org/10.5194/se-6-823-2015 Rodrigo-Comino, J., M. Seeger, J. M. Senciales, J. D. Ruiz-Sinoga, and J. B. Ries. 2016c. Spatial and Temporal Variation of Soil Hydrological Processes on Steep Slope Vineyards (Ruwel-Mosel Valley, Gemany). Cuadernos De Investigacion Geografica 42 (1): 281-306. doi:10.18172/cig.2934.

Reliability beyond Theory and into Practice

ERIC Educational Resources Information Center

Sijtsma, Klaas

2009-01-01

The critical reactions of Bentler (2009, doi: 10.1007/s11336-008-9100-1), Green and Yang (2009a, doi: 10.1007/s11336-008-9098-4 ; 2009b, doi: 10.1007/s11336-008-9099-3), and Revelle and Zinbarg (2009, doi: 10.1007/s11336-008-9102-z) to Sijtsma's (2009, doi: 10.1007/s11336-008-9101-0) paper on Cronbach's alpha are addressed. The dissemination of…

Link-Prediction Enhanced Consensus Clustering for Complex Networks (Open Access)

DTIC Science & Technology

2016-05-20

92:022816. Available from: http://link.aps.org/doi/10.1103/PhysRevE.92.022816. doi: 10. 1103 /PhysRevE.92.022816 16. Aldecoa R, Marín I. Exploring the...from: http://link.aps.org/doi/10.1103/PhysRevE.80.056117. doi: 10. 1103 /PhysRevE.80.056117 18. Dahlin J, Svenson P. Ensemble approaches for improving...046110. Available from: http://link.aps.org/doi/10.1103/PhysRevE.81.046110. doi: 10. 1103 /PhysRevE.81.046110 28. Gfeller D, Chappelier JC, De Los Rios P

It takes two to tango to the melanosome

PubMed Central

Lakkaraju, Aparna; Carvajal-Gonzalez, Jose Maria

2009-01-01

The role of clathrin adaptor proteins in sorting cargo in the biosynthetic and recycling routes is an area of intense research. In this issue, Delevoye et al. (2009. J. Cell Biol. doi:10.1083/jcb.200907122) show that a close interaction between the clathrin adaptor AP-1 and a kinesin motor KIF13A is essential for delivering melanogenic enzymes from recycling endosomes to nascent melanosomes and for organelle biogenesis. PMID:19841135

Implementing RDA Data Citation Recommendations: Case Study in South Africa

NASA Astrophysics Data System (ADS)

Hugo, Wim

2016-04-01

SAEON operates a shared research data infrastructure for its own data sets and for clients and end users in the Earth and Environmental Sciences domain. SAEON has a license to issue Digital Object Identifiers via DataCite on behalf of third parties, and have recently concluded development work to make a universal data deposit, description, and DOI minting facility available. This facility will be used to develop a number of end user gateways, including DataCite South Africa (in collaboration with National Research Foundation and addressing all grant-funded research in the country), DIRISA (Data-intensive Research Infrastructure for South Africa - in collaboration with Meraka Institute and Department of Science and Technology), and SASDI (South African Spatial Data Infrastructure). The RDA recently published Data Citation Recommendations [1], and this was used as a basis for specification of Digital Object Identifier implementation, raising two significant challenges: 1. Synchronisation of frequently harvested meta-data sets where version management practice did not align with the RDA recommendations, and 2. Handling sub-sets of and queries on large, continuously updated data sets. In the first case, we have developed a set of tests that determine the logical course of action when discrepancies are found during synchronization, and we have incorporated these into meta-data harvester configurations. Additionally, we have developed a state diagram and attendant workflow for meta-data that includes problem states emanating from DOI management, reporting services for data depositors, and feedback to end users in respect of synchronisation issues. In the second case, in the absence of firm guidelines from DataCite, we are seeking community consensus and feedback on an approach that caches all queries performed and subsets derived from data, and provide these with anchor-style extensions linked to the dataset's original DOI. This allows extended DOIs to resolve to a meta-data page on which the cached data set is available as an anchored download link.All cached datasets are provided with checksum values to verify the contents against such copies as may exist. The paper reviews recent service-driven portal interface developments, both services and graphical user interfaces, including wizard-style, configurable applications for meta-data management and DOI minting, discovery, download, visualization, and reporting. It showcases examples of the two permanent identifier problem areas and how these were addressed. The paper concludes with contributions to open research questions, including (1) determining optimal meta-data granularity and (2) proposing an implementation guideline for extended DOIs. [1] A. Rauber, D. van Uytvanck, A. Asmi, S. Pröll, "Data Citation Recommendations", November 2015, RDA. https://rd-alliance.org/group/data-citation-wg/outcomes/data-citation-recommendation.htm

78 FR 25097 - Notice of Realty Action: Competitive, Sealed-Bid, Spring SNPLMA Sale of Public Lands in Clark...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-29

... Determination of National Environmental Policy Act Adequacy (DNA). DATES: Interested parties may submit written... December 23, 2004, and a site specific DNA document numbered DOI-BLM-NV-S010-2012-0106-DNA. Sale procedures...

Tools to Compare Diving-Animal Kinematics with Acoustic Behavior and Exposure

DTIC Science & Technology

2010-09-30

2007. Acoustic determination of activity and flipper stroke rate in foraging northern fur seal females. Endanger. Species Res., doi:10.3354/esr00050...sound recording device (Bioacoustic Probe) to document the acoustic environment of a blacktip reef shark (Carcharhinus melanopterus). Aquat . Living

Featured Image: A Galaxy Plunges Into a Cluster Core

NASA Astrophysics Data System (ADS)

Kohler, Susanna

2015-10-01

The galaxy that takes up most of the frame in this stunning image (click for the full view!) is NGC 1427A. This is a dwarf irregular galaxy (unlike the fortuitously-located background spiral galaxy in the lower right corner of the image), and its currently in the process of plunging into the center of the Fornax galaxy cluster. Marcelo Mora (Pontifical Catholic University of Chile) and collaborators have analyzed observations of this galaxy made by both the Very Large Telescope in Chile and the Hubble Advanced Camera for Surveys, which produced the image shown here as a color composite in three channels. The team worked to characterize the clusters of star formation within NGC 1427A identifiable in the image as bright knots within the galaxy and determine how the interactions of this galaxy with its cluster environment affect the star formation within it. For more information and the original image, see the paper below.Citation:Marcelo D. Mora et al 2015 AJ 150 93. doi:10.1088/0004-6256/150/3/93

Numerical solutions of ideal quantum gas dynamical flows governed by semiclassical ellipsoidal-statistical distribution.

PubMed

Yang, Jaw-Yen; Yan, Chih-Yuan; Diaz, Manuel; Huang, Juan-Chen; Li, Zhihui; Zhang, Hanxin

2014-01-08

The ideal quantum gas dynamics as manifested by the semiclassical ellipsoidal-statistical (ES) equilibrium distribution derived in Wu et al. (Wu et al . 2012 Proc. R. Soc. A 468 , 1799-1823 (doi:10.1098/rspa.2011.0673)) is numerically studied for particles of three statistics. This anisotropic ES equilibrium distribution was derived using the maximum entropy principle and conserves the mass, momentum and energy, but differs from the standard Fermi-Dirac or Bose-Einstein distribution. The present numerical method combines the discrete velocity (or momentum) ordinate method in momentum space and the high-resolution shock-capturing method in physical space. A decoding procedure to obtain the necessary parameters for determining the ES distribution is also devised. Computations of two-dimensional Riemann problems are presented, and various contours of the quantities unique to this ES model are illustrated. The main flow features, such as shock waves, expansion waves and slip lines and their complex nonlinear interactions, are depicted and found to be consistent with existing calculations for a classical gas.

Response of radiation belt simulations to different radial diffusion coefficients

NASA Astrophysics Data System (ADS)

Drozdov, A.; Shprits, Y.; Subbotin, D.; Kellerman, A. C.

2013-12-01

Resonant interactions between Ultra Low Frequency (ULF) waves and relativistic electrons may violate the third adiabatic invariant of motion, which produces radial diffusion in the electron radiation belts. This process plays an important role in the formation and structure of the outer electron radiation belt and is important for electron acceleration and losses in that region. Two parameterizations of the resonant wave-particle interaction of electrons with ULF waves in the magnetosphere by Brautigam and Albert [2000] and Ozeke et al. [2012] are evaluated using the Versatile Electron Radiation Belt (VERB) diffusion code to estimate their relative effect on the radiation belt simulation. The period of investigation includes quiet time and storm time geomagnetic activity and is compared to data based on satellite observations. Our calculations take into account wave-particle interactions represented by radial diffusion transport, local acceleration, losses due to pitch-angle diffusion, and mixed diffusion. We show that the results of the 3D diffusion simulations depend on the assumed parametrization of waves. The differences between the simulations and potential missing physical mechanisms are discussed. References Brautigam, D. H., and J. M. Albert (2000), Radial diffusion analysis of outer radiation belt electrons during the October 9, 1990, magnetic storm, J. Geophys. Res., 105(A1), 291-309, doi:10.1029/1999JA900344 Ozeke, L. G., I. R. Mann, K. R. Murphy, I. J. Rae, D. K. Milling, S. R. Elkington, A. A. Chan, and H. J. Singer (2012), ULF wave derived radiation belt radial diffusion coefficients, J. Geophys. Res., 117, A04222, doi:10.1029/2011JA017463.

Concerted action of neuroepithelial basal shrinkage and active epithelial migration ensures efficient optic cup morphogenesis

PubMed Central

Sidhaye, Jaydeep; Norden, Caren

2017-01-01

Organ formation is a multi-scale event that involves changes at the intracellular, cellular and tissue level. Organogenesis often starts with the formation of characteristically shaped organ precursors. However, the cellular mechanisms driving organ precursor formation are often not clear. Here, using zebrafish, we investigate the epithelial rearrangements responsible for the development of the hemispherical retinal neuroepithelium (RNE), a part of the optic cup. We show that in addition to basal shrinkage of RNE cells, active migration of connected epithelial cells into the RNE is a crucial player in its formation. This cellular movement is driven by progressive cell-matrix contacts and actively translocates prospective RNE cells to their correct location before they adopt neuroepithelial fate. Failure of this migration during neuroepithelium formation leads to ectopic determination of RNE cells and consequently impairs optic cup formation. Overall, this study illustrates how spatiotemporal coordination between morphogenic movements and fate determination critically influences organogenesis. DOI: http://dx.doi.org/10.7554/eLife.22689.001 PMID:28372636

Discovering sparse transcription factor codes for cell states and state transitions during development

PubMed Central

Furchtgott, Leon A; Melton, Samuel; Menon, Vilas; Ramanathan, Sharad

2017-01-01

Computational analysis of gene expression to determine both the sequence of lineage choices made by multipotent cells and to identify the genes influencing these decisions is challenging. Here we discover a pattern in the expression levels of a sparse subset of genes among cell types in B- and T-cell developmental lineages that correlates with developmental topologies. We develop a statistical framework using this pattern to simultaneously infer lineage transitions and the genes that determine these relationships. We use this technique to reconstruct the early hematopoietic and intestinal developmental trees. We extend this framework to analyze single-cell RNA-seq data from early human cortical development, inferring a neocortical-hindbrain split in early progenitor cells and the key genes that could control this lineage decision. Our work allows us to simultaneously infer both the identity and lineage of cell types as well as a small set of key genes whose expression patterns reflect these relationships. DOI: http://dx.doi.org/10.7554/eLife.20488.001 PMID:28296636

Mapping transiently formed and sparsely populated conformations on a complex energy landscape

PubMed Central

Wang, Yong; Papaleo, Elena; Lindorff-Larsen, Kresten

2016-01-01

Determining the structures, kinetics, thermodynamics and mechanisms that underlie conformational exchange processes in proteins remains extremely difficult. Only in favourable cases is it possible to provide atomic-level descriptions of sparsely populated and transiently formed alternative conformations. Here we benchmark the ability of enhanced-sampling molecular dynamics simulations to determine the free energy landscape of the L99A cavity mutant of T4 lysozyme. We find that the simulations capture key properties previously measured by NMR relaxation dispersion methods including the structure of a minor conformation, the kinetics and thermodynamics of conformational exchange, and the effect of mutations. We discover a new tunnel that involves the transient exposure towards the solvent of an internal cavity, and show it to be relevant for ligand escape. Together, our results provide a comprehensive view of the structural landscape of a protein, and point forward to studies of conformational exchange in systems that are less characterized experimentally. DOI: http://dx.doi.org/10.7554/eLife.17505.001 PMID:27552057

Determination of ubiquitin fitness landscapes under different chemical stresses in a classroom setting

PubMed Central

Mavor, David; Barlow, Kyle; Thompson, Samuel; Barad, Benjamin A; Bonny, Alain R; Cario, Clinton L; Gaskins, Garrett; Liu, Zairan; Deming, Laura; Axen, Seth D; Caceres, Elena; Chen, Weilin; Cuesta, Adolfo; Gate, Rachel E; Green, Evan M; Hulce, Kaitlin R; Ji, Weiyue; Kenner, Lillian R; Mensa, Bruk; Morinishi, Leanna S; Moss, Steven M; Mravic, Marco; Muir, Ryan K; Niekamp, Stefan; Nnadi, Chimno I; Palovcak, Eugene; Poss, Erin M; Ross, Tyler D; Salcedo, Eugenia C; See, Stephanie K; Subramaniam, Meena; Wong, Allison W; Li, Jennifer; Thorn, Kurt S; Conchúir, Shane Ó; Roscoe, Benjamin P; Chow, Eric D; DeRisi, Joseph L; Kortemme, Tanja; Bolon, Daniel N; Fraser, James S

2016-01-01

Ubiquitin is essential for eukaryotic life and varies in only 3 amino acid positions between yeast and humans. However, recent deep sequencing studies indicate that ubiquitin is highly tolerant to single mutations. We hypothesized that this tolerance would be reduced by chemically induced physiologic perturbations. To test this hypothesis, a class of first year UCSF graduate students employed deep mutational scanning to determine the fitness landscape of all possible single residue mutations in the presence of five different small molecule perturbations. These perturbations uncover 'shared sensitized positions' localized to areas around the hydrophobic patch and the C-terminus. In addition, we identified perturbation specific effects such as a sensitization of His68 in HU and a tolerance to mutation at Lys63 in DTT. Our data show how chemical stresses can reduce buffering effects in the ubiquitin proteasome system. Finally, this study demonstrates the potential of lab-based interdisciplinary graduate curriculum. DOI: http://dx.doi.org/10.7554/eLife.15802.001 PMID:27111525

Active suppression of a leaf meristem orchestrates determinate leaf growth

PubMed Central

Alvarez, John Paul; Furumizu, Chihiro; Efroni, Idan; Eshed, Yuval; Bowman, John L

2016-01-01

Leaves are flat determinate organs derived from indeterminate shoot apical meristems. The presence of a specific leaf meristem is debated, as anatomical features typical of meristems are not present in leaves. Here we demonstrate that multiple NGATHA (NGA) and CINCINNATA-class-TCP (CIN-TCP) transcription factors act redundantly, shortly after leaf initiation, to gradually restrict the activity of a leaf meristem in Arabidopsis thaliana to marginal and basal domains, and that their absence confers persistent marginal growth to leaves, cotyledons and floral organs. Following primordia initiation, the restriction of the broadly acting leaf meristem to the margins is mediated by the juxtaposition of adaxial and abaxial domains and maintained by WOX homeobox transcription factors, whereas other marginal elaboration genes are dispensable for its maintenance. This genetic framework parallels the morphogenetic program of shoot apical meristems and may represent a relic of an ancestral shoot system from which seed plant leaves evolved. DOI: http://dx.doi.org/10.7554/eLife.15023.001 PMID:27710768

Long non-coding RNA produced by RNA polymerase V determines boundaries of heterochromatin

PubMed Central

Böhmdorfer, Gudrun; Sethuraman, Shriya; Rowley, M Jordan; Krzyszton, Michal; Rothi, M Hafiz; Bouzit, Lilia; Wierzbicki, Andrzej T

2016-01-01

RNA-mediated transcriptional gene silencing is a conserved process where small RNAs target transposons and other sequences for repression by establishing chromatin modifications. A central element of this process are long non-coding RNAs (lncRNA), which in Arabidopsis thaliana are produced by a specialized RNA polymerase known as Pol V. Here we show that non-coding transcription by Pol V is controlled by preexisting chromatin modifications located within the transcribed regions. Most Pol V transcripts are associated with AGO4 but are not sliced by AGO4. Pol V-dependent DNA methylation is established on both strands of DNA and is tightly restricted to Pol V-transcribed regions. This indicates that chromatin modifications are established in close proximity to Pol V. Finally, Pol V transcription is preferentially enriched on edges of silenced transposable elements, where Pol V transcribes into TEs. We propose that Pol V may play an important role in the determination of heterochromatin boundaries. DOI: http://dx.doi.org/10.7554/eLife.19092.001 PMID:27779094

Active machine learning-driven experimentation to determine compound effects on protein patterns

PubMed Central

Naik, Armaghan W; Kangas, Joshua D; Sullivan, Devin P; Murphy, Robert F

2016-01-01

High throughput screening determines the effects of many conditions on a given biological target. Currently, to estimate the effects of those conditions on other targets requires either strong modeling assumptions (e.g. similarities among targets) or separate screens. Ideally, data-driven experimentation could be used to learn accurate models for many conditions and targets without doing all possible experiments. We have previously described an active machine learning algorithm that can iteratively choose small sets of experiments to learn models of multiple effects. We now show that, with no prior knowledge and with liquid handling robotics and automated microscopy under its control, this learner accurately learned the effects of 48 chemical compounds on the subcellular localization of 48 proteins while performing only 29% of all possible experiments. The results represent the first practical demonstration of the utility of active learning-driven biological experimentation in which the set of possible phenotypes is unknown in advance. DOI: http://dx.doi.org/10.7554/eLife.10047.001 PMID:26840049

Influence of intertrial interval on basal and drug-induced impulsive action in the 5-choice serial reaction time task: Effects of d-amphetamine and (±)-2,5-dimethoxy-4-iodoamphetamine (DOI).

PubMed

Fitzpatrick, Ciaràn M; Maric, Vojislav S; Bate, Simon T; Andreasen, Jesper T

2018-01-01

Impulsivity is a characteristic of a number of neuropsychiatric disorders such as attention-deficit/hyperactivity disorder. The 5-choice serial reaction time task (5-CSRTT) is a rodent paradigm extensively used to assess attention and impulsivity. Notably, 5-CSRTT studies do not typically account for the reduction in premature responding, the measure of impulsive action, occurring upon repeated exposure to test sessions with long or variable intertrial intervals (ITIs). This present 5-CSRTT study investigated the use of variable ITIs (5, 10 or 15s) across 15 test days (4 training days followed by 1 drug test day per week for three weeks) as previous experience had shown that 4 training days would be sufficient to induce consistent premature response levels in male C57BL/6J mice. Once a steady state was achieved, the effects of dextroamphetamine (AMPH) and (±)-2,5-dimethoxy-4-iodoamphetamine (DOI) were then assessed using a Latin-square design to determine whether pharmacological-induced impulsive actions depended on ITI length. Mice habituated to the variable ITI schedule after only 3days and showed consistently lower premature response levels until the end of the study. AMPH (p<0.05) and DOI (p<0.05) increased the percentage of premature responses at 15s ITI trials, while only DOI (p<0.05) increased impulsive action at 10s ITI trials. Additionally, DOI increased omission rates (p<0.001), mean correct latency (p<0.01), reward collection latency (p<0.001), and reduced the total attempted trials (p<0.001). In summary, we demonstrated that mice habituate to the variable ITI schedule, suggesting that using the variable ITI schedule during training allowed premature response rates to stabilize before commencing pharmacological testing. Moreover, in these habituated mice AMPH and DOI significantly enhanced impulsive action at the long ITI trials only. We propose that experimental design considerations can improve the sensitivity of the 5-CSRTT to detect pharmacologicallyinduced impulsive action. Copyright © 2017 Elsevier B.V. All rights reserved.

Ground-Atmosphere Interactions at Gale: Determination of the Surface Energy Budget, Thermal Inertia and Water Sorption on the Regolith

NASA Astrophysics Data System (ADS)

Martinez, German; Renno, Nilton; Fischer, Erik; Borlina, Caue; Hallet, Bernard; De la Torre Juarez, Manuel; Vasavada, Aswhin; Gomez-Elvira, Javier

2014-05-01

The analysis of the Surface Energy Budget (SEB) yields insights into the local climate and the soil-atmosphere interactions, while the analysis of the thermal inertia of the shallow subsurface augments surface observations, providing information about the local geology. The Mars Global Surveyor Thermal Emission Spectrometer and the Mars Odyssey Thermal Emission Imaging System have measured near subsurface thermal inertia from orbit at scales of ~104 m2 to ~10 km2. Here we report analysis of the thermal inertia at a few locations at Gale Crater at scales of 100 m2. The thermal inertia is calculated by solving the heat conduction equation in the soil using hourly measurements by the Rover Environmental Station (REMS) ground temperature sensor as an upper boundary condition. Three Sols representative of different environmental conditions and soil properties, namely, Sol 82 at Rocknest (RCK), Sol 112 at Point Lake (PL) and Sol 139 at Yellowknife Bay (YKB) are analyzed in detail. The largest thermal inertia (I) value is found at YKB, I = 445 J m-2 K-1 s-1/2 or 445 tiu (thermal inertia unit), followed by PL with I= 300 tiu and RCK withI = 280 tiu [1]. These values are consistent with the type of terrain imaged by MastCam and with previous satellite estimates at Gale Crater [2,3]. The SEB is calculated by using all REMS data products as well as dust opacity values derived from MastCam measurements, whereas previously, the SEB has been calculated using numerical models only [4]. At each location and during the daytime, the SEB is dominated by the downwelling shortwave (SW) solar radiation (~450-500 W/m2) and the upwelling longwave (LW) radiation emitted by the surface (~300-400 W/m2). The sum of these two terms accounts for at least 70% of the net surface heating rate between 0900 and 1400 local solar time. At nighttime, the SEB is dominated by the upwelling LW radiation emitted by the surface (~50-100 W/m2) and the downwelling LW radiation from the atmosphere (~50 W/m2). When the wind speeds exceed 10 m/s at night, the turbulent heat flux can be as large as 25 W/m2, thus playing a secondary but significant role in the SEB. Finally, we estimate the amount of adsorbed water exchanged between the shallow subsurface and the atmosphere at diurnal time scales. We use subsurface temperature profiles, obtained by solving the heat conduction equation in the soil using the calculated value of I, and adsorption and desorption isotherms [5] to analyze critically the correlation between the soil wetness measured by the Dynamic Albedo of Neutrons instrument and the relative humidity measured by REMS. Acknowledgement: This research is supported by a grant from the Mars Science Laboratory and NASA Astrobiology Program Award #09-EXOB09-0050. References: [1] Martinez, G.M. et al. (2014), JGR (submitted). [2] Pelkey, S. M., and B. M. Jakosky (2002), doi:10.1006/icar.2002.6978. [3] Fergason, R., P. et al. (2012), doi:10.1007/s11214-012-9891-3. [4] Savijärvi, H., and A. Määttänen (2010), doi:10.1002/qj.650. [5] Pommerol, A. et al. (2009), doi:10.1016/j.icarus.2009.06.013.

Monte Carlo simulations of time-of-flight PET with double-ended readout: calibration, coincidence resolving times and statistical lower bounds

PubMed Central

Derenzo, Stephen E

2017-01-01

This paper demonstrates through Monte Carlo simulations that a practical positron emission tomograph with (1) deep scintillators for efficient detection, (2) double-ended readout for depth-of-interaction information, (3) fixed-level analog triggering, and (4) accurate calibration and timing data corrections can achieve a coincidence resolving time (CRT) that is not far above the statistical lower bound. One Monte Carlo algorithm simulates a calibration procedure that uses data from a positron point source. Annihilation events with an interaction near the entrance surface of one scintillator are selected, and data from the two photodetectors on the other scintillator provide depth-dependent timing corrections. Another Monte Carlo algorithm simulates normal operation using these corrections and determines the CRT. A third Monte Carlo algorithm determines the CRT statistical lower bound by generating a series of random interaction depths, and for each interaction a set of random photoelectron times for each of the two photodetectors. The most likely interaction times are determined by shifting the depth-dependent probability density function to maximize the joint likelihood for all the photoelectron times in each set. Example calculations are tabulated for different numbers of photoelectrons and photodetector time jitters for three 3 × 3 × 30 mm3 scintillators: Lu2SiO5:Ce,Ca (LSO), LaBr3:Ce, and a hypothetical ultra-fast scintillator. To isolate the factors that depend on the scintillator length and the ability to estimate the DOI, CRT values are tabulated for perfect scintillator-photodetectors. For LSO with 4000 photoelectrons and single photoelectron time jitter of the photodetector J = 0.2 ns (FWHM), the CRT value using the statistically weighted average of corrected trigger times is 0.098 ns FWHM and the statistical lower bound is 0.091 ns FWHM. For LaBr3:Ce with 8000 photoelectrons and J = 0.2 ns FWHM, the CRT values are 0.070 and 0.063 ns FWHM, respectively. For the ultra-fast scintillator with 1 ns decay time, 4000 photoelectrons, and J = 0.2 ns FWHM, the CRT values are 0.021 and 0.017 ns FWHM, respectively. The examples also show that calibration and correction for depth-dependent variations in pulse height and in annihilation and optical photon transit times are necessary to achieve these CRT values. PMID:28327464

Monte Carlo simulations of time-of-flight PET with double-ended readout: calibration, coincidence resolving times and statistical lower bounds

DOE Office of Scientific and Technical Information (OSTI.GOV)

Derenzo, Stephen E.

Here, this paper demonstrates through Monte Carlo simulations that a practical positron emission tomograph with (1) deep scintillators for efficient detection, (2) double-ended readout for depth-of-interaction information, (3) fixed-level analog triggering, and (4) accurate calibration and timing data corrections can achieve a coincidence resolving time (CRT) that is not far above the statistical lower bound. One Monte Carlo algorithm simulates a calibration procedure that uses data from a positron point source. Annihilation events with an interaction near the entrance surface of one scintillator are selected, and data from the two photodetectors on the other scintillator provide depth-dependent timing corrections. Anothermore » Monte Carlo algorithm simulates normal operation using these corrections and determines the CRT. A third Monte Carlo algorithm determines the CRT statistical lower bound by generating a series of random interaction depths, and for each interaction a set of random photoelectron times for each of the two photodetectors. The most likely interaction times are determined by shifting the depth-dependent probability density function to maximize the joint likelihood for all the photoelectron times in each set. Example calculations are tabulated for different numbers of photoelectrons and photodetector time jitters for three 3 × 3 × 30 mm 3 scintillators: Lu 2SiO 5 :Ce,Ca (LSO), LaBr 3:Ce, and a hypothetical ultra-fast scintillator. To isolate the factors that depend on the scintillator length and the ability to estimate the DOI, CRT values are tabulated for perfect scintillator-photodetectors. For LSO with 4000 photoelectrons and single photoelectron time jitter of the photodetector J = 0.2 ns (FWHM), the CRT value using the statistically weighted average of corrected trigger times is 0.098 ns FWHM and the statistical lower bound is 0.091 ns FWHM. For LaBr 3:Ce with 8000 photoelectrons and J = 0.2 ns FWHM, the CRT values are 0.070 and 0.063 ns FWHM, respectively. For the ultra-fast scintillator with 1 ns decay time, 4000 photoelectrons, and J = 0.2 ns FWHM, the CRT values are 0.021 and 0.017 ns FWHM, respectively. Lastly, the examples also show that calibration and correction for depth-dependent variations in pulse height and in annihilation and optical photon transit times are necessary to achieve these CRT values.« less

Monte Carlo simulations of time-of-flight PET with double-ended readout: calibration, coincidence resolving times and statistical lower bounds

DOE PAGES

Derenzo, Stephen E.

2017-04-11

Here, this paper demonstrates through Monte Carlo simulations that a practical positron emission tomograph with (1) deep scintillators for efficient detection, (2) double-ended readout for depth-of-interaction information, (3) fixed-level analog triggering, and (4) accurate calibration and timing data corrections can achieve a coincidence resolving time (CRT) that is not far above the statistical lower bound. One Monte Carlo algorithm simulates a calibration procedure that uses data from a positron point source. Annihilation events with an interaction near the entrance surface of one scintillator are selected, and data from the two photodetectors on the other scintillator provide depth-dependent timing corrections. Anothermore » Monte Carlo algorithm simulates normal operation using these corrections and determines the CRT. A third Monte Carlo algorithm determines the CRT statistical lower bound by generating a series of random interaction depths, and for each interaction a set of random photoelectron times for each of the two photodetectors. The most likely interaction times are determined by shifting the depth-dependent probability density function to maximize the joint likelihood for all the photoelectron times in each set. Example calculations are tabulated for different numbers of photoelectrons and photodetector time jitters for three 3 × 3 × 30 mm 3 scintillators: Lu 2SiO 5 :Ce,Ca (LSO), LaBr 3:Ce, and a hypothetical ultra-fast scintillator. To isolate the factors that depend on the scintillator length and the ability to estimate the DOI, CRT values are tabulated for perfect scintillator-photodetectors. For LSO with 4000 photoelectrons and single photoelectron time jitter of the photodetector J = 0.2 ns (FWHM), the CRT value using the statistically weighted average of corrected trigger times is 0.098 ns FWHM and the statistical lower bound is 0.091 ns FWHM. For LaBr 3:Ce with 8000 photoelectrons and J = 0.2 ns FWHM, the CRT values are 0.070 and 0.063 ns FWHM, respectively. For the ultra-fast scintillator with 1 ns decay time, 4000 photoelectrons, and J = 0.2 ns FWHM, the CRT values are 0.021 and 0.017 ns FWHM, respectively. Lastly, the examples also show that calibration and correction for depth-dependent variations in pulse height and in annihilation and optical photon transit times are necessary to achieve these CRT values.« less

44 CFR 206.348 - Consultation.

Code of Federal Regulations, 2010 CFR

2010-10-01

... designated representative of the Department of the Interior (DOI) at the regional level before approving any.... (a) The consultation shall be by written memorandum to the DOI representative and shall contain the... understanding with DOI, the DOI representative will provide technical information and an opinion whether or not...

44 CFR 206.348 - Consultation.

Code of Federal Regulations, 2011 CFR

2011-10-01

... designated representative of the Department of the Interior (DOI) at the regional level before approving any.... (a) The consultation shall be by written memorandum to the DOI representative and shall contain the... understanding with DOI, the DOI representative will provide technical information and an opinion whether or not...

Implementing DOIs for Oceanographic Satellite Data at PO.DAAC

NASA Astrophysics Data System (ADS)

Hausman, J.; Tauer, E.; Chung, N.; Chen, C.; Moroni, D. F.

2013-12-01

The Physical Oceanographic Distributed Active Archive Center (PO.DAAC) is NASA's archive for physical oceanographic satellite data. It distributes over 500 datasets from gravity, ocean wind, sea surface topography, sea ice, ocean currents, salinity, and sea surface temperature satellite missions. A dataset is a collection of granules/files that share the same mission/project, versioning, processing level, spatial, and temporal characteristics. The large number of datasets is partially due to the number of satellite missions, but mostly because a single satellite mission typically has multiple versions or even temporal and spatial resolutions of data. As a result, a user might mistake one dataset for a different dataset from the same satellite mission. Due to the PO.DAAC'S vast variety and volume of data and growing requirements to report dataset usage, it has begun implementing DOIs for the datasets it archives and distributes. However, this was not as simple as registering a name for a DOI and providing a URL. Before implementing DOIs multiple questions needed to be answered. What are the sponsor and end-user expectations regarding DOIs? At what level does a DOI get assigned (dataset, file/granule)? Do all data get a DOI, or only selected data? How do we create a DOI? How do we create landing pages and manage them? What changes need to be made to the data archive, life cycle policy and web portal to accommodate DOIs? What if the data also exists at another archive and a DOI already exists? How is a DOI included if the data were obtained via a subsetting tool? How does a researcher or author provide a unique, definitive reference (standard citation) for a given dataset? This presentation will discuss how these questions were answered through changes in policy, process, and system design. Implementing DOIs is not a trivial undertaking, but as DOIs are rapidly becoming the de facto approach, it is worth the effort. Researchers have historically referenced the source satellite and data center (or archive), but scientific writings do not typically provide enough detail to point to a singular, uniquely identifiable dataset. DOIs provide the means to help researchers be precise in their data citations and provide needed clarity, standardization and permanence.

Wikipedia as a gateway to biomedical research: The relative distribution and use of citations in the English Wikipedia.

PubMed

Maggio, Lauren A; Willinsky, John M; Steinberg, Ryan M; Mietchen, Daniel; Wass, Joseph L; Dong, Ting

2017-01-01

Wikipedia is a gateway to knowledge. However, the extent to which this gateway ends at Wikipedia or continues via supporting citations is unknown. Wikipedia's gateway functionality has implications for information design and education, notably in medicine. This study aims to establish benchmarks for the relative distribution and referral (click) rate of citations-as indicated by presence of a Digital Object Identifier (DOI)-from Wikipedia, with a focus on medical citations. DOIs referred from the English Wikipedia in August 2016 were obtained from Crossref.org. Next, based on a DOI's presence on a WikiProject Medicine page, all DOIs in Wikipedia were categorized as medical (WP:MED) or non-medical (non-WP:MED). Using this categorization, referred DOIs were classified as WP:MED, non-WP:MED, or BOTH, meaning the DOI may have been referred from either category. Data were analyzed using descriptive and inferential statistics. Out of 5.2 million Wikipedia pages, 4.42% (n = 229,857) included at least one DOI. 68,870 were identified as WP:MED, with 22.14% (n = 15,250) featuring one or more DOIs. WP:MED pages featured on average 8.88 DOI citations per page, whereas non-WP:MED pages had on average 4.28 DOI citations. For DOIs only on WP:MED pages, a DOI was referred every 2,283 pageviews and for non-WP:MED pages every 2,467 pageviews. DOIs from BOTH pages accounted for 12% (n = 58,475). The referral of DOI citations found in BOTH could not be assigned to WP:MED or non-WP:MED, as the page from which the referral was made was not provided with the data. While these results cannot provide evidence of greater citation referral from WP:MED than non-WP:MED, they do provide benchmarks to assess strategies for changing referral patterns. These changes might include editors adopting new methods for designing and presenting citations or the introduction of teaching strategies that address the value of consulting citations as a tool for extending learning.

Duration of immunity for canine and feline vaccines: a review.

PubMed

Schultz, Ronald D

2006-10-05

In our studies aimed at assessing the minimum duration of vaccinal immunity (DOI), approximately 1000 dogs have been vaccinated with products from all the major US veterinary biological companies. The DOI for the various products is determined by antibody titers for all dogs and, by challenge studies in selected groups of dogs. Recently, all major companies that make canine vaccines for the U.S. market have completed their own studies; published data show a 3 years or longer minimum DOI for the canine core products, canine distemper virus (CDV), canine parvovirus type 2 (CPV-2), and canine adenovirus-2 (CAV-2). Studies with feline core vaccines - feline parvovirus (FPV), calicivirus (FCV) and herpes virus type I (FHV-1) have shown a minimum DOI of greater than 3 years. Based on these results, the current canine and feline guidelines (which recommend that the last dose of core vaccines be given to puppies and kittens > or =12 weeks of age or older, then revaccination again at 1 year, then not more often than every 3 years) should provide a level of protection equal to that achieved by annual revaccination. In contrast, the non-core canine and feline vaccines, perhaps with the exception of feline leukaemia vaccines, provide immunity for < or =1 year. In general the effectiveness of the non-core products is less than the core products. Thus, when required, non-core vaccines should be administered yearly, or even more frequently.

43 CFR 17.332 - Mediation.

Code of Federal Regulations, 2011 CFR

2011-10-01

..., and Enforcement Procedures § 17.332 Mediation. (a) Referral of complaints for mediation. DOI will... it. The FMCS shall send the agreement to DOI. DOI, however, retains the right to monitor the... process without prior approval of the head of the mediation agency. (e) DOI will use the mediation process...

A genome-wide resource for the analysis of protein localisation in Drosophila

PubMed Central

Sarov, Mihail; Barz, Christiane; Jambor, Helena; Hein, Marco Y; Schmied, Christopher; Suchold, Dana; Stender, Bettina; Janosch, Stephan; KJ, Vinay Vikas; Krishnan, RT; Krishnamoorthy, Aishwarya; Ferreira, Irene RS; Ejsmont, Radoslaw K; Finkl, Katja; Hasse, Susanne; Kämpfer, Philipp; Plewka, Nicole; Vinis, Elisabeth; Schloissnig, Siegfried; Knust, Elisabeth; Hartenstein, Volker; Mann, Matthias; Ramaswami, Mani; VijayRaghavan, K; Tomancak, Pavel; Schnorrer, Frank

2016-01-01

The Drosophila genome contains >13000 protein-coding genes, the majority of which remain poorly investigated. Important reasons include the lack of antibodies or reporter constructs to visualise these proteins. Here, we present a genome-wide fosmid library of 10000 GFP-tagged clones, comprising tagged genes and most of their regulatory information. For 880 tagged proteins, we created transgenic lines, and for a total of 207 lines, we assessed protein expression and localisation in ovaries, embryos, pupae or adults by stainings and live imaging approaches. Importantly, we visualised many proteins at endogenous expression levels and found a large fraction of them localising to subcellular compartments. By applying genetic complementation tests, we estimate that about two-thirds of the tagged proteins are functional. Moreover, these tagged proteins enable interaction proteomics from developing pupae and adult flies. Taken together, this resource will boost systematic analysis of protein expression and localisation in various cellular and developmental contexts. DOI: http://dx.doi.org/10.7554/eLife.12068.001 PMID:26896675

Task-dependent recurrent dynamics in visual cortex

PubMed Central

Tajima, Satohiro; Koida, Kowa; Tajima, Chihiro I; Suzuki, Hideyuki; Aihara, Kazuyuki; Komatsu, Hidehiko

2017-01-01

The capacity for flexible sensory-action association in animals has been related to context-dependent attractor dynamics outside the sensory cortices. Here, we report a line of evidence that flexibly modulated attractor dynamics during task switching are already present in the higher visual cortex in macaque monkeys. With a nonlinear decoding approach, we can extract the particular aspect of the neural population response that reflects the task-induced emergence of bistable attractor dynamics in a neural population, which could be obscured by standard unsupervised dimensionality reductions such as PCA. The dynamical modulation selectively increases the information relevant to task demands, indicating that such modulation is beneficial for perceptual decisions. A computational model that features nonlinear recurrent interaction among neurons with a task-dependent background input replicates the key properties observed in the experimental data. These results suggest that the context-dependent attractor dynamics involving the sensory cortex can underlie flexible perceptual abilities. DOI: http://dx.doi.org/10.7554/eLife.26868.001 PMID:28737487

Cohabiting family members share microbiota with one another and with their dogs.

PubMed

Song, Se Jin; Lauber, Christian; Costello, Elizabeth K; Lozupone, Catherine A; Humphrey, Gregory; Berg-Lyons, Donna; Caporaso, J Gregory; Knights, Dan; Clemente, Jose C; Nakielny, Sara; Gordon, Jeffrey I; Fierer, Noah; Knight, Rob

2013-04-16

Human-associated microbial communities vary across individuals: possible contributing factors include (genetic) relatedness, diet, and age. However, our surroundings, including individuals with whom we interact, also likely shape our microbial communities. To quantify this microbial exchange, we surveyed fecal, oral, and skin microbiota from 60 families (spousal units with children, dogs, both, or neither). Household members, particularly couples, shared more of their microbiota than individuals from different households, with stronger effects of co-habitation on skin than oral or fecal microbiota. Dog ownership significantly increased the shared skin microbiota in cohabiting adults, and dog-owning adults shared more 'skin' microbiota with their own dogs than with other dogs. Although the degree to which these shared microbes have a true niche on the human body, vs transient detection after direct contact, is unknown, these results suggest that direct and frequent contact with our cohabitants may significantly shape the composition of our microbial communities. DOI:http://dx.doi.org/10.7554/eLife.00458.001.

Cohabiting family members share microbiota with one another and with their dogs

PubMed Central

Song, Se Jin; Lauber, Christian; Costello, Elizabeth K; Lozupone, Catherine A; Humphrey, Gregory; Berg-Lyons, Donna; Caporaso, J Gregory; Knights, Dan; Clemente, Jose C; Nakielny, Sara; Gordon, Jeffrey I; Fierer, Noah; Knight, Rob

2013-01-01

Human-associated microbial communities vary across individuals: possible contributing factors include (genetic) relatedness, diet, and age. However, our surroundings, including individuals with whom we interact, also likely shape our microbial communities. To quantify this microbial exchange, we surveyed fecal, oral, and skin microbiota from 60 families (spousal units with children, dogs, both, or neither). Household members, particularly couples, shared more of their microbiota than individuals from different households, with stronger effects of co-habitation on skin than oral or fecal microbiota. Dog ownership significantly increased the shared skin microbiota in cohabiting adults, and dog-owning adults shared more ‘skin’ microbiota with their own dogs than with other dogs. Although the degree to which these shared microbes have a true niche on the human body, vs transient detection after direct contact, is unknown, these results suggest that direct and frequent contact with our cohabitants may significantly shape the composition of our microbial communities. DOI: http://dx.doi.org/10.7554/eLife.00458.001 PMID:23599893

A bend, flip and trap mechanism for transposon integration

PubMed Central

Morris, Elizabeth R; Grey, Heather; McKenzie, Grant; Jones, Anita C; Richardson, Julia M

2016-01-01

Cut-and-paste DNA transposons of the mariner/Tc1 family are useful tools for genome engineering and are inserted specifically at TA target sites. A crystal structure of the mariner transposase Mos1 (derived from Drosophila mauritiana), in complex with transposon ends covalently joined to target DNA, portrays the transposition machinery after DNA integration. It reveals severe distortion of target DNA and flipping of the target adenines into extra-helical positions. Fluorescence experiments confirm dynamic base flipping in solution. Transposase residues W159, R186, F187 and K190 stabilise the target DNA distortions and are required for efficient transposon integration and transposition in vitro. Transposase recognises the flipped target adenines via base-specific interactions with backbone atoms, offering a molecular basis for TA target sequence selection. Our results will provide a template for re-designing mariner/Tc1 transposases with modified target specificities. DOI: http://dx.doi.org/10.7554/eLife.15537.001 PMID:27223327

Sequential selection of economic good and action in medial frontal cortex of macaques during value-based decisions

PubMed Central

Chen, Xiaomo; Stuphorn, Veit

2015-01-01

Value-based decisions could rely either on the selection of desired economic goods or on the selection of the actions that will obtain the goods. We investigated this question by recording from the supplementary eye field (SEF) of monkeys during a gambling task that allowed us to distinguish chosen good from chosen action signals. Analysis of the individual neuron activity, as well as of the population state-space dynamic, showed that SEF encodes first the chosen gamble option (the desired economic good) and only ~100 ms later the saccade that will obtain it (the chosen action). The action selection is likely driven by inhibitory interactions between different SEF neurons. Our results suggest that during value-based decisions, the selection of economic goods precedes and guides the selection of actions. The two selection steps serve different functions and can therefore not compensate for each other, even when information guiding both processes is given simultaneously. DOI: http://dx.doi.org/10.7554/eLife.09418.001 PMID:26613409

New learning while consolidating memory during sleep is actively blocked by a protein synthesis dependent process

PubMed Central

Levy, Roi; Levitan, David; Susswein, Abraham J

2016-01-01

Brief experiences while a memory is consolidated may capture the consolidation, perhaps producing a maladaptive memory, or may interrupt the consolidation. Since consolidation occurs during sleep, even fleeting experiences when animals are awakened may produce maladaptive long-term memory, or may interrupt consolidation. In a learning paradigm affecting Aplysia feeding, when animals were trained after being awakened from sleep, interactions between new experiences and consolidation were prevented by blocking long-term memory arising from the new experiences. Inhibiting protein synthesis eliminated the block and allowed even a brief, generally ineffective training to produce long-term memory. Memory formation depended on consolidative proteins already expressed before training. After effective training, long term memory required subsequent transcription and translation. Memory formation during the sleep phase was correlated with increased CREB1 transcription, but not CREB2 transcription. Increased C/EBP transcription was a correlate of both effective and ineffective training and of treatments not producing memory. DOI: http://dx.doi.org/10.7554/eLife.17769.001 PMID:27919318

A role for PVRL4-driven cell–cell interactions in tumorigenesis

PubMed Central

Pavlova, Natalya N; Pallasch, Christian; Elia, Andrew EH; Braun, Christian J; Westbrook, Thomas F; Hemann, Michael; Elledge, Stephen J

2013-01-01

During all stages of tumor progression, cancer cells are subjected to inappropriate extracellular matrix environments and must undergo adaptive changes in order to evade growth constraints associated with the loss of matrix attachment. A gain of function screen for genes that enable proliferation independently of matrix anchorage identified a cell adhesion molecule PVRL4 (poliovirus-receptor-like 4), also known as Nectin-4. PVRL4 promotes anchorage-independence by driving cell-to-cell attachment and matrix-independent integrin β4/SHP-2/c-Src activation. Solid tumors frequently have copy number gains of the PVRL4 locus and some have focal amplifications. We demonstrate that the transformation of breast cancer cells is dependent on PVRL4. Furthermore, growth of orthotopically implanted tumors in vivo is inhibited by blocking PVRL4-driven cell-to-cell attachment with monoclonal antibodies, demonstrating a novel strategy for targeted therapy of cancer. DOI: http://dx.doi.org/10.7554/eLife.00358.001 PMID:23682311

Many-molecule encapsulation by an icosahedral shell

PubMed Central

Perlmutter, Jason D; Mohajerani, Farzaneh; Hagan, Michael F

2016-01-01

We computationally study how an icosahedral shell assembles around hundreds of molecules. Such a process occurs during the formation of the carboxysome, a bacterial microcompartment that assembles around many copies of the enzymes ribulose 1,5-bisphosphate carboxylase/ oxygenase and carbonic anhydrase to facilitate carbon fixation in cyanobacteria. Our simulations identify two classes of assembly pathways leading to encapsulation of many-molecule cargoes. In one, shell assembly proceeds concomitantly with cargo condensation. In the other, the cargo first forms a dense globule; then, shell proteins assemble around and bud from the condensed cargo complex. Although the model is simplified, the simulations predict intermediates and closure mechanisms not accessible in experiments, and show how assembly can be tuned between these two pathways by modulating protein interactions. In addition to elucidating assembly pathways and critical control parameters for microcompartment assembly, our results may guide the reengineering of viruses as nanoreactors that self-assemble around their reactants. DOI: http://dx.doi.org/10.7554/eLife.14078.001 PMID:27166515

The evolution of distributed sensing and collective computation in animal populations

PubMed Central

Hein, Andrew M; Rosenthal, Sara Brin; Hagstrom, George I; Berdahl, Andrew; Torney, Colin J; Couzin, Iain D

2015-01-01

Many animal groups exhibit rapid, coordinated collective motion. Yet, the evolutionary forces that cause such collective responses to evolve are poorly understood. Here, we develop analytical methods and evolutionary simulations based on experimental data from schooling fish. We use these methods to investigate how populations evolve within unpredictable, time-varying resource environments. We show that populations evolve toward a distinctive regime in behavioral phenotype space, where small responses of individuals to local environmental cues cause spontaneous changes in the collective state of groups. These changes resemble phase transitions in physical systems. Through these transitions, individuals evolve the emergent capacity to sense and respond to resource gradients (i.e. individuals perceive gradients via social interactions, rather than sensing gradients directly), and to allocate themselves among distinct, distant resource patches. Our results yield new insight into how natural selection, acting on selfish individuals, results in the highly effective collective responses evident in nature. DOI: http://dx.doi.org/10.7554/eLife.10955.001 PMID:26652003

A mammalian pseudogene lncRNA at the interface of inflammation and anti-inflammatory therapeutics

PubMed Central

Rapicavoli, Nicole A; Qu, Kun; Zhang, Jiajing; Mikhail, Megan; Laberge, Remi-Martin; Chang, Howard Y

2013-01-01

Pseudogenes are thought to be inactive gene sequences, but recent evidence of extensive pseudogene transcription raised the question of potential function. Here we discover and characterize the sets of mouse lncRNAs induced by inflammatory signaling via TNFα. TNFα regulates hundreds of lncRNAs, including 54 pseudogene lncRNAs, several of which show exquisitely selective expression in response to specific cytokines and microbial components in a NF-κB-dependent manner. Lethe, a pseudogene lncRNA, is selectively induced by proinflammatory cytokines via NF-κB or glucocorticoid receptor agonist, and functions in negative feedback signaling to NF-κB. Lethe interacts with NF-κB subunit RelA to inhibit RelA DNA binding and target gene activation. Lethe level decreases with organismal age, a physiological state associated with increased NF-κB activity. These findings suggest that expression of pseudogenes lncRNAs are actively regulated and constitute functional regulators of inflammatory signaling. DOI: http://dx.doi.org/10.7554/eLife.00762.001 PMID:23898399

Metabolic network rewiring of propionate flux compensates vitamin B12 deficiency in C. elegans

PubMed Central

Watson, Emma; Olin-Sandoval, Viridiana; Hoy, Michael J; Li, Chi-Hua; Louisse, Timo; Yao, Victoria; Mori, Akihiro; Holdorf, Amy D; Troyanskaya, Olga G; Ralser, Markus; Walhout, Albertha JM

2016-01-01

Metabolic network rewiring is the rerouting of metabolism through the use of alternate enzymes to adjust pathway flux and accomplish specific anabolic or catabolic objectives. Here, we report the first characterization of two parallel pathways for the breakdown of the short chain fatty acid propionate in Caenorhabditis elegans. Using genetic interaction mapping, gene co-expression analysis, pathway intermediate quantification and carbon tracing, we uncover a vitamin B12-independent propionate breakdown shunt that is transcriptionally activated on vitamin B12 deficient diets, or under genetic conditions mimicking the human diseases propionic- and methylmalonic acidemia, in which the canonical B12-dependent propionate breakdown pathway is blocked. Our study presents the first example of transcriptional vitamin-directed metabolic network rewiring to promote survival under vitamin deficiency. The ability to reroute propionate breakdown according to B12 availability may provide C. elegans with metabolic plasticity and thus a selective advantage on different diets in the wild. DOI: http://dx.doi.org/10.7554/eLife.17670.001 PMID:27383050

Unexpected arousal modulates the influence of sensory noise on confidence

PubMed Central

Allen, Micah; Frank, Darya; Schwarzkopf, D Samuel; Fardo, Francesca; Winston, Joel S; Hauser, Tobias U; Rees, Geraint

2016-01-01

Human perception is invariably accompanied by a graded feeling of confidence that guides metacognitive awareness and decision-making. It is often assumed that this arises solely from the feed-forward encoding of the strength or precision of sensory inputs. In contrast, interoceptive inference models suggest that confidence reflects a weighted integration of sensory precision and expectations about internal states, such as arousal. Here we test this hypothesis using a novel psychophysical paradigm, in which unseen disgust-cues induced unexpected, unconscious arousal just before participants discriminated motion signals of variable precision. Across measures of perceptual bias, uncertainty, and physiological arousal we found that arousing disgust cues modulated the encoding of sensory noise. Furthermore, the degree to which trial-by-trial pupil fluctuations encoded this nonlinear interaction correlated with trial level confidence. Our results suggest that unexpected arousal regulates perceptual precision, such that subjective confidence reflects the integration of both external sensory and internal, embodied states. DOI: http://dx.doi.org/10.7554/eLife.18103.001 PMID:27776633

Capturing the temporal evolution of choice across prefrontal cortex

PubMed Central

Hunt, Laurence T; Behrens, Timothy EJ; Hosokawa, Takayuki; Wallis, Jonathan D; Kennerley, Steven W

2015-01-01

Activity in prefrontal cortex (PFC) has been richly described using economic models of choice. Yet such descriptions fail to capture the dynamics of decision formation. Describing dynamic neural processes has proven challenging due to the problem of indexing the internal state of PFC and its trial-by-trial variation. Using primate neurophysiology and human magnetoencephalography, we here recover a single-trial index of PFC internal states from multiple simultaneously recorded PFC subregions. This index can explain the origins of neural representations of economic variables in PFC. It describes the relationship between neural dynamics and behaviour in both human and monkey PFC, directly bridging between human neuroimaging data and underlying neuronal activity. Moreover, it reveals a functionally dissociable interaction between orbitofrontal cortex, anterior cingulate cortex and dorsolateral PFC in guiding cost-benefit decisions. We cast our observations in terms of a recurrent neural network model of choice, providing formal links to mechanistic dynamical accounts of decision-making. DOI: http://dx.doi.org/10.7554/eLife.11945.001 PMID:26653139

Affimer proteins are versatile and renewable affinity reagents

PubMed Central

Tiede, Christian; Bedford, Robert; Heseltine, Sophie J; Smith, Gina; Wijetunga, Imeshi; Ross, Rebecca; AlQallaf, Danah; Roberts, Ashley PE; Balls, Alexander; Curd, Alistair; Hughes, Ruth E; Martin, Heather; Needham, Sarah R; Zanetti-Domingues, Laura C; Sadigh, Yashar; Peacock, Thomas P; Tang, Anna A; Gibson, Naomi; Kyle, Hannah; Platt, Geoffrey W; Ingram, Nicola; Taylor, Thomas; Coletta, Louise P; Manfield, Iain; Knowles, Margaret; Bell, Sandra; Esteves, Filomena; Maqbool, Azhar; Prasad, Raj K; Drinkhill, Mark; Bon, Robin S; Patel, Vikesh; Goodchild, Sarah A; Martin-Fernandez, Marisa; Owens, Ray J; Nettleship, Joanne E; Webb, Michael E; Harrison, Michael; Lippiat, Jonathan D; Ponnambalam, Sreenivasan; Peckham, Michelle; Smith, Alastair; Ferrigno, Paul Ko; Johnson, Matt; McPherson, Michael J; Tomlinson, Darren Charles

2017-01-01

Molecular recognition reagents are key tools for understanding biological processes and are used universally by scientists to study protein expression, localisation and interactions. Antibodies remain the most widely used of such reagents and many show excellent performance, although some are poorly characterised or have stability or batch variability issues, supporting the use of alternative binding proteins as complementary reagents for many applications. Here we report on the use of Affimer proteins as research reagents. We selected 12 diverse molecular targets for Affimer selection to exemplify their use in common molecular and cellular applications including the (a) selection against various target molecules; (b) modulation of protein function in vitro and in vivo; (c) labelling of tumour antigens in mouse models; and (d) use in affinity fluorescence and super-resolution microscopy. This work shows that Affimer proteins, as is the case for other alternative binding scaffolds, represent complementary affinity reagents to antibodies for various molecular and cell biology applications. DOI: http://dx.doi.org/10.7554/eLife.24903.001 PMID:28654419

Structural snapshots of Xer recombination reveal activation by synaptic complex remodeling and DNA bending

PubMed Central

Bebel, Aleksandra; Karaca, Ezgi; Kumar, Banushree; Stark, W Marshall; Barabas, Orsolya

2016-01-01

Bacterial Xer site-specific recombinases play an essential genome maintenance role by unlinking chromosome multimers, but their mechanism of action has remained structurally uncharacterized. Here, we present two high-resolution structures of Helicobacter pylori XerH with its recombination site DNA difH, representing pre-cleavage and post-cleavage synaptic intermediates in the recombination pathway. The structures reveal that activation of DNA strand cleavage and rejoining involves large conformational changes and DNA bending, suggesting how interaction with the cell division protein FtsK may license recombination at the septum. Together with biochemical and in vivo analysis, our structures also reveal how a small sequence asymmetry in difH defines protein conformation in the synaptic complex and orchestrates the order of DNA strand exchanges. Our results provide insights into the catalytic mechanism of Xer recombination and a model for regulation of recombination activity during cell division. DOI: http://dx.doi.org/10.7554/eLife.19706.001 PMID:28009253

FlpStop, a tool for conditional gene control in Drosophila

PubMed Central

Fisher, Yvette E; Yang, Helen H; Isaacman-Beck, Jesse; Xie, Marjorie; Gohl, Daryl M; Clandinin, Thomas R

2017-01-01

Manipulating gene function cell type-specifically is a common experimental goal in Drosophila research and has been central to studies of neural development, circuit computation, and behavior. However, current cell type-specific gene disruption techniques in flies often reduce gene activity incompletely or rely on cell division. Here we describe FlpStop, a generalizable tool for conditional gene disruption and rescue in post-mitotic cells. In proof-of-principle experiments, we manipulated apterous, a regulator of wing development. Next, we produced conditional null alleles of Glutamic acid decarboxylase 1 (Gad1) and Resistant to dieldrin (Rdl), genes vital for GABAergic neurotransmission, as well as cacophony (cac) and paralytic (para), voltage-gated ion channels central to neuronal excitability. To demonstrate the utility of this approach, we manipulated cac in a specific visual interneuron type and discovered differential regulation of calcium signals across subcellular compartments. Thus, FlpStop will facilitate investigations into the interactions between genes, circuits, and computation. DOI: http://dx.doi.org/10.7554/eLife.22279.001 PMID:28211790

Target DNA bending by the Mu transpososome promotes careful transposition and prevents its reversal

PubMed Central

Fuller, James R; Rice, Phoebe A

2017-01-01

The transposition of bacteriophage Mu serves as a model system for understanding DDE transposases and integrases. All available structures of these enzymes at the end of the transposition reaction, including Mu, exhibit significant bends in the transposition target site DNA. Here we use Mu to investigate the ramifications of target DNA bending on the transposition reaction. Enhancing the flexibility of the target DNA or prebending it increases its affinity for transpososomes by over an order of magnitude and increases the overall reaction rate. This and FRET confirm that flexibility is interrogated early during the interaction between the transposase and a potential target site, which may be how other DNA binding proteins can steer selection of advantageous target sites. We also find that the conformation of the target DNA after strand transfer is involved in preventing accidental catalysis of the reverse reaction, as conditions that destabilize this conformation also trigger reversal. DOI: http://dx.doi.org/10.7554/eLife.21777.001 PMID:28177285

Super Spy variants implicate flexibility in chaperone action.

PubMed

Quan, Shu; Wang, Lili; Petrotchenko, Evgeniy V; Makepeace, Karl At; Horowitz, Scott; Yang, Jianyi; Zhang, Yang; Borchers, Christoph H; Bardwell, James Ca

2014-01-01

Experimental study of the role of disorder in protein function is challenging. It has been proposed that proteins utilize disordered regions in the adaptive recognition of their various binding partners. However apart from a few exceptions, defining the importance of disorder in promiscuous binding interactions has proven to be difficult. In this paper, we have utilized a genetic selection that links protein stability to antibiotic resistance to isolate variants of the newly discovered chaperone Spy that show an up to 7 fold improved chaperone activity against a variety of substrates. These "Super Spy" variants show tighter binding to client proteins and are generally more unstable than is wild type Spy and show increases in apparent flexibility. We establish a good relationship between the degree of their instability and the improvement they show in their chaperone activity. Our results provide evidence for the importance of disorder and flexibility in chaperone function. DOI: http://dx.doi.org/10.7554/eLife.01584.001.

Super Spy variants implicate flexibility in chaperone action

PubMed Central

Quan, Shu; Wang, Lili; Petrotchenko, Evgeniy V; Makepeace, Karl AT; Horowitz, Scott; Yang, Jianyi; Zhang, Yang; Borchers, Christoph H; Bardwell, James CA

2014-01-01

Experimental study of the role of disorder in protein function is challenging. It has been proposed that proteins utilize disordered regions in the adaptive recognition of their various binding partners. However apart from a few exceptions, defining the importance of disorder in promiscuous binding interactions has proven to be difficult. In this paper, we have utilized a genetic selection that links protein stability to antibiotic resistance to isolate variants of the newly discovered chaperone Spy that show an up to 7 fold improved chaperone activity against a variety of substrates. These “Super Spy” variants show tighter binding to client proteins and are generally more unstable than is wild type Spy and show increases in apparent flexibility. We establish a good relationship between the degree of their instability and the improvement they show in their chaperone activity. Our results provide evidence for the importance of disorder and flexibility in chaperone function. DOI: http://dx.doi.org/10.7554/eLife.01584.001 PMID:24497545

A dystonia-like movement disorder with brain and spinal neuronal defects is caused by mutation of the mouse laminin β1 subunit, Lamb1

PubMed Central

Liu, Yi Bessie; Tewari, Ambika; Salameh, Johnny; Arystarkhova, Elena; Hampton, Thomas G; Brashear, Allison; Ozelius, Laurie J; Khodakhah, Kamran; Sweadner, Kathleen J

2015-01-01

A new mutant mouse (lamb1t) exhibits intermittent dystonic hindlimb movements and postures when awake, and hyperextension when asleep. Experiments showed co-contraction of opposing muscle groups, and indicated that symptoms depended on the interaction of brain and spinal cord. SNP mapping and exome sequencing identified the dominant causative mutation in the Lamb1 gene. Laminins are extracellular matrix proteins, widely expressed but also known to be important in synapse structure and plasticity. In accordance, awake recording in the cerebellum detected abnormal output from a circuit of two Lamb1-expressing neurons, Purkinje cells and their deep cerebellar nucleus targets, during abnormal postures. We propose that dystonia-like symptoms result from lapses in descending inhibition, exposing excess activity in intrinsic spinal circuits that coordinate muscles. The mouse is a new model for testing how dysfunction in the CNS causes specific abnormal movements and postures. DOI: http://dx.doi.org/10.7554/eLife.11102.001 PMID:26705335

A secreted Ustilago maydis effector promotes virulence by targeting anthocyanin biosynthesis in maize

PubMed Central

Tanaka, Shigeyuki; Brefort, Thomas; Neidig, Nina; Djamei, Armin; Kahnt, Jörg; Vermerris, Wilfred; Koenig, Stefanie; Feussner, Kirstin; Feussner, Ivo; Kahmann, Regine

2014-01-01

The biotrophic fungus Ustilago maydis causes smut disease in maize with characteristic tumor formation and anthocyanin induction. Here, we show that anthocyanin biosynthesis is induced by the virulence promoting secreted effector protein Tin2. Tin2 protein functions inside plant cells where it interacts with maize protein kinase ZmTTK1. Tin2 masks a ubiquitin–proteasome degradation motif in ZmTTK1, thus stabilizing the active kinase. Active ZmTTK1 controls activation of genes in the anthocyanin biosynthesis pathway. Without Tin2, enhanced lignin biosynthesis is observed in infected tissue and vascular bundles show strong lignification. This is presumably limiting access of fungal hyphae to nutrients needed for massive proliferation. Consistent with this assertion, we observe that maize brown midrib mutants affected in lignin biosynthesis are hypersensitive to U. maydis infection. We speculate that Tin2 rewires metabolites into the anthocyanin pathway to lower their availability for other defense responses. DOI: http://dx.doi.org/10.7554/eLife.01355.001 PMID:24473076

A common bacterial metabolite elicits prion-based bypass of glucose repression

PubMed Central

Garcia, David M; Dietrich, David; Clardy, Jon; Jarosz, Daniel F

2016-01-01

Robust preference for fermentative glucose metabolism has motivated domestication of the budding yeast Saccharomyces cerevisiae. This program can be circumvented by a protein-based genetic element, the [GAR+] prion, permitting simultaneous metabolism of glucose and other carbon sources. Diverse bacteria can elicit yeast cells to acquire [GAR+], although the molecular details of this interaction remain unknown. Here we identify the common bacterial metabolite lactic acid as a strong [GAR+] inducer. Transient exposure to lactic acid caused yeast cells to heritably circumvent glucose repression. This trait had the defining genetic properties of [GAR+], and did not require utilization of lactic acid as a carbon source. Lactic acid also induced [GAR+]-like epigenetic states in fungi that diverged from S. cerevisiae ~200 million years ago, and in which glucose repression evolved independently. To our knowledge, this is the first study to uncover a bacterial metabolite with the capacity to potently induce a prion. DOI: http://dx.doi.org/10.7554/eLife.17978.001 PMID:27906649

Essential role of lncRNA binding for WDR5 maintenance of active chromatin and embryonic stem cell pluripotency

PubMed Central

Yang, Yul W; Flynn, Ryan A; Chen, Yong; Qu, Kun; Wan, Bingbing; Wang, Kevin C; Lei, Ming; Chang, Howard Y

2014-01-01

The WDR5 subunit of the MLL complex enforces active chromatin and can bind RNA; the relationship between these two activities is unclear. Here we identify a RNA binding pocket on WDR5, and discover a WDR5 mutant (F266A) that selectively abrogates RNA binding without affecting MLL complex assembly or catalytic activity. Complementation in ESCs shows that WDR5 F266A mutant is unable to accumulate on chromatin, and is defective in gene activation, maintenance of histone H3 lysine 4 trimethylation, and ESC self renewal. We identify a family of ESC messenger and lncRNAs that interact with wild type WDR5 but not F266A mutant, including several lncRNAs known to be important for ESC gene expression. These results suggest that specific RNAs are integral inputs into the WDR5-MLL complex for maintenance of the active chromatin state and embryonic stem cell fates. DOI: http://dx.doi.org/10.7554/eLife.02046.001 PMID:24521543

The dynamic three-dimensional organization of the diploid yeast genome

PubMed Central

Kim, Seungsoo; Liachko, Ivan; Brickner, Donna G; Cook, Kate; Noble, William S; Brickner, Jason H; Shendure, Jay; Dunham, Maitreya J

2017-01-01

The budding yeast Saccharomyces cerevisiae is a long-standing model for the three-dimensional organization of eukaryotic genomes. However, even in this well-studied model, it is unclear how homolog pairing in diploids or environmental conditions influence overall genome organization. Here, we performed high-throughput chromosome conformation capture on diverged Saccharomyces hybrid diploids to obtain the first global view of chromosome conformation in diploid yeasts. After controlling for the Rabl-like orientation using a polymer model, we observe significant homolog proximity that increases in saturated culture conditions. Surprisingly, we observe a localized increase in homologous interactions between the HAS1-TDA1 alleles specifically under galactose induction and saturated growth. This pairing is accompanied by relocalization to the nuclear periphery and requires Nup2, suggesting a role for nuclear pore complexes. Together, these results reveal that the diploid yeast genome has a dynamic and complex 3D organization. DOI: http://dx.doi.org/10.7554/eLife.23623.001 PMID:28537556

Population genomics of intrapatient HIV-1 evolution

PubMed Central

Zanini, Fabio; Brodin, Johanna; Thebo, Lina; Lanz, Christa; Bratt, Göran; Albert, Jan; Neher, Richard A

2015-01-01

Many microbial populations rapidly adapt to changing environments with multiple variants competing for survival. To quantify such complex evolutionary dynamics in vivo, time resolved and genome wide data including rare variants are essential. We performed whole-genome deep sequencing of HIV-1 populations in 9 untreated patients, with 6-12 longitudinal samples per patient spanning 5-8 years of infection. The data can be accessed and explored via an interactive web application. We show that patterns of minor diversity are reproducible between patients and mirror global HIV-1 diversity, suggesting a universal landscape of fitness costs that control diversity. Reversions towards the ancestral HIV-1 sequence are observed throughout infection and account for almost one third of all sequence changes. Reversion rates depend strongly on conservation. Frequent recombination limits linkage disequilibrium to about 100bp in most of the genome, but strong hitch-hiking due to short range linkage limits diversity. DOI: http://dx.doi.org/10.7554/eLife.11282.001 PMID:26652000

Temporal dynamics and developmental memory of 3D chromatin architecture at Hox gene loci

PubMed Central

Noordermeer, Daan; Leleu, Marion; Schorderet, Patrick; Joye, Elisabeth; Chabaud, Fabienne; Duboule, Denis

2014-01-01

Hox genes are essential regulators of embryonic development. Their step-wise transcriptional activation follows their genomic topology and the various states of activation are subsequently memorized into domains of progressively overlapping gene products. We have analyzed the 3D chromatin organization of Hox clusters during their early activation in vivo, using high-resolution circular chromosome conformation capture. Initially, Hox clusters are organized as single chromatin compartments containing all genes and bivalent chromatin marks. Transcriptional activation is associated with a dynamic bi-modal 3D organization, whereby the genes switch autonomously from an inactive to an active compartment. These local 3D dynamics occur within a framework of constitutive interactions within the surrounding Topological Associated Domains, indicating that this regulation process is mostly cluster intrinsic. The step-wise progression in time is fixed at various body levels and thus can account for the chromatin architectures previously described at a later stage for different anterior to posterior levels. DOI: http://dx.doi.org/10.7554/eLife.02557.001 PMID:24843030

The force-sensing peptide VemP employs extreme compaction and secondary structure formation to induce ribosomal stalling

PubMed Central

Su, Ting; Cheng, Jingdong; Sohmen, Daniel; Hedman, Rickard; Berninghausen, Otto; von Heijne, Gunnar; Wilson, Daniel N; Beckmann, Roland

2017-01-01

Interaction between the nascent polypeptide chain and the ribosomal exit tunnel can modulate the rate of translation and induce translational arrest to regulate expression of downstream genes. The ribosomal tunnel also provides a protected environment for initial protein folding events. Here, we present a 2.9 Å cryo-electron microscopy structure of a ribosome stalled during translation of the extremely compacted VemP nascent chain. The nascent chain forms two α-helices connected by an α-turn and a loop, enabling a total of 37 amino acids to be observed within the first 50–55 Å of the exit tunnel. The structure reveals how α-helix formation directly within the peptidyltransferase center of the ribosome interferes with aminoacyl-tRNA accommodation, suggesting that during canonical translation, a major role of the exit tunnel is to prevent excessive secondary structure formation that can interfere with the peptidyltransferase activity of the ribosome. DOI: http://dx.doi.org/10.7554/eLife.25642.001 PMID:28556777

Engineering vanilloid-sensitivity into the rat TRPV2 channel

PubMed Central

Zhang, Feng; Hanson, Sonya M; Jara-Oseguera, Andres; Krepkiy, Dmitriy; Bae, Chanhyung; Pearce, Larry V; Blumberg, Peter M; Newstead, Simon; Swartz, Kenton J

2016-01-01

The TRPV1 channel is a detector of noxious stimuli, including heat, acidosis, vanilloid compounds and lipids. The gating mechanisms of the related TRPV2 channel are poorly understood because selective high affinity ligands are not available, and the threshold for heat activation is extremely high (>50°C). Cryo-EM structures of TRPV1 and TRPV2 reveal that they adopt similar structures, and identify a putative vanilloid binding pocket near the internal side of TRPV1. Here we use biochemical and electrophysiological approaches to investigate the resiniferatoxin(RTx) binding site in TRPV1 and to explore the functional relationships between TRPV1 and TRPV2. Collectively, our results support the interaction of vanilloids with the proposed RTx binding pocket, and demonstrate an allosteric influence of a tarantula toxin on vanilloid binding. Moreover, we show that sensitivity to RTx can be engineered into TRPV2, demonstrating that the gating and permeation properties of this channel are similar to TRPV1. DOI: http://dx.doi.org/10.7554/eLife.16409.001 PMID:27177419

A deleterious gene-by-environment interaction imposed by calcium channel blockers in Marfan syndrome

PubMed Central

Doyle, Jefferson J; Doyle, Alexander J; Wilson, Nicole K; Habashi, Jennifer P; Bedja, Djahida; Whitworth, Ryan E; Lindsay, Mark E; Schoenhoff, Florian; Myers, Loretha; Huso, Nick; Bachir, Suha; Squires, Oliver; Rusholme, Benjamin; Ehsan, Hamid; Huso, David; Thomas, Craig J; Caulfield, Mark J; Van Eyk, Jennifer E; Judge, Daniel P; Dietz, Harry C

2015-01-01

Calcium channel blockers (CCBs) are prescribed to patients with Marfan syndrome for prophylaxis against aortic aneurysm progression, despite limited evidence for their efficacy and safety in the disorder. Unexpectedly, Marfan mice treated with CCBs show accelerated aneurysm expansion, rupture, and premature lethality. This effect is both extracellular signal-regulated kinase (ERK1/2) dependent and angiotensin-II type 1 receptor (AT1R) dependent. We have identified protein kinase C beta (PKCβ) as a critical mediator of this pathway and demonstrate that the PKCβ inhibitor enzastaurin, and the clinically available anti-hypertensive agent hydralazine, both normalize aortic growth in Marfan mice, in association with reduced PKCβ and ERK1/2 activation. Furthermore, patients with Marfan syndrome and other forms of inherited thoracic aortic aneurysm taking CCBs display increased risk of aortic dissection and need for aortic surgery, compared to patients on other antihypertensive agents. DOI: http://dx.doi.org/10.7554/eLife.08648.001 PMID:26506064

Sex-specific processing of social cues in the medial amygdala

PubMed Central

Bergan, Joseph F; Ben-Shaul, Yoram; Dulac, Catherine

2014-01-01

Animal–animal recognition within, and across species, is essential for predator avoidance and social interactions. Despite its essential role in orchestrating responses to animal cues, basic principles of information processing by the vomeronasal system are still unknown. The medial amygdala (MeA) occupies a central position in the vomeronasal pathway, upstream of hypothalamic centers dedicated to defensive and social responses. We have characterized sensory responses in the mouse MeA and uncovered emergent properties that shed new light onto the transformation of vomeronasal information into sex- and species-specific responses. In particular, we show that the MeA displays a degree of stimulus selectivity and a striking sexually dimorphic sensory representation that are not observed in the upstream relay of the accessory olfactory bulb (AOB). Furthermore, our results demonstrate that the development of sexually dimorphic circuits in the MeA requires steroid signaling near the time of puberty to organize the functional representation of sensory stimuli. DOI: http://dx.doi.org/10.7554/eLife.02743.001 PMID:24894465

Conserved functional antagonism of CELF and MBNL proteins controls stem cell-specific alternative splicing in planarians

PubMed Central

Solana, Jordi; Irimia, Manuel; Ayoub, Salah; Orejuela, Marta Rodriguez; Zywitza, Vera; Jens, Marvin; Tapial, Javier; Ray, Debashish; Morris, Quaid; Hughes, Timothy R; Blencowe, Benjamin J; Rajewsky, Nikolaus

2016-01-01

In contrast to transcriptional regulation, the function of alternative splicing (AS) in stem cells is poorly understood. In mammals, MBNL proteins negatively regulate an exon program specific of embryonic stem cells; however, little is known about the in vivo significance of this regulation. We studied AS in a powerful in vivo model for stem cell biology, the planarian Schmidtea mediterranea. We discover a conserved AS program comprising hundreds of alternative exons, microexons and introns that is differentially regulated in planarian stem cells, and comprehensively identify its regulators. We show that functional antagonism between CELF and MBNL factors directly controls stem cell-specific AS in planarians, placing the origin of this regulatory mechanism at the base of Bilaterians. Knockdown of CELF or MBNL factors lead to abnormal regenerative capacities by affecting self-renewal and differentiation sets of genes, respectively. These results highlight the importance of AS interactions in stem cell regulation across metazoans. DOI: http://dx.doi.org/10.7554/eLife.16797.001 PMID:27502555

Adaptation in protein fitness landscapes is facilitated by indirect paths

PubMed Central

Wu, Nicholas C; Dai, Lei; Olson, C Anders; Lloyd-Smith, James O; Sun, Ren

2016-01-01

The structure of fitness landscapes is critical for understanding adaptive protein evolution. Previous empirical studies on fitness landscapes were confined to either the neighborhood around the wild type sequence, involving mostly single and double mutants, or a combinatorially complete subgraph involving only two amino acids at each site. In reality, the dimensionality of protein sequence space is higher (20L) and there may be higher-order interactions among more than two sites. Here we experimentally characterized the fitness landscape of four sites in protein GB1, containing 204 = 160,000 variants. We found that while reciprocal sign epistasis blocked many direct paths of adaptation, such evolutionary traps could be circumvented by indirect paths through genotype space involving gain and subsequent loss of mutations. These indirect paths alleviate the constraint on adaptive protein evolution, suggesting that the heretofore neglected dimensions of sequence space may change our views on how proteins evolve. DOI: http://dx.doi.org/10.7554/eLife.16965.001 PMID:27391790

Generation of shape complexity through tissue conflict resolution

PubMed Central

Rebocho, Alexandra B; Southam, Paul; Kennaway, J Richard; Coen, Enrico

2017-01-01

Out-of-plane tissue deformations are key morphogenetic events during plant and animal development that generate 3D shapes, such as flowers or limbs. However, the mechanisms by which spatiotemporal patterns of gene expression modify cellular behaviours to generate such deformations remain to be established. We use the Snapdragon flower as a model system to address this problem. Combining cellular analysis with tissue-level modelling, we show that an orthogonal pattern of growth orientations plays a key role in generating out-of-plane deformations. This growth pattern is most likely oriented by a polarity field, highlighted by PIN1 protein localisation, and is modulated by dorsoventral gene activity. The orthogonal growth pattern interacts with other patterns of differential growth to create tissue conflicts that shape the flower. Similar shape changes can be generated by contraction as well as growth, suggesting tissue conflict resolution provides a flexible morphogenetic mechanism for generating shape diversity in plants and animals. DOI: http://dx.doi.org/10.7554/eLife.20156.001 PMID:28166865

Internal states drive nutrient homeostasis by modulating exploration-exploitation trade-off

PubMed Central

Corrales-Carvajal, Verónica María; Faisal, Aldo A; Ribeiro, Carlos

2016-01-01

Internal states can profoundly alter the behavior of animals. A quantitative understanding of the behavioral changes upon metabolic challenges is key to a mechanistic dissection of how animals maintain nutritional homeostasis. We used an automated video tracking setup to characterize how amino acid and reproductive states interact to shape exploitation and exploration decisions taken by adult Drosophila melanogaster. We find that these two states have specific effects on the decisions to stop at and leave proteinaceous food patches. Furthermore, the internal nutrient state defines the exploration-exploitation trade-off: nutrient-deprived flies focus on specific patches while satiated flies explore more globally. Finally, we show that olfaction mediates the efficient recognition of yeast as an appropriate protein source in mated females and that octopamine is specifically required to mediate homeostatic postmating responses without affecting internal nutrient sensing. Internal states therefore modulate specific aspects of exploitation and exploration to change nutrient selection. DOI: http://dx.doi.org/10.7554/eLife.19920.001 PMID:27770569

Probing protein flexibility reveals a mechanism for selective promiscuity

PubMed Central

Pabon, Nicolas A; Camacho, Carlos J

2017-01-01

Many eukaryotic regulatory proteins adopt distinct bound and unbound conformations, and use this structural flexibility to bind specifically to multiple partners. However, we lack an understanding of how an interface can select some ligands, but not others. Here, we present a molecular dynamics approach to identify and quantitatively evaluate the interactions responsible for this selective promiscuity. We apply this approach to the anticancer target PD-1 and its ligands PD-L1 and PD-L2. We discover that while unbound PD-1 exhibits a hard-to-drug hydrophilic interface, conserved specific triggers encoded in the cognate ligands activate a promiscuous binding pathway that reveals a flexible hydrophobic binding cavity. Specificity is then established by additional contacts that stabilize the PD-1 cavity into distinct bound-like modes. Collectively, our studies provide insight into the structural basis and evolution of multiple binding partners, and also suggest a biophysical approach to exploit innate binding pathways to drug seemingly undruggable targets. DOI: http://dx.doi.org/10.7554/eLife.22889.001 PMID:28432789

Long-distance communication by specialized cellular projections during pigment pattern development and evolution

PubMed Central

Eom, Dae Seok; Bain, Emily J; Patterson, Larissa B; Grout, Megan E; Parichy, David M

2015-01-01

Changes in gene activity are essential for evolutionary diversification. Yet, elucidating the cellular behaviors that underlie modifications to adult form remains a profound challenge. We use neural crest-derived adult pigmentation of zebrafish and pearl danio to uncover cellular bases for alternative pattern states. We show that stripes in zebrafish require a novel class of thin, fast cellular projection to promote Delta-Notch signaling over long distances from cells of the xanthophore lineage to melanophores. Projections depended on microfilaments and microtubules, exhibited meandering trajectories, and stabilized on target cells to which they delivered membraneous vesicles. By contrast, the uniformly patterned pearl danio lacked such projections, concomitant with Colony stimulating factor 1-dependent changes in xanthophore differentiation that likely curtail signaling available to melanophores. Our study reveals a novel mechanism of cellular communication, roles for differentiation state heterogeneity in pigment cell interactions, and an unanticipated morphogenetic behavior contributing to a striking difference in adult form. DOI: http://dx.doi.org/10.7554/eLife.12401.001 PMID:26701906

Functional subregions of the human entorhinal cortex

PubMed Central

Maass, Anne; Berron, David; Libby, Laura A; Ranganath, Charan; Düzel, Emrah

2015-01-01

The entorhinal cortex (EC) is the primary site of interactions between the neocortex and hippocampus. Studies in rodents and nonhuman primates suggest that EC can be divided into subregions that connect differentially with perirhinal cortex (PRC) vs parahippocampal cortex (PHC) and with hippocampal subfields along the proximo-distal axis. Here, we used high-resolution functional magnetic resonance imaging at 7 Tesla to identify functional subdivisions of the human EC. In two independent datasets, PRC showed preferential intrinsic functional connectivity with anterior-lateral EC and PHC with posterior-medial EC. These EC subregions, in turn, exhibited differential connectivity with proximal and distal subiculum. In contrast, connectivity of PRC and PHC with subiculum followed not only a proximal-distal but also an anterior-posterior gradient. Our data provide the first evidence that the human EC can be divided into functional subdivisions whose functional connectivity closely parallels the known anatomical connectivity patterns of the rodent and nonhuman primate EC. DOI: http://dx.doi.org/10.7554/eLife.06426.001 PMID:26052749

Assembly and positioning of actomyosin rings by contractility and planar cell polarity

PubMed Central

Sehring, Ivonne M; Recho, Pierre; Denker, Elsa; Kourakis, Matthew; Mathiesen, Birthe; Hannezo, Edouard; Dong, Bo; Jiang, Di

2015-01-01

The actomyosin cytoskeleton is a primary force-generating mechanism in morphogenesis, thus a robust spatial control of cytoskeletal positioning is essential. In this report, we demonstrate that actomyosin contractility and planar cell polarity (PCP) interact in post-mitotic Ciona notochord cells to self-assemble and reposition actomyosin rings, which play an essential role for cell elongation. Intriguingly, rings always form at the cells′ anterior edge before migrating towards the center as contractility increases, reflecting a novel dynamical property of the cortex. Our drug and genetic manipulations uncover a tug-of-war between contractility, which localizes cortical flows toward the equator and PCP, which tries to reposition them. We develop a simple model of the physical forces underlying this tug-of-war, which quantitatively reproduces our results. We thus propose a quantitative framework for dissecting the relative contribution of contractility and PCP to the self-assembly and repositioning of cytoskeletal structures, which should be applicable to other morphogenetic events. DOI: http://dx.doi.org/10.7554/eLife.09206.001 PMID:26486861

A dynamic mode of mitotic bookmarking by transcription factors

PubMed Central

Teves, Sheila S; An, Luye; Hansen, Anders S; Xie, Liangqi; Darzacq, Xavier; Tjian, Robert

2016-01-01

During mitosis, transcription is shut off, chromatin condenses, and most transcription factors (TFs) are reported to be excluded from chromosomes. How do daughter cells re-establish the original transcription program? Recent discoveries that a select set of TFs remain bound on mitotic chromosomes suggest a potential mechanism for maintaining transcriptional programs through the cell cycle termed mitotic bookmarking. Here we report instead that many TFs remain associated with chromosomes in mouse embryonic stem cells, and that the exclusion previously described is largely a fixation artifact. In particular, most TFs we tested are significantly enriched on mitotic chromosomes. Studies with Sox2 reveal that this mitotic interaction is more dynamic than in interphase and is facilitated by both DNA binding and nuclear import. Furthermore, this dynamic mode results from lack of transcriptional activation rather than decreased accessibility of underlying DNA sequences in mitosis. The nature of the cross-linking artifact prompts careful re-examination of the role of TFs in mitotic bookmarking. DOI: http://dx.doi.org/10.7554/eLife.22280.001 PMID:27855781

A native interactor scaffolds and stabilizes toxic ATAXIN-1 oligomers in SCA1

PubMed Central

Lasagna-Reeves, Cristian A; Rousseaux, Maxime WC; Guerrero-Muñoz, Marcos J; Park, Jeehye; Jafar-Nejad, Paymaan; Richman, Ronald; Lu, Nan; Sengupta, Urmi; Litvinchuk, Alexandra; Orr, Harry T; Kayed, Rakez; Zoghbi, Huda Y

2015-01-01

Recent studies indicate that soluble oligomers drive pathogenesis in several neurodegenerative proteinopathies, including Alzheimer and Parkinson disease. Curiously, the same conformational antibody recognizes different disease-related oligomers, despite the variations in clinical presentation and brain regions affected, suggesting that the oligomer structure might be responsible for toxicity. We investigated whether polyglutamine-expanded ATAXIN-1, the protein that underlies spinocerebellar ataxia type 1, forms toxic oligomers and, if so, what underlies their toxicity. We found that mutant ATXN1 does form oligomers and that oligomer levels correlate with disease progression in the Atxn1154Q/+ mice. Moreover, oligomeric toxicity, stabilization and seeding require interaction with Capicua, which is expressed at greater ratios with respect to ATXN1 in the cerebellum than in less vulnerable brain regions. Thus, specific interactors, not merely oligomeric structure, drive pathogenesis and contribute to regional vulnerability. Identifying interactors that stabilize toxic oligomeric complexes could answer longstanding questions about the pathogenesis of other proteinopathies. DOI: http://dx.doi.org/10.7554/eLife.07558.001 PMID:25988806

Integrated action of pheromone signals in promoting courtship behavior in male mice

PubMed Central

Haga-Yamanaka, Sachiko; Ma, Limei; He, Jie; Qiu, Qiang; Lavis, Luke D; Looger, Loren L; Yu, C Ron

2014-01-01

The mammalian vomeronasal organ encodes pheromone information about gender, reproductive status, genetic background and individual differences. It remains unknown how pheromone information interacts to trigger innate behaviors. In this study, we identify vomeronasal receptors responsible for detecting female pheromones. A sub-group of V1re clade members recognizes gender-identifying cues in female urine. Multiple members of the V1rj clade are cognate receptors for urinary estrus signals, as well as for sulfated estrogen (SE) compounds. In both cases, the same cue activates multiple homologous receptors, suggesting redundancy in encoding female pheromone cues. Neither gender-specific cues nor SEs alone are sufficient to promote courtship behavior in male mice, whereas robust courtship behavior can be induced when the two cues are applied together. Thus, integrated action of different female cues is required in pheromone-triggered mating behavior. These results suggest a gating mechanism in the vomeronasal circuit in promoting specific innate behavior. DOI: http://dx.doi.org/10.7554/eLife.03025.001 PMID:25073926

A glucose-starvation response regulates the diffusion of macromolecules

PubMed Central

Joyner, Ryan P; Tang, Jeffrey H; Helenius, Jonne; Dultz, Elisa; Brune, Christiane; Holt, Liam J; Huet, Sebastien; Müller, Daniel J; Weis, Karsten

2016-01-01

The organization and biophysical properties of the cytosol implicitly govern molecular interactions within cells. However, little is known about mechanisms by which cells regulate cytosolic properties and intracellular diffusion rates. Here, we demonstrate that the intracellular environment of budding yeast undertakes a startling transition upon glucose starvation in which macromolecular mobility is dramatically restricted, reducing the movement of both chromatin in the nucleus and mRNPs in the cytoplasm. This confinement cannot be explained by an ATP decrease or the physiological drop in intracellular pH. Rather, our results suggest that the regulation of diffusional mobility is induced by a reduction in cell volume and subsequent increase in molecular crowding which severely alters the biophysical properties of the intracellular environment. A similar response can be observed in fission yeast and bacteria. This reveals a novel mechanism by which cells globally alter their properties to establish a unique homeostasis during starvation. DOI: http://dx.doi.org/10.7554/eLife.09376.001 PMID:27003290

Symbiont-induced odorant binding proteins mediate insect host hematopoiesis

PubMed Central

Benoit, Joshua B; Vigneron, Aurélien; Broderick, Nichole A; Wu, Yineng; Sun, Jennifer S; Carlson, John R; Aksoy, Serap; Weiss, Brian L

2017-01-01

Symbiotic bacteria assist in maintaining homeostasis of the animal immune system. However, the molecular mechanisms that underlie symbiont-mediated host immunity are largely unknown. Tsetse flies (Glossina spp.) house maternally transmitted symbionts that regulate the development and function of their host’s immune system. Herein we demonstrate that the obligate mutualist, Wigglesworthia, up-regulates expression of odorant binding protein six in the gut of intrauterine tsetse larvae. This process is necessary and sufficient to induce systemic expression of the hematopoietic RUNX transcription factor lozenge and the subsequent production of crystal cells, which actuate the melanotic immune response in adult tsetse. Larval Drosophila’s indigenous microbiota, which is acquired from the environment, regulates an orthologous hematopoietic pathway in their host. These findings provide insight into the molecular mechanisms that underlie enteric symbiont-stimulated systemic immune system development, and indicate that these processes are evolutionarily conserved despite the divergent nature of host-symbiont interactions in these model systems. DOI: http://dx.doi.org/10.7554/eLife.19535.001 PMID:28079523

Flattop regulates basal body docking and positioning in mono- and multiciliated cells

PubMed Central

Gegg, Moritz; Böttcher, Anika; Burtscher, Ingo; Hasenoeder, Stefan; Van Campenhout, Claude; Aichler, Michaela; Walch, Axel; Grant, Seth G N; Lickert, Heiko

2014-01-01

Planar cell polarity (PCP) regulates basal body (BB) docking and positioning during cilia formation, but the underlying mechanisms remain elusive. In this study, we investigate the uncharacterized gene Flattop (Fltp) that is transcriptionally activated during PCP acquisition in ciliated tissues. Fltp knock-out mice show BB docking and ciliogenesis defects in multiciliated lung cells. Furthermore, Fltp is necessary for kinocilium positioning in monociliated inner ear hair cells. In these cells, the core PCP molecule Dishevelled 2, the BB/spindle positioning protein Dlg3, and Fltp localize directly adjacent to the apical plasma membrane, physically interact and surround the BB at the interface of the microtubule and actin cytoskeleton. Dlg3 and Fltp knock-outs suggest that both cooperatively translate PCP cues for BB positioning in the inner ear. Taken together, the identification of novel BB/spindle positioning components as potential mediators of PCP signaling might have broader implications for other cell types, ciliary disease, and asymmetric cell division. DOI: http://dx.doi.org/10.7554/eLife.03842.001 PMID:25296022

Three ancient hormonal cues co-ordinate shoot branching in a moss

PubMed Central

Coudert, Yoan; Palubicki, Wojtek; Ljung, Karin; Novak, Ondrej; Leyser, Ottoline; Harrison, C Jill

2015-01-01

Shoot branching is a primary contributor to plant architecture, evolving independently in flowering plant sporophytes and moss gametophytes. Mechanistic understanding of branching is largely limited to flowering plants such as Arabidopsis, which have a recent evolutionary origin. We show that in gametophytic shoots of Physcomitrella, lateral branches arise by re-specification of epidermal cells into branch initials. A simple model co-ordinating the activity of leafy shoot tips can account for branching patterns, and three known and ancient hormonal regulators of sporophytic branching interact to generate the branching pattern- auxin, cytokinin and strigolactone. The mode of auxin transport required in branch patterning is a key divergence point from known sporophytic pathways. Although PIN-mediated basipetal auxin transport regulates branching patterns in flowering plants, this is not so in Physcomitrella, where bi-directional transport is required to generate realistic branching patterns. Experiments with callose synthesis inhibitors suggest plasmodesmal connectivity as a potential mechanism for transport. DOI: http://dx.doi.org/10.7554/eLife.06808.001 PMID:25806686

Cortical network architecture for context processing in primate brain

PubMed Central

Chao, Zenas C; Nagasaka, Yasuo; Fujii, Naotaka

2015-01-01

Context is information linked to a situation that can guide behavior. In the brain, context is encoded by sensory processing and can later be retrieved from memory. How context is communicated within the cortical network in sensory and mnemonic forms is unknown due to the lack of methods for high-resolution, brain-wide neuronal recording and analysis. Here, we report the comprehensive architecture of a cortical network for context processing. Using hemisphere-wide, high-density electrocorticography, we measured large-scale neuronal activity from monkeys observing videos of agents interacting in situations with different contexts. We extracted five context-related network structures including a bottom-up network during encoding and, seconds later, cue-dependent retrieval of the same network with the opposite top-down connectivity. These findings show that context is represented in the cortical network as distributed communication structures with dynamic information flows. This study provides a general methodology for recording and analyzing cortical network neuronal communication during cognition. DOI: http://dx.doi.org/10.7554/eLife.06121.001 PMID:26416139

Rheotaxis facilitates upstream navigation of mammalian sperm cells

PubMed Central

Kantsler, Vasily; Dunkel, Jörn; Blayney, Martyn; Goldstein, Raymond E

2014-01-01

A major puzzle in biology is how mammalian sperm maintain the correct swimming direction during various phases of the sexual reproduction process. Whilst chemotaxis may dominate near the ovum, it is unclear which cues guide spermatozoa on their long journey towards the egg. Hypothesized mechanisms range from peristaltic pumping to temperature sensing and response to fluid flow variations (rheotaxis), but little is known quantitatively about them. We report the first quantitative study of mammalian sperm rheotaxis, using microfluidic devices to investigate systematically swimming of human and bull sperm over a range of physiologically relevant shear rates and viscosities. Our measurements show that the interplay of fluid shear, steric surface-interactions, and chirality of the flagellar beat leads to stable upstream spiralling motion of sperm cells, thus providing a generic and robust rectification mechanism to support mammalian fertilisation. A minimal mathematical model is presented that accounts quantitatively for the experimental observations. DOI: http://dx.doi.org/10.7554/eLife.02403.001 PMID:24867640

Contributions of local speech encoding and functional connectivity to audio-visual speech perception

PubMed Central

Giordano, Bruno L; Ince, Robin A A; Gross, Joachim; Schyns, Philippe G; Panzeri, Stefano; Kayser, Christoph

2017-01-01

Seeing a speaker’s face enhances speech intelligibility in adverse environments. We investigated the underlying network mechanisms by quantifying local speech representations and directed connectivity in MEG data obtained while human participants listened to speech of varying acoustic SNR and visual context. During high acoustic SNR speech encoding by temporally entrained brain activity was strong in temporal and inferior frontal cortex, while during low SNR strong entrainment emerged in premotor and superior frontal cortex. These changes in local encoding were accompanied by changes in directed connectivity along the ventral stream and the auditory-premotor axis. Importantly, the behavioral benefit arising from seeing the speaker’s face was not predicted by changes in local encoding but rather by enhanced functional connectivity between temporal and inferior frontal cortex. Our results demonstrate a role of auditory-frontal interactions in visual speech representations and suggest that functional connectivity along the ventral pathway facilitates speech comprehension in multisensory environments. DOI: http://dx.doi.org/10.7554/eLife.24763.001 PMID:28590903

Transcriptome analysis illuminates the nature of the intracellular interaction in a vertebrate-algal symbiosis

PubMed Central

Burns, John A; Zhang, Huanjia; Hill, Elizabeth; Kim, Eunsoo; Kerney, Ryan

2017-01-01

During embryonic development, cells of the green alga Oophila amblystomatis enter cells of the salamander Ambystoma maculatum forming an endosymbiosis. Here, using de novo dual-RNA seq, we compared the host salamander cells that harbored intracellular algae to those without algae and the algae inside the animal cells to those in the egg capsule. This two-by-two-way analysis revealed that intracellular algae exhibit hallmarks of cellular stress and undergo a striking metabolic shift from oxidative metabolism to fermentation. Culturing experiments with the alga showed that host glutamine may be utilized by the algal endosymbiont as a primary nitrogen source. Transcriptional changes in salamander cells suggest an innate immune response to the alga, with potential attenuation of NF-κB, and metabolic alterations indicative of modulation of insulin sensitivity. In stark contrast to its algal endosymbiont, the salamander cells did not exhibit major stress responses, suggesting that the host cell experience is neutral or beneficial. DOI: http://dx.doi.org/10.7554/eLife.22054.001 PMID:28462779

Externally induced frontoparietal synchronization modulates network dynamics and enhances working memory performance

PubMed Central

Violante, Ines R; Li, Lucia M; Carmichael, David W; Lorenz, Romy; Leech, Robert; Hampshire, Adam; Rothwell, John C; Sharp, David J

2017-01-01

Cognitive functions such as working memory (WM) are emergent properties of large-scale network interactions. Synchronisation of oscillatory activity might contribute to WM by enabling the coordination of long-range processes. However, causal evidence for the way oscillatory activity shapes network dynamics and behavior in humans is limited. Here we applied transcranial alternating current stimulation (tACS) to exogenously modulate oscillatory activity in a right frontoparietal network that supports WM. Externally induced synchronization improved performance when cognitive demands were high. Simultaneously collected fMRI data reveals tACS effects dependent on the relative phase of the stimulation and the internal cognitive processing state. Specifically, synchronous tACS during the verbal WM task increased parietal activity, which correlated with behavioral performance. Furthermore, functional connectivity results indicate that the relative phase of frontoparietal stimulation influences information flow within the WM network. Overall, our findings demonstrate a link between behavioral performance in a demanding WM task and large-scale brain synchronization. DOI: http://dx.doi.org/10.7554/eLife.22001.001 PMID:28288700

Dynamic F-actin movement is essential for fertilization in Arabidopsis thaliana

PubMed Central

Kawashima, Tomokazu; Maruyama, Daisuke; Shagirov, Murat; Li, Jing; Hamamura, Yuki; Yelagandula, Ramesh; Toyama, Yusuke; Berger, Frédéric

2014-01-01

In animals, microtubules and centrosomes direct the migration of gamete pronuclei for fertilization. By contrast, flowering plants have lost essential components of the centrosome, raising the question of how flowering plants control gamete nuclei migration during fertilization. Here, we use Arabidopsis thaliana to document a novel mechanism that regulates F-actin dynamics in the female gametes and is essential for fertilization. Live imaging shows that F-actin structures assist the male nucleus during its migration towards the female nucleus. We identify a female gamete-specific Rho-GTPase that regulates F-actin dynamics and further show that actin–myosin interactions are also involved in male gamete nucleus migration. Genetic analyses and imaging indicate that microtubules are dispensable for migration and fusion of male and female gamete nuclei. The innovation of a novel actin-based mechanism of fertilization during plant evolution might account for the complete loss of the centrosome in flowering plants. DOI: http://dx.doi.org/10.7554/eLife.04501.001 PMID:25303363

Fucosylation and protein glycosylation create functional receptors for cholera toxin

PubMed Central

Wands, Amberlyn M; Fujita, Akiko; McCombs, Janet E; Cervin, Jakob; Dedic, Benjamin; Rodriguez, Andrea C; Nischan, Nicole; Bond, Michelle R; Mettlen, Marcel; Trudgian, David C; Lemoff, Andrew; Quiding-Järbrink, Marianne; Gustavsson, Bengt; Steentoft, Catharina; Clausen, Henrik; Mirzaei, Hamid; Teneberg, Susann; Yrlid, Ulf; Kohler, Jennifer J

2015-01-01

Cholera toxin (CT) enters and intoxicates host cells after binding cell surface receptors using its B subunit (CTB). The ganglioside (glycolipid) GM1 is thought to be the sole CT receptor; however, the mechanism by which CTB binding to GM1 mediates internalization of CT remains enigmatic. Here we report that CTB binds cell surface glycoproteins. Relative contributions of gangliosides and glycoproteins to CTB binding depend on cell type, and CTB binds primarily to glycoproteins in colonic epithelial cell lines. Using a metabolically incorporated photocrosslinking sugar, we identified one CTB-binding glycoprotein and demonstrated that the glycan portion of the molecule, not the protein, provides the CTB interaction motif. We further show that fucosylated structures promote CTB entry into a colonic epithelial cell line and subsequent host cell intoxication. CTB-binding fucosylated glycoproteins are present in normal human intestinal epithelia and could play a role in cholera. DOI: http://dx.doi.org/10.7554/eLife.09545.001 PMID:26512888

A molecular portrait of maternal sepsis from Byzantine Troy

PubMed Central

Devault, Alison M; Mortimer, Tatum D; Kitchen, Andrew; Kiesewetter, Henrike; Enk, Jacob M; Golding, G Brian; Southon, John; Kuch, Melanie; Duggan, Ana T; Aylward, William; Gardner, Shea N; Allen, Jonathan E; King, Andrew M; Wright, Gerard; Kuroda, Makoto; Kato, Kengo; Briggs, Derek EG; Fornaciari, Gino; Holmes, Edward C; Poinar, Hendrik N; Pepperell, Caitlin S

2017-01-01

Pregnancy complications are poorly represented in the archeological record, despite their importance in contemporary and ancient societies. While excavating a Byzantine cemetery in Troy, we discovered calcified abscesses among a woman’s remains. Scanning electron microscopy of the tissue revealed ‘ghost cells’, resulting from dystrophic calcification, which preserved ancient maternal, fetal and bacterial DNA of a severe infection, likely chorioamnionitis. Gardnerella vaginalis and Staphylococcus saprophyticus dominated the abscesses. Phylogenomic analyses of ancient, historical, and contemporary data showed that G. vaginalis Troy fell within contemporary genetic diversity, whereas S. saprophyticus Troy belongs to a lineage that does not appear to be commonly associated with human disease today. We speculate that the ecology of S. saprophyticus infection may have differed in the ancient world as a result of close contacts between humans and domesticated animals. These results highlight the complex and dynamic interactions with our microbial milieu that underlie severe maternal infections. DOI: http://dx.doi.org/10.7554/eLife.20983.001 PMID:28072390

YAP controls retinal stem cell DNA replication timing and genomic stability

PubMed Central

Cabochette, Pauline; Vega-Lopez, Guillermo; Bitard, Juliette; Parain, Karine; Chemouny, Romain; Masson, Christel; Borday, Caroline; Hedderich, Marie; Henningfeld, Kristine A; Locker, Morgane; Bronchain, Odile; Perron, Muriel

2015-01-01

The adult frog retina retains a reservoir of active neural stem cells that contribute to continuous eye growth throughout life. We found that Yap, a downstream effector of the Hippo pathway, is specifically expressed in these stem cells. Yap knock-down leads to an accelerated S-phase and an abnormal progression of DNA replication, a phenotype likely mediated by upregulation of c-Myc. This is associated with an increased occurrence of DNA damage and eventually p53-p21 pathway-mediated cell death. Finally, we identified PKNOX1, a transcription factor involved in the maintenance of genomic stability, as a functional and physical interactant of YAP. Altogether, we propose that YAP is required in adult retinal stem cells to regulate the temporal firing of replication origins and quality control of replicated DNA. Our data reinforce the view that specific mechanisms dedicated to S-phase control are at work in stem cells to protect them from genomic instability. DOI: http://dx.doi.org/10.7554/eLife.08488.001 PMID:26393999

Frontal beta-theta network during REM sleep

PubMed Central

Vijayan, Sujith; Lepage, Kyle Q; Kopell, Nancy J; Cash, Sydney S

2017-01-01

We lack detailed knowledge about the spatio-temporal physiological signatures of REM sleep, especially in humans. By analyzing intracranial electrode data from humans, we demonstrate for the first time that there are prominent beta (15–35 Hz) and theta (4–8 Hz) oscillations in both the anterior cingulate cortex (ACC) and the DLPFC during REM sleep. We further show that these theta and beta activities in the ACC and the DLPFC, two relatively distant but reciprocally connected regions, are coherent. These findings suggest that, counter to current prevailing thought, the DLPFC is active during REM sleep and likely interacting with other areas. Since the DLPFC and the ACC are implicated in memory and emotional regulation, and the ACC has motor areas and is thought to be important for error detection, the dialogue between these two areas could play a role in the regulation of emotions and in procedural motor and emotional memory consolidation. DOI: http://dx.doi.org/10.7554/eLife.18894.001 PMID:28121613

Synchronous beta rhythms of frontoparietal networks support only behaviorally relevant representations

PubMed Central

Antzoulatos, Evan G; Miller, Earl K

2016-01-01

Categorization has been associated with distributed networks of the primate brain, including the prefrontal cortex (PFC) and posterior parietal cortex (PPC). Although category-selective spiking in PFC and PPC has been established, the frequency-dependent dynamic interactions of frontoparietal networks are largely unexplored. We trained monkeys to perform a delayed-match-to-spatial-category task while recording spikes and local field potentials from the PFC and PPC with multiple electrodes. We found category-selective beta- and delta-band synchrony between and within the areas. However, in addition to the categories, delta synchrony and spiking activity also reflected irrelevant stimulus dimensions. By contrast, beta synchrony only conveyed information about the task-relevant categories. Further, category-selective PFC neurons were synchronized with PPC beta oscillations, while neurons that carried irrelevant information were not. These results suggest that long-range beta-band synchrony could act as a filter that only supports neural representations of the variables relevant to the task at hand. DOI: http://dx.doi.org/10.7554/eLife.17822.001 PMID:27841747

Lip movements entrain the observers’ low-frequency brain oscillations to facilitate speech intelligibility

PubMed Central

Park, Hyojin; Kayser, Christoph; Thut, Gregor; Gross, Joachim

2016-01-01

During continuous speech, lip movements provide visual temporal signals that facilitate speech processing. Here, using MEG we directly investigated how these visual signals interact with rhythmic brain activity in participants listening to and seeing the speaker. First, we investigated coherence between oscillatory brain activity and speaker’s lip movements and demonstrated significant entrainment in visual cortex. We then used partial coherence to remove contributions of the coherent auditory speech signal from the lip-brain coherence. Comparing this synchronization between different attention conditions revealed that attending visual speech enhances the coherence between activity in visual cortex and the speaker’s lips. Further, we identified a significant partial coherence between left motor cortex and lip movements and this partial coherence directly predicted comprehension accuracy. Our results emphasize the importance of visually entrained and attention-modulated rhythmic brain activity for the enhancement of audiovisual speech processing. DOI: http://dx.doi.org/10.7554/eLife.14521.001 PMID:27146891

ULK3 regulates cytokinetic abscission by phosphorylating ESCRT-III proteins

PubMed Central

Caballe, Anna; Wenzel, Dawn M; Agromayor, Monica; Alam, Steven L; Skalicky, Jack J; Kloc, Magdalena; Carlton, Jeremy G; Labrador, Leticia; Sundquist, Wesley I; Martin-Serrano, Juan

2015-01-01

The endosomal sorting complexes required for transport (ESCRT) machinery mediates the physical separation between daughter cells during cytokinetic abscission. This process is regulated by the abscission checkpoint, a genome protection mechanism that relies on Aurora B and the ESCRT-III subunit CHMP4C to delay abscission in response to chromosome missegregation. In this study, we show that Unc-51-like kinase 3 (ULK3) phosphorylates and binds ESCRT-III subunits via tandem MIT domains, and thereby, delays abscission in response to lagging chromosomes, nuclear pore defects, and tension forces at the midbody. Our structural and biochemical studies reveal an unusually tight interaction between ULK3 and IST1, an ESCRT-III subunit required for abscission. We also demonstrate that IST1 phosphorylation by ULK3 is an essential signal required to sustain the abscission checkpoint and that ULK3 and CHMP4C are functionally linked components of the timer that controls abscission in multiple physiological situations. DOI: http://dx.doi.org/10.7554/eLife.06547.001 PMID:26011858

Evolution of an ancient protein function involved in organized multicellularity in animals

PubMed Central

Anderson, Douglas P; Whitney, Dustin S; Hanson-Smith, Victor; Woznica, Arielle; Campodonico-Burnett, William; Volkman, Brian F; King, Nicole; Thornton, Joseph W; Prehoda, Kenneth E

2016-01-01

To form and maintain organized tissues, multicellular organisms orient their mitotic spindles relative to neighboring cells. A molecular complex scaffolded by the GK protein-interaction domain (GKPID) mediates spindle orientation in diverse animal taxa by linking microtubule motor proteins to a marker protein on the cell cortex localized by external cues. Here we illuminate how this complex evolved and commandeered control of spindle orientation from a more ancient mechanism. The complex was assembled through a series of molecular exploitation events, one of which – the evolution of GKPID’s capacity to bind the cortical marker protein – can be recapitulated by reintroducing a single historical substitution into the reconstructed ancestral GKPID. This change revealed and repurposed an ancient molecular surface that previously had a radically different function. We show how the physical simplicity of this binding interface enabled the evolution of a new protein function now essential to the biological complexity of many animals. DOI: http://dx.doi.org/10.7554/eLife.10147.001 PMID:26740169

Seipin is required for converting nascent to mature lipid droplets

PubMed Central

Wang, Huajin; Becuwe, Michel; Housden, Benjamin E; Chitraju, Chandramohan; Porras, Ashley J; Graham, Morven M; Liu, Xinran N; Thiam, Abdou Rachid; Savage, David B; Agarwal, Anil K; Garg, Abhimanyu; Olarte, Maria-Jesus; Lin, Qingqing; Fröhlich, Florian; Hannibal-Bach, Hans Kristian; Upadhyayula, Srigokul; Perrimon, Norbert; Kirchhausen, Tomas; Ejsing, Christer S; Walther, Tobias C; Farese, Robert V

2016-01-01

How proteins control the biogenesis of cellular lipid droplets (LDs) is poorly understood. Using Drosophila and human cells, we show here that seipin, an ER protein implicated in LD biology, mediates a discrete step in LD formation—the conversion of small, nascent LDs to larger, mature LDs. Seipin forms discrete and dynamic foci in the ER that interact with nascent LDs to enable their growth. In the absence of seipin, numerous small, nascent LDs accumulate near the ER and most often fail to grow. Those that do grow prematurely acquire lipid synthesis enzymes and undergo expansion, eventually leading to the giant LDs characteristic of seipin deficiency. Our studies identify a discrete step of LD formation, namely the conversion of nascent LDs to mature LDs, and define a molecular role for seipin in this process, most likely by acting at ER-LD contact sites to enable lipid transfer to nascent LDs. DOI: http://dx.doi.org/10.7554/eLife.16582.001 PMID:27564575

CTCF and cohesin regulate chromatin loop stability with distinct dynamics

PubMed Central

Hansen, Anders S; Pustova, Iryna; Cattoglio, Claudia; Tjian, Robert; Darzacq, Xavier

2017-01-01

Folding of mammalian genomes into spatial domains is critical for gene regulation. The insulator protein CTCF and cohesin control domain location by folding domains into loop structures, which are widely thought to be stable. Combining genomic and biochemical approaches we show that CTCF and cohesin co-occupy the same sites and physically interact as a biochemically stable complex. However, using single-molecule imaging we find that CTCF binds chromatin much more dynamically than cohesin (~1–2 min vs. ~22 min residence time). Moreover, after unbinding, CTCF quickly rebinds another cognate site unlike cohesin for which the search process is long (~1 min vs. ~33 min). Thus, CTCF and cohesin form a rapidly exchanging 'dynamic complex' rather than a typical stable complex. Since CTCF and cohesin are required for loop domain formation, our results suggest that chromatin loops are dynamic and frequently break and reform throughout the cell cycle. DOI: http://dx.doi.org/10.7554/eLife.25776.001 PMID:28467304

Functional mapping of yeast genomes by saturated transposition

PubMed Central

Michel, Agnès H; Hatakeyama, Riko; Kimmig, Philipp; Arter, Meret; Peter, Matthias; Matos, Joao; De Virgilio, Claudio; Kornmann, Benoît

2017-01-01

Yeast is a powerful model for systems genetics. We present a versatile, time- and labor-efficient method to functionally explore the Saccharomyces cerevisiae genome using saturated transposon mutagenesis coupled to high-throughput sequencing. SAturated Transposon Analysis in Yeast (SATAY) allows one-step mapping of all genetic loci in which transposons can insert without disrupting essential functions. SATAY is particularly suited to discover loci important for growth under various conditions. SATAY (1) reveals positive and negative genetic interactions in single and multiple mutant strains, (2) can identify drug targets, (3) detects not only essential genes, but also essential protein domains, (4) generates both null and other informative alleles. In a SATAY screen for rapamycin-resistant mutants, we identify Pib2 (PhosphoInositide-Binding 2) as a master regulator of TORC1. We describe two antagonistic TORC1-activating and -inhibiting activities located on opposite ends of Pib2. Thus, SATAY allows to easily explore the yeast genome at unprecedented resolution and throughput. DOI: http://dx.doi.org/10.7554/eLife.23570.001 PMID:28481201

30 CFR 250.1001 - Definitions.

Code of Federal Regulations, 2010 CFR

2010-07-01

... used in this subpart shall have the meanings given below: DOI pipelines include: (1) Producer-operated...) Transporter-operated pipelines that DOI and DOT have agreed are to be regulated as DOI pipelines; and (5) All..., maintenance, and operation; (2) Producer-operated pipelines that DOI and DOT have agreed are to be regulated...

43 CFR 17.331 - Complaints.

Code of Federal Regulations, 2010 CFR

2010-10-01

... or on behalf of others, may file a complaint with DOI, alleging discrimination prohibited by the Act... good cause shown, however, DOI may extend this time limit. (b) DOI will consider the date a complaint... described in paragraphs (a) and (c)(1) of this section. (c) DOI will attempt to facilitate the filing of...

43 CFR 17.331 - Complaints.

Code of Federal Regulations, 2011 CFR

2011-10-01

... or on behalf of others, may file a complaint with DOI, alleging discrimination prohibited by the Act... good cause shown, however, DOI may extend this time limit. (b) DOI will consider the date a complaint... described in paragraphs (a) and (c)(1) of this section. (c) DOI will attempt to facilitate the filing of...

30 CFR 1220.033 - Audits.

Code of Federal Regulations, 2011 CFR

2011-07-01

... which are related to NPSL operations shall be subject to audit by DOI or its appointed agent. Where possible, the auditor for DOI shall coordinate audit efforts with other nonoperators, if any. DOI shall... the same manner as the operator is notified. DOI may elect to send an auditor with the audit team...

The interaction with gold suppresses fiber-like conformations of the amyloid β (16-22) peptide

NASA Astrophysics Data System (ADS)

Bellucci, Luca; Ardèvol, Albert; Parrinello, Michele; Lutz, Helmut; Lu, Hao; Weidner, Tobias; Corni, Stefano

2016-04-01

Inorganic surfaces and nanoparticles can accelerate or inhibit the fibrillation process of proteins and peptides, including the biomedically relevant amyloid β peptide. However, the microscopic mechanisms that determine such an effect are still poorly understood. By means of large-scale, state-of-the-art enhanced sampling molecular dynamics simulations, here we identify an interaction mechanism between the segments 16-22 of the amyloid β peptide, known to be fibrillogenic by itself, and the Au(111) surface in water that leads to the suppression of fiber-like conformations from the peptide conformational ensemble. Moreover, thanks to advanced simulation analysis techniques, we characterize the conformational selection vs. induced fit nature of the gold effect. Our results disclose an inhibition mechanism that is rooted in the details of the microscopic peptide-surface interaction rather than in general phenomena such as peptide sequestration from the solution.Inorganic surfaces and nanoparticles can accelerate or inhibit the fibrillation process of proteins and peptides, including the biomedically relevant amyloid β peptide. However, the microscopic mechanisms that determine such an effect are still poorly understood. By means of large-scale, state-of-the-art enhanced sampling molecular dynamics simulations, here we identify an interaction mechanism between the segments 16-22 of the amyloid β peptide, known to be fibrillogenic by itself, and the Au(111) surface in water that leads to the suppression of fiber-like conformations from the peptide conformational ensemble. Moreover, thanks to advanced simulation analysis techniques, we characterize the conformational selection vs. induced fit nature of the gold effect. Our results disclose an inhibition mechanism that is rooted in the details of the microscopic peptide-surface interaction rather than in general phenomena such as peptide sequestration from the solution. Electronic supplementary information (ESI) available: Representative structures for the most populated conformational structures of Aβ16-22 on bulk and on the metal surface. Normalized distribution of the variable s defined as the sum of internal dihedral angles of the peptide in solution and at the gold/water interface. See DOI: 10.1039/C6NR01539E

Dynamical Networks Characterization of Geomagnetic Substorms and Transient Response to the Solar Wind State.

NASA Astrophysics Data System (ADS)

Chapman, S. C.; Dods, J.; Gjerloev, J. W.

2017-12-01

Observations of how the solar wind interacts with earth's magnetosphere, and its dynamical response, are increasingly becoming a data analytics challenge. Constellations of satellites observe the solar corona, the upstream solar wind and throughout earth's magnetosphere. These data are multipoint in space and extended in time, so in principle are ideal for study using dynamical networks to characterize the full time evolving spatial pattern. We focus here on analysis of data from the full set of 100+ auroral ground based magnetometer stations that have been collated by SuperMAG. Spatio-temporal patterns of correlation between the magnetometer time series can be used to form a dynamical network [1]. The properties of the network can then be captured by (time dependent) network parameters. This offers the possibility of characterizing detailed spatio-temporal pattern by a few parameters, so that many events can then be compared [2] with each other. Whilst networks are in widespread use in the data analytics of societal and commercial data, there are additional challenges in their application to physical timeseries. Determining whether two nodes (here, ground based magnetometer stations) are connected in a network (seeing the same dynamics) requires normalization w.r.t. the detailed sensitivities and dynamical responses of specific observing stations and seasonal conductivity variations and we have developed methods to achieve this dynamical normalization. The detailed properties of the network capture time dependent spatial correlation in the magnetometer responses and we will show how this can be used to infer a transient current system response to magnetospheric activity. [l] Dods et al, J. Geophys. Res 120, doi:10.1002/2015JA02 (2015). [2] Dods et al, J. Geophys. Res. 122, doi:10.1002/2016JA02 (2017).

Off-center blast in a shocked medium

NASA Astrophysics Data System (ADS)

Duncan-Miller, G. C.; Stone, W. D.

2018-07-01

When multiple blasts occur at different times, the situation arises in which a blast wave is propagating into a medium that has already been shocked. Determining the evolution in the shape of the second shock is not trivial, as it is propagating into air that is not only non-uniform, but also non-stationary. To accomplish this task, we employ the method of Kompaneets to determine the shape of a shock in a non-uniform media. We also draw from the work of Korycansky (Astrophys J 398:184-189. https://doi.org/10.1086/171847 , 1992) on an off-center explosion in a medium with radially varying density. Extending this to treat non-stationary flow, and making use of approximations to the Sedov solution for the point blast problem, we are able to determine an analytic expression for the evolving shape of the second shock. In particular, we consider the case of a shock in air at standard ambient temperature and pressure, with the second shock occurring shortly after the original blast wave reaches it, as in a sympathetic detonation.

Description of Mixed-Phase Clouds in Weather Forecast and Climate Models

DTIC Science & Technology

2014-09-30

deficits, leading to freeze-up of both sea ice and the ocean surface. The surface albedo and processes impacting the energy content of the upper ocean...appear key to producing a temporal difference be- tween the freeze-up of the sea - ice surface and adjacent open water. While synoptic conditions, atmos...Leck, 2013: Cloud and boundary layer interactions over the Arctic sea - ice in late summer, Atmos. Chem. Phys. Discuss., 13, 13191-13244, doi

The Soft Constraints Hypothesis: A Rational Analysis Approach to Resource Allocation for Interactive Behavior

DTIC Science & Technology

2006-01-01

Gray, Rensselaer Polytechnic Institute, Carnegie Building, 110 8th St., Troy, NY 12180. E-mail: grayw@rpi.edu Psychological Review Copyright 2006 by...the American Psychological Association 2006, Vol. 113, No. 3, 461–482 0033-295X/06/$12.00 DOI: 10.1037/0033-295X.113.3.461 461 Report Documentation...analysis approach from signal-detection theorists (Geisler, 2003; Macmillan & Creelman , 2004) with rational analysis (Anderson, 1990, 1991) to present an

76 FR 77831 - 2012 Presidential Candidate Matching Fund Submission Dates and Post Date of Ineligibility Dates...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-12-14

... statement'') after their dates of ineligibility (``DOI''). Candidates are required to submit a NOCO... notified of their DOI by the Commission. A Candidate who has net outstanding campaign obligations post-DOI... each matching fund request submitted after the candidate's DOI. These statements are due just before...

Time-Resolved Diffuse Optical Spectroscopy and Imaging Using Solid-State Detectors: Characteristics, Present Status, and Research Challenges.

PubMed

Alayed, Mrwan; Deen, M Jamal

2017-09-14

Diffuse optical spectroscopy (DOS) and diffuse optical imaging (DOI) are emerging non-invasive imaging modalities that have wide spread potential applications in many fields, particularly for structural and functional imaging in medicine. In this article, we review time-resolved diffuse optical imaging (TR-DOI) systems using solid-state detectors with a special focus on Single-Photon Avalanche Diodes (SPADs) and Silicon Photomultipliers (SiPMs). These TR-DOI systems can be categorized into two types based on the operation mode of the detector (free-running or time-gated). For the TR-DOI prototypes, the physical concepts, main components, figures-of-merit of detectors, and evaluation parameters are described. The performance of TR-DOI prototypes is evaluated according to the parameters used in common protocols to test DOI systems particularly basic instrumental performance (BIP). In addition, the potential features of SPADs and SiPMs to improve TR-DOI systems and expand their applications in the foreseeable future are discussed. Lastly, research challenges and future developments for TR-DOI are discussed for each component in the prototype separately and also for the entire system.

Brady Stoll | NREL

Science.gov Websites

Renewable Generation Integration Study, she joined the laboratory full-time as a post doc and is now a lead determining the intensity and angular distribution of radiation transmitted through homogenous cloud cover ." Environmental Research Letters 8, no. 1 (March 2013). doi:10.1088/1748-9326/8/1/014042 Full list

The hallucinogen DOI reduces low-frequency oscillations in rat prefrontal cortex: reversal by antipsychotic drugs.

PubMed

Celada, Pau; Puig, M Victoria; Díaz-Mataix, Llorenç; Artigas, Francesc

2008-09-01

Perceptual and psychic alterations and thought disorder are fundamental elements of schizophrenia symptoms, a pathology associated with an abnormal macro- and microcircuitry of several brain areas including the prefrontal cortex (PFC). Alterations in information processing in PFC may partly underlie schizophrenia symptoms. The 5-HT(2A/2C) agonist DOI and antipsychotic drugs were administered to anesthetized rats. Single unit and local field potential (LFP) extracellular recordings were made in medial PFC (mPFC). Electrolytic lesions were performed in the thalamic nuclei. DOI markedly disrupts cellular and network activity in rat PFC. DOI altered pyramidal discharge in mPFC (39% excited, 27% inhibited, 34% unaffected; n = 51). In all instances, DOI concurrently reduced low-frequency oscillations (.3-4 Hz; power spectrum: .25 +/- .02 and .14 +/- .01 microV(2) in basal conditions and after 50-300 microg/kg intravenous (i.v.) DOI, respectively; n = 51). Moreover, DOI disrupted the temporal association between the active phase of LFP and pyramidal discharge. Both effects were reversed by M100907 (5-HT(2A) receptor antagonist) and were not attenuated by thalamic lesions, supporting an intracortical origin of the effects of DOI. The reduction in low-frequency oscillations induced by DOI was significantly reversed by the antipsychotic drugs haloperidol (.1-.2 mg/kg i.v.) and clozapine (1 mg/kg i.v.). DOI disorganizes network activity in PFC, reducing low-frequency oscillations and desynchronizing pyramidal discharge from active phases of LFP. These effects may underlie DOI's psychotomimetic action. The reversal by clozapine and haloperidol indicates that antipsychotic drugs may reduce psychotic symptoms by normalizing an altered PFC function.

Wikipedia as a gateway to biomedical research: The relative distribution and use of citations in the English Wikipedia

PubMed Central

Willinsky, John M.; Steinberg, Ryan M.; Mietchen, Daniel; Wass, Joseph L.; Dong, Ting

2017-01-01

Wikipedia is a gateway to knowledge. However, the extent to which this gateway ends at Wikipedia or continues via supporting citations is unknown. Wikipedia’s gateway functionality has implications for information design and education, notably in medicine. This study aims to establish benchmarks for the relative distribution and referral (click) rate of citations—as indicated by presence of a Digital Object Identifier (DOI)—from Wikipedia, with a focus on medical citations. DOIs referred from the English Wikipedia in August 2016 were obtained from Crossref.org. Next, based on a DOI’s presence on a WikiProject Medicine page, all DOIs in Wikipedia were categorized as medical (WP:MED) or non-medical (non-WP:MED). Using this categorization, referred DOIs were classified as WP:MED, non-WP:MED, or BOTH, meaning the DOI may have been referred from either category. Data were analyzed using descriptive and inferential statistics. Out of 5.2 million Wikipedia pages, 4.42% (n = 229,857) included at least one DOI. 68,870 were identified as WP:MED, with 22.14% (n = 15,250) featuring one or more DOIs. WP:MED pages featured on average 8.88 DOI citations per page, whereas non-WP:MED pages had on average 4.28 DOI citations. For DOIs only on WP:MED pages, a DOI was referred every 2,283 pageviews and for non-WP:MED pages every 2,467 pageviews. DOIs from BOTH pages accounted for 12% (n = 58,475). The referral of DOI citations found in BOTH could not be assigned to WP:MED or non-WP:MED, as the page from which the referral was made was not provided with the data. While these results cannot provide evidence of greater citation referral from WP:MED than non-WP:MED, they do provide benchmarks to assess strategies for changing referral patterns. These changes might include editors adopting new methods for designing and presenting citations or the introduction of teaching strategies that address the value of consulting citations as a tool for extending learning. PMID:29267345

DOE Office of Scientific and Technical Information (OSTI.GOV)

Virador, Patrick R.G.

The author performs image reconstruction for a novel Positron Emission Tomography camera that is optimized for breast cancer imaging. This work addresses for the first time, the problem of fully-3D, tomographic reconstruction using a septa-less, stationary, (i.e. no rotation or linear motion), and rectangular camera whose Field of View (FOV) encompasses the entire volume enclosed by detector modules capable of measuring Depth of Interaction (DOI) information. The camera is rectangular in shape in order to accommodate breasts of varying sizes while allowing for soft compression of the breast during the scan. This non-standard geometry of the camera exacerbates two problems:more » (a) radial elongation due to crystal penetration and (b) reconstructing images from irregularly sampled data. Packing considerations also give rise to regions in projection space that are not sampled which lead to missing information. The author presents new Fourier Methods based image reconstruction algorithms that incorporate DOI information and accommodate the irregular sampling of the camera in a consistent manner by defining lines of responses (LORs) between the measured interaction points instead of rebinning the events into predefined crystal face LORs which is the only other method to handle DOI information proposed thus far. The new procedures maximize the use of the increased sampling provided by the DOI while minimizing interpolation in the data. The new algorithms use fixed-width evenly spaced radial bins in order to take advantage of the speed of the Fast Fourier Transform (FFT), which necessitates the use of irregular angular sampling in order to minimize the number of unnormalizable Zero-Efficiency Bins (ZEBs). In order to address the persisting ZEBs and the issue of missing information originating from packing considerations, the algorithms (a) perform nearest neighbor smoothing in 2D in the radial bins (b) employ a semi-iterative procedure in order to estimate the unsampled data and (c) mash the in plane projections, i.e. 2D data, with the projection data from the first oblique angles, which are then used to reconstruct the preliminary image in the 3D Reprojection Projection algorithm. The author presents reconstructed images of point sources and extended sources in both 2D and 3D. The images show that the camera is anticipated to eliminate radial elongation and produce artifact free and essentially spatially isotropic images throughout the entire FOV. It has a resolution of 1.50 ± 0.75 mm FWHM near the center, 2.25 ±0.75 mm FWHM in the bulk of the FOV, and 3.00 ± 0.75 mm FWHM near the edge and corners of the FOV.« less

Imaging of drug loading distributions in individual microspheres of calcium silicate hydrate - an X-ray spectromicroscopy study

NASA Astrophysics Data System (ADS)

Guo, Xiaoxuan; Wang, Zhiqiang; Wu, Jin; Wang, Jian; Zhu, Ying-Jie; Sham, Tsun-Kong

2015-04-01

Imaging is one of the most direct and ideal ways to track drug loading distributions in drug carriers on the molecular level, which will facilitate the optimization of drug carriers and drug loading capacities. Herein, we report the mapping of an individual mesoporous calcium silicate hydrate (CSH) microsphere before and after the loading of ibuprofen (IBU) and the interactions between drug carriers and drug molecules simultaneously by scanning transmission X-ray microscopy (STXM). Nanoscaled X-ray absorption near edge structure (XANES) spectroscopy clearly indicates that IBU is bonded to calcium and silicate sites via carboxylic acid groups. More importantly, STXM has been successfully used to determine the absolute thickness of IBU, revealing its distribution in the CSH microsphere.Imaging is one of the most direct and ideal ways to track drug loading distributions in drug carriers on the molecular level, which will facilitate the optimization of drug carriers and drug loading capacities. Herein, we report the mapping of an individual mesoporous calcium silicate hydrate (CSH) microsphere before and after the loading of ibuprofen (IBU) and the interactions between drug carriers and drug molecules simultaneously by scanning transmission X-ray microscopy (STXM). Nanoscaled X-ray absorption near edge structure (XANES) spectroscopy clearly indicates that IBU is bonded to calcium and silicate sites via carboxylic acid groups. More importantly, STXM has been successfully used to determine the absolute thickness of IBU, revealing its distribution in the CSH microsphere. Electronic supplementary information (ESI) available. See DOI: 10.1039/c4nr07471h

Scientific integrity - Recent Department of the Interior policies, codes, and their implementation

USGS Publications Warehouse

Thornhill, Alan D.; Coleman, Richard; Gunderson, Linda C.

2017-01-01

Established on January 28, 2011, the Department of Interior's (DOI’s) Scientific and Scholarly Integrity Policy was the first federal agency policy to respond to the Presidential Memorandum on Scientific Integrity (March 9, 2009) and guidance issued by the Office of Science and Technology Policy Memorandum on Scientific Integrity (December 17, 2010). The increasingly important role of science in DOI decision making and heightened awareness of science integrity issues across the science enterprise provided impetus for making this policy a priority and for incorporating it into the DOI Departmental Manual (Part 305: Chapter 3). This paper discusses the history of scientific integrity in the DOI, the key provisions of the first Department-wide policy and its implementation, and the subsequent revision of the policy. During the first 4 years of implementing the scientific integrity policy, the Department received 35 formal complaints. As of March 31, 2015, only two formal scientific integrity complaints resulted in “warranted determinations,” while the other complaints were closed and dismissed as “not warranted.” Based on the experience of the first three years of implementation (2011-2014), the Department policy was revised on December 16, 2014.

43 CFR 17.339 - Exhaustion of administrative remedies.

Code of Federal Regulations, 2010 CFR

2010-10-01

... DOI has made no finding with regard to the complaint; or (2) DOI issues any finding in favor of the recipient. (b) If DOI fails to make a finding within 180 days or issues a finding in favor of the recipient, DOI will: (1) Promptly advise the complainant of this fact; (2) Advise the complainant of his or her...

41 CFR 102-75.635 - What information must the Department of the Interior (DOI) furnish eligible public agencies?

Code of Federal Regulations, 2010 CFR

2010-07-01

... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false What information must the Department of the Interior (DOI) furnish eligible public agencies? 102-75.635 Section 102-75.635... the Interior (DOI) furnish eligible public agencies? Upon request, DOI must furnish eligible public...

75 FR 55315 - Seminole Energy Services, LLC; Seminole Gas Company, LLC; Seminole High Plains, LLC; Lakeshore...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-10

... Investigations (DOI) as non- decisional staff in deliberations by the Commission in this docket. By this order... of Enforcement, Larry Parkinson, Director, DOI, and Geof Hobday of DOI to the January 15, 2009 list of staff excepted from the DOI non-decisional staff designation. Kimberly D. Bose, Secretary. [FR Doc...

41 CFR 102-75.635 - What information must the Department of the Interior (DOI) furnish eligible public agencies?

Code of Federal Regulations, 2011 CFR

2011-01-01

... 41 Public Contracts and Property Management 3 2011-01-01 2011-01-01 false What information must the Department of the Interior (DOI) furnish eligible public agencies? 102-75.635 Section 102-75.635... the Interior (DOI) furnish eligible public agencies? Upon request, DOI must furnish eligible public...

30 CFR 250.1006 - How must I decommission and take out of service a DOI pipeline?

Code of Federal Regulations, 2011 CFR

2011-07-01

... a DOI pipeline? 250.1006 Section 250.1006 Mineral Resources BUREAU OF OCEAN ENERGY MANAGEMENT... out of service a DOI pipeline? (a) The requirements for decommissioning pipelines are listed in § 250.1750 through § 250.1754. (b) The table in this section lists the requirements if you take a DOI...

41 CFR 102-75.665 - What happens after the disposal agency receives the assignment recommendation from DOI?

Code of Federal Regulations, 2011 CFR

2011-01-01

... disposal agency receives the assignment recommendation from DOI? 102-75.665 Section 102-75.665 Public... assignment recommendation from DOI? If, after considering other uses for the property, the disposal agency approves the assignment recommendation from DOI, it must assign the property by letter or other document to...

Use of the PIXEL method to investigate gas adsorption in metal–organic frameworks† †Electronic supplementary information (ESI) available. See DOI: 10.1039/c6ce00555a Click here for additional data file. Click here for additional data file. Click here for additional data file.

PubMed Central

Maloney, Andrew G. P.; Wood, Peter A.

2016-01-01

PIXEL has been used to perform calculations of adsorbate-adsorbent interaction energies between a range of metal–organic frameworks (MOFs) and simple guest molecules. Interactions have been calculated for adsorption between MOF-5 and Ar, H2, and N2; Zn2(BDC)2(TED) (BDC = 1,4-benzenedicarboxylic acid, TED = triethylenediamine) and H2; and HKUST-1 and CO2. The locations of the adsorption sites and the calculated energies, which show differences in the Coulombic or dispersion characteristic of the interaction, compare favourably to experimental data and literature energy values calculated using density functional theory. PMID:28496380

A new compilation of stomach content data for commercially-important pelagic fish species in the Northeast Atlantic

NASA Astrophysics Data System (ADS)

Pinnegar, J. K.; Goñi, N.; Trenkel, V. M.; Arrizabalaga, H.; Melle, W.; Keating, J.; Óskarsson, G.

2014-04-01

There is increasing demand for information on predator-prey interactions in the ocean as a result of legislative commitments aimed at achieving sustainable exploitation. However, comprehensive datasets are lacking for many fish species and this has hampered development of multispecies fisheries models and the formulation of effective food-web indicators. This work describes a new compilation of stomach content data for five pelagic fish species (herring, blue whiting, mackerel, albacore and bluefin tuna) sampled across the northeast Atlantic and submitted to the PANGAEA open-access data portal (www.pangaea.de). We provide detailed descriptions of sample origin and of the corresponding database structures. We describe the main results in terms of diet composition and predator-prey relationships. The feeding preferences of small pelagic fish (herring, blue whiting, mackerel) were sampled over a very broad geographic area within the North Atlantic basin, from Greenland in the west, to the Lofoten Islands in the east and from the Bay of Biscay northwards to the Arctic. This analysis revealed significant differences in the prey items selected in different parts of the region at different times of year. Tunas (albacore and bluefin) were sampled in the Bay of Biscay and Celtic Sea. Dominant prey items for these species varied by location, year and season. This data compilation exercise represents one of the largest and most wide-ranging ever attempted for pelagic fish in the north Atlantic. The earliest data included in the database were collected in 1864, whereas the most recent were collected in 2012.Datasets are available at doi:10.1594/PANGAEA.820041 and doi:10.1594/PANGAEA.826992.

A new compilation of stomach content data for commercially important pelagic fish species in the northeast Atlantic

NASA Astrophysics Data System (ADS)

Pinnegar, J. K.; Goñi, N.; Trenkel, V. M.; Arrizabalaga, H.; Melle, W.; Keating, J.; Óskarsson, G.

2015-02-01

There is increasing demand for information on predator-prey interactions in the ocean as a result of legislative commitments aimed at achieving sustainable exploitation. However, comprehensive data sets are lacking for many fish species and this has hampered development of multispecies fisheries models and the formulation of effective food-web indicators. This work describes a new compilation of stomach content data for five pelagic fish species (herring, blue whiting, mackerel, albacore and bluefin tuna) sampled across the northeast Atlantic and submitted to the PANGAEA open-access data portal (www.pangaea.de). We provide detailed descriptions of sample origin and of the corresponding database structures. We describe the main results in terms of diet composition and predator-prey relationships. The feeding preferences of small pelagic fish (herring, blue whiting, mackerel) were sampled over a very broad geographic area within the North Atlantic basin, from Greenland in the west, to the Lofoten Islands in the east and from the Bay of Biscay northwards to the Arctic. This analysis revealed significant differences in the prey items selected in different parts of the region at different times of year. Tunas (albacore and bluefin) were sampled in the Bay of Biscay and Celtic Sea. Dominant prey items for these species varied by location, year and season. This data compilation exercise represents one of the largest and most wide-ranging ever attempted for pelagic fish in the North Atlantic. The earliest data included in the database were collected in 1864, whereas the most recent were collected in 2012. Data sets are available at doi:10.1594/PANGAEA.820041 and doi:10.1594/PANGAEA.826992.

Development and validation of PCR-GLOBWB 2.0: a 5 arc min resolution global hydrology and water resources model

NASA Astrophysics Data System (ADS)

Sutanudjaja, Edwin H.; van Beek, Ludovicus P. H.; Wada, Yoshihide; Wisser, Dominik; de Graaf, Inge E. M.; Straatsma, Menno W.; Bierkens, Marc F. P.

2014-05-01

PCR-GLOBWB (PCRaster Global Water Balance) is a grid-based global hydrological model developed at the Department of Physical Geography, Utrecht University. For each grid cell, PCR-GLOBWB simulates moisture storage in vertically stacked soil layers, as well as the water exchange to the atmosphere and underlying groundwater reservoir. Exchange to the atmosphere comprises of precipitation, evaporation and transpiration, as well as snow accumulation and melt. All fluxes are all simulated by considering vegetation phenology and sub-grid variations in elevation, land cover and soil saturation. The model includes physically-based schemes for runoff-infiltration partitioning, interflow, groundwater recharge and baseflow, as well as river routing of discharge. Here we present and summarize the latest developments of PCR-GLOBWB. The new version of the model, PCR-GLOBWB 2.0, now runs at a spatial resolution of 5 arc min (about 10 km at the equator) and supersedes the previous generation of the model (30 arc min PCR-GLOBWB 1.0, van Beek et al., 2011). PCR-GLOBWB 2.0 consolidates all components that have been introduced since PCR-GLOWB 1.0 was first published (2011). Examples of these new components are: A comprehensive water demand and irrigation module (Wada et al., 2012). A dynamic attribution and return flow of water demand to surface water and groundwater resources (de Graaf et al., 2013). An advanced surface water routing scheme with wetland, lakes and floodplains of variable extent, thus simulating flooding and flood wave attenuation (Winsemius et al., 2013). An online scheme for dynamic withdrawal, allocation and consumptive use of groundwater and surface water resources, including a progressive introduction of reservoirs (Wada et al., 2013). Further development will include the inclusion of a dynamic reservoir operation/optimization scheme and a MODFLOW lateral groundwater flow module (Sutanudjaja et al., 2011; Sutanudjaja et al., 2014). Also, scripts used for deriving the parameterization from global data sources for the original model have been coupled with the model, resulting in a near-scalable model that facilitates its application for different domains and at varying resolutions. Results are very promising. When comparing simulated discharges to those observed by GRDC stations, the coefficient-of-determination is high. Human impacts, altering the seasonal and inter-annual variability of terrestrial water storage (TWS) signals, are well simulated by PCR-GLOBWB 2.0 and evident in the validation of simulated TWS with GRACE satellite observation (Tapley et al., 2004). Moreover, the simulation results of PCR-GLOBWB 2.0 compare well to several other remote sensing products, such as the soil moisture datasets of ERS/MetOp (Wagner et al., 1999) and AMSR-E (de Jeu and Owe, 2003), as well as the GLEAM evaporation product (Miralles et al., 2011). References: de Graaf et al., Advances in Water Resources (2013), http://dx.doi.org/10.1016/j.advwatres.2013.12.002 de Jeu and Owe, International Journal of Remote Sensing (2003), http://dx.doi.org/10.1080/0143116031000095934 Miralles et al., Hydrology and Earth System Sciences (2011), http://dx.doi.org/10.5194/hess-15-967-2011 Sutanudjaja et al., Hydrology and Earth System Sciences (2011), http://dx.doi.org/10.5194/hess-15-2913-2011 Sutanudjaja et al., Water Resources Research (2014), http://dx.doi.org/10.1002/2013WR013807 Tapley et al., Science (2004), http://dx.doi.org/10.1126/science.1099192 van Beek et al., Water Resources Research (2011), http://dx.doi.org/10.1029/2010WR009791 Wada et al., Water Resources Research (2012), http://dx.doi.org/10.1029/2011WR010562 Wada et al., Earth System Dynamics Discussion (2013), http://dx.doi.org/10.5194/esdd-4-355-2013 Wagner et al., Remote Sensing of Environment (1999), http://dx.doi.org/10.1016/S0034-4257(99)00036-X Winsemius et al., Hydrology and Earth System Sciences (2013), http://dx.doi.org/10.5194/hess-17-1871-2013

Evolution of NASA's Earth Science Digital Object Identifier Registration System

NASA Technical Reports Server (NTRS)

Wanchoo, Lalit; James, Nathan

2017-01-01

NASA's Earth Science Data and Information System (ESDIS) Project has implemented a fully automated system for assigning Digital Object Identifiers (DOIs) to Earth Science data products being managed by its network of 12 distributed active archive centers (DAACs). A key factor in the successful evolution of the DOI registration system over last 7 years has been the incorporation of community input from three focus groups under the NASA's Earth Science Data System Working Group (ESDSWG). These groups were largely composed of DOI submitters and data curators from the 12 data centers serving the user communities of various science disciplines. The suggestions from these groups were formulated into recommendations for ESDIS consideration and implementation. The ESDIS DOI registration system has evolved to be fully functional with over 5,000 publicly accessible DOIs and over 200 DOIs being held in reserve status until the information required for registration is obtained. The goal is to assign DOIs to the entire 8000+ data collections under ESDIS management via its network of discipline-oriented data centers. DOIs make it easier for researchers to discover and use earth science data and they enable users to provide valid citations for the data they use in research. Also for the researcher wishing to reproduce the results presented in science publications, the DOI can be used to locate the exact data or data products being cited.

43 CFR 17.301 - What is the purpose of DOI's age discrimination regulations?

Code of Federal Regulations, 2010 CFR

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false What is the purpose of DOI's age... Age General § 17.301 What is the purpose of DOI's age discrimination regulations? The purpose of these regulations is to set out DOI's policies and procedures under the Age Discrimination Act of 1975 and the...

41 CFR 102-75.670 - What responsibilities does DOI have after receiving the disposal agency's assignment letter?

Code of Federal Regulations, 2010 CFR

2010-07-01

... does DOI have after receiving the disposal agency's assignment letter? 102-75.670 Section 102-75.670... Property for Use As Public Park Or Recreation Areas § 102-75.670 What responsibilities does DOI have after..., the Secretary may proceed with the transfer. DOI must take all necessary actions to accomplish the...

30 CFR 250.1006 - How must I decommission and take out of service a DOI pipeline?

Code of Federal Regulations, 2010 CFR

2010-07-01

... a DOI pipeline? 250.1006 Section 250.1006 Mineral Resources MINERALS MANAGEMENT SERVICE, DEPARTMENT... and Pipeline Rights-of-Way § 250.1006 How must I decommission and take out of service a DOI pipeline...) The table in this section lists the requirements if you take a DOI pipeline out of service: If you...

43 CFR 2.31 - How will DOI respond to my appeal?

Code of Federal Regulations, 2010 CFR

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false How will DOI respond to my appeal? 2.31... OF INFORMATION ACT FOIA Appeals § 2.31 How will DOI respond to my appeal? (a) Appeals will be decided... will state the basis for DOI's decision as follows: (1) Decision to release or withhold records. (i) If...

43 CFR 45.25 - What will DOI do with any hearing requests?

Code of Federal Regulations, 2010 CFR

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false What will DOI do with any hearing requests... PRESCRIPTIONS IN FERC HYDROPOWER LICENSES Hearing Process Initiation of Hearing Process § 45.25 What will DOI do... will refer the case for a hearing as follows: (1) If the hearing is to be conducted by DOI, OEPC will...

41 CFR 102-75.650 - When must DOI request assignment of the property?

Code of Federal Regulations, 2010 CFR

2010-07-01

... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false When must DOI request...-75.650 When must DOI request assignment of the property? Within 30 calendar days after the expiration of the 30-calendar day period specified in § 102-75.640, DOI must submit to the disposal agency an...

41 CFR 102-75.670 - What responsibilities does DOI have after receiving the disposal agency's assignment letter?

Code of Federal Regulations, 2011 CFR

2011-01-01

... does DOI have after receiving the disposal agency's assignment letter? 102-75.670 Section 102-75.670... Property for Use As Public Park Or Recreation Areas § 102-75.670 What responsibilities does DOI have after..., the Secretary may proceed with the transfer. DOI must take all necessary actions to accomplish the...

43 CFR 17.301 - What is the purpose of DOI's age discrimination regulations?

Code of Federal Regulations, 2011 CFR

2011-10-01

... 43 Public Lands: Interior 1 2011-10-01 2011-10-01 false What is the purpose of DOI's age... Age General § 17.301 What is the purpose of DOI's age discrimination regulations? The purpose of these regulations is to set out DOI's policies and procedures under the Age Discrimination Act of 1975 and the...

43 CFR 45.25 - What will DOI do with any hearing requests?

Code of Federal Regulations, 2011 CFR

2011-10-01

... 43 Public Lands: Interior 1 2011-10-01 2011-10-01 false What will DOI do with any hearing requests... PRESCRIPTIONS IN FERC HYDROPOWER LICENSES Hearing Process Initiation of Hearing Process § 45.25 What will DOI do... will refer the case for a hearing as follows: (1) If the hearing is to be conducted by DOI, OEPC will...

41 CFR 102-75.650 - When must DOI request assignment of the property?

Code of Federal Regulations, 2011 CFR

2011-01-01

... 41 Public Contracts and Property Management 3 2011-01-01 2011-01-01 false When must DOI request...-75.650 When must DOI request assignment of the property? Within 30 calendar days after the expiration of the 30-calendar day period specified in § 102-75.640, DOI must submit to the disposal agency an...

43 CFR 2.31 - How will DOI respond to my appeal?

Code of Federal Regulations, 2011 CFR

2011-10-01

... 43 Public Lands: Interior 1 2011-10-01 2011-10-01 false How will DOI respond to my appeal? 2.31... OF INFORMATION ACT FOIA Appeals § 2.31 How will DOI respond to my appeal? (a) Appeals will be decided... will state the basis for DOI's decision as follows: (1) Decision to release or withhold records. (i) If...

Time-Resolved Diffuse Optical Spectroscopy and Imaging Using Solid-State Detectors: Characteristics, Present Status, and Research Challenges

PubMed Central

Alayed, Mrwan

2017-01-01

Diffuse optical spectroscopy (DOS) and diffuse optical imaging (DOI) are emerging non-invasive imaging modalities that have wide spread potential applications in many fields, particularly for structural and functional imaging in medicine. In this article, we review time-resolved diffuse optical imaging (TR-DOI) systems using solid-state detectors with a special focus on Single-Photon Avalanche Diodes (SPADs) and Silicon Photomultipliers (SiPMs). These TR-DOI systems can be categorized into two types based on the operation mode of the detector (free-running or time-gated). For the TR-DOI prototypes, the physical concepts, main components, figures-of-merit of detectors, and evaluation parameters are described. The performance of TR-DOI prototypes is evaluated according to the parameters used in common protocols to test DOI systems particularly basic instrumental performance (BIP). In addition, the potential features of SPADs and SiPMs to improve TR-DOI systems and expand their applications in the foreseeable future are discussed. Lastly, research challenges and future developments for TR-DOI are discussed for each component in the prototype separately and also for the entire system. PMID:28906462

ARC: An open-source library for calculating properties of alkali Rydberg atoms

NASA Astrophysics Data System (ADS)

Šibalić, N.; Pritchard, J. D.; Adams, C. S.; Weatherill, K. J.

2017-11-01

We present an object-oriented Python library for the computation of properties of highly-excited Rydberg states of alkali atoms. These include single-body effects such as dipole matrix elements, excited-state lifetimes (radiative and black-body limited) and Stark maps of atoms in external electric fields, as well as two-atom interaction potentials accounting for dipole and quadrupole coupling effects valid at both long and short range for arbitrary placement of the atomic dipoles. The package is cross-referenced to precise measurements of atomic energy levels and features extensive documentation to facilitate rapid upgrade or expansion by users. This library has direct application in the field of quantum information and quantum optics which exploit the strong Rydberg dipolar interactions for two-qubit gates, robust atom-light interfaces and simulating quantum many-body physics, as well as the field of metrology using Rydberg atoms as precise microwave electrometers. Program Files doi:http://dx.doi.org/10.17632/hm5n8w628c.1 Licensing provisions: BSD-3-Clause Programming language: Python 2.7 or 3.5, with C extension External Routines: NumPy [1], SciPy [1], Matplotlib [2] Nature of problem: Calculating atomic properties of alkali atoms including lifetimes, energies, Stark shifts and dipole-dipole interaction strengths using matrix elements evaluated from radial wavefunctions. Solution method: Numerical integration of radial Schrödinger equation to obtain atomic wavefunctions, which are then used to evaluate dipole matrix elements. Properties are calculated using second order perturbation theory or exact diagonalisation of the interaction Hamiltonian, yielding results valid even at large external fields or small interatomic separation. Restrictions: External electric field fixed to be parallel to quantisation axis. Supplementary material: Detailed documentation (.html), and Jupyter notebook with examples and benchmarking runs (.html and .ipynb). [1] T.E. Oliphant, Comput. Sci. Eng. 9, 10 (2007). http://www.scipy.org/. [2] J.D. Hunter, Comput. Sci. Eng. 9, 90 (2007). http://matplotlib.org/.

Decreased social behaviour following 3,4-methylenedioxymethamphetamine (MDMA) is accompanied by changes in 5-HT2A receptor responsivity.

PubMed

Bull, Eleanor J; Hutson, Peter H; Fone, Kevin C F

2004-02-01

This study examined the involvement of the 5-HT(2A) receptor in the long-term anxiogenic effect of a brief exposure of young rats to 3,4-methylenedioxymethamphetamine (MDMA) using the social interaction and elevated plus-maze paradigms. Wistar rats (post-natal day (PND) 28) received either MDMA (5 mg/kg i.p.) or saline (1 ml/kg i.p.) hourly for 4 h on 2 consecutive days. Locomotor activity was measured for 60 min after the first injection and core body temperature was recorded at regular intervals over 4 h. On PND 84, without further drug administration, social interaction was assessed between treatment-matched rat pairs derived from separate litters. On PND 86, rats received either the 5-HT(2A/2C) receptor agonist, 1-(2,5-dimethoxy-4-iodophenyl)-2-aminopropane (DOI, 1 mg/kg i.p.) or saline and locomotor activity, wet-dog shakes and back muscle contractions were monitored. The change in elevated plus-maze behaviour was assessed following the same injection on PND 87. Acutely, MDMA produced a significant hyperlocomotion and hyperthermia (p<0.01). Following 55 days of abstinence, social interaction was reduced by 27% in MDMA pre-treated rats compared with that in controls (p<0.01). On the elevated plus-maze, pre-treatment with MDMA prevented the anxiogenic effect of DOI. On PND 92, hippocampal, frontal cortical and striatal 5-hydroxytryptamine (5-HT) was significantly reduced in MDMA pre-treated rats by between 16% and 22%, without any accompanying change in [(3)H]paroxetine binding in cortical homogenates. In conclusion, exposure of young rats to repeated MDMA caused serotonin depletion and induced 'anxiety-like' behaviour in the social interaction test accompanied by a long-lasting reduction in specific 5-HT(2A) receptor mediated behaviour.

Dopamine D2 heteroreceptor complexes and their receptor-receptor interactions in ventral striatum: novel targets for antipsychotic drugs.

PubMed

Fuxe, Kjell; Borroto-Escuela, Dasiel O; Tarakanov, Alexander O; Romero-Fernandez, Wilber; Ferraro, Luca; Tanganelli, Sergio; Perez-Alea, Mileidys; Di Palma, Michael; Agnati, Luigi F

2014-01-01

This review is focused on the D2 heteroreceptor complexes within the ventral striatum with their receptor-receptor interactions and relevance for the treatment of schizophrenia. A "guide-and-clasp" manner for receptor-receptor interactions is proposed where "adhesive guides" may be amino acid triplet homologies, which were determined for different kinds of D2 heteroreceptor complexes. The first putative D2 heteroreceptor complex to be discovered in relation to schizophrenia was the A2A-D2 heteroreceptor complex where antagonistic A2A-D2 receptor-receptor interactions were demonstrated after A2A agonist treatment in the ventral striatum. The A2A agonist CGS 21680 with atypical antipsychotic properties may at least in part act by increasing β-arrestin2 signaling over the D2 protomer in the A2A-D2 heteroreceptor complex in the ventral striatum. The antagonistic NTS1-D2 interactions in the NTS1-D2 heteroreceptor complex in the ventral striatum are proposed as one molecular mechanism for the potential antipsychotic effects of NT. Indications were obtained that the psychotic actions of the 5-HT2AR hallucinogens LSD and DOI can involve enhancement of D2R protomer signaling via a biased agonist action at the 5-HT2A protomer in the D2-5-HT2A heteroreceptor complex in the ventral striatum. Facilitatory allosteric D2likeR-OTR interactions in heteroreceptor complexes in nucleus accumbens may have a role in social and emotional behaviors. By blocking the D2 protomers of these heteroreceptor complexes, antipsychotics can fail to reduce the negative symptoms of schizophrenia. The discovery of different types of D2 heteroreceptor complexes gives an increased understanding of molecular mechanisms involved in causing schizophrenia and new strategies for its treatment and understanding the side effects of antipsychotics. © 2014 Elsevier B.V. All rights reserved.

Lightning impact on micro-second long ionospheric variability

NASA Astrophysics Data System (ADS)

Koh, Kuang Liang; Liu, Zhongjian; Fullekrug, Martin

2017-04-01

Lightning discharges cause electron heating and enhanced ionisation in the D region ionosphere which disturb the transmission of VLF communications [Inan et al., 2010]. A disturbance of such nature was measured in a VLF transmission with a sampling rate of 1 MHz, enabling much faster ionospheric variability to be observed when compared to previous studies which typically report results with a time resolution >5-20ms. The disturbance resembles "Long Recovery Early VLF" (LORE) events [Haldoupis et al. 2013, Cotts & Inan 2007]. LOREs exhibit observable ionospheric effects that last longer (>200s) than other lightning related disturbances. It was proposed that the mechanism behind the long-lasting effects of LOREs is different to shorter events [Gordillo-Vázquez et al. 2016]. The ionospheric variability inferred from the transmitted signal is seen to change dramatically after the lightning onset, suggesting that there are fast processes in the ionosphere affected or produced which have not been considered in previous research. The ionospheric variability inferred from the main two frequencies of the transmission is different. A possible explanation is a difference in the propagation paths of the two main frequencies of the transmission [Füllekrug et al., 2015]. References Inan, U.S., Cummer, S.A., Marshall, R.A., 2010. A survey of ELF and VLF research on lightning-ionosphere interactions and causative discharges. J. Geophys. Res. 115, A00E36. doi:10.1029/2009JA014775 Cotts, B.R.T., Inan, U.S., 2007. VLF observation of long ionospheric recovery events. Geophys. Res. Lett. 34, L14809. doi:10.1029/2007GL030094 Haldoupis, C., Cohen, M., Arnone, E., Cotts, B., Dietrich, S., 2013. The VLF fingerprint of elves: Step-like and long-recovery early VLF perturbations caused by powerful ±CG lightning EM pulses. J. Geophys. Res. Space Physics 118, 5392-5402. doi:10.1002/jgra.50489 Gordillo-Vázquez, F.J., Luque, A., Haldoupis, C., 2016. Upper D region chemical kinetic modeling of LORE relaxation times: KINETIC MODEL OF LORE RELAXATION TIMES. Journal of Geophysical Research: Space Physics 121, 3525-3544. doi:10.1002/2015JA021408 Füllekrug, M., Smith, N., Mezentsev, A., Watson, R., Astin, I., Gaffet, S., Evans, A., Rycroft, M., 2015. Multipath propagation of low-frequency radio waves inferred from high-resolution array analysis. Radio Sci. 50, 2015RS005781. doi:10.1002/2015RS005781

An immunocapture/scintillation proximity analysis of G alpha q/11 activation by native serotonin (5-HT)2A receptors in rat cortex: blockade by clozapine and mirtazapine.

PubMed

Mannoury La Cour, C; Chaput, C; Touzard, M; Millan, M J

2009-02-01

Though transduction mechanisms recruited by heterologously expressed 5-HT(2A) receptors have been extensively studied, their interaction with specific subtypes of G-protein remains to be directly evaluated in cerebral tissue. Herein, as shown by an immunocapture/scintillation proximity analysis, 5-HT, the prototypical 5-HT(2A) agonist, DOI, and Ro60,0175 all enhanced [(35)S]GTPgammaS binding to G alpha q/11 in rat cortex with pEC(50) values of 6.22, 7.24 and 6.35, respectively. No activation of G o or G s/olf was seen at equivalent concentrations of DOI. Stimulation of G alpha q/11 by 5-HT (30 microM) and DOI (30 microM) was abolished by the selective 5-HT(2A) vs. 5-HT(2C)/5-HT(2B) antagonists, ketanserin (pK(B) values of 9.11 and 8.88, respectively) and MDL100,907 (9.82 and 9.68). By contrast, 5-HT-induced [(35)S]GTPgammaS binding to G alpha q/11 was only weakly inhibited by the preferential 5-HT(2C) receptor antagonists, RS102,221 (6.94) and SB242,084 (7.39), and the preferential 5-HT(2B) receptor antagonist, LY266,097 (6.66). The antipsychotic, clozapine, which had marked affinity for 5-HT(2A) receptors, blocked the recruitment of G alpha q/11 by 5-HT and DOI with pK(B) values of 8.54 and 8.14, respectively. Its actions were mimicked by the "atypical" antidepressant and 5-HT(2A) receptor antagonist, mirtazapine, which likewise blocked 5-HT and DOI-induced G alpha q/11 protein activation with pK(B) values of 7.90 and 7.76, respectively. In conclusion, by use of an immunocapture/scintillation proximity strategy, this study shows that native 5-HT(2A) receptors in rat frontal cortex specifically recruit G alpha q/11 and that this action is blocked by clozapine and mirtazapine. Quantification of 5-HT(2A) receptor-mediated G alpha q/11 activation in frontal cortex should prove instructive in characterizing the actions of diverse classes of psychotropic agent. 2008 Wiley-Liss, Inc.

Modeling the Role of Bulk and Surface Characteristics of Carbon Fiber on Thermal Conductance across the Carbon Fiber/Matrix Interface (Postprint)

DTIC Science & Technology

2015-11-09

Osguthorpe, D. J.; Wolff, J.; Genest, M.; Hagler, A. T. Structure and Energetics of Ligand Binding to Proteins: Escherichia Coli Dihydrofolate...available at DOI: 10.1021/acsami.5b08591 14. ABSTRACT (Maximum 200 words) The rapid heating of carbon-fiber-reinforced polymer matrix composites leads ...polymer matrix composites leads to complex thermophysical interactions which not only are dependent on the thermal properties of the constituents and

Meta-Analysis of Multiple Simulation-Based Experiments

DTIC Science & Technology

2013-06-01

Alberts et al ., 2010), C2 Approaches differ on at least three major aspects: the allocation of decision rights (ADR), the pattern of interaction among...results obtained from the meta-analysis support the hypothesis that more network-enabled C2 Approaches are more agile (for details see Bernier et al ...consult Bernier, Chan et al . (2013) for more details. DoI PoI ADR Figure 2: Mapping of all CiCs into each axis of the C2 Approach Space. 18th

STS-87 Day 13 Highlights

NASA Technical Reports Server (NTRS)

1997-01-01

On this thirteenth day of the STS-87 mission, the flight crew, Cmdr. Kevin R. Kregel, Pilot Steven W. Lindsey, Mission Specialists Winston E. Scott, Kalpana Chawla, and Takao Doi, and Payload Specialist Leonid K. Kadenyuk continue work in the mini laboratory called the microgravity glovebox facility. This facility allows crew members to interactively work with two different experiments today studying the formation of composite materials in an attempt to accurately map the roles of gravity-induced convection and sedimentation on the samples.

Development of a Silicon Metal-Oxide-Semiconductor-Based Qubit Using Spin Exchange Interactions Alone

DTIC Science & Technology

2016-03-31

Electron spin resonance and spin–valley physics in a silicon double quantum dot, Nature Communications, (05 2014): 0. doi: 10.1038/ncomms4860 Ming...new scheme to better manipulate the exchange-only qubit using a pulsed RF source [5], known as a resonant -exchange-qubit [6,7], in GaAs further...triple points into a quadruple point [10], as shown in Fig. 1. We can also gate control the tunnel coupling over a broad energy range. The

Young Investigator Program (8.5): Preventing Complex Failures of Human Interactive Systems with Erroneous Behavior Generation and Robust Human Task Behavior Patterns

DTIC Science & Technology

2017-11-13

behavior . The International Journal of Human-Computer Studies , 108, 105-121. https://doi.org/10.1016/j.ijhcs.2017.06.006 A second journal article...documenting the erroneous behavior generation approach and the case study analyses is currently being written. Planned submission is Spring 2017. RPPR...Belvoir, 2010. [3] A task-based taxonomy of erroneous human behavior . International Journal of Human-Computer Studies , 108:105–121, 2017. [4] M. L

Water infiltration and hydraulic conductivity in a natural Mediterranean oak forest: impacts of hydrology-oriented silviculture on soil hydraulic properties

NASA Astrophysics Data System (ADS)

Di Prima, Simone; Bagarello, Vincenzo; Bautista, Inmaculada; Cerdà, Artemi; Cullotta, Sebastiano; del Campo, Antonio; González-Sanchis, María; Iovino, Massimo; Maetzke, Federico

2016-04-01

In the last years researchers reported an increasing need to have more awareness on the intimate link between land use and soil hydrological properties (soil organic matter storage, water infiltration, hydraulic conductivity) and their possible effects on water retention (e.g., Bens et al., 2006; del Campo et al., 2014; González-Sanchis et al., 2015; Molina and del Campo, 2012). In the Mediterranean ecosystems, special attention needs to be paid to the forest-water relationships due to the natural scarcity of water. Adaptive forest management (AFM) aims to adapt the forest to water availability by means of an artificial regulation of the forest structure and density in order to promote tree and stand resilience through enhancing soil water availability (del Campo et al., 2014). The opening of the canopy, due to the removal of a certain number of trees, is an important practice for the management of forests. It results in important modifications to the microclimatic conditions that influence the ecophysiological functioning of trees (Aussenac and Granier, 1988). However, the effect of thinning may vary depending on the specific conditions of the forest (Andréassian, 2004; Brooks et al., 2003; Cosandey et al., 2005; Lewis et al., 2000; Molina and del Campo, 2012). Different authors reported that a reduction in forest cover increases water yield due to the subsequent reduction in evapotranspiration (Brooks et al., 2003; González-Sanchis et al., 2015; Hibbert, 1983; Zhang et al., 2001). On the other hand, the water increase may be easily evaporated from the soil surface (Andréassian, 2004). In this context, determining soil hydraulic properties in forests is essential for understanding and simulating the hydrological processes (Alagna et al., 2015; Assouline and Mualem, 2002), in order to adapt a water-saving management to a specific case, or to study the effects of a particular management practice. However, it must be borne in mind that changes brought about by the practice of forest management persist for almost one century. It is therefore important to monitor managed sites over longer periods, since short-term investigations are insufficient to detect changes that may influence e.g. larger parts of watersheds (Bens et al., 2006). In addition, soil hydraulic properties exhibit strong spatial and temporal variations and a large number of determinations are required to assess the magnitude of the variation within the selected area (Logsdon and Jaynes, 1996). The use of simple and rapid field techniques is therefore important to obtain reliable data with a sustainable effort (Bagarello et al., 2014; Di Prima et al., 2016). The Beerkan Estimation of Soil Transfer (BEST) parameters procedure by Lassabatere et al. (2006) is very attractive for practical use since it allows an estimation of both the soil water retention and the hydraulic conductivity functions from cumulative infiltration collected during a ponded field experiment and a few routinely laboratory determinations. Lassabatere et al. (2006) suggested to measure the infiltration time of small volumes of water repeatedly poured on the soil surface confined by a ring inserted to a depth of about 1 cm into the soil. BEST considers a zero ponded infiltration model which was assumed to be appropriate for an infiltration run performed with small, but positive, pressure heads. This assumption was supported by numerical tests carried out by Touma et al. (2007). Recently, Di Prima (2015) developed a method to automate data collection with a compact infiltrometer under constant head conditions. The device, maintaining a small quasi-constant head of water (i.e., 2-3 mm) on the infiltration surface, is equipped with a differential pressure transducer to measure the stepwise drop of water level in the reservoir, and, in turn, to quantify cumulative infiltration into the soil. The data acquisition system has been designed with low cost components and it is based on the open source microcontroller platform, Arduino. The very limited cost of the system could represent a step towards a cheaper and more widespread application of accurate and automated infiltration rate measurement. However, automatic data collection increases measurement speed, permits measurement at short time intervals, improves measurement precision, allows for more efficient data handling and analysis, and reduces the amount of effort involved and the potential for errors that may occur when manual procedures are applied (Di Prima et al., 2016). The main objective of this study was to determine soil hydraulic properties by using the combination of the automated infiltrometer and the BEST algorithm in a natural Mediterranean oak forest. The forest is located in a typical Mediterranean area, within the public forest La Hunde, Valencia (NE Spain). Two contiguous plots established in previous studies conducted by González-Sanchis et al. (2015) were selected, one of them was thinned reducing the forest density from 861 to 414 tree per ha. Control plot was not thinned. These authors studied the water cycle during the period 2012-2013. In particular, they characterized and compared the plots in term of throughfall, stemflow, soil moisture and transpiration, concluding that the AFM results in an increasing water availability, and at the same time in a substantial maintenance of overland and surface flow, precluding therefore enhancement of erosion rate. In this paper, the focus was put on the impacts of thinning on soil hydraulic properties, such as infiltration capacity, hydraulic conductivity and soil water retention, determined by simplified and low-cost methods in connection with a hydrology-oriented silviculture. Acknowledgements This study is a part of research projects: "Indagini sperimentali per la simulazione dei processi di formazione del deflusso superficiale nei suoli boscati, Progetto FIRB 2012 - MIMOSE", and "CGL2011-28776-C02-02, HYDROSIL" References Alagna, V., Bagarello, V., Di Prima, S., Iovino, M., 2015. Determining hydraulic properties of a loam soil by alternative infiltrometer techniques. Hydrol. Process. doi:10.1002/hyp.10607 Andréassian, V., 2004. Waters and forests: from historical controversy to scientific debate. Journal of Hydrology 291, 1-27. doi:10.1016/j.jhydrol.2003.12.015 Assouline, S., Mualem, Y., 2002. Infiltration during soil sealing: The effect of areal heterogeneity of soil hydraulic properties. Water Resour. Res. 38, 1286. doi:10.1029/2001WR001168 Aussenac, G., Granier, A., 1988. Effects of thinning on water stress and growth in Douglas-fir. Canadian Journal of Forest Research 18, 100-105. doi:10.1139/x88-015 Bagarello, V., Di Prima, S., Iovino, M., Provenzano, G., 2014. Estimating field-saturated soil hydraulic conductivity by a simplified Beerkan infiltration experiment. Hydrological Processes 28, 1095-1103. doi:10.1002/hyp.9649 Bens, O., Wahl, N.A., Fischer, H., Hüttl, R.F., 2006. Water infiltration and hydraulic conductivity in sandy cambisols: impacts of forest transformation on soil hydrological properties. Eur J Forest Res 126, 101-109. doi:10.1007/s10342-006-0133-7 Brooks, K.N., Folliott, P.F., Gregersen, H.M., DeBano, L.F., 2003. Hydrology and the Management of Watersheds. Hydrology and the Management of Watersheds 575. Cosandey, C., Andréassian, V., Martin, C., Didon-Lescot, J.F., Lavabre, J., Folton, N., Mathys, N., Richard, D., 2005. The hydrological impact of the mediterranean forest: a review of French research. Journal of Hydrology 301, 235-249. doi:10.1016/j.jhydrol.2004.06.040 del Campo, A.D., Fernandes, T.J.G., Molina, A.J., 2014. Hydrology-oriented (adaptive) silviculture in a semiarid pine plantation: How much can be modified the water cycle through forest management? European Journal of Forest Research 133, 879-894. doi:10.1007/s10342-014-0805-7 Di Prima, S., 2015. Automated single ring infiltrometer with a low-cost microcontroller circuit. Computers and Electronics in Agriculture 118, 390-395. doi:10.1016/j.compag.2015.09.022 Di Prima, S., Lassabatere, L., Bagarello, V., Iovino, M., Angulo-Jaramillo, R., 2016. Testing a new automated single ring infiltrometer for Beerkan infiltration experiments. Geoderma 262, 20-34. doi:10.1016/j.geoderma.2015.08.006 González-Sanchis, M., del Campo, A., Lidón, A., Lull, C., Bautista, I., García-Prats, A., Francés, F., others, 2015. Incorporación de criterios eco-hidrológicos en la gestión forestal: adaptación a la escasez de agua de una masa marginal de encina. Cuadernos de la Sociedad Española de Ciencias Forestales. Hibbert, A.R., 1983. Water Yield Improvement Potential by Vegetation Management on Western Rangelands1. JAWRA Journal of the American Water Resources Association 19, 375-381. doi:10.1111/j.1752-1688.1983.tb04594.x Lassabatère, L., Angulo-Jaramillo, R., Soria Ugalde, J.M., Cuenca, R., Braud, I., Haverkamp, R., 2006. Beerkan Estimation of Soil Transfer Parameters through Infiltration Experiments - BEST. Soil Science Society of America Journal 70, 521. doi:10.2136/sssaj2005.0026 Lewis, D., Singer, M.J., Dahlgren, R.A., Tate, K.W., 2000. Hydrology in a California oak woodland watershed: a 17-year study. Journal of Hydrology 240, 106-117. doi:10.1016/S0022-1694(00)00337-1 Logsdon, S.D., Jaynes, D.B., 1996. Spatial Variability of Hydraulic Conductivity in a Cultivated Field at Different Times. Soil Science Society of America Journal 60, 703. doi:10.2136/sssaj1996.03615995006000030003x Molina, A.J., del Campo, A.D., 2012. The effects of experimental thinning on throughfall and stemflow: A contribution towards hydrology-oriented silviculture in Aleppo pine plantations. Forest Ecology and Management 269, 206-213. doi:10.1016/j.foreco.2011.12.037 Touma, J., Voltz, M., Albergel, J., 2007. Determining soil saturated hydraulic conductivity and sorptivity from single ring infiltration tests. European Journal of Soil Science 58, 229-238. doi:10.1111/j.1365-2389.2006.00830.x Zhang, L., Dawes, W.R., Walker, G.R., 2001. Response of mean annual evapotranspiration to vegetation changes at catchment scale. Water Resour. Res. 37, 701-708. doi:10.1029/2000WR900325

Potential effects of existing and proposed groundwater withdrawals on water levels and natural groundwater discharge in Snake Valley and surrounding areas, Utah and Nevada

USGS Publications Warehouse

Masbruch, Melissa D.; Brooks, Lynette E.

2017-04-14

Several U.S. Department of Interior (DOI) agencies are concerned about the cumulative effects of groundwater development on groundwater resources managed by, and other groundwater resources of interest to, these agencies in Snake Valley and surrounding areas. The new water uses that potentially concern the DOI agencies include 12 water-right applications filed in 2005, totaling approximately 8,864 acre-feet per year. To date, only one of these applications has been approved and partially developed. In addition, the DOI agencies are interested in the potential effects of three new water-right applications (UT 18-756, UT 18-758, and UT 18-759) and one water-right change application (UT a40687), which were the subject of a water-right hearing on April 19, 2016.This report presents a hydrogeologic analysis of areas in and around Snake Valley to assess potential effects of existing and future groundwater development on groundwater resources, specifically groundwater discharge sites, of interest to the DOI agencies. A previously developed steady-state numerical groundwater-flow model was modified to transient conditions with respect to well withdrawals and used to quantify drawdown and capture (withdrawals that result in depletion) of natural discharge from existing and proposed groundwater withdrawals. The original steady-state model simulates and was calibrated to 2009 conditions. To investigate the potential effects of existing and proposed groundwater withdrawals on the groundwater resources of interest to the DOI agencies, 10 withdrawal scenarios were simulated. All scenarios were simulated for periods of 5, 10, 15, 30, 55, and 105 years from the start of 2010; additionally, all scenarios were simulated to a new steady state to determine the ultimate long-term effects of the withdrawals. Capture maps were also constructed as part of this analysis. The simulations used to develop the capture maps test the response of the system, specifically the reduction of natural discharge, to future stresses at a point in the area represented by the model. In this way, these maps can be used as a tool to determine the source of water to, and potential effects at specific areas from, future well withdrawals.Downward trends in water levels measured in wells indicate that existing groundwater withdrawals in Snake Valley are affecting water levels. The numerical model simulates similar downward trends in water levels; simulated drawdowns in the model, however, are generally less than observed water-level declines. At the groundwater discharge sites of interest to the DOI agencies, simulated drawdowns from existing well withdrawals (projected into the future) range from 0 to about 50 feet. Following the addition of the proposed withdrawals, simulated drawdowns at some sites increase by 25 feet. Simulated drawdown resulting from the proposed withdrawals began in as few as 5 years after 2014 at several of the sites. At the groundwater discharge sites of interest to the DOI agencies, simulated capture of natural discharge resulting from the existing withdrawals ranged from 0 to 87 percent. Following the addition of the proposed withdrawals, simulated capture at several of the sites reached 100 percent, indicating that groundwater discharge at that site would cease. Simulated capture following the addition of the proposed withdrawals increased in as few as 5 years after 2014 at several of the sites.

Do gray wolves (Canis lupus) support pack mates during aggressive inter-pack interactions?

PubMed

Cassidy, Kira A; McIntyre, Richard T

2016-09-01

For group-living mammals, social coordination increases success in everything from hunting and foraging (Crofoot and Wrangham in Mind the Gap, Springer, Berlin, 2010; Bailey et al. in Behav Ecol Sociobiol 67:1-17, 2013) to agonism (Mosser and Packer in Anim Behav 78:359-370, 2009; Wilson et al. in Anim Behav 83:277-291, 2012; Cassidy et al. in Behav Ecol 26:1352-1360, 2015). Cooperation is found in many species and, due to its low costs, likely is a determining factor in the evolution of living in social groups (Smith in Anim Behav 92:291-304, 2014). Beyond cooperation, many mammals perform costly behaviors for the benefit of group mates (e.g., parental care, food sharing, grooming). Altruism is considered the most extreme case of cooperation where the altruist increases the fitness of the recipient while decreasing its own fitness (Bell in Selection: the mechanism of evolution. Oxford University Press, Oxford 2008). Gray wolf life history requires intra-pack familiarity, communication, and cooperation in order to succeed in hunting (MacNulty et al. in Behav Ecol doi: 10.1093/beheco/arr159 2011) and protecting group resources (Stahler et al. in J Anim Ecol 82: 222-234, 2013; Cassidy et al. in Behav Ecol 26:1352-1360, 2015). Here, we report 121 territorial aggressive inter-pack interactions in Yellowstone National Park between 1 April 1995 and 1 April 2011 (>5300 days of observation) and examine each interaction where one wolf interferes when its pack mate is being attacked by a rival group. This behavior was recorded six times (17.6 % of interactions involving an attack) and often occurred between dyads of closely related individuals. We discuss this behavior as it relates to the evolution of cooperation, sociality, and altruism.

House Dust Endotoxin and Peripheral Leukocyte Counts: Results from Two Large Epidemiologic Studies.

PubMed

Fessler, Michael B; Carnes, Megan U; Salo, Päivi M; Wilkerson, Jesse; Cohn, Richard D; King, Debra; Hoppin, Jane A; Sandler, Dale P; Travlos, Greg; London, Stephanie; Thorne, Peter; Zeldin, Darryl

2017-05-31

The peripheral leukocyte count is a biomarker of inflammation and is associated with human all-cause mortality. Although causes of acute leukocytosis are well-described, chronic environmental determinants of leukocyte number are less well understood. We investigated the relationship between house dust endotoxin concentration and peripheral leukocyte counts in human subjects. The endotoxin–leukocyte relationship was evaluated by linear regression in the National Health and Nutrition Examination Survey (NHANES) 2005–2006 (n=6,254) and the Agricultural Lung Health Study (ALHS; n=1,708). In the ALHS, we tested for a gene [Toll-like Receptor 4 ( TLR4 ), encoding the endotoxin receptor]-by-environment interaction in the endotoxin–leukocyte relationship using regression models with an interaction term. There is a statistically significant, positive association between endotoxin concentration and total leukocyte number [estimated change, 0.186×10 3 /μL (95% CI: 0.070, 0.301×10 3 /μL) per 10-fold change in endotoxin; p=0.004) in the NHANES. Similar positive associations were found for monocytes, lymphocytes, and neutrophils. Stratified analyses revealed possible effect modification by asthma and chronic obstructive pulmonary disease. We observed similar associations in the ALHS. For total leukocytes, there was suggestive evidence in the ALHS of a gene-by-environment interaction for minor allele carrier status at the TLR4 haplotype defined by rs4986790 and rs4986791 (interaction p=0.15). This is, to our knowledge, the first report of an association between house dust endotoxin and leukocyte count in a national survey. The finding was replicated in a farming population. Peripheral leukocyte count may be influenced by residential endotoxin exposure in diverse settings. https://doi.org/10.1289/EHP661.

House Dust Endotoxin and Peripheral Leukocyte Counts: Results from Two Large Epidemiologic Studies

PubMed Central

Carnes, Megan U.; Salo, Päivi M.; Wilkerson, Jesse; Cohn, Richard D.; King, Debra; Hoppin, Jane A.; Sandler, Dale P.; Travlos, Greg; London, Stephanie J.; Thorne, Peter S.; Zeldin, Darryl C.

2017-01-01

Background: The peripheral leukocyte count is a biomarker of inflammation and is associated with human all-cause mortality. Although causes of acute leukocytosis are well-described, chronic environmental determinants of leukocyte number are less well understood. Objectives: We investigated the relationship between house dust endotoxin concentration and peripheral leukocyte counts in human subjects. Methods: The endotoxin–leukocyte relationship was evaluated by linear regression in the National Health and Nutrition Examination Survey (NHANES) 2005–2006 (n=6,254) and the Agricultural Lung Health Study (ALHS; n=1,708). In the ALHS, we tested for a gene [Toll-like Receptor 4 (TLR4), encoding the endotoxin receptor]-by-environment interaction in the endotoxin–leukocyte relationship using regression models with an interaction term. Results: There is a statistically significant, positive association between endotoxin concentration and total leukocyte number [estimated change, 0.186×103/μL (95% CI: 0.070, 0.301×103/μL) per 10-fold change in endotoxin; p=0.004) in the NHANES. Similar positive associations were found for monocytes, lymphocytes, and neutrophils. Stratified analyses revealed possible effect modification by asthma and chronic obstructive pulmonary disease. We observed similar associations in the ALHS. For total leukocytes, there was suggestive evidence in the ALHS of a gene-by-environment interaction for minor allele carrier status at the TLR4 haplotype defined by rs4986790 and rs4986791 (interaction p=0.15). Conclusions: This is, to our knowledge, the first report of an association between house dust endotoxin and leukocyte count in a national survey. The finding was replicated in a farming population. Peripheral leukocyte count may be influenced by residential endotoxin exposure in diverse settings. https://doi.org/10.1289/EHP661 PMID:28599265

Ligand requirements for involvement of PKCε in synergistic analgesic interactions between spinal μ and δ opioid receptors.

PubMed

Schuster, D J; Metcalf, M D; Kitto, K F; Messing, R O; Fairbanks, C A; Wilcox, G L

2015-01-01

We recently found that PKCε was required for spinal analgesic synergy between two GPCRs, δ opioid receptors and α2 A adrenoceptors, co-located in the same cellular subpopulation. We sought to determine if co-delivery of μ and δ opioid receptor agonists would similarly result in synergy requiring PKCε. Combinations of μ and δ opioid receptor agonists were co-administered intrathecally by direct lumbar puncture to PKCε-wild-type (PKCε-WT) and -knockout (PKCε-KO) mice. Antinociception was assessed using the hot-water tail-flick assay. Drug interactions were evaluated by isobolographic analysis. All agonists produced comparable antinociception in both PKCε-WT and PKCε-KO mice. Of 19 agonist combinations that produced analgesic synergy, only 3 required PKCε for a synergistic interaction. In these three combinations, one of the agonists was morphine, although not all combinations involving morphine required PKCε. Morphine + deltorphin II and morphine + deltorphin I required PKCε for synergy, whereas a similar combination, morphine + deltorphin, did not. Additionally, morphine + oxymorphindole required PKCε for synergy, whereas a similar combination, morphine + oxycodindole, did not. We discovered biased agonism for a specific signalling pathway at the level of spinally co-delivered opioid agonists. As the bias is only revealed by an appropriate ligand combination and cannot be accounted for by a single drug, it is likely that the receptors these agonists act on are interacting with each other. Our results support the existence of μ and δ opioid receptor heteromers at the spinal level in vivo. This article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2. © 2014 The British Pharmacological Society.

Emission Data For Climate-Chemistry Interactions

NASA Astrophysics Data System (ADS)

Smith, S. J.

2012-12-01

Data on anthropogenic and natural emissions of reactive species are a critical input for studies of atmospheric chemistry and climate. The availability and characteristics of anthropogenic emissions data that can be used for such studies are reviewed and pathways for future work discuss Global and regional datasets for historical and future emissions are available, but their characteristics and applicability for specific studies differ. For the first time, a coordinated set of historical emissions (Lamarque et al 2010) and the future projections (van Vuurren et al. 2011) have been developed for use in the CMIP5 and ACCMIP long-term simulation comparison projects. These data have decadal resolution and were designed for long-term, global simulations. These data, however, lack finer-scale spatial and temporal detail that might be needed for some studies. Robust and timely updates of emissions data is generally lacking, although recent updates will be presented. While historical emission data is often treated as known, emissions are uncertain, even though this uncertainty is rarely quantified. Uncertainty varies by species and location. Inverse modeling is starting to indicate where emission data may be uncertain, which opens the way to improving these data overall. Further interaction between the chemistry modeling and inventory development communities are needed. Future projections are intrinsically uncertain, and while institutions and processes are in place to develop and review long-term century-scale scenarios, a need has remained for a wider range in shorter-term (e.g., several decade) projections. Emissions and scenario development communities have been working to fill this need. Communication across disciplines of the assumptions embedded in emissions projections remains a challenge. Atmospheric chemistry models are a central tool needed for studying chemistry-climate interactions. Simpler models, however, are also needed in order to examine interactions between different physical systems and also between the physical and human systems. Statistical models of system responses are particularly needed both to parameterize interactions in models that cannot simulate particular processes directly, and also to represent uncertainty. Coordinated model experiments are necessary to provide the information needed to develop these representations (i.e. Wild et al 2011). Lamarque, J. F, et al. (2010) Historical (1850-2000) gridded anthropogenic and biomass burning emissions of reactive gases and aerosols: methodology and application. Atmospheric Chemistry and Physics 10 pp. 7017-7039. doi:10.5194/acp-10-7017-2010 Van Vuuren, D, JA Edmonds, M Kainuma, K Riahi, AM Thomson, KA Hibbard, G Hurtt, T Kram, V Krey, JF Lamarque, matsui, M Meinhausen, N Nakicenovic, SJ Smith, and SK Rose. 2011. "The Representative Concentration Pathways: An Overview." Climatic Change 109 (1-2) 5-31. doi: 10.1007/s10584-011-0148-z. Wild, O., et al. (2012) Modelling future changes in surface ozone: A parameterized approach. Atmos. Chem. Phys., 12, 2037-2054, doi:10.5194/acp-12-2037-2012.

Spin-Orbit-Enhanced Functionality in LaAlO3/SrTiO3 Nanostructures

DTIC Science & Technology

2015-09-16

34 J. Vis. Exp. 89 , e51886 (2014). http://dx.doi.org/doi:10.3791/51886 J. A. Sulpizio, S. Ilani, P. Irvin, and J. Levy, "Nanoscale Phenomena in Oxide... 89 , e51886 (2014). http://dx.doi.org/doi:10.3791/51886 J. A. Sulpizio, S. Ilani, P. Irvin, and J. Levy, "Nanoscale Phenomena in Oxide

41 CFR 102-75.640 - When must DOI notify the disposal agency that an eligible applicant is interested in acquiring...

Code of Federal Regulations, 2010 CFR

2010-07-01

... 41 Public Contracts and Property Management 3 2010-07-01 2010-07-01 false When must DOI notify the... Disposal Property for Use As Public Park Or Recreation Areas § 102-75.640 When must DOI notify the disposal agency that an eligible applicant is interested in acquiring the property? DOI must notify the disposal...

Keeping it wild: an interagency strategy to monitor trends in wilderness character across the National Wilderness Preservation System

Treesearch

Peter Landres; Chris Barns; John G. Dennis; Tim Devine; Paul Geissler; Curtis S. McCasland; Linda Merigliano; Justin Seastrand; Ralph Swain

2008-01-01

The Interagency Wilderness Character Monitoring Team--representing the Department of the Interior (DOI) Bureau of Land Management, DOI Fish and Wildlife Service, DOI National Park Service, DOI U.S. Geological Survey, and the U.S. Forest Service-offers in this document an interagency strategy to monitor trends in wilderness character across the National Wilderness...

41 CFR 102-75.660 - What happens if DOI does not approve any applications or does not submit an assignment...

Code of Federal Regulations, 2011 CFR

2011-01-01

... 41 Public Contracts and Property Management 3 2011-01-01 2011-01-01 false What happens if DOI does... Disposal Property for Use As Public Park Or Recreation Areas § 102-75.660 What happens if DOI does not approve any applications or does not submit an assignment recommendation? If DOI does not approve any...

41 CFR 102-75.640 - When must DOI notify the disposal agency that an eligible applicant is interested in acquiring...

Code of Federal Regulations, 2011 CFR

2011-01-01

... 41 Public Contracts and Property Management 3 2011-01-01 2011-01-01 false When must DOI notify the... Disposal Property for Use As Public Park Or Recreation Areas § 102-75.640 When must DOI notify the disposal agency that an eligible applicant is interested in acquiring the property? DOI must notify the disposal...

77 FR 52340 - Meeting of the Secretarial Commission on Indian Trust Administration and Reform

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-29

... session the evening of September 13, 2012, at the United Tribes Technical College. DATES: The Commission's... held in the afternoon (time to be determined) on September 12, 2012, and the youth outreach session... Tribes Technical College; further information on these locations will be available at http://www.doi.gov...

Area-specific development of distinct projection neuron subclasses is regulated by postnatal epigenetic modifications

PubMed Central

Harb, Kawssar; Magrinelli, Elia; Nicolas, Céline S; Lukianets, Nikita; Frangeul, Laura; Pietri, Mariel; Sun, Tao; Sandoz, Guillaume; Grammont, Franck; Jabaudon, Denis; Studer, Michèle; Alfano, Christian

2016-01-01

During cortical development, the identity of major classes of long-distance projection neurons is established by the expression of molecular determinants, which become gradually restricted and mutually exclusive. However, the mechanisms by which projection neurons acquire their final properties during postnatal stages are still poorly understood. In this study, we show that the number of neurons co-expressing Ctip2 and Satb2, respectively involved in the early specification of subcerebral and callosal projection neurons, progressively increases after birth in the somatosensory cortex. Ctip2/Satb2 postnatal co-localization defines two distinct neuronal subclasses projecting either to the contralateral cortex or to the brainstem suggesting that Ctip2/Satb2 co-expression may refine their properties rather than determine their identity. Gain- and loss-of-function approaches reveal that the transcriptional adaptor Lmo4 drives this maturation program through modulation of epigenetic mechanisms in a time- and area-specific manner, thereby indicating that a previously unknown genetic program postnatally promotes the acquisition of final subtype-specific features. DOI: http://dx.doi.org/10.7554/eLife.09531.001 PMID:26814051

Molecular dynamics-based refinement and validation for sub-5 Å cryo-electron microscopy maps

PubMed Central

Singharoy, Abhishek; Teo, Ivan; McGreevy, Ryan; Stone, John E; Zhao, Jianhua; Schulten, Klaus

2016-01-01

Two structure determination methods, based on the molecular dynamics flexible fitting (MDFF) paradigm, are presented that resolve sub-5 Å cryo-electron microscopy (EM) maps with either single structures or ensembles of such structures. The methods, denoted cascade MDFF and resolution exchange MDFF, sequentially re-refine a search model against a series of maps of progressively higher resolutions, which ends with the original experimental resolution. Application of sequential re-refinement enables MDFF to achieve a radius of convergence of ~25 Å demonstrated with the accurate modeling of β-galactosidase and TRPV1 proteins at 3.2 Å and 3.4 Å resolution, respectively. The MDFF refinements uniquely offer map-model validation and B-factor determination criteria based on the inherent dynamics of the macromolecules studied, captured by means of local root mean square fluctuations. The MDFF tools described are available to researchers through an easy-to-use and cost-effective cloud computing resource on Amazon Web Services. DOI: http://dx.doi.org/10.7554/eLife.16105.001 PMID:27383269

9Å structure of the COPI coat reveals that the Arf1 GTPase occupies two contrasting molecular environments

PubMed Central

Dodonova, Svetlana O; Aderhold, Patrick; Kopp, Juergen; Ganeva, Iva; Röhling, Simone; Hagen, Wim J H; Sinning, Irmgard; Wieland, Felix; Briggs, John A G

2017-01-01

COPI coated vesicles mediate trafficking within the Golgi apparatus and between the Golgi and the endoplasmic reticulum. Assembly of a COPI coated vesicle is initiated by the small GTPase Arf1 that recruits the coatomer complex to the membrane, triggering polymerization and budding. The vesicle uncoats before fusion with a target membrane. Coat components are structurally conserved between COPI and clathrin/adaptor proteins. Using cryo-electron tomography and subtomogram averaging, we determined the structure of the COPI coat assembled on membranes in vitro at 9 Å resolution. We also obtained a 2.57 Å resolution crystal structure of βδ-COP. By combining these structures we built a molecular model of the coat. We additionally determined the coat structure in the presence of ArfGAP proteins that regulate coat dissociation. We found that Arf1 occupies contrasting molecular environments within the coat, leading us to hypothesize that some Arf1 molecules may regulate vesicle assembly while others regulate coat disassembly. DOI: http://dx.doi.org/10.7554/eLife.26691.001 PMID:28621666

Identity of neocortical layer 4 neurons is specified through correct positioning into the cortex

PubMed Central

Oishi, Koji; Nakagawa, Nao; Tachikawa, Kashiko; Sasaki, Shinji; Aramaki, Michihiko; Hirano, Shinji; Yamamoto, Nobuhiko; Yoshimura, Yumiko; Nakajima, Kazunori

2016-01-01

Many cell-intrinsic mechanisms have been shown to regulate neuronal subtype specification in the mammalian neocortex. However, how much cell environment is crucial for subtype determination still remained unclear. Here, we show that knockdown of Protocadherin20 (Pcdh20), which is expressed in post-migratory neurons of layer 4 (L4) lineage, caused the cells to localize in L2/3. The ectopically positioned “future L4 neurons” lost their L4 characteristics but acquired L2/3 characteristics. Knockdown of a cytoskeletal protein in the future L4 neurons, which caused random disruption of positioning, also showed that those accidentally located in L4 acquired the L4 characteristics. Moreover, restoration of positioning of the Pcdh20-knockdown neurons into L4 rescued the specification failure. We further suggest that the thalamocortical axons provide a positional cue to specify L4 identity. These results suggest that the L4 identity is not completely determined at the time of birth but ensured by the surrounding environment after appropriate positioning. DOI: http://dx.doi.org/10.7554/eLife.10907.001 PMID:26880563

THE RELATIONSHIP BETWEEN THE SEPTEMBER 2017 MARS GLOBAL AURORA EVENT AND CRUSTAL MAGNETIC FIELDS

NASA Astrophysics Data System (ADS)

Nasr, Camella-Rosa; Schneider, Nick; Connour, Kyle; Jain, Sonal; Deighan, Justin; Jakosky, Bruce; MAVEN/IUVS Team

2018-01-01

In September 2017, the Imaging UltraViolet Spectrograph (IUVS) on the MAVEN spacecraft observed global aurora on Mars caused by a surprisingly strong solar energetic particle event. Widespread “diffuse aurora” have previously been detected on Mars through more limited observations (Schneider et al., Science 350, (2015); DOI: 10.1126/science.aad0313), but recent observations established complete coverage of the observable portion of Mars’ nightside. The aurora was global due to Mars’s lack of a global magnetic field, which allowed energetic electrons from the Sun to directly precipitate into the atmosphere. On September 11th, IUVS detected aurora more than 25 times brighter than any prior IUVS observation, with high SNR detections of aurora at the limb and against the disk of the planet. Fainter auroral emission was seen around the nightside limb over 13 orbits spanning nearly 3 days.On September 14th, during the declining phase of the event, faint linear features and patches were detected by the spacecraft, which were higher than the noise floor, with a similar spatial distribution to “discrete aurora” patches observed on Mars by the SPICAM instrument on the Mars Express spacecraft (Bertaux et al., Nature 435, doi :10.1038/nature03603). Discrete aurora occur near areas of the crust affected by the magnetism left over from Mars’ once-strong dipole field. Emission is limited to regions of the crustal magnetic field where the field lines are likely to be open to solar wind interactions. Those regions are concentrated in Mars’ southern hemisphere centered on 180 degrees east longitude.We studied the localized emissions on 14 September to determine whether there might be a connection between the observed diffuse aurora event and discrete auroral processes. First, we investigated the localized emissions to confirm that the observed signal was consistent with expected auroral spectra. Second, their locations were projected on a map of the crustal magnetic fields to determine if they occurred near open magnetic field lines. We will report on the results of these two studies, and the ramifications for Mars auroral processes.

43 CFR 17.336 - Hearings, decisions, post-termination proceedings.

Code of Federal Regulations, 2010 CFR

2010-10-01

...-termination proceedings. Certain DOI procedural provisions applicable to title VI of the Civil Rights Act of 1964 apply to DOI's enforcement of these regulations. The procedural provisions of DOI's Title VI...

43 CFR 17.336 - Hearings, decisions, post-termination proceedings.

Code of Federal Regulations, 2011 CFR

2011-10-01

...-termination proceedings. Certain DOI procedural provisions applicable to title VI of the Civil Rights Act of 1964 apply to DOI's enforcement of these regulations. The procedural provisions of DOI's Title VI...

43 CFR 2.34 - Where can I get a copy of DOI's FOIA annual report?

Code of Federal Regulations, 2010 CFR

2010-10-01

... 43 Public Lands: Interior 1 2010-10-01 2010-10-01 false Where can I get a copy of DOI's FOIA... AND TESTIMONY; FREEDOM OF INFORMATION ACT FOIA Annual Report § 2.34 Where can I get a copy of DOI's FOIA annual report? Under 5 U.S.C. 552(e), DOI is required to prepare an annual report regarding its...

2 CFR 1401.401 - Whom in the DOI does a recipient who is an individual notify about a criminal drug conviction?

Code of Federal Regulations, 2011 CFR

2011-01-01

... 2 Grants and Agreements 1 2011-01-01 2011-01-01 false Whom in the DOI does a recipient who is an individual notify about a criminal drug conviction? 1401.401 Section 1401.401 Grants and Agreements Federal... Whom in the DOI does a recipient who is an individual notify about a criminal drug conviction? The DOI...

Tumor-free distance from outermost layer of cervix is of prognostic value in surgically treated cervical cancer patients: a multicenter study.

PubMed

Saatli, Bahadir; Olgan, Safak; Gorken, Iknur B; Uslu, Turhan; Saygili, Ugur; Dicle, Nilgun; Cingillioglu, Basak; Gumurdulu, Derya; Guzel, Ahmet Baris; Koyuncuoglu, Meral

2014-06-01

This study aimed at determining if tumor-free distance (TFD) from outermost layer of cervix predicts surgicopathologic factors and outcome in surgically treated cervical cancer patients. One hundred sixteen surgically treated cervical squamous cell carcinomas between 1991 and 2010 with FIGO stage IB/2A were identified and re-evaluated histologically regarding the TFD. TFD was defined as the distance between outermost layer of cervix and deepest cervical stromal invasion. Depth of invasion (DOI) and TFD were expressed as continuous variables and compared with traditional surgicopathologic variables and survival to determine their prognostic significance. The mean DOI was 10.3 mm and the mean TFD was 4.2 mm. The most common stage was IB1 (60 patients, 51.7 %). The mean number of removed pelvic lymph nodes was 32.2 (median 30; range 8-78). Positive pelvic lymph nodes were found in 27 (23 %) of the patients. Sixty-eight patients had lymphovascular space involvement (LVSI). Sixty-eight patients (59 %) received postoperative radiotherapy where the following items were present: tumor diameter >4 cm, positive lymph nodes, LVSI and positive surgical margins. With the median follow-up of 53 months (3-219 months); 14 patients had local and 13 patients had distant metastases (5 of the patients had both at the time of recurrence). With logistic regression analysis, TFD was a predictor of pelvic lymph involvement (p = 0.028) and LVSI (p = 0.008) while DOI was a predictor of LVSI (p = 0.044). In Cox regression analysis, increased TFD was associated with improved disease-free survival (DFS) (p = 0.007). DFS curves (for TFD cut off value 2.5 mm) according to Kaplan-Meier were found to be statistically significant (log rank test = 0.002). The results indicate that TFD is predictive of pelvic lymph node involvement, LVSI and patient outcome in surgically treated cervical cancer patients. However, prospective measurement of TFD is still necessary to determine its value in clinical practice.

Developing Data Citations from Digital Object Identifier Metadata

NASA Technical Reports Server (NTRS)

James, Nathan; Wanchoo, Lalit

2015-01-01

NASA's Earth Science Data and Information System (ESDIS) Project has been processing information for the registration of Digital Object Identifiers (DOI) for the last five years of which an automated system has been in operation for the last two years. The ESDIS DOI registration system has registered over 2000 DOIs with over 1000 DOIs held in reserve until all required information has been collected. By working towards the goal of assigning DOIs to the 8000+ data collections under its management, ESDIS has taken the first step towards facilitating the use of data citations with those products. Jeanne Behnke, ESDIS Deputy Project Manager has reviewed and approved the poster.

Catch crops impact on soil water infiltration in vineyards

NASA Astrophysics Data System (ADS)

Cerdà, Artemi; Bagarello, Vincenzo; Iovino, Massimo; Ferro, Vito; Keesstra, Saskia; Rodrigo-Comino, Jesús; García Diaz, Andrés; di Prima, Simone

2017-04-01

Infiltration is the key component of the hydrological cycle (Cerdà, 1999; Bagarello et al.,, 2014; Zema et al., 2016). Infiltration determines the partitioning of rainfall into runoff and subsurface flow (Cerdà, 1996; Bagarello et al., 2006; Wang et al., 2016). In the Mediterranean, agriculture resulted in the degradation of the soil structure, reduction of the organic matter and increase in the soil losses (Cerdà et al., 2009; Laudicina et al., 2015; Iovino et al., 2016; Willaarts et al., 2016). There is an urgent need to restore the agriculture soils to avoid floods, reduce the carbon emissions and avoid reservoir siltation (Aksakal et al., 2016; Ben Slimane et al., 2016; Yagüe et al., 2016). Catch Crops are widespread used due to their impact on the soil fertility (Mwango et al., 2016; Nishigaki et al., 2016 ; Nawaz et al., 2016). Catch crops also increase the amount of organic matter but little is known about the effect on soil infiltration. Two paired plots were selected in Les Alcusses (Moixent municipality) in Eastern Iberian Peninsula to compare the infiltration rates between a 8-years catch crop (Vicia sp) with a control (plough) soil. The measurements were carried out by means of ring infiltrometer in August 2014 and December 2014 under dry and wet conditions (Cerdà, 2001; Di Prima et al., 2016). The results show that the steady-state infiltration rates were 1.8 higher during the summer period, and that the catch crops did not increase the infiltration rates. Acknowledgements The research leading to these results has received funding from the European Union Seventh Framework Programme (FP7/2007-2013) under grant agreement n 603498 (RECARE project) and the CGL2013- 47862-C2-1-R and CGL2016-75178-C2-2-R national research projects. References Aksakal, E. L., Sari, S., & Angin, I. (2016). Effects of vermicompost application on soil aggregation and certain physical properties. Land Degradation and Development, 27(4), 983-995. doi:10.1002/ldr.2350 Bagarello, V., Castellini, M., Di Prima, S., & Iovino, M. (2014). Soil hydraulic properties determined by infiltration experiments and different heights of water pouring. Geoderma, 213, 492-501. Bagarello, V., Elrick, D. E., Iovino, M., & Sgroi, A. (2006). A laboratory analysis of falling head infiltration procedures for estimating the hydraulic conductivity of soils. Geoderma, 135, 322-334. Ben Slimane, A., Raclot, D., Evrard, O., Sanaa, M., Lefevre, I., & Le Bissonnais, Y. (2016). Relative contribution of Rill/Interrill and Gully/Channel erosion to small reservoir siltation in mediterranean environments. Land Degradation and Development, 27(3), 785-797. doi:10.1002/ldr.2387 Cerdà, A. (1996). Seasonal variability of infiltration rates under contrasting slope conditions in southeast spain. Geoderma, 69(3-4), 217-232. Cerdà, A. (1999). Seasonal and spatial variations in infiltration rates in badland surfaces under mediterranean climatic conditions. Water Resources Research, 35(1), 319-328. doi:10.1029/98WR01659 Cerdà, A. (2001). Effects of rock fragment cover on soil infiltration, interrill runoff and erosion. European Journal of Soil Science, 52(1), 59-68. doi:10.1046/j.1365-2389.2001.00354.x Cerdà, A., Morera, A. G., & Bodí, M. B. (2009). Soil and water losses from new citrus orchards growing on sloped soils in the western mediterranean basin. Earth Surface Processes and Landforms, 34(13), 1822-1830. doi:10.1002/esp.1889 di Prima, S., Lassabatère, L., Bagarello, V., Iovino, M., & Angulo-Jaramillo, R. (2016). Testing a new automated single ring infiltrometer for Beerkan infiltration experiments. Geoderma, 262, 20-34. Iovino, M., Castellini, M., Bagarello, V., & Giordano, G. (2016). Using static and dynamic indicators to evaluate soil physical quality in a sicilian area. Land Degradation and Development, 27(2), 200-210. doi:10.1002/ldr.2263 Laudicina, V. A., Novara, A., Barbera, V., Egli, M., & Badalucco, L. (2015). Long-term tillage and cropping system effects on chemical and biochemical characteristics of soil organic matter in a mediterranean semiarid environment. Land Degradation and Development, 26(1), 45-53. doi:10.1002/ldr.2293 Mamedov, A. I., Bar-Yosef, B., Levkovich, I., Rosenberg, R., Silber, A., Fine, P., & Levy, G. J. (2016). Amending soil with sludge, manure, humic acid, orthophosphate and phytic acid: Effects on infiltration, runoff and sediment loss. Land Degradation and Development, 27(6), 1629-1639. doi:10.1002/ldr.2474 Mwango, S. B., Msanya, B. M., Mtakwa, P. W., Kimaro, D. N., Deckers, J., & Poesen, J. (2016). Effectiveness OF mulching under miraba in controlling soil erosion, fertility restoration and crop yield in the usambara mountains, tanzania. Land Degradation and Development, 27(4), 1266-1275. doi:10.1002/ldr.2332 Nawaz, A., Farooq, M., Lal, R., Rehman, A., Hussain, T., & Nadeem, A. (2016). Influence of sesbania brown manuring and rice residue mulch on soil health, weeds and system productivity of conservation rice-wheat systems. Land Degradation and Development, doi:10.1002/ldr.2578 Nishigaki, T., Shibata, M., Sugihara, S., Mvondo-Ze, A. D., Araki, S., & Funakawa, S. (2016). Effect of mulching with vegetative residues on soil water erosion and water balance in an oxisol cropped by cassava in east cameroon. Land Degradation and Development, doi:10.1002/ldr.2568 Wang, Y., Fan, J., Cao, L., & Liang, Y. (2016). Infiltration and runoff generation under various cropping patterns in the red soil region of china. Land Degradation and Development, 27(1), 83-91. doi:10.1002/ldr.2460 Willaarts, B. A., Oyonarte, C., Muñoz-Rojas, M., Ibáñez, J. J., & Aguilera, P. A. (2016). Environmental factors controlling soil organic carbon stocks in two contrasting mediterranean climatic areas of southern spain. Land Degradation and Development, 27(3), 603-611. doi:10.1002/ldr.2417 Yagüe, M. R., Domingo-Olivé, F., Bosch-Serra, À. D., Poch, R. M., & Boixadera, J. (2016). Dairy cattle manure effects on soil quality: Porosity, earthworms, aggregates and soil organic carbon fractions. Land Degradation and Development, 27(7), 1753-1762. doi:10.1002/ldr.2477 Zema, D. A., Labate, A., Martino, D., & Zimbone, S. M. (2016). Comparing different infiltration methods of the HEC-HMS model: The case study of the mésima torrent (southern italy). Land Degradation and Development, doi:10.1002/ldr.2591

An optimal control framework for dynamic induction control of wind farms and their interaction with the atmospheric boundary layer.

PubMed

Munters, W; Meyers, J

2017-04-13

Complex turbine wake interactions play an important role in overall energy extraction in large wind farms. Current control strategies optimize individual turbine power, and lead to significant energy losses in wind farms compared with lone-standing wind turbines. In recent work, an optimal coordinated control framework was introduced (Goit & Meyers 2015 J. Fluid Mech. 768 , 5-50 (doi:10.1017/jfm.2015.70)). Here, we further elaborate on this framework, quantify the influence of optimization parameters and introduce new simulation results for which gains in power production of up to 21% are observed.This article is part of the themed issue 'Wind energy in complex terrains'. © 2017 The Authors.

Detonator Performance Characterization using Multi-Frame Laser Schlieren Imaging

NASA Astrophysics Data System (ADS)

Clarke, Steven; Landon, Colin; Murphy, Michael; Martinez, Michael; Mason, Thomas; Thomas, Keith

2009-06-01

Multi-frame Laser Schlieren Imaging of shock waves produced by detonators in transparent witness materials can be used to evaluate detonator performance. We use inverse calculations of the 2D propagation of shock waves in the EPIC finite element model computer code to calculate a temporal-spatial-pressure profile on the surface of the detonator that is consistent with the experimental shock waves from the schlieren imaging. Examples of calculated 2D temporal-spatial-pressure profiles from a range of detonator types (EFI --exploding foil initiators, DOI -- direct optical initiation, EBW -- exploding bridge wire, hotwire), detonator HE materials (PETN, HMX, etc), and HE densities. Also pressure interaction profiles from the interaction of multiple shock waves will be shown. LA-UR-09-00909.

An optimal control framework for dynamic induction control of wind farms and their interaction with the atmospheric boundary layer

PubMed Central

Munters, W.

2017-01-01

Complex turbine wake interactions play an important role in overall energy extraction in large wind farms. Current control strategies optimize individual turbine power, and lead to significant energy losses in wind farms compared with lone-standing wind turbines. In recent work, an optimal coordinated control framework was introduced (Goit & Meyers 2015 J. Fluid Mech. 768, 5–50 (doi:10.1017/jfm.2015.70)). Here, we further elaborate on this framework, quantify the influence of optimization parameters and introduce new simulation results for which gains in power production of up to 21% are observed. This article is part of the themed issue ‘Wind energy in complex terrains’. PMID:28265024

A Model for Data Citation in Astronomical Research Using Digital Object Identifiers (DOIs)

NASA Astrophysics Data System (ADS)

Novacescu, Jenny; Peek, Joshua E. G.; Weissman, Sarah; Fleming, Scott W.; Levay, Karen; Fraser, Elizabeth

2018-05-01

Standardizing and incentivizing the use of digital object identifiers (DOIs) to aggregate and identify both data analyzed and data generated by a research project will advance the field of astronomy to match best practices in other research fields like geoscience and medicine. An increase in the use of DOIs will prepare the discipline for changing expectations among funding agencies and publishers, who increasingly expect accurate and thorough data citation to accompany scientific outputs. The use of DOIs ensures a robust, sustainable, and interoperable approach to data citation in which due credit is given to the researchers and institutions who produce and maintain the primary data. We describe in this work the advantages of DOIs for data citation and best practices for integrating a DOI service in an astronomical archive. We report on a pilot project carried out in collaboration with AAS journals. During the course of the 1.5-year long pilot, over 75% of submitting authors opted to use the integrated DOI service to clearly identify data analyzed during their research project when prompted at the time of paper submission.

Data always getting bigger -- A scalable DOI architecture for big and expanding scientific data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Prakash, Giri; Shrestha, Biva; Younkin, Katarina

The Atmospheric Radiation Measurement (ARM) Data Archive established a data citation strategy based on Digital Object Identifiers (DOIs) for the ARM datasets in order to facilitate citing continuous and diverse ARM datasets in articles and other papers. This strategy eases the tracking of data provided as supplements to articles and papers. Additionally, it allows future data users and the ARM Climate Research Facility to easily locate the exact data used in various articles. Traditionally, DOIs are assigned to individual digital objects (a report or a data table), but for ARM datasets, these DOIs are assigned to an ARM data product.more » This eliminates the need for creating DOIs for numerous components of the ARM data product, in turn making it easier for users to manage and cite the ARM data with fewer DOIs. In addition, the ARM data infrastructure team, with input from scientific users, developed a citation format and an online data citation generation tool for continuous data streams. As a result, this citation format includes DOIs along with additional details such as spatial and temporal information.« less