Sample records for target limit state

  1. Perceiving the target's state or state provoked by the target? An analysis of the descriptive and evaluative knowledge in person perception.

    PubMed

    Mignon, Astrid; Mollaret, Patrick

    2012-12-01

    In line with the theory of traits as generalized affordances, the present article argues that target's states (TSs) and states provoked by a target (other's states (OSs) towards target) are two components of the meaning of traits referring, respectively, to a descriptive and to an evaluative knowledge of people. A preliminary study confirmed that TS and OS were equally representative of a trait. Two studies were designed to study the effects of practising the use of traits as either TS or OS categories (an induction procedure) on a subsequent person perception task, requiring participants to rate photographed targets on a series of traits. Results show that both the differentiation between targets and evaluative consistency of ratings were enhanced under the OS condition compared to TS and control (with no practice of traits) conditions. Importantly, Study 2 tends to show that the effects of the induction procedure are not limited to the practised traits but also generalize to unpractised traits. Implications of these findings for social perception research are discussed. ©2011 The British Psychological Society.

  2. Alternative method of quantum state tomography toward a typical target via a weak-value measurement

    NASA Astrophysics Data System (ADS)

    Chen, Xi; Dai, Hong-Yi; Yang, Le; Zhang, Ming

    2018-03-01

    There is usually a limitation of weak interaction on the application of weak-value measurement. This limitation dominates the performance of the quantum state tomography toward a typical target in the finite and high-dimensional complex-valued superposition of its basis states, especially when the compressive sensing technique is also employed. Here we propose an alternative method of quantum state tomography, presented as a general model, toward such typical target via weak-value measurement to overcome such limitation. In this model the pointer for the weak-value measurement is a qubit, and the target-pointer coupling interaction is no longer needed within the weak interaction limitation, meanwhile this interaction under the compressive sensing can be described with the Taylor series of the unitary evolution operator. The postselection state at the target is the equal superposition of all basis states, and the pointer readouts are gathered under multiple Pauli operator measurements. The reconstructed quantum state is generated from an optimization algorithm of total variation augmented Lagrangian alternating direction algorithm. Furthermore, we demonstrate an example of this general model for the quantum state tomography toward the planar laser-energy distribution and discuss the relations among some parameters at both our general model and the original first-order approximate model for this tomography.

  3. Nurse opinions and pulse oximeter saturation target limits for preterm infants.

    PubMed

    Nghiem, Tuyet-Hang; Hagadorn, James I; Terrin, Norma; Syke, Sally; MacKinnon, Brenda; Cole, Cynthia H

    2008-05-01

    The objectives of this study were to compare pulse oximeter saturation limits targeted by nurses for extremely preterm infants during routine care with nurse opinions regarding appropriate pulse oximeter saturation limits and with policy-specified pulse oximeter saturation limits and to identify factors that influence pulse oximeter saturation limits targeted by nurses. We surveyed nurses in US NICUs with neonatal-perinatal fellowships in 2004. Data collected included pulse oximeter saturation limits targeted by nurses and by NICU policy when present, nurses' opinions about appropriate pulse oximeter saturation limits, and NICU and nurse characteristics. Factors associated with pulse oximeter saturation limits targeted by nurses were identified with hierarchical linear modeling. Among those eligible, 2805 (45%) nurses in 59 (60%) NICUs responded. Forty (68%) of 59 NICUs had a policy that specified a pulse oximeter saturation target range for extremely preterm infants. Among 1957 nurses at NICUs with policies, 540 (28%) accurately identified the upper and lower limits of their NICU's policy and also targeted these values in practice. NICU-specific SDs for individual nurse target limits were less at NICUs with versus without a policy for both upper and lower limits. Hierarchical linear modeling identified presence of pulse oximeter saturation policy, NICU-specific nurse group opinion, and individual nurse opinion as factors significantly associated with individual pulse oximeter saturation target limits. For each percentage point increase in individual opinion upper limit, the individual target upper limit increased by 0.41 percentage point at NICUs with a policy compared with 0.6 percentage point at NICUs with no policy. Presence of policy-specified pulse oximeter saturation limits, nurse group opinion, and individual nurse opinion were independently associated with individual nurse pulse oximeter saturation target limits during routine care of extremely preterm

  4. 76 FR 34953 - Funding Opportunity Title: Risk Management Education in Targeted States (Targeted States Program...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-06-15

    ... Corporation Funding Opportunity Title: Risk Management Education in Targeted States (Targeted States Program... Corporation (FCIC), operating through the Risk Management Agency (RMA), announces its intent to award... same time as funding availability for similar but separate program, the Risk Management Education and...

  5. Polarized Solid State Target

    NASA Astrophysics Data System (ADS)

    Dutz, Hartmut; Goertz, Stefan; Meyer, Werner

    2017-01-01

    The polarized solid state target is an indispensable experimental tool to study single and double polarization observables at low intensity particle beams like tagged photons. It was one of the major components of the Crystal-Barrel experiment at ELSA. Besides the operation of the 'CB frozen spin target' within the experimental program of the Crystal-Barrel collaboration both collaborative groups of the D1 project, the polarized target group of the Ruhr Universität Bochum and the Bonn polarized target group, have made significant developments in the field of polarized targets within the CRC16. The Bonn polarized target group has focused its work on the development of technically challenging polarized solid target systems towards the so called '4π continuous mode polarized target' to operate them in combination with 4π-particle detection systems. In parallel, the Bochum group has developed various highly polarized deuterated target materials and high precision NMR-systems, in the meantime used for polarization experiments at CERN, JLAB and MAMI, too.

  6. Compendium of Mechanical Limit-States

    NASA Technical Reports Server (NTRS)

    Kowal, Michael

    1996-01-01

    A compendium was compiled and is described to provide a diverse set of limit-state relationships for use in demonstrating the application of probabilistic reliability methods to mechanical systems. The different limit-state relationships can be used to analyze the reliability of a candidate mechanical system. In determining the limit-states to be included in the compendium, a comprehensive listing of the possible failure modes that could affect mechanical systems reliability was generated. Previous literature defining mechanical modes of failure was studied, and cited failure modes were included. From this, classifications for failure modes were derived and are described in some detail.

  7. Bombing Target Identification from Limited Transect Data

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

    Roberts, Barry L.; Hathaway, John E.; Pulsipher, Brent A.

    2006-08-07

    A series of sensor data combined with geostatistical techniques were used to determine likely target areas for a historic military aerial bombing range. Primary data consisted of magnetic anomaly information from limited magnetometer transects across the site. Secondary data included airborne LIDAR, orthophotography, and other general site characterization information. Identification of likely target areas relied primarily upon kriging estimates of magnetic anomaly densities across the site. Secondary information, such as impact crater locations, was used to refine the boundary delineations.

  8. Laser targets compensate for limitations in inertial confinement fusion drivers

    NASA Astrophysics Data System (ADS)

    Kilkenny, J. D.; Alexander, N. B.; Nikroo, A.; Steinman, D. A.; Nobile, A.; Bernat, T.; Cook, R.; Letts, S.; Takagi, M.; Harding, D.

    2005-10-01

    Success in inertial confinement fusion (ICF) requires sophisticated, characterized targets. The increasing fidelity of three-dimensional (3D), radiation hydrodynamic computer codes has made it possible to design targets for ICF which can compensate for limitations in the existing single shot laser and Z pinch ICF drivers. Developments in ICF target fabrication technology allow more esoteric target designs to be fabricated. At present, requirements require new deterministic nano-material fabrication on micro scale.

  9. 34 CFR 300.602 - State use of targets and reporting.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 34 Education 2 2011-07-01 2010-07-01 true State use of targets and reporting. 300.602 Section 300..., Technical Assistance, and Enforcement § 300.602 State use of targets and reporting. (a) General. Each State must use the targets established in the State's performance plan under § 300.601 and the priority areas...

  10. Examining the target levels of state renewable portfolio standards

    NASA Astrophysics Data System (ADS)

    Helwig, Laurence Douglas

    At present 37 U.S. states have passed Renewable Portfolio Standards (RPS) or have a legislative driven goal that supports investment in renewable energy (RE) technologies. Previous research has identified economic, governmental, ideological and infrastructural characteristics as key predictors of policy adoption and renewable energy deployment efforts (Carley, 2009; Davis & Davis, 2009; Bohn & Lant, 2009; Lyon & Yin, 2010). To date, only a few studies have investigated the target levels of renewable portfolio standards. Carley & Miller (2012) found that policies of differing stringencies were motivated by systematically different factors that included governmental ideology. The purpose of this dissertation is to replicate and expand upon earlier models that predicted RPS adoption and RE deployment efforts by adding regulatory, infrastructural and spatial characteristics to predict RPS target levels. Hypotheses were tested using three alternative measurements of RPS target level strength to determine to what extent a combination of explanatory variables explain variation in policy target levels. Multivariate linear regression and global spatial autocorrelation results indicated that multiple state internal determinants influenced RPS target level including average electricity price, state government ideology and to a lesser extent actual RE potential capacity. In addition, some diffusion effects were found to exist that indicated that states are setting their RPS target levels lower than their neighboring states and a local geo-spatial clustering effect was observed in the target levels for a grouping of northeastern states.

  11. Limitations of contrast enhancement for infrared target identification

    NASA Astrophysics Data System (ADS)

    Du Bosq, Todd W.; Fanning, Jonathan D.

    2009-05-01

    Contrast enhancement and dynamic range compression are currently being used to improve the performance of infrared imagers by increasing the contrast between the target and the scene content. Automatic contrast enhancement techniques do not always achieve this improvement. In some cases, the contrast can increase to a level of target saturation. This paper assesses the range-performance effects of contrast enhancement for target identification as a function of image saturation. Human perception experiments were performed to determine field performance using contrast enhancement on the U.S. Army RDECOM CERDEC NVESD standard military eight target set using an un-cooled LWIR camera. The experiments compare the identification performance of observers viewing contrast enhancement processed images at various levels of saturation. Contrast enhancement is modeled in the U.S. Army thermal target acquisition model (NVThermIP) by changing the scene contrast temperature. The model predicts improved performance based on any improved target contrast, regardless of specific feature saturation or enhancement. The measured results follow the predicted performance based on the target task difficulty metric used in NVThermIP for the non-saturated cases. The saturated images reduce the information contained in the target and performance suffers. The model treats the contrast of the target as uniform over spatial frequency. As the contrast is enhanced, the model assumes that the contrast is enhanced uniformly over the spatial frequencies. After saturation, the spatial cues that differentiate one tank from another are located in a limited band of spatial frequencies. A frequency dependent treatment of target contrast is needed to predict performance of over-processed images.

  12. Targeting excited states in all-trans polyenes with electron-pair states.

    PubMed

    Boguslawski, Katharina

    2016-12-21

    Wavefunctions restricted to electron pair states are promising models for strongly correlated systems. Specifically, the pair Coupled Cluster Doubles (pCCD) ansatz allows us to accurately describe bond dissociation processes and heavy-element containing compounds with multiple quasi-degenerate single-particle states. Here, we extend the pCCD method to model excited states using the equation of motion (EOM) formalism. As the cluster operator of pCCD is restricted to electron-pair excitations, EOM-pCCD allows us to target excited electron-pair states only. To model singly excited states within EOM-pCCD, we modify the configuration interaction ansatz of EOM-pCCD to contain also single excitations. Our proposed model represents a simple and cost-effective alternative to conventional EOM-CC methods to study singly excited electronic states. The performance of the excited state models is assessed against the lowest-lying excited states of the uranyl cation and the two lowest-lying excited states of all-trans polyenes. Our numerical results suggest that EOM-pCCD including single excitations is a good starting point to target singly excited states.

  13. Assessment of target detection limits in hyperspectral data

    NASA Astrophysics Data System (ADS)

    Gross, W.; Boehler, J.; Schilling, H.; Middelmann, W.; Weyermann, J.; Wellig, P.; Oechslin, R.; Kneubuehler, M.

    2015-10-01

    Hyperspectral remote sensing data can be used for civil and military applications to detect and classify target objects that cannot be reliably separated using broadband sensors. The comparably low spatial resolution is compensated by the fact that small targets, even below image resolution, can still be classified. The goal of this paper is to determine the target size to spatial resolution ratio for successful classification of different target and background materials. Airborne hyperspectral data is used to simulate data with known mixture ratios and to estimate the detection threshold for given false alarm rates. The data was collected in July 2014 over Greding, Germany, using airborne aisaEAGLE and aisaHAWK hyperspectral sensors. On the ground, various target materials were placed on natural background. The targets were four quadratic molton patches with an edge length of 7 meters in the colors black, white, grey and green. Also, two different types of polyethylene (camouflage nets) with an edge length of approximately 5.5 meters were deployed. Synthetic data is generated from the original data using spectral mixtures. Target signatures are linearly combined with different background materials in specific ratios. The simulated mixtures are appended to the original data and the target areas are removed for evaluation. Commonly used classification algorithms, e.g. Matched Filtering, Adaptive Cosine Estimator are used to determine the detection limit. Fixed false alarm rates are employed to find and analyze certain regions where false alarms usually occur first. A combination of 18 targets and 12 backgrounds is analyzed for three VNIR and two SWIR data sets of the same area.

  14. Pharmacokinetic Steady-States Highlight Interesting Target-Mediated Disposition Properties.

    PubMed

    Gabrielsson, Johan; Peletier, Lambertus A

    2017-05-01

    In this paper, we derive explicit expressions for the concentrations of ligand L, target R and ligand-target complex RL at steady state for the classical model describing target-mediated drug disposition, in the presence of a constant-rate infusion of ligand. We demonstrate that graphing the steady-state values of ligand, target and ligand-target complex, we obtain striking and often singular patterns, which yield a great deal of insight and understanding about the underlying processes. Deriving explicit expressions for the dependence of L, R and RL on the infusion rate, and displaying graphs of the relations between L, R and RL, we give qualitative and quantitive information for the experimentalist about the processes involved. Understanding target turnover is pivotal for optimising these processes when target-mediated drug disposition (TMDD) prevails. By a combination of mathematical analysis and simulations, we also show that the evolution of the three concentration profiles towards their respective steady-states can be quite complex, especially for lower infusion rates. We also show how parameter estimates obtained from iv bolus studies can be used to derive steady-state concentrations of ligand, target and complex. The latter may serve as a template for future experimental designs.

  15. Collapse limit states of reinforced earth retaining walls

    NASA Astrophysics Data System (ADS)

    Bolton, M. D.; Pang, P. L. R.

    The use of systems of earth reinforcement or anchorage is gaining in popularity. It therefore becomes important to assess whether the methods of design which were adopted for such constructions represent valid predictions of realistic limit states. Confidence can only be gained with regard to the effectiveness of limit state criteria if a wide variety of representative limit states were observed. Over 80 centrifugal model tests of simple reinforced earth retaining walls were carried out, with the main purpose of clarifying the nature of appropriate collapse criteria. Collapses due to an insufficiency of friction were shown to be repeatable and therefore subject to fairly simple limit state calculations.

  16. Quantum speed limit for arbitrary initial states

    PubMed Central

    Zhang, Ying-Jie; Han, Wei; Xia, Yun-Jie; Cao, Jun-Peng; Fan, Heng

    2014-01-01

    The minimal time a system needs to evolve from an initial state to its one orthogonal state is defined as the quantum speed limit time, which can be used to characterize the maximal speed of evolution of a quantum system. This is a fundamental question of quantum physics. We investigate the generic bound on the minimal evolution time of the open dynamical quantum system. This quantum speed limit time is applicable to both mixed and pure initial states. We then apply this result to the damped Jaynes-Cummings model and the Ohimc-like dephasing model starting from a general time-evolution state. The bound of this time-dependent state at any point in time can be found. For the damped Jaynes-Cummings model, when the system starts from the excited state, the corresponding bound first decreases and then increases in the Markovian dynamics. While in the non-Markovian regime, the speed limit time shows an interesting periodic oscillatory behavior. For the case of Ohimc-like dephasing model, this bound would be gradually trapped to a fixed value. In addition, the roles of the relativistic effects on the speed limit time for the observer in non-inertial frames are discussed. PMID:24809395

  17. On the adiabatic limit of Hadamard states

    NASA Astrophysics Data System (ADS)

    Drago, Nicolò; Gérard, Christian

    2017-08-01

    We consider the adiabatic limit of Hadamard states for free quantum Klein-Gordon fields, when the background metric and the field mass are slowly varied from their initial to final values. If the Klein-Gordon field stays massive, we prove that the adiabatic limit of the initial vacuum state is the (final) vacuum state, by extending to the symplectic framework the adiabatic theorem of Avron-Seiler-Yaffe. In cases when only the field mass is varied, using an abstract version of the mode decomposition method we can also consider the case when the initial or final mass vanishes, and the initial state is either a thermal state or a more general Hadamard state.

  18. Multi-Target State Extraction for the SMC-PHD Filter

    PubMed Central

    Si, Weijian; Wang, Liwei; Qu, Zhiyu

    2016-01-01

    The sequential Monte Carlo probability hypothesis density (SMC-PHD) filter has been demonstrated to be a favorable method for multi-target tracking. However, the time-varying target states need to be extracted from the particle approximation of the posterior PHD, which is difficult to implement due to the unknown relations between the large amount of particles and the PHD peaks representing potential target locations. To address this problem, a novel multi-target state extraction algorithm is proposed in this paper. By exploiting the information of measurements and particle likelihoods in the filtering stage, we propose a validation mechanism which aims at selecting effective measurements and particles corresponding to detected targets. Subsequently, the state estimates of the detected and undetected targets are performed separately: the former are obtained from the particle clusters directed by effective measurements, while the latter are obtained from the particles corresponding to undetected targets via clustering method. Simulation results demonstrate that the proposed method yields better estimation accuracy and reliability compared to existing methods. PMID:27322274

  19. Positive allosteric modulators as an approach to nicotinic acetylcholine receptor- targeted therapeutics: advantages and limitations

    PubMed Central

    Williams, Dustin K.; Wang, Jingyi; Papke, Roger L.

    2011-01-01

    Neuronal nicotinic acetylcholine receptors (nAChR), recognized targets for drug development in cognitive and neuro-degenerative disorders, are allosteric proteins with dynamic interconversions between multiple functional states. Activation of the nAChR ion channel is primarily controlled by the binding of ligands (agonists, partial agonists, competitive antagonists) at conventional agonist binding sites, but is also regulated in either negative or positive ways by the binding of ligands to other modulatory sites. In this review, we discuss models for the activation and desensitization of nAChR, and the discovery of multiple types of ligands that influence those processes in both heteromeric nAChR, such as the high affinity nicotine receptors of the brain, and homomeric α7-type receptors. In recent years, α7 nAChRs have been identified as a potential target for therapeutic indications leading to the development of α7-selective agonists and partial agonists. However, unique properties of α7 nAChR, including low probability of channel opening and rapid desensitization, may limit the therapeutic usefulness of ligands binding exclusively to conventional agonist binding sites. New enthusiasm for the therapeutic targeting of α7 has come from the identification of α7-selective positive allosteric modulators (PAMs) that work effectively on the intrinsic factors that limit α7 ion channel activation. While these new drugs appear promising for therapeutic development, we also consider potential caveats and possible limitations for their use, including PAM-insensitive forms of desensitization and cytotoxicity issues. PMID:21575610

  20. Positive allosteric modulators as an approach to nicotinic acetylcholine receptor-targeted therapeutics: advantages and limitations.

    PubMed

    Williams, Dustin K; Wang, Jingyi; Papke, Roger L

    2011-10-15

    Neuronal nicotinic acetylcholine receptors (nAChR), recognized targets for drug development in cognitive and neuro-degenerative disorders, are allosteric proteins with dynamic interconversions between multiple functional states. Activation of the nAChR ion channel is primarily controlled by the binding of ligands (agonists, partial agonists, competitive antagonists) at conventional agonist binding sites, but is also regulated in either negative or positive ways by the binding of ligands to other modulatory sites. In this review, we discuss models for the activation and desensitization of nAChR, and the discovery of multiple types of ligands that influence those processes in both heteromeric nAChR, such as the high-affinity nicotine receptors of the brain, and homomeric α7-type receptors. In recent years, α7 nAChRs have been identified as a potential target for therapeutic indications leading to the development of α7-selective agonists and partial agonists. However, unique properties of α7 nAChR, including low probability of channel opening and rapid desensitization, may limit the therapeutic usefulness of ligands binding exclusively to conventional agonist binding sites. New enthusiasm for the therapeutic targeting of α7 has come from the identification of α7-selective positive allosteric modulators (PAMs) that work effectively on the intrinsic factors that limit α7 ion channel activation. While these new drugs appear promising for therapeutic development, we also consider potential caveats and possible limitations for their use, including PAM-insensitive forms of desensitization and cytotoxicity issues. Copyright © 2011 Elsevier Inc. All rights reserved.

  1. Heisenberg limit for displacements with semiclassical states

    NASA Astrophysics Data System (ADS)

    Luis, Alfredo

    2004-04-01

    We analyze the quantum limit to the sensitivity of the detection of small displacements. We focus on the case of free particles and harmonic oscillators as the systems experiencing the displacement. We show that the minimum displacement detectable is proportional to the inverse of the square root of the mean value of the energy in the state experiencing the displacement (Heisenberg limit). We present a measuring scheme that reaches this limit using semiclassical states. We examine the performance of this strategy under realistic practical conditions by computing the effect of imperfections such as losses and nonunit detection efficiencies. This analysis confirms the robustness of this measuring strategy by showing that the experimental imperfections can be suitably compensated by increasing the mean energy of the input state.

  2. 7 CFR 1944.525 - Targeting of TSA funds to States.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 13 2010-01-01 2009-01-01 true Targeting of TSA funds to States. 1944.525 Section... § 1944.525 Targeting of TSA funds to States. (a) The Administrator will determine, based on the most... portion of the available funds for TSA to these States, leaving the balance available for national...

  3. Determination of target detection limits in hyperspectral data using band selection and dimensionality reduction

    NASA Astrophysics Data System (ADS)

    Gross, W.; Boehler, J.; Twizer, K.; Kedem, B.; Lenz, A.; Kneubuehler, M.; Wellig, P.; Oechslin, R.; Schilling, H.; Rotman, S.; Middelmann, W.

    2016-10-01

    Hyperspectral remote sensing data can be used for civil and military applications to robustly detect and classify target objects. High spectral resolution of hyperspectral data can compensate for the comparatively low spatial resolution, which allows for detection and classification of small targets, even below image resolution. Hyperspectral data sets are prone to considerable spectral redundancy, affecting and limiting data processing and algorithm performance. As a consequence, data reduction strategies become increasingly important, especially in view of near-real-time data analysis. The goal of this paper is to analyze different strategies for hyperspectral band selection algorithms and their effect on subpixel classification for different target and background materials. Airborne hyperspectral data is used in combination with linear target simulation procedures to create a representative amount of target-to-background ratios for evaluation of detection limits. Data from two different airborne hyperspectral sensors, AISA Eagle and Hawk, are used to evaluate transferability of band selection when using different sensors. The same target objects were recorded to compare the calculated detection limits. To determine subpixel classification results, pure pixels from the target materials are extracted and used to simulate mixed pixels with selected background materials. Target signatures are linearly combined with different background materials in varying ratios. The commonly used classification algorithms Adaptive Coherence Estimator (ACE) is used to compare the detection limit for the original data with several band selection and data reduction strategies. The evaluation of the classification results is done by assuming a fixed false alarm ratio and calculating the mean target-to-background ratio of correctly detected pixels. The results allow drawing conclusions about specific band combinations for certain target and background combinations. Additionally

  4. Central Limit Theorems for the Shrinking Target Problem

    NASA Astrophysics Data System (ADS)

    Haydn, Nicolai; Nicol, Matthew; Vaienti, Sandro; Zhang, Licheng

    2013-12-01

    Suppose B i := B( p, r i ) are nested balls of radius r i about a point p in a dynamical system ( T, X, μ). The question of whether T i x∈ B i infinitely often (i.o.) for μ a.e. x is often called the shrinking target problem. In many dynamical settings it has been shown that if diverges then there is a quantitative rate of entry and for μ a.e. x∈ X. This is a self-norming type of strong law of large numbers. We establish self-norming central limit theorems (CLT) of the form (in distribution) for a variety of hyperbolic and non-uniformly hyperbolic dynamical systems, the normalization constants are . Dynamical systems to which our results apply include smooth expanding maps of the interval, Rychlik type maps, Gibbs-Markov maps, rational maps and, in higher dimensions, piecewise expanding maps. For such central limit theorems the main difficulty is to prove that the non-stationary variance has a limit in probability.

  5. Limit states and reliability-based pipeline design. Final report

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

    Zimmerman, T.J.E.; Chen, Q.; Pandey, M.D.

    1997-06-01

    This report provides the results of a study to develop limit states design (LSD) procedures for pipelines. Limit states design, also known as load and resistance factor design (LRFD), provides a unified approach to dealing with all relevant failure modes combinations of concern. It explicitly accounts for the uncertainties that naturally occur in the determination of the loads which act on a pipeline and in the resistance of the pipe to failure. The load and resistance factors used are based on reliability considerations; however, the designer is not faced with carrying out probabilistic calculations. This work is done during developmentmore » and periodic updating of the LSD document. This report provides background information concerning limits states and reliability-based design (Section 2), gives the limit states design procedures that were developed (Section 3) and provides results of the reliability analyses that were undertaken in order to partially calibrate the LSD method (Section 4). An appendix contains LSD design examples in order to demonstrate use of the method. Section 3, Limit States Design has been written in the format of a recommended practice. It has been structured so that, in future, it can easily be converted to a limit states design code format. Throughout the report, figures and tables are given at the end of each section, with the exception of Section 3, where to facilitate understanding of the LSD method, they have been included with the text.« less

  6. Data and methodological problems in establishing state gasoline-conservation targets

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

    Greene, D.L.; Walton, G.H.

    The Emergency Energy Conservation Act of 1979 gives the President the authority to set gasoline-conservation targets for states in the event of a supply shortage. This paper examines data and methodological problems associated with setting state gasoline-conservation targets. The target-setting method currently used is examined and found to have some flaws. Ways of correcting these deficiencies through the use of Box-Jenkins time-series analysis are investigated. A successful estimation of Box-Jenkins models for all states included the estimation of the magnitude of the supply shortages of 1979 in each state and a preliminary estimation of state short-run price elasticities, which weremore » found to vary about a median value of -0.16. The time-series models identified were very simple in structure and lent support to the simple consumption growth model assumed by the current target method. The authors conclude that the flaws in the current method can be remedied either by replacing the current procedures with time-series models or by using the models in conjunction with minor modifications of the current method.« less

  7. Targeted Analyte Detection by Standard Addition Improves Detection Limits in MALDI Mass Spectrometry

    PubMed Central

    Eshghi, Shadi Toghi; Li, Xingde; Zhang, Hui

    2014-01-01

    Matrix-assisted laser desorption/ionization has proven an effective tool for fast and accurate determination of many molecules. However, the detector sensitivity and chemical noise compromise the detection of many invaluable low-abundance molecules from biological and clinical samples. To challenge this limitation, we developed a targeted analyte detection (TAD) technique. In TAD, the target analyte is selectively elevated by spiking a known amount of that analyte into the sample, thereby raising its concentration above the noise level, where we take advantage of the improved sensitivity to detect the presence of the endogenous analyte in the sample. We assessed TAD on three peptides in simple and complex background solutions with various exogenous analyte concentrations in two MALDI matrices. TAD successfully improved the limit of detection (LOD) of target analytes when the target peptides were added to the sample in a concentration close to optimum concentration. The optimum exogenous concentration was estimated through a quantitative method to be approximately equal to the original LOD for each target. Also, we showed that TAD could achieve LOD improvements on an average of 3-fold in a simple and 2-fold in a complex sample. TAD provides a straightforward assay to improve the LOD of generic target analytes without the need for costly hardware modifications. PMID:22877355

  8. Timelines in the management of adrenal crisis - targets, limits and reality.

    PubMed

    Hahner, Stefanie; Hemmelmann, Nina; Quinkler, Marcus; Beuschlein, Felix; Spinnler, Christina; Allolio, Bruno

    2015-04-01

    To evaluate current management timelines in adrenal crisis (AC) and to establish time targets and time limits for emergency treatment. Patients from a prospective study who had reported an AC (n = 46) were contacted and asked about management of their AC. A survey among 24 European endocrinologists collected expert recommendations concerning time targets and time limits for contact-arrival time of emergency health professionals and presentation of emergency card-glucocorticoid (GC) injection time. Median time targets and time limits regarded by experts as adequate for contact-arrival time were 45 and 90 min, respectively, and for card-injection time 15 and 30 min, respectively. Thirty-seven of 46 patients could be interviewed. All patients were equipped with an emergency card but only 23 (62%) with an emergency kit. Seven patients (19%) were trained in GC self-injection. The median time interval between contacting a health professional and arrival was 20 min (range 2-2880 min); ≤45 min: n = 32 (86%), <90 min: n = 34 (92%). The median time interval between arrival and administration of GC was 30 min (range 2-2400 min); ≤15 min: n = 17 (46%), ≤30 min: n = 20 (54%). While the time between contacting health professionals and their arrival was within the limits set by experts, initiation of GC administration was delayed in 46% of patients. Thus, improved management of AC needs to focus on shortening the presentation of card-injection time. Given the current reality in the management of AC, promotion of self-injection of GC (s.c. or i.m.) is warranted. © 2014 John Wiley & Sons Ltd.

  9. Tightening Quantum Speed Limits for Almost All States.

    PubMed

    Campaioli, Francesco; Pollock, Felix A; Binder, Felix C; Modi, Kavan

    2018-02-09

    Conventional quantum speed limits perform poorly for mixed quantum states: They are generally not tight and often significantly underestimate the fastest possible evolution speed. To remedy this, for unitary driving, we derive two quantum speed limits that outperform the traditional bounds for almost all quantum states. Moreover, our bounds are significantly simpler to compute as well as experimentally more accessible. Our bounds have a clear geometric interpretation; they arise from the evaluation of the angle between generalized Bloch vectors.

  10. Evaluation of the Washington State Target Zero teams project.

    DOT National Transportation Integrated Search

    2015-01-01

    As part of its Target Zero strategic highway safety plan that has the goal to reduce traffic fatalities in Washington to zero by the year 2030, the State of Washington established three detachments of Washington State Patrol (WSP) troopers to f...

  11. Performance limits for exo-clutter Ground Moving Target Indicator (GMTI) radar.

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

    Doerry, Armin Walter

    2010-09-01

    The performance of a Ground Moving Target Indicator (GMTI) radar system depends on a variety of factors, many which are interdependent in some manner. It is often difficult to 'get your arms around' the problem of ascertaining achievable performance limits, and yet those limits exist and are dictated by physics. This report identifies and explores those limits, and how they depend on hardware system parameters and environmental conditions. Ultimately, this leads to a characterization of parameters that offer optimum performance for the overall GMTI radar system. While the information herein is not new to the literature, its collection into amore » single report hopes to offer some value in reducing the 'seek time'.« less

  12. Role of target thickness in proton acceleration from near-critical mass-limited plasmas

    NASA Astrophysics Data System (ADS)

    Kuri, Deep Kumar; Das, Nilakshi; Patel, Kartik

    2017-07-01

    The role played by the target thickness in generating high energetic protons by a circularly polarized laser from near-critical mass-limited targets (MLT) has been investigated with the help of three-dimensional (3D) particle-in-cell (PIC) simulations. The radiation pressure accelerates protons from the front side of the target. Due to hole boring, the target front side gets deformed resulting in a change in the effective angle of incidence which causes vacuum heating and hence generates hot electrons. These hot electrons travel through the target at an angle with the laser axis and hence get more diverged along transverse directions for large target thickness. The hot electrons form sheath fields on the target rear side which accelerates protons via target normal sheath acceleration (TNSA). It is observed that the collimation of radiation pressure accelerated protons gets degraded on reaching the target rear side due to TNSA. The effect of transverse hot electron recirculations gets suppressed and the energetic protons get highly collimated on decreasing target thickness as the radiation pressure acceleration (RPA) starts dominating the acceleration process.

  13. Influences on Adoption of Greenhouse Gas Reduction Targets among US States, 1998-2008

    PubMed Central

    Cale, Tabitha M.; Reams, Margaret A.

    2016-01-01

    While the United States has not established federal regulations for greenhouse gas (GHG) reduction targets, many US states have adopted their own standards and guidelines. In this study we examine state adoption of targets for GHG reductions during the ten-year period of 1998–2008, and identify factors that explain variation in target adoption. Potential influences are drawn from research from the public policy formulation and diffusion literature, and from studies specific to climate policy adoption. Potential influences on GHG reduction efforts among US states include socioeconomic attributes of residents, political and ideological orientations of citizens and state government, interest group activities, environmental pressures, and proximity to other states that have adopted GHG reduction targets. The findings of the multinomial logistic regression analysis indicate that states are more likely to adopt GHG reduction targets if they share a border with another state with a similar climate program and if their citizens are more ideologically liberal. Other factors including socioeconomic resources and interest group activities were not found to be associated with policy adoption. The findings yield insights into the conditions under which states are more likely to take action to reduce GHG’s, and are relevant both to state policy makers and residents with an interest in climate planning, and for researchers attempting to estimate future greenhouse gas reduction scenarios. PMID:27471657

  14. Summary - National Dissemination and the Five Target States, Part 3, Final Report for Phase II--Dissemination, Rural Shared Services.

    ERIC Educational Resources Information Center

    Northern Montana Coll., Havre.

    The dissemination phase (Phase II) of the Rural Shared Services Project is reported in this document. Efforts of the dissemination phase were concentrated in 5 target states: Vermont, Georgia, Wyoming, Montana, and New Mexico; national dissemination was limited to attendance at national conferences, the U. S. Office of Education PREP materials for…

  15. 50 CFR 648.53 - Acceptable biological catch (ABC), annual catch limits (ACL), annual catch targets (ACT), DAS...

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... catch limits (ACL), annual catch targets (ACT), DAS allocations, and individual fishing quotas (IFQ... limits (ACL), annual catch targets (ACT), DAS allocations, and individual fishing quotas (IFQ). (a... process specified in § 648.55 and is equal to the overall scallop fishery ACL. The ABC/ACL shall be...

  16. 50 CFR 648.53 - Acceptable biological catch (ABC), annual catch limits (ACL), annual catch targets (ACT), DAS...

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... catch limits (ACL), annual catch targets (ACT), DAS allocations, and individual fishing quotas (IFQ... limits (ACL), annual catch targets (ACT), DAS allocations, and individual fishing quotas (IFQ). (a... process specified in § 648.55 and is equal to the overall scallop fishery ACL. The ABC/ACL shall be...

  17. 28 CFR 29.6 - Limited participation by states and localities permitted.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 28 Judicial Administration 1 2010-07-01 2010-07-01 false Limited participation by states and localities permitted. 29.6 Section 29.6 Judicial Administration DEPARTMENT OF JUSTICE MOTOR VEHICLE THEFT PREVENTION ACT REGULATIONS § 29.6 Limited participation by states and localities permitted. A State or...

  18. Accurate State Estimation and Tracking of a Non-Cooperative Target Vehicle

    NASA Technical Reports Server (NTRS)

    Thienel, Julie K.; Sanner, Robert M.

    2006-01-01

    Autonomous space rendezvous scenarios require knowledge of the target vehicle state in order to safely dock with the chaser vehicle. Ideally, the target vehicle state information is derived from telemetered data, or with the use of known tracking points on the target vehicle. However, if the target vehicle is non-cooperative and does not have the ability to maintain attitude control, or transmit attitude knowledge, the docking becomes more challenging. This work presents a nonlinear approach for estimating the body rates of a non-cooperative target vehicle, and coupling this estimation to a tracking control scheme. The approach is tested with the robotic servicing mission concept for the Hubble Space Telescope (HST). Such a mission would not only require estimates of the HST attitude and rates, but also precision control to achieve the desired rate and maintain the orientation to successfully dock with HST.

  19. Pulse oximeter saturation target limits for preterm infants: a survey among European neonatal intensive care units.

    PubMed

    Huizing, Maurice J; Villamor-Martínez, Eduardo; Vento, Máximo; Villamor, Eduardo

    2017-01-01

    The optimum range of pulse oximeter oxygen saturation (SpO 2 ) for preterm infants remains controversial. Between November 2015 and February 2016, we conducted a web-based survey aimed to investigate the current and former practices on SpO 2 targets in European neonatal intensive care units (NICUs). We obtained valid responses from 193 NICUs, treating 8590 newborns ≤28 weeks per year, across 27 countries. Forty different saturation ranges were reported, ranging from 82-93 to 94-99%. The most frequently utilized SpO 2 ranges were 90-95% (28%), 88-95% (12%), 90-94% (5%), and 91-95% (5%). A total of 156 NICUs (81%) changed their SpO 2 limits over the last 10 years. The most frequently reported former limits were 88-92% (18%), 85-95% (9%), 88-93 (7%), and 85-92% (6%). The NICUs that increased their SpO 2 ranges expected to obtain a reduction in mortality. A 54% of the NICUs found the scientific evidence supporting their SpO 2 targeting policy strong or very strong. We detected a high degree of heterogeneity in pulse oximeter SpO 2 target limits across European NICUs. The currently used limits are 3 to 5% higher than the former limits, and the most extreme limits, such as lower below 85% or upper above 96%, have almost been abandoned. What is Known: • For preterm infants requiring supplemental oxygen, the optimum range of pulse oximeter oxygen saturation (SpO 2 ) to minimize organ damage, without causing hypoxic injury, remains controversial. What is New: • This survey highlights the lack of consensus regarding SpO 2 target limits for preterm infants among European neonatal intensive care units (NICUs). We detected 40 different SpO 2 ranges, and even the most frequently reported range (i.e., 90-95%) was used in only 28% of the 193 respondent NICUs. • A total of 156 NICUs (81%) changed their SpO 2 limits over the last 10 years. The currently used limits are 3 to 5% higher than the former limits, and the most extreme limits, such as lower below 85% or upper

  20. 34 CFR 300.602 - State use of targets and reporting.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 34 Education 2 2010-07-01 2010-07-01 false State use of targets and reporting. 300.602 Section 300.602 Education Regulations of the Offices of the Department of Education (Continued) OFFICE OF SPECIAL EDUCATION AND REHABILITATIVE SERVICES, DEPARTMENT OF EDUCATION ASSISTANCE TO STATES FOR THE EDUCATION OF...

  1. Achieving quantum precision limit in adaptive qubit state tomography

    NASA Astrophysics Data System (ADS)

    Hou, Zhibo; Zhu, Huangjun; Xiang, Guo-Yong; Li, Chuan-Feng; Guo, Guang-Can

    2016-02-01

    The precision limit in quantum state tomography is of great interest not only to practical applications but also to foundational studies. However, little is known about this subject in the multiparameter setting even theoretically due to the subtle information trade-off among incompatible observables. In the case of a qubit, the theoretic precision limit was determined by Hayashi as well as Gill and Massar, but attaining the precision limit in experiments has remained a challenging task. Here we report the first experiment that achieves this precision limit in adaptive quantum state tomography on optical polarisation qubits. The two-step adaptive strategy used in our experiment is very easy to implement in practice. Yet it is surprisingly powerful in optimising most figures of merit of practical interest. Our study may have significant implications for multiparameter quantum estimation problems, such as quantum metrology. Meanwhile, it may promote our understanding about the complementarity principle and uncertainty relations from the information theoretic perspective.

  2. The United States should forego a damage-limitation capability against China

    NASA Astrophysics Data System (ADS)

    Glaser, Charles L.

    2017-11-01

    Bottom Lines • THE KEY STRATEGIC NUCLEAR CHOICE. Whether to attempt to preserve its damage-limitation capability against China is the key strategic nuclear choice facing the United States. The answer is much less clear-cut than when the United States faced the Soviet Union during the Cold War. • FEASIBILITY OF DAMAGE LIMITATION. Although technology has advanced significantly over the past three decades, future military competition between the U.S. and Chinese forces will favor large-scale nuclear retaliation over significant damage limitation. • BENEFITS AND RISKS OF A DAMAGE-LIMITATION CAPABILITY. The benefits provided by a modest damage-limitation capability would be small, because the United States can meet its most important regional deterrent requirements without one. In comparison, the risks, which include an increased probability of accidental and unauthorized Chinese attacks, as well as strained U.S.—China relations, would be large. • FOREGO DAMAGE LIMITATION. These twin findings—the poor prospects for prevailing in the military competition, and the small benefits and likely overall decrease in U.S. security—call for a U.S. policy that foregoes efforts to preserve or enhance its damage-limitation capability.

  3. Possible impact of multi-electron loss events on the average beam charge state in an HIF target chamber and a neutral beam approach

    NASA Astrophysics Data System (ADS)

    Grisham, L. R.

    2001-05-01

    Experiments were carried out during the early 1980s to assess the obtainable atomic neutralization of energetic beams of negative ions ranging from lithium to silicon. The experiments found (Grisham et al. Rev. Sci. Instrum. 53 (1982) 281; Princeton Plasma Physics Laboratory Report PPPL-1857, 1981) that, for higher atomic number elements than lithium, it appeared that a substantial fraction of the time more than one electron was being lost in a single collision. This result was inferred from the existence of more than one ionization state in the product beam for even the thinnest line densities at which any electron removal took place. Because of accelerator limitations, these experiments were limited to maximum energies of 7 MeV. However, based upon these results, it is possible that multi-electron loss events may also play a significant role in determining the average ion charge state of the much higher Z and more energetic beams traversing the medium in an heavy ion fusion chamber. This could result in the beam charge state being considerably higher than previously anticipated, and might require designers to consider harder vacuum ballistic focusing approaches, or the development of additional space charge neutralization schemes. This paper discusses the measurements that gave rise for these concerns, as well as a description of further measurements that are proposed to be carried out for atomic numbers and energies per amu which would be closer to those required for heavy ion fusion drivers. With a very low current beam of a massive, but low charge state energetic ion, the charge state distribution emerging from a target gas cell could be measured as a function of line density and medium composition. Varying the line density would allow one to simulate the charge state evolution of the beam as a function of distance into the target chamber. This paper also briefly discusses a possible alternative driver approach using photodetachment-neutralized atomic beams

  4. Detection of Stimulus Displacements Across Saccades is Capacity-Limited and Biased in Favor of the Saccade Target

    PubMed Central

    Irwin, David E.; Robinson, Maria M.

    2015-01-01

    Retinal image displacements caused by saccadic eye movements are generally unnoticed. Recent theories have proposed that perceptual stability across saccades depends on a local evaluation process centered on the saccade target object rather than on remapping and evaluating the positions of all objects in a display. In three experiments, we examined whether objects other than the saccade target also influence perceptual stability by measuring displacement detection thresholds across saccades for saccade targets and a variable number of non-saccade objects. We found that the positions of multiple objects are maintained across saccades, but with variable precision, with the saccade target object having priority in the perception of displacement, most likely because it is the focus of attention before the saccade and resides near the fovea after the saccade. The perception of displacement of objects that are not the saccade target is affected by acuity limitations, attentional limitations, and limitations on memory capacity. Unlike previous studies that have found that a postsaccadic blank improves the detection of displacement direction across saccades, we found that postsaccadic blanking hurt the detection of displacement per se by increasing false alarms. Overall, our results are consistent with the hypothesis that visual working memory underlies the perception of stability across saccades. PMID:26640430

  5. Ultimate Limit State Assessment of Timber Bolt Connection Subjected to Double Unequal Shears

    NASA Astrophysics Data System (ADS)

    Musilek, Josef; Plachy, Jan

    2017-10-01

    Nowadays the problems occur when a structure engineer need to assess the ultimate limit state of timber bolt connection which is subjected to double unequal shears. This assessment of ultimate limit state shows the reliability of these connections. In assessing the reliability of this connection in ultimate limit state is a problem, because the formulas and equations that are currently available in design standards and available literature, describing only connections loaded symmetrically - this mean that they describe the timber bolt connection subjected to double equal shears. This fact causes problems because structural engineers have no available support, according to which they could assess reliability of the connection in terms of the ultimate limit state. They must therefore often report following an asymmetrically loaded connections carry about using formulas, which are primarily designed for checking connections loaded symmetrically. This leads logically to the fact that it is not respected by the actual behaviour of the connection in the ultimate limit state. Formulas derived in this paper provide the possibility to assess the ultimate limit state for such connection. The formulas derived in this article allow to carry out a reliability assessment of the ultimate limit state of timber bolt connection subjected to double shear. The using of the formulas derived in this paper leads to better description of the behaviour of this type of connection and also to the more economic design. An example of using these derived formulas is shown. There is shown in this example, how to assess the reliability of timber bolt connection subjected to double unequal shears in terms of ultimate limit states.

  6. Fuzzy analysis of serviceability limit state of slender steel beam under bending

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

    Kala, Zdeněk; Valeš, Jan

    In the present paper, deformations of a beam under equal end moments solved with influence of lateral buckling are studied. It has been found by numerical studies that the lateral deflection of slender beam under major axis bending can be relatively high.The acceptability of high values of lateral deflections within the framework of serviceability limit state is discussed. In the next part of the paper, the limit value of maximum deflection was introduced as a fuzzy number. The fuzzy analysis of the maximum moment which causes the maximum deflection was carried out. The slendernesses of beams for which the serviceabilitymore » limit state is the limiting state for design were identified.« less

  7. Target-oriented retrieval of subsurface wave fields - Pushing the resolution limits in seismic imaging

    NASA Astrophysics Data System (ADS)

    Vasconcelos, Ivan; Ozmen, Neslihan; van der Neut, Joost; Cui, Tianci

    2017-04-01

    Travelling wide-bandwidth seismic waves have long been used as a primary tool in exploration seismology because they can probe the subsurface over large distances, while retaining relatively high spatial resolution. The well-known Born resolution limit often seems to be the lower bound on spatial imaging resolution in real life examples. In practice, data acquisition cost, time constraints and other factors can worsen the resolution achieved by wavefield imaging. Could we obtain images whose resolution beats the Born limits? Would it be practical to achieve it, and what are we missing today to achieve this? In this talk, we will cover aspects of linear and nonlinear seismic imaging to understand elements that play a role in obtaining "super-resolved" seismic images. New redatuming techniques, such as the Marchenko method, enable the retrieval of subsurface fields that include multiple scattering interactions, while requiring relatively little knowledge of model parameters. Together with new concepts in imaging, such as Target-Enclosing Extended Images, these new redatuming methods enable new targeted imaging frameworks. We will make a case as to why target-oriented approaches to reconstructing subsurface-domain wavefields from surface data may help in increasing the resolving power of seismic imaging, and in pushing the limits on parameter estimation. We will illustrate this using a field data example. Finally, we will draw connections between seismic and other imaging modalities, and discuss how this framework could be put to use in other applications

  8. Improved Limit on Direct α Decay of the Hoyle State

    NASA Astrophysics Data System (ADS)

    Kirsebom, O. S.; Alcorta, M.; Borge, M. J. G.; Cubero, M.; Diget, C. Aa.; Fraile, L. M.; Fulton, B. R.; Fynbo, H. O. U.; Galaviz, D.; Jonson, B.; Madurga, M.; Nilsson, T.; Nyman, G.; Riisager, K.; Tengblad, O.; Turrión, M.

    2012-05-01

    The current evaluation of the triple-α reaction rate assumes that the α decay of the 7.65 MeV, 0+ state in C12, commonly known as the Hoyle state, proceeds sequentially via the ground state of Be8. This assumption is challenged by the recent identification of two direct α-decay branches with a combined branching ratio of 17(5)%. If correct, this would imply a corresponding reduction in the triple-α reaction rate with important astrophysical consequences. We have used the B11(He3,d) reaction to populate the Hoyle state and measured the decay to three α particles in complete kinematics. We find no evidence for direct α-decay branches, and hence our data do not support a revision of the triple-α reaction rate. We obtain an upper limit of 5×10-3 on the direct α decay of the Hoyle state at 95% C.L., which is 1 order of magnitude better than a previous upper limit.

  9. Methods and limitations in radar target imagery

    NASA Astrophysics Data System (ADS)

    Bertrand, P.

    An analytical examination of the reflectivity of radar targets is presented for the two-dimensional case of flat targets. A complex backscattering coefficient is defined for the amplitude and phase of the received field in comparison with the emitted field. The coefficient is dependent on the frequency of the emitted signal and the orientation of the target with respect to the transmitter. The target reflection is modeled in terms of the density of illumined, colored points independent from one another. The target therefore is represented as an infinite family of densities indexed by the observational angle. Attention is given to the reflectivity parameters and their distribution function, and to the conjunct distribution function for the color, position, and the directivity of bright points. It is shown that a fundamental ambiguity exists between the localization of the illumined points and the determination of their directivity and color.

  10. Efficient Nonlocal M-Control and N-Target Controlled Unitary Gate Using Non-symmetric GHZ States

    NASA Astrophysics Data System (ADS)

    Chen, Li-Bing; Lu, Hong

    2018-03-01

    Efficient local implementation of a nonlocal M-control and N-target controlled unitary gate is considered. We first show that with the assistance of two non-symmetric qubit(1)-qutrit(N) Greenberger-Horne-Zeilinger (GHZ) states, a nonlocal 2-control and N-target controlled unitary gate can be constructed from 2 local two-qubit CNOT gates, 2 N local two-qutrit conditional SWAP gates, N local qutrit-qubit controlled unitary gates, and 2 N single-qutrit gates. At each target node, the two third levels of the two GHZ target qutrits are used to expose one and only one initial computational state to the local qutrit-qubit controlled unitary gate, instead of being used to hide certain states from the conditional dynamics. This scheme can be generalized straightforwardly to implement a higher-order nonlocal M-control and N-target controlled unitary gate by using M non-symmetric qubit(1)-qutrit(N) GHZ states as quantum channels. Neither the number of the additional levels of each GHZ target particle nor that of single-qutrit gates needs to increase with M. For certain realistic physical systems, the total gate time may be reduced compared with that required in previous schemes.

  11. Practical limitation for continuous-variable quantum cryptography using coherent States.

    PubMed

    Namiki, Ryo; Hirano, Takuya

    2004-03-19

    In this Letter, first, we investigate the security of a continuous-variable quantum cryptographic scheme with a postselection process against individual beam splitting attack. It is shown that the scheme can be secure in the presence of the transmission loss owing to the postselection. Second, we provide a loss limit for continuous-variable quantum cryptography using coherent states taking into account excess Gaussian noise on quadrature distribution. Since the excess noise is reduced by the loss mechanism, a realistic intercept-resend attack which makes a Gaussian mixture of coherent states gives a loss limit in the presence of any excess Gaussian noise.

  12. Targeted therapy in biliary tract cancers-current limitations and potentials in the future.

    PubMed

    Sahu, Selley; Sun, Weijing

    2017-04-01

    Biliary tract cancers (BTC)/Cholangiocarcinoma (CCA) is an aggressive biliary tract epithelial malignancy from varying locations within the biliary tree with cholangiocyte depreciation., including intrahepatic cholangiocarcinoma (iCCA) (iCCA), extrahepatic cholangiocarcinoma (eCCA) and gallbladder carcinoma (GBC). The disease is largely heterogeneous in etiology, epidemiology, and molecular profile. There are limited treatment options and low survival rates for those patients with advanced or metastatic disease. Systemic treatment is confined to cytotoxic chemotherapy with the combination of gemcitabine and cisplatin. Lack of a stereotype genetic signature makes difficult in identification of potential actionable target directly, which may also explain lack of obvious clinic benefit with target oriented agents from current studies. It is crucial to understand of BTC carcinogenesis, tumor-stroma interactions, and key molecular pathways, and herald to establish targeted, individualized therapies for the heterogeneous disease, and eventually to improve the survival and overall outcome of patients.

  13. σ -SCF: A Direct Energy-targeting Method To Mean-field Excited States

    NASA Astrophysics Data System (ADS)

    Ye, Hongzhou; Welborn, Matthew; Ricke, Nathan; van Voorhis, Troy

    The mean-field solutions of electronic excited states are much less accessible than ground state (e.g. Hartree-Fock) solutions. Energy-based optimization methods for excited states, like Δ-SCF, tend to fall into the lowest solution consistent with a given symmetry - a problem known as ``variational collapse''. In this work, we combine the ideas of direct energy-targeting and variance-based optimization in order to describe excited states at the mean-field level. The resulting method, σ-SCF, has several advantages. First, it allows one to target any desired excited state by specifying a single parameter: a guess of the energy of that state. It can therefore, in principle, find all excited states. Second, it avoids variational collapse by using a variance-based, unconstrained local minimization. As a consequence, all states - ground or excited - are treated on an equal footing. Third, it provides an alternate approach to locate Δ-SCF solutions that are otherwise hardly accessible by the usual non-aufbau configuration initial guess. We present results for this new method for small atoms (He, Be) and molecules (H2, HF). This work was funded by a Grant from NSF (CHE-1464804).

  14. Targeted analyte detection by standard addition improves detection limits in matrix-assisted laser desorption/ionization mass spectrometry.

    PubMed

    Toghi Eshghi, Shadi; Li, Xingde; Zhang, Hui

    2012-09-18

    Matrix-assisted laser desorption/ionization (MALDI) has proven an effective tool for fast and accurate determination of many molecules. However, the detector sensitivity and chemical noise compromise the detection of many invaluable low-abundance molecules from biological and clinical samples. To challenge this limitation, we developed a targeted analyte detection (TAD) technique. In TAD, the target analyte is selectively elevated by spiking a known amount of that analyte into the sample, thereby raising its concentration above the noise level, where we take advantage of the improved sensitivity to detect the presence of the endogenous analyte in the sample. We assessed TAD on three peptides in simple and complex background solutions with various exogenous analyte concentrations in two MALDI matrices. TAD successfully improved the limit of detection (LOD) of target analytes when the target peptides were added to the sample in a concentration close to optimum concentration. The optimum exogenous concentration was estimated through a quantitative method to be approximately equal to the original LOD for each target. Also, we showed that TAD could achieve LOD improvements on an average of 3-fold in a simple and 2-fold in a complex sample. TAD provides a straightforward assay to improve the LOD of generic target analytes without the need for costly hardware modifications.

  15. Communication target object recognition for D2D connection with feature size limit

    NASA Astrophysics Data System (ADS)

    Ok, Jiheon; Kim, Soochang; Kim, Young-hoon; Lee, Chulhee

    2015-03-01

    Recently, a new concept of device-to-device (D2D) communication, which is called "point-and-link communication" has attracted great attentions due to its intuitive and simple operation. This approach enables user to communicate with target devices without any pre-identification information such as SSIDs, MAC addresses by selecting the target image displayed on the user's own device. In this paper, we present an efficient object matching algorithm that can be applied to look(point)-and-link communications for mobile services. Due to the limited channel bandwidth and low computational power of mobile terminals, the matching algorithm should satisfy low-complexity, low-memory and realtime requirements. To meet these requirements, we propose fast and robust feature extraction by considering the descriptor size and processing time. The proposed algorithm utilizes a HSV color histogram, SIFT (Scale Invariant Feature Transform) features and object aspect ratios. To reduce the descriptor size under 300 bytes, a limited number of SIFT key points were chosen as feature points and histograms were binarized while maintaining required performance. Experimental results show the robustness and the efficiency of the proposed algorithm.

  16. Optoelectronically probing the density of nanowire surface trap states to the single state limit

    NASA Astrophysics Data System (ADS)

    Dan, Yaping

    2015-02-01

    Surface trap states play a dominant role in the optoelectronic properties of nanoscale devices. Understanding the surface trap states allows us to properly engineer the device surfaces for better performance. But characterization of surface trap states at nanoscale has been a formidable challenge using the traditional capacitive techniques. Here, we demonstrate a simple but powerful optoelectronic method to probe the density of nanowire surface trap states to the single state limit. In this method, we choose to tune the quasi-Fermi level across the bandgap of a silicon nanowire photoconductor, allowing for capture and emission of photogenerated charge carriers by surface trap states. The experimental data show that the energy density of nanowire surface trap states is in a range from 109 cm-2/eV at deep levels to 1012 cm-2/eV near the conduction band edge. This optoelectronic method allows us to conveniently probe trap states of ultra-scaled nano/quantum devices at extremely high precision.

  17. Comparative Analysis of State Fish Consumption Advisories Targeting Sensitive Populations

    PubMed Central

    Scherer, Alison C.; Tsuchiya, Ami; Younglove, Lisa R.; Burbacher, Thomas M.; Faustman, Elaine M.

    2008-01-01

    Objective Fish consumption advisories are issued to warn the public of possible toxicological threats from consuming certain fish species. Although developing fetuses and children are particularly susceptible to toxicants in fish, fish also contain valuable nutrients. Hence, formulating advice for sensitive populations poses challenges. We conducted a comparative analysis of advisory Web sites issued by states to assess health messages that sensitive populations might access. Data sources We evaluated state advisories accessed via the National Listing of Fish Advisories issued by the U.S. Environmental Protection Agency. Data extraction We created criteria to evaluate advisory attributes such as risk and benefit message clarity. Data synthesis All 48 state advisories issued at the time of this analysis targeted children, 90% (43) targeted pregnant women, and 58% (28) targeted women of childbearing age. Only six advisories addressed single contaminants, while the remainder based advice on 2–12 contaminants. Results revealed that advisories associated a dozen contaminants with specific adverse health effects. Beneficial health effects of any kind were specifically associated only with omega-3 fatty acids found in fish. Conclusions These findings highlight the complexity of assessing and communicating information about multiple contaminant exposure from fish consumption. Communication regarding potential health benefits conferred by specific fish nutrients was minimal and focused primarily on omega-3 fatty acids. This overview suggests some lessons learned and highlights a lack of both clarity and consistency in providing the breadth of information that sensitive populations such as pregnant women need to make public health decisions about fish consumption during pregnancy. PMID:19079708

  18. Motion state analysis of space target based on optical cross section

    NASA Astrophysics Data System (ADS)

    Tian, Qichen; Li, Zhi; Xu, Can; Liu, Chenghao

    2017-10-01

    In order to solve the problem that the movement state analysis method of the space target based on OCS is not related to the real motion state. This paper proposes a method based on OCS for analyzing the state of space target motion. This paper first establish a three-dimensional model of real STSS satellite, then change the satellite's surface into element, and assign material to each panel according to the actual conditions of the satellite. This paper set up a motion scene according to the orbit parameters of STSS satellite in STK, and the motion states are set to three axis steady state and slowly rotating unstable state respectively. In these two states, the occlusion condition of the surface element is firstly determined, and the effective face element is selected. Then, the coordinates of the observation station and the solar coordinates in the satellite body coordinate system are input into the OCS calculation program, and the OCS variation curves of the three axis steady state and the slow rotating unstable state STSS satellite are obtained. Combining the satellite surface structure and the load situation, the OCS change curve of the three axis stabilized satellite is analyzed, and the conclude that the OCS curve fluctuates up and down when the sunlight is irradiated to the load area; By using Spectral analysis method, autocorrelation analysis and the cross residual method, the rotation speed of OCS satellite in slow rotating unstable state is analyzed, and the rotation speed of satellite is successfully reversed. By comparing the three methods, it is found that the cross residual method is more accurate.

  19. 49 CFR 172.822 - Limitation on actions by states, local governments, and Indian tribes.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ..., and Indian tribes. 172.822 Section 172.822 Transportation Other Regulations Relating to Transportation... Limitation on actions by states, local governments, and Indian tribes. A law, order, or other directive of a state, political subdivision of a state, or an Indian tribe that designates, limits, or prohibits the...

  20. 49 CFR 172.822 - Limitation on actions by states, local governments, and Indian tribes.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ..., and Indian tribes. 172.822 Section 172.822 Transportation Other Regulations Relating to Transportation... Limitation on actions by states, local governments, and Indian tribes. A law, order, or other directive of a state, political subdivision of a state, or an Indian tribe that designates, limits, or prohibits the...

  1. Revealing kinetics and state-dependent binding properties of IKur-targeting drugs that maximize atrial fibrillation selectivity

    NASA Astrophysics Data System (ADS)

    Ellinwood, Nicholas; Dobrev, Dobromir; Morotti, Stefano; Grandi, Eleonora

    2017-09-01

    The KV1.5 potassium channel, which underlies the ultra-rapid delayed-rectifier current (IKur) and is predominantly expressed in atria vs. ventricles, has emerged as a promising target to treat atrial fibrillation (AF). However, while numerous KV1.5-selective compounds have been screened, characterized, and tested in various animal models of AF, evidence of antiarrhythmic efficacy in humans is still lacking. Moreover, current guidelines for pre-clinical assessment of candidate drugs heavily rely on steady-state concentration-response curves or IC50 values, which can overlook adverse cardiotoxic effects. We sought to investigate the effects of kinetics and state-dependent binding of IKur-targeting drugs on atrial electrophysiology in silico and reveal the ideal properties of IKur blockers that maximize anti-AF efficacy and minimize pro-arrhythmic risk. To this aim, we developed a new Markov model of IKur that describes KV1.5 gating based on experimental voltage-clamp data in atrial myocytes from patient right-atrial samples in normal sinus rhythm. We extended the IKur formulation to account for state-specificity and kinetics of KV1.5-drug interactions and incorporated it into our human atrial cell model. We simulated 1- and 3-Hz pacing protocols in drug-free conditions and with a [drug] equal to the IC50 value. The effects of binding and unbinding kinetics were determined by examining permutations of the forward (kon) and reverse (koff) binding rates to the closed, open, and inactivated states of the KV1.5 channel. We identified a subset of ideal drugs exhibiting anti-AF electrophysiological parameter changes at fast pacing rates (effective refractory period prolongation), while having little effect on normal sinus rhythm (limited action potential prolongation). Our results highlight that accurately accounting for channel interactions with drugs, including kinetics and state-dependent binding, is critical for developing safer and more effective pharmacological anti

  2. σ-SCF: A direct energy-targeting method to mean-field excited states.

    PubMed

    Ye, Hong-Zhou; Welborn, Matthew; Ricke, Nathan D; Van Voorhis, Troy

    2017-12-07

    The mean-field solutions of electronic excited states are much less accessible than ground state (e.g., Hartree-Fock) solutions. Energy-based optimization methods for excited states, like Δ-SCF (self-consistent field), tend to fall into the lowest solution consistent with a given symmetry-a problem known as "variational collapse." In this work, we combine the ideas of direct energy-targeting and variance-based optimization in order to describe excited states at the mean-field level. The resulting method, σ-SCF, has several advantages. First, it allows one to target any desired excited state by specifying a single parameter: a guess of the energy of that state. It can therefore, in principle, find all excited states. Second, it avoids variational collapse by using a variance-based, unconstrained local minimization. As a consequence, all states-ground or excited-are treated on an equal footing. Third, it provides an alternate approach to locate Δ-SCF solutions that are otherwise hardly accessible by the usual non-aufbau configuration initial guess. We present results for this new method for small atoms (He, Be) and molecules (H 2 , HF). We find that σ-SCF is very effective at locating excited states, including individual, high energy excitations within a dense manifold of excited states. Like all single determinant methods, σ-SCF shows prominent spin-symmetry breaking for open shell states and our results suggest that this method could be further improved with spin projection.

  3. σ-SCF: A direct energy-targeting method to mean-field excited states

    NASA Astrophysics Data System (ADS)

    Ye, Hong-Zhou; Welborn, Matthew; Ricke, Nathan D.; Van Voorhis, Troy

    2017-12-01

    The mean-field solutions of electronic excited states are much less accessible than ground state (e.g., Hartree-Fock) solutions. Energy-based optimization methods for excited states, like Δ-SCF (self-consistent field), tend to fall into the lowest solution consistent with a given symmetry—a problem known as "variational collapse." In this work, we combine the ideas of direct energy-targeting and variance-based optimization in order to describe excited states at the mean-field level. The resulting method, σ-SCF, has several advantages. First, it allows one to target any desired excited state by specifying a single parameter: a guess of the energy of that state. It can therefore, in principle, find all excited states. Second, it avoids variational collapse by using a variance-based, unconstrained local minimization. As a consequence, all states—ground or excited—are treated on an equal footing. Third, it provides an alternate approach to locate Δ-SCF solutions that are otherwise hardly accessible by the usual non-aufbau configuration initial guess. We present results for this new method for small atoms (He, Be) and molecules (H2, HF). We find that σ-SCF is very effective at locating excited states, including individual, high energy excitations within a dense manifold of excited states. Like all single determinant methods, σ-SCF shows prominent spin-symmetry breaking for open shell states and our results suggest that this method could be further improved with spin projection.

  4. 50 CFR 622.457 - Annual catch limits (ACLs), annual catch targets (ACTs), and accountability measures (AMs).

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... OF THE CARIBBEAN, GULF OF MEXICO, AND SOUTH ATLANTIC Spiny Lobster Fishery of Puerto Rico and the U.S. Virgin Islands § 622.457 Annual catch limits (ACLs), annual catch targets (ACTs), and accountability...

  5. 50 CFR 622.439 - Annual catch limits (ACLs), annual catch targets (ACTs), and accountability measures (AMs).

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... OF THE CARIBBEAN, GULF OF MEXICO, AND SOUTH ATLANTIC Reef Fish Fishery of Puerto Rico and the U.S. Virgin Islands § 622.439 Annual catch limits (ACLs), annual catch targets (ACTs), and accountability...

  6. 50 CFR 622.457 - Annual catch limits (ACLs), annual catch targets (ACTs), and accountability measures (AMs).

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... OF THE CARIBBEAN, GULF OF MEXICO, AND SOUTH ATLANTIC Spiny Lobster Fishery of Puerto Rico and the U.S. Virgin Islands § 622.457 Annual catch limits (ACLs), annual catch targets (ACTs), and accountability...

  7. 50 CFR 622.496 - Annual catch limits (ACLs), annual catch targets (ACTs), and accountability measures (AMs).

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... OF THE CARIBBEAN, GULF OF MEXICO, AND SOUTH ATLANTIC Queen Conch Resources of Puerto Rico and the U.S. Virgin Islands § 622.496 Annual catch limits (ACLs), annual catch targets (ACTs), and accountability...

  8. 50 CFR 622.496 - Annual catch limits (ACLs), annual catch targets (ACTs), and accountability measures (AMs).

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... OF THE CARIBBEAN, GULF OF MEXICO, AND SOUTH ATLANTIC Queen Conch Resources of Puerto Rico and the U.S. Virgin Islands § 622.496 Annual catch limits (ACLs), annual catch targets (ACTs), and accountability...

  9. 50 CFR 622.439 - Annual catch limits (ACLs), annual catch targets (ACTs), and accountability measures (AMs).

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... OF THE CARIBBEAN, GULF OF MEXICO, AND SOUTH ATLANTIC Reef Fish Fishery of Puerto Rico and the U.S. Virgin Islands § 622.439 Annual catch limits (ACLs), annual catch targets (ACTs), and accountability...

  10. Glycemic targets and medication limitations for type 2 diabetes mellitus in the older adult.

    PubMed

    Thompson, Angela M; Linnebur, Sunny A; Vande Griend, Joseph P; Saseen, Joseph J

    2014-02-01

    To review the optimal management of type 2 diabetes mellitus (T2DM) in the older adult. A PubMed search was completed to identify publications in the English language from 1947 to 2013 using combinations of the search terms: geriatrics, aged, diabetes mellitus, and type 2 diabetes mellitus. References of articles were also reviewed for inclusion if not identified in the PubMed search. Original studies, clinical reviews, and guidelines were identified and evaluated for clinical relevance. Although the number of older adults with T2DM is growing, evidence for the treatment of T2DM in this population is lacking. Barriers such as polypharmacy, comorbid conditions, economic limitations, cognitive impairment, and increased risk of hypoglycemia may limit optimal glycemic control in older adults. Several organizations provide recommendations for glycemic targets and recommend using standard glycemic goals in most healthy older adults. However, less stringent goals are necessary in certain older populations such as those patients with limited life expectancy and severe hypoglycemia. In general, glycemic goals should be individualized in older patients. Age-related pharmacokinetic and pharmacodynamic changes, comorbid conditions, adverse drug reactions, ease of medication administration, and cost of medications necessitate the need to individualize pharmacologic therapy. Glycemic targets and medication use for T2DM should be individualized in older adults.

  11. State-Targeted Funding and Technical Assistance to Increase Access to Medication Treatment for Opioid Use Disorder.

    PubMed

    Abraham, Amanda J; Andrews, Christina M; Grogan, Colleen M; Pollack, Harold A; D'Aunno, Thomas; Humphreys, Keith; Friedmann, Peter D

    2018-04-01

    As the United States grapples with an opioid epidemic, expanding access to effective treatment for opioid use disorder is a major public health priority. Identifying effective policy tools that can be used to expand access to care is critically important. This article examines the relationship between state-targeted funding and technical assistance and adoption of three medications for treating opioid use disorder: oral naltrexone, injectable naltrexone, and buprenorphine. This study draws from the 2013-2014 wave of the National Drug Abuse Treatment System Survey, a nationally representative, longitudinal study of substance use disorder treatment programs. The sample includes data from 695 treatment programs (85.5% response rate) and representatives from single-state agencies in 49 states and Washington, D.C. (98% response rate). Logistic regression was used to examine the relationships of single-state agency targeted funding and technical assistance to availability of opioid use disorder medications among treatment programs. State-targeted funding was associated with increased program-level adoption of oral naltrexone (adjusted odds ratio [AOR]=3.14, 95% confidence interval [CI]=1.49-6.60, p=.004) and buprenorphine (AOR=2.47, 95% CI=1.31-4.67, p=.006). Buprenorphine adoption was also correlated with state technical assistance to support medication provision (AOR=1.18, 95% CI=1.00-1.39, p=.049). State-targeted funding for medications may be a viable policy lever for increasing access to opioid use disorder medications. Given the historically low rates of opioid use disorder medication adoption in treatment programs, single-state agency targeted funding is a potentially important tool to reduce mortality and morbidity associated with opioid disorders and misuse.

  12. Projections of limiting states for load-bearing structures of reflectors made of polymer composites

    NASA Astrophysics Data System (ADS)

    Doronin, S. V.

    2017-12-01

    This paper deals with limiting states typical for reflector antennas for terrestrial satellite communication systems. Reflectors made of polymer composites are studied. These limiting states are projected by results of the numerical analysis of the stress and strain states. The analysis is executed for reflectors under conditions of static and dynamic loading. It takes into account both overshoot of the state variables of allowed level and the processes of long-term structural material degradation.

  13. The Impact of State Laws Limiting Malpractice Damage Awards on Health Care Expenditures

    PubMed Central

    Hellinger, Fred J.; Encinosa, William E.

    2006-01-01

    Twenty-eight states have laws that limit payments in malpractice cases, and several studies indicate that these laws reduce the frequency and severity of malpractice claims and lower premiums. Moreover, proponents believe that such laws reduce health care expenditures by reducing the practice of defensive medicine. However, there is a dearth of empirical evidence about the impact of these laws on the cost of health care. We used multivariate models and relatively recent data to estimate the impact of state tort reform laws that directly limit malpractice damage payments on health care expenditures. Estimates from these models suggest that laws limiting malpractice payments lower state health care expenditures by between 3% and 4%. PMID:16809580

  14. Reaching quantum limits for phase-shift detection with semiclassical states

    NASA Astrophysics Data System (ADS)

    Luis, Alfredo

    2004-01-01

    We present two measuring strategies reaching the Heisenberg limit for phase-shift measurements using semiclassical coherent states exclusively. We examine their performance by assuming practical experimental conditions such as losses and nonideal detectors.

  15. 78 FR 70414 - Pricing for the 2013 United States Mint Limited Edition Silver Proof SetTM

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-11-25

    ... DEPARTMENT OF THE TREASURY United States Mint Pricing for the 2013 United States Mint Limited Edition Silver Proof Set TM AGENCY: United States Mint, Department of the Treasury. ACTION: Notice. SUMMARY: The United States Mint is announcing a price of $139.95 for the 2013 United States Mint Limited...

  16. Historical trends in creel limits, length-based limits, and season restrictions for black basses in the United States and Canada

    USGS Publications Warehouse

    Paukert, C.; McInerny, M.; Schultz, Ronald

    2007-01-01

    We determined for largemouth bass (Micropterus salmoides), smallmouth bass (M. dolomeui), and spotted bass (M. punctulatus) historical trends in state- and province-wide creel limits, length limits, and season closures along with the rationale justifying these regulations. Based on data gathered via mail surveys and the Internet, 55 jurisdictions had state- or province-wide creel limits, minimum length limits, or season closures, with each regulation type enacted as early as pre-1900. Most early regulations were established to protect spawning bass, but providing equitable distribution of harvest and increasing the quality of bass catch or harvest were the most common rationales for current regulations. Spatial and temporal trends in regulations were similar among species, were affected by geographic location, were not affected by angler preference except for season closures, and were frequently uninfluenced by advances in scientific knowledge of black bass biology.

  17. An Energy-Based Limit State Function for Estimation of Structural Reliability in Shock Environments

    DOE PAGES

    Guthrie, Michael A.

    2013-01-01

    limit state function is developed for the estimation of structural reliability in shock environments. This limit state function uses peak modal strain energies to characterize environmental severity and modal strain energies at failure to characterize the structural capacity. The Hasofer-Lind reliability index is briefly reviewed and its computation for the energy-based limit state function is discussed. Applications to two degree of freedom mass-spring systems and to a simple finite element model are considered. For these examples, computation of the reliability index requires little effort beyond a modal analysis, but still accounts for relevant uncertainties in both the structure and environment.more » For both examples, the reliability index is observed to agree well with the results of Monte Carlo analysis. In situations where fast, qualitative comparison of several candidate designs is required, the reliability index based on the proposed limit state function provides an attractive metric which can be used to compare and control reliability.« less

  18. Risk maps for targeting exotic plant pest detection programs in the United States

    Treesearch

    R.D. Magarey; D.M. Borchert; J.S. Engle; M Garcia-Colunga; Frank H. Koch; et al

    2011-01-01

    In the United States, pest risk maps are used by the Cooperative Agricultural Pest Survey for spatial and temporal targeting of exotic plant pest detection programs. Methods are described to create standardized host distribution, climate and pathway risk maps for the top nationally ranked exotic pest targets. Two examples are provided to illustrate the risk mapping...

  19. Exploring the engineering limit of heat flux of a W/RAFM divertor target for fusion reactors

    NASA Astrophysics Data System (ADS)

    Mao, X.; Fursdon, M.; Chang, X. B.; Zhang, J. W.; Liu, P.; Ellwood, G.; Qian, X. Y.; Qin, S. J.; Peng, X. B.; Barrett, T. R.; Liu, P.

    2018-06-01

    The design and development of a fusion reactor divertor plasma facing component (PFC) is one of the many challenging issues on the road to commercial use of fusion energy. The divertor PFC is expected to exhaust steady state heat loads in the region of 10 MW m‑2 while keeping temperatures and thermo-mechanical stresses in its structure within the allowable limits. For ITER (International Thermo-Nuclear Experimental Reactor) a water cooled W/CuCrZr divertor PFC concept has been developed. However, this concept is not necessarily assured for use in future fusion reactors mainly because the neutron radiation dose would be at least an order magnitude higher, resulting in limited thermo-mechanical performance and considerably more activated waste products. In the present study, a water cooled divertor PFC using reduced activation ferritic-martensitic (RAFM) steel as the heat sink pipe has been designed with pressurised water reactor-like cooling conditions (pressure of 15.5 MPa, velocity of 10–20 m s‑1 and temperature of 300 °C). The PFC is made up of a number of rectangular tungsten tiles, each with an inner circular hole (so-called monoblocks), joined onto a RAFM steel pipe with copper interlayers. The thermo-mechanical performance of the PFC has been studied in detail. The heat transfer coefficient between the RAFM pipe inner surface and the water was calculated using published correlations. Geometric parameters and water velocity were optimized with finite element (FE) thermal analysis, to achieve acceptable temperatures in the structure given the target exhaust heat load of 10 MW m‑2. Under this heat load and the optimised thermal design parameters, the structure of the PFC was further assessed by mechanical analysis. We find that under these conditions the RAFM steel pipe experiences cyclic plasticity, and fails the common linear elastic ratchetting (3 Sm) rule. Nevertheless, the designed W/RAFM divertor PFU can withstand 10 MW m‑2 heat load, albeit

  20. State Child Care Policies for Limited English Proficient Families

    ERIC Educational Resources Information Center

    Firgens, Emily; Matthews, Hannah

    2012-01-01

    The Child Care and Development Block Grant (CCDBG), the largest source of federal funding for child care assistance available to states, provides low-income families with help paying for child care. Studies have shown that low-income LEP (limited English proficient), as well as immigrant families, are less likely to receive child care assistance.…

  1. The Effect of Local Limitations on General State Aid in Illinois.

    ERIC Educational Resources Information Center

    Bush, Erik

    2002-01-01

    Study to determine if a substantive relationship exits between the progression of a federal Tax Increment Financing (TIF) district, the long-term effects of the state Property Tax Extension Limitation Law (PTELL), and the General State Aid funding of school districts in Illinois. Finds that both TIF and PTELL lead to an increase in General State…

  2. Targeting global conservation funding to limit immediate biodiversity declines

    PubMed Central

    Waldron, Anthony; Mooers, Arne O.; Miller, Daniel C.; Nibbelink, Nate; Redding, David; Kuhn, Tyler S.; Roberts, J. Timmons; Gittleman, John L.

    2013-01-01

    Inadequate funding levels are a major impediment to effective global biodiversity conservation and are likely associated with recent failures to meet United Nations biodiversity targets. Some countries are more severely underfunded than others and therefore represent urgent financial priorities. However, attempts to identify these highly underfunded countries have been hampered for decades by poor and incomplete data on actual spending, coupled with uncertainty and lack of consensus over the relative size of spending gaps. Here, we assemble a global database of annual conservation spending. We then develop a statistical model that explains 86% of variation in conservation expenditures, and use this to identify countries where funding is robustly below expected levels. The 40 most severely underfunded countries contain 32% of all threatened mammalian diversity and include neighbors in some of the world’s most biodiversity-rich areas (Sundaland, Wallacea, and Near Oceania). However, very modest increases in international assistance would achieve a large improvement in the relative adequacy of global conservation finance. Our results could therefore be quickly applied to limit immediate biodiversity losses at relatively little cost. PMID:23818619

  3. Targeting global conservation funding to limit immediate biodiversity declines.

    PubMed

    Waldron, Anthony; Mooers, Arne O; Miller, Daniel C; Nibbelink, Nate; Redding, David; Kuhn, Tyler S; Roberts, J Timmons; Gittleman, John L

    2013-07-16

    Inadequate funding levels are a major impediment to effective global biodiversity conservation and are likely associated with recent failures to meet United Nations biodiversity targets. Some countries are more severely underfunded than others and therefore represent urgent financial priorities. However, attempts to identify these highly underfunded countries have been hampered for decades by poor and incomplete data on actual spending, coupled with uncertainty and lack of consensus over the relative size of spending gaps. Here, we assemble a global database of annual conservation spending. We then develop a statistical model that explains 86% of variation in conservation expenditures, and use this to identify countries where funding is robustly below expected levels. The 40 most severely underfunded countries contain 32% of all threatened mammalian diversity and include neighbors in some of the world's most biodiversity-rich areas (Sundaland, Wallacea, and Near Oceania). However, very modest increases in international assistance would achieve a large improvement in the relative adequacy of global conservation finance. Our results could therefore be quickly applied to limit immediate biodiversity losses at relatively little cost.

  4. Solid-state electron spin lifetime limited by phononic vacuum modes.

    PubMed

    Astner, T; Gugler, J; Angerer, A; Wald, S; Putz, S; Mauser, N J; Trupke, M; Sumiya, H; Onoda, S; Isoya, J; Schmiedmayer, J; Mohn, P; Majer, J

    2018-04-01

    Longitudinal relaxation is the process by which an excited spin ensemble decays into its thermal equilibrium with the environment. In solid-state spin systems, relaxation into the phonon bath usually dominates over the coupling to the electromagnetic vacuum 1-9 . In the quantum limit, the spin lifetime is determined by phononic vacuum fluctuations 10 . However, this limit was not observed in previous studies due to thermal phonon contributions 11-13 or phonon-bottleneck processes 10, 14,15 . Here we use a dispersive detection scheme 16,17 based on cavity quantum electrodynamics 18-21 to observe this quantum limit of spin relaxation of the negatively charged nitrogen vacancy (NV - ) centre 22 in diamond. Diamond possesses high thermal conductivity even at low temperatures 23 , which eliminates phonon-bottleneck processes. We observe exceptionally long longitudinal relaxation times T 1 of up to 8 h. To understand the fundamental mechanism of spin-phonon coupling in this system we develop a theoretical model and calculate the relaxation time ab initio. The calculations confirm that the low phononic density of states at the NV - transition frequency enables the spin polarization to survive over macroscopic timescales.

  5. Target Detection of Quantum Illumination Receiver Based on Photon-subtracted Entanglement State

    NASA Astrophysics Data System (ADS)

    Chi, Jiao; Liu, HongJun; Huang, Nan; Wang, ZhaoLu

    2017-12-01

    We theoretically propose a quantum illumination receiver based on the ideal photon-subtracted two-mode squeezed state (PSTMSS) to efficiently detect the noise-hidden target. This receiver is generated by applying an optical parametric amplifier (OPA) to the cross correlation detection. With analyzing the output performance, it is found that OPA as a preposition technology of the receiver can contribute to the PSTMSS by significantly reducing the error probability than that of the general two-mode squeezed state (TMSS). Comparing with TMSS, the signal-to-noise ratio of quantum illumination based on ideal PSTMSS and OPA is improved more than 4 dB under an optimal gain of OPA. This work may provide a potential improvement in the application of accurate target detection when two kinds of resource have the identical real squeezing parameter.

  6. 12 CFR 303.15 - Certain limited liability companies deemed incorporated under State law.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 4 2010-01-01 2010-01-01 false Certain limited liability companies deemed... liability companies deemed incorporated under State law. (a) For purposes of the definition of “State bank... liability company (LLC) under the law of any State is deemed to be “incorporated” under the law of the State...

  7. Improved Limits on $$B^{0}$$ Decays to Invisible $(+gamma)$ Final States

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

    Lees, J.P.; Poireau, V.; Tisserand, V.

    2013-11-01

    We establish improved upper limits on branching fractions for B{sup 0} decays to final states where the decay products are purely invisible (i.e., no observable final state particles) and for final states where the only visible product is a photon. Within the Standard Model, these decays have branching fractions that are below the current experimental sensitivity, but various models of physics beyond the Standard Model predict significant contributions for these channels. Using 471 million B{bar B} pairs collected at the {Upsilon} (4S) resonance by the BABAR experiment at the PEP-II e{sup +}e{sup -} storage ring at the SLAC National Acceleratormore » Laboratory, we establish upper limits at the 90% confidence level of 2.4 x 10{sup -5} for the branching fraction of B{sup 0} {yields} invisible and 1.7 x 10{sup -5} for the branching fraction of B{sup 0} {yields} invisible + {gamma}.« less

  8. Glovebox Integrated Microgravity Isolation Technology (g-LIMIT): A Linearized State-Space Model

    NASA Technical Reports Server (NTRS)

    Hampton, R. David; Calhoun, Philip C.; Whorton, Mark S.

    2001-01-01

    Vibration acceleration levels on large space platforms exceed the requirements of many space experiments. The Glovebox Integrated Microgravity Isolation Technology (g-LIMIT) is being built by the NASA Marshall Space Flight Center to attenuate these disturbances to acceptable levels. G-LIMIT uses Lorentz (voice-coil) magnetic actuators to levitate and isolate payloads at the individual experiment/sub-experiment (versus rack) level. Payload acceleration, relative position, and relative orientation measurements are fed to a state-space controller. The controller, in turn, determines the actuator Currents needed for effective experiment isolation. This paper presents the development of an algebraic, state-space model of g-LIMIT, in a form suitable for optimal controller design. The equations are first derived using Newton's Second Law directly, then simplified to a linear form for the purpose of controller design.

  9. Surpassing the no-cloning limit with a heralded hybrid linear amplifier for coherent states

    PubMed Central

    Haw, Jing Yan; Zhao, Jie; Dias, Josephine; Assad, Syed M.; Bradshaw, Mark; Blandino, Rémi; Symul, Thomas; Ralph, Timothy C.; Lam, Ping Koy

    2016-01-01

    The no-cloning theorem states that an unknown quantum state cannot be cloned exactly and deterministically due to the linearity of quantum mechanics. Associated with this theorem is the quantitative no-cloning limit that sets an upper bound to the quality of the generated clones. However, this limit can be circumvented by abandoning determinism and using probabilistic methods. Here, we report an experimental demonstration of probabilistic cloning of arbitrary coherent states that clearly surpasses the no-cloning limit. Our scheme is based on a hybrid linear amplifier that combines an ideal deterministic linear amplifier with a heralded measurement-based noiseless amplifier. We demonstrate the production of up to five clones with the fidelity of each clone clearly exceeding the corresponding no-cloning limit. Moreover, since successful cloning events are heralded, our scheme has the potential to be adopted in quantum repeater, teleportation and computing applications. PMID:27782135

  10. Enhancing transit polio vaccination in collaboration with targeted stakeholders in Kaduna State, Nigeria: Lessons learnt: 2014-2015.

    PubMed

    Musa, Audu; Abba, Bashir; Ningi, Adamu M I; Gali, Emanuel; Bawa, Samuel; Manneh, Fadninding; Mkanda, Pascal; Banda, Richard; Yehuluashet, Yared G; Tegegne, Sisay G; Umeh, Gregory; Nsubuga, Peter; Etsano, Andrew; Shuaib, Faisal; Mohammed, Ado; Vaz, Rui G

    2016-10-10

    In Kaduna State of Nigeria, the high influx of people from neighboring states with eligible children for polio vaccination represents a significant proportion of the target population. Many of these children are often missed by the vaccination team. The purpose of the study was to determine the contribution of targeted stakeholders in transit polio vaccination. We used the trends of vaccinated children at transit points, motor parks and markets, well as total children vaccinated by transit teams in Chikun, Igabi and Sabon Gari Local Government Areas (LGAs) of Kaduna State, Nigeria, four rounds before and after the introduction of transit polio vaccination with targeted stakeholders in Kaduna State. A total of 87,502 under-5 children were vaccinated by the various transit teams in the three LGAs, which accounted for 3.2% of the total 2,781,162 children vaccinated by the three LGAs. For transit point vaccination, the number of vaccinated children increased from 1026 to 19,289 (302%), while motor park vaccination increased from 1289 to 4106 (318%) and market vaccination increased from 10,488 to 14,511 (138%), four rounds after the introduction of transit polio vaccination with targeted stakeholders. Engagement of targeted stakeholders significantly enhanced transit polio vaccination in Kaduna State, Nigeria. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  11. Off-target model based OPC

    NASA Astrophysics Data System (ADS)

    Lu, Mark; Liang, Curtis; King, Dion; Melvin, Lawrence S., III

    2005-11-01

    Model-based Optical Proximity correction has become an indispensable tool for achieving wafer pattern to design fidelity at current manufacturing process nodes. Most model-based OPC is performed considering the nominal process condition, with limited consideration of through process manufacturing robustness. This study examines the use of off-target process models - models that represent non-nominal process states such as would occur with a dose or focus variation - to understands and manipulate the final pattern correction to a more process robust configuration. The study will first examine and validate the process of generating an off-target model, then examine the quality of the off-target model. Once the off-target model is proven, it will be used to demonstrate methods of generating process robust corrections. The concepts are demonstrated using a 0.13 μm logic gate process. Preliminary indications show success in both off-target model production and process robust corrections. With these off-target models as tools, mask production cycle times can be reduced.

  12. 45 CFR 400.210 - Time limits for obligating and expending funds and for filing State claims.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... the funds. (2) A State's final financial report on expenditures of CMA grants, including CMA.... A State's final financial report on expenditures of social services and targeted assistance grants..., if a State's final financial expenditure report has not been received, the Department will deobligate...

  13. Potential for reducing air-pollutants while achieving 2 °C global temperature change limit target.

    PubMed

    Hanaoka, Tatsuya; Akashi, Osamu; Fujiwara, Kazuya; Motoki, Yuko; Hibino, Go

    2014-12-01

    This study analyzes the potential to reduce air pollutants while achieving the 2 °C global temperature change limit target above pre-industrial levels, by using the bottom-up optimization model, AIM/Enduse[Global]. This study focuses on; 1) estimating mitigation potentials and costs for achieving 2 °C, 2.5 °C, and 3 °C target scenarios, 2) assessing co-benefits of reducing air pollutants such as NOx, SO2, BC, PM, and 3) analyzing features of sectoral attributions in Annex I and Non-Annex I groups of countries. The carbon tax scenario at 50 US$/tCO2-eq in 2050 can reduce GHG emissions more than the 3 °C target scenario, but a higher carbon price around 400 US$/tCO2-eq in 2050 is required to achieve the 2 °C target scenario. However, there is also a co-benefit of large reduction potential of air pollutants, in the range of 60-80% reductions in 2050 from the reference scenario while achieving the 2 °C target. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. 49 CFR 172.822 - Limitation on actions by states, local governments, and Indian tribes.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... REGULATIONS HAZARDOUS MATERIALS TABLE, SPECIAL PROVISIONS, HAZARDOUS MATERIALS COMMUNICATIONS, EMERGENCY... state, political subdivision of a state, or an Indian tribe that designates, limits, or prohibits the use of a rail line (other than a rail line owned by a state, political subdivision of a state, or an...

  15. 33 CFR 328.5 - Changes in limits of waters of the United States.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... OF THE ARMY, DEPARTMENT OF DEFENSE DEFINITION OF WATERS OF THE UNITED STATES § 328.5 Changes in... drainage may remove an area from waters of the United States. Man-made changes may affect the limits of...

  16. Eikonal Scattering in the sdg Interacting Boson Model:. Analytical Results in the SUsdg(3) Limit and Their Generalizations

    NASA Astrophysics Data System (ADS)

    Kota, V. K. B.

    General expression for the representation matrix elements in the SUsdg(3) limit of the sdg interacting boson model (sdgIBM) is derived that determine the scattering amplitude in the eikonal approximation for medium energy proton-nucleus scattering when the target nucleus is deformed and it is described by the SUsdg(3) limit. The SUsdg(3) result is generalized to two important situations: (i) when the target nucleus ground band states are described as states arising out of angular momentum projection from a general single Kπ = 0+ intrinsic state in sdg space; (ii) for rotational bands built on one-phonon excitations in sdgIBM.

  17. Targeting glioblastoma-derived pericytes improves chemotherapeutic outcome.

    PubMed

    Guerra, Daniel A P; Paiva, Ana E; Sena, Isadora F G; Azevedo, Patrick O; Silva, Walison N; Mintz, Akiva; Birbrair, Alexander

    2018-05-14

    Glioblastoma is the most common malignant brain cancer in adults, with poor prognosis. The blood-brain barrier limits the arrival of several promising anti-glioblastoma drugs, and restricts the design of efficient therapies. Recently, by using state-of-the-art technologies, including thymidine kinase targeting system in combination with glioblastoma xenograft mouse models, it was revealed that targeting glioblastoma-derived pericytes improves chemotherapy efficiency. Strikingly, ibrutinib treatment enhances chemotherapeutic effectiveness, by targeting pericytes, improving blood-brain barrier permeability, and prolonging survival. This study identifies glioblastoma-derived pericyte as a novel target in the brain tumor microenvironment during carcinogenesis. Here, we summarize and evaluate recent advances in the understanding of pericyte's role in the glioblastoma microenvironment.

  18. Motor vehicle driver death and high state maximum speed limits: 1991-1993.

    PubMed

    Yamane, Grover K; Bradshaw, Benjamin S

    2008-09-01

    To measure the association between motor vehicle crash (MVC) driver death and high state maximum speed limits. This study used a case-control design and assessed driver deaths from three major types of MVCs: non-collision; collision with motor vehicles in transit; and collision with stationary objects. The study period was 1991-1993. For each type of crash, case subject populations of fatally injured drivers were obtained from the U.S. Department of Transportation Fatality Analysis Reporting System. Four control subject populations, each associated with a different cause of death, were obtained from a U.S. national death certificate database (the causes of death were unintentional poisoning, non-Hodgkin lymphoma, drowning, and diabetes mellitus). Subjects were considered exposed if the state in which they crashed (for cases) or died (for controls) had a maximum speed limit greater than 55 mph. Each of the three case subject populations was compared against each of the four control subject populations. Odds ratios (ORs) were adjusted for age and gender. For non-collision driver death, ORs ranged from 3.06 to 6.56, depending on the year and control group; all the ORs were significant. For collision with motor vehicles in transit driver death, ORs ranged from 1.12 to 2.22; all the ORs were significant. For collision with stationary objects driver death, ORs ranged from 0.87 to 1.83. There was a moderately strong and significant association between non-collision driver death and high state maximum speed limits. For collision with motor vehicles in transit driver death, the association was somewhat milder but still consistent. For collision with stationary objects driver death, the presence of an association was unclear. During 1991-1993, the effects of high state maximum speed limits may have been different for different types of MVCs.

  19. Negotiating targets with patients: choice of target in relation to occupational state.

    PubMed

    Robinson, Sandra M; Walker, David J

    2012-02-01

    Following the recent National Institute for Health and Clinical Excellence guidance on the management of RA, we were interested to see if we could negotiate targets for treatment with patients in routine clinics, how they would express this and whether staying at work would be a target. One hundred RA patients were recruited. They were consecutive within clinics, but not all clinics were used. They were asked their understanding of the DAS score and a target for treatment negotiated. Any impact of the RA on their paid employment was then explored. Four participants were unable to specify a target for their RA. Negotiated targets were expressed as restricted activities and either as maintaining an activity (70) if the disease was stable, or regaining an activity (26) if the treatment was being increased. Targets were walking a distance for 50% of patients; leisure activities for 18%; domestic activities for 17%; work for 14% and personal care for 2%. For the 21 participants currently working, maintaining work was the target for 12, with 1 wishing to regain lost hours. No patient currently not working expressed returning to work as a target. There were some differences in targets between men and women. Patients are able to negotiate a target for their treatment, expressed as maintaining or regaining a physical activity. Work ceases to be a target once it is lost. Therefore, preventing loss of occupation is likely to be more effective than trying to regain it.

  20. 49 CFR 174.2 - Limitation on actions by states, local governments, and Indian tribes.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ..., and Indian tribes. 174.2 Section 174.2 Transportation Other Regulations Relating to Transportation..., and Indian tribes. Sections 5125 and 20106 of Title 49, United States Code, limit the authority of states, political subdivisions of states, and Indian tribes to impose requirements on the transportation...

  1. 49 CFR 179.8 - Limitation on actions by states, local governments, and Indian tribes.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ..., and Indian tribes. 179.8 Section 179.8 Transportation Other Regulations Relating to Transportation... governments, and Indian tribes. Sections 5125 and 20106 of Title 49, United States Code, limit the authority of states, political subdivisions of states, and Indian tribes to impose requirements on the...

  2. 49 CFR 174.2 - Limitation on actions by states, local governments, and Indian tribes.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ..., and Indian tribes. 174.2 Section 174.2 Transportation Other Regulations Relating to Transportation..., and Indian tribes. Sections 5125 and 20106 of Title 49, United States Code, limit the authority of states, political subdivisions of states, and Indian tribes to impose requirements on the transportation...

  3. 49 CFR 179.8 - Limitation on actions by states, local governments, and Indian tribes.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ..., and Indian tribes. 179.8 Section 179.8 Transportation Other Regulations Relating to Transportation... governments, and Indian tribes. Sections 5125 and 20106 of Title 49, United States Code, limit the authority of states, political subdivisions of states, and Indian tribes to impose requirements on the...

  4. 49 CFR 179.8 - Limitation on actions by states, local governments, and Indian tribes.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ..., and Indian tribes. 179.8 Section 179.8 Transportation Other Regulations Relating to Transportation... governments, and Indian tribes. Sections 5125 and 20106 of Title 49, United States Code, limit the authority of states, political subdivisions of states, and Indian tribes to impose requirements on the...

  5. 49 CFR 179.8 - Limitation on actions by states, local governments, and Indian tribes.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ..., and Indian tribes. 179.8 Section 179.8 Transportation Other Regulations Relating to Transportation... governments, and Indian tribes. Sections 5125 and 20106 of Title 49, United States Code, limit the authority of states, political subdivisions of states, and Indian tribes to impose requirements on the...

  6. Projective limits of state spaces II. Quantum formalism

    NASA Astrophysics Data System (ADS)

    Lanéry, Suzanne; Thiemann, Thomas

    2017-06-01

    In this series of papers, we investigate the projective framework initiated by Kijowski (1977) and Okołów (2009, 2014, 2013), which describes the states of a quantum theory as projective families of density matrices. A short reading guide to the series can be found in Lanéry (2016). After discussing the formalism at the classical level in a first paper (Lanéry, 2017), the present second paper is devoted to the quantum theory. In particular, we inspect in detail how such quantum projective state spaces relate to inductive limit Hilbert spaces and to infinite tensor product constructions (Lanéry, 2016, subsection 3.1) [1]. Regarding the quantization of classical projective structures into quantum ones, we extend the results by Okołów (2013), that were set up in the context of linear configuration spaces, to configuration spaces given by simply-connected Lie groups, and to holomorphic quantization of complex phase spaces (Lanéry, 2016, subsection 2.2) [1].

  7. Limits in Proton Nuclear Singlet-State Lifetimes Measured with para-Hydrogen-Induced Polarization.

    PubMed

    Zhang, Yuning; Duan, Xueyou; Soon, Pei Che; Sychrovský, Vladimír; Canary, James W; Jerschow, Alexej

    2016-10-05

    The synthesis of a hyperpolarized molecule was developed, where the polarization and the singlet state were preserved over two controlled chemical steps. Nuclear singlet-state lifetimes close to 6 min for protons are reported in dimethyl fumarate. Owing to the high symmetry (AA'X 3 X 3 ' and A 2 systems), the singlet-state readout requires either a chemical desymmetrization or a long and repeated spin lock. Using DFT calculations and relaxation models, we further determine nuclear spin singlet lifetime limiting factors, which include the intramolecular dipolar coupling mechanism (proton-proton and proton-deuterium), the chemical shift anisotropy mechanism (symmetric and antisymmetric), and the intermolecular dipolar coupling mechanism (to oxygen and deuterium). If the limit of paramagnetic relaxation caused by residual oxygen could be lifted, the intramolecular dipolar coupling to deuterium would become the limiting relaxation mechanism and proton lifetimes upwards of 26 min could become available in the molecules considered here (dimethyl maleate and dimethyl fumarate). © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Steady states of OQBM: Central Limit Theorem, Gaussian and non-Gaussian behavior

    NASA Astrophysics Data System (ADS)

    Petruccione, Francesco; Sinayskiy, Ilya

    Open Quantum Brownian Motion (OQBM) describes a Brownian particle with an additional internal quantum degree of freedom. Originally, it was introduced as a scaling limit of Open Quantum Walks (OQWs). Recently, it was noted, that for the model of free OQBM with a two-level system as an internal degree of freedom and decoherent coupling to a dissipative environment, one could use weak external driving of the internal degree of freedom to manipulate the steady-state position of the walker. This observation establishes a useful connection between controllable parameters of the OQBM, e.g. driving strengths and magnitude of detuning, and its steady state properties. Although OQWs satisfy a central limit theorem (CLT), it is known, that OQBM, in general, does not. The aim of this work is to derive steady states for some particular OQBMs and observe possible transitions from Gaussian to non-Gaussian behavior depending on the choice of quantum coin and as a function of diffusion coefficient and dissipation strength.

  9. Targeting pH regulating proteins for cancer therapy-Progress and limitations.

    PubMed

    Parks, Scott K; Pouysségur, Jacques

    2017-04-01

    Tumour acidity induced by metabolic alterations and incomplete vascularisation sets cancer cells apart from normal cellular physiology. This distinguishing tumour characteristic has been an area of intense study, as cellular pH (pH i ) disturbances disrupt protein function and therefore multiple cellular processes. Tumour cells effectively utilise pH i regulating machinery present in normal cells with enhancements provided by additional oncogenic or hypoxia induced protein modifications. This overall improvement of pH regulation enables maintenance of an alkaline pH i in the continued presence of external acidification (pH e ). Considerable experimentation has revealed targets that successfully disrupt tumour pH i regulation in efforts to develop novel means to weaken or kill tumour cells. However, redundancy in these pH-regulating proteins, which include Na + /H + exchangers (NHEs), carbonic anhydrases (CAs), Na + /HCO 3 - co-transporters (NBCs) and monocarboxylate transporters (MCTs) has prevented effective disruption of tumour pH i when individual protein targeting is performed. Here we synthesise recent advances in understanding both normoxic and hypoxic pH regulating mechanisms in tumour cells with an ultimate focus on the disruption of tumour growth, survival and metastasis. Interactions between tumour acidity and other cell types are also proving to be important in understanding therapeutic applications such as immune therapy. Promising therapeutic developments regarding pH manipulation along with current limitations are highlighted to provide a framework for future research directives. Copyright © 2017 Elsevier Ltd. All rights reserved.

  10. Analytical steady-state solutions for water-limited cropping systems using saline irrigation water

    USDA-ARS?s Scientific Manuscript database

    Due to the diminishing availability of good quality water for irrigation, it is increasingly important that irrigation and salinity management tools be able to target submaximal crop yields and support the use of marginal quality waters. In this work, we present a steady-state irrigated systems mod...

  11. Computation of the target state and feedback controls for time optimal consensus in multi-agent systems

    NASA Astrophysics Data System (ADS)

    Mulla, Ameer K.; Patil, Deepak U.; Chakraborty, Debraj

    2018-02-01

    N identical agents with bounded inputs aim to reach a common target state (consensus) in the minimum possible time. Algorithms for computing this time-optimal consensus point, the control law to be used by each agent and the time taken for the consensus to occur, are proposed. Two types of multi-agent systems are considered, namely (1) coupled single-integrator agents on a plane and, (2) double-integrator agents on a line. At the initial time instant, each agent is assumed to have access to the state information of all the other agents. An algorithm, using convexity of attainable sets and Helly's theorem, is proposed, to compute the final consensus target state and the minimum time to achieve this consensus. Further, parts of the computation are parallelised amongst the agents such that each agent has to perform computations of O(N2) run time complexity. Finally, local feedback time-optimal control laws are synthesised to drive each agent to the target point in minimum time. During this part of the operation, the controller for each agent uses measurements of only its own states and does not need to communicate with any neighbouring agents.

  12. U.s. State and federal laws targeting distracted driving.

    PubMed

    Catherine Chase, J D

    2014-01-01

    Distracted driving has burgeoned with the proliferation of cell phones, global positioning systems and other in-vehicle and personal electronic devices. Annually more than 3,300 people are killed and an additional 400,000 are injured in the United States in distracted driving crashes. The United States (U.S.) federal and state governments have responded to this public health problem with policies and laws; however, a more comprehensive and more effective approach is still needed. Some restrictions on the use of electronic devices while driving by federal employees and some voluntary guidelines and recommendations have been issued. Public opinion polls show support for addressing the issue of distracted driving with state laws. The majority of states have laws banning text messaging while driving and prohibiting the use of an electronic device by teenage or novice drivers. Some states prohibit all drivers from using a hand-held cellphone. Currently no state has a total ban on the use of personal electronic devices while driving. Successful past traffic safety campaigns changing driver behavior have demonstrated the necessity to adopt a "three Es" approach of Enactment of a law, Education of the public about the law, and rigorous Enforcement of the law. Experience reveals that this approach, along with future federal regulation of in-vehicle electronic devices and the employment of technology to limit the use of electronic devices while driving, is needed to alter personal behavior in order to reduce distractions and keep drivers focused on the driving task.

  13. Finding agreement to limit life-sustaining treatment for children who are in state custody.

    PubMed

    Savage, T; Michalak, D R

    2001-01-01

    For children in state custody with extensive disabilities who reside in a skilled nursing facility, it is possible and, at times, desirable to limit treatment in the form of withholding resuscitation. With demonstration and documentation of the benefits and burdens of resuscitation for a particular child, the child protection agency will authorize a "Do Not Resuscitate" order. This article discusses the procedural as well as ethical issues involved in the process of finding agreement to limit life-sustaining treatment for children who are in state custody.

  14. Projective limits of state spaces I. Classical formalism

    NASA Astrophysics Data System (ADS)

    Lanéry, Suzanne; Thiemann, Thomas

    2017-01-01

    In this series of papers, we investigate the projective framework initiated by Jerzy Kijowski (1977) and Andrzej Okołów (2009, 2013, 2014), which describes the states of a quantum (field) theory as projective families of density matrices. A short reading guide to the series can be found in [27]. The present first paper aims at clarifying the classical structures that underlies this formalism, namely projective limits of symplectic manifolds [27, subsection 2.1]. In particular, this allows us to discuss accurately the issues hindering an easy implementation of the dynamics in this context, and to formulate a strategy for overcoming them [27, subsection 4.1].

  15. The Academic Achievement of Limited English Proficient (LEP) Youth in New and Established Immigrant States: Lessons from the National Assessment of Educational Progress (NAEP)

    PubMed Central

    Spees, Lisa P.; Potochnick, Stephanie; Perreira, Krista M.

    2018-01-01

    The dramatic growth and dispersal of immigrant families has changed the face of public education at a time when states are experiencing increased school accountability pressures under the No Child Left Behind (NCLB) and its recent successor the Every Student Succeeds Act. Of particular concern is how these demographic shifts affect the academic well-being of Limited English Proficient (LEP) youth, the protected sub-group that most directly targets children from immigrant families. Using individual-level data from the National Association of Educational Progress, we examine how 8th grade test scores of LEP youth differ across new and established immigrant destination states. Results show that achievement for LEP youth is higher in new than in established immigrant states but that this advantage is not consistent across ethnic/racial groups. LEP youth in new immigrant states benefit from more favorable demographic characteristics and more family and school resources, but these differences only explain a small portion of the achievement gap. PMID:29527112

  16. Targeting nursing homes under the Quality Improvement Organization program's 9th statement of work.

    PubMed

    Stevenson, David G; Mor, Vincent

    2009-09-01

    In the Quality Improvement Organization (QIO) program's latest Statement of Work, the Centers for Medicare and Medicaid Services (CMS) is targeting its nursing home activities toward facilities that perform poorly on two quality measures-pressure ulcers and restraint use. The designation of target facilities is a shift in strategy for CMS and a direct response to criticism that QIO program resources were not being targeted effectively to facilities or clinical areas that most needed improvement. Using administrative data, this article analyzes implications of using narrowly defined criteria to identify facilities that need improvement, particularly in light of considerable evidence showing that nursing home quality is multidimensional and may change over time. The analyses show that one in four facilities is targeted for improvement nationally but that approximately half of some states' facilities are targeted while other states have almost none targeted. The analyses also convey deeper limitations to using threshold values on individual measures to identify poorly performing homes. Target facilities can be among the top performers on a range of other quality measures, and their performance on targeted measures themselves may change over time. The implication of these features is that a very different group of facilities would have been chosen had the QIO program targeted other measures or examined performance at a different point in time. Ultimately, CMS has chosen a blunt instrument to identify poorly performing nursing homes, and supplemental strategies-such as soliciting input from state survey agencies and more closely aligning quality improvement and quality assurance efforts-should be considered to address potential limitations.

  17. Absorption spectroscopy at the ultimate quantum limit from single-photon states

    NASA Astrophysics Data System (ADS)

    Whittaker, R.; Erven, C.; Neville, A.; Berry, M.; O'Brien, J. L.; Cable, H.; Matthews, J. C. F.

    2017-02-01

    Absorption spectroscopy is routinely used to characterise chemical and biological samples. For the state-of-the-art in laser absorption spectroscopy, precision is theoretically limited by shot-noise due to the fundamental Poisson-distribution of photon number in laser radiation. In practice, the shot-noise limit can only be achieved when all other sources of noise are eliminated. Here, we use wavelength-correlated and tuneable photon pairs to demonstrate how absorption spectroscopy can be performed with precision beyond the shot-noise limit and near the ultimate quantum limit by using the optimal probe for absorption measurement—single photons. We present a practically realisable scheme, which we characterise both the precision and accuracy of by measuring the response of a control feature. We demonstrate that the technique can successfully probe liquid samples and using two spectrally similar types of haemoglobin we show that obtaining a given precision in resolution requires fewer heralded single probe photons compared to using an idealised laser.

  18. Enhancing emotional-based target prediction

    NASA Astrophysics Data System (ADS)

    Gosnell, Michael; Woodley, Robert

    2008-04-01

    This work extends existing agent-based target movement prediction to include key ideas of behavioral inertia, steady states, and catastrophic change from existing psychological, sociological, and mathematical work. Existing target prediction work inherently assumes a single steady state for target behavior, and attempts to classify behavior based on a single emotional state set. The enhanced, emotional-based target prediction maintains up to three distinct steady states, or typical behaviors, based on a target's operating conditions and observed behaviors. Each steady state has an associated behavioral inertia, similar to the standard deviation of behaviors within that state. The enhanced prediction framework also allows steady state transitions through catastrophic change and individual steady states could be used in an offline analysis with additional modeling efforts to better predict anticipated target reactions.

  19. U.S. State and Federal Laws Targeting Distracted Driving

    PubMed Central

    Catherine Chase, J.D.

    2014-01-01

    Distracted driving has burgeoned with the proliferation of cell phones, global positioning systems and other in-vehicle and personal electronic devices. Annually more than 3,300 people are killed and an additional 400,000 are injured in the United States in distracted driving crashes. The United States (U.S.) federal and state governments have responded to this public health problem with policies and laws; however, a more comprehensive and more effective approach is still needed. Some restrictions on the use of electronic devices while driving by federal employees and some voluntary guidelines and recommendations have been issued. Public opinion polls show support for addressing the issue of distracted driving with state laws. The majority of states have laws banning text messaging while driving and prohibiting the use of an electronic device by teenage or novice drivers. Some states prohibit all drivers from using a hand-held cellphone. Currently no state has a total ban on the use of personal electronic devices while driving. Successful past traffic safety campaigns changing driver behavior have demonstrated the necessity to adopt a “three Es” approach of Enactment of a law, Education of the public about the law, and rigorous Enforcement of the law. Experience reveals that this approach, along with future federal regulation of in-vehicle electronic devices and the employment of technology to limit the use of electronic devices while driving, is needed to alter personal behavior in order to reduce distractions and keep drivers focused on the driving task. PMID:24776229

  20. Using cost and health impacts to prioritize the targeted testing of tuberculosis in the United States.

    PubMed

    Miller, Thaddeus L; Hilsenrath, Peter; Lykens, Kristine; McNabb, Scott J N; Moonan, Patrick K; Weis, Stephen E

    2006-04-01

    Evaluation improves efficiency and effectiveness. Current U.S. tuberculosis (TB) control policies emphasize the treatment of latent TB infection (LTBI). However, this policy, if not targeted, may be inefficient. We determined the efficiency of a state-law mandated TB screening program and a non state-law mandated one in terms of cost, morbidity, treatment, and disease averted. We evaluated two publicly funded metropolitan TB prevention and control programs through retrospective analyses and modeling. Main outcomes measured were TB incidence and prevalence, TB cases averted, and cost. A non state-law mandated TB program for homeless persons in Tarrant County screened 4.5 persons to identify one with LTBI and 82 persons to identify one with TB. A state-law mandated TB program for jail inmates screened 109 persons to identify one with LTBI and 3274 persons to identify one with TB. The number of patients with LTBI treated to prevent one TB case was 12.1 and 15.3 for the homeless and jail inmate TB programs, respectively. Treatment of LTBI by the homeless and jail inmate TB screening programs will avert 11.9 and 7.9 TB cases at a cost of 14,350 US dollars and 34,761 US dollars per TB case, respectively. Mandated TB screening programs should be risk-based, not population-based. Non mandated targeted testing for TB in congregate settings for the homeless was more efficient than state-law mandated targeted testing for TB among jailed inmates.

  1. An Economic Approach to Setting Contribution Limits in Qualified State-Sponsored Tuition Savings Plans.

    ERIC Educational Resources Information Center

    Ma, Jennifer; Warshawsky, Mark J.; Ameriks, John; Blohm, Julia A.

    This study used an expected utility framework with a mean-lower partial moment specification for investor utility to determine the asset allocation and the allowable contribution limits for qualified state-sponsored tuition savings plans. Given the assumptions about state policymakers' perceptions of investor utility, the study determined the…

  2. Current Law Limits the State Department’s Authority to Manage Certain Overseas Properties Cost Effectively

    DTIC Science & Technology

    2002-07-11

    GAO-02-790R Management of Overseas Property United States General Accounting Office Washington, DC 20548 July 11, 2002 The Honorable Christopher...Representatives Subject: Current Law Limits the State Department’s Authority to Manage Certain Overseas Properties Cost Effectively Dear Mr. Chairman: The...limits the Department of State’s authority to implement cost -effective decisions about sales of unneeded overseas property and the use of sales proceeds

  3. Successes and limitations of targeted therapies in renal cell carcinoma.

    PubMed

    Pracht, Marc; Berthold, Dominik

    2014-01-01

    Until recently, the standard treatment for metastatic renal cell carcinoma (RCC) was nonspecific immunotherapy based on interleukin-2 or interferon-α. This was associated with a modest survival benefit and with significant clinical toxicities. The understanding of numerous molecular pathways in RCC, including HIF, VEGF, mTOR, and the consecutive use of targeted therapies since the beginning of 2005 have significantly improved outcomes for patients with metastatic RCC with an overall survival greater than 2 years. At present, at least 7 targeted agents are approved for first and consecutive lines of treatment of clear cell metastatic RCC. Long-term benefit and extended survival may be achieved through the optimal use of targeted therapies: optimal dosing, adverse event management and treatment duration and compliance. Advances in the finding of prognostic factors highlight the potential for personalizing treatment for patients with metastatic RCC. Data regarding the best sequencing of targeted therapies, predictive biomarkers, best timing of surgery, patient risk profiles, understanding of resistance mechanisms and safety of targeted therapies are growing and will provide a further step ahead in the management of advanced RCC. In parallel, a new class of therapeutics is emerging in RCC: immunotherapy; in particular check-point blockade antibodies are showing very promising results. © 2014 S. Karger AG, Basel.

  4. Thermal limits on MV x-ray production by bremsstrahlung targets in the context of novel linear accelerators.

    PubMed

    Wang, Jinghui; Trovati, Stefania; Borchard, Philipp M; Loo, Billy W; Maxim, Peter G; Fahrig, Rebecca

    2017-12-01

    To study the impact of target geometrical and linac operational parameters, such as target material and thickness, electron beam size, repetition rate, and mean current on the ability of the radiotherapy treatment head to deliver high-dose-rate x-ray irradiation in the context of novel linear accelerators capable of higher repetition rates/duty cycle than conventional clinical linacs. The depth dose in a water phantom without a flattening filter and heat deposition in an x-ray target by 10 MeV pulsed electron beams were calculated using the Monte-Carlo code MCNPX, and the transient temperature behavior of the target was simulated by ANSYS. Several parameters that affect both the dose distribution and temperature behavior were investigated. The target was tungsten with a thickness ranging from 0 to 3 mm and a copper heat remover layer. An electron beam with full width at half maximum (FWHM) between 0 and3 mm and mean current of 0.05-2 mA was used as the primary beam at repetition rates of 100, 200, 400, and 800 Hz. For a 10 MeV electron beam with FWHM of 1 mm, pulse length of 5 μs, by using a thin tungsten target with thickness of 0.2 mm instead of 1 mm, and by employing a high repetition rate of 800 Hz instead of 100 Hz, the maximum dose rate delivered can increase two times from 0.57 to 1.16 Gy/s. In this simple model, the limiting factor on dose rate is the copper heat remover's softening temperature, which was considered to be 500°C in our study. A high dose rate can be obtained by employing thin targets together with high repetition rate electron beams enabled by novel linac designs, whereas the benefit of thin targets is marginal at conventional repetition rates. Next generation linacs used to increase dose rate need different target designs compared to conventional linacs. © 2017 American Association of Physicists in Medicine.

  5. Investigation of limit state criteria for amorphous metals

    NASA Astrophysics Data System (ADS)

    Comanici, A. M.; Sandovici, A.; Barsanescu, P. D.

    2016-08-01

    The name of amorphous metals is assigned to metals that have a non-crystalline structure, but they are also very similar to glass if we look into their properties. A very distinguished feature is the fact that amorphous metals, also known as metallic glasses, show a good electrical conductivity. The extension of the limit state criteria for different materials makes this type of alloy a choice to validate the new criterions. Using a new criterion developed for biaxial and triaxial state of stress, the results are investigated in order to determine the applicability of the mathematical model for these amorphous metals. Especially for brittle materials, it is extremely important to find suitable fracture criterion. Mohr-Coulomb criterion, which is permitting a linear failure envelope, is often used for very brittle materials. But for metallic glasses this criterion is not consistent with the experimental determinations. For metallic glasses, and other high-strength materials, Rui Tao Qu and Zhe Feng Zhang proposed a failure envelope modeling with an ellipse in σ-τ coordinates. In this paper this model is being developed for principal stresses space. It is also proposed a method for transforming σ-τ coordinates in principal stresses coordinates and the theoretical results are consistent with the experimental ones.

  6. A method for simultaneously delineating multiple targets in 3D-FISH using limited channels, lasers, and fluorochromes.

    PubMed

    Zhao, F Y; Yang, X; Chen, D Y; Ma, W Y; Zheng, J G; Zhang, X M

    2014-01-01

    Many studies have suggested a link between the spatial organization of genomes and fundamental biological processes such as genome reprogramming, gene expression, and differentiation. Multicolor fluorescence in situ hybridization on three-dimensionally preserved nuclei (3D-FISH), in combination with confocal microscopy, has become an effective technique for analyzing 3D genome structure and spatial patterns of defined nucleus targets including entire chromosome territories and single gene loci. This technique usually requires the simultaneous visualization of numerous targets labeled with different colored fluorochromes. Thus, the number of channels and lasers must be sufficient for the commonly used labeling scheme of 3D-FISH, "one probe-one target". However, these channels and lasers are usually restricted by a given microscope system. This paper presents a method for simultaneously delineating multiple targets in 3D-FISH using limited channels, lasers, and fluorochromes. In contrast to other labeling schemes, this method is convenient and simple for multicolor 3D-FISH studies, which may result in widespread adoption of the technique. Lastly, as an application of the method, the nucleus locations of chromosome territory 18/21 and centromere 18/21/13 in normal human lymphocytes were analyzed, which might present evidence of a radial higher order chromatin arrangement.

  7. Classification tree analyses reveal limited potential for early targeted prevention against childhood overweight.

    PubMed

    Beyerlein, Andreas; Kusian, Dennis; Ziegler, Anette-Gabriele; Schaffrath-Rosario, Angelika; von Kries, Rüdiger

    2014-02-01

    Whether specific combinations of risk factors in very early life might allow identification of high-risk target groups for overweight prevention programs was examined. Data of n = 8981 children from the German KiGGS study were analyzed. Using a classification tree approach, predictive risk factor combinations were assessed for overweight in 3-6, 7-10, and 11-17-year-old children. In preschool children, the subgroup with the highest overweight risk were migrant children with at least one obese parent, with a prevalence of 36.6 (95% confidence interval or CI: 22.9, 50.4)%, compared to an overall prevalence of 10.0 (8.9, 11.2)%. The prevalence of overweight increased from 18.3 (16.8, 19.8)% to 57.9 (46.6, 69.3)% in 7-10-year-old children, if at least one parent was obese and the child had been born large-for-gestational-age. In 11-17-year-olds, the overweight risk increased from 20.1 (18.9, 21.3)% to 63.0 (46.4, 79.7)% in the highest risk group. However, high prevalence ratios were found only in small subgroups, containing <10% of all overweight cases in the respective age group. Our results indicate only a limited potential for early targeted preventions against overweight in children and adolescents. Copyright © 2013 The Obesity Society.

  8. 27 CFR 70.226 - Suspension of running of period of limitation; taxpayer outside of United States.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2011-04-01 2011-04-01 false Suspension of running of... Limitations § 70.226 Suspension of running of period of limitation; taxpayer outside of United States. The running of the period of limitations on collection after assessment prescribed in 26 U.S.C. 6502 (relating...

  9. 27 CFR 70.226 - Suspension of running of period of limitation; taxpayer outside of United States.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 27 Alcohol, Tobacco Products and Firearms 2 2010-04-01 2010-04-01 false Suspension of running of... Limitations § 70.226 Suspension of running of period of limitation; taxpayer outside of United States. The running of the period of limitations on collection after assessment prescribed in 26 U.S.C. 6502 (relating...

  10. Limitations to the study of man in the United States space program

    NASA Technical Reports Server (NTRS)

    Bishop, Phillip A.; Greenisen, Mike

    1992-01-01

    Research on humans conducted during space flight is fraught both with great opportunities and great obstacles. The purpose of this paper is to review some of the limitations to United States research in space in the hope that an informed scientific community may lead to more rapid and efficient solution of these problems. Limitations arise because opportunities to study the same astronauts in well-controlled situations on repeated space flights are practically non-existent. Human research opportunities are further limited by the necessity of avoiding simultaneous mutually-interfereing experiments. Environmental factors including diet and other physiological perturbations concomitant with space flight also complicates research design and interpretation. Technical limitations to research methods and opportunities further restrict the development of the knowledge base. Finally, earth analogues of space travel all suffer from inadequacies. Though all of these obstacles will eventually be overcome; creativity, diligence, and persistence are required to further our knowledge of humans in space.

  11. 40 CFR 122.44 - Establishing limitations, standards, and other permit conditions (applicable to State NPDES...

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... CWA; (6) Ensure consistency with the requirements of a Water Quality Management plan approved by EPA..., or controls a pollutant or practice not limited in the permit. (d) Water quality standards and State... quality standards established under section 303 of the CWA, including State narrative criteria for water...

  12. What does the 2°C target imply for a global climate agreement in 2020? The limits study on Durban Platform scenarios

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

    KRIEGLER, ELMAR; TAVONI, MASSIMO; ABOUMAHBOUB, TINO

    This paper provides a novel and comprehensive model-based assessment of possible outcomes of the Durban Platform negotiations with a focus on emissions reduction requirements, the consistency with the 2°C target and global economic impacts. The Durban Platform scenarios investigated in the LIMITS study — all assuming the implementation of comprehensive global emission reductions after 2020, but assuming different 2020 emission reduction levels as well as different long-term concentration targets — exhibit a probability of exceeding the 2°C limit of 22–41% when reaching 450 (450–480) ppm CO 2e, and 35–59% when reaching 500 (480–520) ppm CO 2e in 2100. Forcing andmore » temperature show a peak and decline pattern for both targets. Consistency of the resulting temperature trajectory with the 2°C target is a societal choice, and may be based on the maximum exceedance probability at the time of the peak and the long run exceedance probability, e.g., in the year 2100. The challenges of implementing a long-term target after a period of fragmented near-term climate policy can be significant as reflected in steep reductions of emissions intensity and transitional and long-term economic impacts. In particular, the challenges of adopting the target are significantly higher in 2030 than in 2020, both in terms of required emissions intensity decline rates and economic impacts. Finally, we conclude that an agreement on comprehensive emissions reductions to be implemented from 2020 onwards has particular significance for meeting long-term climate policy objectives.« less

  13. 40 CFR 1400.11 - Limitation on dissemination to State and local government officials.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 32 2010-07-01 2010-07-01 false Limitation on dissemination to State and local government officials. 1400.11 Section 1400.11 Protection of Environment ENVIRONMENTAL PROTECTION AGENCY AND DEPARTMENT OF JUSTICE ACCIDENTAL RELEASE PREVENTION REQUIREMENTS; RISK MANAGEMENT...

  14. Influence of polarization characteristic of targets on synthetic aperture imaging ladar

    NASA Astrophysics Data System (ADS)

    Xu, Qian; Sun, Jianfeng; Lu, Zhiyong; Wang, Lijuan; Hou, Peipei; Lu, Wei; Liu, Liren

    2017-09-01

    Synthetic aperture imaging ladar (SAIL) is one of the most possible optical active imaging methods to break the diffraction limit and achieve super-resolution in a long distance. Nevertheless, two-dimensional reconstructed images of the natural targets have not been achieved. Polarization state change of the backscattered light, which is always determined by the interaction of the light and the materials on the target plane, will affect the imaging of SAIL. The Mueller matrices can describe the complex polarization features of the target reflection and treat this interaction. In this paper, a measurement of the Mueller matrices for different target materials will be designed, and the influences of polarization characteristic of targets on resolution element imaging in side-looking and down-looking SAILs will be theoretically analyzed.

  15. 40 CFR 1400.11 - Limitation on dissemination to State and local government officials.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... PROGRAMS UNDER THE CLEAN AIR ACT SECTION 112(r)(7); DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION Other Provisions § 1400.11 Limitation on... prohibited from disseminating OCA information to State and local government officials. Violation of this...

  16. 40 CFR 1400.11 - Limitation on dissemination to State and local government officials.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... PROGRAMS UNDER THE CLEAN AIR ACT SECTION 112(r)(7); DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION Other Provisions § 1400.11 Limitation on... prohibited from disseminating OCA information to State and local government officials. Violation of this...

  17. 40 CFR 1400.11 - Limitation on dissemination to State and local government officials.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... PROGRAMS UNDER THE CLEAN AIR ACT SECTION 112(r)(7); DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION Other Provisions § 1400.11 Limitation on... prohibited from disseminating OCA information to State and local government officials. Violation of this...

  18. 40 CFR 1400.11 - Limitation on dissemination to State and local government officials.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... PROGRAMS UNDER THE CLEAN AIR ACT SECTION 112(r)(7); DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION DISTRIBUTION OF OFF-SITE CONSEQUENCE ANALYSIS INFORMATION Other Provisions § 1400.11 Limitation on... prohibited from disseminating OCA information to State and local government officials. Violation of this...

  19. Magneto-conductance fingerprints of purely quantum states in the open quantum dot limit

    NASA Astrophysics Data System (ADS)

    Mendoza, Michel; Ujevic, Sebastian

    2012-06-01

    We present quantum magneto-conductance simulations, at the quantum low energy condition, to study the open quantum dot limit. The longitudinal conductance G(E,B) of spinless and non-interacting electrons is mapped as a function of the magnetic field B and the energy E of the electrons. The quantum dot linked to the semi-infinite leads is tuned by quantum point contacts of variable width w. We analyze the transition from a quantum wire to an open quantum dot and then to an effective closed system. The transition, as a function of w, occurs in the following sequence: evolution of quasi-Landau levels to Fano resonances and quasi-bound states between the quasi-Landau levels, followed by the formation of crossings that evolve to anti-crossings inside the quasi-Landau level region. After that, Fano resonances are created between the quasi-Landau states with the final generation of resonant tunneling peaks. By comparing the G(E,B) maps, we identify the closed and open-like limits of the system as a function of the applied magnetic field. These results were used to build quantum openness diagrams G(w,B). Also, these maps allow us to determine the w-limit value from which we can qualitatively relate the closed system properties to the open one. The above analysis can be used to identify single spinless particle effects in experimental measurements of the open quantum dot limit.

  20. Mapping the Coastline Limits of the Mexican State Sinaloa Using GPS

    NASA Astrophysics Data System (ADS)

    Vazquez, G. E.

    2007-12-01

    This research work presents the delimitation of the coastline limits of Sinaloa (one of the richest states of northwestern Mexico). In order to achieve this big task, it was required to use GPS (Global Positioning System) together with leveling spirit measurements. Based on the appropriate selection of the cited measurement techniques, the objective was to map the Sinaloa's state coastline to have the cartography of approximate 1600 km of littoral. The GPS measurements were performed and referred with respect to a GPS network located across the state. This GPS network consists of at least one first-order-site at each of the sixteen counties that constitute the state, and three to four second-order-sites of the ten counties of the state surrounded by sea. The leveling spirit measurements were referred to local benchmarks pre-established by the Mexican agency SEMARNAT (SEcretaría Del Medio Ambiente y Recursos NATurales). Within the main specifications of the GPS measurements and equipment, we used geodetic-dual-frequency GPS receivers in kinematic mode for both base stations (first and second order sites of the GPS state network) and rover stations (points forming the state littoral) with 5-sec log-rate interval and 10 deg cut-off angle. The GPS data processing was performed using the commercial software Trimble Geomatics Office (TGO) with Double Differences (DD) in post-processing mode. To this point, the field measurements had been totally covered including the cartography (scale 1:1000) and this includes the specifications and appropriate labeling according to the Mexican norm NOM-146-SEMARNAT-2005.

  1. CDCC calculations of fusion of 6Li with targets 144Sm and 154Sm: effect of resonance states

    NASA Astrophysics Data System (ADS)

    Gómez Camacho, A.; Lubian, J.; Zhang, H. Q.; Zhou, Shan-Gui

    2017-12-01

    Continuum Discretized Coupled-Channel (CDCC) model calculations of total, complete and incomplete fusion cross sections for reactions of the weakly bound 6Li with 144,154Sm targets at energies around the Coulomb barrier are presented. In the cluster structure frame of 6Li→α+d, short-range absorption potentials are considered for the interactions between the ground state of the projectile 6Li and α-d fragments with the target. In order to separately calculate complete and incomplete fusion and to reduce double-counting, the corresponding absorption potentials are chosen to be of different range. Couplings to low-lying excited states 2+, 3- of 144Sm and 2+, 4+ of 154Sm are included. So, the effect on total fusion from the excited states of the target is investigated. Similarly, the effect on fusion due to couplings to resonance breakup states of 6Li, namely, l=2, J π =3+,2+,1+ is also calculated. The latter effect is determined by using two approaches, (a) by considering only resonance state couplings and (b) by omitting these states from the full discretized energy space. Among other things, it is found that both resonance and non-resonance continuum breakup couplings produce fusion suppression at all the energies considered. A. Gómez Camacho from CONACYT, México, J. Lubian from CNPq, FAPERJ, Pronex, Brazil. S.G.Z was partly supported by the NSF of China (11120101005, 11275248, 11525524, 11621131001, 11647601, 11711540016), 973 Program of China (2013CB834400) and the Key Research Program of Frontier Sciences of CAS. H.Q.Z. from NSF China (11375266)

  2. Writing Progression of Students with Limited English Proficiency on Texas State Exams

    ERIC Educational Resources Information Center

    Heckman, Jill S.

    2009-01-01

    One of the purposes of this study was to examine whether or not the present and past standardized tests in the state of Texas had any positive impact on the writing abilities of the limited English proficient (LEP) Mexican-American students. Another objective of the study was to determine if one test was more effective than another. In this case,…

  3. Translational Approaches Targeting Reconsolidation

    PubMed Central

    Kroes, Marijn C.W.; LeDoux, Joseph E.; Phelps, Elizabeth A.

    2017-01-01

    Maladaptive learned responses and memories contribute to psychiatric disorders that constitute a significant socio-economic burden. Primary treatment methods teach patients to inhibit maladaptive responses, but do not get rid of the memory itself, which explains why many patients experience a return of symptoms even after initially successful treatment. This highlights the need to discover more persistent and robust techniques to diminish maladaptive learned behaviours. One potentially promising approach is to alter the original memory, as opposed to inhibiting it, by targeting memory reconsolidation. Recent research shows that reactivating an old memory results in a period of memory flexibility and requires restorage, or reconsolidation, for the memory to persist. This reconsolidation period allows a window for modification of a specific old memory. Renewal of memory flexibility following reactivation holds great clinical potential as it enables targeting reconsolidation and changing of specific learned responses and memories that contribute to maladaptive mental states and behaviours. Here, we will review translational research on non-human animals, healthy human subjects, and clinical populations aimed at altering memories by targeting reconsolidation using biological treatments (electrical stimulation, noradrenergic antagonists) or behavioural interference (reactivation–extinction paradigm). Both approaches have been used successfully to modify aversive and appetitive memories, yet effectiveness in treating clinical populations has been limited. We will discuss that memory flexibility depends on the type of memory tested and the brain regions that underlie specific types of memory. Further, when and how we can most effectively reactivate a memory and induce flexibility is largely unclear. Finally, the development of drugs that can target reconsolidation and are safe for use in humans would optimize cross-species translations. Increasing the understanding of

  4. Synthesis and evaluation of the service limit state of engineered fills for bridge support.

    DOT National Transportation Integrated Search

    2016-02-02

    This report synthesizes the current service limit state (SLS) design and analyses of engineered fills for bridge support used as shallow foundations. The SLS for settlement and deformations of bridge supports are summarized. Extensive literature revi...

  5. 31 CFR 515.519 - Limited payments from accounts of United States citizens abroad.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Limited payments from accounts of United States citizens abroad. 515.519 Section 515.519 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY CUBAN...

  6. 31 CFR 500.519 - Limited payments from accounts of United States citizens abroad.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 31 Money and Finance: Treasury 3 2010-07-01 2010-07-01 false Limited payments from accounts of United States citizens abroad. 500.519 Section 500.519 Money and Finance: Treasury Regulations Relating to Money and Finance (Continued) OFFICE OF FOREIGN ASSETS CONTROL, DEPARTMENT OF THE TREASURY FOREIGN...

  7. Fiscal Shenanigans, Targeted Federal Health Care Funds, and Patient Mortality

    PubMed Central

    Baicker, Katherine; Staiger, Douglas

    2007-01-01

    We explore the effectiveness of matching grants when lower levels of government can expropriate some of the funds for other uses. Using data on the Medicaid Disproportionate Share program, we identify states that were most able to expropriate funds. Payments to public hospitals in these states were systematically diverted and had no significant impact on patient mortality. Payments that were not expropriated were associated with significant declines in patient mortality. Overall, subsidies were an effective mechanism for improving outcomes for the poor, but the impact was limited by the ability of state and local governments to divert the targeted funds. PMID:18084627

  8. The relationship of mental illness to targeted contact behavior toward state government agencies and officials.

    PubMed

    Scalora, Mario J; Baumgartner, Jerome V; Plank, Gary L

    2003-01-01

    Research in the burgeoning field of threat assessment has illuminated the importance of mental illness factors when considering risk of targeted violence-particularly related to government agencies and officials. The authors analyzed 127 cases investigated by a state law enforcement agency regarding threatening or other contacts toward public officials or state agency employees prompting security intervention. Univariate and discriminant analysis indicated that mentally ill subjects were significantly more likely to engage in more contacts as well as to make specific demands during such contacts. Mentally ill subjects were also more likely to articulate help-seeking concerns and employ religious themes, as opposed to using insulting, degrading, or ominous language toward the target or issuing complaints regarding policy issues. Contrary to other research, the mentally ill subjects within this sample were not significantly more likely to engage in approach behavior, a threshold for higher risk of violence. Implications for threat assessment activity are discussed. Copyright 2003 John Wiley & Sons, Ltd.

  9. 78 FR 51736 - Notice of FY 2013 Refugee Targeted Assistance Formula Awards to States and Wilson/Fish...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-08-21

    ...The Office of Refugee Resettlement (ORR), Administration for Children and Families (ACF), announces the allocation of Refugee Targeted Assistance formula awards to States and Wilson/Fish Alternative Project grantees.

  10. Liberty and the Limits to the Extraterrestrial State

    NASA Astrophysics Data System (ADS)

    Cockell, C. S.

    The physical conditions that inhere in extraterrestrial environments have a tendency to drive society toward collectivist mechanisms of political and economic order to successfully cope with, and prevent possible disaster caused by, the lethal external conditions. Liberty will therefore be eroded by deliberate human action, through extraterrestrial authorities, and through a natural restriction in concepts of liberty that will attend the development and behaviour of people in confined environments. The emergence of extraterrestrial governance that nurtures liberty in outer space will require the formation of many institutions that encourage competition and reduce political and economic monopolies - with the legal system to sustain them. This problem is most clearly manifest in oxygen production. These considerations allow the purpose and limits of the extraterrestrial state and precursor forms of governance to be circumscribed. Far from being a purely speculative enquiry, this discussion allows requirements in physical architecture and social organisation to be identified that can be considered from the earliest stages of space exploration and settlement.

  11. Educational Targeting in the Fight against Poverty: Limits, Omissions and Opportunities

    ERIC Educational Resources Information Center

    Tarabini, Aina

    2008-01-01

    Educational targeting has become one of the hegemonic mechanisms in the fight against poverty. Both international organisms and developing countries support targeting as one of the best strategies in order to simultaneously guarantee poverty reduction and economic growth, and consequently to tackle the challenges generated by globalisation. The…

  12. Economic Burden of Chronic Lymphocytic Leukemia in the Era of Oral Targeted Therapies in the United States

    PubMed Central

    Chen, Qiushi; Jain, Nitin; Ayer, Turgay; Wierda, William G.; Flowers, Christopher R.; O’Brien, Susan M.; Keating, Michael J.; Kantarjian, Hagop M.

    2017-01-01

    Purpose Oral targeted therapies represent a significant advance for the treatment of patients with chronic lymphocytic leukemia (CLL); however, their high cost has raised concerns about affordability and the economic impact on society. Our objective was to project the future prevalence and cost burden of CLL in the era of oral targeted therapies in the United States. Methods We developed a simulation model that evaluated the evolving management of CLL from 2011 to 2025: chemoimmunotherapy (CIT) as the standard of care before 2014, oral targeted therapies for patients with del(17p) and relapsed CLL from 2014, and for first-line treatment from 2016 onward. A comparator scenario also was simulated where CIT remained the standard of care throughout. Disease progression and survival parameters for each therapy were based on published clinical trials. Results The number of people living with CLL in the United States is projected to increase from 128,000 in 2011 to 199,000 by 2025 (55% increase) due to improved survival; meanwhile, the annual cost of CLL management will increase from $0.74 billion to $5.13 billion (590% increase). The per-patient lifetime cost of CLL treatment will increase from $147,000 to $604,000 (310% increase) as oral targeted therapies become the first-line treatment. For patients enrolled in Medicare, the corresponding total out-of-pocket cost will increase from $9,200 to $57,000 (520% increase). Compared with the CIT scenario, oral targeted therapies resulted in an incremental cost-effectiveness ratio of $189,000 per quality-adjusted life-year. Conclusion The increased benefit and cost of oral targeted therapies is projected to enhance CLL survivorship but can impose a substantial financial burden on both patients and payers. More sustainable pricing strategies for targeted therapies are needed to avoid financial toxicity to patients. PMID:27870563

  13. Can quantum transition state theory be defined as an exact t = 0+ limit?

    NASA Astrophysics Data System (ADS)

    Jang, Seogjoo; Voth, Gregory A.

    2016-02-01

    The definition of the classical transition state theory (TST) as a t → 0+ limit of the flux-side time correlation function relies on the assumption that simultaneous measurement of population and flux is a well defined physical process. However, the noncommutativity of the two measurements in quantum mechanics makes the extension of such a concept to the quantum regime impossible. For this reason, quantum TST (QTST) has been generally accepted as any kind of quantum rate theory reproducing the TST in the classical limit, and there has been a broad consensus that no unique QTST retaining all the properties of TST can be defined. Contrary to this widely held view, Hele and Althorpe (HA) [J. Chem. Phys. 138, 084108 (2013)] recently suggested that a true QTST can be defined as the exact t → 0+ limit of a certain kind of quantum flux-side time correlation function and that it is equivalent to the ring polymer molecular dynamics (RPMD) TST. This work seeks to question and clarify certain assumptions underlying these suggestions and their implications. First, the time correlation function used by HA as a starting expression is not related to the kinetic rate constant by virtue of linear response theory, which is the first important step in relating a t = 0+ limit to a physically measurable rate. Second, a theoretical analysis calls into question a key step in HA's proof which appears not to rely on an exact quantum mechanical identity. The correction of this makes the true t = 0+ limit of HA's QTST different from the RPMD-TST rate expression, but rather equal to the well-known path integral quantum transition state theory rate expression for the case of centroid dividing surface. An alternative quantum rate expression is then formulated starting from the linear response theory and by applying a recently developed formalism of real time dynamics of imaginary time path integrals [S. Jang, A. V. Sinitskiy, and G. A. Voth, J. Chem. Phys. 140, 154103 (2014)]. It is shown

  14. State policies targeting junk food in schools: racial/ethnic differences in the effect of policy change on soda consumption.

    PubMed

    Taber, Daniel R; Stevens, June; Evenson, Kelly R; Ward, Dianne S; Poole, Charles; Maciejewski, Matthew L; Murray, David M; Brownson, Ross C

    2011-09-01

    We estimated the association between state policy changes and adolescent soda consumption and body mass index (BMI) percentile, overall and by race/ethnicity. We obtained data on whether states required or recommended that schools prohibit junk food in vending machines, snack bars, concession stands, and parties from the 2000 and 2006 School Health Policies and Programs Study. We used linear mixed models to estimate the association between 2000-2006 policy changes and 2007 soda consumption and BMI percentile, as reported by 90 730 students in 33 states and the District of Columbia in the Youth Risk Behavior Survey, and to test for racial/ethnic differences in the associations. Policy changes targeting concession stands were associated with 0.09 fewer servings of soda per day among students (95% confidence interval [CI] = -0.17, -0.01); the association was more pronounced among non-Hispanic Blacks (0.19 fewer servings per day). Policy changes targeting parties were associated with 0.07 fewer servings per day (95% CI = -0.13, 0.00). Policy changes were not associated with BMI percentile in any group. State policies targeting junk food in schools may reduce racial/ethnic disparities in adolescent soda consumption, but their impact appears to be too weak to reduce adolescent BMI percentile.

  15. Ubiquitin ligase Nedd4L targets activated Smad2/3 to limit TGF-beta signaling.

    PubMed

    Gao, Sheng; Alarcón, Claudio; Sapkota, Gopal; Rahman, Sadia; Chen, Pan-Yu; Goerner, Nina; Macias, Maria J; Erdjument-Bromage, Hediye; Tempst, Paul; Massagué, Joan

    2009-11-13

    TGF-beta induces phosphorylation of the transcription factors Smad2 and Smad3 at the C terminus as well as at an interdomain linker region. TGF-beta-induced linker phosphorylation marks the activated Smad proteins for proteasome-mediated destruction. Here, we identify Nedd4L as the ubiquitin ligase responsible for this step. Through its WW domain, Nedd4L specifically recognizes a TGF-beta-induced phosphoThr-ProTyr motif in the linker region, resulting in Smad2/3 polyubiquitination and degradation. Nedd4L is not interchangeable with Smurf1, a ubiquitin ligase that targets BMP-activated, linker-phosphorylated Smad1. Nedd4L limits the half-life of TGF-beta-activated Smads and restricts the amplitude and duration of TGF-beta gene responses, and in mouse embryonic stem cells, it limits the induction of mesoendodermal fates by Smad2/3-activating factors. Hierarchical regulation is provided by SGK1, which phosphorylates Nedd4L to prevent binding of Smad2/3. Previously identified as a regulator of renal sodium channels, Nedd4L is shown here to play a broader role as a general modulator of Smad turnover during TGF-beta signal transduction.

  16. Generalizing Evidence From Randomized Clinical Trials to Target Populations

    PubMed Central

    Cole, Stephen R.; Stuart, Elizabeth A.

    2010-01-01

    Properly planned and conducted randomized clinical trials remain susceptible to a lack of external validity. The authors illustrate a model-based method to standardize observed trial results to a specified target population using a seminal human immunodeficiency virus (HIV) treatment trial, and they provide Monte Carlo simulation evidence supporting the method. The example trial enrolled 1,156 HIV-infected adult men and women in the United States in 1996, randomly assigned 577 to a highly active antiretroviral therapy and 579 to a largely ineffective combination therapy, and followed participants for 52 weeks. The target population was US people infected with HIV in 2006, as estimated by the Centers for Disease Control and Prevention. Results from the trial apply, albeit muted by 12%, to the target population, under the assumption that the authors have measured and correctly modeled the determinants of selection that reflect heterogeneity in the treatment effect. In simulations with a heterogeneous treatment effect, a conventional intent-to-treat estimate was biased with poor confidence limit coverage, but the proposed estimate was largely unbiased with appropriate confidence limit coverage. The proposed method standardizes observed trial results to a specified target population and thereby provides information regarding the generalizability of trial results. PMID:20547574

  17. Analytical steady-state solutions for water-limited cropping systems using saline irrigation water

    NASA Astrophysics Data System (ADS)

    Skaggs, T. H.; Anderson, R. G.; Corwin, D. L.; Suarez, D. L.

    2014-12-01

    Due to the diminishing availability of good quality water for irrigation, it is increasingly important that irrigation and salinity management tools be able to target submaximal crop yields and support the use of marginal quality waters. In this work, we present a steady-state irrigated systems modeling framework that accounts for reduced plant water uptake due to root zone salinity. Two explicit, closed-form analytical solutions for the root zone solute concentration profile are obtained, corresponding to two alternative functional forms of the uptake reduction function. The solutions express a general relationship between irrigation water salinity, irrigation rate, crop salt tolerance, crop transpiration, and (using standard approximations) crop yield. Example applications are illustrated, including the calculation of irrigation requirements for obtaining targeted submaximal yields, and the generation of crop-water production functions for varying irrigation waters, irrigation rates, and crops. Model predictions are shown to be mostly consistent with existing models and available experimental data. Yet the new solutions possess advantages over available alternatives, including: (i) the solutions were derived from a complete physical-mathematical description of the system, rather than based on an ad hoc formulation; (ii) the analytical solutions are explicit and can be evaluated without iterative techniques; (iii) the solutions permit consideration of two common functional forms of salinity induced reductions in crop water uptake, rather than being tied to one particular representation; and (iv) the utilized modeling framework is compatible with leading transient-state numerical models.

  18. Employment and activity limitations among adults with chronic obstructive pulmonary disease--United States, 2013.

    PubMed

    Wheaton, Anne G; Cunningham, Timothy J; Ford, Earl S; Croft, Janet B

    2015-03-27

    Chronic obstructive pulmonary disease (COPD) is a group of progressive respiratory conditions, including emphysema and chronic bronchitis, characterized by airflow obstruction and symptoms such as shortness of breath, chronic cough, and sputum production. COPD is an important contributor to mortality and disability in the United States. Healthy People 2020 has several COPD-related objectives,* including to reduce activity limitations among adults with COPD. To assess the state-level prevalence of COPD and the association of COPD with various activity limitations among U.S. adults, CDC analyzed data from the 2013 Behavioral Risk Factor Surveillance System (BRFSS). Among U.S. adults in all 50 states, the District of Columbia (DC), and two U.S. territories, 6.4% (an estimated 15.7 million adults) had been told by a physician or other health professional that they have COPD. Adults who reported having COPD were more likely to report being unable to work (24.3% versus 5.3%), having an activity limitation caused by health problems (49.6% versus 16.9%), having difficulty walking or climbing stairs (38.4% versus 11.3%), or using special equipment to manage health problems (22.1% versus 6.7%), compared with adults without COPD. Smokers who have been diagnosed with COPD are encouraged to quit smoking, which can slow the progression of the disease and reduce mobility impairment. In addition, COPD patients should consider participation in a pulmonary rehabilitation program that combines patient education and exercise training to address barriers to physical activity, such as respiratory symptoms and muscle wasting.

  19. Monitoring the World Health Organization Global Target 2025 for Exclusive Breastfeeding: Experience From the United States.

    PubMed

    Gupta, Priya M; Perrine, Cria G; Chen, Jian; Elam-Evans, Laurie D; Flores-Ayala, Rafael

    2017-08-01

    Exclusive breastfeeding under 6 months, calculated from a single 24-hour recall among mothers of children 0 to 5 months of age, is a World Health Organization (WHO) indicator used to monitor progress on the 2025 global breastfeeding target. Many upper-middle-income and high-income countries, including the United States, do not have estimates for this indicator. Research aim: To describe the prevalence of exclusive breastfeeding under 6 months in the United States. We used a single 24-hour dietary recall from the National Health and Nutrition Examination Survey 2009-2012 to calculate the prevalence of exclusive breastfeeding under 6 months. We discuss our results in the context of routine breastfeeding surveillance, which is reported from a national survey with different methodology. Among children younger than 6 months, 24.4%, 95% confidence interval [17.6, 31.1], were exclusively breastfed the previous day. To our knowledge, this is the first estimate of the WHO indicator of exclusive breastfeeding under 6 months for the United States. This study supports the global surveillance and data strategy for reporting to the WHO on the 2025 target for exclusive breastfeeding.

  20. State Clean Energy Policies Analysis (SCEPA): State Tax Incentives

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

    Lantz, E.; Doris, E.

    As a policy tool, state tax incentives can be structured to help states meet clean energy goals. Policymakers often use state tax incentives in concert with state and federal policies to support renewable energy deployment or reduce market barriers. This analysis used case studies of four states to assess the contributions of state tax incentives to the development of renewable energy markets. State tax incentives that are appropriately paired with complementary state and federal policies generally provide viable mechanisms to support renewable energy deployment. However, challenges to successful implementation of state tax incentives include serving project owners with limited statemore » tax liability, assessing appropriate incentive levels, and differentiating levels of incentives for technologies with different costs. Additionally, state tax incentives may result in moderately higher federal tax burdens. These challenges notwithstanding, state tax incentives that consider certain policy design characteristics can support renewable energy markets and state clean energy goals.The scale of their impact though is directly related to the degree to which they support the renewable energy markets for targeted sectors and technologies. This report highlights important policy design considerations for policymakers using state tax incentives to meet clean energy goals.« less

  1. Rule of five in 2015 and beyond: Target and ligand structural limitations, ligand chemistry structure and drug discovery project decisions.

    PubMed

    Lipinski, Christopher A

    2016-06-01

    The rule of five (Ro5), based on physicochemical profiles of phase II drugs, is consistent with structural limitations in protein targets and the drug target ligands. Three of four parameters in Ro5 are fundamental to the structure of both target and drug binding sites. The chemical structure of the drug ligand depends on the ligand chemistry and design philosophy. Two extremes of chemical structure and design philosophy exist; ligands constructed in the medicinal chemistry synthesis laboratory without input from natural selection and natural product (NP) metabolites biosynthesized based on evolutionary selection. Exceptions to Ro5 are found mostly among NPs. Chemistry chameleon-like behavior of some NPs due to intra-molecular hydrogen bonding as exemplified by cyclosporine A is a strong contributor to NP Ro5 outliers. The fragment derived, drug Navitoclax is an example of the extensive expertise, resources, time and key decisions required for the rare discovery of a non-NP Ro5 outlier. Copyright © 2016 Elsevier B.V. All rights reserved.

  2. [Target volume margins for lung cancer: internal target volume/clinical target volume].

    PubMed

    Jouin, A; Pourel, N

    2013-10-01

    The aim of this study was to carry out a review of margins that should be used for the delineation of target volumes in lung cancer, with a focus on margins from gross tumour volume (GTV) to clinical target volume (CTV) and internal target volume (ITV) delineation. Our review was based on a PubMed literature search with, as a cornerstone, the 2010 European Organisation for Research and Treatment of Cancer (EORTC) recommandations by De Ruysscher et al. The keywords used for the search were: radiotherapy, lung cancer, clinical target volume, internal target volume. The relevant information was categorized under the following headings: gross tumour volume definition (GTV), CTV-GTV margin (first tumoural CTV then nodal CTV definition), in field versus elective nodal irradiation, metabolic imaging role through the input of the PET scanner for tumour target volume and limitations of PET-CT imaging for nodal target volume definition, postoperative radiotherapy target volume definition, delineation of target volumes after induction chemotherapy; then the internal target volume is specified as well as tumoural mobility for lung cancer and respiratory gating techniques. Finally, a chapter is dedicated to planning target volume definition and another to small cell lung cancer. For each heading, the most relevant and recent clinical trials and publications are mentioned. Copyright © 2013. Published by Elsevier SAS.

  3. State Policies Targeting Junk Food in Schools: Racial/Ethnic Differences in the Effect of Policy Change on Soda Consumption

    PubMed Central

    Stevens, June; Evenson, Kelly R.; Ward, Dianne S.; Poole, Charles; Maciejewski, Matthew L.; Murray, David M.; Brownson, Ross C.

    2011-01-01

    Objectives. We estimated the association between state policy changes and adolescent soda consumption and body mass index (BMI) percentile, overall and by race/ethnicity. Methods. We obtained data on whether states required or recommended that schools prohibit junk food in vending machines, snack bars, concession stands, and parties from the 2000 and 2006 School Health Policies and Programs Study. We used linear mixed models to estimate the association between 2000–2006 policy changes and 2007 soda consumption and BMI percentile, as reported by 90 730 students in 33 states and the District of Columbia in the Youth Risk Behavior Survey, and to test for racial/ethnic differences in the associations. Results. Policy changes targeting concession stands were associated with 0.09 fewer servings of soda per day among students (95% confidence interval [CI] = −0.17, −0.01); the association was more pronounced among non-Hispanic Blacks (0.19 fewer servings per day). Policy changes targeting parties were associated with 0.07 fewer servings per day (95% CI = −0.13, 0.00). Policy changes were not associated with BMI percentile in any group. Conclusions. State policies targeting junk food in schools may reduce racial/ethnic disparities in adolescent soda consumption, but their impact appears to be too weak to reduce adolescent BMI percentile. PMID:21778484

  4. State of the art on targeted memory reactivation: Sleep your way to enhanced cognition.

    PubMed

    Schouten, Daphne I; Pereira, Sofia I R; Tops, Mattie; Louzada, Fernando M

    2017-04-01

    Targeted memory reactivation is a fairly simple technique that has the potential to influence the course of memory formation through application of cues during sleep. Studies have shown that cueing memory during sleep can lead to either an enhanced or decreased representation of the information encoded in the targeted networks, depending on experimental variations. The effects have been associated with sleep parameters and accompanied by activation of memory related brain areas. The findings suggest a causal role of neuronal replay in memory consolidation and provide evidence for the active system consolidation hypothesis. However, the observed inconsistencies across studies suggest that further research is warranted regarding the underlying neural mechanisms and optimal conditions for the application of targeted memory reactivation. The goal of the present review is to integrate the currently available experimental data and to provide an overview of this technique's limitations and pitfalls, as well as its potential applications in everyday use and clinical treatment. Exploring the open questions herein identified should lead to insight into safer and more effective ways of adjusting memory representations to better suit individual needs. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Gaining insights into the consequences of target-mediated drug disposition of monoclonal antibodies using quasi-steady-state approximations.

    PubMed

    Grimm, Hans Peter

    2009-10-01

    Target-mediated drug disposition (TMDD) is frequently reported for therapeutic monoclonal antibodies and is linked to the high affinity and high specificity of antibody molecules for their target. Understanding TMDD of a monoclonal antibody should go beyond the empirical description of its non-linear PK since valuable insights on the antibody-target interaction itself can be gained. This makes its mechanistic understanding precious for the drug development process, in particular for the optimization of new antibody molecules, for the design and interpretation of pharmacokinetic studies, and possibly even for the evaluation of efficacy and dose selection of drug candidates. Using the observation that the molecular (microscopic) processes are usually much more rapid than the pharmacokinetic (macroscopic) processes, a series of quasi-steady-state conditions on the microscopic level is proposed to bridge the gap between simple empirical and complex mechanistic descriptions of TMDD. These considerations show the impact of parameters such as target turnover, target expression, and target accessibility on the pharmacokinetics and pharmacodynamics of monoclonal antibodies.

  6. New steady-state models for water-limited cropping systems using saline irrigation waters: Analytical solutions and applications

    USDA-ARS?s Scientific Manuscript database

    Due to the diminishing availability of good quality water for irrigation, it is increasingly important that irrigation and salinity management tools be able to target submaximal crop yields and support the use of marginal quality waters. In this work, we present a steady-state irrigated systems mod...

  7. New steady-state models for water-limited cropping systems using saline irrigation waters: Analytical solutions and applications

    USDA-ARS?s Scientific Manuscript database

    Due to the diminishing availability of good quality water for irrigation, it is increasingly important that irrigation and salinity management tools be able to target submaximal crop yields and support the use of marginal quality waters. In this work, we present a steady-state irrigated systems mode...

  8. Detection and Imaging of Moving Targets with LiMIT SAR Data

    DTIC Science & Technology

    2017-03-03

    include space time adaptive processing (STAP) or displaced phase center antenna (DPCA) [4]–[7]. Page et al. combined constant acceleration target...motion focusing with space-time adaptive processing (STAP), and included the refocusing parameters in the STAP steering vector. Due to inhomogenous...wavelength λ and slow time t, of a moving target after matched filter and passband equalization processing can be expressed as: P (t) = exp ( −j 4π λ ||~rp

  9. Discriminating quantum-optical beam-splitter channels with number-diagonal signal states: Applications to quantum reading and target detection

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

    Nair, Ranjith

    2011-09-15

    We consider the problem of distinguishing, with minimum probability of error, two optical beam-splitter channels with unequal complex-valued reflectivities using general quantum probe states entangled over M signal and M' idler mode pairs of which the signal modes are bounced off the beam splitter while the idler modes are retained losslessly. We obtain a lower bound on the output state fidelity valid for any pure input state. We define number-diagonal signal (NDS) states to be input states whose density operator in the signal modes is diagonal in the multimode number basis. For such input states, we derive series formulas formore » the optimal error probability, the output state fidelity, and the Chernoff-type upper bounds on the error probability. For the special cases of quantum reading of a classical digital memory and target detection (for which the reflectivities are real valued), we show that for a given input signal photon probability distribution, the fidelity is minimized by the NDS states with that distribution and that for a given average total signal energy N{sub s}, the fidelity is minimized by any multimode Fock state with N{sub s} total signal photons. For reading of an ideal memory, it is shown that Fock state inputs minimize the Chernoff bound. For target detection under high-loss conditions, a no-go result showing the lack of appreciable quantum advantage over coherent state transmitters is derived. A comparison of the error probability performance for quantum reading of number state and two-mode squeezed vacuum state (or EPR state) transmitters relative to coherent state transmitters is presented for various values of the reflectances. While the nonclassical states in general perform better than the coherent state, the quantitative performance gains differ depending on the values of the reflectances. The experimental outlook for realizing nonclassical gains from number state transmitters with current technology at moderate to high values of

  10. A tale of two sequences: microRNA-target chimeric reads.

    PubMed

    Broughton, James P; Pasquinelli, Amy E

    2016-04-04

    In animals, a functional interaction between a microRNA (miRNA) and its target RNA requires only partial base pairing. The limited number of base pair interactions required for miRNA targeting provides miRNAs with broad regulatory potential and also makes target prediction challenging. Computational approaches to target prediction have focused on identifying miRNA target sites based on known sequence features that are important for canonical targeting and may miss non-canonical targets. Current state-of-the-art experimental approaches, such as CLIP-seq (cross-linking immunoprecipitation with sequencing), PAR-CLIP (photoactivatable-ribonucleoside-enhanced CLIP), and iCLIP (individual-nucleotide resolution CLIP), require inference of which miRNA is bound at each site. Recently, the development of methods to ligate miRNAs to their target RNAs during the preparation of sequencing libraries has provided a new tool for the identification of miRNA target sites. The chimeric, or hybrid, miRNA-target reads that are produced by these methods unambiguously identify the miRNA bound at a specific target site. The information provided by these chimeric reads has revealed extensive non-canonical interactions between miRNAs and their target mRNAs, and identified many novel interactions between miRNAs and noncoding RNAs.

  11. U.S. School Reform Policy, State Accountability Systems and the Limited English Proficient Student.

    ERIC Educational Resources Information Center

    Reyes, Pedro; Rorrer, Andrea

    2001-01-01

    Addresses the political and policy environment that has shaped the educational agenda for rising U.S. state accountability systems, highlighting these policies' effects on the limited-English-proficient learner. The hope for language-minority students lies in pressures on school officials to narrow the white/minority achievement gap. (Contains 64…

  12. Optimal control theory with continuously distributed target states: An application to NaK

    NASA Astrophysics Data System (ADS)

    Kaiser, Andreas; May, Volkhard

    2006-01-01

    Laser pulse control of molecular dynamics is studied theoretically by using optimal control theory. The control theory is extended to target states which are distributed in time as well as in a space of parameters which are responsible for a change of individual molecular properties. This generalized treatment of a control task is first applied to wave packet formation in randomly oriented diatomic systems. Concentrating on an ensemble of NaK molecules which are not aligned the control yield decreases drastically when compared with an aligned ensemble. Second, we demonstrate for NaK the maximization of the probe pulse transient absorption in a pump-probe scheme with an optimized pump pulse. These computations suggest an overall optical control scheme, whereby a flexible technique is suggested to form particular wave packets in the excited state potential energy surface. In particular, it is shown that considerable wave packet localization at the turning points of the first-excited Σ-state potential energy surfaces of NaK may be achieved. The dependency of the control yield on the probe pulse parameters is also discussed.

  13. Term limits and the tobacco industry.

    PubMed

    Apollonio, Dorie E; Glantz, Stanton A; Bero, Lisa A

    2014-03-01

    In the 1990s several American states passed term limits on legislators with the stated intention of reducing the influence of wealthy industries on career legislators. Although term limits in the United States do not have a direct relationship to public health, the tobacco industry anticipated that term limits could have indirect effects by either limiting or expanding industry influence. We detail the strategy of the tobacco industry in the wake of term limits using internal tobacco company documents and a database of campaign contributions made to legislators in term limited states between 1988 and 2002. Despite some expectations that term limits would limit tobacco industry access to state legislators, term limits appear to have had the opposite effect. Copyright © 2013 Elsevier Ltd. All rights reserved.

  14. Targeting the IL-33/IL-13 Axis for Respiratory Viral Infections.

    PubMed

    Donovan, Chantal; Bourke, Jane E; Vlahos, Ross

    2016-04-01

    Lung diseases, such as asthma and chronic obstructive pulmonary disease (COPD), are highly prevalent worldwide. One of the major factors that limits the efficacy of current medication in these patients are viral infections, leading to exacerbations of symptoms and decreased quality of life. Current pharmacological strategies targeting virus-induced lung disease are problematic due to antiviral resistance and the requirement for strain-specific vaccination. Thus, new therapeutic strategies are urgently required. In this Opinion article, we provide state-of-the-art evidence from humans and preclinical animal models implicating the interleukin (IL)-33/IL-13 axis in virus-induced lung disease. Thus, targeting the IL-33/IL-13 axis may be a feasible way to overcome the limitations of current therapy used to treat virus-induced exacerbations of lung disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Superconducting cosmic string: Equation of state for spacelike and timelike current in the neutral limit

    NASA Astrophysics Data System (ADS)

    Peter, Patrick

    1992-02-01

    The equation of state relating the tension T and the energy per unit length U of a cosmic string is investigated in the simplest nontrivial case, namely, that of a field theory with U(1)local×U(1)global invariance, in four dimensions, which is interpretable as the zero-charge-coupling-constant limit of the more general superconducting string models that have been previously investigated. This limit has the advantage of giving vacuum vortex defects that are strictly local so that the quantities such as U and T that are relevant for the macroscopic description can be computed without ambiguity. In the case of ``electric'' states (with timelike current) for which no comparable previous calculations exist, it is shown there is a critical frequency wc beyond which the vortex becomes unstable due to ``charge'' carrier emission. In the case of ``magnetic'' states (with spacelike current), the present analysis provides more precise results than those of previous investigations, whose predictions are broadly confirmed for typical moderate models in which the tension T remains comparable to the energy density U though not for extreme models, in which serious discrepancies are revealed.

  16. Determination of the Limiting Magnitude

    NASA Technical Reports Server (NTRS)

    Kingery, Aaron; Blaauw, Rhiannon

    2017-01-01

    The limiting magnitude of an optical camera system is an important property to understand since it is used to find the completeness limit of observations. Limiting magnitude depends on the hardware and software of the system, current weather conditions, and the angular speed of the objects observed. If an object exhibits a substantial angular rate during the exposure, its light spreads out over more pixels than the stationary stars. This spreading causes the limiting magnitude to be brighter when compared to the stellar limiting magnitude. The effect, which begins to become important when the object moves a full width at half max during a single exposure or video frame. For targets with high angular speeds or camera systems with narrow field of view or long exposures, this correction can be significant, up to several magnitudes. The stars in an image are often used to measure the limiting magnitude since they are stationary, have known brightness, and are present in large numbers, making the determination of the limiting magnitude fairly simple. In order to transform stellar limiting magnitude to object limiting magnitude, a correction must be applied accounting for the angular velocity. This technique is adopted in meteor and other fast-moving object observations, as the lack of a statistically significant sample of targets makes it virtually impossible to determine the limiting magnitude before the weather conditions change. While the weather is the dominant factor in observing satellites, the limiting magnitude for meteors also changes throughout the night due to the motion of a meteor shower or sporadic source radiant across the sky. This paper presents methods for determining the limiting stellar magnitude and the conversion to the target limiting magnitude.

  17. Limitations Of The Current State Space Modelling Approach In Multistage Machining Processes Due To Operation Variations

    NASA Astrophysics Data System (ADS)

    Abellán-Nebot, J. V.; Liu, J.; Romero, F.

    2009-11-01

    The State Space modelling approach has been recently proposed as an engineering-driven technique for part quality prediction in Multistage Machining Processes (MMP). Current State Space models incorporate fixture and datum variations in the multi-stage variation propagation, without explicitly considering common operation variations such as machine-tool thermal distortions, cutting-tool wear, cutting-tool deflections, etc. This paper shows the limitations of the current State Space model through an experimental case study where the effect of the spindle thermal expansion, cutting-tool flank wear and locator errors are introduced. The paper also discusses the extension of the current State Space model to include operation variations and its potential benefits.

  18. Lower limits of spin detection efficiency for two-parameter two-qubit (TPTQ) states with non-ideal ferromagnetic detectors

    NASA Astrophysics Data System (ADS)

    Majd, Nayereh; Ghasemi, Zahra

    2016-10-01

    We have investigated a TPTQ state as an input state of a non-ideal ferromagnetic detectors. Minimal spin polarization required to demonstrate spin entanglement according to entanglement witness and CHSH inequality with respect to (w.r.t.) their two free parameters have been found, and we have numerically shown that the entanglement witness is less stringent than the direct tests of Bell's inequality in the form of CHSH in the entangled limits of its free parameters. In addition, the lower limits of spin detection efficiency fulfilling secure cryptographic key against eavesdropping have been derived. Finally, we have considered TPTQ state as an output of spin decoherence channel and the region of ballistic transmission time w.r.t. spin relaxation time and spin dephasing time has been found.

  19. Target-adaptive polarimetric synthetic aperture radar target discrimination using maximum average correlation height filters.

    PubMed

    Sadjadi, Firooz A; Mahalanobis, Abhijit

    2006-05-01

    We report the development of a technique for adaptive selection of polarization ellipse tilt and ellipticity angles such that the target separation from clutter is maximized. From the radar scattering matrix [S] and its complex components, in phase and quadrature phase, the elements of the Mueller matrix are obtained. Then, by means of polarization synthesis, the radar cross section of the radar scatters are obtained at different transmitting and receiving polarization states. By designing a maximum average correlation height filter, we derive a target versus clutter distance measure as a function of four transmit and receive polarization state angles. The results of applying this method on real synthetic aperture radar imagery indicate a set of four transmit and receive angles that lead to maximum target versus clutter discrimination. These optimum angles are different for different targets. Hence, by adaptive control of the state of polarization of polarimetric radar, one can noticeably improve the discrimination of targets from clutter.

  20. Update of the equations of the limit state of the structural material with the realization of their deformation

    NASA Astrophysics Data System (ADS)

    Zenkov, E. V.

    2018-01-01

    Two methods are given in the article by considering the type of stressed-Deformed state (SDS) based on equations limit condition and analyzing the results of laboratory tests of special specimens for mechanical testing, focus having destruction thereof in the same view of SDS as in focus possible destruction of the structural member. The considered limited use of these methods in terms of considering physically consistent strength criterion type Pisarenko-Lebedev. A revised design-experimental procedure for determining the strength of the material of the structure, combining therein the elements of these two methods, consisting in determining the strength parameters of construction material, entering criterion equation Pisarenko-Lebedev, considering the actual appearance of the region-of-interest SDS structure. The implementation of the procedure is performed on the basis of the selection of the respective experimental laboratory specimens for mechanical testing, plan SDS in working zone coinciding with a SDS: structure whose strength is evaluated. The refinement process limit state equations demonstrated in determining 50CrV4 steel strength parameters, being in a state of biaxial stretching. Design-experimentally determined by, that steel for a given voltage limit value is almost a quarter of its value is reduced compared to the conventional tensile strength. value is reduced compared to the conventional tensile strength.

  1. Attentional Control via Parallel Target-Templates in Dual-Target Search

    PubMed Central

    Barrett, Doug J. K.; Zobay, Oliver

    2014-01-01

    Simultaneous search for two targets has been shown to be slower and less accurate than independent searches for the same two targets. Recent research suggests this ‘dual-target cost’ may be attributable to a limit in the number of target-templates than can guide search at any one time. The current study investigated this possibility by comparing behavioural responses during single- and dual-target searches for targets defined by their orientation. The results revealed an increase in reaction times for dual- compared to single-target searches that was largely independent of the number of items in the display. Response accuracy also decreased on dual- compared to single-target searches: dual-target accuracy was higher than predicted by a model restricting search guidance to a single target-template and lower than predicted by a model simulating two independent single-target searches. These results are consistent with a parallel model of dual-target search in which attentional control is exerted by more than one target-template at a time. The requirement to maintain two target-templates simultaneously, however, appears to impose a reduction in the specificity of the memory representation that guides search for each target. PMID:24489793

  2. Biological and targeted therapies of systemic lupus erythematosus: evidence and the state of the art.

    PubMed

    Mok, Chi Chiu

    2017-07-01

    Systemic lupus erythematosus (SLE) is a multi-systemic disease characterized by an unpredictable disease course and periods of remission and flare, leading to organ damage and mortality. Novel biological agents are being developed (targeting the lymphocytes, accessory molecules and cytokines) that aim to enhance the therapeutic efficacy when combined with standard therapies. Areas covered: This article updates recent data on the use of biological and targeted therapies in SLE. Expert commentary: B cells remain the main target of development of novel therapeutics in SLE. Similar to the intravenous preparation, subcutaneous belimumab has been shown to be superior to placebo when added to the standard of care in SLE. However, two phase III trials of epratuzumab and blisibimod did not meet their primary endpoints. Recent data on the inhibition of type I interferons (anifrolumab) appear promising. Newer calcineurin inhibitors and combination strategies using conventional immunosuppressive agents are being tested in lupus nephritis. Finally, international groups are developing consensus definitions on disease remission and low disease activity state to explore the benefits of the treat-to-target strategy in SLE. Hopefully, the armamentarium for the treatment of SLE can be expanded in the near future, so that the longevity and quality of life of patients can be further improved.

  3. A State Space Model for Spatial Updating of Remembered Visual Targets during Eye Movements

    PubMed Central

    Mohsenzadeh, Yalda; Dash, Suryadeep; Crawford, J. Douglas

    2016-01-01

    In the oculomotor system, spatial updating is the ability to aim a saccade toward a remembered visual target position despite intervening eye movements. Although this has been the subject of extensive experimental investigation, there is still no unifying theoretical framework to explain the neural mechanism for this phenomenon, and how it influences visual signals in the brain. Here, we propose a unified state-space model (SSM) to account for the dynamics of spatial updating during two types of eye movement; saccades and smooth pursuit. Our proposed model is a non-linear SSM and implemented through a recurrent radial-basis-function neural network in a dual Extended Kalman filter (EKF) structure. The model parameters and internal states (remembered target position) are estimated sequentially using the EKF method. The proposed model replicates two fundamental experimental observations: continuous gaze-centered updating of visual memory-related activity during smooth pursuit, and predictive remapping of visual memory activity before and during saccades. Moreover, our model makes the new prediction that, when uncertainty of input signals is incorporated in the model, neural population activity and receptive fields expand just before and during saccades. These results suggest that visual remapping and motor updating are part of a common visuomotor mechanism, and that subjective perceptual constancy arises in part from training the visual system on motor tasks. PMID:27242452

  4. Targeted therapies for cancer

    MedlinePlus

    Targeted therapies are promising new treatments, but they have limitations. Cancer cells can become resistant to these drugs. The target sometimes changes, so the treatment no longer works. The cancer may find a different way to grow and survive that ...

  5. Targets and timelines for reducing salt in processed food in the Americas.

    PubMed

    Campbell, Norm; Legowski, Barbara; Legetic, Branka; Ferrante, Daniel; Nilson, Eduardo; Campbell, Christine; L'Abbé, Mary

    2014-09-01

    Reducing dietary salt is one of the most effective interventions to lessen the burden of premature death and disability. In high-income countries and those in nutrition transition, processed foods are a significant if not the main source of dietary salt. Reformulating these products to reduce their salt content is recommended as a best buy to prevent chronic diseases across populations. In the Americas, there are targets and timelines for reduced salt content of processed foods in 8 countries--Argentina, Brazil, Canada, Chile, Ecuador, Mexico, and the National Salt Reduction Initiative in the United States and Paraguay. While there are common elements across the countries, there are notable differences in their approaches: 4 countries have exclusively voluntary targets, 2 countries have combined voluntary and regulated components, and 1 country has only regulations. The countries have set different types of targets and in some cases combined them: averages, sales-weighted averages, upper limits, and percentage reductions. The foods to which the targets apply vary from single categories to comprehensive categories accounting for all processed products. The most accessible and transparent targets are upper limits per food category. Most likely to have a substantive and sustained impact on salt intake across whole populations is the combination of sales-weighted averages and upper limits. To assist all countries with policies to improve the overall nutritional value of processed foods, the authors call for food companies to supply food composition data and product sales volume data to transparent and open-access platforms and for global companies to supply the products that meet the strictest targets to all markets. Countries participating in common markets at the subregional level can consider harmonizing targets, nutrition labels, and warning labels. ©2014 Wiley Periodicals, Inc.

  6. Targeting pre-exposure prophylaxis among men who have sex with men in the United States and Peru: partnership types, contact rates, and sexual role.

    PubMed

    Carnegie, Nicole B; Goodreau, Steven M; Liu, Albert; Vittinghoff, Eric; Sanchez, Jorge; Lama, Javier R; Buchbinder, Susan

    2015-05-01

    We aim to identify optimal strategies for deploying pre-exposure prophylaxis among men who have sex with men (MSM) in the United States and Peru to maximize population-level effectiveness in an efficient manner. We use epidemic models to simulate the impact of targeting strategies. Most studies have focused on targeting either the general population or high-risk MSM. Alternative strategies, including serodiscordant couples, may better balance effectiveness and efficiency. We use dynamic stochastic sexual network models based on exponential-family random graph modeling, parameterized from behavioral surveys of MSM in the United States and Peru. These models represent main partnerships and casual contacts separately, permitting modeling of interventions targeting men whose risk derives from combinations of relational types. We also model varying rates of uptake and adherence to pre-exposure prophylaxis (PrEP). We assess sensitivity of results to risk compensation through increases in condomless casual contacts and condomless sex in main partnerships. Targeting all men who are not exclusively insertive has the largest impact on HIV incidence, but targeting only those with high levels of casual activity yields comparable results using fewer person-years on PrEP. The effect is robust to risk compensation in the United States, but less so in Peru. Targeting serodiscordant main partnerships does not significantly impact incidence, but requires fewer person-years on PrEP per infection averted than other strategies. PrEP could be effective in reducing new infections at the population level in both settings. Serodiscordant partnerships are an attractive component of a targeting program, but targeting should include other high-risk men.

  7. The enemy within: Targeting host-parasite interaction for antileishmanial drug discovery.

    PubMed

    Lamotte, Suzanne; Späth, Gerald F; Rachidi, Najma; Prina, Eric

    2017-06-01

    The state of antileishmanial chemotherapy is strongly compromised by the emergence of drug-resistant Leishmania. The evolution of drug-resistant phenotypes has been linked to the parasites' intrinsic genome instability, with frequent gene and chromosome amplifications causing fitness gains that are directly selected by environmental factors, including the presence of antileishmanial drugs. Thus, even though the unique eukaryotic biology of Leishmania and its dependence on parasite-specific virulence factors provide valid opportunities for chemotherapeutical intervention, all strategies that target the parasite in a direct fashion are likely prone to select for resistance. Here, we review the current state of antileishmanial chemotherapy and discuss the limitations of ongoing drug discovery efforts. We finally propose new strategies that target Leishmania viability indirectly via mechanisms of host-parasite interaction, including parasite-released ectokinases and host epigenetic regulation, which modulate host cell signaling and transcriptional regulation, respectively, to establish permissive conditions for intracellular Leishmania survival.

  8. Qualitative Contrast between Knowledge-Limited Mixed-State and Variable-Resources Models of Visual Change Detection

    ERIC Educational Resources Information Center

    Nosofsky, Robert M.; Donkin, Chris

    2016-01-01

    We report an experiment designed to provide a qualitative contrast between knowledge-limited versions of mixed-state and variable-resources (VR) models of visual change detection. The key data pattern is that observers often respond "same" on big-change trials, while simultaneously being able to discriminate between same and small-change…

  9. 42 CFR § 414.1385 - Targeted review and review limitations.

    Code of Federal Regulations, 2010 CFR

    2017-10-01

    ... SERVICES (CONTINUED) MEDICARE PROGRAM (CONTINUED) PAYMENT FOR PART B MEDICAL AND OTHER HEALTH SERVICES Merit-Based Incentive Payment System and Alternative Payment Model Incentive § 414.1385 Targeted review... review of the calculation of the MIPS payment adjustment factor under section 1848(q)(6)(A) of the Act...

  10. Distribution of eigenfrequencies for oscillations of the ground state in the Thomas-Fermi limit

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

    Kevrekidis, P. G.; Pelinovsky, D. E.

    In this work, we present a systematic derivation of the distribution of eigenfrequencies for oscillations of the ground state of a repulsive Bose-Einstein condensate in the semi-classical (Thomas-Fermi) limit. Our calculations are performed in one, two, and three-dimensional settings. Connections with the earlier work of Stringari, with numerical computations, and with theoretical expectations for invariant frequencies based on symmetry principles are also given.

  11. Limiting the protein corona: A successful strategy for in vivo active targeting of anti-HER2 nanobody-functionalized nanostars.

    PubMed

    D'Hollander, Antoine; Jans, Hilde; Velde, Greetje Vande; Verstraete, Charlotte; Massa, Sam; Devoogdt, Nick; Stakenborg, Tim; Muyldermans, Serge; Lagae, Liesbet; Himmelreich, Uwe

    2017-04-01

    Gold nanoparticles hold great promise as anti-cancer theranostic agents against cancer by actively targeting the tumor cells. As this potential has been supported numerously during in vitro experiments, the effective application is hampered by our limited understanding and control of the interactions within complex in vivo biological systems. When these nanoparticles are exposed to a biological environment, their surfaces become covered with proteins and biomolecules, referred to as the protein corona, reducing the active targeting capabilities. We demonstrate a chemical strategy to overcome this issue by reducing the protein corona's thickness by blocking the active groups of the self-assembled monolayer on gold nanostars. An optimal blocking agent, 2-mercapto ethanol, has been selected based on charge and length of the carbon chain. By using a nanobody as a biological ligand of the human epidermal growth factor 2 receptor (HER2), the active targeting is demonstrated in vitro and in vivo in an experimental tumor model by using darkfield microscopy and photoacoustic imaging. In this study, we have established gold nanostars as a conceivable theranostic agent with a specificity for HER2-positive tumors. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. A tumor-targeting p53 nanodelivery system limits chemoresistance to temozolomide prolonging survival in a mouse model of glioblastoma multiforme.

    PubMed

    Kim, Sang-Soo; Rait, Antonina; Kim, Eric; Pirollo, Kathleen F; Chang, Esther H

    2015-02-01

    Development of temozolomide (TMZ) resistance contributes to the poor prognosis for glioblastoma multiforme (GBM) patients. It was previously demonstrated that delivery of exogenous wild-type tumor suppressor gene p53 via a tumor-targeted nanocomplex (SGT-53) which crosses the blood-brain barrier could sensitize highly TMZ-resistant GBM tumors to TMZ. Here we assessed whether SGT-53 could inhibit development of TMZ resistance. SGT-53 significantly chemosensitized TMZ-sensitive human GBM cell lines (U87 and U251), in vitro and in vivo. Furthermore, in an intracranial GBM tumor model, two cycles of concurrent treatment with systemically administered SGT-53 and TMZ inhibited tumor growth, increased apoptosis and most importantly, significantly prolonged median survival. In contrast TMZ alone had no significant effect on median survival compared to a single cycle of TMZ. These results suggest that combining SGT-53 with TMZ appears to limit development of TMZ resistance, prolonging its anti-tumor effect and could be a more effective therapy for GBM. Using human glioblastoma multiforma cell lines, this research team demonstrated that the delivery of exogenous wild-type tumor suppressor gene p53 via a tumor-targeted nanocomplex limited the development of temozolomide resistance and prolonged its anti-tumor effect, which may enable future human application of this or similar techniques. Copyright © 2015 Elsevier Inc. All rights reserved.

  13. Faithful conditional quantum state transfer between weakly coupled qubits

    NASA Astrophysics Data System (ADS)

    Miková, M.; Straka, I.; Mičuda, M.; Krčmarský, V.; Dušek, M.; Ježek, M.; Fiurášek, J.; Filip, R.

    2016-08-01

    One of the strengths of quantum information theory is that it can treat quantum states without referring to their particular physical representation. In principle, quantum states can be therefore fully swapped between various quantum systems by their mutual interaction and this quantum state transfer is crucial for many quantum communication and information processing tasks. In practice, however, the achievable interaction time and strength are often limited by decoherence. Here we propose and experimentally demonstrate a procedure for faithful quantum state transfer between two weakly interacting qubits. Our scheme enables a probabilistic yet perfect unidirectional transfer of an arbitrary unknown state of a source qubit onto a target qubit prepared initially in a known state. The transfer is achieved by a combination of a suitable measurement of the source qubit and quantum filtering on the target qubit depending on the outcome of measurement on the source qubit. We experimentally verify feasibility and robustness of the transfer using a linear optical setup with qubits encoded into polarization states of single photons.

  14. A fast ellipse extended target PHD filter using box-particle implementation

    NASA Astrophysics Data System (ADS)

    Zhang, Yongquan; Ji, Hongbing; Hu, Qi

    2018-01-01

    This paper presents a box-particle implementation of the ellipse extended target probability hypothesis density (ET-PHD) filter, called the ellipse extended target box particle PHD (EET-BP-PHD) filter, where the extended targets are described as a Poisson model developed by Gilholm et al. and the term "box" is here equivalent to the term "interval" used in interval analysis. The proposed EET-BP-PHD filter is capable of dynamically tracking multiple ellipse extended targets and estimating the target states and the number of targets, in the presence of clutter measurements, false alarms and missed detections. To derive the PHD recursion of the EET-BP-PHD filter, a suitable measurement likelihood is defined for a given partitioning cell, and the main implementation steps are presented along with the necessary box approximations and manipulations. The limitations and capabilities of the proposed EET-BP-PHD filter are illustrated by simulation examples. The simulation results show that a box-particle implementation of the ET-PHD filter can avoid the high number of particles and reduce computational burden, compared to a particle implementation of that for extended target tracking.

  15. Intrinsic limits to gene regulation by global crosstalk

    NASA Astrophysics Data System (ADS)

    Friedlander, Tamar; Prizak, Roshan; Guet, Calin; Barton, Nicholas H.; Tkacik, Gasper

    Gene activity is mediated by the specificity of binding interactions between special proteins, called transcription factors, and short regulatory sequences on the DNA, where different protein species preferentially bind different DNA targets. Limited interaction specificity may lead to crosstalk: a regulatory state in which a gene is either incorrectly activated due to spurious interactions or remains erroneously inactive. Since each protein can potentially interact with numerous DNA targets, crosstalk is inherently a global problem, yet has previously not been studied as such. We construct a theoretical framework to analyze the effects of global crosstalk on gene regulation, using statistical mechanics. We find that crosstalk in regulatory interactions puts fundamental limits on the reliability of gene regulation that are not easily mitigated by tuning proteins concentrations or by complex regulatory schemes proposed in the literature. Our results suggest that crosstalk imposes a previously unexplored global constraint on the functioning and evolution of regulatory networks, which is qualitatively distinct from the known constraints that act at the level of individual gene regulatory elements. The research leading to these results has received funding from the People Programme (Marie Curie Actions) of the European Union's Seventh Framework Programme (FP7/2007-2013) under REA Grant agreement Nr. 291734 (T.F.) and ERC Grant Nr. 250152 (N.B.).

  16. High-efficiency free-form condenser overcoming rotational symmetry limitations.

    PubMed

    Miñano, Juan C; Benítez, Pablo; Blen, José; Santamaría, Asunción

    2008-12-08

    Conventional condensers using rotational symmetric devices perform far from their theoretical limits when transferring optical power from sources such as arc lamps or halogen bulbs to the rectangular entrance of homogenizing prisms (target). We present a free-form condenser design (calculated with the SMS method) that overcomes the limitations inherent to rotational devices and can send to the target 1.8 times the power sent by an equivalent elliptical condenser for a 4:1 target aspect ratio and 1.5 times for 16:9 target and for practical values of target etendue.

  17. A systematic review of suicide prevention interventions targeting indigenous peoples in Australia, United States, Canada and New Zealand

    PubMed Central

    2013-01-01

    Background Indigenous peoples of Australia, Canada, United States and New Zealand experience disproportionately high rates of suicide. As such, the methodological quality of evaluations of suicide prevention interventions targeting these Indigenous populations should be rigorously examined, in order to determine the extent to which they are effective for reducing rates of Indigenous suicide and suicidal behaviours. This systematic review aims to: 1) identify published evaluations of suicide prevention interventions targeting Indigenous peoples in Australia, Canada, United States and New Zealand; 2) critique their methodological quality; and 3) describe their main characteristics. Methods A systematic search of 17 electronic databases and 13 websites for the period 1981–2012 (inclusive) was undertaken. The reference lists of reviews of suicide prevention interventions were hand-searched for additional relevant studies not identified by the electronic and web search. The methodological quality of evaluations of suicide prevention interventions was assessed using a standardised assessment tool. Results Nine evaluations of suicide prevention interventions were identified: five targeting Native Americans; three targeting Aboriginal Australians; and one First Nation Canadians. The main intervention strategies employed included: Community Prevention, Gatekeeper Training, and Education. Only three of the nine evaluations measured changes in rates of suicide or suicidal behaviour, all of which reported significant improvements. The methodological quality of evaluations was variable. Particular problems included weak study designs, reliance on self-report measures, highly variable consent and follow-up rates, and the absence of economic or cost analyses. Conclusions There is an urgent need for an increase in the number of evaluations of preventive interventions targeting reductions in Indigenous suicide using methodologically rigorous study designs across geographically

  18. A systematic review of suicide prevention interventions targeting indigenous peoples in Australia, United States, Canada and New Zealand.

    PubMed

    Clifford, Anton C; Doran, Christopher M; Tsey, Komla

    2013-05-13

    Indigenous peoples of Australia, Canada, United States and New Zealand experience disproportionately high rates of suicide. As such, the methodological quality of evaluations of suicide prevention interventions targeting these Indigenous populations should be rigorously examined, in order to determine the extent to which they are effective for reducing rates of Indigenous suicide and suicidal behaviours. This systematic review aims to: 1) identify published evaluations of suicide prevention interventions targeting Indigenous peoples in Australia, Canada, United States and New Zealand; 2) critique their methodological quality; and 3) describe their main characteristics. A systematic search of 17 electronic databases and 13 websites for the period 1981-2012 (inclusive) was undertaken. The reference lists of reviews of suicide prevention interventions were hand-searched for additional relevant studies not identified by the electronic and web search. The methodological quality of evaluations of suicide prevention interventions was assessed using a standardised assessment tool. Nine evaluations of suicide prevention interventions were identified: five targeting Native Americans; three targeting Aboriginal Australians; and one First Nation Canadians. The main intervention strategies employed included: Community Prevention, Gatekeeper Training, and Education. Only three of the nine evaluations measured changes in rates of suicide or suicidal behaviour, all of which reported significant improvements. The methodological quality of evaluations was variable. Particular problems included weak study designs, reliance on self-report measures, highly variable consent and follow-up rates, and the absence of economic or cost analyses. There is an urgent need for an increase in the number of evaluations of preventive interventions targeting reductions in Indigenous suicide using methodologically rigorous study designs across geographically and culturally diverse Indigenous

  19. [Health targets for health promotion in an area of conflict between individual freedom, state paternalism and common welfare].

    PubMed

    Michelsen, K

    2010-01-01

    In Germany, a growing number of health targets has been adopted in the last years by various actors. While health targets are a useful instrument of governance, the priority setting and a respective redistribution of resources have to be legitimised in the cause of their advantages and disadvantages for population groups. The involved sciences including ethics can support decision-making, but not fully justify decisions. Therefore, decisions on health targets must be made in a transparent and participative process. In spite of a growing number of health targets, the lack of targets in health policies is to be criticised. Within the health targets, those measures assigned to curative medicine and prevention have a greater weight than health promotion. Health promotion should follow the WHO Ottawa-Charter and be embedded in the concept of "capabilities". Under these conditions, a stronger consideration of health promotion in the health target process would be desirable. However, the present actor constellations within health target processes make such a direction improbable. The struggle around capabilities and individual freedom occurs through, in and about institutions of the civil society as well as political and legal institutions. To restrict the discussion about public health and health promotions to an juxtaposition of individual freedom and state paternalism minimises societal and social restrictions of individual freedom as well as the possibility of a safeguard and enlargement of individual freedoms through political and legal institutions.

  20. Identifying Drug-Target Interactions with Decision Templates.

    PubMed

    Yan, Xiao-Ying; Zhang, Shao-Wu

    2018-01-01

    During the development process of new drugs, identification of the drug-target interactions wins primary concerns. However, the chemical or biological experiments bear the limitation in coverage as well as the huge cost of both time and money. Based on drug similarity and target similarity, chemogenomic methods can be able to predict potential drug-target interactions (DTIs) on a large scale and have no luxurious need about target structures or ligand entries. In order to reflect the cases that the drugs having variant structures interact with common targets and the targets having dissimilar sequences interact with same drugs. In addition, though several other similarity metrics have been developed to predict DTIs, the combination of multiple similarity metrics (especially heterogeneous similarities) is too naïve to sufficiently explore the multiple similarities. In this paper, based on Gene Ontology and pathway annotation, we introduce two novel target similarity metrics to address above issues. More importantly, we propose a more effective strategy via decision template to integrate multiple classifiers designed with multiple similarity metrics. In the scenarios that predict existing targets for new drugs and predict approved drugs for new protein targets, the results on the DTI benchmark datasets show that our target similarity metrics are able to enhance the predictive accuracies in two scenarios. And the elaborate fusion strategy of multiple classifiers has better predictive power than the naïve combination of multiple similarity metrics. Compared with other two state-of-the-art approaches on the four popular benchmark datasets of binary drug-target interactions, our method achieves the best results in terms of AUC and AUPR for predicting available targets for new drugs (S2), and predicting approved drugs for new protein targets (S3).These results demonstrate that our method can effectively predict the drug-target interactions. The software package can

  1. Comparing federal and state healthcare provider performance in villages targeted by the conditional cash transfer programme of Mexico.

    PubMed

    Bustamante, Arturo Vargas

    2011-10-01

    This study investigates household out-of-pocket healthcare expenditures (OPH) and preventive care utilization (PHU) to compare federal and state healthcare provider performance in villages targeted by conditional cash transfer (CCT) programmes in poor rural areas of Mexico. Lower OPH and higher PHU are indicative of better performance in the study setting. Log-linear and probit regression models were used to compare outcomes in households from treatment and control villages reached by federal and state healthcare providers. In treatment villages, eligible households receive cash grants from the CCT programme. In control villages, eligible households do not receive cash grants from the CCT programme at the time of the survey. Families who live in treatment villages reported lower OPH (-52.5% for federal and -46.2% for state clinics) and higher PHU (21% for federal and 20% for state clinics) regardless of clinic setting. As the reduction in OPH is higher in areas reached by the federal clinics, it implies better performance from this healthcare delivery system. Additionally, federal clinic outcomes were also more homogeneous because OPH are not significantly different between treatment and control villages. Alternative measures such as drug and physician expenditures, diabetes and hypertension tests and nutritional-supplement receipt confirmed these findings. Mexico has two healthcare delivery systems that cater to identical rural populations. The better-funded and more centralized federal system is more effective at providing health care in poor rural villages of Mexico regardless of CCT participation. State clinics in villages targeted by the CCT programme, however, perform significantly better. © 2011 Blackwell Publishing Ltd.

  2. Genetically Validated Drug Targets in Leishmania: Current Knowledge and Future Prospects.

    PubMed

    Jones, Nathaniel G; Catta-Preta, Carolina M C; Lima, Ana Paula C A; Mottram, Jeremy C

    2018-04-13

    There has been a very limited number of high-throughput screening campaigns carried out with Leishmania drug targets. In part, this is due to the small number of suitable target genes that have been shown by genetic or chemical methods to be essential for the parasite. In this perspective, we discuss the state of genetic target validation in the field of Leishmania research and review the 200 Leishmania genes and 36 Trypanosoma cruzi genes for which gene deletion attempts have been made since the first published case in 1990. We define a quality score for the different genetic deletion techniques that can be used to identify potential drug targets. We also discuss how the advances in genome-scale gene disruption techniques have been used to assist target-based and phenotypic-based drug development in other parasitic protozoa and why Leishmania has lacked a similar approach so far. The prospects for this scale of work are considered in the context of the application of CRISPR/Cas9 gene editing as a useful tool in Leishmania.

  3. The enemy within: Targeting host–parasite interaction for antileishmanial drug discovery

    PubMed Central

    Späth, Gerald F.; Rachidi, Najma; Prina, Eric

    2017-01-01

    The state of antileishmanial chemotherapy is strongly compromised by the emergence of drug-resistant Leishmania. The evolution of drug-resistant phenotypes has been linked to the parasites’ intrinsic genome instability, with frequent gene and chromosome amplifications causing fitness gains that are directly selected by environmental factors, including the presence of antileishmanial drugs. Thus, even though the unique eukaryotic biology of Leishmania and its dependence on parasite-specific virulence factors provide valid opportunities for chemotherapeutical intervention, all strategies that target the parasite in a direct fashion are likely prone to select for resistance. Here, we review the current state of antileishmanial chemotherapy and discuss the limitations of ongoing drug discovery efforts. We finally propose new strategies that target Leishmania viability indirectly via mechanisms of host–parasite interaction, including parasite-released ectokinases and host epigenetic regulation, which modulate host cell signaling and transcriptional regulation, respectively, to establish permissive conditions for intracellular Leishmania survival. PMID:28594938

  4. Quantitative risk stratification in Markov chains with limiting conditional distributions.

    PubMed

    Chan, David C; Pollett, Philip K; Weinstein, Milton C

    2009-01-01

    Many clinical decisions require patient risk stratification. The authors introduce the concept of limiting conditional distributions, which describe the equilibrium proportion of surviving patients occupying each disease state in a Markov chain with death. Such distributions can quantitatively describe risk stratification. The authors first establish conditions for the existence of a positive limiting conditional distribution in a general Markov chain and describe a framework for risk stratification using the limiting conditional distribution. They then apply their framework to a clinical example of a treatment indicated for high-risk patients, first to infer the risk of patients selected for treatment in clinical trials and then to predict the outcomes of expanding treatment to other populations of risk. For the general chain, a positive limiting conditional distribution exists only if patients in the earliest state have the lowest combined risk of progression or death. The authors show that in their general framework, outcomes and population risk are interchangeable. For the clinical example, they estimate that previous clinical trials have selected the upper quintile of patient risk for this treatment, but they also show that expanded treatment would weakly dominate this degree of targeted treatment, and universal treatment may be cost-effective. Limiting conditional distributions exist in most Markov models of progressive diseases and are well suited to represent risk stratification quantitatively. This framework can characterize patient risk in clinical trials and predict outcomes for other populations of risk.

  5. Cooperative pulses for pseudo-pure state preparation

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

    Wei, Daxiu; Chang, Yan; Yang, Xiaodong, E-mail: steffen.glaser@tum.de, E-mail: xiaodong.yang@sibet.ac.cn

    2014-06-16

    Using an extended version of the optimal-control-based gradient ascent pulse engineering algorithm, cooperative (COOP) pulses are designed for multi-scan experiments to prepare pseudo-pure states in quantum computation. COOP pulses can cancel undesired signal contributions, complementing and generalizing phase cycles. They also provide more flexibility and, in particular, eliminate the need to select specific individual target states and achieve the fidelity of theoretical limit by flexibly choosing appropriate number of scans and duration of pulses. The COOP approach is experimentally demonstrated for three-qubit and four-qubit systems.

  6. Polymer space-charge-limited transistor as a solid-state vacuum tube triode

    NASA Astrophysics Data System (ADS)

    Chao, Yu-Chiang; Ku, Ming-Che; Tsai, Wu-Wei; Zan, Hsiao-Wen; Meng, Hsin-Fei; Tsai, Hung-Kuo; Horng, Sheng-Fu

    2010-11-01

    We report the construction of a polymer space-charge-limited transistor (SCLT), a solid-state version of vacuum tube triode. The SCLT achieves a high on/off ratio of 3×105 at a low operation voltage of 1.5 V by using high quality insulators both above and below the grid base electrode. Applying a greater bias to the base increases the barrier potential, and turns off the channel current, without introducing a large parasitic leakage current. Simulation result verifies the influence of base bias on channel potential distribution. The output current density is 1.7 mA/cm2 with current gain greater than 1000.

  7. Internal Targeting and External Control: Phototriggered Targeting in Nanomedicine.

    PubMed

    Arrue, Lily; Ratjen, Lars

    2017-12-07

    The photochemical control of structure and reactivity bears great potential for chemistry, biology, and life sciences. A key feature of photochemistry is the spatiotemporal control over secondary events. Well-established applications of photochemistry in medicine are photodynamic therapy (PDT) and photopharmacology (PP). However, although both are highly localizable through the application of light, they lack cell- and tissue-specificity. The combination of nanomaterial-based drug delivery and targeting has the potential to overcome limitations for many established therapy concepts. Even more privileged seems the merger of nanomedicine and cell-specific targeting (internal targeting) controlled by light (external control), as it can potentially be applied to many different areas of medicine and pharmaceutical research, including the aforementioned PDT and PP. In this review a survey of the interface of photochemistry, medicine and targeted drug delivery is given, especially focusing on phototriggered targeting in nanomedicine. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  8. Accuracy of mechanical torque-limiting devices for dental implants.

    PubMed

    L'Homme-Langlois, Emilie; Yilmaz, Burak; Chien, Hua-Hong; McGlumphy, Edwin

    2015-10-01

    A common complication in implant dentistry is unintentional implant screw loosening. The critical factor in the prevention of screw loosening is the delivery of the appropriate target torque value. Mechanical torque-limiting devices (MTLDs) are the most frequently recommended devices by the implant manufacturers to deliver the target torque value to the screw. Two types of MTLDs are available: friction-style and spring-style. Limited information is available regarding the influence of device type on the accuracy of MTLDs. The purpose of this study was to determine and compare the accuracy of spring-style and friction-style MTLDs. Five MTLDs from 6 different dental implant manufacturers (Astra Tech/Dentsply, Zimmer Dental, Biohorizons, Biomet 3i, Straumann [ITI], and Nobel Biocare) (n=5 per manufacturer) were selected to determine their accuracy in delivering target torque values preset by their manufacturers. All torque-limiting devices were new and there were 3 manufacturers for the friction-style and 3 manufacturers for the spring-style. The procedure of target torque measurement was performed 10 times for each device and a digital torque gauge (Chatillon Model DFS2-R-ND; Ametek) was used to record the measurements. Statistical analysis used nonparametric tests to determine the accuracy of the MTLDs in delivering target torque values and Bonferroni post hoc tests were used to assess pairwise comparisons. Median absolute difference between delivered torque values and target torque values of friction-style and spring-style MTLDs were not significantly different (P>.05). Accuracy of Astra Tech and Zimmer Dental friction-style torque-limiting devices were significantly different than Biohorizons torque-limiting devices (P<.05). There is no difference between the accuracy of new friction-style MTLDs and new spring-style MTLDs. All MTLDs fell within ±10% of the target torque value. Astra Tech and Zimmer Dental friction-style torque-limiting devices were significantly

  9. The Effects of Target and Missile Characteristics on Theoretical Minimum Miss Distance for a Beam-Rider Guidance System in the Presence of Noise

    NASA Technical Reports Server (NTRS)

    Stewart, Elwood C.; Druding, Frank; Nishiura, Togo

    1959-01-01

    A study has been made to determine the relative importance of those factors which place an inherent limitation on the minimum obtainable miss distance for a beam-rider navigation system operating in the presence of glint noise and target evasive maneuver. Target and missile motions are assumed to be coplanar. The factors considered are the missile natural frequencies and damping ratios, missile steady-state acceleration capabilities, target evasive maneuver characteristics, and angular scintillation noise characteristics.

  10. Basic/Translational Development of Forthcoming Opioid- and Nonopioid-Targeted Pain Therapeutics.

    PubMed

    Knezevic, Nebojsa Nick; Yekkirala, Ajay; Yaksh, Tony L

    2017-11-01

    Opioids represent an efficacious therapeutic modality for some, but not all pain states. Singular reliance on opioid therapy for pain management has limitations, and abuse potential has deleterious consequences for patient and society. Our understanding of pain biology has yielded insights and opportunities for alternatives to conventional opioid agonists. The aim is to have efficacious therapies, with acceptable side effect profiles and minimal abuse potential, which is to say an absence of reinforcing activity in the absence of a pain state. The present work provides a nonexclusive overview of current drug targets and potential future directions of research and development. We discuss channel activators and blockers, including sodium channel blockers, potassium channel activators, and calcium channel blockers; glutamate receptor-targeted agents, including N-methyl-D-aspartate, α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid, and metabotropic receptors. Furthermore, we discuss therapeutics targeted at γ-aminobutyric acid, α2-adrenergic, and opioid receptors. We also considered antagonists of angiotensin 2 and Toll receptors and agonists/antagonists of adenosine, purine receptors, and cannabinoids. Novel targets considered are those focusing on lipid mediators and anti-inflammatory cytokines. Of interest is development of novel targeting strategies, which produce long-term alterations in pain signaling, including viral transfection and toxins. We consider issues in the development of druggable molecules, including preclinical screening. While there are examples of successful translation, mechanistically promising preclinical candidates may unexpectedly fail during clinical trials because the preclinical models may not recapitulate the particular human pain condition being addressed. Molecular target characterization can diminish the disconnect between preclinical and humans' targets, which should assist in developing nonaddictive analgesics.

  11. Limited mobility of target pests crucially lowers controllability when sterile insect releases are spatiotemporally biased.

    PubMed

    Ikegawa, Yusuke; Himuro, Chihiro

    2017-05-21

    The sterile insect technique (SIT) is a genetic pest control method wherein mass-reared sterile insects are periodically released into the wild, thereby impeding the successful reproduction of fertile pests. In Okinawa Prefecture, Japan, the SIT has been implemented to eradicate the West Indian sweet potato weevil Euscepes postfasciatus (Fairmaire), which is a flightless agricultural pest of sweet potatoes. It is known that E. postfasciatus is much less mobile than other insects to which the SIT has been applied. However, previous theoretical studies have rarely examined effects of low mobility of target pests and variation in the spatiotemporal evenness of sterile insect releases. To theoretically examine the effects of spatiotemporal evenness on the regional eradication of less mobile pests, we constructed a simple two-patch population model comprised of a pest and sterile insect moving between two habitats, and numerically simulated different release strategies (varying the number of released sterile insects and release intervals). We found that spatially biased releases allowed the pest to spatially escape from the sterile insect, and thus intensively lowered its controllability. However, we showed that the temporally counterbalancing spatially biased releases by swapping the number of released insects in the two habitats at every release (called temporal balancing) could greatly mitigate this negative effect and promote the controllability. We also showed that the negative effect of spatiotemporally biased releases was a result of the limited mobility of the target insect. Although directed dispersal of the insects in response to habitats of differing quality could lower the controllability in the more productive habitat, the temporal balancing could promote and eventually maximize the controllability as released insects increased. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. [More] evidence to support oral health promotion services targeted to smokers calling tobacco quitlines in the United States.

    PubMed

    McClure, Jennifer B; Riggs, Karin; St John, Jackie; Catz, Sheryl L

    2013-04-11

    Prior research demonstrated a need and opportunity to target smokers calling a free, state-funded tobacco quitline to provide behavioral counseling for oral health promotion; however, it is unclear whether these results generalize to tobacco quitline callers of higher socioeconomic status receiving services through commercially-funded quitlines. This knowledge will inform planning for a future public oral health promotion program targeted to tobacco quitline callers. We surveyed smokers (n = 455) who had recently received tobacco quitline services through their medical insurance. Participants were asked about their self-reported oral health indicators, key behavioral risk factors for oral disease, motivation for changing their oral self-care behavior, and interest in future oral health promotion services. Where applicable, results were compared against those from a representative sample of callers to a free, state-funded quitline (n = 816) in the same geographic region. Callers to a commercially-funded quitline had higher socioeconomic status, were more likely to have dental insurance, and reported better overall oral health indicators and routine self-care (oral hygiene, dental visits) than callers to a state-funded quitline. Nevertheless opportunities for oral health promotion were identified. Nearly 80% of commercial quitline callers failed to meet basic daily hygiene recommendations, 32.8% had not visited the dentist in more than a year, and 63.3% reported daily alcohol consumption (which reacts synergistically with tobacco to increase oral cancer risk). Nearly half (44%) were interested in learning how to improve their oral health status and, on average, moderately high levels of motivation for oral health care were reported. Many participants also had dental insurance, eliminating an important barrier to professional dental care. Future public oral health promotion efforts should focus on callers to both free state-supported and commercially

  13. Limited Efficiency of Drug Delivery to Specific Intracellular Organelles Using Subcellularly "Targeted" Drug Delivery Systems.

    PubMed

    Maity, Amit Ranjan; Stepensky, David

    2016-01-04

    Many drugs have been designed to act on intracellular targets and to affect intracellular processes inside target cells. For the desired effects to be exerted, these drugs should permeate target cells and reach specific intracellular organelles. This subcellular drug targeting approach has been proposed for enhancement of accumulation of these drugs in target organelles and improved efficiency. This approach is based on drug encapsulation in drug delivery systems (DDSs) and/or their decoration with specific targeting moieties that are intended to enhance the drug/DDS accumulation in the intracellular organelle of interest. During recent years, there has been a constant increase in interest in DDSs targeted to specific intracellular organelles, and many different approaches have been proposed for attaining efficient drug delivery to specific organelles of interest. However, it appears that in many studies insufficient efforts have been devoted to quantitative analysis of the major formulation parameters of the DDSs disposition (efficiency of DDS endocytosis and endosomal escape, intracellular trafficking, and efficiency of DDS delivery to the target organelle) and of the resulting pharmacological effects. Thus, in many cases, claims regarding efficient delivery of drug/DDS to a specific organelle and efficient subcellular targeting appear to be exaggerated. On the basis of the available experimental data, it appears that drugs/DDS decoration with specific targeting residues can affect their intracellular fate and result in preferential drug accumulation within an organelle of interest. However, it is not clear whether these approaches will be efficient in in vivo settings and be translated into preclinical and clinical applications. Studies that quantitatively assess the mechanisms, barriers, and efficiencies of subcellular drug delivery and of the associated toxic effects are required to determine the therapeutic potential of subcellular DDS targeting.

  14. Integrin Targeted Therapeutics

    PubMed Central

    Millard, Melissa; Odde, Srinivas; Neamati, Nouri

    2011-01-01

    Integrins are heterodimeric, transmembrane receptors that function as mechanosensors, adhesion molecules and signal transduction platforms in a multitude of biological processes. As such, integrins are central to the etiology and pathology of many disease states. Therefore, pharmacological inhibition of integrins is of great interest for the treatment and prevention of disease. In the last two decades several integrin-targeted drugs have made their way into clinical use, many others are in clinical trials and still more are showing promise as they advance through preclinical development. Herein, this review examines and evaluates the various drugs and compounds targeting integrins and the disease states in which they are implicated. PMID:21547158

  15. Assessing Reliability of Cold Spray Sputter Targets in Photovoltaic Manufacturing

    NASA Astrophysics Data System (ADS)

    Hardikar, Kedar; Vlcek, Johannes; Bheemreddy, Venkata; Juliano, Daniel

    2017-10-01

    Cold spray has been used to manufacture more than 800 Cu-In-Ga (CIG) sputter targets for deposition of high-efficiency photovoltaic thin films. It is a preferred technique since it enables high deposit purity and transfer of non-equilibrium alloy states to the target material. In this work, an integrated approach to reliability assessment of such targets with deposit weight in excess of 50 lb. is undertaken, involving thermal-mechanical characterization of the material in as-deposited condition, characterization of the interface adhesion on cylindrical substrate in as-deposited condition, and developing means to assess target integrity under thermal-mechanical loads during the physical vapor deposition (PVD) sputtering process. Mechanical characterization of cold spray deposited CIG alloy is accomplished through the use of indentation testing and adaptation of Brazilian disk test. A custom lever test was developed to characterize adhesion along the cylindrical interface between the CIG deposit and cylindrical substrate, overcoming limitations of current standards. A cohesive zone model for crack initiation and propagation at the deposit interface is developed and validated using the lever test and later used to simulate the potential catastrophic target failure in the PVD process. It is shown that this approach enables reliability assessment of sputter targets and improves robustness.

  16. Multi-Agent Cooperative Target Search

    PubMed Central

    Hu, Jinwen; Xie, Lihua; Xu, Jun; Xu, Zhao

    2014-01-01

    This paper addresses a vision-based cooperative search for multiple mobile ground targets by a group of unmanned aerial vehicles (UAVs) with limited sensing and communication capabilities. The airborne camera on each UAV has a limited field of view and its target discriminability varies as a function of altitude. First, by dividing the whole surveillance region into cells, a probability map can be formed for each UAV indicating the probability of target existence within each cell. Then, we propose a distributed probability map updating model which includes the fusion of measurement information, information sharing among neighboring agents, information decay and transmission due to environmental changes such as the target movement. Furthermore, we formulate the target search problem as a multi-agent cooperative coverage control problem by optimizing the collective coverage area and the detection performance. The proposed map updating model and the cooperative control scheme are distributed, i.e., assuming that each agent only communicates with its neighbors within its communication range. Finally, the effectiveness of the proposed algorithms is illustrated by simulation. PMID:24865884

  17. Spatially inhomogeneous electron state deep in the extreme quantum limit of strontium titanate

    DOE PAGES

    Bhattacharya, Anand; Skinner, Brian; Khalsa, Guru; ...

    2016-09-29

    When an electronic system is subjected to a sufficiently strong magnetic field that the cyclotron energy is much larger than the Fermi energy, the system enters the extreme quantum limit (EQL) and becomes susceptible to a number of instabilities. Bringing a three-dimensional electronic system deeply into the EQL can be difficult however, since it requires a small Fermi energy, large magnetic field, and low disorder. Here we present an experimental study of the EQL in lightly-doped single crystals of strontium titanate. Our experiments probe deeply into the regime where theory has long predicted an interaction-driven charge density wave or Wignermore » crystal state. A number of interesting features arise in the transport in this regime, including a striking re-entrant nonlinearity in the current-voltage characteristics. As a result, we discuss these features in the context of possible correlated electron states, and present an alternative picture based on magnetic-field induced puddling of electrons.« less

  18. Importance of limiting hohlraum leaks at cryogenic temperatures on NIF targets

    DOE PAGES

    Bhandarkar, Suhas; Teslich, Nick; Haid, Ben; ...

    2017-08-18

    Inertial confinement fusion targets are complex systems designed to allow fine control of temperature and pressure for making precise spherical ice layers of hydrogen isotopes at cryogenic temperatures. We discuss the various technical considerations for a maximum leak rate based on heat load considerations. This maximum flow rate turns out to bemore » $$5\\times 10^{-6}$$ standard cc per second, which can be caused by an orifice less than half a micron in diameter. This makes the identification of the location and resolution of the leak a significant challenge. To illustrate this, we showcase one example of a peculiar failure mode that appeared suddenly but persisted whereby target production yield was severely lowered. Identification of the leak source and the root cause requires very careful analysis of multiple thermomechanical aspects to ensure that the end solution is indeed the right remedy and is robust.« less

  19. States Get Flexibility on Targets

    ERIC Educational Resources Information Center

    Hoff, David J.

    2008-01-01

    As President Bush nears the end of his tenure, his administration is putting its final stamp on the No Child Left Behind Act and trying to lay the groundwork for the law's future. This article reports on the latest effort of President Bush's administration that will allow as many as 10 states to create alternative interventions for schools that…

  20. High energy bursts from a solid state laser operated in the heat capacity limited regime

    DOEpatents

    Albrecht, G.; George, E.V.; Krupke, W.F.; Sooy, W.; Sutton, S.B.

    1996-06-11

    High energy bursts are produced from a solid state laser operated in a heat capacity limited regime. Instead of cooling the laser, the active medium is thermally well isolated. As a result, the active medium will heat up until it reaches some maximum acceptable temperature. The waste heat is stored in the active medium itself. Therefore, the amount of energy the laser can put out during operation is proportional to its mass, the heat capacity of the active medium, and the temperature difference over which it is being operated. The high energy burst capacity of a heat capacity operated solid state laser, together with the absence of a heavy, power consuming steady state cooling system for the active medium, will make a variety of applications possible. Alternately, cooling takes place during a separate sequence when the laser is not operating. Industrial applications include new material working processes. 5 figs.

  1. High energy bursts from a solid state laser operated in the heat capacity limited regime

    DOEpatents

    Albrecht, Georg; George, E. Victor; Krupke, William F.; Sooy, Walter; Sutton, Steven B.

    1996-01-01

    High energy bursts are produced from a solid state laser operated in a heat capacity limited regime. Instead of cooling the laser, the active medium is thermally well isolated. As a result, the active medium will heat up until it reaches some maximum acceptable temperature. The waste heat is stored in the active medium itself. Therefore, the amount of energy the laser can put out during operation is proportional to its mass, the heat capacity of the active medium, and the temperature difference over which it is being operated. The high energy burst capacity of a heat capacity operated solid state laser, together with the absence of a heavy, power consuming steady state cooling system for the active medium, will make a variety of applications possible. Alternately, cooling takes place during a separate sequence when the laser is not operating. Industrial applications include new material working processes.

  2. 42 CFR 457.310 - Targeted low-income child.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 4 2013-10-01 2013-10-01 false Targeted low-income child. 457.310 Section 457.310... (CONTINUED) STATE CHILDREN'S HEALTH INSURANCE PROGRAMS (SCHIPs) ALLOTMENTS AND GRANTS TO STATES State Plan Requirements: Eligibility, Screening, Applications, and Enrollment § 457.310 Targeted low-income child. (a...

  3. 42 CFR 457.310 - Targeted low-income child.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 4 2012-10-01 2012-10-01 false Targeted low-income child. 457.310 Section 457.310... (CONTINUED) STATE CHILDREN'S HEALTH INSURANCE PROGRAMS (SCHIPs) ALLOTMENTS AND GRANTS TO STATES State Plan Requirements: Eligibility, Screening, Applications, and Enrollment § 457.310 Targeted low-income child. (a...

  4. 42 CFR 457.310 - Targeted low-income child.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 4 2011-10-01 2011-10-01 false Targeted low-income child. 457.310 Section 457.310... (CONTINUED) STATE CHILDREN'S HEALTH INSURANCE PROGRAMS (SCHIPs) ALLOTMENTS AND GRANTS TO STATES State Plan Requirements: Eligibility, Screening, Applications, and Enrollment § 457.310 Targeted low-income child. (a...

  5. 42 CFR 457.310 - Targeted low-income child.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 4 2014-10-01 2014-10-01 false Targeted low-income child. 457.310 Section 457.310... (CONTINUED) STATE CHILDREN'S HEALTH INSURANCE PROGRAMS (SCHIPs) ALLOTMENTS AND GRANTS TO STATES State Plan Requirements: Eligibility, Screening, Applications, and Enrollment § 457.310 Targeted low-income child. (a...

  6. 42 CFR 457.310 - Targeted low-income child.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 4 2010-10-01 2010-10-01 false Targeted low-income child. 457.310 Section 457.310... (CONTINUED) STATE CHILDREN'S HEALTH INSURANCE PROGRAMS (SCHIPs) ALLOTMENTS AND GRANTS TO STATES State Plan Requirements: Eligibility, Screening, Applications, and Enrollment § 457.310 Targeted low-income child. (a...

  7. A mathematical analysis of multiple-target SELEX.

    PubMed

    Seo, Yeon-Jung; Chen, Shiliang; Nilsen-Hamilton, Marit; Levine, Howard A

    2010-10-01

    SELEX (Systematic Evolution of Ligands by Exponential Enrichment) is a procedure by which a mixture of nucleic acids can be fractionated with the goal of identifying those with specific biochemical activities. One combines the mixture with a specific target molecule and then separates the target-NA complex from the resulting reactions. The target-NA complex is separated from the unbound NA by mechanical means (such as by filtration), the NA is eluted from the complex, amplified by PCR (polymerase chain reaction), and the process repeated. After several rounds, one should be left with the nucleic acids that best bind to the target. The problem was first formulated mathematically in Irvine et al. (J. Mol. Biol. 222:739-761, 1991). In Levine and Nilsen-Hamilton (Comput. Biol. Chem. 31:11-25, 2007), a mathematical analysis of the process was given. In Vant-Hull et al. (J. Mol. Biol. 278:579-597, 1998), multiple target SELEX was considered. It was assumed that each target has a single nucleic acid binding site that permits occupation by no more than one nucleic acid. Here, we revisit Vant-Hull et al. (J. Mol. Biol. 278:579-597, 1998) using the same assumptions. The iteration scheme is shown to be convergent and a simplified algorithm is given. Our interest here is in the behavior of the multiple target SELEX process as a discrete "time" dynamical system. Our goal is to characterize the limiting states and their dependence on the initial distribution of nucleic acid and target fraction components. (In multiple target SELEX, we vary the target component fractions, but not their concentrations, as fixed and the initial pool of nucleic acids as a variable starting condition). Given N nucleic acids and a target consisting of M subtarget component species, there is an M × N matrix of affinities, the (i,j) entry corresponding to the affinity of the jth nucleic acid for the ith subtarget. We give a structure condition on this matrix that is equivalent to the following

  8. Public Opinion on Tax and Expenditure Limitations: Attitudes in Four States. ECS Finance Facts. Special Issue.

    ERIC Educational Resources Information Center

    Education Commission of the States, Denver, CO. Education Finance Center.

    This survey examined the attitudes of people in four states where tax or spending limitations appeared on the ballot in November 1978. It found that people had positive attitudes toward schools in their communities, believed schools are doing an above-average job, and viewed schools as a public service that should not be reduced. Results suggest…

  9. Extrapolating target tracks

    NASA Astrophysics Data System (ADS)

    Van Zandt, James R.

    2012-05-01

    Steady-state performance of a tracking filter is traditionally evaluated immediately after a track update. However, there is commonly a further delay (e.g., processing and communications latency) before the tracks can actually be used. We analyze the accuracy of extrapolated target tracks for four tracking filters: Kalman filter with the Singer maneuver model and worst-case correlation time, with piecewise constant white acceleration, and with continuous white acceleration, and the reduced state filter proposed by Mookerjee and Reifler.1, 2 Performance evaluation of a tracking filter is significantly simplified by appropriate normalization. For the Kalman filter with the Singer maneuver model, the steady-state RMS error immediately after an update depends on only two dimensionless parameters.3 By assuming a worst case value of target acceleration correlation time, we reduce this to a single parameter without significantly changing the filter performance (within a few percent for air tracking).4 With this simplification, we find for all four filters that the RMS errors for the extrapolated state are functions of only two dimensionless parameters. We provide simple analytic approximations in each case.

  10. Fabrication of high-k dielectric Calcium Copper Titanate (CCTO) target by solid state route

    NASA Astrophysics Data System (ADS)

    Tripathy, N.; Das, K. C.; Ghosh, S. P.; Bose, G.; Kar, J. P.

    2016-02-01

    CaCu3Ti4O12 (CCTO) ceramic pellet of 10mm diameter has been synthesized by adopting solid state route. The structural and morphological characterization of the ceramics sample was carried out by X-ray diffraction (XRD) and scanning electron microscope (SEM), respectively. XRD pattern revealed the CCTO phase formation, where as SEM micrograph shows the sample consisting of well defined grain and grain boundaries. The room temperature dielectric constant of the sample was found to be ∼ 5000 at 1kHz. After successful preparation of CCTO pellet, a 2 inch diameter CCTO sputtering target is also fabricated in order to deposit CCTO thin films for microelectronic applications.

  11. Exploratory investigation of the HIPPO gas-jet target fluid dynamic properties

    NASA Astrophysics Data System (ADS)

    Meisel, Zach; Shi, Ke; Jemcov, Aleksandar; Couder, Manoel

    2016-08-01

    In order to optimize the performance of gas-jet targets for future nuclear reaction measurements, a detailed understanding of the dependence of the gas-jet properties on experiment design parameters is required. Common methods of gas-jet characterization rely on measuring the effective thickness using nuclear elastic scattering and energy loss techniques; however, these tests are time intensive and limit the range of design modifications which can be explored to improve the properties of the jet as a nuclear reaction target. Thus, a more rapid jet-characterization method is desired. We performed the first steps towards characterizing the gas-jet density distribution of the HIPPO gas-jet target at the University of Notre Dame's Nuclear Science Laboratory by reproducing results from 20Ne(α,α)20Ne elastic scattering measurements with computational fluid dynamics (CFD) simulations performed with the state-of-the-art CFD software ANSYS Fluent. We find a strong sensitivity to experimental design parameters of the gas-jet target, such as the jet nozzle geometry and ambient pressure of the target chamber. We argue that improved predictive power will require moving to three-dimensional simulations and additional benchmarking with experimental data.

  12. Al K x-ray production for incident /sup 16/O ions: The influence of target thickness effects on observed target x-ray yields

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

    Gray, T.J.; Richard, P.; Gealy, G.

    1979-04-01

    Thin solid Al targets ranging in thickness from approx. 1 to 30 ..mu..g/cm/sup 2/ were bombarded by /sup 16/O ions wih incident energies from 0.25 to 2.25 MeV/amu. The effects of target thickness on the measured Al K x-ray yield for ions incident without an initial K-shell vacancy were determined. Comparisons of the data for Al K x-ray production in vanishingly thin targets (and 29-..mu..g/cm/sup 2/ targets) were made to perturbed-stationary-state calculations (PSS) for O ions on Al targets. The PSS calculations contained corrections for Coulomb deflection and binding energy (PSS(CB)) and for Coulomb deflection, binding energy, and polarization (PSS(CBP)).more » Further, two different PSS calculation procedures were employed: calculations without radial cutoffs employed in the binding-energy contribution (PSS), and calculations with radial cutoffs employed in the binding-energy correction (NPSS). The PSS(CBP) calculations agree with the measured Al K x-ray production cross section for data taken in the limit of a vanishingly thin target. The NPSS(CBP) calculations agree with the data taken for a 29-..mu..g/cm/sup 2/ Al target. The latter agreement is fortuitous, as the increase observed in the measured target x-ray yield for the 29-..mu..g/cm/sup 2/ target, in comparison to the yield extracted as rhox ..-->.. 0 at each bombarding energy, is due to K-shell--to--K-shell charge exchange. Comparisons are made with previously published data for /sup 16/O ions incident on finite-thickness Al targets.« less

  13. New limits for the 2 νββ decay of 96Zr to excited nuclear states of 96Mo

    NASA Astrophysics Data System (ADS)

    Finch, Sean; Tornow, Werner

    2015-10-01

    The final results from our search for the 2 νββ decay of 96Zr to excited 0+ and 2+ states of 96Mo are presented. Such measurements provide valuable test cases for 2 νββ -decay nuclear matrix element calculations, which in turn are used to tune 0 νββ -decay nuclear matrix element calculations. After undergoing double- β decay to an excited state, the excited daughter nucleus decays to the ground state, emitting two coincident γ rays. These two γ rays are detected in coincidence by two HPGe detectors sandwiching the 96Zr sample, with a NaI veto in anti-coincidence. This experimental apparatus, located at the Kimballton Underground Research Facility (KURF), has previously measured the 2 νββ decay of 100Mo and 150Nd to excited nuclear states. Experimental limits on the T1 / 2 and corresponding nuclear matrix element are presented for each of these decays. As a byproduct of this experiment, limits were also set on the single- β decay of 96Zr. Supported by DOE Grant: DE-FG02-97ER41033.

  14. Bioinformatics approaches to predict target genes from transcription factor binding data.

    PubMed

    Essebier, Alexandra; Lamprecht, Marnie; Piper, Michael; Bodén, Mikael

    2017-12-01

    Transcription factors regulate gene expression and play an essential role in development by maintaining proliferative states, driving cellular differentiation and determining cell fate. Transcription factors are capable of regulating multiple genes over potentially long distances making target gene identification challenging. Currently available experimental approaches to detect distal interactions have multiple weaknesses that have motivated the development of computational approaches. Although an improvement over experimental approaches, existing computational approaches are still limited in their application, with different weaknesses depending on the approach. Here, we review computational approaches with a focus on data dependency, cell type specificity and usability. With the aim of identifying transcription factor target genes, we apply available approaches to typical transcription factor experimental datasets. We show that approaches are not always capable of annotating all transcription factor binding sites; binding sites should be treated disparately; and a combination of approaches can increase the biological relevance of the set of genes identified as targets. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Housing growth in and near United States protected areas limits their conservation value

    USGS Publications Warehouse

    Radeloff, V.C.; Stewart, S.I.; Hawbaker, T.J.; Gimmi, U.; Pidgeon, A.M.; Flather, C.H.; Hammer, R.B.; Helmers, D.P.

    2010-01-01

    Protected areas are crucial for biodiversity conservation because they provide safe havens for species threatened by land-use change and resulting habitat loss. However, protected areas are only effective when they stop habitat loss within their boundaries, and are connected via corridors to other wild areas. The effectiveness of protected areas is threatened by development; however, the extent of this threat is unknown. We compiled spatially-detailed housing growth data from 1940 to 2030, and quantified growth for each wilderness area, national park, and national forest in the conterminous United States. Our findings show that housing development in the United States may severely limit the ability of protected areas to function as a modern "Noah's Ark." Between 1940 and 2000, 28 million housing units were built within 50 km of protected areas, and 940,000 were built within national forests. Housing growth rates during the 1990s within 1 km of protected areas (20% per decade) outpaced the national average (13%). If long-term trends continue, another 17 million housing units will be built within 50 km of protected areas by 2030 (1 million within 1 km), greatly diminishing their conservation value. US protected areas are increasingly isolated, housing development in their surroundings is decreasing their effective size, and national forests are even threatened by habitat loss within their administrative boundaries. Protected areas in the United States are thus threatened similarly to those in developing countries. However, housing growth poses the main threat to protected areas in the United States whereas deforestation is the main threat in developing countries.

  16. Housing growth in and near United States protected areas limits their conservation value.

    PubMed

    Radeloff, Volker C; Stewart, Susan I; Hawbaker, Todd J; Gimmi, Urs; Pidgeon, Anna M; Flather, Curtis H; Hammer, Roger B; Helmers, David P

    2010-01-12

    Protected areas are crucial for biodiversity conservation because they provide safe havens for species threatened by land-use change and resulting habitat loss. However, protected areas are only effective when they stop habitat loss within their boundaries, and are connected via corridors to other wild areas. The effectiveness of protected areas is threatened by development; however, the extent of this threat is unknown. We compiled spatially-detailed housing growth data from 1940 to 2030, and quantified growth for each wilderness area, national park, and national forest in the conterminous United States. Our findings show that housing development in the United States may severely limit the ability of protected areas to function as a modern "Noah's Ark." Between 1940 and 2000, 28 million housing units were built within 50 km of protected areas, and 940,000 were built within national forests. Housing growth rates during the 1990s within 1 km of protected areas (20% per decade) outpaced the national average (13%). If long-term trends continue, another 17 million housing units will be built within 50 km of protected areas by 2030 (1 million within 1 km), greatly diminishing their conservation value. US protected areas are increasingly isolated, housing development in their surroundings is decreasing their effective size, and national forests are even threatened by habitat loss within their administrative boundaries. Protected areas in the United States are thus threatened similarly to those in developing countries. However, housing growth poses the main threat to protected areas in the United States whereas deforestation is the main threat in developing countries.

  17. An Accurate Non-Cooperative Method for Measuring Textureless Spherical Target Based on Calibrated Lasers.

    PubMed

    Wang, Fei; Dong, Hang; Chen, Yanan; Zheng, Nanning

    2016-12-09

    Strong demands for accurate non-cooperative target measurement have been arising recently for the tasks of assembling and capturing. Spherical objects are one of the most common targets in these applications. However, the performance of the traditional vision-based reconstruction method was limited for practical use when handling poorly-textured targets. In this paper, we propose a novel multi-sensor fusion system for measuring and reconstructing textureless non-cooperative spherical targets. Our system consists of four simple lasers and a visual camera. This paper presents a complete framework of estimating the geometric parameters of textureless spherical targets: (1) an approach to calibrate the extrinsic parameters between a camera and simple lasers; and (2) a method to reconstruct the 3D position of the laser spots on the target surface and achieve the refined results via an optimized scheme. The experiment results show that our proposed calibration method can obtain a fine calibration result, which is comparable to the state-of-the-art LRF-based methods, and our calibrated system can estimate the geometric parameters with high accuracy in real time.

  18. An Accurate Non-Cooperative Method for Measuring Textureless Spherical Target Based on Calibrated Lasers

    PubMed Central

    Wang, Fei; Dong, Hang; Chen, Yanan; Zheng, Nanning

    2016-01-01

    Strong demands for accurate non-cooperative target measurement have been arising recently for the tasks of assembling and capturing. Spherical objects are one of the most common targets in these applications. However, the performance of the traditional vision-based reconstruction method was limited for practical use when handling poorly-textured targets. In this paper, we propose a novel multi-sensor fusion system for measuring and reconstructing textureless non-cooperative spherical targets. Our system consists of four simple lasers and a visual camera. This paper presents a complete framework of estimating the geometric parameters of textureless spherical targets: (1) an approach to calibrate the extrinsic parameters between a camera and simple lasers; and (2) a method to reconstruct the 3D position of the laser spots on the target surface and achieve the refined results via an optimized scheme. The experiment results show that our proposed calibration method can obtain a fine calibration result, which is comparable to the state-of-the-art LRF-based methods, and our calibrated system can estimate the geometric parameters with high accuracy in real time. PMID:27941705

  19. Proton induced target fragmentation studies on solid state nuclear track detectors using Carbon radiators

    NASA Astrophysics Data System (ADS)

    Szabó, J.; Pálfalvi, J. K.; Strádi, A.; Bilski, P.; Swakoń, J.; Stolarczyk, L.

    2018-04-01

    One of the limiting factors of an astronaut's career is the dose received from space radiation. High energy protons, being the main components of the complex radiation field present on a spacecraft, give a significant contribution to the dose. To investigate the behavior of solid state nuclear track detectors (SSNTDs) if they are irradiated by such particles, SSNTD stacks containing carbon blocks were exposed to high energy proton beams (70, 100, 150 and 230 MeV) at the Proteus cyclotron, IFJ PAN -Krakow. The incident protons cannot be detected directly; however, tracks of secondary particles, recoils and fragments of the constituent atoms of the detector material and of the carbon radiator are formed. It was found that as the proton energy increases, the number of tracks induced in the PADC material by secondary particles decreases. From the measured geometrical parameters of the tracks the linear energy transfer (LET) spectrum and the dosimetric quantities were determined, applying appropriate calibration. In the LET spectra the LET range of the most important secondary particles could be identified and their abundance showed differences in the spectra if the detectors were short or long etched. The LET spectra obtained on the SSNTDs irradiated by protons were compared to LET spectra of detectors flown on the International Space Station (ISS): they were quite similar, resulting in a quality factor difference of only 5%. Thermoluminescent detectors (TLDs) were applied in each case to measure the dose from primary protons and other lower LET particles present in space. Comparing and analyzing the results of the TLD and SSNTD measurements, it was obtained that proton induced target fragments contributed to the total absorbed dose in 3.2% and to the dose equivalent in 14.2% in this particular space experiment.

  20. Towards new methods for the determination of dose limiting toxicities and the assessment of the recommended dose for further studies of molecularly targeted agents--dose-Limiting Toxicity and Toxicity Assessment Recommendation Group for Early Trials of Targeted therapies, an European Organisation for Research and Treatment of Cancer-led study.

    PubMed

    Postel-Vinay, Sophie; Collette, Laurence; Paoletti, Xavier; Rizzo, Elisa; Massard, Christophe; Olmos, David; Fowst, Camilla; Levy, Bernard; Mancini, Pierre; Lacombe, Denis; Ivy, Percy; Seymour, Lesley; Le Tourneau, Christophe; Siu, Lillian L; Kaye, Stan B; Verweij, Jaap; Soria, Jean-Charles

    2014-08-01

    Traditional dose-limiting toxicity (DLT) definition, which uses grade (G) 3-4 toxicity data from cycle 1 (C1) only, may not be appropriate for molecularly targeted agents (MTAs) of prolonged administration, for which late or lower grade toxicities also deserve attention. In collaboration with pharmaceutical companies and academia, an European Organisation for Research and Treatment of Cancer (EORTC)-led initiative, Dose-Limiting Toxicity and Toxicity Assessment Recommendation Group for Early Trials of Targeted therapies (DLT-TARGETT), collected data from completed phase 1 trials evaluating MTAs as monotherapy. All toxicities at least possibly related to the study drugs that occurred during C1-6, their type, grade (CTCAEv3.0), and duration as well as patients' relative dose-intensity (RDI), were recorded. The 54 eligible trials enrolled 2084 evaluable adult patients with solid tumours between 1999 and 2013, and evaluated small molecules (40), antibodies (seven), recombinant peptides (five) and antisense oligodeoxynucleotides (two). A maximum tolerated dose was set in 43 trials. Fifteen percent of the patients received <75% of the intended RDI in C1, but only 9.1% of them presented protocol-defined DLTs. After C1, 16-19% of patients received <75% of the intended RDI. A similar proportion of G ⩾ 3 toxicities was recorded in C1 and after C1 (936 and 1087 toxicities, respectively), with the first G⩾3 toxicity occurring after C1 in 18.6% of patients. Although protocol-defined DLT period is traditionally limited to C1, almost 20% of patients present significant reductions in RDI at any time in phase 1 trials of MTAs. Recommended phase 2 dose assessment should incorporate all available information from any cycle (notably lower grade toxicities leading to such RDI decrease), and be based on achieving >75% RDI. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. TLR stimulation initiates a CD39-based autoregulatory mechanism that limits macrophage inflammatory responses

    PubMed Central

    Cohen, Heather B.; Briggs, Katharine T.; Marino, John P.; Ravid, Katya; Robson, Simon C.

    2013-01-01

    Sepsis is a highly fatal disease caused by an initial hyperinflammatory response followed by a state of profound immunosuppression. Although it is well appreciated that the initial production of proinflammatory cytokines by macrophages accompanies the onset of sepsis, it remains unclear what causes the transition to an immunosuppressive state. In this study, we reveal that macrophages themselves are key regulators of this transition and that the surface enzyme CD39 plays a critical role in self-limiting the activation process. We demonstrate that Toll-like receptor (TLR)-stimulated macrophages modulate their activation state by increasing the synthesis and secretion of adenosine triphosphate (ATP). This endogenous ATP is paradoxically immunosuppressive due to its rapid catabolism into adenosine by CD39. Macrophages lacking CD39 are unable to transition to a regulatory state and consequently continue to produce inflammatory cytokines. The importance of this transition is demonstrated in a mouse model of sepsis, where small numbers of CD39-deficient macrophages were sufficient to induce lethal endotoxic shock. Thus, these data implicate CD39 as a key “molecular switch” that allows macrophages to self-limit their activation state. We propose that therapeutics targeting the release and hydrolysis of ATP by macrophages may represent new ways to treat inflammatory diseases. PMID:23908469

  2. Twistacene contained molecule for optical nonlinearity: Excited-state based negative refraction and optical limiting

    NASA Astrophysics Data System (ADS)

    Wu, Xingzhi; Xiao, Jinchong; Sun, Ru; Jia, Jidong; Yang, Junyi; Ao, Guanghong; Shi, Guang; Wang, Yuxiao; Zhang, Xueru; Song, Yinglin

    2018-06-01

    Spindle-type molecules containing twisted acenes (PyBTA-1 &PyBTA-2) are designed, synthesized characterized. Picosecond Z-scan experiments under 532 nm show reverse saturable absorption and negative nonlinear refraction, indicating large third-order optical nonlinearity in PyBTA-1. The mechanism of the optical nonlinearity is investigated and the results show that the nonlinear absorption and refraction in PyBTA-1 originates from a charge transfer (CT) state. Furthermore, relatively long lifetime and absorptive cross section of the CT state are measured. Based on the excited state absorption in PyBTA-1, strong optical limiting with ∼0.3 J/cm2 thresholds are obtained when excited by picoseconds and nanoseconds pulses. The findings on nonlinear optics suggest PyBTA-1 a promising material of all optical modulation and laser protection, which enrich the potential applications of these spindle-type molecules. Comparing to the previously reported spindle-type molecules with analogous structures, the introduction of ICT in PyBTA-1 &PyBTA-2 dramatically decreases the two-photon absorption while enhances the nonlinear refraction. The results could be used to selectively tailor the optical nonlinearity in such kind of compounds.

  3. Systematic continuum-discretized coupled-channels calculations of total fusion for 6Li with targets 28Si, 59Co, 96Zr, 198Pt, and 209Bi: Effect of resonance states

    NASA Astrophysics Data System (ADS)

    Gómez Camacho, A.; Wang, Bing; Zhang, H. Q.

    2018-05-01

    Continuum discretized coupled-channel (CDCC) calculations of total fusion cross sections for reactions induced by the weakly bound nucleus 6Li with targets 28Si, 59Co, 96Zr, 198Pt, and 209Bi at energies around the Coulomb barrier are presented. In the cluster structure frame of 6Li→α +d , short-range absorption potentials are considered for the interactions between the α and d fragments with the targets. The effect of resonance (l =2 , Jπ=3+,2+,1+ ) and nonresonance states of 6Li on fusion is studied by using two approaches: (1) by omitting the resonance states from the full discretized CDCC breakup space and (2) by considering only the resonance subspace. A systematic analysis of the effect on fusion from resonance breakup couplings is carried out from light to heavy mass targets. Among other things, it is found that resonance breakup states produce strong repulsive polarization potentials that lead to fusion suppression. Couplings from nonresonance states give place to weak repulsive potentials at high energies; however, these become attractive for the heavier targets at low energies.

  4. Kalman filter data assimilation: targeting observations and parameter estimation.

    PubMed

    Bellsky, Thomas; Kostelich, Eric J; Mahalov, Alex

    2014-06-01

    This paper studies the effect of targeted observations on state and parameter estimates determined with Kalman filter data assimilation (DA) techniques. We first provide an analytical result demonstrating that targeting observations within the Kalman filter for a linear model can significantly reduce state estimation error as opposed to fixed or randomly located observations. We next conduct observing system simulation experiments for a chaotic model of meteorological interest, where we demonstrate that the local ensemble transform Kalman filter (LETKF) with targeted observations based on largest ensemble variance is skillful in providing more accurate state estimates than the LETKF with randomly located observations. Additionally, we find that a hybrid ensemble Kalman filter parameter estimation method accurately updates model parameters within the targeted observation context to further improve state estimation.

  5. Petri net-based prediction of therapeutic targets that recover abnormally phosphorylated proteins in muscle atrophy.

    PubMed

    Jung, Jinmyung; Kwon, Mijin; Bae, Sunghwa; Yim, Soorin; Lee, Doheon

    2018-03-05

    Muscle atrophy, an involuntary loss of muscle mass, is involved in various diseases and sometimes leads to mortality. However, therapeutics for muscle atrophy thus far have had limited effects. Here, we present a new approach for therapeutic target prediction using Petri net simulation of the status of phosphorylation, with a reasonable assumption that the recovery of abnormally phosphorylated proteins can be a treatment for muscle atrophy. The Petri net model was employed to simulate phosphorylation status in three states, i.e. reference, atrophic and each gene-inhibited state based on the myocyte-specific phosphorylation network. Here, we newly devised a phosphorylation specific Petri net that involves two types of transitions (phosphorylation or de-phosphorylation) and two types of places (activation with or without phosphorylation). Before predicting therapeutic targets, the simulation results in reference and atrophic states were validated by Western blotting experiments detecting five marker proteins, i.e. RELA, SMAD2, SMAD3, FOXO1 and FOXO3. Finally, we determined 37 potential therapeutic targets whose inhibition recovers the phosphorylation status from an atrophic state as indicated by the five validated marker proteins. In the evaluation, we confirmed that the 37 potential targets were enriched for muscle atrophy-related terms such as actin and muscle contraction processes, and they were also significantly overlapping with the genes associated with muscle atrophy reported in the Comparative Toxicogenomics Database (p-value < 0.05). Furthermore, we noticed that they included several proteins that could not be characterized by the shortest path analysis. The three potential targets, i.e. BMPR1B, ROCK, and LEPR, were manually validated with the literature. In this study, we suggest a new approach to predict potential therapeutic targets of muscle atrophy with an analysis of phosphorylation status simulated by Petri net. We generated a list of the potential

  6. Direction information in multiple object tracking is limited by a graded resource.

    PubMed

    Horowitz, Todd S; Cohen, Michael A

    2010-10-01

    Is multiple object tracking (MOT) limited by a fixed set of structures (slots), a limited but divisible resource, or both? Here, we answer this question by measuring the precision of the direction representation for tracked targets. The signature of a limited resource is a decrease in precision as the square root of the tracking load. The signature of fixed slots is a fixed precision. Hybrid models predict a rapid decrease to asymptotic precision. In two experiments, observers tracked moving disks and reported target motion direction by adjusting a probe arrow. We derived the precision of representation of correctly tracked targets using a mixture distribution analysis. Precision declined with target load according to the square-root law up to six targets. This finding is inconsistent with both pure and hybrid slot models. Instead, directional information in MOT appears to be limited by a continuously divisible resource.

  7. Naive-like Conversion Overcomes the Limited Differentiation Capacity of Induced Pluripotent Stem Cells*

    PubMed Central

    Honda, Arata; Hatori, Masanori; Hirose, Michiko; Honda, Chizumi; Izu, Haruna; Inoue, Kimiko; Hirasawa, Ryutaro; Matoba, Shogo; Togayachi, Sumie; Miyoshi, Hiroyuki; Ogura, Atsuo

    2013-01-01

    Although induced pluripotent stem (iPS) cells are indistinguishable from ES cells in their expression of pluripotent markers, their differentiation into targeted cells is often limited. Here, we examined whether the limited capacity of iPS cells to differentiate into neural lineage cells could be mitigated by improving their base-line level of pluripotency, i.e. by converting them into the so-called “naive” state. In this study, we used rabbit iPS and ES cells because of the easy availability of both cell types and their typical primed state characters. Repeated passages of the iPS cells permitted their differentiation into early neural cell types (neural stem cells, neurons, and glial astrocytes) with efficiencies similar to ES cells. However, unlike ES cells, their ability to differentiate later into neural cells (oligodendrocytes) was severely compromised. In contrast, after these iPS cells had been converted to a naive-like state, they readily differentiated into mature oligodendrocytes developing characteristic ramified branches, which could not be attained even with ES cells. These results suggest that the naive-like conversion of iPS cells might endow them with a higher differentiation capacity. PMID:23880763

  8. A Retrospective Analysis on the Occurrence of Arsenic in Ground-Water Resources of the United States and Limitations in Drinking-Water-Supply Characterizations

    USGS Publications Warehouse

    Focazio, Michael J.; Welch, Alan H.; Watkins, Sharon A.; Helsel, Dennis R.; Horn, Marilee A.

    2000-01-01

    ,000 and less than 10,000 people) in the United States. The arsenic data were summarized for the selected counties by associating the arsenic concentrations measured in the ground-water resource with the numbers and sizes of public water-supply systems using ground water in those counties. Targeted arsenic concentrations of 1, 2, 5, 10, 20, and 50 ug/L were exceeded in the ground-water resource associated with 36, 25, 14, 8, 3, and 1 percent respectively of all public water-supply systems accounted for in the analysis.Contributions to uncertainty such as changes in sampling methods and changes in laboratory reporting appear to be less important to the national occurrence estimates than other factors such as temporal variability in arsenic concentrations at a given well, the types of wells sampled, and density and types of sampling locations. In addition, no attempt was made to quantify arsenic concentrations in relation to depth within aquifers. With these qualifications, the USGS data represent the ground-water resource in general and are not restricted to wells currently used for public drinking-water sources. In this way, the broad spatial extent, large number of water samples, and low detection limits used for the USGS data provide a unique source of information to determine where targeted concentrations of arsenic are likely to occur in the ground-water resources within much of the United States.These results indicate USGS data can be effectively used to augment national estimates of arsenic occurrence in the nation's ground-water resources if limitations are recognized. Existing estimates of the occurrence of arsenic in ground water that are used as a source of drinking water can be supplemented with the USGS arsenic concentration data when associated with the public water-supply data base. One such supplementary application is the additional insight gained by establishing relations between arsenic concentration data in the ground-water resource and small public wat

  9. Housing growth in and near United States protected areas limits their conservation value

    PubMed Central

    Radeloff, Volker C.; Stewart, Susan I.; Hawbaker, Todd J.; Gimmi, Urs; Pidgeon, Anna M.; Flather, Curtis H.; Hammer, Roger B.; Helmers, David P.

    2009-01-01

    Protected areas are crucial for biodiversity conservation because they provide safe havens for species threatened by land-use change and resulting habitat loss. However, protected areas are only effective when they stop habitat loss within their boundaries, and are connected via corridors to other wild areas. The effectiveness of protected areas is threatened by development; however, the extent of this threat is unknown. We compiled spatially-detailed housing growth data from 1940 to 2030, and quantified growth for each wilderness area, national park, and national forest in the conterminous United States. Our findings show that housing development in the United States may severely limit the ability of protected areas to function as a modern “Noah’s Ark.” Between 1940 and 2000, 28 million housing units were built within 50 km of protected areas, and 940,000 were built within national forests. Housing growth rates during the 1990s within 1 km of protected areas (20% per decade) outpaced the national average (13%). If long-term trends continue, another 17 million housing units will be built within 50 km of protected areas by 2030 (1 million within 1 km), greatly diminishing their conservation value. US protected areas are increasingly isolated, housing development in their surroundings is decreasing their effective size, and national forests are even threatened by habitat loss within their administrative boundaries. Protected areas in the United States are thus threatened similarly to those in developing countries. However, housing growth poses the main threat to protected areas in the United States whereas deforestation is the main threat in developing countries. PMID:20080780

  10. Limited English Proficient Individuals in the United States: Number, Share, Growth, and Linguistic Diversity. LEP Data Brief

    ERIC Educational Resources Information Center

    Pandya, Chhandasi; McHugh, Margie; Batalova, Jeanne

    2011-01-01

    The number of US residents who are deemed to be Limited English Proficient (LEP) has increased substantially in recent decades, consistent with the growth in the US foreign-born population. While many LEP individuals are still attracted to the historic immigrant-destination states of California, Texas, New York, New Jersey, Florida, and Illinois,…

  11. Targeted surveillance for highly pathogenic avian influenza in migratory waterfowl across the conterminous United States: chapter 12

    USGS Publications Warehouse

    Farnsworth, Matthew L.; Kendall, William L.; Doherty, Paul F.; Miller, Ryan S.; White, Gary C.; Nichols, James D.; Burnham, Kenneth P.; Franklin, Alan B.; Majumdar, S.; Brenner, F.J.; Huffman, J.E.; McLean, R.G.; Panah, A.I.; Pietrobon, P.J.; Keeler, S.P.; Shive, S.

    2011-01-01

    Introduction of Asian strain H5N1 Highly Pathogenic avian influenca via waterfowl migration is one potential route of entry into the United States. In conjunction with state, tribe, and laboratory partners, the United States Department of Agriculture collected and tested 124,603 wild bird samples in 2006 as part of a national surveillance effort. A sampling plan was devised to increase the probability fo detecting Asian strain H5N1 at a national scale. Band recovery data were used to identify and prioritize sampling for wild migratory waterfowl, resulting in spatially targeted sampling recommendations focused on reads with high numbers of recoveries. We also compared the spatial and temporal distribution of the 2006 cloacal and fecal waterfowl sampling effort to the bird banding recovery data and found concordance between the two .Finally, we present improvements made to the 2007 fecal sampling component of the surveillance plan and suggest further improvements for future sampling.

  12. Complementary Approaches to Existing Target Based Drug Discovery for Identifying Novel Drug Targets.

    PubMed

    Vasaikar, Suhas; Bhatia, Pooja; Bhatia, Partap G; Chu Yaiw, Koon

    2016-11-21

    In the past decade, it was observed that the relationship between the emerging New Molecular Entities and the quantum of R&D investment has not been favorable. There might be numerous reasons but few studies stress the introduction of target based drug discovery approach as one of the factors. Although a number of drugs have been developed with an emphasis on a single protein target, yet identification of valid target is complex. The approach focuses on an in vitro single target, which overlooks the complexity of cell and makes process of validation drug targets uncertain. Thus, it is imperative to search for alternatives rather than looking at success stories of target-based drug discovery. It would be beneficial if the drugs were developed to target multiple components. New approaches like reverse engineering and translational research need to take into account both system and target-based approach. This review evaluates the strengths and limitations of known drug discovery approaches and proposes alternative approaches for increasing efficiency against treatment.

  13. Kalman filter data assimilation: Targeting observations and parameter estimation

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

    Bellsky, Thomas, E-mail: bellskyt@asu.edu; Kostelich, Eric J.; Mahalov, Alex

    2014-06-15

    This paper studies the effect of targeted observations on state and parameter estimates determined with Kalman filter data assimilation (DA) techniques. We first provide an analytical result demonstrating that targeting observations within the Kalman filter for a linear model can significantly reduce state estimation error as opposed to fixed or randomly located observations. We next conduct observing system simulation experiments for a chaotic model of meteorological interest, where we demonstrate that the local ensemble transform Kalman filter (LETKF) with targeted observations based on largest ensemble variance is skillful in providing more accurate state estimates than the LETKF with randomly locatedmore » observations. Additionally, we find that a hybrid ensemble Kalman filter parameter estimation method accurately updates model parameters within the targeted observation context to further improve state estimation.« less

  14. State-dependent compound inhibition of Nav1.2 sodium channels using the FLIPR Vm dye: on-target and off-target effects of diverse pharmacological agents.

    PubMed

    Benjamin, Elfrida R; Pruthi, Farhana; Olanrewaju, Shakira; Ilyin, Victor I; Crumley, Gregg; Kutlina, Elena; Valenzano, Kenneth J; Woodward, Richard M

    2006-02-01

    Voltage-gated sodium channels (NaChs) are relevant targets for pain, epilepsy, and a variety of neurological and cardiac disorders. Traditionally, it has been difficult to develop structure-activity relationships for NaCh inhibitors due to rapid channel kinetics and state-dependent compound interactions. Membrane potential (Vm) dyes in conjunction with a high-throughput fluorescence imaging plate reader (FLIPR) offer a satisfactory 1st-tier solution. Thus, the authors have developed a FLIPR Vm assay of rat Nav1.2 NaCh. Channels were opened by addition of veratridine, and Vm dye responses were measured. The IC50 values from various structural classes of compounds were compared to the resting state binding constant (Kr)and inactivated state binding constant (Ki)obtained using patch-clamp electrophysiology (EP). The FLIPR values correlated with Ki but not Kr. FLIPRIC50 values fell within 0.1-to 1.5-fold of EP Ki values, indicating that the assay generally reports use-dependent inhibition rather than resting state block. The Library of Pharmacologically Active Compounds (LOPAC, Sigma) was screened. Confirmed hits arose from diverse classes such as dopamine receptor antagonists, serotonin transport inhibitors, and kinase inhibitors. These data suggest that NaCh inhibition is inherent in a diverse set of biologically active molecules and may warrant counterscreening NaChs to avoid unwanted secondary pharmacology.

  15. The Legal Limits of Targeting the Cyber Capabilities of a Neutral State

    DTIC Science & Technology

    2015-10-01

    power-grid off-line for weeks, pipelines unable to move gas and oil, trains sidelined, ACSC/Williams, Ja Rai A./AY16 10 airlines grounded, banks...Graduation Requirements for the Degree of MASTER OF OPERATIONAL ARTS AND SCIENCES Advisor: Wing Commander Graem Corfield, RAF Maxwell Air Force...Base, Alabama October 2015 DISTRIBUTION A. Approved for public release: distribution unlimited. ACSC/Williams, Ja Rai A./AY16 2 Disclaimer

  16. Advances in targeted proteomics and applications to biomedical research

    PubMed Central

    Shi, Tujin; Song, Ehwang; Nie, Song; Rodland, Karin D.; Liu, Tao; Qian, Wei-Jun; Smith, Richard D.

    2016-01-01

    Targeted proteomics technique has emerged as a powerful protein quantification tool in systems biology, biomedical research, and increasing for clinical applications. The most widely used targeted proteomics approach, selected reaction monitoring (SRM), also known as multiple reaction monitoring (MRM), can be used for quantification of cellular signaling networks and preclinical verification of candidate protein biomarkers. As an extension to our previous review on advances in SRM sensitivity herein we review recent advances in the method and technology for further enhancing SRM sensitivity (from 2012 to present), and highlighting its broad biomedical applications in human bodily fluids, tissue and cell lines. Furthermore, we also review two recently introduced targeted proteomics approaches, parallel reaction monitoring (PRM) and data-independent acquisition (DIA) with targeted data extraction on fast scanning high-resolution accurate-mass (HR/AM) instruments. Such HR/AM targeted quantification with monitoring all target product ions addresses SRM limitations effectively in specificity and multiplexing; whereas when compared to SRM, PRM and DIA are still in the infancy with a limited number of applications. Thus, for HR/AM targeted quantification we focus our discussion on method development, data processing and analysis, and its advantages and limitations in targeted proteomics. Finally, general perspectives on the potential of achieving both high sensitivity and high sample throughput for large-scale quantification of hundreds of target proteins are discussed. PMID:27302376

  17. Allowable carbon emissions lowered by multiple climate targets.

    PubMed

    Steinacher, Marco; Joos, Fortunat; Stocker, Thomas F

    2013-07-11

    Climate targets are designed to inform policies that would limit the magnitude and impacts of climate change caused by anthropogenic emissions of greenhouse gases and other substances. The target that is currently recognized by most world governments places a limit of two degrees Celsius on the global mean warming since preindustrial times. This would require large sustained reductions in carbon dioxide emissions during the twenty-first century and beyond. Such a global temperature target, however, is not sufficient to control many other quantities, such as transient sea level rise, ocean acidification and net primary production on land. Here, using an Earth system model of intermediate complexity (EMIC) in an observation-informed Bayesian approach, we show that allowable carbon emissions are substantially reduced when multiple climate targets are set. We take into account uncertainties in physical and carbon cycle model parameters, radiative efficiencies, climate sensitivity and carbon cycle feedbacks along with a large set of observational constraints. Within this framework, we explore a broad range of economically feasible greenhouse gas scenarios from the integrated assessment community to determine the likelihood of meeting a combination of specific global and regional targets under various assumptions. For any given likelihood of meeting a set of such targets, the allowable cumulative emissions are greatly reduced from those inferred from the temperature target alone. Therefore, temperature targets alone are unable to comprehensively limit the risks from anthropogenic emissions.

  18. Summary of available state ambient stream-water-quality data, 1990-98, and limitations for national assessment

    USGS Publications Warehouse

    Pope, Larry M.; Rosner, Stacy M.; Hoffman, Darren C.; Ziegler, Andrew C.

    2004-01-01

    The investigation described in this report summarized data from State ambient stream-water-quality monitoring sites for 10 water-quality constituents or measurements (suspended solids, fecal coliform bacteria, ammonia as nitrogen, nitrite plus nitrate as nitrogen, total phosphorus, total arsenic, dissolved solids, chloride, sulfate, and pH). These 10 water-quality constituents or measurements commonly are listed nationally as major contributors to degradation of surface water. Water-quality data were limited to that electronically accessible from the U.S. Environmental Protection Agency Storage and Retrieval System (STORET), the U.S. Geological Survey National Water Information System (NWIS), or individual State databases. Forty-two States had ambient stream-water-quality data electronically accessible for some or all of the constituents or measurements summarized during this investigation. Ambient in this report refers to data collected for the purpose of evaluating stream ecosystems in relation to human health, environmental and ecological conditions, and designated uses. Generally, data were from monitoring sites assessed for State 305(b) reports. Comparisons of monitoring data among States are problematic for several reasons, including differences in the basic spatial design of monitoring networks; water-quality constituents for which samples are analyzed; water-quality criteria to which constituent concentrations are compared; quantity and comprehensiveness of water-quality data; sample collection, processing, and handling; analytical methods; temporal variability in sample collection; and quality-assurance practices. Large differences among the States in number of monitoring sites precluded a general assumption that statewide water-quality conditions were represented by data from these sites. Furthermore, data from individual monitoring sites may not represent water-quality conditions at the sites because sampling conditions and protocols are unknown. Because

  19. The Technology Acceptance Model for Resource-Limited Settings (TAM-RLS): A Novel Framework for Mobile Health Interventions Targeted to Low-Literacy End-Users in Resource-Limited Settings.

    PubMed

    Campbell, Jeffrey I; Aturinda, Isaac; Mwesigwa, Evans; Burns, Bridget; Santorino, Data; Haberer, Jessica E; Bangsberg, David R; Holden, Richard J; Ware, Norma C; Siedner, Mark J

    2017-11-01

    Although mobile health (mHealth) technologies have shown promise in improving clinical care in resource-limited settings (RLS), they are infrequently brought to scale. One limitation to the success of many mHealth interventions is inattention to end-user acceptability, which is an important predictor of technology adoption. We conducted in-depth interviews with 43 people living with HIV in rural Uganda who had participated in a clinical trial of a short messaging system (SMS)-based intervention designed to prompt return to clinic after an abnormal laboratory test. Interviews focused on established features of technology acceptance models, including perceived ease of use and perceived usefulness, and included open-ended questions to gain insight into unexplored issues related to the intervention's acceptability. We used conventional (inductive) and direct content analysis to derive categories describing use behaviors and acceptability. Interviews guided development of a proposed conceptual framework, the technology acceptance model for resource-limited settings (TAM-RLS). This framework incorporates both classic technology acceptance model categories as well as novel factors affecting use in this setting. Participants described how SMS message language, phone characteristics, and experience with similar technologies contributed to the system's ease of use. Perceived usefulness was shaped by the perception that the system led to augmented HIV care services and improved access to social support from family and colleagues. Emergent themes specifically related to mHealth acceptance among PLWH in Uganda included (1) the importance of confidentiality, disclosure, and stigma, and (2) the barriers and facilitators downstream from the intervention that impacted achievement of the system's target outcome. The TAM-RLS is a proposed model of mHealth technology acceptance based upon end-user experiences in rural Uganda. Although the proposed model requires validation, the TAM

  20. Impact of an Australian mass media campaign targeting physical activity in 1998.

    PubMed

    Bauman, A E; Bellew, B; Owen, N; Vita, P

    2001-07-01

    Physical activity is now a public health priority, but there is only limited evidence on the effectiveness of mass-reach campaigns. Paid and unpaid television and print-media advertising, physician mail-outs, and community-level support programs and strategies. A mass-media statewide campaign to promote regular moderate-intensity activity was conducted during February 1998. The target group was adults aged 25 to 60 who were motivated but insufficiently active. Cohort and independent-sample, cross-sectional representative population surveys, before and after the campaign. The intervention was conducted in the state of New South Wales, with the other states of Australia as the comparison region. Telephone survey items on physical activity, media message awareness, physical activity knowledge, self-efficacy, and intentions. Unprompted recall of the activity messages in the campaign state increased substantially from 2.1% to 20.9% (p<0.01), with small changes elsewhere in Australia (1.2% to 2.6%). There were large changes in prompted awareness from 12.9% to 50.7% (p<0.0001), much larger than changes elsewhere (14.1% to 16%, p=0.06). Knowledge of appropriate moderate-intensity activity and physical activity self-efficacy increased significantly and only in the campaign state. Compared to all others, those in the target group who recalled the media message were 2.08 times more likely to increase their activity by at least an hour per week (95% confidence interval = 1.51-2.86). This integrated campaign positively influenced short-term physical activity message recall, knowledge, and behavior of the target population, compared to the population in the region who were not exposed.

  1. Nanomedicines for cancer therapy: state-of-the-art and limitations to pre-clinical studies that hinder future developments

    NASA Astrophysics Data System (ADS)

    Dawidczyk, Charlene; Russell, Luisa; Searson, Peter

    2014-08-01

    The ability to efficiently deliver a drug or gene to a tumor site is dependent on a wide range of factors including circulation time, interactions with the mononuclear phagocyte system, extravasation from circulation at the tumor site, targeting strategy, release from the delivery vehicle, and uptake in cancer cells. Nanotechnology provides the possibility of creating delivery systems where the design constraints are decoupled, allowing new approaches for reducing the unwanted side effects of systemic delivery, increasing tumor accumulation, and improving efficacy. The physico-chemical properties of nanoparticle-based delivery platforms introduce additional complexity associated with pharmacokinetics and tumor accumulation. To assess the impact of nanoparticle-based delivery systems, we first review the design strategies and pharmacokinetics of FDA-approved nanomedicines. Next we review nanomedicines under development, summarizing the range of nanoparticle platforms, strategies for targeting, and pharmacokinetics. We show how the lack of uniformity in preclinical trials prevents systematic comparison and hence limits advances in the field.

  2. Resource targets for advanced underground coal extraction systems

    NASA Technical Reports Server (NTRS)

    Hoag, J. H.; Whipple, D. W.; Habib-Agahi, H.; Lavin, M. L.

    1982-01-01

    Resource targets appropriate for federal sponsorship of research and development of advanced underground coal mining systems are identified. A comprehensive examination of conventional and unconventional coals with particular attention to exceptionally thin and thick seams, steeply dipping beds, and multiple seam geometry was made. The results indicate that the resource of primary importance is flat lying bituminous coal of moderate thickness, under moderate cover, and located within the lower 48 states. Resources of secondary importance are the flat lying multiple seams and thin seams (especially those in Appalachia). Steeply dipping coals, abandoned pillars, and exceptionally thick western coals may be important in some regions of subregions, but the limited tonnage available places them in a position of tertiary importance.

  3. Projectile n distributions following charge transfer of Ar+ and Na+ in a Na Rydberg target

    NASA Astrophysics Data System (ADS)

    MacAdam, K. B.; Gray, L. G.; Rolfes, R. G.

    1990-11-01

    The n distributions produced by charge transfer of Ar+ and Na+ ions in a target of Na(nl) Rydberg atoms were extensively measured at intermediate velocities. The 60-2100-eV ions bombarded a laser-excited atomic-beam target. The projectiles were neutralized by capture into Rydberg states of Ar and Na and were analyzed by field ionization in an inhomogeneous-field detector whose response over states and energies was carefully mapped. The choice of initially prepared Na states, 24d, 25s, 28d, 29s, 33d, and 34s, allowed a comparison of l=0 and >=2 targets at nearly equal binding energies over a range of reduced velocity v~=0.187 to 1.95. Capture populates m sublevels broadly, not merely m~=0. Overlapping contributions from adiabatic and diabatic modes of field ionization were accommodated in the analysis, which used a maximum-entropy-principle parametric form to fit the observed final-state distributions. The peak of the distributions, nmax, shifts upward from a value less than the initial state ni to a value one to three units higher than ni at v~ between 0.7 and 0.9 and ultimately shifts downward below ni as v~ is further increased. The distributions become significantly sharper where the maximum upward shift occurs. Two ratios were defined to express the widths of final-state distributions in relative terms, one measuring the spread of orbital kinetic energy and the other the spread of Bohr-orbit velocity. By these ratios a universal behavior over energies, states, and projectile species is observed, and small differences between l=0 and >=2 targets may be seen. A theoretical understanding of the present results, which span velocities where both molecular and perturbative theories are normally used, will require a quantal formulation that models the free-ranging response that is a hallmark of the high-quantum-number limit.

  4. Reliability analysis of component-level redundant topologies for solid-state fault current limiter

    NASA Astrophysics Data System (ADS)

    Farhadi, Masoud; Abapour, Mehdi; Mohammadi-Ivatloo, Behnam

    2018-04-01

    Experience shows that semiconductor switches in power electronics systems are the most vulnerable components. One of the most common ways to solve this reliability challenge is component-level redundant design. There are four possible configurations for the redundant design in component level. This article presents a comparative reliability analysis between different component-level redundant designs for solid-state fault current limiter. The aim of the proposed analysis is to determine the more reliable component-level redundant configuration. The mean time to failure (MTTF) is used as the reliability parameter. Considering both fault types (open circuit and short circuit), the MTTFs of different configurations are calculated. It is demonstrated that more reliable configuration depends on the junction temperature of the semiconductor switches in the steady state. That junction temperature is a function of (i) ambient temperature, (ii) power loss of the semiconductor switch and (iii) thermal resistance of heat sink. Also, results' sensitivity to each parameter is investigated. The results show that in different conditions, various configurations have higher reliability. The experimental results are presented to clarify the theory and feasibility of the proposed approaches. At last, levelised costs of different configurations are analysed for a fair comparison.

  5. Defined by Limitations

    ERIC Educational Resources Information Center

    Arriola, Sonya; Murphy, Katy

    2010-01-01

    Undocumented students are a population defined by limitations. Their lack of legal residency and any supporting paperwork (e.g., Social Security number, government issued identification) renders them essentially invisible to the American and state governments. They cannot legally work. In many states, they cannot legally drive. After the age of…

  6. Drug Target Validation Methods in Malaria - Protein Interference Assay (PIA) as a Tool for Highly Specific Drug Target Validation.

    PubMed

    Meissner, Kamila A; Lunev, Sergey; Wang, Yuan-Ze; Linzke, Marleen; de Assis Batista, Fernando; Wrenger, Carsten; Groves, Matthew R

    2017-01-01

    The validation of drug targets in malaria and other human diseases remains a highly difficult and laborious process. In the vast majority of cases, highly specific small molecule tools to inhibit a proteins function in vivo are simply not available. Additionally, the use of genetic tools in the analysis of malarial pathways is challenging. These issues result in difficulties in specifically modulating a hypothetical drug target's function in vivo. The current "toolbox" of various methods and techniques to identify a protein's function in vivo remains very limited and there is a pressing need for expansion. New approaches are urgently required to support target validation in the drug discovery process. Oligomerisation is the natural assembly of multiple copies of a single protein into one object and this self-assembly is present in more than half of all protein structures. Thus, oligomerisation plays a central role in the generation of functional biomolecules. A key feature of oligomerisation is that the oligomeric interfaces between the individual parts of the final assembly are highly specific. However, these interfaces have not yet been systematically explored or exploited to dissect biochemical pathways in vivo. This mini review will describe the current state of the antimalarial toolset as well as the potentially druggable malarial pathways. A specific focus is drawn to the initial efforts to exploit oligomerisation surfaces in drug target validation. As alternative to the conventional methods, Protein Interference Assay (PIA) can be used for specific distortion of the target protein function and pathway assessment in vivo. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  7. Effects of neonicotinoids and fipronil on non-target invertebrates.

    PubMed

    Pisa, L W; Amaral-Rogers, V; Belzunces, L P; Bonmatin, J M; Downs, C A; Goulson, D; Kreutzweiser, D P; Krupke, C; Liess, M; McField, M; Morrissey, C A; Noome, D A; Settele, J; Simon-Delso, N; Stark, J D; Van der Sluijs, J P; Van Dyck, H; Wiemers, M

    2015-01-01

    We assessed the state of knowledge regarding the effects of large-scale pollution with neonicotinoid insecticides and fipronil on non-target invertebrate species of terrestrial, freshwater and marine environments. A large section of the assessment is dedicated to the state of knowledge on sublethal effects on honeybees (Apis mellifera) because this important pollinator is the most studied non-target invertebrate species. Lepidoptera (butterflies and moths), Lumbricidae (earthworms), Apoidae sensu lato (bumblebees, solitary bees) and the section "other invertebrates" review available studies on the other terrestrial species. The sections on freshwater and marine species are rather short as little is known so far about the impact of neonicotinoid insecticides and fipronil on the diverse invertebrate fauna of these widely exposed habitats. For terrestrial and aquatic invertebrate species, the known effects of neonicotinoid pesticides and fipronil are described ranging from organismal toxicology and behavioural effects to population-level effects. For earthworms, freshwater and marine species, the relation of findings to regulatory risk assessment is described. Neonicotinoid insecticides exhibit very high toxicity to a wide range of invertebrates, particularly insects, and field-realistic exposure is likely to result in both lethal and a broad range of important sublethal impacts. There is a major knowledge gap regarding impacts on the grand majority of invertebrates, many of which perform essential roles enabling healthy ecosystem functioning. The data on the few non-target species on which field tests have been performed are limited by major flaws in the outdated test protocols. Despite large knowledge gaps and uncertainties, enough knowledge exists to conclude that existing levels of pollution with neonicotinoids and fipronil resulting from presently authorized uses frequently exceed the lowest observed adverse effect concentrations and are thus likely to have large

  8. Online compensation for target motion with scanned particle beams: simulation environment.

    PubMed

    Li, Qiang; Groezinger, Sven Oliver; Haberer, Thomas; Rietzel, Eike; Kraft, Gerhard

    2004-07-21

    Target motion is one of the major limitations of each high precision radiation therapy. Using advanced active beam delivery techniques, such as the magnetic raster scanning system for particle irradiation, the interplay between time-dependent beam and target position heavily distorts the applied dose distribution. This paper presents a simulation environment in which the time-dependent effect of target motion on heavy-ion irradiation can be calculated with dynamically scanned ion beams. In an extension of the existing treatment planning software for ion irradiation of static targets (TRiP) at GSI, the expected dose distribution is calculated as the sum of several sub-distributions for single target motion states. To investigate active compensation for target motion by adapting the position of the therapeutic beam during irradiation, the planned beam positions can be altered during the calculation. Applying realistic parameters to the planned motion-compensation methods at GSI, the effect of target motion on the expected dose uniformity can be simulated for different target configurations and motion conditions. For the dynamic dose calculation, experimentally measured profiles of the beam extraction in time were used. Initial simulations show the feasibility and consistency of an active motion compensation with the magnetic scanning system and reveal some strategies to improve the dose homogeneity inside the moving target. The simulation environment presented here provides an effective means for evaluating the dose distribution for a moving target volume with and without motion compensation. It contributes a substantial basis for the experimental research on the irradiation of moving target volumes with scanned ion beams at GSI which will be presented in upcoming papers.

  9. 50 CFR 622.278 - Commercial trip limits.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... ADMINISTRATION, DEPARTMENT OF COMMERCE FISHERIES OF THE CARIBBEAN, GULF OF MEXICO, AND SOUTH ATLANTIC Dolphin and Wahoo Fishery Off the Atlantic States § 622.278 Commercial trip limits. Commercial trip limits are... in this section with any trip or possession limit applicable to state waters. A species subject to a...

  10. 50 CFR 622.278 - Commercial trip limits.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... ADMINISTRATION, DEPARTMENT OF COMMERCE FISHERIES OF THE CARIBBEAN, GULF OF MEXICO, AND SOUTH ATLANTIC Dolphin and Wahoo Fishery Off the Atlantic States § 622.278 Commercial trip limits. Commercial trip limits are... in this section with any trip or possession limit applicable to state waters. A species subject to a...

  11. Constrained target controllability of complex networks

    NASA Astrophysics Data System (ADS)

    Guo, Wei-Feng; Zhang, Shao-Wu; Wei, Ze-Gang; Zeng, Tao; Liu, Fei; Zhang, Jingsong; Wu, Fang-Xiang; Chen, Luonan

    2017-06-01

    It is of great theoretical interest and practical significance to study how to control a system by applying perturbations to only a few driver nodes. Recently, a hot topic of modern network researches is how to determine driver nodes that allow the control of an entire network. However, in practice, to control a complex network, especially a biological network, one may know not only the set of nodes which need to be controlled (i.e. target nodes), but also the set of nodes to which only control signals can be applied (i.e. constrained control nodes). Compared to the general concept of controllability, we introduce the concept of constrained target controllability (CTC) of complex networks, which concerns the ability to drive any state of target nodes to their desirable state by applying control signals to the driver nodes from the set of constrained control nodes. To efficiently investigate the CTC of complex networks, we further design a novel graph-theoretic algorithm called CTCA to estimate the ability of a given network to control targets by choosing driver nodes from the set of constrained control nodes. We extensively evaluate the CTC of numerous real complex networks. The results indicate that biological networks with a higher average degree are easier to control than biological networks with a lower average degree, while electronic networks with a lower average degree are easier to control than web networks with a higher average degree. We also show that our CTCA can more efficiently produce driver nodes for target-controlling the networks than existing state-of-the-art methods. Moreover, we use our CTCA to analyze two expert-curated bio-molecular networks and compare to other state-of-the-art methods. The results illustrate that our CTCA can efficiently identify proven drug targets and new potentials, according to the constrained controllability of those biological networks.

  12. Vital Signs: Prevalence of Doctor-Diagnosed Arthritis and Arthritis-Attributable Activity Limitation - United States, 2013-2015.

    PubMed

    Barbour, Kamil E; Helmick, Charles G; Boring, Michael; Brady, Teresa J

    2017-03-10

    In the United States, doctor-diagnosed arthritis is a common and disabling chronic condition. Arthritis can lead to severe joint pain and poor physical function, and it can negatively affect quality of life. CDC analyzed 2013-2015 data from the National Health Interview Survey, an annual, nationally representative, in-person interview survey of the health status and behaviors of the noninstitutionalized civilian U.S. adult population, to update previous prevalence estimates of arthritis and arthritis-attributable activity limitations. On average, during 2013-2015, 54.4 million (22.7%) adults had doctor-diagnosed arthritis, and 23.7 million (43.5% of those with arthritis) had arthritis-attributable activity limitations (an age-adjusted increase of approximately 20% in the proportion of adults with arthritis reporting activity limitations since 2002 [p-trend <0.001]). Among adults with heart disease, diabetes, and obesity, the prevalences of doctor-diagnosed arthritis were 49.3%, 47.1%, and 30.6%, respectively; the prevalences of arthritis-attributable activity limitations among adults with these conditions and arthritis were 54.5% (heart disease), 54.0% (diabetes), and 49.0% (obesity). The prevalence of arthritis is high, particularly among adults with comorbid conditions, such as heart disease, diabetes, and obesity. Furthermore, the prevalence of arthritis-attributable activity limitations is high and increasing over time. Approximately half of adults with arthritis and heart disease, arthritis and diabetes, or arthritis and obesity are limited by their arthritis. Greater use of evidence-based physical activity and self-management education interventions can reduce pain and improve function and quality of life for adults with arthritis and also for adults with other chronic conditions who might be limited by their arthritis.

  13. A preliminary assessment of the impact of lowering the illegal per se limit to 0.08 in five states

    DOT National Transportation Integrated Search

    1994-12-01

    Author's abstract: This report contains the results of a preliminary assessment of the impact of lowering the illegal blood alcohol concentration (BAC) per se limit to 0.08 in five states (California, Maine, Oregon, Utah, and Vermont). The report pro...

  14. Treatment planning with intensity modulated particle therapy for multiple targets in stage IV non-small cell lung cancer

    NASA Astrophysics Data System (ADS)

    Anderle, Kristjan; Stroom, Joep; Vieira, Sandra; Pimentel, Nuno; Greco, Carlo; Durante, Marco; Graeff, Christian

    2018-01-01

    Intensity modulated particle therapy (IMPT) can produce highly conformal plans, but is limited in advanced lung cancer patients with multiple lesions due to motion and planning complexity. A 4D IMPT optimization including all motion states was expanded to include multiple targets, where each target (isocenter) is designated to specific field(s). Furthermore, to achieve stereotactic treatment planning objectives, target and OAR weights plus objective doses were automatically iteratively adapted. Finally, 4D doses were calculated for different motion scenarios. The results from our algorithm were compared to clinical stereotactic body radiation treatment (SBRT) plans. The study included eight patients with 24 lesions in total. Intended dose regimen for SBRT was 24 Gy in one fraction, but lower fractionated doses had to be delivered in three cases due to OAR constraints or failed plan quality assurance. The resulting IMPT treatment plans had no significant difference in target coverage compared to SBRT treatment plans. Average maximum point dose and dose to specific volume in OARs were on average 65% and 22% smaller with IMPT. IMPT could also deliver 24 Gy in one fraction in a patient where SBRT was limited due to the OAR vicinity. The developed algorithm shows the potential of IMPT in treatment of multiple moving targets in a complex geometry.

  15. Epidemiology of Hepatitis C Virus in Pennsylvania State Prisons, 2004–2012: Limitations of 1945–1965 Birth Cohort Screening in Correctional Settings

    PubMed Central

    Mahowald, Madeline K.; Scharff, Nicholas; Flanigan, Timothy P.; Beckwith, Curt G.; Zaller, Nickolas D.

    2014-01-01

    Objectives. We described hepatitis C virus antibody (anti-HCV) prevalence in a state prison system and retrospectively evaluated the case-finding performance of targeted testing of the 1945 to 1965 birth cohort in this population. Methods. We used observational data from universal testing of Pennsylvania state prison entrants (June 2004–December 2012) to determine anti-HCV prevalence by birth cohort. We compared anti-HCV prevalence and the burden of anti-HCV in the 1945 to 1965 birth cohort with that in all other birth years. Results. Anti-HCV prevalence among 101 727 adults entering prison was 18.1%. Prevalence was highest among those born from 1945 to 1965, but most anti-HCV cases were in people born after 1965. Targeted testing of the 1945 to 1965 birth cohort would have identified a decreasing proportion of cases with time. Conclusions. HCV is endemic in correctional populations. Targeted testing of the 1945 to 1965 birth cohort would produce a high yield of positive test results but would identify only a minority of cases. We recommend universal anti-HCV screening in correctional settings to allow for maximum case identification, secondary prevention, and treatment of affected prisoners. PMID:24825235

  16. Advances in targeted proteomics and applications to biomedical research

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

    Shi, Tujin; Song, Ehwang; Nie, Song

    Targeted proteomics technique has emerged as a powerful protein quantification tool in systems biology, biomedical research, and increasing for clinical applications. The most widely used targeted proteomics approach, selected reaction monitoring (SRM), also known as multiple reaction monitoring (MRM), can be used for quantification of cellular signaling networks and preclinical verification of candidate protein biomarkers. As an extension to our previous review on advances in SRM sensitivity (Shi et al., Proteomics, 12, 1074–1092, 2012) herein we review recent advances in the method and technology for further enhancing SRM sensitivity (from 2012 to present), and highlighting its broad biomedical applications inmore » human bodily fluids, tissue and cell lines. Furthermore, we also review two recently introduced targeted proteomics approaches, parallel reaction monitoring (PRM) and data-independent acquisition (DIA) with targeted data extraction on fast scanning high-resolution accurate-mass (HR/AM) instruments. Such HR/AM targeted quantification with monitoring all target product ions addresses SRM limitations effectively in specificity and multiplexing; whereas when compared to SRM, PRM and DIA are still in the infancy with a limited number of applications. Thus, for HR/AM targeted quantification we focus our discussion on method development, data processing and analysis, and its advantages and limitations in targeted proteomics. Finally, general perspectives on the potential of achieving both high sensitivity and high sample throughput for large-scale quantification of hundreds of target proteins are discussed.« less

  17. Targeting the RAS oncogene

    PubMed Central

    Takashima, Asami

    2013-01-01

    Introduction The Ras proteins (K-Ras, N-Ras, H-Ras) are GTPases that function as molecular switches for a variety of critical cellular activities and their function is tightly and temporally regulated in normal cells. Oncogenic mutations in the RAS genes, which create constitutively-active Ras proteins, can result in uncontrolled proliferation or survival in tumor cells. Areas covered The paper discusses three therapeutic approaches targeting the Ras pathway in cancer: 1) Ras itself, 2) Ras downstream pathways, and 3) synthetic lethality. The most adopted approach is targeting Ras downstream signaling, and specifically the PI3K-AKT-mTOR and Raf-MEK pathways, as they are frequently major oncogenic drivers in cancers with high Ras signaling. Although direct targeting of Ras has not been successful clinically, newer approaches being investigated in preclinical studies, such as RNA interference-based and synthetic lethal approaches, promise great potential for clinical application. Expert opinion The challenges of current and emerging therapeutics include the lack of “tumor specificity” and their limitation to those cancers which are “dependent” upon aberrant Ras signaling for survival. While the newer approaches have the potential to overcome these limitations, they also highlight the importance of robust preclinical studies and bidirectional translational research for successful clinical development of Ras-related targeted therapies. PMID:23360111

  18. Inflammation as target in cancer therapy.

    PubMed

    Marelli, Giulia; Sica, Antonio; Vannucci, Luca; Allavena, Paola

    2017-08-01

    Cells of the innate immunity infiltrating tumour tissues promote, rather than halt, cancer cell proliferation and distant spreading. Tumour-Associated Macrophages (TAMs) are abundantly present in the tumour milieu and here trigger and perpetrate a state of chronic inflammation which ultimately supports disease development and contributes to an immune-suppressive environment. Therapeutic strategies to limit inflammatory cells and their products have been successful in pre-clinical tumour models. Early clinical trials with specific cytokine and chemokine inhibitors, or with strategies designed to target TAMs, are on their way in different solid malignancies. Partial clinical responses and stabilization of diseases were observed in some patients, in the absence of significant toxicity. These encouraging results open new perspectives of combination treatments aimed at reducing cancer-promoting inflammation to maximize the anti-tumour efficacy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Predicting Drug-Target Interactions With Multi-Information Fusion.

    PubMed

    Peng, Lihong; Liao, Bo; Zhu, Wen; Li, Zejun; Li, Keqin

    2017-03-01

    Identifying potential associations between drugs and targets is a critical prerequisite for modern drug discovery and repurposing. However, predicting these associations is difficult because of the limitations of existing computational methods. Most models only consider chemical structures and protein sequences, and other models are oversimplified. Moreover, datasets used for analysis contain only true-positive interactions, and experimentally validated negative samples are unavailable. To overcome these limitations, we developed a semi-supervised based learning framework called NormMulInf through collaborative filtering theory by using labeled and unlabeled interaction information. The proposed method initially determines similarity measures, such as similarities among samples and local correlations among the labels of the samples, by integrating biological information. The similarity information is then integrated into a robust principal component analysis model, which is solved using augmented Lagrange multipliers. Experimental results on four classes of drug-target interaction networks suggest that the proposed approach can accurately classify and predict drug-target interactions. Part of the predicted interactions are reported in public databases. The proposed method can also predict possible targets for new drugs and can be used to determine whether atropine may interact with alpha1B- and beta1- adrenergic receptors. Furthermore, the developed technique identifies potential drugs for new targets and can be used to assess whether olanzapine and propiomazine may target 5HT2B. Finally, the proposed method can potentially address limitations on studies of multitarget drugs and multidrug targets.

  20. Orion Exploration Mission Entry Interface Target Line

    NASA Technical Reports Server (NTRS)

    Rea, Jeremy R.

    2016-01-01

    The Orion Multi-Purpose Crew Vehicle is required to return to the continental United States at any time during the month. In addition, it is required to provide a survivable entry from a wide range of trans-lunar abort trajectories. The Entry Interface (EI) state must be targeted to ensure that all requirements are met for all possible return scenarios, even in the event of no communication with the Mission Control Center to provide an updated EI target. The challenge then is to functionalize an EI state constraint manifold that can be used in the on-board targeting algorithm, as well as the ground-based trajectory optimization programs. This paper presents the techniques used to define the EI constraint manifold and to functionalize it as a set of polynomials in several dimensions.

  1. Tunable emission and excited state absorption induced optical limiting in Tb2(MoO4)3: Sm3+/Eu3+ nanophosphors

    NASA Astrophysics Data System (ADS)

    Mani, Kamal P.; Sreekanth, Perumbilavil; Vimal, G.; Biju, P. R.; Unnikrishnan, N. V.; Ittyachen, M. A.; Philip, Reji; Joseph, Cyriac

    2016-12-01

    Photoluminescence properties and optical limiting behavior of pure and Sm3+/Eu3+ doped Tb2(MoO4)3 nanophosphors are investigated. The prepared nanophosphors exhibit excellent emission when excited by UV light. Color-tunable emissions in Tb2-xSmx(MoO4)3 and Tb2-xEux(MoO4)3 are realized by employing different excitation wavelengths or by controlling the doping concentration of Sm3+ and Eu3+. Luminescence quantum yield and CIE chromatic coordinates of the prepared phosphors were also presented. Optical limiting properties of the samples are investigated by open aperture Z-scan technique using 5 ns laser pulses at 532 nm. Numerical fitting of the measured Z-scan data to the relevant nonlinear transmission equations reveals that the nonlinear absorption is arising from strong excited state absorption, along with weak absorption saturation and it is found that the optical nonlinearity of Tb2(MoO4)3 increases with Sm3+/Eu3+doping. Parameters such as saturation fluence, excited state absorption cross section and ground state absorption cross section of the samples have been determined numerically, from which the figure of merit for nonlinear absorption is calculated. The excited state absorption cross-section of the samples is found to be one order of magnitude higher than that of the ground state absorption cross-section, indicating strong reverse saturable absorption. These results indicate that Sm3+/Eu3+ doped Tb2(MoO4)3 nanophosphors are efficient media for UV/n-UV pumped LEDs, and are also potential candidates for designing efficient optical limiting devices for the protection of human eyes and sensitive optical detectors from harmful laser radiation.

  2. Immigration, Statecraft and Public Health: The 1920 Aliens Order, Medical Examinations and the Limitations of the State in England

    PubMed Central

    Taylor, Becky

    2016-01-01

    This article considers the medical measures of the 1920 Aliens Order barring aliens from Britain. Building on existing local and port public health inspection, the requirement for aliens to be medically inspected before landing significantly expanded the duties of these state agencies and necessitated the creation of a new level of physical infrastructure and administrative machinery. This article closely examines the workings and limitations of alien medical inspection in two of England’s major ports—Liverpool and London—and sheds light on the everyday working of the Act. In doing so it reflects on the ambitions, actions and limitations of the state and so extends research by historians of the nineteenth and early twentieth century on the disputed histories of public health and the complexities of statecraft. Overall it suggests the importance of developing nuanced understandings of the gaps and failures arising from the translation of legislation into practice. PMID:27482146

  3. Lessons from pediatrics residency program directors' experiences with work hour limitations in New York State.

    PubMed

    Samuels, Ronald C; Chi, Grace W; Rauch, Daniel A; Palfrey, Judith S; Shelov, Steven P

    2005-05-01

    To evaluate the impact of residency work hour limitations on pediatrics residency programs in New York State, and to learn lessons that can be used nationally with the implementation of the Accreditation Council of Graduate Medical Education's similar rules. A three-page questionnaire was mailed to all pediatrics residency program directors in New York. The questionnaire assessed methods used to accommodate the work hour limitations and perceptions of the limitations' effects. Twenty-one program directors responded (68%). Only large programs used night floats and night teams to meet work hour requirements. Programs of all sizes and in all settings used cross coverage and sent residents home immediately post call. About half of the programs hired additional nonresident staff, usually nurse practitioners, physician assistants, and/or attendings. The most frequently reported effects were decreases in the amount of time residents spent in inpatient settings, patient continuity in inpatient settings, flexibility of residents' scheduling, and increased logistical work needed to maintain continuity clinic. A summary of advice to other program directors was "be creative" and "be flexible." New York's pediatrics residency programs used a variety of mechanisms to meet work hour restrictions. Smaller programs had fewer methods available to them to meet such restrictions. Although the logistical work needed to maintain continuity clinic increased greatly, continuity and outpatient settings themselves were not greatly affected by work hour limitations. Inpatient settings were more affected and experienced much more in the way of change.

  4. Ground moving target geo-location from monocular camera mounted on a micro air vehicle

    NASA Astrophysics Data System (ADS)

    Guo, Li; Ang, Haisong; Zheng, Xiangming

    2011-08-01

    The usual approaches to unmanned air vehicle(UAV)-to-ground target geo-location impose some severe constraints to the system, such as stationary objects, accurate geo-reference terrain database, or ground plane assumption. Micro air vehicle(MAV) works with characteristics including low altitude flight, limited payload and onboard sensors' low accuracy. According to these characteristics, a method is developed to determine the location of ground moving target which imaged from the air using monocular camera equipped on MAV. This method eliminates the requirements for terrain database (elevation maps) and altimeters that can provide MAV's and target's altitude. Instead, the proposed method only requires MAV flight status provided by its inherent onboard navigation system which includes inertial measurement unit(IMU) and global position system(GPS). The key is to get accurate information on the altitude of the ground moving target. First, Optical flow method extracts background static feature points. Setting a local region around the target in the current image, The features which are on the same plane with the target in this region are extracted, and are retained as aided features. Then, inverse-velocity method calculates the location of these points by integrated with aircraft status. The altitude of object, which is calculated by using position information of these aided features, combining with aircraft status and image coordinates, geo-locate the target. Meanwhile, a framework with Bayesian estimator is employed to eliminate noise caused by camera, IMU and GPS. Firstly, an extended Kalman filter(EKF) provides a simultaneous localization and mapping solution for the estimation of aircraft states and aided features location which defines the moving target local environment. Secondly, an unscented transformation(UT) method determines the estimated mean and covariance of target location from aircraft states and aided features location, and then exports them for the

  5. Identification of SSR and retrotransposon-based molecular markers linked to morphological characters in oily sunfl ower (Helianthus annuus L.) under natural and water-limited states.

    PubMed

    Ali, Soleimani Gezeljeh; Darvishzadeh, Reza; Ebrahimi, Asa; Bihamta, Mohammad Reza

    2018-03-01

    Sunflower is an important source of edible oil. Drought is known as an important factor limiting the growth and productivity of field crops in most parts of the world. Agricultural biotechnology mainly aims at developing crops with higher tolerance to the challenging environmental conditions, such as drought. This study examined a number of morphological characters, along with relative water content (RWC) in 100 inbred sunflower lines. A 10 × 10 simple lattice design with two replications was employed to measure the mentioned parameters under natural and water-limited states during two successive years. In molecular trial, 30 simple sequence repeat (SSR) primer pairs, as well as 14 inter-retrotransposon amplified polymorphism (IRAP) and 14 retrotransposon-microsatellite amplified polymorphism (REMAP) primer combinations were used for DNA fingerprinting of the lines. Most of the examined characters had lower average values under water-limited than natural states. Maximum and minimum reductions were observed in the cases of yield and oil percentage, respectively. The broad-sense heritabilities for all the examined characters were 0.20-0.73 and 0.10-0.34 under natural and water-limited states, respectively. In the studied samples, 8.97% of the 435 possible locus pairs of the SSRs represented significant linkage disequilibrium (LD) levels. In the association analysis using SSR markers, 22 and 21 markers were identified (P ≤ 0.05) for the studied characters under natural and water-limited states, respectively. The corresponding values were 50 and 37 using retrotransposon-based molecular markers. Some detected markers were communal between the characters under water-limited and natural states. This was in line with the phenotypic correlations detected between the characters. Communal markers facilitate the simultaneous selection of several characters and can thus improve the efficacy of selection based on markers in the plant-breeding activities.

  6. Current limit diagrams for dendrite formation in solid-state electrolytes for Li-ion batteries

    NASA Astrophysics Data System (ADS)

    Raj, R.; Wolfenstine, J.

    2017-03-01

    We build upon the concept that nucleation of lithium dendrites at the lithium anode-solid state electrolyte interface is instigated by the higher resistance of grain boundaries that raises the local electro-chemical potential of lithium, near the lithium-electrode. This excess electro-chemo-mechanical potential, however, is reduced by the mechanical back stress generated when the dendrite is formed within the electrolyte. These parameters are coalesced into an analytical model that prescribes a specific criterion for dendrite formation. The results are presented in the form of current limit diagrams that show the "safe" and "fail" regimes for battery function. A higher conductivity of the electrolyte can reduce dendrite formation.

  7. Resurrecting Limited War Theory

    DTIC Science & Technology

    2008-05-01

    indirectly with an appreciation of the principles and guidelines for limited war. 15. SUBJECT TERMS Limited War, Political Objectives, Total War...conflict between other nations may require the United States to act indirectly with an appreciation of the principles and guidelines for limited war...in war, echoing Clausewitz’s principle of political primacy. Like Clausewitz, he was also a student of

  8. Projective limits of state spaces IV. Fractal label sets

    NASA Astrophysics Data System (ADS)

    Lanéry, Suzanne; Thiemann, Thomas

    2018-01-01

    Instead of formulating the state space of a quantum field theory over one big Hilbert space, it has been proposed by Kijowski (1977) to represent quantum states as projective families of density matrices over a collection of smaller, simpler Hilbert spaces (see Lanéry (2016) [1] for a concise introduction to this formalism). One can thus bypass the need to select a vacuum state for the theory, and still be provided with an explicit and constructive description of the quantum state space, at least as long as the label set indexing the projective structure is countable. Because uncountable label sets are much less practical in this context, we develop in the present article a general procedure to trim an originally uncountable label set down to countable cardinality. In particular, we investigate how to perform this tightening of the label set in a way that preserves both the physical content of the algebra of observables and its symmetries. This work is notably motivated by applications to the holonomy-flux algebra underlying Loop Quantum Gravity. Building on earlier work by Okołów (2013), a projective state space was introduced for this algebra in Lanéry and Thiemann (2016). However, the non-trivial structure of the holonomy-flux algebra prevents the construction of satisfactory semi-classical states (Lanéry and Thiemann, 2017). Implementing the general procedure just mentioned in the case of a one-dimensional version of this algebra, we show how a discrete subalgebra can be extracted without destroying universality nor diffeomorphism invariance. On this subalgebra, quantum states can then be constructed which are more regular than was possible on the original algebra. In particular, this allows the design of semi-classical states whose semi-classicality is enforced step by step, starting from collective, macroscopic degrees of freedom and going down progressively toward smaller and smaller scales.

  9. Prediction of miRNA targets.

    PubMed

    Oulas, Anastasis; Karathanasis, Nestoras; Louloupi, Annita; Pavlopoulos, Georgios A; Poirazi, Panayiota; Kalantidis, Kriton; Iliopoulos, Ioannis

    2015-01-01

    Computational methods for miRNA target prediction are currently undergoing extensive review and evaluation. There is still a great need for improvement of these tools and bioinformatics approaches are looking towards high-throughput experiments in order to validate predictions. The combination of large-scale techniques with computational tools will not only provide greater credence to computational predictions but also lead to the better understanding of specific biological questions. Current miRNA target prediction tools utilize probabilistic learning algorithms, machine learning methods and even empirical biologically defined rules in order to build models based on experimentally verified miRNA targets. Large-scale protein downregulation assays and next-generation sequencing (NGS) are now being used to validate methodologies and compare the performance of existing tools. Tools that exhibit greater correlation between computational predictions and protein downregulation or RNA downregulation are considered the state of the art. Moreover, efficiency in prediction of miRNA targets that are concurrently verified experimentally provides additional validity to computational predictions and further highlights the competitive advantage of specific tools and their efficacy in extracting biologically significant results. In this review paper, we discuss the computational methods for miRNA target prediction and provide a detailed comparison of methodologies and features utilized by each specific tool. Moreover, we provide an overview of current state-of-the-art high-throughput methods used in miRNA target prediction.

  10. Improved Limits for Higgs-Portal Dark Matter from LHC Searches.

    PubMed

    Hoferichter, Martin; Klos, Philipp; Menéndez, Javier; Schwenk, Achim

    2017-11-03

    Searches for invisible Higgs decays at the Large Hadron Collider constrain dark matter Higgs-portal models, where dark matter interacts with the standard model fields via the Higgs boson. While these searches complement dark matter direct-detection experiments, a comparison of the two limits depends on the coupling of the Higgs boson to the nucleons forming the direct-detection nuclear target, typically parametrized in a single quantity f_{N}. We evaluate f_{N} using recent phenomenological and lattice-QCD calculations, and include for the first time the coupling of the Higgs boson to two nucleons via pion-exchange currents. We observe a partial cancellation for Higgs-portal models that makes the two-nucleon contribution anomalously small. Our results, summarized as f_{N}=0.308(18), show that the uncertainty of the Higgs-nucleon coupling has been vastly overestimated in the past. The improved limits highlight that state-of-the-art nuclear physics input is key to fully exploiting experimental searches.

  11. Probing the limits to positional information

    PubMed Central

    Gregor, Thomas; Tank, David W.; Wieschaus, Eric F.; Bialek, William

    2008-01-01

    The reproducibility and precision of biological patterning is limited by the accuracy with which concentration profiles of morphogen molecules can be established and read out by their targets. We consider four measures of precision for the Bicoid morphogen in the Drosophila embryo: The concentration differences that distinguish neighboring cells, the limits set by the random arrival of Bicoid molecules at their targets (which depends on absolute concentration), the noise in readout of Bicoid by the activation of Hunchback, and the reproducibility of Bicoid concentration at corresponding positions in multiple embryos. We show, through a combination of different experiments, that all of these quantities are ~10%. This agreement among different measures of accuracy indicates that the embryo is not faced with noisy input signals and readout mechanisms; rather the system exerts precise control over absolute concentrations and responds reliably to small concentration differences, approaching the limits set by basic physical principles. PMID:17632062

  12. HER2 Targeted Breast Cancer Therapy with Switchable "Off/On" Multifunctional "Smart" Magnetic Polymer Core-Shell Nanocomposites.

    PubMed

    Vivek, Raju; Thangam, Ramar; Kumar, Selvaraj Rajesh; Rejeeth, Chandrababu; Kumar, Gopal Senthil; Sivasubramanian, Srinivasan; Vincent, Savariar; Gopi, Dhanaraj; Kannan, Soundarapandian

    2016-01-27

    Multifunctional magnetic polymer nanocombinations are gaining importance in cancer nanotheranostics due to their safety and their potential in delivering targeted functions. Herein, we report a novel multifunctional core-shell magnetic polymer therapeutic nanocomposites (NCs) exhibiting pH dependent "Off-On" release of drug against breast cancer cells. The NCs are intact in blood circulation ("Off" state), i.e., at physiological pH, whereas activated ("On" state) at intracellular acidic pH environment of the targeted breast cancer cells. The NCs are prepared by coating the cannonball (iron nanocore) with hydrophobic nanopockets of pH-responsive poly(d,l-lactic-co-glycolic acid) (PLGA) polymer nanoshell that allows efficient loading of therapeutics. Further, the nanocore-polymer shell is stabilized by poly(vinylpyrrolidone) (PVP) and functionalized with a targeting HER2 ligand. The prepared Her-Fe3O4@PLGA-PVP nanocomposites facilitate packing of anticancer drug (Tamoxifen) without premature release in the bloodstream, recognizing the target cells through binding of Herceptin antibody to HER2, a cell surface receptor expressed by breast cancer cells to promote HER2 receptor mediated endocytosis and finally releasing the drug at the intracellular site of tumor cells ("On" state) to induce apoptosis. The therapeutic efficiency of hemo/cytocompatible NCs drug delivery system (DDS) in terms of targeted delivery and sustained release of therapeutic agent against breast cancer cells was substantiated by in vitro and in vivo studies. The multifunctional properties of Her-Tam-Fe3O4@PLGA-PVP NCs may open up new avenues in cancer therapy through overcoming the limitations of conventional cancer therapy.

  13. Targeting a Dark Excited State of HIV-1 Nucleocapsid by Antiretroviral Thioesters Revealed by NMR Spectroscopy.

    PubMed

    Deshmukh, Lalit; Tugarinov, Vitali; Appella, Daniel H; Clore, G Marius

    2018-03-01

    HIV-1 nucleocapsid (NCp7) is a two Cys 2 HisCys zinc knuckle (N-Zn and C-Zn) protein that plays a key role in viral replication. NCp7 conformational dynamics is characterized by NMR relaxation dispersion and chemical exchange saturation transfer measurements. While the N-Zn knuckle is conformationally stable, the C-Zn knuckle interconverts on the millisecond timescale between the major state, in which the zinc is coordinated by three cysteines and a histidine, and two folded minor species (with populations around 1 %) in which one of the coordination bonds (Cys413-Sγ-Zn or His421-Nϵ2-Zn) is hydrolyzed. These findings explain why antiretroviral thioesters specifically disrupt the C-Zn knuckle by initial acylation of Cys413, and show that transient, sparsely-populated ("dark"), excited states of proteins can present effective targets for rational drug design. © 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Switchable DNA interfaces for the highly sensitive detection of label-free DNA targets.

    PubMed

    Rant, Ulrich; Arinaga, Kenji; Scherer, Simon; Pringsheim, Erika; Fujita, Shozo; Yokoyama, Naoki; Tornow, Marc; Abstreiter, Gerhard

    2007-10-30

    We report a method to detect label-free oligonucleotide targets. The conformation of surface-tethered probe nucleic acids is modulated by alternating electric fields, which cause the molecules to extend away from or fold onto the biased surface. Binding (hybridization) of targets to the single-stranded probes results in a pronounced enhancement of the layer-height modulation amplitude, monitored optically in real time. The method features an exceptional detection limit of <3 x 10(8) bound targets per cm(2) sensor area. Single base-pair mismatches in the sequences of DNA complements may readily be identified; moreover, binding kinetics and binding affinities can be determined with high accuracy. When driving the DNA to oscillate at frequencies in the kHz regime, distinct switching kinetics are revealed for single- and double-stranded DNA. Molecular dynamics are used to identify the binding state of molecules according to their characteristic kinetic fingerprints by using a chip-compatible detection format.

  15. Switchable DNA interfaces for the highly sensitive detection of label-free DNA targets

    PubMed Central

    Rant, Ulrich; Arinaga, Kenji; Scherer, Simon; Pringsheim, Erika; Fujita, Shozo; Yokoyama, Naoki; Tornow, Marc; Abstreiter, Gerhard

    2007-01-01

    We report a method to detect label-free oligonucleotide targets. The conformation of surface-tethered probe nucleic acids is modulated by alternating electric fields, which cause the molecules to extend away from or fold onto the biased surface. Binding (hybridization) of targets to the single-stranded probes results in a pronounced enhancement of the layer-height modulation amplitude, monitored optically in real time. The method features an exceptional detection limit of <3 × 108 bound targets per cm2 sensor area. Single base-pair mismatches in the sequences of DNA complements may readily be identified; moreover, binding kinetics and binding affinities can be determined with high accuracy. When driving the DNA to oscillate at frequencies in the kHz regime, distinct switching kinetics are revealed for single- and double-stranded DNA. Molecular dynamics are used to identify the binding state of molecules according to their characteristic kinetic fingerprints by using a chip-compatible detection format. PMID:17951434

  16. Student research with 400keV beams: {sup 13}N radioisotope production target development

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

    Fru, L. Che; Clymer, J.; Compton, N.

    2013-04-19

    The AN400 Van de Graaff accelerator at the Minnesota State University, Mankato, Applied Nuclear Science Lab has demonstrated utility as an accessible and versatile platform for student research. Despite the limits of low energy, the research team successfully developed projects with applications to the wider radioisotope production community. A target system has been developed for producing and extracting {sup 13}N by the {sup 12}C(d,n){sup 13}N reaction below 400keV. The system is both reusable and robust, with future applications to higher energy machines producing this important radioisotope for physiological imaging studies with Positron Emission Tomography. Up to 36({+-}1)% of the {supmore » 13}N was extracted from the graphite matrix when 35 A current was externally applied to the graphite target while simultaneously flushing the target chamber with CO{sub 2} gas.« less

  17. Quantum Limits of Space-to-Ground Optical Communications

    NASA Technical Reports Server (NTRS)

    Hemmati, H.; Dolinar, S.

    2012-01-01

    For a pure loss channel, the ultimate capacity can be achieved with classical coherent states (i.e., ideal laser light): (1) Capacity-achieving receiver (measurement) is yet to be determined. (2) Heterodyne detection approaches the ultimate capacity at high mean photon numbers. (3) Photon-counting approaches the ultimate capacity at low mean photon numbers. A number of current technology limits drive the achievable performance of free-space communication links. Approaching fundamental limits in the bandwidth-limited regime: (1) Heterodyne detection with high-order coherent-state modulation approaches ultimate limits. SOA improvements to laser phase noise, adaptive optics systems for atmospheric transmission would help. (2) High-order intensity modulation and photon-counting can approach heterodyne detection within approximately a factor of 2. This may have advantages over coherent detection in the presence of turbulence. Approaching fundamental limits in the photon-limited regime (1) Low-duty cycle binary coherent-state modulation (OOK, PPM) approaches ultimate limits. SOA improvements to laser extinction ratio, receiver dark noise, jitter, and blocking would help. (2) In some link geometries (near field links) number-state transmission could improve over coherent-state transmission

  18. Contrasting Eutrophication Risks and Countermeasures in Different Water Bodies: Assessments to Support Targeted Watershed Management.

    PubMed

    Li, Tong; Chu, Chunli; Zhang, Yinan; Ju, Meiting; Wang, Yuqiu

    2017-06-29

    Eutrophication is a major problem in China. To combat this issue, the country needs to establish water quality targets, monitoring systems, and intelligent watershed management. This study explores a new watershed management method. Water quality is first assessed using a single factor index method. Then, changes in total nitrogen/total phosphorus (TN/TP) are analyzed to determine the limiting factor. Next, the study compares the eutrophication status of two water function districts, using a comprehensive nutritional state index method and geographic information system (GIS) visualization. Finally, nutrient sources are qualitatively analyzed. Two functional water areas in Tianjin, China were selected and analyzed: Qilihai National Wetland Nature Reserve and Yuqiao Reservoir. The reservoir is a drinking water source. Results indicate that total nitrogen (TN) and total phosphorus (TP) pollution are the main factors driving eutrophication in the Qilihai Wetland and Yuqiao Reservoir. Phosphorus was the limiting factor in the Yuqiao Reservoir; nitrogen was the limiting factor in the Qilihai Wetland. Pollution in Qilihai Wetland is more serious than in Yuqiao Reservoir. The study found that external sources are the main source of pollution. These two functional water areas are vital for Tianjin; as such, the study proposes targeted management measures.

  19. A line-imaging velocity interferometer technique for shock diagnostics without x-ray preheat limitation

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

    Wang Feng; Peng Xiaoshi; Liu Shenye

    2011-10-15

    A study was conducted with a line-imaging velocity interferometer on sandwich targets at the Shen Guang-III prototype laser facility in China, with the goal of eliminating the preheat effect. A sandwich target structure was used to reduce the x-ray preheat limitation (radiation temperature {approx}170 eV) in a radiative drive shock experiment. With a thick ablator, the preheat effect appeared before the shock arrived at the window. After adding a shield layer of high-Z material on the ablator, x-rays which penetrated the ablator were so weak that the blank-out effect could not be measured. This experiment indicates that the sandwich targetmore » may provide a valuable technique in experiments such as equation of state and shock timing for inertial confinement fusion studies.« less

  20. Space-charge-limited solid-state triode

    NASA Technical Reports Server (NTRS)

    Shumka, A. (Inventor)

    1975-01-01

    A solid-state triode is provided from a wafer of nearinstrinsic semiconductor material sliced into filaments of rectangular cross section. Before slicing, emitter and collector regions are formed on the narrow sides of the filaments, and after slicing gate regions are formed in arrow strips extending longitudinally along the midsections of the wide sides of the filaments. Contacts are then formed on the emitter, collector and gate regions of each filament individually for a single filament device, or in parallel for an array of filament devices to increase load current.

  1. Unification of automatic target tracking and automatic target recognition

    NASA Astrophysics Data System (ADS)

    Schachter, Bruce J.

    2014-06-01

    The subject being addressed is how an automatic target tracker (ATT) and an automatic target recognizer (ATR) can be fused together so tightly and so well that their distinctiveness becomes lost in the merger. This has historically not been the case outside of biology and a few academic papers. The biological model of ATT∪ATR arises from dynamic patterns of activity distributed across many neural circuits and structures (including retina). The information that the brain receives from the eyes is "old news" at the time that it receives it. The eyes and brain forecast a tracked object's future position, rather than relying on received retinal position. Anticipation of the next moment - building up a consistent perception - is accomplished under difficult conditions: motion (eyes, head, body, scene background, target) and processing limitations (neural noise, delays, eye jitter, distractions). Not only does the human vision system surmount these problems, but it has innate mechanisms to exploit motion in support of target detection and classification. Biological vision doesn't normally operate on snapshots. Feature extraction, detection and recognition are spatiotemporal. When vision is viewed as a spatiotemporal process, target detection, recognition, tracking, event detection and activity recognition, do not seem as distinct as they are in current ATT and ATR designs. They appear as similar mechanism taking place at varying time scales. A framework is provided for unifying ATT and ATR.

  2. Improved GGIW-PHD filter for maneuvering non-ellipsoidal extended targets or group targets tracking based on sub-random matrices.

    PubMed

    Liang, Zhibing; Liu, Fuxian; Gao, Jiale

    2018-01-01

    For non-ellipsoidal extended targets and group targets tracking (NETT and NGTT), using an ellipsoid to approximate the target extension may not be accurate enough because of the lack of shape and orientation information. In consideration of this, we model a non-ellipsoidal extended target or target group as a combination of multiple ellipsoidal sub-objects, each represented by a random matrix. Based on these models, an improved gamma Gaussian inverse Wishart probability hypothesis density (GGIW-PHD) filter is proposed to estimate the measurement rates, kinematic states, and extension states of the sub-objects for each extended target or target group. For maneuvering NETT and NGTT, a multi-model (MM) approach based GGIW-PHD (MM-GGIW-PHD) filter is proposed. The common and the individual dynamics of the sub-objects belonging to the same extended target or target group are described by means of the combination between the overall maneuver model and the sub-object models. For the merging of updating components, an improved merging criterion and a new merging method are derived. A specific implementation of prediction partition with pseudo-likelihood method is presented. Two scenarios for non-maneuvering and maneuvering NETT and NGTT are simulated. The results demonstrate the effectiveness of the proposed algorithms.

  3. Improved GGIW-PHD filter for maneuvering non-ellipsoidal extended targets or group targets tracking based on sub-random matrices

    PubMed Central

    Liu, Fuxian; Gao, Jiale

    2018-01-01

    For non-ellipsoidal extended targets and group targets tracking (NETT and NGTT), using an ellipsoid to approximate the target extension may not be accurate enough because of the lack of shape and orientation information. In consideration of this, we model a non-ellipsoidal extended target or target group as a combination of multiple ellipsoidal sub-objects, each represented by a random matrix. Based on these models, an improved gamma Gaussian inverse Wishart probability hypothesis density (GGIW-PHD) filter is proposed to estimate the measurement rates, kinematic states, and extension states of the sub-objects for each extended target or target group. For maneuvering NETT and NGTT, a multi-model (MM) approach based GGIW-PHD (MM-GGIW-PHD) filter is proposed. The common and the individual dynamics of the sub-objects belonging to the same extended target or target group are described by means of the combination between the overall maneuver model and the sub-object models. For the merging of updating components, an improved merging criterion and a new merging method are derived. A specific implementation of prediction partition with pseudo-likelihood method is presented. Two scenarios for non-maneuvering and maneuvering NETT and NGTT are simulated. The results demonstrate the effectiveness of the proposed algorithms. PMID:29444144

  4. Complementing carbon prices with technology policies to keep climate targets within reach

    NASA Astrophysics Data System (ADS)

    Bertram, Christoph; Luderer, Gunnar; Pietzcker, Robert C.; Schmid, Eva; Kriegler, Elmar; Edenhofer, Ottmar

    2015-03-01

    Economic theory suggests that comprehensive carbon pricing is most efficient to reach ambitious climate targets, and previous studies indicated that the carbon price required for limiting global mean warming to 2 °C is between US$16 and US$73 per tonne of CO2 in 2015 (ref. ). Yet, a global implementation of such high carbon prices is unlikely to be politically feasible in the short term. Instead, most climate policies enacted so far are technology policies or fragmented and moderate carbon pricing schemes. This paper shows that ambitious climate targets can be kept within reach until 2030 despite a sub-optimal policy mix. With a state-of-the-art energy-economy model we quantify the interactions and unique effects of three major policy components: (1) a carbon price starting at US$7 per tonne of CO2 in 2015 to incentivize economy-wide mitigation, flanked by (2) support for low-carbon energy technologies to pave the way for future decarbonization, and (3) a moratorium on new coal-fired power plants to limit stranded assets. We find that such a mix limits the efficiency losses compared with the optimal policy, and at the same time lowers distributional impacts. Therefore, we argue that this instrument mix might be a politically more feasible alternative to the optimal policy based on a comprehensive carbon price alone.

  5. A culture gap in the United States: Implications for policy on limiting access to firearms for suicidal persons.

    PubMed

    Marino, Elizabeth; Wolsko, Christopher; Keys, Susan G; Pennavaria, Laura

    2016-09-01

    Suicide is a critical public health problem worldwide. In the United States (US), firearm ownership is common, and firearms account for the majority of deaths by suicide. While suicide prevention strategies may include limiting access to firearms, the contentious nature of gun regulations in the US, particularly among members of rural communities, often gives rise to constitutional concerns and political polarization that could inhibit suicidal persons from seeking the help they need. We examine potential outcomes of public health strategies in the US that encourage limiting access to firearms for populations who both value firearm ownership and are vulnerable to suicide. Based on preliminary results from a firearm safety study, we argue that attempts to limit access to firearms among those at risk of suicide will only succeed when the most affected cultural groups are engaged in collaborative discussions.

  6. Joint sparsity based heterogeneous data-level fusion for target detection and estimation

    NASA Astrophysics Data System (ADS)

    Niu, Ruixin; Zulch, Peter; Distasio, Marcello; Blasch, Erik; Shen, Dan; Chen, Genshe

    2017-05-01

    Typical surveillance systems employ decision- or feature-level fusion approaches to integrate heterogeneous sensor data, which are sub-optimal and incur information loss. In this paper, we investigate data-level heterogeneous sensor fusion. Since the sensors monitor the common targets of interest, whose states can be determined by only a few parameters, it is reasonable to assume that the measurement domain has a low intrinsic dimensionality. For heterogeneous sensor data, we develop a joint-sparse data-level fusion (JSDLF) approach based on the emerging joint sparse signal recovery techniques by discretizing the target state space. This approach is applied to fuse signals from multiple distributed radio frequency (RF) signal sensors and a video camera for joint target detection and state estimation. The JSDLF approach is data-driven and requires minimum prior information, since there is no need to know the time-varying RF signal amplitudes, or the image intensity of the targets. It can handle non-linearity in the sensor data due to state space discretization and the use of frequency/pixel selection matrices. Furthermore, for a multi-target case with J targets, the JSDLF approach only requires discretization in a single-target state space, instead of discretization in a J-target state space, as in the case of the generalized likelihood ratio test (GLRT) or the maximum likelihood estimator (MLE). Numerical examples are provided to demonstrate that the proposed JSDLF approach achieves excellent performance with near real-time accurate target position and velocity estimates.

  7. Infrared variation reduction by simultaneous background suppression and target contrast enhancement for deep convolutional neural network-based automatic target recognition

    NASA Astrophysics Data System (ADS)

    Kim, Sungho

    2017-06-01

    Automatic target recognition (ATR) is a traditionally challenging problem in military applications because of the wide range of infrared (IR) image variations and the limited number of training images. IR variations are caused by various three-dimensional target poses, noncooperative weather conditions (fog and rain), and difficult target acquisition environments. Recently, deep convolutional neural network-based approaches for RGB images (RGB-CNN) showed breakthrough performance in computer vision problems, such as object detection and classification. The direct use of RGB-CNN to the IR ATR problem fails to work because of the IR database problems (limited database size and IR image variations). An IR variation-reduced deep CNN (IVR-CNN) to cope with the problems is presented. The problem of limited IR database size is solved by a commercial thermal simulator (OKTAL-SE). The second problem of IR variations is mitigated by the proposed shifted ramp function-based intensity transformation. This can suppress the background and enhance the target contrast simultaneously. The experimental results on the synthesized IR images generated by the thermal simulator (OKTAL-SE) validated the feasibility of IVR-CNN for military ATR applications.

  8. 40 CFR 35.348 - Award limitation.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... ASSISTANCE Environmental Program Grants Pollution Prevention State Grants (section 6605) § 35.348 Award limitation. If a State includes a Pollution Prevention State Grant in a Performance Partnership Grant, the...

  9. Cooperative tumour cell membrane targeted phototherapy

    NASA Astrophysics Data System (ADS)

    Kim, Heegon; Lee, Junsung; Oh, Chanhee; Park, Ji-Ho

    2017-06-01

    The targeted delivery of therapeutics using antibodies or nanomaterials has improved the precision and safety of cancer therapy. However, the paucity and heterogeneity of identified molecular targets within tumours have resulted in poor and uneven distribution of targeted agents, thus compromising treatment outcomes. Here, we construct a cooperative targeting system in which synthetic and biological nanocomponents participate together in the tumour cell membrane-selective localization of synthetic receptor-lipid conjugates (SR-lipids) to amplify the subsequent targeting of therapeutics. The SR-lipids are first delivered selectively to tumour cell membranes in the perivascular region using fusogenic liposomes. By hitchhiking with extracellular vesicles secreted by the cells, the SR-lipids are transferred to neighbouring cells and further spread throughout the tumour tissues where the molecular targets are limited. We show that this tumour cell membrane-targeted delivery of SR-lipids leads to uniform distribution and enhanced phototherapeutic efficacy of the targeted photosensitizer.

  10. Clarifying the Rules for Targeted Killing: An Analytical Framework for Policies Involving Long-Range Armed Drones

    DTIC Science & Technology

    2016-09-08

    the ability of the United States to influence how countries will use these systems ex post facto is always limited, as demonstrated by Saudi...Greg Miller, “CIA Didn’t Know Strike Would Hit al-Qaeda Leader,” Washington Post , June 17, 2015 (as of February 29, 2016: https...Targets Two Leaders of Somali Group Allied with al-Qaeda,” Washington Post , June 29, 2011 (as of February 29, 2016: https://www.washingtonpost.com

  11. Modeling pressure rise in gas targets

    NASA Astrophysics Data System (ADS)

    Jahangiri, P.; Lapi, S. E.; Publicover, J.; Buckley, K.; Martinez, D. M.; Ruth, T. J.; Hoehr, C.

    2017-05-01

    The purpose of this work is to introduce a universal mathematical model to explain a gas target behaviour at steady-state time scale. To obtain our final goal, an analytical model is proposed to study the pressure rise in the targets used to produce medical isotopes on low-energy cyclotrons. The model is developed based on the assumption that during irradiation the system reaches steady-state. The model is verified by various experiments performed at different beam currents, gas type, and initial pressures at 13 MeV cyclotron at TRIUMF. Excellent agreement is achieved.

  12. Targeted Drug-Carrying Bacteriophages as Antibacterial Nanomedicines▿

    PubMed Central

    Yacoby, Iftach; Bar, Hagit; Benhar, Itai

    2007-01-01

    While the resistance of bacteria to traditional antibiotics is a major public health concern, the use of extremely potent antibacterial agents is limited by their lack of selectivity. As in cancer therapy, antibacterial targeted therapy could provide an opportunity to reintroduce toxic substances to the antibacterial arsenal. A desirable targeted antibacterial agent should combine binding specificity, a large drug payload per binding event, and a programmed drug release mechanism. Recently, we presented a novel application of filamentous bacteriophages as targeted drug carriers that could partially inhibit the growth of Staphylococcus aureus bacteria. This partial success was due to limitations of drug-loading capacity that resulted from the hydrophobicity of the drug. Here we present a novel drug conjugation chemistry which is based on connecting hydrophobic drugs to the phage via aminoglycoside antibiotics that serve as solubility-enhancing branched linkers. This new formulation allowed a significantly larger drug-carrying capacity of the phages, resulting in a drastic improvement in their performance as targeted drug-carrying nanoparticles. As an example for a potential systemic use for potent agents that are limited for topical use, we present antibody-targeted phage nanoparticles that carry a large payload of the hemolytic antibiotic chloramphenicol connected through the aminoglycoside neomycin. We demonstrate complete growth inhibition toward the pathogens Staphylococcus aureus, Streptococcus pyogenes, and Escherichia coli with an improvement in potency by a factor of ∼20,000 compared to the free drug. PMID:17404004

  13. Synergistic target combination prediction from curated signaling networks: Machine learning meets systems biology and pharmacology.

    PubMed

    Chua, Huey Eng; Bhowmick, Sourav S; Tucker-Kellogg, Lisa

    2017-10-01

    Given a signaling network, the target combination prediction problem aims to predict efficacious and safe target combinations for combination therapy. State-of-the-art in silico methods use Monte Carlo simulated annealing (mcsa) to modify a candidate solution stochastically, and use the Metropolis criterion to accept or reject the proposed modifications. However, such stochastic modifications ignore the impact of the choice of targets and their activities on the combination's therapeutic effect and off-target effects, which directly affect the solution quality. In this paper, we present mascot, a method that addresses this limitation by leveraging two additional heuristic criteria to minimize off-target effects and achieve synergy for candidate modification. Specifically, off-target effects measure the unintended response of a signaling network to the target combination and is often associated with toxicity. Synergy occurs when a pair of targets exerts effects that are greater than the sum of their individual effects, and is generally a beneficial strategy for maximizing effect while minimizing toxicity. mascot leverages on a machine learning-based target prioritization method which prioritizes potential targets in a given disease-associated network to select more effective targets (better therapeutic effect and/or lower off-target effects); and on Loewe additivity theory from pharmacology which assesses the non-additive effects in a combination drug treatment to select synergistic target activities. Our experimental study on two disease-related signaling networks demonstrates the superiority of mascot in comparison to existing approaches. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Target Acquisition for Projectile Vision-Based Navigation

    DTIC Science & Technology

    2014-03-01

    Future Work 20 8. References 21 Appendix A. Simulation Results 23 Appendix B. Derivation of Ground Resolution for a Diffraction-Limited Pinhole Camera...results for visual acquisition (left) and target recognition (right). ..........19 Figure B-1. Differential object and image areas for pinhole camera...projectile and target (measured in terms of the angle ) will depend on target heading. In particular, because we have aligned the x axis along the

  15. Target sequence accessibility limits activation-induced cytidine deaminase activity in primary mediastinal B-cell lymphoma.

    PubMed

    Popov, Sergey W; Moldenhauer, Gerhard; Wotschke, Beate; Brüderlein, Silke; Barth, Thomas F; Dorsch, Karola; Ritz, Olga; Möller, Peter; Leithäuser, Frank

    2007-07-15

    Activation-induced cytidine deaminase (AID) initiates somatic hypermutation (SHM) and class switch recombination (CSR) in activated B lymphocytes and is potentially implicated in genomic instability of B-cell malignancies. For unknown reasons, B-cell neoplasms often lack SHM and CSR in spite of high AID expression. Here, we show that primary mediastinal B-cell lymphoma (PMBL), an immunoglobulin (Ig)-negative lymphoma that possesses hypermutated, class-switched Ig genes, expresses high levels of AID with an intact primary structure but does not do CSR in 14 of 16 cases analyzed. Absence of CSR coincided with low Ig germ-line transcription, whereas high level germ-line transcription was observed only in those two cases with active CSR. Interleukin-4/CD40L costimulation induced CSR and a marked up-regulation of germ-line transcription in the PMBL-derived cell line MedB-1. In the PMBL cell line Karpas 1106P, CSR was not inducible and germ-line transcription remained low on stimulation. However, Karpas 1106P, but not MedB-1, had ongoing SHM of the Ig gene and BCL6. These genes were transcribed in Karpas 1106P, whereas transcription was undetectable or low in MedB-1 cells. Thus, accessibility of the target sequences seems to be a major limiting factor for AID-dependent somatic gene diversification in PMBL.

  16. Nonlinear Acoustic Characterization of Targets

    DTIC Science & Technology

    2008-01-01

    these technologies, however, are limited in their ability to differentiate targets from other debris in the soil . 2 Furthermore, they must heavily rely...for landmine detection in which two tones are used to insonify the soil . Here insonify is used to describe the process of exposing the target to...the surrounding soil . Because of the compliant nature of the landmine top plate, a nonlinear interaction is created between it and the soil above. It is

  17. Tumor-targeting delivery of herb-based drugs with cell-penetrating/tumor-targeting peptide-modified nanocarriers

    PubMed Central

    Kebebe, Dereje; Liu, Yuanyuan; Wu, Yumei; Vilakhamxay, Maikhone; Liu, Zhidong; Li, Jiawei

    2018-01-01

    Cancer has become one of the leading causes of mortality globally. The major challenges of conventional cancer therapy are the failure of most chemotherapeutic agents to accumulate selectively in tumor cells and their severe systemic side effects. In the past three decades, a number of drug delivery approaches have been discovered to overwhelm the obstacles. Among these, nanocarriers have gained much attention for their excellent and efficient drug delivery systems to improve specific tissue/organ/cell targeting. In order to enhance targeting efficiency further and reduce limitations of nanocarriers, nanoparticle surfaces are functionalized with different ligands. Several kinds of ligand-modified nanomedicines have been reported. Cell-penetrating peptides (CPPs) are promising ligands, attracting the attention of researchers due to their efficiency to transport bioactive molecules intracellularly. However, their lack of specificity and in vivo degradation led to the development of newer types of CPP. Currently, activable CPP and tumor-targeting peptide (TTP)-modified nanocarriers have shown dramatically superior cellular specific uptake, cytotoxicity, and tumor growth inhibition. In this review, we discuss recent advances in tumor-targeting strategies using CPPs and their limitations in tumor delivery systems. Special emphasis is given to activable CPPs and TTPs. Finally, we address the application of CPPs and/or TTPs in the delivery of plant-derived chemotherapeutic agents. PMID:29563797

  18. Effect of co-administration of probiotics with polysaccharide based colon targeted delivery systems to optimize site specific drug release.

    PubMed

    Prudhviraj, G; Vaidya, Yogyata; Singh, Sachin Kumar; Yadav, Ankit Kumar; Kaur, Puneet; Gulati, Monica; Gowthamarajan, K

    2015-11-01

    Significant clinical success of colon targeted dosage forms has been limited by their inappropriate release profile at the target site. Their failure to release the drug completely in the colon may be attributed to changes in the colonic milieu because of pathological state, drug effect and psychological stress accompanying the diseased state or, a combination of these. Alteration in normal colonic pH and bacterial picture leads to incomplete release of drug from the designed delivery system. We report the effectiveness of a targeted delivery system wherein the constant replenishment of the colonic microbiota is achieved by concomitant administration of probiotics along with the polysaccharide based drug delivery system. Guar gum coated spheroids of sulfasalazine were prepared. In the dissolution studies, these spheroids showed markedly higher release in the simulated colonic fluid. In vivo experiments conducted in rats clearly demonstrated the therapeutic advantage of co-administration of probiotics with guar gum coated spheroids. Our results suggest that concomitant use of probiotics along with the polysaccharide based delivery systems can be a simple strategy to achieve satisfactory colon targeting of drugs. Copyright © 2015 Elsevier B.V. All rights reserved.

  19. Postsynaptic ERG potassium channels limit muscle excitability to allow distinct egg-laying behavior states in C. elegans

    PubMed Central

    Collins, Kevin M.; Koelle, Michael R.

    2013-01-01

    C. elegans regulates egg laying by alternating between an inactive phase and a serotonin-triggered active phase. We found that the conserved ERG potassium channel UNC-103 enables this two-state behavior by limiting excitability of the egg-laying muscles. Using both high-speed video recording and calcium imaging of egg-laying muscles in behaving animals, we found that the muscles appear to be excited at a particular phase of each locomotor body bend. During the inactive phase, this rhythmic excitation infrequently evokes calcium transients or contraction of the egg-laying muscles. During the serotonin-triggered active phase, however, these muscles are more excitable and each body bend is accompanied by a calcium transient that drives twitching or full contraction of the egg-laying muscles. We found that ERG null mutants lay eggs too frequently, and that ERG function is necessary and sufficient in the egg-laying muscles to limit egg laying. ERG K+ channels localize to postsynaptic sites in the egg-laying muscle, and mutants lacking ERG have more frequent calcium transients and contractions of the egg-laying muscles even during the inactive phase. Thus ERG channels set postsynaptic excitability at a threshold so that further adjustments of excitability by serotonin generate two distinct behavioral states. PMID:23303953

  20. Effect of humoral immunity on HIV-1 dynamics with virus-to-target and infected-to-target infections

    NASA Astrophysics Data System (ADS)

    Elaiw, A. M.; Raezah, A. A.; Alofi, A. S.

    2016-08-01

    We consider an HIV-1 dynamics model by incorporating (i) two routes of infection via, respectively, binding of a virus to a receptor on the surface of a target cell to start genetic reactions (virus-to-target infection), and the direct transmission from infected cells to uninfected cells through the concept of virological synapse in vivo (infected-to-target infection); (ii) two types of distributed-time delays to describe the time between the virus or infected cell contacts an uninfected CD4+ T cell and the emission of new active viruses; (iii) humoral immune response, where the HIV-1 particles are attacked by the antibodies that are produced from the B lymphocytes. The existence and stability of all steady states are completely established by two bifurcation parameters, R 0 (the basic reproduction number) and R 1 (the viral reproduction number at the chronic-infection steady state without humoral immune response). By constructing Lyapunov functionals and using LaSalle's invariance principle, we have proven that, if R 0 ≤ 1 , then the infection-free steady state is globally asymptotically stable, if R 1 ≤ 1 < R 0 , then the chronic-infection steady state without humoral immune response is globally asymptotically stable, and if R 1 > 1 , then the chronic-infection steady state with humoral immune response is globally asymptotically stable. We have performed numerical simulations to confirm our theoretical results.

  1. Sparsity based target detection for compressive spectral imagery

    NASA Astrophysics Data System (ADS)

    Boada, David Alberto; Arguello Fuentes, Henry

    2016-09-01

    Hyperspectral imagery provides significant information about the spectral characteristics of objects and materials present in a scene. It enables object and feature detection, classification, or identification based on the acquired spectral characteristics. However, it relies on sophisticated acquisition and data processing systems able to acquire, process, store, and transmit hundreds or thousands of image bands from a given area of interest which demands enormous computational resources in terms of storage, computationm, and I/O throughputs. Specialized optical architectures have been developed for the compressed acquisition of spectral images using a reduced set of coded measurements contrary to traditional architectures that need a complete set of measurements of the data cube for image acquisition, dealing with the storage and acquisition limitations. Despite this improvement, if any processing is desired, the image has to be reconstructed by an inverse algorithm in order to be processed, which is also an expensive task. In this paper, a sparsity-based algorithm for target detection in compressed spectral images is presented. Specifically, the target detection model adapts a sparsity-based target detector to work in a compressive domain, modifying the sparse representation basis in the compressive sensing problem by means of over-complete training dictionaries and a wavelet basis representation. Simulations show that the presented method can achieve even better detection results than the state of the art methods.

  2. Target Control in Logical Models Using the Domain of Influence of Nodes.

    PubMed

    Yang, Gang; Gómez Tejeda Zañudo, Jorge; Albert, Réka

    2018-01-01

    Dynamical models of biomolecular networks are successfully used to understand the mechanisms underlying complex diseases and to design therapeutic strategies. Network control and its special case of target control, is a promising avenue toward developing disease therapies. In target control it is assumed that a small subset of nodes is most relevant to the system's state and the goal is to drive the target nodes into their desired states. An example of target control would be driving a cell to commit to apoptosis (programmed cell death). From the experimental perspective, gene knockout, pharmacological inhibition of proteins, and providing sustained external signals are among practical intervention techniques. We identify methodologies to use the stabilizing effect of sustained interventions for target control in Boolean network models of biomolecular networks. Specifically, we define the domain of influence (DOI) of a node (in a certain state) to be the nodes (and their corresponding states) that will be ultimately stabilized by the sustained state of this node regardless of the initial state of the system. We also define the related concept of the logical domain of influence (LDOI) of a node, and develop an algorithm for its identification using an auxiliary network that incorporates the regulatory logic. This way a solution to the target control problem is a set of nodes whose DOI can cover the desired target node states. We perform greedy randomized adaptive search in node state space to find such solutions. We apply our strategy to in silico biological network models of real systems to demonstrate its effectiveness.

  3. Time limits during visual foraging reveal flexible working memory templates.

    PubMed

    Kristjánsson, Tómas; Thornton, Ian M; Kristjánsson, Árni

    2018-06-01

    During difficult foraging tasks, humans rarely switch between target categories, but switch frequently during easier foraging. Does this reflect fundamental limits on visual working memory (VWM) capacity or simply strategic choice due to effort? Our participants performed time-limited or unlimited foraging tasks where they tapped stimuli from 2 target categories while avoiding items from 2 distractor categories. These time limits should have no effect if capacity imposes limits on VWM representations but more flexible VWM could allow observers to use VWM according to task demands in each case. We found that with time limits, participants switched more frequently and switch-costs became much smaller than during unlimited foraging. Observers can therefore switch between complex (conjunction) target categories when needed. We propose that while maintaining many complex templates in working memory is effortful and observers avoid this, they can do so if this fits task demands, showing the flexibility of working memory representations used for visual exploration. This is in contrast with recent proposals, and we discuss the implications of these findings for theoretical accounts of working memory. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

  4. State medical marijuana laws: understanding the laws and their limitations.

    PubMed

    Pacula, Rosalie Liccardo; Chriqui, Jamie F; Reichmann, Deborah A; Terry-McElrath, Yvonne M

    2002-01-01

    Significant attention has been given to the debate regarding allowances for medical marijuana use since the 1996 California and Arizona ballot initiatives. State medical marijuana allowances, however, have existed since the mid-1970s. Much of the current debate stems from confusion about the various ways states approach the issue. In this paper, we present original legal research on current state medical marijuana laws identifying four different ways states statutorily enable the medical use of marijuana. We discuss the tension these approaches have with federal law as well as their implications regarding real access for patients. In addition, we present information on how a small number of states are trying to deal with the issue of access within the context of their medical marijuana laws, and discuss the implication of various supply approaches on the enforcement of other state marijuana laws.

  5. 40 CFR 35.348 - Award limitation.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE STATE AND LOCAL ASSISTANCE Environmental Program Grants Pollution Prevention State Grants (section 6605) § 35.348 Award limitation. If a State includes a Pollution Prevention State Grant in a Performance Partnership Grant, the...

  6. 40 CFR 35.348 - Award limitation.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Protection of Environment ENVIRONMENTAL PROTECTION AGENCY GRANTS AND OTHER FEDERAL ASSISTANCE STATE AND LOCAL ASSISTANCE Environmental Program Grants Pollution Prevention State Grants (section 6605) § 35.348 Award limitation. If a State includes a Pollution Prevention State Grant in a Performance Partnership Grant, the...

  7. Airborne target tracking algorithm against oppressive decoys in infrared imagery

    NASA Astrophysics Data System (ADS)

    Sun, Xiechang; Zhang, Tianxu

    2009-10-01

    This paper presents an approach for tracking airborne target against oppressive infrared decoys. Oppressive decoy lures infrared guided missile by its high infrared radiation. Traditional tracking algorithms have degraded stability even come to tracking failure when airborne target continuously throw out many decoys. The proposed approach first determines an adaptive tracking window. The center of the tracking window is set at a predicted target position which is computed based on uniform motion model. Different strategies are applied for determination of tracking window size according to target state. The image within tracking window is segmented and multi features of candidate targets are extracted. The most similar candidate target is associated to the tracking target by using a decision function, which calculates a weighted sum of normalized feature differences between two comparable targets. Integrated intensity ratio of association target and tracking target, and target centroid are examined to estimate target state in the presence of decoys. The tracking ability and robustness of proposed approach has been validated by processing available real-world and simulated infrared image sequences containing airborne targets and oppressive decoys.

  8. Ion beam sputter target and method of manufacture

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

    Higdon, Clifton; Elmoursi, Alaa A.; Goldsmith, Jason

    A target for use in an ion beam sputtering apparatus made of at least two target tiles where at least two of the target tiles are made of different chemical compositions and are mounted on a main tile and geometrically arranged on the main tile to yield a desired chemical composition on a sputtered substrate. In an alternate embodiment, the tiles are of varied thickness according to the desired chemical properties of the sputtered film. In yet another alternate embodiment, the target is comprised of plugs pressed in a green state which are disposed in cavities formed in a mainmore » tile also formed in a green state and the assembly can then be compacted and then sintered.« less

  9. A robust close-range photogrammetric target extraction algorithm for size and type variant targets

    NASA Astrophysics Data System (ADS)

    Nyarko, Kofi; Thomas, Clayton; Torres, Gilbert

    2016-05-01

    The Photo-G program conducted by Naval Air Systems Command at the Atlantic Test Range in Patuxent River, Maryland, uses photogrammetric analysis of large amounts of real-world imagery to characterize the motion of objects in a 3-D scene. Current approaches involve several independent processes including target acquisition, target identification, 2-D tracking of image features, and 3-D kinematic state estimation. Each process has its own inherent complications and corresponding degrees of both human intervention and computational complexity. One approach being explored for automated target acquisition relies on exploiting the pixel intensity distributions of photogrammetric targets, which tend to be patterns with bimodal intensity distributions. The bimodal distribution partitioning algorithm utilizes this distribution to automatically deconstruct a video frame into regions of interest (ROI) that are merged and expanded to target boundaries, from which ROI centroids are extracted to mark target acquisition points. This process has proved to be scale, position and orientation invariant, as well as fairly insensitive to global uniform intensity disparities.

  10. Review of metastable states in heavy nuclei

    DOE PAGES

    Dracoulis, G. D.; Walker, P. M.; Kondev, F. G.

    2016-05-31

    Here, the structure of nuclear isomeric states is reviewed in the context of their role in contemporary nuclear physics research. Emphasis is given to high-spin isomers in heavy nuclei, with A ≳ 150. The possibility to exploit isomers to study some of the most exotic nuclei is a recurring theme. In spherical nuclei, the role of octupole collectivity is discussed in detail, while in deformed nuclei the limitations of the K quantum number are addressed. Isomer targets and isomer beams are considered, along with applications related to energy storage, astrophysics, medicine, and experimental advances.

  11. Laser-driven collimated tens-GeV monoenergetic protons from mass-limited target plus preformed channel

    NASA Astrophysics Data System (ADS)

    Zheng, F. L.; Wu, S. Z.; Wu, H. C.; Zhou, C. T.; Cai, H. B.; Yu, M. Y.; Tajima, T.; Yan, X. Q.; He, X. T.

    2013-01-01

    Proton acceleration by ultra-intense laser pulse irradiating a target with cross-section smaller than the laser spot size and connected to a parabolic density channel is investigated. The target splits the laser into two parallel propagating parts, which snowplow the back-side plasma electrons along their paths, creating two adjacent parallel wakes and an intense return current in the gap between them. The radiation-pressure pre-accelerated target protons trapped in the wake fields now undergo acceleration as well as collimation by the quasistatic wake electrostatic and magnetic fields. Particle-in-cell simulations show that stable long-distance acceleration can be realized, and a 30 fs monoenergetic ion beam of >10 GeV peak energy and <2° divergence can be produced by a circularly polarized laser pulse at an intensity of about 1022 W/cm2.

  12. The Persistence of Experience: Prior Attentional and Emotional State Affects Network Functioning in a Target Detection Task.

    PubMed

    Stern, Emily R; Muratore, Alexandra F; Taylor, Stephan F; Abelson, James L; Hof, Patrick R; Goodman, Wayne K

    2015-09-01

    Efficient, adaptive behavior relies on the ability to flexibly move between internally focused (IF) and externally focused (EF) attentional states. Despite evidence that IF cognitive processes such as event imagination comprise a significant amount of awake cognition, the consequences of internal absorption on the subsequent recruitment of brain networks during EF tasks are unknown. The present functional magnetic resonance imaging (fMRI) study employed a novel attentional state switching task. Subjects imagined positive and negative events (IF task) or performed a working memory task (EF task) before switching to a target detection (TD) task also requiring attention to external information, allowing for the investigation of neural functioning during external attention based on prior attentional state. There was a robust increase of activity in frontal, parietal, and temporal regions during TD when subjects were previously performing the EF compared with IF task, an effect that was most pronounced following negative IF. Additionally, dorsolateral prefrontal cortex was less negatively coupled with ventromedial prefrontal and posterior cingulate cortices during TD following IF compared with EF. These findings reveal the striking consequences for brain activity following immersion in an IF attentional state, which have strong implications for psychiatric disorders characterized by excessive internal focus. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  13. Tracking Multiple Video Targets with an Improved GM-PHD Tracker

    PubMed Central

    Zhou, Xiaolong; Yu, Hui; Liu, Honghai; Li, Youfu

    2015-01-01

    Tracking multiple moving targets from a video plays an important role in many vision-based robotic applications. In this paper, we propose an improved Gaussian mixture probability hypothesis density (GM-PHD) tracker with weight penalization to effectively and accurately track multiple moving targets from a video. First, an entropy-based birth intensity estimation method is incorporated to eliminate the false positives caused by noisy video data. Then, a weight-penalized method with multi-feature fusion is proposed to accurately track the targets in close movement. For targets without occlusion, a weight matrix that contains all updated weights between the predicted target states and the measurements is constructed, and a simple, but effective method based on total weight and predicted target state is proposed to search the ambiguous weights in the weight matrix. The ambiguous weights are then penalized according to the fused target features that include spatial-colour appearance, histogram of oriented gradient and target area and further re-normalized to form a new weight matrix. With this new weight matrix, the tracker can correctly track the targets in close movement without occlusion. For targets with occlusion, a robust game-theoretical method is used. Finally, the experiments conducted on various video scenarios validate the effectiveness of the proposed penalization method and show the superior performance of our tracker over the state of the art. PMID:26633422

  14. Radiation pressure acceleration: The factors limiting maximum attainable ion energy

    DOE PAGES

    Bulanov, S. S.; Esarey, E.; Schroeder, C. B.; ...

    2016-04-15

    Radiation pressure acceleration (RPA) is a highly efficient mechanism of laser-driven ion acceleration, with near complete transfer of the laser energy to the ions in the relativistic regime. However, there is a fundamental limit on the maximum attainable ion energy, which is determined by the group velocity of the laser. The tightly focused laser pulses have group velocities smaller than the vacuum light speed, and, since they offer the high intensity needed for the RPA regime, it is plausible that group velocity effects would manifest themselves in the experiments involving tightly focused pulses and thin foils. However, in this case,more » finite spot size effects are important, and another limiting factor, the transverse expansion of the target, may dominate over the group velocity effect. As the laser pulse diffracts after passing the focus, the target expands accordingly due to the transverse intensity profile of the laser. Due to this expansion, the areal density of the target decreases, making it transparent for radiation and effectively terminating the acceleration. The off-normal incidence of the laser on the target, due either to the experimental setup, or to the deformation of the target, will also lead to establishing a limit on maximum ion energy.« less

  15. 40 CFR 35.298 - Award limitations.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... STATE AND LOCAL ASSISTANCE Environmental Program Grants State Indoor Radon Grants (section 306) § 35.298 Award limitations. (a) The Regional Administrator shall not include State Indoor Radon funds in a... has the primary responsibility for radon programs as designated by the Governor of the affected State...

  16. Application of Smoothing Techniques for Tracking Maneuvering Targets. Multiple Target Tracking in Clutter: New Approaches

    DTIC Science & Technology

    1992-07-01

    target state estimation is affected not only by the measurement noise but also by the uncertainty in the origins of the measurements. To improve the...to identify targets in the presence of anticipated background noise (including earth, lunar, star backgrounds, complicated spacecraft structures...each other. Futhermore, those frames are often degraded versions of the original scene due to blur and noise . Through the task of image registration

  17. Drug-induced amplification of nanoparticle targeting to tumors

    PubMed Central

    Lin, Kevin Y.; Kwon, Ester J.; Lo, Justin H.; Bhatia, Sangeeta N.

    2018-01-01

    Summary Nanomedicines have the potential to significantly impact cancer therapy by improving drug efficacy and decreasing off-target effects, yet our ability to efficiently home nanoparticles to disease sites remains limited. One frequently overlooked constraint of current active targeting schemes is the relative dearth of targetable antigens within tumors, which restricts the amount of cargo that can be delivered in a tumor-specific manner. To address this limitation, we exploit tumor-specific responses to drugs to construct a cooperative targeting system where a small molecule therapeutic modulates the disease microenvironment to amplify nanoparticle recruitment in vivo. We first administer a vascular disrupting agent, ombrabulin, which selectively affects tumors and leads to locally elevated presentation of the stress-related protein, p32. This increase in p32 levels provides more binding sites for circulating p32-targeted nanoparticles, enhancing their delivery of diagnostic or therapeutic cargos to tumors. We show that this cooperative targeting system recruits over five times higher doses of nanoparticles to tumors and decreases tumor burden when compared with non-cooperative controls. These results suggest that using nanomedicine in conjunction with drugs that enhance the presentation of target antigens in the tumor environment may be an effective strategy for improving the diagnosis and treatment of cancer. PMID:29731806

  18. Targeted health department expenditures benefit birth outcomes at the county level.

    PubMed

    Bekemeier, Betty; Yang, Youngran; Dunbar, Matthew D; Pantazis, Athena; Grembowski, David E

    2014-06-01

    Public health leaders lack evidence for making decisions about the optimal allocation of resources across local health department (LHD) services, even as limited funding has forced cuts to public health services while local needs grow. A lack of data has also limited examination of the outcomes of targeted LHD investments in specific service areas. This study used unique, detailed LHD expenditure data gathered from state health departments to examine the influence of maternal and child health (MCH) service investments by LHDs on health outcomes. A multivariate panel time-series design was used in 2013 to estimate ecologic relationships between 2000-2010 LHD expenditures on MCH and county-level rates of low birth weight and infant mortality. The unit of analysis was 102 LHD jurisdictions in Washington and Florida. Results indicate that LHD expenditures on MCH services have a beneficial relationship with county-level low birth weight rates, particularly in counties with high concentrations of poverty. This relationship is stronger for more targeted expenditure categories, with expenditures in each of the three specific examined MCH service areas demonstrating the strongest effects. Findings indicate that specific LHD investments in MCH have an important effect on related health outcomes for populations in poverty and likely help reduce the costly burden of poor birth outcomes for families and communities. These findings underscore the importance of monitoring the impact of these evolving investments and ensuring that targeted, beneficial investments are not lost but expanded upon across care delivery systems. Copyright © 2014 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

  19. Target concentration intervention: beyond Y2K

    PubMed Central

    Holford, Nicholas H G

    1999-01-01

    Target concentration intervention (TCI) is proposed as an alternative conceptual strategy to therapeutic drug monitoring (TDM). It is argued that the idea of a therapeutic range has limited the interpretation of measured drug concentrations and diminished the anticipated clinical benefit to patients by use of an oversimplified pharmacodynamic model. TCI on the other hand embraces pharmacokinetic and pharmacodynamic concepts and uses the idea of a target effect and associated target concentration to make rational individual dose decisions. PMID:10383553

  20. Target concentration intervention: beyond Y2K.

    PubMed

    Holford, N H

    2001-01-01

    Target concentration intervention (TCI) is proposed as an alternative conceptual strategy to therapeutic drug monitoring (TDM). It is argued that the idea of a therapeutic range has limited the interpretation of measured drug concentrations and diminished the anticipated clinical benefit to patients by use of an oversimplified pharmacodynamic model. TCI on the other hand embraces pharmacokinetic and pharmacodynamic concepts and uses the idea of a target effect and associated target concentration to make rational individual dose decisions.

  1. Target concentration intervention: beyond Y2K

    PubMed Central

    Holford, Nicholas H G

    2001-01-01

    Target concentration intervention (TCI) is proposed as an alternative conceptual strategy to therapeutic drug monitoring (TDM). It is argued that the idea of a therapeutic range has limited the interpretation of measured drug concentrations and diminished the anticipated clinical benefit to patients by use of an oversimplified pharmacodynamic model. TCI on the other hand embraces pharmacokinetic and pharmacodynamic concepts and uses the idea of a target effect and associated target concentration to make rational individual dose decisions. PMID:11564053

  2. Instructional Services for Limited English Proficient Children.

    ERIC Educational Resources Information Center

    O'Malley, J. Michael

    1982-01-01

    The 1978 Children's English and Services Study (United States) contains five findings for limited English proficient children aged 5-14, e.g., one-third are served by bilingual education/English (second language); Federal and state support for special types of instruction are received predominantly by limited English proficient children within the…

  3. Motor Cortical Visuomotor Feedback Activity Is Initially Isolated from Downstream Targets in Output-Null Neural State Space Dimensions.

    PubMed

    Stavisky, Sergey D; Kao, Jonathan C; Ryu, Stephen I; Shenoy, Krishna V

    2017-07-05

    Neural circuits must transform new inputs into outputs without prematurely affecting downstream circuits while still maintaining other ongoing communication with these targets. We investigated how this isolation is achieved in the motor cortex when macaques received visual feedback signaling a movement perturbation. To overcome limitations in estimating the mapping from cortex to arm movements, we also conducted brain-machine interface (BMI) experiments where we could definitively identify neural firing patterns as output-null or output-potent. This revealed that perturbation-evoked responses were initially restricted to output-null patterns that cancelled out at the neural population code readout and only later entered output-potent neural dimensions. This mechanism was facilitated by the circuit's large null space and its ability to strongly modulate output-potent dimensions when generating corrective movements. These results show that the nervous system can temporarily isolate portions of a circuit's activity from its downstream targets by restricting this activity to the circuit's output-null neural dimensions. Copyright © 2017 Elsevier Inc. All rights reserved.

  4. Exploiting bacterial DNA gyrase as a drug target: current state and perspectives.

    PubMed

    Collin, Frédéric; Karkare, Shantanu; Maxwell, Anthony

    2011-11-01

    DNA gyrase is a type II topoisomerase that can introduce negative supercoils into DNA at the expense of ATP hydrolysis. It is essential in all bacteria but absent from higher eukaryotes, making it an attractive target for antibacterials. The fluoroquinolones are examples of very successful gyrase-targeted drugs, but the rise in bacterial resistance to these agents means that we not only need to seek new compounds, but also new modes of inhibition of this enzyme. We review known gyrase-specific drugs and toxins and assess the prospects for developing new antibacterials targeted to this enzyme.

  5. Solid-State Fault Current Limiter Development : Design and Testing Update of a 15kV SSCL Power Stack

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

    Dr. Ram Adapa; Mr. Dante Piccone

    2012-04-30

    ABSTRACT The Solid-State Fault Current Limiter (SSCL) is a promising technology that can be applied to utility power delivery systems to address the problem of increasing fault currents associated with load growth. As demand continues to grow, more power is added to utility system either by increasing generator capacity or by adding distributed generators, resulting in higher available fault currents, often beyond the capabilities of the present infrastructure. The SSCL is power-electronics based equipment designed to work with the present utility system to address this problem. The SSCL monitors the line current and dynamically inserts additional impedance into the linemore » in the event of a fault being detected. The SSCL is based on a modular design and can be configured for 5kV through 69kV systems at nominal current ratings of 1000A to 4000A. Results and Findings This report provides the final test results on the development of 15kV class SSCL single phase power stack. The scope of work included the design of the modular standard building block sub-assemblies, the design and manufacture of the power stack and the testing of the power stack for the key functional tests of continuous current capability and fault current limiting action. Challenges and Objectives Solid-State Current Limiter technology impacts a wide spectrum of utility engineering and operating personnel. It addresses the problems associated with load growth both at Transmission and Distribution class networks. The design concept is pioneering in terms of developing the most efficient and compact power electronics equipment for utility use. The initial test results of the standard building blocks are promising. The independent laboratory tests of the power stack are promising. However the complete 3 phase system needs rigorous testing for performance and reliability. Applications, Values, and Use The SSCL is an intelligent power-electronics device which is modular in design and can provide

  6. Target Housing Material Options

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

    Woloshun, Keith Albert

    2016-02-11

    With gas cooling, heat transfer coefficients are low compared to water. The benefit of gas from a heat transfer point of view is that there is really no upper temperature limit for the coolant, as compared to water, which is limited ultimately by the critical point, and in practice the critical heat flux. In our case with parallel flow channels, water is limited to even lower operating limits by nucleate boiling. So gas can get as hot as the containment material will allow, but to get the density and heat transfer up to something reasonable, we must also increase pressure,more » thus increasing stress on the containment, namely the front and back faces. We are designing to ASME BPVC, which, for most materials allows a maximum stress of UTS/3. So we want the highest possible UTS. For reference, the front face stress in the 12 mm target at 300 psi was about 90 MPa. The inconel 718 allowable stress at 900°C is 1/3 of 517 or 172 MPa. So we are in a very safe place, but the uTS is dropping rapidly with temperature above 900°C. As we increase target diameter, the challenge will be to keep the stress down. We are probably looking at keeping the allowable at or above the present value, and at as high a temperature as possible.« less

  7. Contrasting Eutrophication Risks and Countermeasures in Different Water Bodies: Assessments to Support Targeted Watershed Management

    PubMed Central

    Li, Tong; Chu, Chunli; Zhang, Yinan; Ju, Meiting; Wang, Yuqiu

    2017-01-01

    Eutrophication is a major problem in China. To combat this issue, the country needs to establish water quality targets, monitoring systems, and intelligent watershed management. This study explores a new watershed management method. Water quality is first assessed using a single factor index method. Then, changes in total nitrogen/total phosphorus (TN/TP) are analyzed to determine the limiting factor. Next, the study compares the eutrophication status of two water function districts, using a comprehensive nutritional state index method and geographic information system (GIS) visualization. Finally, nutrient sources are qualitatively analyzed. Two functional water areas in Tianjin, China were selected and analyzed: Qilihai National Wetland Nature Reserve and Yuqiao Reservoir. The reservoir is a drinking water source. Results indicate that total nitrogen (TN) and total phosphorus (TP) pollution are the main factors driving eutrophication in the Qilihai Wetland and Yuqiao Reservoir. Phosphorus was the limiting factor in the Yuqiao Reservoir; nitrogen was the limiting factor in the Qilihai Wetland. Pollution in Qilihai Wetland is more serious than in Yuqiao Reservoir. The study found that external sources are the main source of pollution. These two functional water areas are vital for Tianjin; as such, the study proposes targeted management measures. PMID:28661417

  8. How reliable are ligand-centric methods for Target Fishing?

    NASA Astrophysics Data System (ADS)

    Peon, Antonio; Dang, Cuong; Ballester, Pedro

    2016-04-01

    Computational methods for Target Fishing (TF), also known as Target Prediction or Polypharmacology Prediction, can be used to discover new targets for small-molecule drugs. This may result in repositioning the drug in a new indication or improving our current understanding of its efficacy and side effects. While there is a substantial body of research on TF methods, there is still a need to improve their validation, which is often limited to a small part of the available targets and not easily interpretable by the user. Here we discuss how target-centric TF methods are inherently limited by the number of targets that can possibly predict (this number is by construction much larger in ligand-centric techniques). We also propose a new benchmark to validate TF methods, which is particularly suited to analyse how predictive performance varies with the query molecule. On average over approved drugs, we estimate that only five predicted targets will have to be tested to find two true targets with submicromolar potency (a strong variability in performance is however observed). In addition, we find that an approved drug has currently an average of eight known targets, which reinforces the notion that polypharmacology is a common and strong event. Furthermore, with the assistance of a control group of randomly-selected molecules, we show that the targets of approved drugs are generally harder to predict.

  9. Enhancing and targeting nucleic acid delivery by magnetic force.

    PubMed

    Plank, Christian; Anton, Martina; Rudolph, Carsten; Rosenecker, Joseph; Krötz, Florian

    2003-08-01

    Insufficient contact of inherently highly active nucleic acid delivery systems with target cells is a primary reason for their often observed limited efficacy. Physical methods of targeting can overcome this limitation and reduce the risk of undesired side effects due to non-target site delivery. The authors and others have developed a novel means of physical targeting, exploiting magnetic force acting on nucleic acid vectors associated with magnetic particles in order to mediate the rapid contact of vectors with target cells. Here, the principles of magnetic drug and nucleic acid delivery are reviewed, and the facts and potentials of the technique for research and therapeutic applications are discussed. Magnetically enhanced nucleic acid delivery - magnetofection - is universally applicable to viral and non-viral vectors, is extraordinarily rapid, simple and yields saturation level transfection at low dose in vitro. The method is useful for site-specific vector targeting in vivo. Exploiting the full potential of the technique requires an interdisciplinary research effort in magnetic field physics, magnetic particle chemistry, pharmaceutical formulation and medical application.

  10. Marketing and alcohol-related traffic fatalities: impact of alcohol advertising targeting minors.

    PubMed

    Smith, Ryan C; Geller, E Scott

    2009-10-01

    Alcohol-related youth traffic fatalities continue as a major public-health concern. While state and federal laws can be useful in tackling this problem, the efficacy of many laws has not been empirically demonstrated. We examined the impact of state laws prohibiting alcohol advertising to target minors. Using statistics obtained from the Fatality Analysis Reporting System (FARS), youth alcohol-related, single-vehicle, driver traffic fatalities were compared by state as a function of whether the state has a law prohibiting alcohol advertising that targets minors. Overall, states possessing this law experienced 32.9% fewer of the above specified traffic fatalities. DISCUSSION AND IMPACT ON INDUSTRY: The results suggest that not only are youth drinking rates affected by alcohol advertisements targeting youth, but also drink-driving behaviors. Indeed, we estimate that if this type of legislation were adopted in the 26 states that do not prohibit targeting of minors with alcohol advertising, then 400 youth lives could be saved annually.

  11. Exercise and limitations in physical activity levels among new dialysis patients in the United States: an epidemiologic study.

    PubMed

    Stack, Austin G; Murthy, Bhamidipati

    2008-12-01

    Epidemiologic studies of physical activity among patients with end-stage renal disease (ESRD) are lacking. The aim of this study was to describe the patterns of physical activity among new dialysis patients in the United States. Multivariate logistic regression analyses examined associations of self-reported limitations in physical activity and exercise frequency with sociodemographic and clinical variables in 2,264 patients from Wave 2 of the Dialysis Morbidity and Mortality Study. Overall, 56% of patients exercised less than once a week, 75% reported severe limitations in vigorous activities, whereas 42% had severe limitations in moderate physical activities. Fewer limitations in moderate or vigorous activities correlated positively with male gender (odds-ratio [OR] = 1.61), black race OR =1.49), Hispanic ethnicity (OR = 2.39), serum albumin (OR = 1.69 per 1 g/L higher), positive affect (OR = 2.33), peritoneal dialysis (OR = 1.90), and negatively with age (OR = 0.67), heart failure (OR = 0.75), peripheral vascular disease (OR = 0.69), malnutrition (OR = 0.67), and depression (OR = 0.39). Patients reporting fewer limitations in moderate or vigorous activities (OR = 1.35 and 1.28, respectively), or frequent visits with a dietitian (2 to 3 times per week vs. less) (OR = 1.21) in the pre-ESRD period exercised more frequently. Limitations in physical activity are common among new ESRD patients and these, in part, are related to pre-existing cardiovascular disease, malnutrition, and mental health.

  12. Bioenergy Sorghum Crop Model Predicts VPD-Limited Transpiration Traits Enhance Biomass Yield in Water-Limited Environments

    PubMed Central

    Truong, Sandra K.; McCormick, Ryan F.; Mullet, John E.

    2017-01-01

    Bioenergy sorghum is targeted for production in water-limited annual cropland therefore traits that improve plant water capture, water use efficiency, and resilience to water deficit are necessary to maximize productivity. A crop modeling framework, APSIM, was adapted to predict the growth and biomass yield of energy sorghum and to identify potentially useful traits for crop improvement. APSIM simulations of energy sorghum development and biomass accumulation replicated results from field experiments across multiple years, patterns of rainfall, and irrigation schemes. Modeling showed that energy sorghum's long duration of vegetative growth increased water capture and biomass yield by ~30% compared to short season crops in a water-limited production region. Additionally, APSIM was extended to enable modeling of VPD-limited transpiration traits that reduce crop water use under high vapor pressure deficits (VPDs). The response of transpiration rate to increasing VPD was modeled as a linear response until a VPD threshold was reached, at which the slope of the response decreases, representing a range of responses to VPD observed in sorghum germplasm. Simulation results indicated that the VPD-limited transpiration trait is most beneficial in hot and dry regions of production where crops are exposed to extended periods without rainfall during the season or to a terminal drought. In these environments, slower but more efficient transpiration increases biomass yield and prevents or delays the exhaustion of soil water and onset of leaf senescence. The VPD-limited transpiration responses observed in sorghum germplasm increased biomass accumulation by 20% in years with lower summer rainfall, and the ability to drastically reduce transpiration under high VPD conditions could increase biomass by 6% on average across all years. This work indicates that the productivity and resilience of bioenergy sorghum grown in water-limited environments could be further enhanced by development

  13. Bioenergy Sorghum Crop Model Predicts VPD-Limited Transpiration Traits Enhance Biomass Yield in Water-Limited Environments.

    PubMed

    Truong, Sandra K; McCormick, Ryan F; Mullet, John E

    2017-01-01

    Bioenergy sorghum is targeted for production in water-limited annual cropland therefore traits that improve plant water capture, water use efficiency, and resilience to water deficit are necessary to maximize productivity. A crop modeling framework, APSIM, was adapted to predict the growth and biomass yield of energy sorghum and to identify potentially useful traits for crop improvement. APSIM simulations of energy sorghum development and biomass accumulation replicated results from field experiments across multiple years, patterns of rainfall, and irrigation schemes. Modeling showed that energy sorghum's long duration of vegetative growth increased water capture and biomass yield by ~30% compared to short season crops in a water-limited production region. Additionally, APSIM was extended to enable modeling of VPD-limited transpiration traits that reduce crop water use under high vapor pressure deficits (VPDs). The response of transpiration rate to increasing VPD was modeled as a linear response until a VPD threshold was reached, at which the slope of the response decreases, representing a range of responses to VPD observed in sorghum germplasm. Simulation results indicated that the VPD-limited transpiration trait is most beneficial in hot and dry regions of production where crops are exposed to extended periods without rainfall during the season or to a terminal drought. In these environments, slower but more efficient transpiration increases biomass yield and prevents or delays the exhaustion of soil water and onset of leaf senescence. The VPD-limited transpiration responses observed in sorghum germplasm increased biomass accumulation by 20% in years with lower summer rainfall, and the ability to drastically reduce transpiration under high VPD conditions could increase biomass by 6% on average across all years. This work indicates that the productivity and resilience of bioenergy sorghum grown in water-limited environments could be further enhanced by development

  14. Bioenergy sorghum crop model predicts VPD-limited transpiration traits enhance biomass yield in water-limited environments

    DOE PAGES

    Truong, Sandra K.; McCormick, Ryan F.; Mullet, John E.

    2017-03-21

    Bioenergy sorghum is targeted for production in water-limited annual cropland therefore traits that improve plant water capture, water use efficiency, and resilience to water deficit are necessary to maximize productivity. A crop modeling framework, APSIM, was adapted to predict the growth and biomass yield of energy sorghum and to identify potentially useful traits for crop improvement. APSIM simulations of energy sorghum development and biomass accumulation replicated results from field experiments across multiple years, patterns of rainfall, and irrigation schemes. Modeling showed that energy sorghum’s long duration of vegetative growth increased water capture and biomass yield by ~30% compared to shortmore » season crops in a water-limited production region. Additionally, APSIM was extended to enable modeling of VPD-limited transpiration traits that reduce crop water use under high vapor pressure deficits (VPDs). The response of transpiration rate to increasing VPD was modeled as a linear response until a VPD threshold was reached, at which the slope of the response decreases, representing a range of responses to VPD observed in sorghum germplasm. Simulation results indicated that the VPD-limited transpiration trait is most beneficial in hot and dry regions of production where crops are exposed to extended periods without rainfall during the season or to a terminal drought. In these environments, slower but more efficient transpiration increases biomass yield and prevents or delays the exhaustion of soil water and onset of leaf senescence. The VPD-limited transpiration responses observed in sorghum germplasm increased biomass accumulation by 20% in years with lower summer rainfall, and the ability to drastically reduce transpiration under high VPD conditions could increase biomass by 6% on average across all years. This work indicates that the productivity and resilience of bioenergy sorghum grown in water-limited environments could be further enhanced by

  15. Bioenergy sorghum crop model predicts VPD-limited transpiration traits enhance biomass yield in water-limited environments

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

    Truong, Sandra K.; McCormick, Ryan F.; Mullet, John E.

    Bioenergy sorghum is targeted for production in water-limited annual cropland therefore traits that improve plant water capture, water use efficiency, and resilience to water deficit are necessary to maximize productivity. A crop modeling framework, APSIM, was adapted to predict the growth and biomass yield of energy sorghum and to identify potentially useful traits for crop improvement. APSIM simulations of energy sorghum development and biomass accumulation replicated results from field experiments across multiple years, patterns of rainfall, and irrigation schemes. Modeling showed that energy sorghum’s long duration of vegetative growth increased water capture and biomass yield by ~30% compared to shortmore » season crops in a water-limited production region. Additionally, APSIM was extended to enable modeling of VPD-limited transpiration traits that reduce crop water use under high vapor pressure deficits (VPDs). The response of transpiration rate to increasing VPD was modeled as a linear response until a VPD threshold was reached, at which the slope of the response decreases, representing a range of responses to VPD observed in sorghum germplasm. Simulation results indicated that the VPD-limited transpiration trait is most beneficial in hot and dry regions of production where crops are exposed to extended periods without rainfall during the season or to a terminal drought. In these environments, slower but more efficient transpiration increases biomass yield and prevents or delays the exhaustion of soil water and onset of leaf senescence. The VPD-limited transpiration responses observed in sorghum germplasm increased biomass accumulation by 20% in years with lower summer rainfall, and the ability to drastically reduce transpiration under high VPD conditions could increase biomass by 6% on average across all years. This work indicates that the productivity and resilience of bioenergy sorghum grown in water-limited environments could be further enhanced by

  16. Targeting ubiquitination for cancer therapies.

    PubMed

    Morrow, John Kenneth; Lin, Hui-Kuan; Sun, Shao-Cong; Zhang, Shuxing

    2015-01-01

    Ubiquitination, the structured degradation and turnover of cellular proteins, is regulated by the ubiquitin-proteasome system (UPS). Most proteins that are critical for cellular regulations and functions are targets of the process. Ubiquitination is comprised of a sequence of three enzymatic steps, and aberrations in the pathway can lead to tumor development and progression as observed in many cancer types. Recent evidence indicates that targeting the UPS is effective for certain cancer treatment, but many more potential targets might have been previously overlooked. In this review, we will discuss the current state of small molecules that target various elements of ubiquitination. Special attention will be given to novel inhibitors of E3 ubiquitin ligases, especially those in the SCF family.

  17. Current limiter circuit system

    DOEpatents

    Witcher, Joseph Brandon; Bredemann, Michael V.

    2017-09-05

    An apparatus comprising a steady state sensing circuit, a switching circuit, and a detection circuit. The steady state sensing circuit is connected to a first, a second and a third node. The first node is connected to a first device, the second node is connected to a second device, and the steady state sensing circuit causes a scaled current to flow at the third node. The scaled current is proportional to a voltage difference between the first and second node. The switching circuit limits an amount of current that flows between the first and second device. The detection circuit is connected to the third node and the switching circuit. The detection circuit monitors the scaled current at the third node and controls the switching circuit to limit the amount of the current that flows between the first and second device when the scaled current is greater than a desired level.

  18. Deorbit targeting

    NASA Technical Reports Server (NTRS)

    Tempelman, W. H.

    1973-01-01

    The navigation and control of the space shuttle during atmospheric entry are discussed. A functional flow diagram presenting the basic approach to the deorbit targeting problem is presented. The major inputs to be considered are: (1) vehicle state vector, (2) landing site location, (3) entry interface parameters, (4) earliest desired time of landing, and (5) maximum cross range. Mathematical models of the navigational procedures based on controlled thrust times are developed.

  19. Development of Bone Targeting Drugs.

    PubMed

    Stapleton, Molly; Sawamoto, Kazuki; Alméciga-Díaz, Carlos J; Mackenzie, William G; Mason, Robert W; Orii, Tadao; Tomatsu, Shunji

    2017-06-23

    The skeletal system, comprising bones, ligaments, cartilage and their connective tissues, is critical for the structure and support of the body. Diseases that affect the skeletal system can be difficult to treat, mainly because of the avascular cartilage region. Targeting drugs to the site of action can not only increase efficacy but also reduce toxicity. Bone-targeting drugs are designed with either of two general targeting moieties, aimed at the entire skeletal system or a specific cell type. Most bone-targeting drugs utilize an affinity to hydroxyapatite, a major component of the bone matrix that includes a high concentration of positively-charged Ca 2+ . The strategies for designing such targeting moieties can involve synthetic and/or biological components including negatively-charged amino acid peptides or bisphosphonates. Efficient delivery of bone-specific drugs provides significant impact in the treatment of skeletal related disorders including infectious diseases (osteoarthritis, osteomyelitis, etc.), osteoporosis, and metabolic skeletal dysplasia. Despite recent advances, however, both delivering the drug to its target without losing activity and avoiding adverse local effects remain a challenge. In this review, we investigate the current development of bone-targeting moieties, their efficacy and limitations, and discuss future directions for the development of these specific targeted treatments.

  20. Development of Bone Targeting Drugs

    PubMed Central

    Stapleton, Molly; Sawamoto, Kazuki; Alméciga-Díaz, Carlos J.; Mackenzie, William G.; Mason, Robert W.; Orii, Tadao; Tomatsu, Shunji

    2017-01-01

    The skeletal system, comprising bones, ligaments, cartilage and their connective tissues, is critical for the structure and support of the body. Diseases that affect the skeletal system can be difficult to treat, mainly because of the avascular cartilage region. Targeting drugs to the site of action can not only increase efficacy but also reduce toxicity. Bone-targeting drugs are designed with either of two general targeting moieties, aimed at the entire skeletal system or a specific cell type. Most bone-targeting drugs utilize an affinity to hydroxyapatite, a major component of the bone matrix that includes a high concentration of positively-charged Ca2+. The strategies for designing such targeting moieties can involve synthetic and/or biological components including negatively-charged amino acid peptides or bisphosphonates. Efficient delivery of bone-specific drugs provides significant impact in the treatment of skeletal related disorders including infectious diseases (osteoarthritis, osteomyelitis, etc.), osteoporosis, and metabolic skeletal dysplasia. Despite recent advances, however, both delivering the drug to its target without losing activity and avoiding adverse local effects remain a challenge. In this review, we investigate the current development of bone-targeting moieties, their efficacy and limitations, and discuss future directions for the development of these specific targeted treatments. PMID:28644392

  1. Scale invariant SURF detector and automatic clustering segmentation for infrared small targets detection

    NASA Astrophysics Data System (ADS)

    Zhang, Haiying; Bai, Jiaojiao; Li, Zhengjie; Liu, Yan; Liu, Kunhong

    2017-06-01

    The detection and discrimination of infrared small dim targets is a challenge in automatic target recognition (ATR), because there is no salient information of size, shape and texture. Many researchers focus on mining more discriminative information of targets in temporal-spatial. However, such information may not be available with the change of imaging environments, and the targets size and intensity keep changing in different imaging distance. So in this paper, we propose a novel research scheme using density-based clustering and backtracking strategy. In this scheme, the speeded up robust feature (SURF) detector is applied to capture candidate targets in single frame at first. And then, these points are mapped into one frame, so that target traces form a local aggregation pattern. In order to isolate the targets from noises, a newly proposed density-based clustering algorithm, fast search and find of density peak (FSFDP for short), is employed to cluster targets by the spatial intensive distribution. Two important factors of the algorithm, percent and γ , are exploited fully to determine the clustering scale automatically, so as to extract the trace with highest clutter suppression ratio. And at the final step, a backtracking algorithm is designed to detect and discriminate target trace as well as to eliminate clutter. The consistence and continuity of the short-time target trajectory in temporal-spatial is incorporated into the bounding function to speed up the pruning. Compared with several state-of-arts methods, our algorithm is more effective for the dim targets with lower signal-to clutter ratio (SCR). Furthermore, it avoids constructing the candidate target trajectory searching space, so its time complexity is limited to a polynomial level. The extensive experimental results show that it has superior performance in probability of detection (Pd) and false alarm suppressing rate aiming at variety of complex backgrounds.

  2. Surface Modified Multifunctional and Stimuli Responsive Nanoparticles for Drug Targeting: Current Status and Uses

    PubMed Central

    Siafaka, Panoraia I.; Üstündağ Okur, Neslihan; Karavas, Evangelos; Bikiaris, Dimitrios N.

    2016-01-01

    Nanocarriers, due to their unique features, are of increased interest among researchers working with pharmaceutical formulations. Polymeric nanoparticles and nanocapsules, involving non-toxic biodegradable polymers, liposomes, solid lipid nanoparticles, and inorganic–organic nanomaterials, are among the most used carriers for drugs for a broad spectrum of targeted diseases. In fact, oral, injectable, transdermal-dermal and ocular formulations mainly consist of the aforementioned nanomaterials demonstrating promising characteristics such as long circulation, specific targeting, high drug loading capacity, enhanced intracellular penetration, and so on. Over the last decade, huge advances in the development of novel, safer and less toxic nanocarriers with amended properties have been made. In addition, multifunctional nanocarriers combining chemical substances, vitamins and peptides via coupling chemistry, inorganic particles coated by biocompatible materials seem to play a key role considering that functionalization can enhance characteristics such as biocompatibility, targetability, environmental friendliness, and intracellular penetration while also have limited side effects. This review aims to summarize the “state of the art” of drug delivery carriers in nanosize, paying attention to their surface functionalization with ligands and other small or polymeric compounds so as to upgrade active and passive targeting, different release patterns as well as cell targeting and stimuli responsibility. Lastly, future aspects and potential uses of nanoparticulated drug systems are outlined. PMID:27589733

  3. Optimal Control for Fast and Robust Generation of Entangled States in Anisotropic Heisenberg Chains

    NASA Astrophysics Data System (ADS)

    Zhang, Xiong-Peng; Shao, Bin; Zou, Jian

    2017-05-01

    Motivated by some recent results of the optimal control (OC) theory, we study anisotropic XXZ Heisenberg spin-1/2 chains with control fields acting on a single spin, with the aim of exploring how maximally entangled state can be prepared. To achieve the goal, we use a numerical optimization algorithm (e.g., the Krotov algorithm, which was shown to be capable of reaching the quantum speed limit) to search an optimal set of control parameters, and then obtain OC pulses corresponding to the target fidelity. We find that the minimum time for implementing our target state depending on the anisotropy parameter Δ of the model. Finally, we analyze the robustness of the obtained results for the optimal fidelities and the effectiveness of the Krotov method under some realistic conditions.

  4. 50 CFR 622.43 - Commercial trip limits.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... ADMINISTRATION, DEPARTMENT OF COMMERCE FISHERIES OF THE CARIBBEAN, GULF OF MEXICO, AND SOUTH ATLANTIC Reef Fish Resources of the Gulf of Mexico § 622.43 Commercial trip limits. Commercial trip limits are limits on the... with any trip or possession limit applicable to state waters. A species subject to a trip limit...

  5. Target Acquired: Progress and Promise of Targeted Therapeutics in the Treatment of Prostate Cancer.

    PubMed

    Stuchbery, Ryan; Kurganovs, Natalie J; McCoy, Patrick J; Nelson, Colleen C; Hayes, Vanessa M; Corcoran, Niall M; Hovens, Christopher M

    2015-01-01

    Cancer is fundamentally a genomic disease caused by mutations or rearrangements in the DNA or epigenetic machinery of a patient. An emerging field in cancer treatment targets key aberrations arising from the mutational landscape of an individual patient's disease rather than employing a cancer-wide cytotoxic therapy approach. In prostate cancer in particular, where there is an observed variation in response to standard treatments between patients with disease of a similar pathological stage and grade, mutationdirected treatment may grow to be a viable tool for clinicians to tailor more effective treatments. This review will describe a number of mutations across multiple forms of cancer that have been successfully antagonised by targeted therapeutics including their identification, the development of targeted compounds to combat them and the development of resistance to these therapies. This review will continue to examine these same mutations in the treatment and management of prostate cancer; the prevalence of targetable mutations in prostate cancer, recent clinical trials of targeted-agents and the potential or limitations for their use.

  6. Fusion of radar and satellite target measurements

    NASA Astrophysics Data System (ADS)

    Moy, Gabriel; Blaty, Donald; Farber, Morton; Nealy, Carlton

    2011-06-01

    A potentially high payoff for the ballistic missile defense system (BMDS) is the ability to fuse the information gathered by various sensor systems. In particular, it may be valuable in the future to fuse measurements made using ground based radars with passive measurements obtained from satellite-based EO/IR sensors. This task can be challenging in a multitarget environment in view of the widely differing resolution between active ground-based radar and an observation made by a sensor at long range from a satellite platform. Additionally, each sensor system could have a residual pointing bias which has not been calibrated out. The problem is further compounded by the possibility that an EO/IR sensor may not see exactly the same set of targets as a microwave radar. In order to better understand the problems involved in performing the fusion of metric information from EO/IR satellite measurements with active microwave radar measurements, we have undertaken a study of this data fusion issue and of the associated data processing techniques. To carry out this analysis, we have made use of high fidelity simulations to model the radar observations from a missile target and the observations of the same simulated target, as gathered by a constellation of satellites. In the paper, we discuss the improvements seen in our tests when fusing the state vectors, along with the improvements in sensor bias estimation. The limitations in performance due to the differing phenomenology between IR and microwave radar are discussed as well.

  7. Beam-target double-spin asymmetry in quasielastic electron scattering off the deuteron with CLAS

    NASA Astrophysics Data System (ADS)

    Mayer, M.; Kuhn, S. E.; Adhikari, K. P.; Akbar, Z.; Anefalos Pereira, S.; Asryan, G.; Avakian, H.; Badui, R. A.; Ball, J.; Baltzell, N. A.; Battaglieri, M.; Bedlinskiy, I.; Biselli, A. S.; Boiarinov, S.; Bosted, P.; Briscoe, W. J.; Brooks, W. K.; Bültmann, S.; Burkert, V. D.; Carman, D. S.; Celentano, A.; Charles, G.; Chetry, T.; Ciullo, G.; Clark, L.; Colaneri, L.; Cole, P. L.; Compton, N.; Contalbrigo, M.; Crede, V.; D'Angelo, A.; Dashyan, N.; De Vita, R.; De Sanctis, E.; Deur, A.; Djalali, C.; Dupre, R.; El Alaoui, A.; El Fassi, L.; Elouadrhiri, L.; Eugenio, P.; Fanchini, E.; Fedotov, G.; Fersch, R.; Filippi, A.; Fleming, J. A.; Forest, T. A.; Ghandilyan, Y.; Gilfoyle, G. P.; Giovanetti, K. L.; Girod, F. X.; Gleason, C.; Gothe, R. W.; Griffioen, K. A.; Guidal, M.; Guler, N.; Guo, L.; Hakobyan, H.; Hanretty, C.; Hattawy, M.; Hicks, K.; Holtrop, M.; Hughes, S. M.; Hyde, C. E.; Ilieva, Y.; Ireland, D. G.; Ishkhanov, B. S.; Isupov, E. L.; Jiang, H.; Keith, C.; Keller, D.; Khachatryan, G.; Khachatryan, M.; Khandaker, M.; Kim, A.; Kim, W.; Klein, A.; Kubarovsky, V.; Lanza, L.; Lenisa, P.; Livingston, K.; MacGregor, I. J. D.; McKinnon, B.; Meekins, D.; Mirazita, M.; Mokeev, V.; Movsisyan, A.; Net, L. A.; Niccolai, S.; Niculescu, G.; Osipenko, M.; Ostrovidov, A. I.; Paremuzyan, R.; Park, K.; Pasyuk, E.; Phelps, W.; Pogorelko, O.; Price, J. W.; Prok, Y.; Puckett, A. J. R.; Ripani, M.; Rizzo, A.; Rosner, G.; Rossi, P.; Sabatié, F.; Schumacher, R. A.; Sharabian, Y. G.; Skorodumina, Iu.; Smith, G. D.; Sokhan, D.; Sparveris, N.; Stankovic, I.; Stepanyan, S.; Strauch, S.; Sytnik, V.; Taiuti, M.; Tian, Ye; Torayev, B.; Ungaro, M.; Voskanyan, H.; Voutier, E.; Walford, N. K.; Weinstein, L. B.; Wood, M. H.; Zachariou, N.; Zhang, J.; Zonta, I.; CLAS Collaboration

    2017-02-01

    Background: The deuteron plays a pivotal role in nuclear and hadronic physics, as both the simplest bound multinucleon system and as an effective neutron target. Quasielastic electron scattering on the deuteron is a benchmark reaction to test our understanding of deuteron structure and the properties and interactions of the two nucleons bound in the deuteron. Purpose: The experimental data presented here can be used to test state-of-the-art models of the deuteron and the two-nucleon interaction in the final state after two-body breakup of the deuteron. Focusing on polarization degrees of freedom, we gain information on spin-momentum correlations in the deuteron ground state (due to the D -state admixture) and on the limits of the impulse approximation (IA) picture as it applies to measurements of spin-dependent observables like spin structure functions for bound nucleons. Information on this reaction can also be used to reduce systematic uncertainties on the determination of neutron form factors or deuteron polarization through quasielastic polarized electron scattering. Method: We measured the beam-target double-spin asymmetry (A||) for quasielastic electron scattering off the deuteron at several beam energies (1.6 -1.7 , 2.5, 4.2, and 5.6 -5.8 GeV ), using the CEBAF Large Acceptance Spectrometer (CLAS) at the Thomas Jefferson National Accelerator Facility. The deuterons were polarized along (or opposite to) the beam direction. The double-spin asymmetries were measured as a function of photon virtuality Q2(0.13 -3.17 (GeV/c ) 2) , missing momentum (pm=0.0 -0.5 GeV /c ), and the angle between the (inferred) spectator neutron and the momentum transfer direction (θn q). Results: The results are compared with a recent model that includes final-state interactions (FSI) using a complete parametrization of nucleon-nucleon scattering, as well as a simplified model using the plane wave impulse approximation (PWIA). We find overall good agreement with both the PWIA and FSI

  8. 7 CFR 52.3185 - Moisture limits.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 2 2012-01-01 2012-01-01 false Moisture limits. 52.3185 Section 52.3185 Agriculture... United States Standards for Grades of Dried Prunes Moisture, Uniformity of Size, Defects § 52.3185 Moisture limits. Dried prunes shall not exceed the moisture limits for the applicable grades and kind and...

  9. 7 CFR 52.3185 - Moisture limits.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 2 2013-01-01 2013-01-01 false Moisture limits. 52.3185 Section 52.3185 Agriculture... CERTAIN OTHER PROCESSED FOOD PRODUCTS 1 United States Standards for Grades of Dried Prunes Moisture, Uniformity of Size, Defects § 52.3185 Moisture limits. Dried prunes shall not exceed the moisture limits for...

  10. 7 CFR 52.3185 - Moisture limits.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 2 2014-01-01 2014-01-01 false Moisture limits. 52.3185 Section 52.3185 Agriculture... CERTAIN OTHER PROCESSED FOOD PRODUCTS 1 United States Standards for Grades of Dried Prunes Moisture, Uniformity of Size, Defects § 52.3185 Moisture limits. Dried prunes shall not exceed the moisture limits for...

  11. Environmental limitation mapping of potential biomass resources across the conterminous United States

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

    Daly, Christopher; Halbleib, Michael D.; Hannaway, David B.

    Several crops have recently been identified as potential dedicated bioenergy feedstocks for the production of power, fuels, and bioproducts. Despite being identified as early as the 1980s, no systematic work has been undertaken to characterize the spatial distribution of their long-term production potentials in the United states. Such information is a starting point for planners and economic modelers, and there is a need for this spatial information to be developed in a consistent manner for a variety of crops, so that their production potentials can be intercompared to support crop selection decisions. As part of the Sun Grant Regional Feedstockmore » Partnership (RFP), an approach to mapping these potential biomass resources was developed to take advantage of the informational synergy realized when bringing together coordinated field trials, close interaction with expert agronomists, and spatial modeling into a single, collaborative effort. A modeling and mapping system called PRISM-ELM was designed to answer a basic question: How do climate and soil characteristics affect the spatial distribution and long-term production patterns of a given crop? This empirical/mechanistic/biogeographical hybrid model employs a limiting factor approach, where productivity is determined by the most limiting of the factors addressed in submodels that simulate water balance, winter low-temperature response, summer high-temperature response, and soil pH, salinity, and drainage. Yield maps are developed through linear regressions relating soil and climate attributes to reported yield data. The model was parameterized and validated using grain yield data for winter wheat and maize, which served as benchmarks for parameterizing the model for upland and lowland switchgrass, CRP grasses, Miscanthus, biomass sorghum, energycane, willow, and poplar. The resulting maps served as potential production inputs to analyses comparing the viability of biomass crops under various economic

  12. Environmental limitation mapping of potential biomass resources across the conterminous United States

    DOE PAGES

    Daly, Christopher; Halbleib, Michael D.; Hannaway, David B.; ...

    2017-12-22

    Several crops have recently been identified as potential dedicated bioenergy feedstocks for the production of power, fuels, and bioproducts. Despite being identified as early as the 1980s, no systematic work has been undertaken to characterize the spatial distribution of their long-term production potentials in the United states. Such information is a starting point for planners and economic modelers, and there is a need for this spatial information to be developed in a consistent manner for a variety of crops, so that their production potentials can be intercompared to support crop selection decisions. As part of the Sun Grant Regional Feedstockmore » Partnership (RFP), an approach to mapping these potential biomass resources was developed to take advantage of the informational synergy realized when bringing together coordinated field trials, close interaction with expert agronomists, and spatial modeling into a single, collaborative effort. A modeling and mapping system called PRISM-ELM was designed to answer a basic question: How do climate and soil characteristics affect the spatial distribution and long-term production patterns of a given crop? This empirical/mechanistic/biogeographical hybrid model employs a limiting factor approach, where productivity is determined by the most limiting of the factors addressed in submodels that simulate water balance, winter low-temperature response, summer high-temperature response, and soil pH, salinity, and drainage. Yield maps are developed through linear regressions relating soil and climate attributes to reported yield data. The model was parameterized and validated using grain yield data for winter wheat and maize, which served as benchmarks for parameterizing the model for upland and lowland switchgrass, CRP grasses, Miscanthus, biomass sorghum, energycane, willow, and poplar. The resulting maps served as potential production inputs to analyses comparing the viability of biomass crops under various economic

  13. Simultaneous Proteomic Discovery and Targeted Monitoring using Liquid Chromatography, Ion Mobility Spectrometry, and Mass Spectrometry*

    PubMed Central

    Burnum-Johnson, Kristin E.; Nie, Song; Casey, Cameron P.; Monroe, Matthew E.; Orton, Daniel J.; Ibrahim, Yehia M.; Gritsenko, Marina A.; Clauss, Therese R. W.; Shukla, Anil K.; Moore, Ronald J.; Purvine, Samuel O.; Shi, Tujin; Qian, Weijun; Liu, Tao; Baker, Erin S.; Smith, Richard D.

    2016-01-01

    Current proteomic approaches include both broad discovery measurements and quantitative targeted analyses. In many cases, discovery measurements are initially used to identify potentially important proteins (e.g. candidate biomarkers) and then targeted studies are employed to quantify a limited number of selected proteins. Both approaches, however, suffer from limitations. Discovery measurements aim to sample the whole proteome but have lower sensitivity, accuracy, and quantitation precision than targeted approaches, whereas targeted measurements are significantly more sensitive but only sample a limited portion of the proteome. Herein, we describe a new approach that performs both discovery and targeted monitoring (DTM) in a single analysis by combining liquid chromatography, ion mobility spectrometry and mass spectrometry (LC-IMS-MS). In DTM, heavy labeled target peptides are spiked into tryptic digests and both the labeled and unlabeled peptides are detected using LC-IMS-MS instrumentation. Compared with the broad LC-MS discovery measurements, DTM yields greater peptide/protein coverage and detects lower abundance species. DTM also achieved detection limits similar to selected reaction monitoring (SRM) indicating its potential for combined high quality discovery and targeted analyses, which is a significant step toward the convergence of discovery and targeted approaches. PMID:27670688

  14. Occupational exposure limits for nanomaterials: state of the art

    NASA Astrophysics Data System (ADS)

    Schulte, P. A.; Murashov, V.; Zumwalde, R.; Kuempel, E. D.; Geraci, C. L.

    2010-08-01

    Assessing the need for and effectiveness of controlling airborne exposures to engineered nanomaterials in the workplace is difficult in the absence of occupational exposure limits (OELs). At present, there are practically no OELs specific to nanomaterials that have been adopted or promulgated by authoritative standards and guidance organizations. The vast heterogeneity of nanomaterials limits the number of specific OELs that are likely to be developed in the near future, but OELs could be developed more expeditiously for nanomaterials by applying dose-response data generated from animal studies for specific nanoparticles across categories of nanomaterials with similar properties and modes of action. This article reviews the history, context, and approaches for developing OELs for particles in general and nanoparticles in particular. Examples of approaches for developing OELs for titanium dioxide and carbon nanotubes are presented and interim OELs from various organizations for some nanomaterials are discussed. When adequate dose-response data are available in animals or humans, quantitative risk assessment methods can provide estimates of adverse health risk of nanomaterials in workers and, in conjunction with workplace exposure and control data, provide a basis for determining appropriate exposure limits. In the absence of adequate quantitative data, qualitative approaches to hazard assessment, exposure control, and safe work practices are prudent measures to reduce hazards in workers.

  15. On the tensionless limit of gauged WZW models

    NASA Astrophysics Data System (ADS)

    Bakas, I.; Sourdis, C.

    2004-06-01

    The tensionless limit of gauged WZW models arises when the level of the underlying Kac-Moody algebra assumes its critical value, equal to the dual Coxeter number, in which case the central charge of the Virasoro algebra becomes infinite. We examine this limit from the world-sheet and target space viewpoint and show that gravity decouples naturally from the spectrum. Using the two-dimensional black-hole coset SL(2,Bbb R)k/U(1) as illustrative example, we find for k = 2 that the world-sheet symmetry is described by a truncated version of Winfty generated by chiral fields with integer spin s geq 3, whereas the Virasoro algebra becomes abelian and it can be consistently factored out. The geometry of target space looks like an infinitely curved hyperboloid, which invalidates the effective field theory description and conformal invariance can no longer be used to yield reliable space-time interpretation. We also compare our results with the null gauging of WZW models, which correspond to infinite boost in target space and they describe the Liouville mode that decouples in the tensionless limit. A formal BRST analysis of the world-sheet symmetry suggests that the central charge of all higher spin generators should be fixed to a critical value, which is not seen by the contracted Virasoro symmetry. Generalizations to higher dimensional coset models are also briefly discussed in the tensionless limit, where similar observations are made.

  16. Robust Targeting for the Smartphone Video Guidance Sensor

    NASA Technical Reports Server (NTRS)

    Carter, Christopher

    2017-01-01

    The Smartphone Video Guidance Sensor (SVGS) is a miniature, self-contained autonomous rendezvous and docking sensor developed using a commercial off the shelf Android-based smartphone. It aims to provide a miniaturized solution for rendezvous and docking, enabling small satellites to conduct proximity operations and formation flying while minimizing interference with a primary payload. Previously, the sensor was limited by a slow (2 Hz) refresh rate and its use of retro-reflectors, both of which contributed to a limited operating environment. To advance the technology readiness level, a modified approach was developed, combining a multi-colored LED target with a focused target-detection algorithm. Alone, the use of an LED system was determined to be much more reliable, though slower, than the retro-reflector system. The focused target-detection system was developed in response to this problem to mitigate the speed reduction of using color. However, it also improved the reliability. In combination these two methods have been demonstrated to dramatically increase sensor speed and allow the sensor to select the target even with significant noise interfering with the sensor, providing millimeter level accuracy at a range of two meters with a 1U target.

  17. Robust Targeting for the Smartphone Video Guidance Sensor

    NASA Technical Reports Server (NTRS)

    Carter, C.

    2017-01-01

    The Smartphone Video Guidance Sensor (SVGS) is a miniature, self-contained autonomous rendezvous and docking sensor developed using a commercial off the shelf Android-based smartphone. It aims to provide a miniaturized solution for rendezvous and docking, enabling small satellites to conduct proximity operations and formation flying while minimizing interference with a primary payload. Previously, the sensor was limited by a slow (2 Hz) refresh rate and its use of retro-reflectors, both of which contributed to a limited operating environment. To advance the technology readiness level, a modified approach was developed, combining a multi-colored LED target with a focused target-detection algorithm. Alone, the use of an LED system was determined to be much more reliable, though slower, than the retro-reflector system. The focused target-detection system was developed in response to this problem to mitigate the speed reduction of using color. However it also improved the reliability. In combination these two methods have been demonstrated to dramatically increase sensor speed and allow the sensor to select the target even with significant noise interfering with the sensor, providing millimeter level precision at a range of two meters with a 1U target.

  18. 50 CFR 622.275 - Size limits.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ..., DEPARTMENT OF COMMERCE FISHERIES OF THE CARIBBEAN, GULF OF MEXICO, AND SOUTH ATLANTIC Dolphin and Wahoo Fishery Off the Atlantic States § 622.275 Size limits. All size limits in this section are minimum size...

  19. 50 CFR 622.275 - Size limits.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ..., DEPARTMENT OF COMMERCE FISHERIES OF THE CARIBBEAN, GULF OF MEXICO, AND SOUTH ATLANTIC Dolphin and Wahoo Fishery Off the Atlantic States § 622.275 Size limits. All size limits in this section are minimum size...

  20. Adenylylation of mycobacterial Glnk (PII) protein is induced by nitrogen limitation

    PubMed Central

    Williams, Kerstin J.; Bennett, Mark H.; Barton, Geraint R.; Jenkins, Victoria A.; Robertson, Brian D.

    2013-01-01

    Summary PII proteins are pivotal regulators of nitrogen metabolism in most prokaryotes, controlling the activities of many targets, including nitrogen assimilation enzymes, two component regulatory systems and ammonium transport proteins. Escherichia coli contains two PII-like proteins, PII (product of glnB) and GlnK, both of which are uridylylated under nitrogen limitation at a conserved Tyrosine-51 residue by GlnD (a uridylyl transferase). PII-uridylylation in E. coli controls glutamine synthetase (GS) adenylylation by GlnE and mediates the NtrB/C transcriptomic response. Mycobacteria contain only one PII protein (GlnK) which in environmental Actinomycetales is adenylylated by GlnD under nitrogen limitation. However in mycobacteria, neither the type of GlnK (PII) covalent modification nor its precise role under nitrogen limitation is known. In this study, we used LC-Tandem MS to analyse the modification state of mycobacterial GlnK (PII), and demonstrate that during nitrogen limitation GlnK from both non-pathogenic Mycobacterium smegmatis and pathogenic Mycobacterium tuberculosis is adenylylated at the Tyrosine-51 residue; we also show that GlnD is the adenylyl transferase enzyme responsible. Further analysis shows that in contrast to E. coli, GlnK (PII) adenylylation in M. tuberculosis does not regulate GS adenylylation, nor does it mediate the transcriptomic response to nitrogen limitation. PMID:23352854

  1. Variability and Limits of US State Laws Regulating Workplace Wellness Programs.

    PubMed

    Pomeranz, Jennifer L; Garcia, Andrea M; Vesprey, Randy; Davey, Adam

    2016-06-01

    We examined variability in state laws related to workplace wellness programs for public and private employers. We conducted legal research using LexisNexis and Westlaw to create a master list of US state laws that existed in 2014 dedicated to workplace wellness programs. The master list was then divided into laws focusing on public employers and private employers. We created 2 codebooks to describe the variables used to examine the laws. Coders used LawAtlas(SM) Workbench to code the laws related to workplace wellness programs. Thirty-two states and the District of Columbia had laws related to workplace wellness programs in 2014. Sixteen states and the District of Columbia had laws dedicated to public employers, and 16 states had laws dedicated to private employers. Nine states and the District of Columbia had laws that did not specify employer type. State laws varied greatly in their methods of encouraging or shaping wellness program requirements. Few states have comprehensive requirements or incentives to support evidence-based workplace wellness programs.

  2. THINK OUTSIDE THE COLOR BOX: PROBABILISTIC TARGET SELECTION AND THE SDSS-XDQSOQUASAR TARGETING CATALOG

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

    BOVY, J.; Sheldon, E.; Hennawi, J.F.

    2011-03-10

    We present the SDSS-XDQSO quasar targeting catalog for efficient flux-based quasar target selection down to the faint limit of the Sloan Digital Sky Survey (SDSS) catalog, even at medium redshifts (2.5 {approx}< z {approx}< 3) where the stellar contamination is significant. We build models of the distributions of stars and quasars in flux space down to the flux limit by applying the extreme-deconvolution method to estimate the underlying density. We convolve this density with the flux uncertainties when evaluating the probability that an object is a quasar. This approach results in a targeting algorithm that is more principled, more efficient,more » and faster than other similar methods. We apply the algorithm to derive low-redshift (z < 2.2), medium-redshift (2.2 {le} z {le} 3.5), and high-redshift (z > 3.5) quasar probabilities for all 160,904,060 point sources with dereddened i-band magnitude between 17.75 and 22.45 mag in the 14,555 deg{sup 2} of imaging from SDSS Data Release 8. The catalog can be used to define a uniformly selected and efficient low- or medium-redshift quasar survey, such as that needed for the SDSS-III's Baryon Oscillation Spectroscopic Survey project. We show that the XDQSO technique performs as well as the current best photometric quasar-selection technique at low redshift, and outperforms all other flux-based methods for selecting the medium-redshift quasars of our primary interest. We make code to reproduce the XDQSO quasar target selection publicly available.« less

  3. Debt capacity and debt limits : a state road fund perspective.

    DOT National Transportation Integrated Search

    2004-06-01

    State governments are facing major transportation infrastructure financing challenges as highway or Road Fund revenue growth has slowed and resistance to tax increases has strengthened. As a result, state transportation officials have turned to other...

  4. Dendritic Cells Limit Fibro-Inflammatory Injury in NASH

    PubMed Central

    Henning, Justin R.; Graffeo, Christopher S.; Rehman, Adeel; Fallon, Nina C.; Zambirinis, Constantinos P.; Ochi, Atsuo; Barilla, Rocky; Jamal, Mohsin; Deutsch, Michael; Greco, Stephanie; Ego-Osuala, Melvin; Saeed, Usama Bin; Rao, Raghavendra S.; Badar, Sana; Quesada, Juan P.; Acehan, Devrim; Miller, George

    2013-01-01

    Non-alcoholic steatohepatitis (NASH) is the most common etiology of chronic liver dysfunction in the United States and can progress to cirrhosis and liver failure. Inflammatory insult resulting from fatty infiltration of the liver is central to disease pathogenesis. Dendritic cells (DC) are antigen presenting cells with an emerging role in hepatic inflammation. We postulated that DC are important in the progression of NASH. We found that intrahepatic DC expand and mature in NASH liver and assume an activated immune-phenotype. However, rather than mitigating the severity of NASH, DC depletion markedly exacerbated intrahepatic fibro-inflammation. Our mechanistic studies support a regulatory role for DC in NASH by limiting sterile inflammation via their role in clearance of apoptotic cells and necrotic debris. We found that DC limit CD8+ T cell expansion and restrict Toll-like receptor expression and cytokine production in innate immune effector cells in NASH, including Kupffer cells, neutrophils, and inflammatory monocytes. Consistent with their regulatory role in NASH, during the recovery phase of disease, ablation of DC populations results in delayed resolution of intrahepatic inflammation and fibroplasia. Conclusion Our findings support a role for DC in modulating NASH. Targeting DC functional properties may hold promise for therapeutic intervention in NASH. PMID:23322710

  5. Blue and Black Cloth Targets: Effects of Size, Shape, and Color on Stable Fly (Diptera: Muscidae) Attraction.

    PubMed

    Hogsette, Jerome A; Foil, Lane D

    2018-04-02

    Stable fly management is challenging because of the fly's dispersal behavior and its tendency to remain on the host only while feeding. Optically attractive traps have been used to survey and sometimes reduce adult populations. Insecticide-treated blue and black cloth targets developed for tsetse fly management in Africa were found to be attractive to stable flies in the United States, and various evaluations were conducted in Louisiana and Florida. Tests using untreated targets were designed to answer questions about configuration, size, and color relative to efficacy and stability in high winds. Studies with electric grid targets and with targets paired with Olson traps showed cloth target color attraction in the following decreasing order: black > blue-black > blue. A solid black target is easier to make than a blue-black target because no sewing is involved. Attraction was not affected when flat 1-m2 targets were formed into cylinders, despite the limited view of the blue and black colors together. There was no reduction in attraction when the 1-m2 cylindrical targets were compared with smaller (63 × 30 cm high) cylindrical targets. In addition, there was no difference in attraction between the small blue-black, blue, and black targets. Significance of findings and implications of potential uses for treated targets are discussed. Target attraction was indicated by the numbers of stable flies captured on an Olson sticky trap placed 30 cm from the target. Although this system is adequate for field research, it greatly underestimates the actual numbers of stable flies attracted to treated targets.

  6. Targeting the (Un)differentiated State of Cancer.

    PubMed

    Kemeny, Lajos V; Fisher, David E

    2018-05-14

    Dedifferentation in cancer is associated with intrinsic and acquired resistance to therapies. In this issue of Cancer Cell, Tsoi et al. identify four differentiation states in melanoma and provide evidence that melanoma cells develop drug resistance through a stepwise dedifferentiation process, making them vulnerable to ferroptotic cell death-inducing compounds. Copyright © 2018 Elsevier Inc. All rights reserved.

  7. Continuous movement decoding using a target-dependent model with EMG inputs.

    PubMed

    Sachs, Nicholas A; Corbett, Elaine A; Miller, Lee E; Perreault, Eric J

    2011-01-01

    Trajectory-based models that incorporate target position information have been shown to accurately decode reaching movements from bio-control signals, such as muscle (EMG) and cortical activity (neural spikes). One major hurdle in implementing such models for neuroprosthetic control is that they are inherently designed to decode single reaches from a position of origin to a specific target. Gaze direction can be used to identify appropriate targets, however information regarding movement intent is needed to determine when a reach is meant to begin and when it has been completed. We used linear discriminant analysis to classify limb states into movement classes based on recorded EMG from a sparse set of shoulder muscles. We then used the detected state transitions to update target information in a mixture of Kalman filters that incorporated target position explicitly in the state, and used EMG activity to decode arm movements. Updating the target position initiated movement along new trajectories, allowing a sequence of appropriately timed single reaches to be decoded in series and enabling highly accurate continuous control.

  8. Exotic magnetic states in Pauli-limited superconductors.

    PubMed

    Kenzelmann, M

    2017-03-01

    Magnetism and superconductivity compete or interact in complex and intricate ways. Here we review the special case where novel magnetic phenomena appear due to superconductivity, but do not exist without it. Such states have recently been identified in unconventional superconductors. They are different from the mere coexistence of magnetic order and superconductivity in conventional superconductors, or from competing magnetic and superconducting phases in many materials. We describe the recent progress in the study of such exotic magnetic phases, and articulate the many open questions in this field.

  9. A Solid-State Fault Current Limiting Device for VSC-HVDC Systems

    NASA Astrophysics Data System (ADS)

    Larruskain, D. Marene; Zamora, Inmaculada; Abarrategui, , Oihane; Iturregi, Araitz

    2013-08-01

    Faults in the DC circuit constitute one of the main limitations of voltage source converter VSC-HVDC systems, as the high fault currents can damage seriously the converters. In this article, a new design for a fault current limiter (FCL) is proposed, which is capable of limiting the fault current as well as interrupting it, isolating the DC grid. The operation of the proposed FCL is analysed and verified with the most usual faults that can occur in overhead lines.

  10. Greenhouse-gas emission targets for limiting global warming to 2 degrees C.

    PubMed

    Meinshausen, Malte; Meinshausen, Nicolai; Hare, William; Raper, Sarah C B; Frieler, Katja; Knutti, Reto; Frame, David J; Allen, Myles R

    2009-04-30

    More than 100 countries have adopted a global warming limit of 2 degrees C or below (relative to pre-industrial levels) as a guiding principle for mitigation efforts to reduce climate change risks, impacts and damages. However, the greenhouse gas (GHG) emissions corresponding to a specified maximum warming are poorly known owing to uncertainties in the carbon cycle and the climate response. Here we provide a comprehensive probabilistic analysis aimed at quantifying GHG emission budgets for the 2000-50 period that would limit warming throughout the twenty-first century to below 2 degrees C, based on a combination of published distributions of climate system properties and observational constraints. We show that, for the chosen class of emission scenarios, both cumulative emissions up to 2050 and emission levels in 2050 are robust indicators of the probability that twenty-first century warming will not exceed 2 degrees C relative to pre-industrial temperatures. Limiting cumulative CO(2) emissions over 2000-50 to 1,000 Gt CO(2) yields a 25% probability of warming exceeding 2 degrees C-and a limit of 1,440 Gt CO(2) yields a 50% probability-given a representative estimate of the distribution of climate system properties. As known 2000-06 CO(2) emissions were approximately 234 Gt CO(2), less than half the proven economically recoverable oil, gas and coal reserves can still be emitted up to 2050 to achieve such a goal. Recent G8 Communiqués envisage halved global GHG emissions by 2050, for which we estimate a 12-45% probability of exceeding 2 degrees C-assuming 1990 as emission base year and a range of published climate sensitivity distributions. Emissions levels in 2020 are a less robust indicator, but for the scenarios considered, the probability of exceeding 2 degrees C rises to 53-87% if global GHG emissions are still more than 25% above 2000 levels in 2020.

  11. Progress on the chemical separation of fission fragments from 236Np produced by proton irradiation of natural uranium target

    NASA Astrophysics Data System (ADS)

    Larijani, C.; Jerome, S. M.; Lorusso, G.; Ivanov, P.; Russell, B.; Pearce, A. K.; Regan, P. H.

    2017-11-01

    The aim of the current work is to develop and validate a radiochemical separation scheme capable of separating both 236gNp and 236Pu from a uranium target of natural isotopic composition ( 1 g uranium) and 200 MBq of fission decay products. A target containing 1.2 g of UO2 was irradiated with a beam of 25 MeV protons with a typical beam current of 30 μA for 19 h in December 2013 at the University of Birmingham Cyclotron facility. Using literature values for the production cross-section for fusion of protons with uranium targets, we estimate that an upper limit of approximately 250 Bq of activity from the 236Np ground state was produced in this experiment. Using a radiochemical separation scheme, Np and Pu fractions were separated from the produced fission decay products, with analyses of the target-based final reaction products made using Inductively Couple Plasma Mass Spectrometry (ICP-MS) and high-resolution α particle and γ-ray spectrometry.

  12. Design of an algorithm for autonomous docking with a freely tumbling target

    NASA Astrophysics Data System (ADS)

    Nolet, Simon; Kong, Edmund; Miller, David W.

    2005-05-01

    For complex unmanned docking missions, limited communication bandwidth and delays do not allow ground operators to have immediate access to all real-time state information and hence prevent them from playing an active role in the control loop. Advanced control algorithms are needed to make mission critical decisions to ensure safety of both spacecraft during close proximity maneuvers. This is especially true when unexpected contingencies occur. These algorithms will enable multiple space missions, including servicing of damaged spacecraft and missions to Mars. A key characteristic of spacecraft servicing missions is that the target spacecraft is likely to be freely tumbling due to various mechanical failures or fuel depletion. Very few technical references in the literature can be found on autonomous docking with a freely tumbling target and very few such maneuvers have been attempted. The MIT Space Systems Laboratory (SSL) is currently performing research on the subject. The objective of this research is to develop a control architecture that will enable safe and fuel-efficient docking of a thruster based spacecraft with a freely tumbling target in presence of obstacles and contingencies. The approach is to identify, select and implement state estimation, fault detection, isolation and recovery, optimal path planning and thruster management algorithms that, once properly integrated, can accomplish such a maneuver autonomously. Simulations and demonstrations on the SPHERES testbed developed by the MIT SSL will be executed to assess the performance of different combinations of algorithms. To date, experiments have been carried out at the MIT SSL 2-D Laboratory and at the NASA Marshall Space Flight Center (MSFC) flat floor.

  13. Development of high resolution target monitor.

    DOT National Transportation Integrated Search

    2008-01-01

    The proposed High-resolution Target Movement Monitor uses triangulation theory but in a unique way. Unlike the commercially available triangulation systems which use sensing diodes to perceive reflected laser signatures and are limited to very short ...

  14. Vital Signs: Prevalence of Doctor-Diagnosed Arthritis and Arthritis-Attributable Activity Limitation — United States, 2013–2015

    PubMed Central

    Helmick, Charles G.; Boring, Michael; Brady, Teresa J.

    2017-01-01

    Background In the United States, doctor-diagnosed arthritis is a common and disabling chronic condition. Arthritis can lead to severe joint pain and poor physical function, and it can negatively affect quality of life. Methods CDC analyzed 2013–2015 data from the National Health Interview Survey, an annual, nationally representative, in-person interview survey of the health status and behaviors of the noninstitutionalized civilian U.S. adult population, to update previous prevalence estimates of arthritis and arthritis-attributable activity limitations. Results On average, during 2013–2015, 54.4 million (22.7%) adults had doctor-diagnosed arthritis, and 23.7 million (43.5% of those with arthritis) had arthritis-attributable activity limitations (an age-adjusted increase of approximately 20% in the proportion of adults with arthritis reporting activity limitations since 2002 [p-trend <0.001]). Among adults with heart disease, diabetes, and obesity, the prevalences of doctor-diagnosed arthritis were 49.3%, 47.1%, and 30.6%, respectively; the prevalences of arthritis-attributable activity limitations among adults with these conditions and arthritis were 54.5% (heart disease), 54.0% (diabetes), and 49.0% (obesity). Conclusions and Comments The prevalence of arthritis is high, particularly among adults with comorbid conditions, such as heart disease, diabetes, and obesity. Furthermore, the prevalence of arthritis-attributable activity limitations is high and increasing over time. Approximately half of adults with arthritis and heart disease, arthritis and diabetes, or arthritis and obesity are limited by their arthritis. Greater use of evidence-based physical activity and self-management education interventions can reduce pain and improve function and quality of life for adults with arthritis and also for adults with other chronic conditions who might be limited by their arthritis. PMID:28278145

  15. 26 CFR 1.904(i)-1 - Limitation on use of deconsolidation to avoid foreign tax credit limitations.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... foreign tax credit limitations. 1.904(i)-1 Section 1.904(i)-1 Internal Revenue INTERNAL REVENUE SERVICE... United States § 1.904(i)-1 Limitation on use of deconsolidation to avoid foreign tax credit limitations... applying the foreign tax credit provisions of section 59(a), sections 901 through 908, and section 960, the...

  16. Molecular pathways: targeting p21-activated kinase 1 signaling in cancer--opportunities, challenges, and limitations.

    PubMed

    Eswaran, Jeyanthy; Li, Da-Qiang; Shah, Anil; Kumar, Rakesh

    2012-07-15

    The evolution of cancer cells involves deregulation of highly regulated fundamental pathways that are central to normal cellular architecture and functions. p21-activated kinase 1 (PAK1) was initially identified as a downstream effector of the GTPases Rac and Cdc42. Subsequent studies uncovered a variety of new functions for this kinase in growth factor and steroid receptor signaling, cytoskeleton remodeling, cell survival, oncogenic transformation, and gene transcription, largely through systematic discovery of its direct, physiologically relevant substrates. PAK1 is widely upregulated in several human cancers, such as hormone-dependent cancer, and is intimately linked to tumor progression and therapeutic resistance. These exciting developments combined with the kinase-independent role of PAK1-centered phenotypic signaling in cancer cells elevated PAK1 as an attractive drug target. Structural and biochemical studies revealed the precise mechanism of PAK1 activation, offering the possibility to develop PAK1-targeted cancer therapeutic approaches. In addition, emerging reports suggest the potential of PAK1 and its specific phosphorylated substrates as cancer prognostic markers. Here, we summarize recent findings about the PAK1 molecular pathways in human cancer and discuss the current status of PAK1-targeted anticancer therapies.

  17. Producing superfluid circulation states using phase imprinting

    NASA Astrophysics Data System (ADS)

    Kumar, Avinash; Dubessy, Romain; Badr, Thomas; De Rossi, Camilla; de Goër de Herve, Mathieu; Longchambon, Laurent; Perrin, Hélène

    2018-04-01

    We propose a method to prepare states of given quantized circulation in annular Bose-Einstein condensates (BEC) confined in a ring trap using the method of phase imprinting without relying on a two-photon angular momentum transfer. The desired phase profile is imprinted on the atomic wave function using a short light pulse with a tailored intensity pattern generated with a spatial light modulator. We demonstrate the realization of "helicoidal" intensity profiles suitable for this purpose. Due to the diffraction limit, the theoretical steplike intensity profile is not achievable in practice. We investigate the effect of imprinting an intensity profile smoothed by a finite optical resolution onto the annular BEC with a numerical simulation of the time-dependent Gross-Pitaevskii equation. This allows us to optimize the intensity pattern for a given target circulation to compensate for the limited resolution.

  18. Molecular Targets for PET Imaging of Activated Microglia: The Current Situation and Future Expectations.

    PubMed

    Tronel, Claire; Largeau, Bérenger; Santiago Ribeiro, Maria Joao; Guilloteau, Denis; Dupont, Anne-Claire; Arlicot, Nicolas

    2017-04-11

    Microglia, as cellular mediators of neuroinflammation, are implicated in the pathogenesis of a wide range of neurodegenerative diseases. Positron emission tomography (PET) imaging of microglia has matured over the last 20 years, through the development of radiopharmaceuticals targeting several molecular biomarkers of microglial activation and, among these, mainly the translocator protein-18 kDa (TSPO). Nevertheless, current limitations of TSPO as a PET microglial biomarker exist, such as low brain density, even in a neurodegenerative setting, expression by other cells than the microglia (astrocytes, peripheral macrophages in the case of blood brain barrier breakdown), genetic polymorphism, inducing a variation for most of TSPO PET radiopharmaceuticals' binding affinity, or similar expression in activated microglia regardless of its polarization (pro- or anti-inflammatory state), and these limitations narrow its potential interest. We overview alternative molecular targets, for which dedicated radiopharmaceuticals have been proposed, including receptors (purinergic receptors P2X7, cannabinoid receptors, α7 and α4β2 nicotinic acetylcholine receptors, adenosine 2A receptor, folate receptor β) and enzymes (cyclooxygenase, nitric oxide synthase, matrix metalloproteinase, β-glucuronidase, and enzymes of the kynurenine pathway), with a particular focus on their respective contribution for the understanding of microglial involvement in neurodegenerative diseases. We discuss opportunities for these potential molecular targets for PET imaging regarding their selectivity for microglia expression and polarization, in relation to the mechanisms by which microglia actively participate in both toxic and neuroprotective actions in brain diseases, and then take into account current clinicians' expectations.

  19. Simultaneous Proteomic Discovery and Targeted Monitoring using Liquid Chromatography, Ion Mobility Spectrometry, and Mass Spectrometry.

    PubMed

    Burnum-Johnson, Kristin E; Nie, Song; Casey, Cameron P; Monroe, Matthew E; Orton, Daniel J; Ibrahim, Yehia M; Gritsenko, Marina A; Clauss, Therese R W; Shukla, Anil K; Moore, Ronald J; Purvine, Samuel O; Shi, Tujin; Qian, Weijun; Liu, Tao; Baker, Erin S; Smith, Richard D

    2016-12-01

    Current proteomic approaches include both broad discovery measurements and quantitative targeted analyses. In many cases, discovery measurements are initially used to identify potentially important proteins (e.g. candidate biomarkers) and then targeted studies are employed to quantify a limited number of selected proteins. Both approaches, however, suffer from limitations. Discovery measurements aim to sample the whole proteome but have lower sensitivity, accuracy, and quantitation precision than targeted approaches, whereas targeted measurements are significantly more sensitive but only sample a limited portion of the proteome. Herein, we describe a new approach that performs both discovery and targeted monitoring (DTM) in a single analysis by combining liquid chromatography, ion mobility spectrometry and mass spectrometry (LC-IMS-MS). In DTM, heavy labeled target peptides are spiked into tryptic digests and both the labeled and unlabeled peptides are detected using LC-IMS-MS instrumentation. Compared with the broad LC-MS discovery measurements, DTM yields greater peptide/protein coverage and detects lower abundance species. DTM also achieved detection limits similar to selected reaction monitoring (SRM) indicating its potential for combined high quality discovery and targeted analyses, which is a significant step toward the convergence of discovery and targeted approaches. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  20. Virus-Based Cancer Therapeutics for Targeted Photodynamic Therapy.

    PubMed

    Cao, Binrui; Xu, Hong; Yang, Mingying; Mao, Chuanbin

    2018-01-01

    Cancer photodynamic therapy (PDT) involves the absorption of light by photosensitizers (PSs) to generate cytotoxic singlet oxygen for killing cancer cells. The success of this method is usually limited by the lack of selective accumulation of the PS at cancer cells. Bioengineered viruses with cancer cell-targeting peptides fused on their surfaces are great drug carriers that can guide the PS to cancer cells for targeted cancer treatment. Here, we use cell-targeting fd bacteriophages (phages) as an example to describe how to chemically conjugate PSs (e.g., pyropheophorbide-a (PPa)) onto a phage particle to achieve targeted PDT.

  1. Measurement of Isobaric Analogue Resonances of 47Ar with the Active-Target Time Projection Chamber

    NASA Astrophysics Data System (ADS)

    Bradt, Joshua William

    While the nuclear shell model accurately describes the structure of nuclei near stability, the structure of unstable, neutron-rich nuclei is still an area of active research. One region of interest is the set of nuclei near N=28. The shell model suggests that these nuclei should be approximately spherical due to the shell gap predicted by their magic number of neutrons; however, experiments have shown that the nuclei in this region rapidly become deformed as protons are removed from the spherical 48Ca. This makes 46Ar a particularly interesting system as it lies in a transition region between 48Ca and lighter isotones that are known to be deformed. An experiment was performed at the National Superconducting Cyclotron Laboratory (NSCL) to measure resonant proton scattering on 46Ar. The resonances observed in this reaction correspond to unbound levels in the 47K intermediate state nucleus which are isobaric analogues of states in the 47Ar nucleus. By measuring the spectroscopic factors of these states in 47Ar, we gain information about the single-particle structure of this system, which is directly related to the size of the N=28 shell gap. Four resonances were observed: one corresponding to the ground state in 47Ar, one corresponding its first excited 1/2- state, and two corresponding to 1/2+ states in either 47Ar or the intermediate state nucleus. However, only a limited amount of information about these states could be recovered due to the low experimental statistics and limited angular resolution caused by pileup rejection and the inability to accurately reconstruct the beam particle track. In addition to the nuclear physics motivations, this experiment served as the radioactive beam commissioning for the Active-Target Time Projection Chamber (AT-TPC). The AT-TPC is a new gas-filled charged particle detector built at the NSCL to measure low-energy radioactive beams from the ReA3 facility. Since the gas inside the detector serves as both the tracking medium and

  2. Simultaneous Proteomic Discovery and Targeted Monitoring using Liquid Chromatography, Ion Mobility Spectrometry, and Mass Spectrometry

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

    Burnum-Johnson, Kristin E.; Nie, Song; Casey, Cameron P.

    Current proteomics approaches are comprised of both broad discovery measurements as well as more quantitative targeted measurements. These two different measurement types are used to initially identify potentially important proteins (e.g., candidate biomarkers) and then enable improved quantification for a limited number of selected proteins. However, both approaches suffer from limitations, particularly the lower sensitivity, accuracy, and quantitation precision for discovery approaches compared to targeted approaches, and the limited proteome coverage provided by targeted approaches. Herein, we describe a new proteomics approach that allows both discovery and targeted monitoring (DTM) in a single analysis using liquid chromatography, ion mobility spectrometrymore » and mass spectrometry (LC-IMS-MS). In DTM, heavy labeled peptides for target ions are spiked into tryptic digests and both the labeled and unlabeled peptides are broadly detected using LC-IMS-MS instrumentation, allowing the benefits of discovery and targeted approaches. To understand the possible improvement of the DTM approach, it was compared to LC-MS broad measurements using an accurate mass and time tag database and selected reaction monitoring (SRM) targeted measurements. The DTM results yielded greater peptide/protein coverage and a significant improvement in the detection of lower abundance species compared to LC-MS discovery measurements. DTM was also observed to have similar detection limits as SRM for the targeted measurements indicating its potential for combining the discovery and targeted approaches.« less

  3. Computer-aided solvent selection for multiple scenarios operation of limited-known properties solute

    NASA Astrophysics Data System (ADS)

    Anantpinijwatna, Amata

    2017-12-01

    Solvents have been applied for both production and separation of the complex chemical substance such as the pyrrolidine-2-carbonyl chloride (C5H8ClNO). Since the properties of the target substance itself are largely unknown, the selection of the solvent is limited by experiment only. However, the reaction carried out in conventional solvents are either afforded low yields or obtained slow reaction rates. Moreover, the solvents are also highly toxic and environmental unfriendly. Alternative solvents are required to enhance the production and lessen the harmful effect toward both organism and environment. A costly, time-consuming, and laborious experiments are required for acquiring a better solvent suite for production and separation of these complex compounds; whereas, a limited improvement can be obtained. On the other hand, the combination of the state-of-the-art thermodynamic models can provide faster and more robust solutions to this solvent selection problem. In this work, a framework for solvents selection in complex chemical production process is presented. The framework combines a group-contribution thermodynamic model and a segment activity coefficient model for predicting chemical properties and solubilities of the target chemical in newly formulated solvents. A guideline for solvent selection is also included. The potential of the selected solvents is then analysed and verified. The improvement toward the production yield, production rate, and product separation is then discussed.

  4. New Equilibrium Models of Drug-Receptor Interactions Derived from Target-Mediated Drug Disposition.

    PubMed

    Peletier, Lambertus A; Gabrielsson, Johan

    2018-05-14

    In vivo analyses of pharmacological data are traditionally based on a closed system approach not incorporating turnover of target and ligand-target kinetics, but mainly focussing on ligand-target binding properties. This study incorporates information about target and ligand-target kinetics parallel to binding. In a previous paper, steady-state relationships between target- and ligand-target complex versus ligand exposure were derived and a new expression of in vivo potency was derived for a circulating target. This communication is extending the equilibrium relationships and in vivo potency expression for (i) two separate targets competing for one ligand, (ii) two different ligands competing for a single target and (iii) a single ligand-target interaction located in tissue. The derived expressions of the in vivo potencies will be useful both in drug-related discovery projects and mechanistic studies. The equilibrium states of two targets and one ligand may have implications in safety assessment, whilst the equilibrium states of two competing ligands for one target may cast light on when pharmacodynamic drug-drug interactions are important. The proposed equilibrium expressions for a peripherally located target may also be useful for small molecule interactions with extravascularly located targets. Including target turnover, ligand-target complex kinetics and binding properties in expressions of potency and efficacy will improve our understanding of within and between-individual (and across species) variability. The new expressions of potencies highlight the fact that the level of drug-induced target suppression is very much governed by target turnover properties rather than by the target expression level as such.

  5. The effect of state anxiety on the online and offline control of fast target-directed movements.

    PubMed

    Lawrence, Gavin P; Khan, Michael A; Hardy, Lew

    2013-07-01

    In target-directed aiming, afferent information is used to adjust limb trajectories during movement execution (i.e. online) and to enhance the programming of subsequent trials (i.e. offline). The objective of the present study was to determine the influence of state anxiety on both online and offline afferent information processing for the first time. Participants practiced either a directional aiming task (Experiment 1) or an amplitude aiming task (Experiment 2) without anxiety before being transferred to a high anxiety condition. In both experiments, results revealed that anxiety resulted in a decrement in performance. Furthermore, use of afferent information to adjust movement trajectories online was disrupted when movements were performed with anxiety, whereas there were no differences in the offline processing of afferent information between the low anxiety and high anxiety conditions.

  6. Glutamatergic targets for new alcohol medications

    PubMed Central

    Spanagel, Rainer; Krystal, John H.

    2013-01-01

    Rationale An increasingly compelling literature points to a major role for the glutamate system in mediating the effects of alcohol on behavior and the pathophysiology of alcoholism. Preclinical studies indicate that glutamate signaling mediates certain aspects of ethanol’s intoxicating and rewarding effects, and undergoes adaptations following chronic alcohol exposure that may contribute to the withdrawal, craving and compulsive drug-seeking that drive alcohol abuse and alcoholism. Objectives We discuss the potential for targeting the glutamate system as a novel pharmacotherapeutic approach to treating alcohol use disorders, focusing on five major components of the glutamate system: the N-methyl-D-aspartate (NMDA) receptor and specific NMDA subunits, the glycineB site on the NMDA receptors (NMDAR), L-alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid ionotropic (AMPA) and kainate (KAR) receptors, metabotropic receptors (mGluR), and glutamate transporters. Results Chronic alcohol abuse produces a hyperglutamatergic state, characterized by elevated extracellular glutamate and altered glutamate receptors and transporters. Pharmacologically manipulating glutamatergic neurotransmission alters alcohol-related behaviors including intoxication, withdrawal, and alcohol-seeking, in rodents and human subjects. Blocking NMDA and AMPA receptors reduces alcohol consumption in rodents, but side-effects may limit this as a therapeutic approach. Selectively targeting NMDA and AMPA receptor subunits (e.g., GluN2B, GluA3), or the NMDAR glycineB site offers an alternative approach. Blocking mGluR5 potently affects various alcohol-related behaviors in rodents, and mGluR2/3 agonism also suppresses alcohol consumption. Finally, glutamate transporter upregulation may mitigate behavioral and neurotoxic sequelae of excess glutamate caused by alcohol. Conclusions Despite the many challenges that remain, targeting the glutamate system offers genuine promise for developing new

  7. 40 CFR Table 2 to Subpart Ddddd of... - Operating Limits for Boilers and Process Heaters With Particulate Matter Emission Limits

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Process Heaters With Particulate Matter Emission Limits 2 Table 2 to Subpart DDDDD of Part 63 Protection... Heaters With Particulate Matter Emission Limits As stated in § 63.7500, you must comply with the applicable operating limits: If you demonstrate compliance with applicable particulate matter emission limits...

  8. 40 CFR Table 2 to Subpart Ddddd of... - Operating Limits for Boilers and Process Heaters With Particulate Matter Emission Limits

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Process Heaters With Particulate Matter Emission Limits 2 Table 2 to Subpart DDDDD of Part 63 Protection... Heaters With Particulate Matter Emission Limits As stated in § 63.7500, you must comply with the applicable operating limits: If you demonstrate compliance with applicable particulate matter emission limits...

  9. Lifetimes and wave functions of ozone metastable vibrational states near the dissociation limit in a full-symmetry approach

    NASA Astrophysics Data System (ADS)

    Lapierre, David; Alijah, Alexander; Kochanov, Roman; Kokoouline, Viatcheslav; Tyuterev, Vladimir

    2016-10-01

    Energies and lifetimes (widths) of vibrational states above the lowest dissociation limit of O163 were determined using a previously developed efficient approach, which combines hyperspherical coordinates and a complex absorbing potential. The calculations are based on a recently computed potential energy surface of ozone determined with a spectroscopic accuracy [Tyuterev et al., J. Chem. Phys. 139, 134307 (2013), 10.1063/1.4821638]. The effect of permutational symmetry on rovibrational dynamics and the density of resonance states in O3 is discussed in detail. Correspondence between quantum numbers appropriate for short- and long-range parts of wave functions of the rovibrational continuum is established. It is shown, by symmetry arguments, that the allowed purely vibrational (J =0 ) levels of O163 and O183, both made of bosons with zero nuclear spin, cannot dissociate on the ground-state potential energy surface. Energies and wave functions of bound states of the ozone isotopologue O163 with rotational angular momentum J =0 and 1 up to the dissociation threshold were also computed. For bound levels, good agreement with experimental energies is found: The rms deviation between observed and calculated vibrational energies is 1 cm-1. Rotational constants were determined and used for a simple identification of vibrational modes of calculated levels.

  10. Construction safety research in the United States: targeting the Hispanic workforce

    PubMed Central

    Brunette, M

    2004-01-01

    While it is known that Hispanics have a continuous growing participation in the construction workforce and that their fatal and non-fatal occupational injuries are higher than any other ethnic group, very little construction safety and health research has been conducted in the United States. Research that focuses on safety and health of Hispanic workers employed in the construction industry might prove beneficial in reducing injuries and promoting safe and decent workplaces for all. The purpose of this article was twofold. First, to propose a research agenda where topics such as surveillance, intervention research on high risk occupations, intervention effectiveness evaluation, design and development of effective and appropriate safety training and educational materials, and the socioeconomic impact of injuries and illnesses, are investigated among the Hispanic construction workforce. Second, to present relevant aspects inherent to this particular population that need to be incorporated into the design and development stages of any safety and health research initiative. They include the occupational, social, economic, and cultural background of Hispanic workers; use of a participatory approach, proper selection and use of translation methods; and conducting collaborative research. Certain limitations and challenges related to the availability of resources for conducting safety and health research on Hispanic workers are further discussed. PMID:15314054

  11. Construction safety research in the United States: targeting the Hispanic workforce.

    PubMed

    Brunette, M J

    2004-08-01

    While it is known that Hispanics have a continuous growing participation in the construction workforce and that their fatal and non-fatal occupational injuries are higher than any other ethnic group, very little construction safety and health research has been conducted in the United States. Research that focuses on safety and health of Hispanic workers employed in the construction industry might prove beneficial in reducing injuries and promoting safe and decent workplaces for all. The purpose of this article was twofold. First, to propose a research agenda where topics such as surveillance, intervention research on high risk occupations, intervention effectiveness evaluation, design and development of effective and appropriate safety training and educational materials, and the socioeconomic impact of injuries and illnesses, are investigated among the Hispanic construction workforce. Second, to present relevant aspects inherent to this particular population that need to be incorporated into the design and development stages of any safety and health research initiative. They include the occupational, social, economic, and cultural background of Hispanic workers; use of a participatory approach, proper selection and use of translation methods; and conducting collaborative research. Certain limitations and challenges related to the availability of resources for conducting safety and health research on Hispanic workers are further discussed.

  12. Limits in decision making arise from limits in memory retrieval

    PubMed Central

    Giguère, Gyslain; Love, Bradley C.

    2013-01-01

    Some decisions, such as predicting the winner of a baseball game, are challenging in part because outcomes are probabilistic. When making such decisions, one view is that humans stochastically and selectively retrieve a small set of relevant memories that provides evidence for competing options. We show that optimal performance at test is impossible when retrieving information in this fashion, no matter how extensive training is, because limited retrieval introduces noise into the decision process that cannot be overcome. One implication is that people should be more accurate in predicting future events when trained on idealized rather than on the actual distributions of items. In other words, we predict the best way to convey information to people is to present it in a distorted, idealized form. Idealization of training distributions is predicted to reduce the harmful noise induced by immutable bottlenecks in people’s memory retrieval processes. In contrast, machine learning systems that selectively weight (i.e., retrieve) all training examples at test should not benefit from idealization. These conjectures are strongly supported by several studies and supporting analyses. Unlike machine systems, people’s test performance on a target distribution is higher when they are trained on an idealized version of the distribution rather than on the actual target distribution. Optimal machine classifiers modified to selectively and stochastically sample from memory match the pattern of human performance. These results suggest firm limits on human rationality and have broad implications for how to train humans tasked with important classification decisions, such as radiologists, baggage screeners, intelligence analysts, and gamblers. PMID:23610402

  13. Limits in decision making arise from limits in memory retrieval.

    PubMed

    Giguère, Gyslain; Love, Bradley C

    2013-05-07

    Some decisions, such as predicting the winner of a baseball game, are challenging in part because outcomes are probabilistic. When making such decisions, one view is that humans stochastically and selectively retrieve a small set of relevant memories that provides evidence for competing options. We show that optimal performance at test is impossible when retrieving information in this fashion, no matter how extensive training is, because limited retrieval introduces noise into the decision process that cannot be overcome. One implication is that people should be more accurate in predicting future events when trained on idealized rather than on the actual distributions of items. In other words, we predict the best way to convey information to people is to present it in a distorted, idealized form. Idealization of training distributions is predicted to reduce the harmful noise induced by immutable bottlenecks in people's memory retrieval processes. In contrast, machine learning systems that selectively weight (i.e., retrieve) all training examples at test should not benefit from idealization. These conjectures are strongly supported by several studies and supporting analyses. Unlike machine systems, people's test performance on a target distribution is higher when they are trained on an idealized version of the distribution rather than on the actual target distribution. Optimal machine classifiers modified to selectively and stochastically sample from memory match the pattern of human performance. These results suggest firm limits on human rationality and have broad implications for how to train humans tasked with important classification decisions, such as radiologists, baggage screeners, intelligence analysts, and gamblers.

  14. Combining local and global limitations of visual search.

    PubMed

    Põder, Endel

    2017-04-01

    There are different opinions about the roles of local interactions and central processing capacity in visual search. This study attempts to clarify the problem using a new version of relevant set cueing. A central precue indicates two symmetrical segments (that may contain a target object) within a circular array of objects presented briefly around the fixation point. The number of objects in the relevant segments, and density of objects in the array were varied independently. Three types of search experiments were run: (a) search for a simple visual feature (color, size, and orientation); (b) conjunctions of simple features; and (c) spatial configuration of simple features (rotated Ts). For spatial configuration stimuli, the results were consistent with a fixed global processing capacity and standard crowding zones. For simple features and their conjunctions, the results were different, dependent on the features involved. While color search exhibits virtually no capacity limits or crowding, search for an orientation target was limited by both. Results for conjunctions of features can be partly explained by the results from the respective features. This study shows that visual search is limited by both local interference and global capacity, and the limitations are different for different visual features.

  15. 40 CFR Table 4 to Subpart Ddddd of... - Operating Limits for Boilers and Process Heaters With Hydrogen Chloride Emission Limits

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Process Heaters With Hydrogen Chloride Emission Limits 4 Table 4 to Subpart DDDDD of Part 63 Protection of... Heaters With Hydrogen Chloride Emission Limits As stated in § 63.7500, you must comply with the following applicable operating limits: If you demonstrate compliance with applicable hydrogen chloride emission limits...

  16. 40 CFR Table 4 to Subpart Ddddd of... - Operating Limits for Boilers and Process Heaters With Hydrogen Chloride Emission Limits

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Process Heaters With Hydrogen Chloride Emission Limits 4 Table 4 to Subpart DDDDD of Part 63 Protection of... Heaters With Hydrogen Chloride Emission Limits As stated in § 63.7500, you must comply with the following applicable operating limits: If you demonstrate compliance with applicable hydrogen chloride emission limits...

  17. 40 CFR Table 4 to Subpart Ddddd of... - Operating Limits for Boilers and Process Heaters With Hydrogen Chloride Emission Limits

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Process Heaters With Hydrogen Chloride Emission Limits 4 Table 4 to Subpart DDDDD of Part 63 Protection of... Heaters With Hydrogen Chloride Emission Limits As stated in § 63.7500, you must comply with the following applicable operating limits: If you demonstrate compliance with applicable hydrogen chloride emission limits...

  18. Interpreting Recruitment Limitation in Forests

    Treesearch

    J.S. Clark; B. Beckage; P. Camill; B. Cleveland; J. HilleRisLambers; J. Lichter; J. McLachlan; J. Mohan; P. Wyckoff

    1999-01-01

    Studies of tree recruitment are many, but they provide few general insights into the role of recruitment limitation for population dynamics. That role depends on the vital rates (transitions) from seed production to sapling stages and on overall population growth. To determine the state of our understanding of recruitment limitation we examined how well we can estimate...

  19. Effect of visual target blurring on accommodation under distance viewing

    NASA Astrophysics Data System (ADS)

    Iwata, Yo; Handa, Tomoya; Ishikawa, Hitoshi

    2018-04-01

    Abstract Purpose To examine the effect of visual target blurring on accommodation. Methods We evaluated the objective refraction values when the visual target (asterisk; 8°) was changed from the state without Gaussian blur (15 s) to the state with Gaussian blur adapted [0(without blur) → 10, 0 → 50, 0 → 100: 15 s each]. Results In Gaussian blur 10, when blurring of the target occurred, refraction value did not change significantly. In Gaussian blur 50 and 100, when blurring of the target occurred, the refraction value became significantly myopic. Conclusion Blurring of the distant visual target results in intervention of accommodation.

  20. Acute Pesticide Illnesses Associated with Off-Target Pesticide Drift from Agricultural Applications: 11 States, 1998–2006

    PubMed Central

    Lee, Soo-Jeong; Mehler, Louise; Beckman, John; Diebolt-Brown, Brienne; Prado, Joanne; Lackovic, Michelle; Waltz, Justin; Mulay, Prakash; Schwartz, Abby; Mitchell, Yvette; Moraga-McHaley, Stephanie; Gergely, Rita

    2011-01-01

    Background: Pesticides are widely used in agriculture, and off-target pesticide drift exposes workers and the public to harmful chemicals. Objective: We estimated the incidence of acute illnesses from pesticide drift from outdoor agricultural applications and characterized drift exposure and illnesses. Methods: Data were obtained from the National Institute for Occupational Safety and Health’s Sentinel Event Notification System for Occupational Risks–Pesticides program and the California Department of Pesticide Regulation. Drift included off-target movement of pesticide spray, volatiles, and contaminated dust. Acute illness cases were characterized by demographics, pesticide and application variables, health effects, and contributing factors. Results: From 1998 through 2006, we identified 2,945 cases associated with agricultural pesticide drift from 11 states. Our findings indicate that 47% were exposed at work, 92% experienced low-severity illness, and 14% were children (< 15 years). The annual incidence ranged from 1.39 to 5.32 per million persons over the 9-year period. The overall incidence (in million person-years) was 114.3 for agricultural workers, 0.79 for other workers, 1.56 for nonoccupational cases, and 42.2 for residents in five agriculture-intensive counties in California. Soil applications with fumigants were responsible for the largest percentage (45%) of cases. Aerial applications accounted for 24% of cases. Common factors contributing to drift cases included weather conditions, improper seal of the fumigation site, and applicator carelessness near nontarget areas. Conclusions: Agricultural workers and residents in agricultural regions had the highest rate of pesticide poisoning from drift exposure, and soil fumigations were a major hazard, causing large drift incidents. Our findings highlight areas where interventions to reduce off-target drift could be focused. PMID:21642048

  1. Within-Hemifield Competition in Early Visual Areas Limits the Ability to Track Multiple Objects with Attention

    PubMed Central

    Alvarez, George A.; Cavanagh, Patrick

    2014-01-01

    It is much easier to divide attention across the left and right visual hemifields than within the same visual hemifield. Here we investigate whether this benefit of dividing attention across separate visual fields is evident at early cortical processing stages. We measured the steady-state visual evoked potential, an oscillatory response of the visual cortex elicited by flickering stimuli, of moving targets and distractors while human observers performed a tracking task. The amplitude of responses at the target frequencies was larger than that of the distractor frequencies when participants tracked two targets in separate hemifields, indicating that attention can modulate early visual processing when it is divided across hemifields. However, these attentional modulations disappeared when both targets were tracked within the same hemifield. These effects were not due to differences in task performance, because accuracy was matched across the tracking conditions by adjusting target speed (with control conditions ruling out effects due to speed alone). To investigate later processing stages, we examined the P3 component over central-parietal scalp sites that was elicited by the test probe at the end of the trial. The P3 amplitude was larger for probes on targets than on distractors, regardless of whether attention was divided across or within a hemifield, indicating that these higher-level processes were not constrained by visual hemifield. These results suggest that modulating early processing stages enables more efficient target tracking, and that within-hemifield competition limits the ability to modulate multiple target representations within the hemifield maps of the early visual cortex. PMID:25164651

  2. Artificial Chemical Reporter Targeting Strategy Using Bioorthogonal Click Reaction for Improving Active-Targeting Efficiency of Tumor.

    PubMed

    Yoon, Hong Yeol; Shin, Min Lee; Shim, Man Kyu; Lee, Sangmin; Na, Jin Hee; Koo, Heebeom; Lee, Hyukjin; Kim, Jong-Ho; Lee, Kuen Yong; Kim, Kwangmeyung; Kwon, Ick Chan

    2017-05-01

    Biological ligands such as aptamer, antibody, glucose, and peptide have been widely used to bind specific surface molecules or receptors in tumor cells or subcellular structures to improve tumor-targeting efficiency of nanoparticles. However, this active-targeting strategy has limitations for tumor targeting due to inter- and intraheterogeneity of tumors. In this study, we demonstrated an alternative active-targeting strategy using metabolic engineering and bioorthogonal click reaction to improve tumor-targeting efficiency of nanoparticles. We observed that azide-containing chemical reporters were successfully generated onto surface glycans of various tumor cells such as lung cancer (A549), brain cancer (U87), and breast cancer (BT-474, MDA-MB231, MCF-7) via metabolic engineering in vitro. In addition, we compared tumor targeting of artificial azide reporter with bicyclononyne (BCN)-conjugated glycol chitosan nanoparticles (BCN-CNPs) and integrin α v β 3 with cyclic RGD-conjugated CNPs (cRGD-CNPs) in vitro and in vivo. Fluorescence intensity of azide-reporter-targeted BCN-CNPs in tumor tissues was 1.6-fold higher and with a more uniform distribution compared to that of cRGD-CNPs. Moreover, even in the isolated heterogeneous U87 cells, BCN-CNPs could bind artificial azide reporters on tumor cells more uniformly (∼92.9%) compared to cRGD-CNPs. Therefore, the artificial azide-reporter-targeting strategy can be utilized for targeting heterogeneous tumor cells via bioorthogonal click reaction and may provide an alternative method of tumor targeting for further investigation in cancer therapy.

  3. Optimal control of the population dynamics of the ground vibrational state of a polyatomic molecule

    NASA Astrophysics Data System (ADS)

    de Clercq, Ludwig E.; Botha, Lourens R.; Rohwer, Erich G.; Uys, Hermann; Du Plessis, Anton

    2011-03-01

    Simulating coherent control with femtosecond pulses on a polyatomic molecule with anharmonic splitting was demonstrated. The simulation mimicked pulse shaping of a Spatial Light Modulator (SLM) and the interaction was described with the Von Neumann equation. A transform limited pulse with a fluence of 600 J/m2 produced 18% of the population in an arbitrarily chosen upper vibrational state, n =2. Phase only and amplitude only shaped pulse produced optimum values of 60% and 40% respectively, of the population in the vibrational state, n=2, after interaction with the ultra short pulse. The combination of phase and amplitude shaping produced the best results, 80% of the population was in the targeted vibrational state, n=2, after interaction. These simulations were carried out with all the population initially in the ground vibrational level. It was found that even at room temperatures (300 Kelvin) that the population in the selected level is comparable with the case where all population is initially in the ground vibrational state. With a 10% noise added to the amplitude and phase masks, selective excitation of the targeted vibrational state is still possible.

  4. Are there benefits or harm from pressure targeting during lung-protective ventilation?

    PubMed

    MacIntyre, Neil R; Sessler, Curtis N

    2010-02-01

    Mechanically, breath design is usually either flow/volume-targeted or pressure-targeted. Both approaches can effectively provide lung-protective ventilation, but they prioritize different ventilation parameters, so their responses to changing respiratory-system mechanics and patient effort are different. These different response behaviors have advantages and disadvantages that can be important in specific circumstances. Flow/volume targeting guarantees a set minute ventilation but sometimes may be difficult to synchronize with patient effort, and it will not limit inspiratory pressure. In contrast, pressure targeting, with its variable flow, may be easier to synchronize and will limit inspiratory pressure, but it provides no control over delivered volume. Skilled clinicians can maximize benefits and minimize problems with either flow/volume targeting or pressure targeting. Indeed, as is often the case in managing complex life-support devices, it is operator expertise rather than the device design features that most impacts patient outcomes.

  5. 5 CFR 582.402 - Maximum garnishment limitations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Maximum garnishment limitations. 582.402... Maximum garnishment limitations. Pursuant to section 1673(a)(1) of title 15 of the United States Code (the... Federal Regulations, part 870, the following limitations are applicable: (a) Unless a lower maximum...

  6. 5 CFR 581.402 - Maximum garnishment limitations.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 5 Administrative Personnel 1 2010-01-01 2010-01-01 false Maximum garnishment limitations. 581.402... § 581.402 Maximum garnishment limitations. (a) Except as provided in paragraph (b) of this section... Protection Act, as amended), unless a lower maximum garnishment limitation is provided by applicable State or...

  7. Prevalence of Arthritis and Arthritis-Attributable Activity Limitation by Urban-Rural County Classification - United States, 2015.

    PubMed

    Boring, Michael A; Hootman, Jennifer M; Liu, Yong; Theis, Kristina A; Murphy, Louise B; Barbour, Kamil E; Helmick, Charles G; Brady, Terry J; Croft, Janet B

    2017-05-26

    Rural populations in the United States have well documented health disparities, including higher prevalences of chronic health conditions (1,2). Doctor-diagnosed arthritis is one of the most prevalent health conditions (22.7%) in the United States, affecting approximately 54.4 million adults (3). The impact of arthritis is considerable: an estimated 23.7 million adults have arthritis-attributable activity limitation (AAAL). The age-standardized prevalence of AAAL increased nearly 20% from 2002 to 2015 (3). Arthritis prevalence varies widely by state (range = 19%-36%) and county (range = 16%-39%) (4). Despite what is known about arthritis prevalence at the national, state, and county levels and the substantial impact of arthritis, little is known about the prevalence of arthritis and AAAL across urban-rural areas overall and among selected subgroups. To estimate the prevalence of arthritis and AAAL by urban-rural categories CDC analyzed data from the 2015 Behavioral Risk Factor Surveillance System (BRFSS). The unadjusted prevalence of arthritis in the most rural areas was 31.8% (95% confidence intervals [CI] = 31.0%-32.5%) and in the most urban, was 20.5% (95% CI = 20.1%-21.0%). The unadjusted AAAL prevalence among adults with arthritis was 55.3% in the most rural areas and 49.7% in the most urban. Approximately 1 in 3 adults in the most rural areas have arthritis and over half of these adults have AAAL. Wider use of evidence-based interventions including physical activity and self-management education in rural areas might help reduce the impact of arthritis and AAAL.

  8. Targeting ALK: Precision Medicine Takes On Drug Resistance

    PubMed Central

    Lin, Jessica J.; Riely, Gregory J.; Shaw, Alice T.

    2017-01-01

    Anaplastic lymphoma kinase (ALK) is a validated molecular target in several ALK-rearranged malignancies, including non-small-cell lung cancer (NSCLC). However, the clinical benefit of targeting ALK using tyrosine kinase inhibitors (TKIs) is almost universally limited by the emergence of drug resistance. Diverse mechanisms of resistance to ALK TKIs have now been discovered, and these basic mechanisms are informing the development of novel therapeutic strategies to overcome resistance in the clinic. In this Review, we summarize the current successes and challenges of targeting ALK. PMID:28122866

  9. The frontal eye fields limit the capacity of visual short-term memory in rhesus monkeys.

    PubMed

    Lee, Kyoung-Min; Ahn, Kyung-Ha

    2013-01-01

    The frontal eye fields (FEF) in rhesus monkeys have been implicated in visual short-term memory (VSTM) as well as control of visual attention. Here we examined the importance of the area in the VSTM capacity and the relationship between VSTM and attention, using the chemical inactivation technique and multi-target saccade tasks with or without the need of target-location memory. During FEF inactivation, serial saccades to targets defined by color contrast were unaffected, but saccades relying on short-term memory were impaired when the target count was at the capacity limit of VSTM. The memory impairment was specific to the FEF-coded retinotopic locations, and subject to competition among targets distributed across visual fields. These results together suggest that the FEF plays a crucial role during the entry of information into VSTM, by enabling attention deployment on targets to be remembered. In this view, the memory capacity results from the limited availability of attentional resources provided by FEF: The FEF can concurrently maintain only a limited number of activations to register the targets into memory. When lesions render part of the area unavailable for activation, the number would decrease, further reducing the capacity of VSTM.

  10. Reading data stored in the state of metastable defects in silicon using band-band photoluminescence: Proof of concept and physical limits to the data storage density

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

    Rougieux, F. E.; Macdonald, D.

    2014-03-24

    The state of bistable defects in crystalline silicon such as iron-boron pairs or the boron-oxygen defect can be changed at room temperature. In this letter, we experimentally demonstrate that the chemical state of a group of defects can be changed to represent a bit of information. The state can then be read without direct contact via the intensity of the emitted band-band photoluminescence signal of the group of defects, via their impact on the carrier lifetime. The theoretical limit of the information density is then computed. The information density is shown to be low for two-dimensional storage but significant formore » three-dimensional data storage. Finally, we compute the maximum storage capacity as a function of the lower limit of the photoluminescence detector sensitivity.« less

  11. TargetSpy: a supervised machine learning approach for microRNA target prediction.

    PubMed

    Sturm, Martin; Hackenberg, Michael; Langenberger, David; Frishman, Dmitrij

    2010-05-28

    Virtually all currently available microRNA target site prediction algorithms require the presence of a (conserved) seed match to the 5' end of the microRNA. Recently however, it has been shown that this requirement might be too stringent, leading to a substantial number of missed target sites. We developed TargetSpy, a novel computational approach for predicting target sites regardless of the presence of a seed match. It is based on machine learning and automatic feature selection using a wide spectrum of compositional, structural, and base pairing features covering current biological knowledge. Our model does not rely on evolutionary conservation, which allows the detection of species-specific interactions and makes TargetSpy suitable for analyzing unconserved genomic sequences.In order to allow for an unbiased comparison of TargetSpy to other methods, we classified all algorithms into three groups: I) no seed match requirement, II) seed match requirement, and III) conserved seed match requirement. TargetSpy predictions for classes II and III are generated by appropriate postfiltering. On a human dataset revealing fold-change in protein production for five selected microRNAs our method shows superior performance in all classes. In Drosophila melanogaster not only our class II and III predictions are on par with other algorithms, but notably the class I (no-seed) predictions are just marginally less accurate. We estimate that TargetSpy predicts between 26 and 112 functional target sites without a seed match per microRNA that are missed by all other currently available algorithms. Only a few algorithms can predict target sites without demanding a seed match and TargetSpy demonstrates a substantial improvement in prediction accuracy in that class. Furthermore, when conservation and the presence of a seed match are required, the performance is comparable with state-of-the-art algorithms. TargetSpy was trained on mouse and performs well in human and drosophila

  12. TargetSpy: a supervised machine learning approach for microRNA target prediction

    PubMed Central

    2010-01-01

    Background Virtually all currently available microRNA target site prediction algorithms require the presence of a (conserved) seed match to the 5' end of the microRNA. Recently however, it has been shown that this requirement might be too stringent, leading to a substantial number of missed target sites. Results We developed TargetSpy, a novel computational approach for predicting target sites regardless of the presence of a seed match. It is based on machine learning and automatic feature selection using a wide spectrum of compositional, structural, and base pairing features covering current biological knowledge. Our model does not rely on evolutionary conservation, which allows the detection of species-specific interactions and makes TargetSpy suitable for analyzing unconserved genomic sequences. In order to allow for an unbiased comparison of TargetSpy to other methods, we classified all algorithms into three groups: I) no seed match requirement, II) seed match requirement, and III) conserved seed match requirement. TargetSpy predictions for classes II and III are generated by appropriate postfiltering. On a human dataset revealing fold-change in protein production for five selected microRNAs our method shows superior performance in all classes. In Drosophila melanogaster not only our class II and III predictions are on par with other algorithms, but notably the class I (no-seed) predictions are just marginally less accurate. We estimate that TargetSpy predicts between 26 and 112 functional target sites without a seed match per microRNA that are missed by all other currently available algorithms. Conclusion Only a few algorithms can predict target sites without demanding a seed match and TargetSpy demonstrates a substantial improvement in prediction accuracy in that class. Furthermore, when conservation and the presence of a seed match are required, the performance is comparable with state-of-the-art algorithms. TargetSpy was trained on mouse and performs well

  13. America's Climate Choices: Limiting the Magnitude of Future Climate Change (Invited)

    NASA Astrophysics Data System (ADS)

    Carlson, A.; Fri, R.; Brown, M.; Geller, L.

    2010-12-01

    At the request of Congress, the National Academy of Sciences convened a series of coordinated activities to provide advice on actions and strategies the nation can take to respond to climate change. This suite of activities included a study on strategies for limiting the magnitude of future climate change (i.e. mitigation). Limiting climate change is a global effort that will require significant reductions of greenhouse gas emissions by countries around the world. U.S. action alone is not sufficient, but it is clearly necessary for the U.S. to make significant contributions to the global effort. While efforts to limit climate change are already underway across the U.S. (by state and local governments, businesses, non-governmental organizations, and individual households), we currently lack a framework of federal policies to help assure that all key actors participating and working towards coherent national goals. This study recommends a U.S. policy goal stated as a budget for cumulative greenhouse gas emissions through the year 2050, and offers an illustrative range of budget numbers derived from recent work of the Energy Modeling Forum. The report evaluates the types of changes to our nation's energy system that are needed to meet a budget in the proposed range, which leads to a conclusion that the U.S. must get started now in aggressively pursuing available emission reduction opportunities, while also investing heavily in R&D to create new emission reduction opportunities. The study offers a series of recommendations for how to move ahead in pursing these near-term and longer-term opportunities. The recommendations address the need for a carbon pricing system and strategically-targeted complimentary policies, for effective international engagement, for careful balancing of federal with state/local action, and for consideration of equity and employment impacts of response policies. The study also discusses the need to design policies that are both durable over the

  14. Quantum teleportation from light beams to vibrational states of a macroscopic diamond

    PubMed Central

    Hou, P.-Y.; Huang, Y.-Y.; Yuan, X.-X.; Chang, X.-Y.; Zu, C.; He, L.; Duan, L.-M.

    2016-01-01

    With the recent development of optomechanics, the vibration in solids, involving collective motion of trillions of atoms, gradually enters into the realm of quantum control. Here, building on the recent remarkable progress in optical control of motional states of diamonds, we report an experimental demonstration of quantum teleportation from light beams to vibrational states of a macroscopic diamond under ambient conditions. Through quantum process tomography, we demonstrate average teleportation fidelity (90.6±1.0)%, clearly exceeding the classical limit of 2/3. The experiment pushes the target of quantum teleportation to the biggest object so far, with interesting implications for optomechanical quantum control and quantum information science. PMID:27240553

  15. Changing paradigm from one target one ligand towards multi target directed ligand design for key drug targets of Alzheimer disease: An important role of Insilco methods in multi target directed ligands design.

    PubMed

    Kumar, Akhil; Tiwari, Ashish; Sharma, Ashok

    2018-03-15

    Alzheimer disease (AD) is now considered as a multifactorial neurodegenerative disorder and rapidly increasing to an alarming situation and causing higher death rate. One target one ligand hypothesis is not able to provide complete solution of AD due to multifactorial nature of disease and one target one drug seems to fail to provide better treatment against AD. Moreover, current available treatments are limited and most of the upcoming treatments under clinical trials are based on modulating single target. So the current AD drug discovery research shifting towards new approach for better solution that simultaneously modulate more than one targets in the neurodegenerative cascade. This can be achieved by network pharmacology, multi-modal therapies, multifaceted, and/or the more recently proposed term "multi-targeted designed drugs. Drug discovery project is tedious, costly and long term project. Moreover, multi target AD drug discovery added extra challenges such as good binding affinity of ligands for multiple targets, optimal ADME/T properties, no/less off target side effect and crossing of the blood brain barrier. These hurdles may be addressed by insilico methods for efficient solution in less time and cost as computational methods successfully applied to single target drug discovery project. Here we are summarizing some of the most prominent and computationally explored single target against AD and further we discussed successful example of dual or multiple inhibitors for same targets. Moreover we focused on ligand and structure based computational approach to design MTDL against AD. However is not an easy task to balance dual activity in a single molecule but computational approach such as virtual screening docking, QSAR, simulation and free energy are useful in future MTDLs drug discovery alone or in combination with fragment based method. However, rational and logical implementations of computational drug designing methods are capable of assisting AD drug

  16. Game theoretic sensor management for target tracking

    NASA Astrophysics Data System (ADS)

    Shen, Dan; Chen, Genshe; Blasch, Erik; Pham, Khanh; Douville, Philip; Yang, Chun; Kadar, Ivan

    2010-04-01

    This paper develops and evaluates a game-theoretic approach to distributed sensor-network management for target tracking via sensor-based negotiation. We present a distributed sensor-based negotiation game model for sensor management for multi-sensor multi-target tacking situations. In our negotiation framework, each negotiation agent represents a sensor and each sensor maximizes their utility using a game approach. The greediness of each sensor is limited by the fact that the sensor-to-target assignment efficiency will decrease if too many sensor resources are assigned to a same target. It is similar to the market concept in real world, such as agreements between buyers and sellers in an auction market. Sensors are willing to switch targets so that they can obtain their highest utility and the most efficient way of applying their resources. Our sub-game perfect equilibrium-based negotiation strategies dynamically and distributedly assign sensors to targets. Numerical simulations are performed to demonstrate our sensor-based negotiation approach for distributed sensor management.

  17. Extreme plasma states in laser-governed vacuum breakdown.

    PubMed

    Efimenko, Evgeny S; Bashinov, Aleksei V; Bastrakov, Sergei I; Gonoskov, Arkady A; Muraviev, Alexander A; Meyerov, Iosif B; Kim, Arkady V; Sergeev, Alexander M

    2018-02-05

    Triggering vacuum breakdown at laser facility is expected to provide rapid electron-positron pair production for studies in laboratory astrophysics and fundamental physics. However, the density of the produced plasma may cease to increase at a relativistic critical density, when the plasma becomes opaque. Here, we identify the opportunity of breaking this limit using optimal beam configuration of petawatt-class lasers. Tightly focused laser fields allow generating plasma in a small focal volume much less than λ 3 and creating extreme plasma states in terms of density and produced currents. These states can be regarded to be a new object of nonlinear plasma physics. Using 3D QED-PIC simulations we demonstrate a possibility of reaching densities over 10 25  cm -3 , which is an order of magnitude higher than expected earlier. Controlling the process via initial target parameters provides an opportunity to reach the discovered plasma states at the upcoming laser facilities.

  18. Brain-state classification and a dual-state decoder dramatically improve the control of cursor movement through a brain-machine interface.

    PubMed

    Sachs, Nicholas A; Ruiz-Torres, Ricardo; Perreault, Eric J; Miller, Lee E

    2016-02-01

    It is quite remarkable that brain machine interfaces (BMIs) can be used to control complex movements with fewer than 100 neurons. Success may be due in part to the limited range of dynamical conditions under which most BMIs are tested. Achieving high-quality control that spans these conditions with a single linear mapping will be more challenging. Even for simple reaching movements, existing BMIs must reduce the stochastic noise of neurons by averaging the control signals over time, instead of over the many neurons that normally control movement. This forces a compromise between a decoder with dynamics allowing rapid movement and one that allows postures to be maintained with little jitter. Our current work presents a method for addressing this compromise, which may also generalize to more highly varied dynamical situations, including movements with more greatly varying speed. We have developed a system that uses two independent Wiener filters as individual components in a single decoder, one optimized for movement, and the other for postural control. We computed an LDA classifier using the same neural inputs. The decoder combined the outputs of the two filters in proportion to the likelihood assigned by the classifier to each state. We have performed online experiments with two monkeys using this neural-classifier, dual-state decoder, comparing it to a standard, single-state decoder as well as to a dual-state decoder that switched states automatically based on the cursor's proximity to a target. The performance of both monkeys using the classifier decoder was markedly better than that of the single-state decoder and comparable to the proximity decoder. We have demonstrated a novel strategy for dealing with the need to make rapid movements while also maintaining precise cursor control when approaching and stabilizing within targets. Further gains can undoubtedly be realized by optimizing the performance of the individual movement and posture decoders.

  19. Dual Target Design for CLAS12

    NASA Astrophysics Data System (ADS)

    Alam, Omair; Gilfoyle, Gerard; Christo, Steve

    2015-10-01

    An experiment to measure the neutron magnetic form factor (GnM) is planned for the new CLAS12 detector in Hall B at Jefferson Lab. This form factor will be extracted from the ratio of the quasielastic electron-neutron to electron-proton scattering off a liquid deuterium (LD2) target. A collinear liquid hydrogen (LH2) target will be used to measure efficiencies at the same time as production data is collected from the LD2 target. To test target designs we have simulated CLAS12 and the target geometry. Electron-nucleon events are produced first with the QUasiElastic Event Generator (QUEEG) which models the internal motion of the nucleons in deuterium.1 The results are used as input to the CLAS12 Monte Caro code gemc; a Geant4-based program that simulates the particle's interactions with each component of CLAS12 including the target material. The dual target geometry has been added to gemc including support structures and cryogenic transport systems. A Perl script was written to define the target materials and geometries. The output of the script is a set of database entries read by gemc at runtime. An initial study of the impact of this dual-target structure revealed limited effects on the electron momentum and angular resolutions. Work supported by the University of Richmond and the US Department of Energy.

  20. Improved genome-scale multi-target virtual screening via a novel collaborative filtering approach to cold-start problem

    PubMed Central

    Lim, Hansaim; Gray, Paul; Xie, Lei; Poleksic, Aleksandar

    2016-01-01

    Conventional one-drug-one-gene approach has been of limited success in modern drug discovery. Polypharmacology, which focuses on searching for multi-targeted drugs to perturb disease-causing networks instead of designing selective ligands to target individual proteins, has emerged as a new drug discovery paradigm. Although many methods for single-target virtual screening have been developed to improve the efficiency of drug discovery, few of these algorithms are designed for polypharmacology. Here, we present a novel theoretical framework and a corresponding algorithm for genome-scale multi-target virtual screening based on the one-class collaborative filtering technique. Our method overcomes the sparseness of the protein-chemical interaction data by means of interaction matrix weighting and dual regularization from both chemicals and proteins. While the statistical foundation behind our method is general enough to encompass genome-wide drug off-target prediction, the program is specifically tailored to find protein targets for new chemicals with little to no available interaction data. We extensively evaluate our method using a number of the most widely accepted gene-specific and cross-gene family benchmarks and demonstrate that our method outperforms other state-of-the-art algorithms for predicting the interaction of new chemicals with multiple proteins. Thus, the proposed algorithm may provide a powerful tool for multi-target drug design. PMID:27958331

  1. Improved genome-scale multi-target virtual screening via a novel collaborative filtering approach to cold-start problem.

    PubMed

    Lim, Hansaim; Gray, Paul; Xie, Lei; Poleksic, Aleksandar

    2016-12-13

    Conventional one-drug-one-gene approach has been of limited success in modern drug discovery. Polypharmacology, which focuses on searching for multi-targeted drugs to perturb disease-causing networks instead of designing selective ligands to target individual proteins, has emerged as a new drug discovery paradigm. Although many methods for single-target virtual screening have been developed to improve the efficiency of drug discovery, few of these algorithms are designed for polypharmacology. Here, we present a novel theoretical framework and a corresponding algorithm for genome-scale multi-target virtual screening based on the one-class collaborative filtering technique. Our method overcomes the sparseness of the protein-chemical interaction data by means of interaction matrix weighting and dual regularization from both chemicals and proteins. While the statistical foundation behind our method is general enough to encompass genome-wide drug off-target prediction, the program is specifically tailored to find protein targets for new chemicals with little to no available interaction data. We extensively evaluate our method using a number of the most widely accepted gene-specific and cross-gene family benchmarks and demonstrate that our method outperforms other state-of-the-art algorithms for predicting the interaction of new chemicals with multiple proteins. Thus, the proposed algorithm may provide a powerful tool for multi-target drug design.

  2. Correlation between clinical signs of depth of anaesthesia and cerebral state index responses in dogs with different target-controlled infusions of propofol.

    PubMed

    Ribeiro, Lénio M; Ferreira, David A; Brás, Susana; Gonzalo-Orden, Jose M; Antunes, Luis M

    2012-01-01

    To evaluate if the cerebral state index (CSI), measured by a Cerebral State Monitor (CSM), can predict depth of anaesthesia as assessed clinically or by estimated propofol plasma concentrations. Prospective clinical study. Fourteen mixed breed dogs, weighing 24.5 ± 4.7 kg, scheduled to undergo neutering procedures. Dogs were premedicated with 0.05 mg kg(-1) acepromazine intramuscularly. The CSM and cardiovascular monitoring equipment were attached. Anaesthesia was induced with propofol using a target controlled infusion (TCI) to varying plasma propofol targets (PropCp). Following endotracheal intubation the dogs were ventilated with oxygen. Anaesthetic maintenance was with propofol by TCI. A PropCp of 3 μg dL(-1) was set initially, then PropCps were increased in 1 μg dL(-1) steps to 7, 9 and then 11 μg dL(-1). Each PropCp was held constant for a 5 minute period, at the end of which depth of anaesthesia was classified using a previously evaluated scale of 'planes' based on palpebral and corneal reflexes and eye position. Cerebral state index (CSI), burst suppression (BSR) and electromyogram were measured at these time points. The prediction probability (PK) of these variables, or of the PropCp in predicting depth of anaesthesia was calculated. The PKs for predicting anaesthetic planes were 0.74, 0.91, 0.76 and 0.78 for CSI, BSR, EMG and PropCp, respectively. The PKs for PropCp to predict CSI, BSR and EMG were 0.65, 0.71 and 0.65 respectively. The Cerebral State Monitor was able to detect very deep planes of anaesthesia when BSR occurs, but was not able to distinguish between the intermediate anaesthetic planes likely to be used in clinical anaesthesia. © 2011 The Authors. Veterinary Anaesthesia and Analgesia. © 2011 Association of Veterinary Anaesthetists and the American College of Veterinary Anesthesiologists.

  3. ChemCam Targeted Science at Gale Crater

    NASA Astrophysics Data System (ADS)

    Wiens, R. C.; Blaney, D. L.; Clark, B. C.; Bridges, N. T.; Clegg, S. M.; Maurice, S.; Newsom, H. E.; Vaniman, D. T.; Herkenhoff, K. E.; Ollila, A. M.; Gasnault, O.; Pinet, P. C.; Dromart, G.; Barraclough, B. L.; Lasue, J.

    2011-12-01

    The MSL rover, Curiosity, uses a novel remote-sensing instrument, ChemCam, which combines laser-induced breakdown spectroscopy (LIBS) with a high resolution remote micro-imager (RMI). ChemCam uses a focused, pulsed laser beam at targets up to 7 m away to excite a light-emitting plasma. Spectral analysis identifies elements present and provides rapid semi-quantitative analyses. Repeated laser pulses remove dust and weathering coatings from rock samples to depths >0.5 mm and ~0.4 mm in diameter. The RMI, with ~20x20 mrad field of view, provides a broad-band image with 100 μm resolution. LIBS yields abundances of H, Li, Be, B, C, N, O, F, Na, Mg, Al, Si, P, Cl, K, Ca, Ti, V, Cr, Fe, Ni, Zr, Rb, Sr, As, Ba, and Pb. Interference from atmospheric constituents raises the detection limits of C, N, and O (e.g., >2% wt for C). LIBS is very sensitive to alkali and alkali earth elements, with some detection limits to ~1 ppm at close range. Conversely, LIBS is insensitive to F, Cl, S, P, and N, with detection limits of several wt. %. Pointing accuracy is ~3 mrad, however relative pointing accuracy is better, so line scans and rasters will enable analyses of targeted features to ~1 mm. At Gale Crater, determination of elements not previously analyzed in-situ, i.e., H, Li, Rb, Sr, and Ba, along with other elements will constrain aqueous, hydrothermal and vapor geochemical transport processes. Initial analyses after landing will characterize air fall dust and weathering coatings on local rocks, and profile the soil and surfacial materials including bedforms to investigate compositional differences in near-surface layers. Targets within the landing ellipse include fan and inverted channel deposits derived from the crater rim, which may contain alteration minerals produced by impact hydrothermal processes. Enigmatic deposits with bright fracture fill could represent lake sediments modified by injection of deposits from groundwater. During the drive to the Gale mound, ChemCam will

  4. Defining an end state for CO2 sequestration and EOR in North America

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

    Friedmann, S J

    2006-04-20

    CO{sub 2} capture and storage (CCS) presents a challenge to long-range planners, economic interests, regulators, law-makers, and other stakeholders and decision makers. To improve and optimize the use of limited resources and finances, it is important to define an end state for CCS. This ends state should be defined around desired goals and reasonable timelines for execution. While this definition may have substantial technology, policy or economic implications, it need not be prescriptive in terms of technology pathway, policy mechanism, or economic targets. To illustrate these concerns, this paper will present a credible vision of what an end state formore » North American might look like. From that, examples of key investment and planning decisions are provided to illustrate the value of end-state characterization.« less

  5. Voyager 2 Neptune targeting strategy

    NASA Technical Reports Server (NTRS)

    Potts, C. L.; Francis, K.; Matousek, S. E.; Cesarone, R. J.; Gray, D. L.

    1989-01-01

    The success of the Voyager 2 flybys of Neptune and Triton depends upon the ability to correct the spacecraft's trajectory. Accurate spacecraft delivery to the desired encounter conditions will promote the maximum science return. However, Neptune's great distance causes large a priori uncertainties in Neptune and Triton ephemerides and planetary system parameters. Consequently, the 'ideal' trajectory is unknown beforehand. The targeting challenge is to utilize the gradually improving knowledge as the spacecraft approaches Neptune to meet the science objectives, but with an overriding concern for spacecraft safety and a desire to limit propellant expenditure. A unique targeting strategy has been developed in response to this challenge. Through the use of a Monte Carlo simulation, candidate strategies are evaluated by the degree to which they meet these objectives and are compared against each other in determining the targeting strategy to be adopted.

  6. Community engagement and the social context of targeted malaria treatment: a qualitative study in Kayin (Karen) State, Myanmar.

    PubMed

    Sahan, Kate; Pell, Christopher; Smithuis, Frank; Phyo, Aung Kyaw; Maung, Sai Maung; Indrasuta, Chanida; Dondorp, Arjen M; White, Nicholas J; Day, Nicholas P J; von Seidlein, Lorenz; Cheah, Phaik Yeong

    2017-02-14

    The spread of artemisinin-resistance in Plasmodium falciparum is a threat to current global malaria control initiatives. Targeted malaria treatment (TMT), which combines mass anti-malarial administration with conventional malaria prevention and control measures, has been proposed as a strategy to tackle this problem. The effectiveness of TMT depends on high levels of population coverage and is influenced by accompanying community engagement activities and the local social context. The article explores how these factors influenced attitudes and behaviours towards TMT in Kayin (Karen) State, Myanmar. Semi-structured interviews were conducted with villagers from study villages (N = 31) and TMT project staff (N = 14) between March and July 2015. Community engagement consisted of a range of activities to communicate the local malaria situation (including anti-malarial drug resistance and asymptomatic malaria), the aims of the TMT project, and its potential benefits. Community engagement was seen by staff as integral to the TMT project as a whole and not a sub-set of activities. Attitudes towards TMT (including towards community engagement) showed that developing trusting relationships helped foster participation. After initial wariness, staff received hospitality and acceptance among villagers. Offering healthcare alongside TMT proved mutually beneficial for the study and villagers. A handful of more socially-mobile and wealthy community members were reluctant to participate. The challenges of community engagement included time constraints and the isolation of the community with its limited infrastructure and a history of conflict. Community engagement had to be responsive to the local community even though staff faced time constraints. Understanding the social context of engagement helped TMT to foster respectful and trusting relationships. The complex relationship between the local context and community engagement complicated evaluation of the community strategy

  7. Emerging therapeutic targets for treatment of leishmaniasis.

    PubMed

    Sundar, Shyam; Singh, Bhawana

    2018-06-01

    Parasitic diseases that pose a threat to human life include leishmaniasis - caused by protozoan parasite Leishmania species. Existing drugs have limitations due to deleterious side effects like teratogenicity, high cost and drug resistance. This calls for the need to have an insight into therapeutic aspects of disease. Areas covered: We have identified different drug targets via. molecular, imuunological, metabolic as well as by system biology approaches. We bring these promising drug targets into light so that they can be explored to their maximum. In an effort to bridge the gaps between existing knowledge and prospects of drug discovery, we have compiled interesting studies on drug targets, thereby paving the way for establishment of better therapeutic aspects. Expert opinion: Advancements in technology shed light on many unexplored pathways. Further probing of well established pathways led to the discovery of new drug targets. This review is a comprehensive report on current and emerging drug targets, with emphasis on several metabolic targets, organellar biochemistry, salvage pathways, epigenetics, kinome and more. Identification of new targets can contribute significantly towards strengthening the pipeline for disease elimination.

  8. Molecular mechanisms for vascular complications of targeted cancer therapies.

    PubMed

    Gopal, Srila; Miller, Kenneth B; Jaffe, Iris Z

    2016-10-01

    Molecularly targeted anti-cancer therapies have revolutionized cancer treatment by improving both quality of life and survival in cancer patients. However, many of these drugs are associated with cardiovascular toxicities that are sometimes dose-limiting. Moreover, the long-term cardiovascular consequences of these drugs, some of which are used chronically, are not yet known. Although the scope and mechanisms of the cardiac toxicities are better defined, the mechanisms for vascular toxicities are only beginning to be elucidated. This review summarizes what is known about the vascular adverse events associated with three classes of novel anti-cancer therapies: vascular endothelial growth factor (VEGF) inhibitors, breakpoint cluster-Abelson (BCR-ABL) kinase inhibitors used to treat chronic myelogenous leukaemia (CML) and immunomodulatory agents (IMiDs) used in myeloma therapeutics. Three of the best described vascular toxicities are reviewed including hypertension, increased risk of acute cardiovascular ischaemic events and arteriovenous thrombosis. The available data regarding the mechanism by which each therapy causes vascular complication are summarized. When data are limited, potential mechanisms are inferred from the known effects of inhibiting each target on vascular cell function and disease. Enhanced understanding of the molecular mechanisms of vascular side effects of targeted cancer therapy is necessary to effectively manage cancer patients and to design safer targeted cancer therapies for the future. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

  9. Limitations on quantum key repeaters.

    PubMed

    Bäuml, Stefan; Christandl, Matthias; Horodecki, Karol; Winter, Andreas

    2015-04-23

    A major application of quantum communication is the distribution of entangled particles for use in quantum key distribution. Owing to noise in the communication line, quantum key distribution is, in practice, limited to a distance of a few hundred kilometres, and can only be extended to longer distances by use of a quantum repeater, a device that performs entanglement distillation and quantum teleportation. The existence of noisy entangled states that are undistillable but nevertheless useful for quantum key distribution raises the question of the feasibility of a quantum key repeater, which would work beyond the limits of entanglement distillation, hence possibly tolerating higher noise levels than existing protocols. Here we exhibit fundamental limits on such a device in the form of bounds on the rate at which it may extract secure key. As a consequence, we give examples of states suitable for quantum key distribution but unsuitable for the most general quantum key repeater protocol.

  10. Ballistic Experiments with Titanium and Aluminum Targets

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

    Gogolewski, R.; Morgan, B.R.

    1999-11-23

    During the course of the project we conducted two sets of fundamental experiments in penetration mechanics in the LLNL Terminal Ballistics Laboratory of the Physics Directorate. The first set of full-scale experiments was conducted with a 14.5mm air propelled launcher. The object of the experiments was to determine the ballistic limit speed of 6Al-4V-alloy titanium, low fineness ratio projectiles centrally impacting 2024-T3 alloy aluminum flat plates and the failure modes of the projectiles and the targets. The second set of one-third scale experiments was conducted with a 14.5mm powder launcher. The object of these experiments was to determine the ballisticmore » limit speed of 6Al-4V alloy titanium high fineness ratio projectiles centrally impacting 6Al-4V alloy titanium flat plates and the failure modes of the projectiles and the target. We employed radiography to observe a projectile just before and after interaction with a target plate. Early on, we employed a non-damaging ''soft-catch'' technique to capture projectiles after they perforated targets. Once we realized that a projectile was not damaged during interaction with a target, we used a 4-inch thick 6061-T6-alloy aluminum witness block with a 6.0-inch x 6.0-inch cross-section to measure projectile residual penetration. We have recorded and tabulated below projectile impact speed, projectile residual (post-impact) speed, projectile failure mode, target failure mode, and pertinent comments for the experiments. The ballistic techniques employed for the experiments are similar to those employed in an earlier study.« less

  11. State Recognition of High Voltage Isolation Switch Based on Background Difference and Iterative Search

    NASA Astrophysics Data System (ADS)

    Xu, Jiayuan; Yu, Chengtao; Bo, Bin; Xue, Yu; Xu, Changfu; Chaminda, P. R. Dushantha; Hu, Chengbo; Peng, Kai

    2018-03-01

    The automatic recognition of the high voltage isolation switch by remote video monitoring is an effective means to ensure the safety of the personnel and the equipment. The existing methods mainly include two ways: improving monitoring accuracy and adopting target detection technology through equipment transformation. Such a method is often applied to specific scenarios, with limited application scope and high cost. To solve this problem, a high voltage isolation switch state recognition method based on background difference and iterative search is proposed in this paper. The initial position of the switch is detected in real time through the background difference method. When the switch starts to open and close, the target tracking algorithm is used to track the motion trajectory of the switch. The opening and closing state of the switch is determined according to the angle variation of the switch tracking point and the center line. The effectiveness of the method is verified by experiments on different switched video frames of switching states. Compared with the traditional methods, this method is more robust and effective.

  12. 26 CFR 20.2011-2 - Limitation on credit if a deduction for State death taxes is allowed under section 2053(d).

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 26 Internal Revenue 14 2010-04-01 2010-04-01 false Limitation on credit if a deduction for State death taxes is allowed under section 2053(d). 20.2011-2 Section 20.2011-2 Internal Revenue INTERNAL REVENUE SERVICE, DEPARTMENT OF THE TREASURY (CONTINUED) ESTATE AND GIFT TAXES ESTATE TAX; ESTATES OF DECEDENTS DYING AFTER AUGUST 16, 1954 Credits...

  13. Signal enhancement for the sensitivity-limited solid state NMR experiments using a continuous, non-uniform acquisition scheme

    NASA Astrophysics Data System (ADS)

    Qiang, Wei

    2011-12-01

    We describe a sampling scheme for the two-dimensional (2D) solid state NMR experiments, which can be readily applied to the sensitivity-limited samples. The sampling scheme utilizes continuous, non-uniform sampling profile for the indirect dimension, i.e. the acquisition number decreases as a function of the evolution time ( t1) in the indirect dimension. For a beta amyloid (Aβ) fibril sample, we observed overall 40-50% signal enhancement by measuring the cross peak volume, while the cross peak linewidths remained comparable to the linewidths obtained by regular sampling and processing strategies. Both the linear and Gaussian decay functions for the acquisition numbers result in similar percentage of increment in signal. In addition, we demonstrated that this sampling approach can be applied with different dipolar recoupling approaches such as radiofrequency assisted diffusion (RAD) and finite-pulse radio-frequency-driven recoupling (fpRFDR). This sampling scheme is especially suitable for the sensitivity-limited samples which require long signal averaging for each t1 point, for instance the biological membrane proteins where only a small fraction of the sample is isotopically labeled.

  14. Novel alpha-MSH peptide analogs for melanoma targeting

    NASA Astrophysics Data System (ADS)

    Flook, Adam Michael

    Skin cancer is the one of the most diagnosed cancers in the United States with increasing incidence over the past two decades. There are three major forms of skin cancer but melanoma is the deadliest. It is estimated that 76,690 new diagnoses of melanoma and 9,480 deaths will occur in 2013. Melanoma accounts for approximately 1.6% of all cancer related deaths and is the 5 th leading diagnosed cancer in the United States. The mean survival rate of patients diagnosed with metastatic melanoma is six months, with five year survival rates of less than 5%. In this project, we describe the design and characterization of novel melanoma-targeting peptide analogs for use in diagnostic imaging of both primary and metastatic melanoma lesions. Novel alpha-MSH peptide conjugates were designed to target the melanocortin-1 receptor present and over-expressed on melanoma cells. These peptides were synthesized and their in-vitro melanocortin-1 receptor binding affinities were established in murine melanoma cells. Once binding affinities were determined, the peptides were radiolabeled with 99mTc utilizing a novel direct radiolabeling technique developed in our laboratory. The peptides were purified via reverse-phase high performance liquid chromatography and in-vivo melanoma targeting and pharmacokinetic properties were determined in B16/F1 melanoma-bearing female C57BL/6 mice. Biodistribution and SPECT/CT imaging studies were performed with the promising 99m Tc-labeled peptide conjugates. All alpha-MSH peptide conjugates tested showed low nanomolar binding affinity for the melanocortin-1 receptor. All peptides were readily radiolabeld with 99mTc with greater than 95% radiochemical purity. All 99mTc-labeled peptides displayed high specific in-vivo melanoma tumor uptake while maintaining low normal organ accumulation, and were excreted through the urinary system in a timely fashion. In addition, all tested 99mTc-labeld alpha-MSH peptides demonstrated clear visualization of in

  15. Reconstruction from limited single-particle diffraction data via simultaneous determination of state, orientation, intensity, and phase

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

    Donatelli, Jeffrey J.; Sethian, James A.; Zwart, Peter H.

    Free-electron lasers now have the ability to collect X-ray diffraction patterns from individual molecules; however, each sample is delivered at unknown orientation and may be in one of several conformational states, each with a different molecular structure. Hit rates are often low, typically around 0.1%, limiting the number of useful images that can be collected. Determining accurate structural information requires classifying and orienting each image, accurately assembling them into a 3D diffraction intensity function, and determining missing phase information. Additionally, single particles typically scatter very few photons, leading to high image noise levels. We develop a multitiered iterative phasing algorithmmore » to reconstruct structural information from singleparticle diffraction data by simultaneously determining the states, orientations, intensities, phases, and underlying structure in a single iterative procedure. We leverage real-space constraints on the structure to help guide optimization and reconstruct underlying structure from very few images with excellent global convergence properties. We show that this approach can determine structural resolution beyond what is suggested by standard Shannon sampling arguments for ideal images and is also robust to noise.« less

  16. Reconstruction from limited single-particle diffraction data via simultaneous determination of state, orientation, intensity, and phase

    DOE PAGES

    Donatelli, Jeffrey J.; Sethian, James A.; Zwart, Peter H.

    2017-06-26

    Free-electron lasers now have the ability to collect X-ray diffraction patterns from individual molecules; however, each sample is delivered at unknown orientation and may be in one of several conformational states, each with a different molecular structure. Hit rates are often low, typically around 0.1%, limiting the number of useful images that can be collected. Determining accurate structural information requires classifying and orienting each image, accurately assembling them into a 3D diffraction intensity function, and determining missing phase information. Additionally, single particles typically scatter very few photons, leading to high image noise levels. We develop a multitiered iterative phasing algorithmmore » to reconstruct structural information from singleparticle diffraction data by simultaneously determining the states, orientations, intensities, phases, and underlying structure in a single iterative procedure. We leverage real-space constraints on the structure to help guide optimization and reconstruct underlying structure from very few images with excellent global convergence properties. We show that this approach can determine structural resolution beyond what is suggested by standard Shannon sampling arguments for ideal images and is also robust to noise.« less

  17. Transition of yeast Can1 transporter to the inward-facing state unveils an α-arrestin target sequence promoting its ubiquitylation and endocytosis.

    PubMed

    Gournas, Christos; Saliba, Elie; Krammer, Eva-Maria; Barthelemy, Céline; Prévost, Martine; André, Bruno

    2017-10-15

    Substrate-transport-elicited endocytosis is a common control mechanism of membrane transporters avoiding excess uptake of external compounds, though poorly understood at the molecular level. In yeast, endocytosis of transporters is triggered by their ubiquitylation mediated by the Rsp5 ubiquitin-ligase, recruited by α-arrestin-family adaptors. We here report that transport-elicited ubiquitylation of the arginine transporter Can1 is promoted by transition to an inward-facing state. This conformational change unveils a region of the N-terminal cytosolic tail targeted by the Art1 α-arrestin, which is activated via the TORC1 kinase complex upon arginine uptake. Can1 mutants altered in the arginine-binding site or a cytosolic tripeptide sequence permanently expose the α-arrestin-targeted region so that Art1 activation via TORC1 is sufficient to trigger their endocytosis. We also provide evidence that substrate-transport elicited endocytosis of other amino acid permeases similarly involves unmasking of a cytosolic Art1-target region coupled to activation of Art1 via TORC1. Our results unravel a mechanism likely involved in regulation of many other transporters by their own substrates. They also support the emerging view that transporter ubiquitylation relies on combinatorial interaction rules such that α-arrestins, stimulated via signaling cascades or in their basal state, recognize transporter regions permanently facing the cytosol or unveiled during transport. © 2017 Gournas et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  18. Limited time perspective increases the value of calm.

    PubMed

    Jiang, Da; Fung, Helene H; Sims, Tamara; Tsai, Jeanne L; Zhang, Fan

    2016-02-01

    Previous findings indirectly suggest that the more people perceive their time in life as limited, the more they value calm. No study, however, has directly tested this hypothesis. To this end, using a combination of survey, experience sampling, and experimental methods, we examined the relationship between future time perspective and the affective states that people ideally want to feel (i.e., their "ideal affect"). In Study 1, the more people reported a limited time perspective, the more they wanted to feel calm and experience other low-arousal positive states. In Study 2, participants were randomly assigned to a limited time or an expanded time condition. Participants in the limited time condition reported valuing calm and other low arousal positive states more than those in the expanded time condition. We discuss the implications of these findings for broadening our understanding of the factors that shape how people ideally want to feel, and their consequences for decision making. (c) 2016 APA, all rights reserved).

  19. Fixed target experiments at the Fermilab Tevatron

    DOE PAGES

    Gutierrez, Gaston; Reyes, Marco A.

    2014-11-10

    This paper presents a review of the study of Exclusive Central Production at a Center of Mass energy of √s = 40 GeV at the Fermilab Fixed Target program. In all reactions reviewed in this paper, protons with an energy of 800 GeV were extracted from the Tevatron accelerator at Fermilab and directed to a Liquid Hydrogen target. The states reviewed include π⁺π⁻, K⁰ s K⁰ s, K⁰ s K ±π ∓, φφ and D *±. Partial Wave Analysis results will be presented on the light states but only the cross-section will be reviewed in the diffractive production of Dmore » *±.« less

  20. Drugs and Targets in Fibrosis

    PubMed Central

    Li, Xiaoyi; Zhu, Lixin; Wang, Beibei; Yuan, Meifei; Zhu, Ruixin

    2017-01-01

    Fibrosis contributes to the development of many diseases and many target molecules are involved in fibrosis. Currently, the majority of fibrosis treatment strategies are limited to specific diseases or organs. However, accumulating evidence demonstrates great similarities among fibroproliferative diseases, and more and more drugs are proved to be effective anti-fibrotic therapies across different diseases and organs. Here we comprehensively review the current knowledge on the pathological mechanisms of fibrosis, and divide factors mediating fibrosis progression into extracellular and intracellular groups. Furthermore, we systematically summarize both single and multiple component drugs that target fibrosis. Future directions of fibrosis drug discovery are also proposed. PMID:29218009

  1. Maximum angular accuracy of pulsed laser radar in photocounting limit.

    PubMed

    Elbaum, M; Diament, P; King, M; Edelson, W

    1977-07-01

    To estimate the angular position of targets with pulsed laser radars, their images may be sensed with a fourquadrant noncoherent detector and the image photocounting distribution processed to obtain the angular estimates. The limits imposed on the accuracy of angular estimation by signal and background radiation shot noise, dark current noise, and target cross-section fluctuations are calculated. Maximum likelihood estimates of angular positions are derived for optically rough and specular targets and their performances compared with theoretical lower bounds.

  2. Hit and go CAS9 delivered through a lentiviral based self-limiting circuit.

    PubMed

    Petris, Gianluca; Casini, Antonio; Montagna, Claudia; Lorenzin, Francesca; Prandi, Davide; Romanel, Alessandro; Zasso, Jacopo; Conti, Luciano; Demichelis, Francesca; Cereseto, Anna

    2017-05-22

    In vivo application of the CRISPR-Cas9 technology is still limited by unwanted Cas9 genomic cleavages. Long-term expression of Cas9 increases the number of genomic loci non-specifically cleaved by the nuclease. Here we develop a Self-Limiting Cas9 circuit for Enhanced Safety and specificity (SLiCES) which consists of an expression unit for Streptococcus pyogenes Cas9 (SpCas9), a self-targeting sgRNA and a second sgRNA targeting a chosen genomic locus. The self-limiting circuit results in increased genome editing specificity by controlling Cas9 levels. For its in vivo utilization, we next integrate SLiCES into a lentiviral delivery system (lentiSLiCES) via circuit inhibition to achieve viral particle production. Upon delivery into target cells, the lentiSLiCES circuit switches on to edit the intended genomic locus while simultaneously stepping up its own neutralization through SpCas9 inactivation. By preserving target cells from residual nuclease activity, our hit and go system increases safety margins for genome editing.

  3. 47 CFR 5.93 - Limited market studies.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 47 Telecommunication 1 2010-10-01 2010-10-01 false Limited market studies. 5.93 Section 5.93...) Applications and Licenses § 5.93 Limited market studies. Unless otherwise stated in the instrument of authorization, licenses granted for the purpose of limited market studies pursuant to § 5.3(j) of this part are...

  4. 47 CFR 5.93 - Limited market studies.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 47 Telecommunication 1 2011-10-01 2011-10-01 false Limited market studies. 5.93 Section 5.93...) Applications and Licenses § 5.93 Limited market studies. Unless otherwise stated in the instrument of authorization, licenses granted for the purpose of limited market studies pursuant to § 5.3(j) of this part are...

  5. Problems and Limitations in Studies on Screening for Language Delay

    ERIC Educational Resources Information Center

    Eriksson, Marten; Westerlund, Monica; Miniscalco, Carmela

    2010-01-01

    This study discusses six common methodological limitations in screening for language delay (LD) as illustrated in 11 recent studies. The limitations are (1) whether the studies define a target population, (2) whether the recruitment procedure is unbiased, (3) attrition, (4) verification bias, (5) small sample size and (6) inconsistencies in choice…

  6. Enhanced processing of threat stimuli under limited attentional resources.

    PubMed

    De Martino, Benedetto; Kalisch, Raffael; Rees, Geraint; Dolan, Raymond J

    2009-01-01

    The ability to process stimuli that convey potential threat, under conditions of limited attentional resources, confers adaptive advantages. This study examined the neurobiology underpinnings of this capacity. Employing an attentional blink paradigm, in conjunction with functional magnetic resonance imaging, we manipulated the salience of the second of 2 face target stimuli (T2), by varying emotionality. Behaviorally, fearful T2 faces were identified significantly more than neutral faces. Activity in fusiform face area increased with correct identification of T2 faces. Enhanced activity in rostral anterior cingulate cortex (rACC) accounted for the benefit in detection of fearful stimuli reflected in a significant interaction between target valence and correct identification. Thus, under conditions of limited attention resources activation in rACC correlated with enhanced processing of emotional stimuli. We suggest that these data support a model in which a prefrontal "gate" mechanism controls conscious access of emotional information under conditions of limited attentional resources.

  7. Mechanical Computing Redux: Limitations at the Nanoscale

    NASA Astrophysics Data System (ADS)

    Liu, Tsu-Jae King

    2014-03-01

    Technology solutions for overcoming the energy efficiency limits of nanoscale complementary metal oxide semiconductor (CMOS) technology ultimately will be needed in order to address the growing issue of integrated-circuit chip power density. Off-state leakage current sets a fundamental lower limit in energy per operation for any voltage-level-based digital logic implemented with transistors (CMOS and beyond), which leads to practical limits for device density (i.e. cost) and operating frequency (i.e. system performance). Mechanical switches have zero off-state leakag and hence can overcome this fundamental limit. Contact adhesive force sets a lower limit for the switching energy of a mechanical switch, however, and also directly impacts its performance. This paper will review recent progress toward the development of nano-electro-mechanical relay technology and discuss remaining challenges for realizing the promise of mechanical computing for ultra-low-power computing. Supported by the Center for Energy Efficient Electronics Science (NSF Award 0939514).

  8. Care Cascade for targeted tuberculosis testing and linkage to Care in Homeless Populations in the United States: a meta-analysis.

    PubMed

    Parriott, Andrea; Malekinejad, Mohsen; Miller, Amanda P; Marks, Suzanne M; Horvath, Hacsi; Kahn, James G

    2018-04-12

    Homelessness increases the risk of tuberculosis (TB) disease and latent TB infection (LTBI), but persons experiencing homelessness often lack access to testing and treatment. We assessed the yield of TB testing and linkage to care for programs targeting homeless populations in the United States. We conducted a comprehensive search of peer-reviewed and grey literature, adapting Cochrane systematic review methods. Two reviewers independently assessed study eligibility and abstracted key data on the testing to care cascade: number of persons reached, recruited for testing, tested for LTBI, with valid test results, referred to follow-up care, and initiating care. We used random effects to calculate pooled proportions and 95% confidence intervals (CI) of persons retained in each step via inverse-variance weighted meta-analysis, and cumulative proportions as products of adjacent step proportions. We identified 23 studies published between 1986 and 2014, conducted in 12 states and 15 cities. Among studies using tuberculin skin tests (TST) we found that 93.7% (CI 72.4-100%) of persons reached were recruited, 97.9% (89.3-100%) of those recruited had tests placed, 85.5% (78.6-91.3%) of those with tests placed returned for reading, 99.9% (99.6-100%) of those with tests read had valid results, and 24.7% (21.0-28.5%) with valid results tested positive. All persons testing positive were referred to follow-up care, and 99.8% attended at least one session of follow-up care. Heterogeneity was high for most pooled proportions. For a hypothetical cohort of 1000 persons experiencing homelessness reached by a targeted testing program using TST, an estimated 917 were tested, 194 were positive, and all of these initiated follow-up care. Targeted TB testing of persons experiencing homelessness appears effective in detecting LTBI and connecting persons to care and potential treatment. Future evaluations should assess diagnostic use of interferon gamma release assays and completion of

  9. Underwater linear polarization: physical limitations to biological functions

    PubMed Central

    Shashar, Nadav; Johnsen, Sönke; Lerner, Amit; Sabbah, Shai; Chiao, Chuan-Chin; Mäthger, Lydia M.; Hanlon, Roger T.

    2011-01-01

    Polarization sensitivity is documented in a range of marine animals. The variety of tasks for which animals can use this sensitivity, and the range over which they do so, are confined by the visual systems of these animals and by the propagation of the polarization information in the aquatic environment. We examine the environmental physical constraints in an attempt to reveal the depth, range and other limitations to the use of polarization sensitivity by marine animals. In clear oceanic waters, navigation that is based on the polarization pattern of the sky appears to be limited to shallow waters, while solar-based navigation is possible down to 200–400 m. When combined with intensity difference, polarization sensitivity allows an increase in target detection range by 70–80% with an upper limit of 15 m for large-eyed animals. This distance will be significantly smaller for small animals, such as plankton, and in turbid waters. Polarization-contrast detection, which is relevant to object detection and communication, is strongly affected by water conditions and in clear waters its range limit may reach 15 m as well. We show that polarization sensitivity may also serve for target distance estimation, when examining point source bioluminescent objects in the photic mesopelagic depth range. PMID:21282168

  10. 50 CFR 38.13 - Speed limits.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 50 Wildlife and Fisheries 8 2011-10-01 2011-10-01 false Speed limits. 38.13 Section 38.13 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR (CONTINUED) THE NATIONAL WILDLIFE REFUGE SYSTEM MIDWAY ATOLL NATIONAL WILDLIFE REFUGE Prohibitions § 38.13 Speed limits. No...

  11. 50 CFR 38.13 - Speed limits.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 50 Wildlife and Fisheries 9 2013-10-01 2013-10-01 false Speed limits. 38.13 Section 38.13 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR (CONTINUED) THE NATIONAL WILDLIFE REFUGE SYSTEM MIDWAY ATOLL NATIONAL WILDLIFE REFUGE Prohibitions § 38.13 Speed limits. No...

  12. 50 CFR 38.13 - Speed limits.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 50 Wildlife and Fisheries 9 2014-10-01 2014-10-01 false Speed limits. 38.13 Section 38.13 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR (CONTINUED) THE NATIONAL WILDLIFE REFUGE SYSTEM MIDWAY ATOLL NATIONAL WILDLIFE REFUGE Prohibitions § 38.13 Speed limits. No...

  13. 50 CFR 38.13 - Speed limits.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 50 Wildlife and Fisheries 9 2012-10-01 2012-10-01 false Speed limits. 38.13 Section 38.13 Wildlife and Fisheries UNITED STATES FISH AND WILDLIFE SERVICE, DEPARTMENT OF THE INTERIOR (CONTINUED) THE NATIONAL WILDLIFE REFUGE SYSTEM MIDWAY ATOLL NATIONAL WILDLIFE REFUGE Prohibitions § 38.13 Speed limits. No...

  14. Targetting and guidance program documentation. [a user's manual

    NASA Technical Reports Server (NTRS)

    Harrold, E. F.; Neyhard, J. F.

    1974-01-01

    A FORTRAN computer program was developed which automatically targets two and three burn rendezvous missions and performs feedback guidance using the GUIDE algorithm. The program was designed to accept a large class of orbit specifications and to automatically choose a two or three burn mission depending upon the time alignment of the vehicle and target. The orbits may be specified as any combination of circular and elliptical orbits and may be coplanar or inclined, but must be aligned coaxially with their perigees in the same direction. The program accomplishes the required targeting by repeatedly converging successively more complex missions. It solves the coplanar impulsive version of the mission, then the finite burn coplanar mission, and finally, the full plane change mission. The GUIDE algorithm is exercised in a feedback guidance mode by taking the targeted solution and moving the vehicle state step by step ahead in time, adding acceleration and navigational errors, and reconverging from the perturbed states at fixed guidance update intervals. A program overview is presented, along with a user's guide which details input, output, and the various subroutines.

  15. Singular vector-based targeted observations of chemical constituents: description and first application of the EURAD-IM-SVA v1.0

    NASA Astrophysics Data System (ADS)

    Goris, N.; Elbern, H.

    2015-12-01

    Measurements of the large-dimensional chemical state of the atmosphere provide only sparse snapshots of the state of the system due to their typically insufficient temporal and spatial density. In order to optimize the measurement configurations despite those limitations, the present work describes the identification of sensitive states of the chemical system as optimal target areas for adaptive observations. For this purpose, the technique of singular vector analysis (SVA), which has proven effective for targeted observations in numerical weather prediction, is implemented in the EURAD-IM (EURopean Air pollution and Dispersion - Inverse Model) chemical transport model, yielding the EURAD-IM-SVA v1.0. Besides initial values, emissions are investigated as critical simulation controlling targeting variables. For both variants, singular vectors are applied to determine the optimal placement for observations and moreover to quantify which chemical compounds have to be observed with preference. Based on measurements of the airship based ZEPTER-2 campaign, the EURAD-IM-SVA v1.0 has been evaluated by conducting a comprehensive set of model runs involving different initial states and simulation lengths. For the sake of brevity, we concentrate our attention on the following chemical compounds, O3, NO, NO2, HCHO, CO, HONO, and OH, and focus on their influence on selected O3 profiles. Our analysis shows that the optimal placement for observations of chemical species is not entirely determined by mere transport and mixing processes. Rather, a combination of initial chemical concentrations, chemical conversions, and meteorological processes determines the influence of chemical compounds and regions. We furthermore demonstrate that the optimal placement of observations of emission strengths is highly dependent on the location of emission sources and that the benefit of including emissions as target variables outperforms the value of initial value optimization with growing

  16. Deep-Learning-Based Drug-Target Interaction Prediction.

    PubMed

    Wen, Ming; Zhang, Zhimin; Niu, Shaoyu; Sha, Haozhi; Yang, Ruihan; Yun, Yonghuan; Lu, Hongmei

    2017-04-07

    Identifying interactions between known drugs and targets is a major challenge in drug repositioning. In silico prediction of drug-target interaction (DTI) can speed up the expensive and time-consuming experimental work by providing the most potent DTIs. In silico prediction of DTI can also provide insights about the potential drug-drug interaction and promote the exploration of drug side effects. Traditionally, the performance of DTI prediction depends heavily on the descriptors used to represent the drugs and the target proteins. In this paper, to accurately predict new DTIs between approved drugs and targets without separating the targets into different classes, we developed a deep-learning-based algorithmic framework named DeepDTIs. It first abstracts representations from raw input descriptors using unsupervised pretraining and then applies known label pairs of interaction to build a classification model. Compared with other methods, it is found that DeepDTIs reaches or outperforms other state-of-the-art methods. The DeepDTIs can be further used to predict whether a new drug targets to some existing targets or whether a new target interacts with some existing drugs.

  17. The detection and stabilisation of limit cycle for deterministic finite automata

    NASA Astrophysics Data System (ADS)

    Han, Xiaoguang; Chen, Zengqiang; Liu, Zhongxin; Zhang, Qing

    2018-04-01

    In this paper, the topological structure properties of deterministic finite automata (DFA), under the framework of the semi-tensor product of matrices, are investigated. First, the dynamics of DFA are converted into a new algebraic form as a discrete-time linear system by means of Boolean algebra. Using this algebraic description, the approach of calculating the limit cycles of different lengths is given. Second, we present two fundamental concepts, namely, domain of attraction of limit cycle and prereachability set. Based on the prereachability set, an explicit solution of calculating domain of attraction of a limit cycle is completely characterised. Third, we define the globally attractive limit cycle, and then the necessary and sufficient condition for verifying whether all state trajectories of a DFA enter a given limit cycle in a finite number of transitions is given. Fourth, the problem of whether a DFA can be stabilised to a limit cycle by the state feedback controller is discussed. Criteria for limit cycle-stabilisation are established. All state feedback controllers which implement the minimal length trajectories from each state to the limit cycle are obtained by using the proposed algorithm. Finally, an illustrative example is presented to show the theoretical results.

  18. Generalized Geometric Quantum Speed Limits

    NASA Astrophysics Data System (ADS)

    Pires, Diego Paiva; Cianciaruso, Marco; Céleri, Lucas C.; Adesso, Gerardo; Soares-Pinto, Diogo O.

    2016-04-01

    The attempt to gain a theoretical understanding of the concept of time in quantum mechanics has triggered significant progress towards the search for faster and more efficient quantum technologies. One of such advances consists in the interpretation of the time-energy uncertainty relations as lower bounds for the minimal evolution time between two distinguishable states of a quantum system, also known as quantum speed limits. We investigate how the nonuniqueness of a bona fide measure of distinguishability defined on the quantum-state space affects the quantum speed limits and can be exploited in order to derive improved bounds. Specifically, we establish an infinite family of quantum speed limits valid for unitary and nonunitary evolutions, based on an elegant information geometric formalism. Our work unifies and generalizes existing results on quantum speed limits and provides instances of novel bounds that are tighter than any established one based on the conventional quantum Fisher information. We illustrate our findings with relevant examples, demonstrating the importance of choosing different information metrics for open system dynamics, as well as clarifying the roles of classical populations versus quantum coherences, in the determination and saturation of the speed limits. Our results can find applications in the optimization and control of quantum technologies such as quantum computation and metrology, and might provide new insights in fundamental investigations of quantum thermodynamics.

  19. 7 CFR 761.208 - Target participation rates for socially disadvantaged groups.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 7 Agriculture 7 2011-01-01 2011-01-01 false Target participation rates for socially disadvantaged... Farm Loan Programs Funds to State Offices § 761.208 Target participation rates for socially disadvantaged groups. (a) General. (1) The Agency establishes target participation rates for providing FO, CL...

  20. Beam-target double-spin asymmetry in quasielastic electron scattering off the deuteron with CLAS

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

    Mayer, M.; Kuhn, S. E.; Adhikari, K. P.

    Background: The deuteron plays a pivotal role in nuclear and hadronic physics, as both the simplest bound multi-nucleon system and as an ``effective neutron target''. Quasi-elastic electron scattering on the deuteron is a benchmark reaction to test our understanding of deuteron structure and the properties and interactions of the two nucleons bound in the deuteron. Purpose: The experimental data presented here test state-of-the-art models of the deuteron and the two-nucleon interaction in the final state after two-body breakup of the deuteron. Focusing on polarization degrees of freedom, we gain information on the limits of the Impulse Approximation (IA) picture andmore » put the interpretation of spin structure measurements with deuterium on a firmer footing. Information on this reaction can also be used to improve the determination of the deuteron polarization through quasi-elastic electron scattering. Method: We measured the beam-target double spin asymmetry (A||) for quasi-elastic electron scattering off the deuteron at several beam energies (1.6-1.7 GeV, 2.5 GeV, 4.2 GeV and 5.6-5.8 GeV), using the CEBAF Large Acceptance Spectrometer (CLAS) at Thomas Jefferson National Accelerator Facility. The deuterons were polarized along (or opposite to) the beam direction. The double spin asymmetries were measured as a function of photon virtuality Q2 (0.13-3.17 (GeV/c)2), missing momentum (pm = 0.0 - 0.5 GeV/c), and the angle between the (inferred) ``spectator'' neutron and the momentum transfer direction (θnq). Results: The results are compared with a recent model that includes Final State Interactions (FSI) using a complete parameterization of nucleon-nucleon scattering, as well as a simplified model using the Plane Wave Impulse Approximation (PWIA). We find overall good agreement with both the PWIA and FSI expectations at low to medium missing momenta (pm ≤ 0.25 GeV/c), including the change of the asymmetry due to the contribution of the deuteron D-state at

  1. Within-hemifield competition in early visual areas limits the ability to track multiple objects with attention.

    PubMed

    Störmer, Viola S; Alvarez, George A; Cavanagh, Patrick

    2014-08-27

    It is much easier to divide attention across the left and right visual hemifields than within the same visual hemifield. Here we investigate whether this benefit of dividing attention across separate visual fields is evident at early cortical processing stages. We measured the steady-state visual evoked potential, an oscillatory response of the visual cortex elicited by flickering stimuli, of moving targets and distractors while human observers performed a tracking task. The amplitude of responses at the target frequencies was larger than that of the distractor frequencies when participants tracked two targets in separate hemifields, indicating that attention can modulate early visual processing when it is divided across hemifields. However, these attentional modulations disappeared when both targets were tracked within the same hemifield. These effects were not due to differences in task performance, because accuracy was matched across the tracking conditions by adjusting target speed (with control conditions ruling out effects due to speed alone). To investigate later processing stages, we examined the P3 component over central-parietal scalp sites that was elicited by the test probe at the end of the trial. The P3 amplitude was larger for probes on targets than on distractors, regardless of whether attention was divided across or within a hemifield, indicating that these higher-level processes were not constrained by visual hemifield. These results suggest that modulating early processing stages enables more efficient target tracking, and that within-hemifield competition limits the ability to modulate multiple target representations within the hemifield maps of the early visual cortex. Copyright © 2014 the authors 0270-6474/14/3311526-08$15.00/0.

  2. Recognition of dual targets by a molecular beacon-based sensor: subtyping of influenza A virus.

    PubMed

    Lee, Chun-Ching; Liao, Yu-Chieh; Lai, Yu-Hsuan; Lee, Chang-Chun David; Chuang, Min-Chieh

    2015-01-01

    A molecular beacon (MB)-based sensor to offer a decisive answer in combination with information originated from dual-target inputs is designed. The system harnesses an assistant strand and thermodynamically favored designation of unpaired nucleotides (UNs) to process the binary targets in "AND-gate" format and report fluorescence in "off-on" mechanism via a formation of a DNA four-way junction (4WJ). By manipulating composition of the UNs, the dynamic fluorescence difference between the binary targets-coexisting circumstance and any other scenario was maximized. Characteristic equilibrium constant (K), change of entropy (ΔS), and association rate constant (k) between the association ("on") and dissociation ("off") states of the 4WJ were evaluated to understand unfolding behavior of MB in connection to its sensing capability. Favorable MB and UNs were furthermore designed toward analysis of genuine genetic sequences of hemagglutinin (HA) and neuraminidase (NA) in an influenza A H5N2 isolate. The MB-based sensor was demonstrated to yield a linear calibration range from 1.2 to 240 nM and detection limit of 120 pM. Furthermore, high-fidelity subtyping of influenza virus was implemented in a sample of unpurified amplicons. The strategy opens an alternative avenue of MB-based sensors for dual targets toward applications in clinical diagnosis.

  3. Performing target specific band reduction using artificial neural networks and assessment of its efficacy using various target detection algorithms

    NASA Astrophysics Data System (ADS)

    Yadav, Deepti; Arora, M. K.; Tiwari, K. C.; Ghosh, J. K.

    2016-04-01

    Hyperspectral imaging is a powerful tool in the field of remote sensing and has been used for many applications like mineral detection, detection of landmines, target detection etc. Major issues in target detection using HSI are spectral variability, noise, small size of the target, huge data dimensions, high computation cost, complex backgrounds etc. Many of the popular detection algorithms do not work for difficult targets like small, camouflaged etc. and may result in high false alarms. Thus, target/background discrimination is a key issue and therefore analyzing target's behaviour in realistic environments is crucial for the accurate interpretation of hyperspectral imagery. Use of standard libraries for studying target's spectral behaviour has limitation that targets are measured in different environmental conditions than application. This study uses the spectral data of the same target which is used during collection of the HSI image. This paper analyze spectrums of targets in a way that each target can be spectrally distinguished from a mixture of spectral data. Artificial neural network (ANN) has been used to identify the spectral range for reducing data and further its efficacy for improving target detection is verified. The results of ANN proposes discriminating band range for targets; these ranges were further used to perform target detection using four popular spectral matching target detection algorithm. Further, the results of algorithms were analyzed using ROC curves to evaluate the effectiveness of the ranges suggested by ANN over full spectrum for detection of desired targets. In addition, comparative assessment of algorithms is also performed using ROC.

  4. Forming Uniform Deuterium-Ice Layers in Cryogenic Targets: Experiences Using the OMEGA Cryogenic Target Handling System

    NASA Astrophysics Data System (ADS)

    Harding, D. R.; Wittman, M. D.; Elasky, L.; Iwan, L. S.; Lund, L.

    2001-10-01

    The OMEGA Cryogenic Target Handling System (OCTHS) allows variable-thickness ice layers (nominal 100-μm) to be formed inside OMEGA-size (1-mm-diam., 3-μm-wall) plastic shells. The OCTHS design provides the most straightforward thermal environment for layering targets: permeation filled spherical targets are in a spherical isothermal environment. The layered target can be rotated 360^o to acquire multiple views of the ice layer. However, the capability of providing cryogenic targets for implosion experiments imposes constraints that do not exist in test systems dedicated to ice-layering studies. Most affected is the ability to characterize the target: space constraints and the need for multiple sets of windows limit the viewing access to f/5 optics, which affects the image quality. With these features, the OCTS provides the most relevant test system, to date, for layering targets and quantifying the overall ice roughness. No single layering protocol provides repeatable ice smoothness. All techniques require extensive operator interaction, and the layering process is lengthy. Typical ice rms smoothness varied from 5 to 10 μm for all targets studied. Characterizing the ice layer from different views shows a ~30% variation in the ice rms smoothness and a greater difference in the power spectra, depending on the view axis. This work was supported by the U.S. DOE Office of Inertial Confinement Fusion under Cooperative Agreement No. DE-FC03-92SF19460.

  5. 40 CFR 229.2 - Transport of target vessels.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 40 Protection of Environment 25 2011-07-01 2011-07-01 false Transport of target vessels. 229.2... PERMITS § 229.2 Transport of target vessels. (a) The U.S. Navy is hereby granted a general permit to transport vessels from the United States or from any other location for the purpose of sinking such vessels...

  6. Limiting Forces on Transit Trucks in Steady-State Curving

    DOT National Transportation Integrated Search

    1981-05-01

    This study develops conservative bounds on wheel/rail forces and flange forces for several types of rigid and flexible trucks in steady-state curving conditions. The approximate analysis presented provides closed-form relations for estimating forces,...

  7. Drug resistance to targeted therapies: déjà vu all over again.

    PubMed

    Groenendijk, Floris H; Bernards, René

    2014-09-12

    A major limitation of targeted anticancer therapies is intrinsic or acquired resistance. This review emphasizes similarities in the mechanisms of resistance to endocrine therapies in breast cancer and those seen with the new generation of targeted cancer therapeutics. Resistance to single-agent cancer therapeutics is frequently the result of reactivation of the signaling pathway, indicating that a major limitation of targeted agents lies in their inability to fully block the cancer-relevant signaling pathway. The development of mechanism-based combinations of targeted therapies together with non-invasive molecular disease monitoring is a logical way forward to delay and ultimately overcome drug resistance development. Copyright © 2014 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  8. Multisensor fusion for 3D target tracking using track-before-detect particle filter

    NASA Astrophysics Data System (ADS)

    Moshtagh, Nima; Romberg, Paul M.; Chan, Moses W.

    2015-05-01

    This work presents a novel fusion mechanism for estimating the three-dimensional trajectory of a moving target using images collected by multiple imaging sensors. The proposed projective particle filter avoids the explicit target detection prior to fusion. In projective particle filter, particles that represent the posterior density (of target state in a high-dimensional space) are projected onto the lower-dimensional observation space. Measurements are generated directly in the observation space (image plane) and a marginal (sensor) likelihood is computed. The particles states and their weights are updated using the joint likelihood computed from all the sensors. The 3D state estimate of target (system track) is then generated from the states of the particles. This approach is similar to track-before-detect particle filters that are known to perform well in tracking dim and stealthy targets in image collections. Our approach extends the track-before-detect approach to 3D tracking using the projective particle filter. The performance of this measurement-level fusion method is compared with that of a track-level fusion algorithm using the projective particle filter. In the track-level fusion algorithm, the 2D sensor tracks are generated separately and transmitted to a fusion center, where they are treated as measurements to the state estimator. The 2D sensor tracks are then fused to reconstruct the system track. A realistic synthetic scenario with a boosting target was generated, and used to study the performance of the fusion mechanisms.

  9. Target detection cycle criteria when using the targeting task performance metric

    NASA Astrophysics Data System (ADS)

    Hixson, Jonathan G.; Jacobs, Eddie L.; Vollmerhausen, Richard H.

    2004-12-01

    The US Army RDECOM CERDEC Night Vision and Electronic Sensors Directorate of the US Army (NVESD) has developed a new target acquisition metric to better predict the performance of modern electro-optical imagers. The TTP metric replaces the Johnson criteria. One problem with transitioning to the new model is that the difficulty of searching in a terrain has traditionally been quantified by an "N50." The N50 is the number of Johnson criteria cycles needed for the observer to detect the target half the time, assuming that the observer is not time limited. In order to make use of this empirical data base, a conversion must be found relating Johnson cycles for detection to TTP cycles for detection. This paper describes how that relationship is established. We have found that the relationship between Johnson and TTP is 1:2.7 for the recognition and identification tasks.

  10. New and emerging targeted therapies for cystic fibrosis.

    PubMed

    Quon, Bradley S; Rowe, Steven M

    2016-03-30

    Cystic fibrosis (CF) is a monogenic autosomal recessive disorder that affects about 70,000 people worldwide. The clinical manifestations of the disease are caused by defects in the cystic fibrosis transmembrane conductance regulator (CFTR) protein. The discovery of the CFTR gene in 1989 has led to a sophisticated understanding of how thousands of mutations in the CFTR gene affect the structure and function of the CFTR protein. Much progress has been made over the past decade with the development of orally bioavailable small molecule drugs that target defective CFTR proteins caused by specific mutations. Furthermore, there is considerable optimism about the prospect of gene replacement or editing therapies to correct all mutations in cystic fibrosis. The recent approvals of ivacaftor and lumacaftor represent the genesis of a new era of precision medicine in the treatment of this condition. These drugs are having a positive impact on the lives of people with cystic fibrosis and are potentially disease modifying. This review provides an update on advances in our understanding of the structure and function of the CFTR, with a focus on state of the art targeted drugs that are in development. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

  11. Myc-Driven Glycolysis Is a Therapeutic Target in Glioblastoma.

    PubMed

    Tateishi, Kensuke; Iafrate, A John; Ho, Quan; Curry, William T; Batchelor, Tracy T; Flaherty, Keith T; Onozato, Maristela L; Lelic, Nina; Sundaram, Sudhandra; Cahill, Daniel P; Chi, Andrew S; Wakimoto, Hiroaki

    2016-09-01

    Deregulated Myc drives an oncogenic metabolic state, including pseudohypoxic glycolysis, adapted for the constitutive production of biomolecular precursors to feed rapid tumor cell growth. In glioblastoma, Myc facilitates renewal of the tumor-initiating cell reservoir contributing to tumor maintenance. We investigated whether targeting the Myc-driven metabolic state could be a selectively toxic therapeutic strategy for glioblastoma. The glycolytic dependency of Myc-driven glioblastoma was tested using (13)C metabolic flux analysis, glucose-limiting culture assays, and glycolysis inhibitors, including inhibitors of the NAD(+) salvage enzyme nicotinamide phosphoribosyl-transferase (NAMPT), in MYC and MYCN shRNA knockdown and lentivirus overexpression systems and in patient-derived glioblastoma tumorspheres with and without MYC/MYCN amplification. The in vivo efficacy of glycolyic inhibition was tested using NAMPT inhibitors in MYCN-amplified patient-derived glioblastoma orthotopic xenograft mouse models. Enforced Myc overexpression increased glucose flux and expression of glycolytic enzymes in glioblastoma cells. Myc and N-Myc knockdown and Myc overexpression systems demonstrated that Myc activity determined sensitivity and resistance to inhibition of glycolysis. Small-molecule inhibitors of glycolysis, particularly NAMPT inhibitors, were selectively toxic to MYC/MYCN-amplified patient-derived glioblastoma tumorspheres. NAMPT inhibitors were potently cytotoxic, inducing apoptosis and significantly extended the survival of mice bearing MYCN-amplified patient-derived glioblastoma orthotopic xenografts. Myc activation in glioblastoma generates a dependency on glycolysis and an addiction to metabolites required for glycolysis. Glycolytic inhibition via NAMPT inhibition represents a novel metabolically targeted therapeutic strategy for MYC or MYCN-amplified glioblastoma and potentially other cancers genetically driven by Myc. Clin Cancer Res; 22(17); 4452-65. ©2016 AACR

  12. One target, different effects: a comparison of distinct therapeutic antibodies against the same targets.

    PubMed

    Shim, Hyunbo

    2011-10-31

    To date, more than 30 antibodies have been approved worldwide for therapeutic use. While the monoclonal antibody market is rapidly growing, the clinical use of therapeutic antibodies is mostly limited to treatment of cancers and immunological disorders. Moreover, antibodies against only five targets (TNF-α, HER2, CD20, EGFR, and VEGF) account for more than 80 percent of the worldwide market of therapeutic antibodies. The shortage of novel, clinically proven targets has resulted in the development of many distinct therapeutic antibodies against a small number of proven targets, based on the premise that different antibody molecules against the same target antigen have distinct biological and clinical effects from one another. For example, four antibodies against TNF-α have been approved by the FDA -- infliximab, adalimumab, golimumab, and certolizumab pegol -- with many more in clinical and preclinical development. The situation is similar for HER2, CD20, EGFR, and VEGF, each having one or more approved antibodies and many more under development. This review discusses the different binding characteristics, mechanisms of action, and biological and clinical activities of multiple monoclonal antibodies against TNF-α, HER-2, CD20, and EGFR and provides insights into the development of therapeutic antibodies.

  13. Effects of practice on tip-of-the-tongue states.

    PubMed

    Smith, S M; Balfour, S P; Brown, J M

    1994-03-01

    Tip-of-the-tongue (TOT) states were examined in relation to acquisition manipulations, using named imaginary animals (TOTimals) as targets. High levels of TOT states were found in three experiments. In the first experiment an increase in the duration of initial exposure to target material improved recall and recognition, and reduced the number of unrecalled items not in TOT states (NTOTs), but did not affect TOT levels. In Experiment 2 practice at writing target names, as compared with only reading them, improved recall performance and decreased TOT levels, but did not reduce NTOTs. Experiment 3 replicated the finding that writing during practice reduced TOT states, but did not reduce NTOTs, and also found that more frequent practice trials increased recall without affecting TOT levels. The results suggest that practice writing target names prevents TOT states by strengthening otherwise deficient phonological connections in memory, a deficiency that can cause TOT states when visual-to-lexical connections give only partial access to a target in memory. The results also demonstrate the usefulness of the TOTimal technique for testing effects of acquisition variables on TOT experiences.

  14. Pharmacophore based design of some multi-targeted compounds targeted against pathways of diabetic complications.

    PubMed

    Chadha, Navriti; Silakari, Om

    2017-09-01

    Diabetic complications is a complex metabolic disorder developed primarily due to prolonged hyperglycemia in the body. The complexity of the disease state as well as the unifying pathophysiology discussed in the literature reports exhibited that the use of multi-targeted agents with multiple complementary biological activities may offer promising therapy for the intervention of the disease over the single-target drugs. In the present study, novel thiazolidine-2,4-dione analogues were designed as multi-targeted agents implicated against the molecular pathways involved in diabetic complications using knowledge based as well as in-silico approaches such as pharmacophore mapping, molecular docking etc. The hit molecules were duly synthesized and biochemical estimation of these molecules against aldose reductase (ALR2), protein kinase Cβ (PKCβ) and poly (ADP-ribose) polymerase 1 (PARP-1) led to identification of compound 2 that showed good potency against PARP-1 and ALR2 enzymes. These positive results support the progress of a low cost multi-targeted agent with putative roles in diabetic complications. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Targeting Resources for Local Growth.

    ERIC Educational Resources Information Center

    Casto, James E.

    2001-01-01

    Focusing state and federal dollars on targeted areas, the Kentucky Appalachian Community Development Initiative helps communities in eastern Kentucky fund their own strategies for economic growth. In Hindman, the project focuses on creating the Kentucky School of Crafts, to train master artisans; supporting the Kentucky Appalachian Artisan Center;…

  16. Quantitative Determination of Wax Contamination in Polystyrene HIPE Foam Using Solid-State NMR

    DOE PAGES

    Cluff, Kyle James; Goodwin, Lynne Alese; Hamilton, Christopher Eric; ...

    2017-11-29

    Differences in molecular mobility between polystyrene foam and Brij-78 wax results in vast differences in the 1H nuclear magnetic resonance (NMR) linewidth. This allows for the convenient determination of wax content in the polystyrene foam components of inertial confinement fusion targets via solid-state NMR. Lastly, contamination levels as low as 0.1% are easily recognized and quantified, and the detection limit is calculated to be 0.02% even when only 32 transients are recorded.

  17. Quantitative Determination of Wax Contamination in Polystyrene HIPE Foam Using Solid-State NMR

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

    Cluff, Kyle James; Goodwin, Lynne Alese; Hamilton, Christopher Eric

    Differences in molecular mobility between polystyrene foam and Brij-78 wax results in vast differences in the 1H nuclear magnetic resonance (NMR) linewidth. This allows for the convenient determination of wax content in the polystyrene foam components of inertial confinement fusion targets via solid-state NMR. Lastly, contamination levels as low as 0.1% are easily recognized and quantified, and the detection limit is calculated to be 0.02% even when only 32 transients are recorded.

  18. Multi-Maneuver Clohessy-Wiltshire Targeting

    NASA Technical Reports Server (NTRS)

    Dannemiller, David P.

    2011-01-01

    Orbital rendezvous involves execution of a sequence of maneuvers by a chaser vehicle to bring the chaser to a desired state relative to a target vehicle while meeting intermediate and final relative constraints. Intermediate and final relative constraints are necessary to meet a multitude of requirements such as to control approach direction, ensure relative position is adequate for operation of space-to-space communication systems and relative sensors, provide fail-safe trajectory features, and provide contingency hold points. The effect of maneuvers on constraints is often coupled, so the maneuvers must be solved for as a set. For example, maneuvers that affect orbital energy change both the chaser's height and downrange position relative to the target vehicle. Rendezvous designers use experience and rules-of-thumb to design a sequence of maneuvers and constraints. A non-iterative method is presented for targeting a rendezvous scenario that includes a sequence of maneuvers and relative constraints. This method is referred to as Multi-Maneuver Clohessy-Wiltshire Targeting (MM_CW_TGT). When a single maneuver is targeted to a single relative position, the classic CW targeting solution is obtained. The MM_CW_TGT method involves manipulation of the CW state transition matrix to form a linear system. As a starting point for forming the algorithm, the effects of a series of impulsive maneuvers on the state are derived. Simple and moderately complex examples are used to demonstrate the pattern of the resulting linear system. The general form of the pattern results in an algorithm for formation of the linear system. The resulting linear system relates the effect of maneuver components and initial conditions on relative constraints specified by the rendezvous designer. Solution of the linear system includes the straight-forward inverse of a square matrix. Inversion of the square matrix is assured if the designer poses a controllable scenario - a scenario where the the

  19. 50 CFR 640.23 - Bag/possession limits.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... Florida and off the Gulf states, other than Florida—(1) Commercial and recreational fishing season. Except... the EEZ off Florida and off the Gulf states, other than Florida, is six per person. (2) Special... daily bag or possession limit of spiny lobster— (i) In or from the EEZ off the Gulf states, other than...

  20. Global Comparison of Warring Groups in 2002–2007: Fatalities from Targeting Civilians vs. Fighting Battles

    PubMed Central

    Hicks, Madelyn Hsiao-Rei; Lee, Uih Ran; Sundberg, Ralph; Spagat, Michael

    2011-01-01

    Background Warring groups that compete to dominate a civilian population confront contending behavioral options: target civilians or battle the enemy. We aimed to describe degrees to which combatant groups concentrated lethal behavior into intentionally targeting civilians as opposed to engaging in battle with opponents in contemporary armed conflict. Methodology/Principal Findings We identified all 226 formally organized state and non-state groups (i.e. actors) that engaged in lethal armed conflict during 2002–2007: 43 state and 183 non-state. We summed civilians killed by an actor's intentional targeting with civilians and combatants killed in battles in which the actor was involved for total fatalities associated with each actor, indicating overall scale of armed conflict. We used a Civilian Targeting Index (CTI), defined as the proportion of total fatalities caused by intentional targeting of civilians, to measure the concentration of lethal behavior into civilian targeting. We report actor-specific findings and four significant trends: 1.) 61% of all 226 actors (95% CI 55% to 67%) refrained from targeting civilians. 2.) Logistic regression showed actors were more likely to have targeted civilians if conflict duration was three or more years rather than one year. 3.) In the 88 actors that targeted civilians, multiple regressions showed an inverse correlation between CTI values and the total number of fatalities. Conflict duration of three or more years was associated with lower CTI values than conflict duration of one year. 4.) When conflict scale and duration were accounted for, state and non-state actors did not differ. We describe civilian targeting by actors in prolonged conflict. We discuss comparable patterns found in nature and interdisciplinary research. Conclusions/Significance Most warring groups in 2002–2007 did not target civilians. Warring groups that targeted civilians in small-scale, brief conflict concentrated more lethal behavior into