A Single Unexpected Change in Target- but Not Distractor Motion Impairs Multiple Object Tracking

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Hauke S. Meyerhoff

2013-02-01

Full Text Available Recent research addresses the question whether motion information of multiple objects contributes to maintaining a selection of objects across a period of motion. Here, we investigate whether target and/or distractor motion information is used during attentive tracking. We asked participants to track four objects and changed either the motion direction of targets, the motion direction of distractors, neither, or both during a brief flash in the middle of a tracking interval. We observed that a single direction change of targets is sufficient to impair tracking performance. In contrast, changing the motion direction of distractors had no effect on performance. This indicates that target- but not distractor motion information is evaluated during tracking.

ProSelection: A Novel Algorithm to Select Proper Protein Structure Subsets for in Silico Target Identification and Drug Discovery Research.

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Wang, Nanyi; Wang, Lirong; Xie, Xiang-Qun

2017-11-27

Molecular docking is widely applied to computer-aided drug design and has become relatively mature in the recent decades. Application of docking in modeling varies from single lead compound optimization to large-scale virtual screening. The performance of molecular docking is highly dependent on the protein structures selected. It is especially challenging for large-scale target prediction research when multiple structures are available for a single target. Therefore, we have established ProSelection, a docking preferred-protein selection algorithm, in order to generate the proper structure subset(s). By the ProSelection algorithm, protein structures of "weak selectors" are filtered out whereas structures of "strong selectors" are kept. Specifically, the structure which has a good statistical performance of distinguishing active ligands from inactive ligands is defined as a strong selector. In this study, 249 protein structures of 14 autophagy-related targets are investigated. Surflex-dock was used as the docking engine to distinguish active and inactive compounds against these protein structures. Both t test and Mann-Whitney U test were used to distinguish the strong from the weak selectors based on the normality of the docking score distribution. The suggested docking score threshold for active ligands (SDA) was generated for each strong selector structure according to the receiver operating characteristic (ROC) curve. The performance of ProSelection was further validated by predicting the potential off-targets of 43 U.S. Federal Drug Administration approved small molecule antineoplastic drugs. Overall, ProSelection will accelerate the computational work in protein structure selection and could be a useful tool for molecular docking, target prediction, and protein-chemical database establishment research.

Selectivity in multiple quantum nuclear magnetic resonance

International Nuclear Information System (INIS)

Warren, W.S.

1980-11-01

The observation of multiple-quantum nuclear magnetic resonance transitions in isotropic or anisotropic liquids is shown to give readily interpretable information on molecular configurations, rates of motional processes, and intramolecular interactions. However, the observed intensity of high multiple-quantum transitions falls off dramatically as the number of coupled spins increases. The theory of multiple-quantum NMR is developed through the density matrix formalism, and exact intensities are derived for several cases (isotropic first-order systems and anisotropic systems with high symmetry) to shown that this intensity decrease is expected if standard multiple-quantum pulse sequences are used. New pulse sequences are developed which excite coherences and produce population inversions only between selected states, even though other transitions are simultaneously resonant. One type of selective excitation presented only allows molecules to absorb and emit photons in groups of n. Coherent averaging theory is extended to describe these selective sequences, and to design sequences which are selective to arbitrarily high order in the Magnus expansion. This theory and computer calculations both show that extremely good selectivity and large signal enhancements are possible

Selectivity in multiple quantum nuclear magnetic resonance

Energy Technology Data Exchange (ETDEWEB)

Warren, Warren Sloan [Univ. of California, Berkeley, CA (United States). Dept. of Chemistry; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Materials Sciences Division

1980-11-01

The observation of multiple-quantum nuclear magnetic resonance transitions in isotropic or anisotropic liquids is shown to give readily interpretable information on molecular configurations, rates of motional processes, and intramolecular interactions. However, the observed intensity of high multiple-quantum transitions falls off dramatically as the number of coupled spins increases. The theory of multiple-quantum NMR is developed through the density matrix formalism, and exact intensities are derived for several cases (isotropic first-order systems and anisotropic systems with high symmetry) to shown that this intensity decrease is expected if standard multiple-quantum pulse sequences are used. New pulse sequences are developed which excite coherences and produce population inversions only between selected states, even though other transitions are simultaneously resonant. One type of selective excitation presented only allows molecules to absorb and emit photons in groups of n. Coherent averaging theory is extended to describe these selective sequences, and to design sequences which are selective to arbitrarily high order in the Magnus expansion. This theory and computer calculations both show that extremely good selectivity and large signal enhancements are possible.

Simple and Efficient Targeting of Multiple Genes Through CRISPR-Cas9 in Physcomitrella patens

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Mauricio Lopez-Obando

2016-11-01

Full Text Available Powerful genome editing technologies are needed for efficient gene function analysis. The CRISPR-Cas9 system has been adapted as an efficient gene-knock-out technology in a variety of species. However, in a number of situations, knocking out or modifying a single gene is not sufficient; this is particularly true for genes belonging to a common family, or for genes showing redundant functions. Like many plants, the model organism Physcomitrella patens has experienced multiple events of polyploidization during evolution that has resulted in a number of families of duplicated genes. Here, we report a robust CRISPR-Cas9 system, based on the codelivery of a CAS9 expressing cassette, multiple sgRNA vectors, and a cassette for transient transformation selection, for gene knock-out in multiple gene families. We demonstrate that CRISPR-Cas9-mediated targeting of five different genes allows the selection of a quintuple mutant, and all possible subcombinations of mutants, in one experiment, with no mutations detected in potential off-target sequences. Furthermore, we confirmed the observation that the presence of repeats in the vicinity of the cutting region favors deletion due to the alternative end joining pathway, for which induced frameshift mutations can be potentially predicted. Because the number of multiple gene families in Physcomitrella is substantial, this tool opens new perspectives to study the role of expanded gene families in the colonization of land by plants.

Multiple relay selection for delay-limited applications

KAUST Repository

Alsharoa, Ahmad M.; Abediseid, Walid; Alouini, Mohamed-Slim

2013-01-01

A multiple relay selection system model that implements the decode-and-forward mode is investigated. All communication nodes are assumed to be equipped by multiple antennas. Furthermore, lattices space-time coded multiple-input multiple-output half

Nuclease Target Site Selection for Maximizing On-target Activity and Minimizing Off-target Effects in Genome Editing

Science.gov (United States)

Lee, Ciaran M; Cradick, Thomas J; Fine, Eli J; Bao, Gang

2016-01-01

The rapid advancement in targeted genome editing using engineered nucleases such as ZFNs, TALENs, and CRISPR/Cas9 systems has resulted in a suite of powerful methods that allows researchers to target any genomic locus of interest. A complementary set of design tools has been developed to aid researchers with nuclease design, target site selection, and experimental validation. Here, we review the various tools available for target selection in designing engineered nucleases, and for quantifying nuclease activity and specificity, including web-based search tools and experimental methods. We also elucidate challenges in target selection, especially in predicting off-target effects, and discuss future directions in precision genome editing and its applications. PMID:26750397

Advancing the sensitivity of selected reaction monitoring-based targeted quantitative proteomics

Energy Technology Data Exchange (ETDEWEB)

Shi, Tujin; Su, Dian; Liu, Tao; Tang, Keqi; Camp, David G.; Qian, Weijun; Smith, Richard D.

2012-04-01

Selected reaction monitoring (SRM)—also known as multiple reaction monitoring (MRM)—has emerged as a promising high-throughput targeted protein quantification technology for candidate biomarker verification and systems biology applications. A major bottleneck for current SRM technology, however, is insufficient sensitivity for e.g., detecting low-abundance biomarkers likely present at the pg/mL to low ng/mL range in human blood plasma or serum, or extremely low-abundance signaling proteins in the cells or tissues. Herein we review recent advances in methods and technologies, including front-end immunoaffinity depletion, fractionation, selective enrichment of target proteins/peptides or their posttranslational modifications (PTMs), as well as advances in MS instrumentation, which have significantly enhanced the overall sensitivity of SRM assays and enabled the detection of low-abundance proteins at low to sub- ng/mL level in human blood plasma or serum. General perspectives on the potential of achieving sufficient sensitivity for detection of pg/mL level proteins in plasma are also discussed.

Adaptive Waveform Design for Cognitive Radar in Multiple Targets Situations

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Xiaowen Zhang

2018-02-01

Full Text Available In this paper, the problem of cognitive radar (CR waveform optimization design for target detection and estimation in multiple extended targets situations is investigated. This problem is analyzed in signal-dependent interference, as well as additive channel noise for extended targets with unknown target impulse response (TIR. To address this problem, an improved algorithm is employed for target detection by maximizing the detection probability of the received echo on the promise of ensuring the TIR estimation precision. In this algorithm, an additional weight vector is introduced to achieve a trade-off among different targets. Both the estimate of TIR and transmit waveform can be updated at each step based on the previous step. Under the same constraint on waveform energy and bandwidth, the information theoretical approach is also considered. In addition, the relationship between the waveforms that are designed based on the two criteria is discussed. Unlike most existing works that only consider single target with temporally correlated characteristics, waveform design for multiple extended targets is considered in this method. Simulation results demonstrate that compared with linear frequency modulated (LFM signal, waveforms designed based on maximum detection probability and maximum mutual information (MI criteria can make radar echoes contain more multiple-target information and improve radar performance as a result.

Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE)

DEFF Research Database (Denmark)

Peyrin-Biroulet, L; Sandborn, W; Sands, B E

2015-01-01

OBJECTIVES: The Selecting Therapeutic Targets in Inflammatory Bowel Disease (STRIDE) program was initiated by the International Organization for the Study of Inflammatory Bowel Diseases (IOIBD). It examined potential treatment targets for inflammatory bowel disease (IBD) to be used for a "treat-t...... target. CONCLUSIONS: Evidence- and consensus-based recommendations for selecting the goals for treat-to-target strategies in patients with IBD are made available. Prospective studies are needed to determine how these targets will change disease course and patients' quality of life....

Tracking and Recognition of Multiple Human Targets Moving in a Wireless Pyroelectric Infrared Sensor Network

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Ji Xiong

2014-04-01

Full Text Available With characteristics of low-cost and easy deployment, the distributed wireless pyroelectric infrared sensor network has attracted extensive interest, which aims to make it an alternate infrared video sensor in thermal biometric applications for tracking and identifying human targets. In these applications, effectively processing signals collected from sensors and extracting the features of different human targets has become crucial. This paper proposes the application of empirical mode decomposition and the Hilbert-Huang transform to extract features of moving human targets both in the time domain and the frequency domain. Moreover, the support vector machine is selected as the classifier. The experimental results demonstrate that by using this method the identification rates of multiple moving human targets are around 90%.

Deep convolutional neural network based antenna selection in multiple-input multiple-output system

Science.gov (United States)

Cai, Jiaxin; Li, Yan; Hu, Ying

2018-03-01

Antenna selection of wireless communication system has attracted increasing attention due to the challenge of keeping a balance between communication performance and computational complexity in large-scale Multiple-Input MultipleOutput antenna systems. Recently, deep learning based methods have achieved promising performance for large-scale data processing and analysis in many application fields. This paper is the first attempt to introduce the deep learning technique into the field of Multiple-Input Multiple-Output antenna selection in wireless communications. First, the label of attenuation coefficients channel matrix is generated by minimizing the key performance indicator of training antenna systems. Then, a deep convolutional neural network that explicitly exploits the massive latent cues of attenuation coefficients is learned on the training antenna systems. Finally, we use the adopted deep convolutional neural network to classify the channel matrix labels of test antennas and select the optimal antenna subset. Simulation experimental results demonstrate that our method can achieve better performance than the state-of-the-art baselines for data-driven based wireless antenna selection.

Target and Tissue Selectivity Prediction by Integrated Mechanistic Pharmacokinetic-Target Binding and Quantitative Structure Activity Modeling.

Science.gov (United States)

Vlot, Anna H C; de Witte, Wilhelmus E A; Danhof, Meindert; van der Graaf, Piet H; van Westen, Gerard J P; de Lange, Elizabeth C M

2017-12-04

Selectivity is an important attribute of effective and safe drugs, and prediction of in vivo target and tissue selectivity would likely improve drug development success rates. However, a lack of understanding of the underlying (pharmacological) mechanisms and availability of directly applicable predictive methods complicates the prediction of selectivity. We explore the value of combining physiologically based pharmacokinetic (PBPK) modeling with quantitative structure-activity relationship (QSAR) modeling to predict the influence of the target dissociation constant (K D ) and the target dissociation rate constant on target and tissue selectivity. The K D values of CB1 ligands in the ChEMBL database are predicted by QSAR random forest (RF) modeling for the CB1 receptor and known off-targets (TRPV1, mGlu5, 5-HT1a). Of these CB1 ligands, rimonabant, CP-55940, and Δ 8 -tetrahydrocanabinol, one of the active ingredients of cannabis, were selected for simulations of target occupancy for CB1, TRPV1, mGlu5, and 5-HT1a in three brain regions, to illustrate the principles of the combined PBPK-QSAR modeling. Our combined PBPK and target binding modeling demonstrated that the optimal values of the K D and k off for target and tissue selectivity were dependent on target concentration and tissue distribution kinetics. Interestingly, if the target concentration is high and the perfusion of the target site is low, the optimal K D value is often not the lowest K D value, suggesting that optimization towards high drug-target affinity can decrease the benefit-risk ratio. The presented integrative structure-pharmacokinetic-pharmacodynamic modeling provides an improved understanding of tissue and target selectivity.

Category-based attentional guidance can operate in parallel for multiple target objects.

Science.gov (United States)

Jenkins, Michael; Grubert, Anna; Eimer, Martin

2018-04-30

The question whether the control of attention during visual search is always feature-based or can also be based on the category of objects remains unresolved. Here, we employed the N2pc component as an on-line marker for target selection processes to compare the efficiency of feature-based and category-based attentional guidance. Two successive displays containing pairs of real-world objects (line drawings of kitchen or clothing items) were separated by a 10 ms SOA. In Experiment 1, target objects were defined by their category. In Experiment 2, one specific visual object served as target (exemplar-based search). On different trials, targets appeared either in one or in both displays, and participants had to report the number of targets (one or two). Target N2pc components were larger and emerged earlier during exemplar-based search than during category-based search, demonstrating the superior efficiency of feature-based attentional guidance. On trials where target objects appeared in both displays, both targets elicited N2pc components that overlapped in time, suggesting that attention was allocated in parallel to these target objects. Critically, this was the case not only in the exemplar-based task, but also when targets were defined by their category. These results demonstrate that attention can be guided by object categories, and that this type of category-based attentional control can operate concurrently for multiple target objects. Copyright © 2018 Elsevier B.V. All rights reserved.

Through-Wall Multiple Targets Vital Signs Tracking Based on VMD Algorithm

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Jiaming Yan

2016-08-01

Full Text Available Targets located at the same distance are easily neglected in most through-wall multiple targets detecting applications which use the single-input single-output (SISO ultra-wideband (UWB radar system. In this paper, a novel multiple targets vital signs tracking algorithm for through-wall detection using SISO UWB radar has been proposed. Taking advantage of the high-resolution decomposition of the Variational Mode Decomposition (VMD based algorithm, the respiration signals of different targets can be decomposed into different sub-signals, and then, we can track the time-varying respiration signals accurately when human targets located in the same distance. Intensive evaluation has been conducted to show the effectiveness of our scheme with a 0.15 m thick concrete brick wall. Constant, piecewise-constant and time-varying vital signs could be separated and tracked successfully with the proposed VMD based algorithm for two targets, even up to three targets. For the multiple targets’ vital signs tracking issues like urban search and rescue missions, our algorithm has superior capability in most detection applications.

Multiple-Targeted Graphene-based Nanocarrier for Intracellular Imaging of mRNAs

Energy Technology Data Exchange (ETDEWEB)

Wang, Ying; Li, Zhaohui; Liu, Misha; Hu, Dehong; Lin, Yuehe; Li, Jinghong

2017-08-29

Simultaneous detection and imaging of multiple intracellular messenger RNA (mRNAs) hold great significant for early cancer diagnostics and preventive medicine development. Herein, we propose a multiple-targeted graphene oxide (GO) nanocarrier that can simultaneously detect and image different type mRNAs in living cells. First of all, in vitro detection of multiple targets have been realized successfully based on the multiple-targeted GO nanocarrier with linear relationship ranging from 3 nM to 200 nM, as well as sensitive detection limit of 1.84 nM for manganese superoxide dismutase (Mn-SOD) mRNA and 2.45 nM for β-actin mRNA. Additionally, this nanosensing platform composed of fluorescent labeled single strand DNA probes and GO nanocarrier can identify Mn-SOD mRNA and endogenous mRNA of β-actin in living cancer cells, showing rapid response, high specificity, nuclease stability, and good biocompatibility during the cell imaging. Thirdly, changes of the expression levels of mRNA in living cells before or after the drug treatment can be monitored successfully. By using multiple ssDNA as probes and GO nanocarrier as the cellular delivery cargo, the proposed simultaneous multiple-targeted sensing platform will be of great potential as a powerful tool for intracellular trafficking process from basic research to clinical diagnosis.

Targeted therapy of multiple myeloma.

Science.gov (United States)

Dolloff, Nathan G; Talamo, Giampaolo

2013-01-01

Multiple myeloma (MM) is a plasma cell malignancy and the second most common hematologic cancer. MM is characterized by the accumulation of malignant plasma cells within the bone marrow, and presents clinically with a broad range of symptoms, including hypercalcemia, renal insufficiency, anemia, and lytic bone lesions. MM is a heterogeneous disease associated with genomic instability, where patients may express multiple genetic abnormalities that affect several oncogenic pathways. Commonly detected genetic aberrations are translocations involving immunoglobulin heavy chain (IgH) switch regions (chromosome 14q32) and oncogenes such as c-maf [t(14:16)], cyclin D1 [t(11:14)], and FGFR3/MMSET [t(4:14)]. Advances in the basic understanding of MM and the development of novel agents, such as the immunomodulatory drugs (IMiDs) thalidomide and lenalidomide and the proteasome inhibitor bortezomib, have increased therapeutic response rates and prolonged patient survival. Despite these advances MM remains incurable in the majority of patients, and it is therefore critical to identify additional therapeutic strategies and targets for its treatment. In this chapter, we review the underlying genetic components of MM and discuss the results of recent clinical trials that demonstrate the effectiveness of targeted agents in the management of MM. In addition, we discuss experimental therapies that are currently in clinical development along with their molecular rationale in the treatment of MM.

Molecular Connectivity Predefines Polypharmacology: Aliphatic Rings, Chirality, and sp3 Centers Enhance Target Selectivity

Directory of Open Access Journals (Sweden)

Stefania Monteleone

2017-08-01

Full Text Available Dark chemical matter compounds are small molecules that have been recently identified as highly potent and selective hits. For this reason, they constitute a promising class of possible candidates in the process of drug discovery and raise the interest of the scientific community. To this purpose, Wassermann et al. (2015 have described the application of 2D descriptors to characterize dark chemical matter. However, their definition was based on the number of reported positive assays rather than the number of known targets. As there might be multiple assays for one single target, the number of assays does not fully describe target selectivity. Here, we propose an alternative classification of active molecules that is based on the number of known targets. We cluster molecules in four classes: black, gray, and white compounds are active on one, two to four, and more than four targets respectively, whilst inactive compounds are found to be inactive in the considered assays. In this study, black and inactive compounds are found to have not only higher solubility, but also a higher number of chiral centers, sp3 carbon atoms and aliphatic rings. On the contrary, white compounds contain a higher number of double bonds and fused aromatic rings. Therefore, the design of a screening compound library should consider these molecular properties in order to achieve target selectivity or polypharmacology. Furthermore, analysis of four main target classes (GPCRs, kinases, proteases, and ion channels shows that GPCR ligands are more selective than the other classes, as the number of black compounds is higher in this target superfamily. On the other side, ligands that hit kinases, proteases, and ion channels bind to GPCRs more likely than to other target classes. Consequently, depending on the target protein family, appropriate screening libraries can be designed in order to minimize the likelihood of unwanted side effects early in the drug discovery process

A Targeted "Capture" and "Removal" Scavenger toward Multiple Pollutants for Water Remediation based on Molecular Recognition.

Science.gov (United States)

Wang, Jie; Shen, Haijing; Hu, Xiaoxia; Li, Yan; Li, Zhihao; Xu, Jinfan; Song, Xiufeng; Zeng, Haibo; Yuan, Quan

2016-03-01

For the water remediation techniques based on adsorption, the long-standing contradictories between selectivity and multiple adsorbability, as well as between affinity and recyclability, have put it on weak defense amid more and more severe environment crisis. Here, a pollutant-targeting hydrogel scavenger is reported for water remediation with both high selectivity and multiple adsorbability for several pollutants, and with strong affinity and good recyclability through rationally integrating the advantages of multiple functional materials. In the scavenger, aptamers fold into binding pockets to accommodate the molecular structure of pollutants to afford perfect selectivity, and Janus nanoparticles with antibacterial function as well as anisotropic surfaces to immobilize multiple aptamers allow for simultaneously handling different kinds of pollutants. The scavenger exhibits high efficiencies in removing pollutants from water and it can be easily recycled for many times without significant loss of loading capacities. Moreover, the residual concentrations of each contaminant are well below the drinking water standards. Thermodynamic behavior of the adsorption process is investigated and the rate-controlling process is determined. Furthermore, a point of use device is constructed and it displays high efficiency in removing pollutants from environmental water. The scavenger exhibits great promise to be applied in the next generation of water purification systems.

In-silico Leishmania Target Selectivity of Antiparasitic Terpenoids

Directory of Open Access Journals (Sweden)

Ifedayo Victor Ogungbe

2013-07-01

Full Text Available Neglected Tropical Diseases (NTDs, like leishmaniasis, are major causes of mortality in resource-limited countries. The mortality associated with these diseases is largely due to fragile healthcare systems, lack of access to medicines, and resistance by the parasites to the few available drugs. Many antiparasitic plant-derived isoprenoids have been reported, and many of them have good in vitro activity against various forms of Leishmania spp. In this work, potential Leishmania biochemical targets of antiparasitic isoprenoids were studied in silico. Antiparasitic monoterpenoids selectively docked to L. infantum nicotinamidase, L. major uridine diphosphate-glucose pyrophosphorylase and methionyl t-RNA synthetase. The two protein targets selectively targeted by germacranolide sesquiterpenoids were L. major methionyl t-RNA synthetase and dihydroorotate dehydrogenase. Diterpenoids generally favored docking to L. mexicana glycerol-3-phosphate dehydrogenase. Limonoids also showed some selectivity for L. mexicana glycerol-3-phosphate dehydrogenase and L. major dihydroorotate dehydrogenase while withanolides docked more selectively with L. major uridine diphosphate-glucose pyrophosphorylase. The selectivity of the different classes of antiparasitic compounds for the protein targets considered in this work can be explored in fragment- and/or structure-based drug design towards the development of leads for new antileishmanial drugs.

Combinatorial support vector machines approach for virtual screening of selective multi-target serotonin reuptake inhibitors from large compound libraries.

Science.gov (United States)

Shi, Z; Ma, X H; Qin, C; Jia, J; Jiang, Y Y; Tan, C Y; Chen, Y Z

2012-02-01

Selective multi-target serotonin reuptake inhibitors enhance antidepressant efficacy. Their discovery can be facilitated by multiple methods, including in silico ones. In this study, we developed and tested an in silico method, combinatorial support vector machines (COMBI-SVMs), for virtual screening (VS) multi-target serotonin reuptake inhibitors of seven target pairs (serotonin transporter paired with noradrenaline transporter, H(3) receptor, 5-HT(1A) receptor, 5-HT(1B) receptor, 5-HT(2C) receptor, melanocortin 4 receptor and neurokinin 1 receptor respectively) from large compound libraries. COMBI-SVMs trained with 917-1951 individual target inhibitors correctly identified 22-83.3% (majority >31.1%) of the 6-216 dual inhibitors collected from literature as independent testing sets. COMBI-SVMs showed moderate to good target selectivity in misclassifying as dual inhibitors 2.2-29.8% (majority virtual hits correlate with the reported effects of their predicted targets. COMBI-SVM is potentially useful for searching selective multi-target agents without explicit knowledge of these agents. Copyright © 2011 Elsevier Inc. All rights reserved.

Effects of multiple scattering and target structure on photon emission

International Nuclear Information System (INIS)

Blankenbecler, R.

1996-05-01

The Landau-Pomeranchuk-Migdal effect is the suppression of Bethe-Heitler radiation caused by multiple scattering in the target medium. The quantum treatment given by S.D. Drell and the author for homogeneous targets of finite thickness will be reviewed. It will then be extended to structured targets. In brief, it is shown that radiators composed of separated plates or of a medium with a spatially varying radiation length can exhibit unexpected structure, even coherence maxima and minima, in their photon spectra. Finally, a functional integral method for performing the averaging implicit in multiple scattering will be briefly discussed and the leading corrections to previous results evaluated

Multiple-targeted graphene-based nanocarrier for intracellular imaging of mRNAs

International Nuclear Information System (INIS)

Wang, Ying; Li, Zhaohui; Liu, Misha; Xu, Jinjin; Hu, Dehong; Lin, Yuehe; Li, Jinghong

2017-01-01

Simultaneous detection and imaging of multiple intracellular messenger RNA (mRNAs) hold great significant for early cancer diagnostics and preventive medicine development. Herein, we propose a multiple-targeted graphene oxide (GO) nanocarrier that can simultaneously detect and image different type mRNAs in living cells. First of all, in vitro detection of multiple targets have been realized successfully based on the multiple-targeted GO nanocarrier with linear relationship ranging from 3 nM to 200 nM, as well as sensitive detection limit of 1.84 nM for manganese superoxide dismutase (Mn-SOD) mRNA and 2.45 nM for β-actin mRNA. Additionally, this nanosensing platform composed of fluorescent labelled single strand DNA probes and GO nanocarrier can identify Mn-SOD mRNA and endogenous mRNA of β-actin in living cancer cells, showing rapid response, high specificity, nuclease stability, and good biocompatibility during the cell imaging. Thirdly, changes of the expression levels of mRNA in living cells before or after the drug treatment can be monitored successfully. By using multiple ssDNA as probes and GO nanocarrier as the cellular delivery cargo, the proposed simultaneous multiple-targeted sensing platform will be of great potential as a powerful tool for intracellular trafficking process from basic research to clinical diagnosis. - Graphical abstract: Schematic illustration of simultaneously multiple mRNAs monitoring inside single living breast cancer cell based on GO nanocarrier. In particular, the fluorescent signals could be monitored when Mn-SOD probe (red) and β-actin probe (green) hybridizes with their mRNA targets inside the living cells. Random probe (orange) was regarded as control probe for the sensing strategy. - Highlights: • A multiple-targeted GO nanocarrier was used for mRNAs imaging and expression changes after drug treatment can be monitored successfully. • Sensitive detection limit of 1.84 nM for manganese superoxide dismutase (Mn-SOD) m

Target selection for the HRIBF Project

International Nuclear Information System (INIS)

Dellwo, J.; Alton, G.D.; Batchelder, J.C.

1994-01-01

Experiments are in progress at the Oak Ridge National Laboratory (ORNL) which are designed to select the most appropriate target materials for generating particular radioactive ion beams for the Holifield Radioactive Ion Beam Facility (HRIBF). The 25-MV tandem accelerator is used to implant stable complements of interesting radioactive elements into refractory targets mounted in a high-temperature FEBIAD ion source which is on-line at the UNISOR facility. These experiments permit selection of the target material most appropriate for the rapid release of the element of interest, as well as realistic estimates of the efficiency of the FEBIAD source. From diffusion release data information on the release times and diffusion coefficients can be derived. Diffusion coefficients for CI implanted into and diffused from CeS and Zr 5 Si 3 and As, Br, and Se implanted into and diffused from Zr 5 Ge 3 have been derived from the resulting intensity versus time profiles

Target selection biases from recent experience transfer across effectors.

Science.gov (United States)

Moher, Jeff; Song, Joo-Hyun

2016-02-01

Target selection is often biased by an observer's recent experiences. However, not much is known about whether these selection biases influence behavior across different effectors. For example, does looking at a red object make it easier to subsequently reach towards another red object? In the current study, we asked observers to find the uniquely colored target object on each trial. Randomly intermixed pre-trial cues indicated the mode of action: either an eye movement or a visually guided reach movement to the target. In Experiment 1, we found that priming of popout, reflected in faster responses following repetition of the target color on consecutive trials, occurred regardless of whether the effector was repeated from the previous trial or not. In Experiment 2, we examined whether an inhibitory selection bias away from a feature could transfer across effectors. While priming of popout reflects both enhancement of the repeated target features and suppression of the repeated distractor features, the distractor previewing effect isolates a purely inhibitory component of target selection in which a previewed color is presented in a homogenous display and subsequently inhibited. Much like priming of popout, intertrial suppression biases in the distractor previewing effect transferred across effectors. Together, these results suggest that biases for target selection driven by recent trial history transfer across effectors. This indicates that representations in memory that bias attention towards or away from specific features are largely independent from their associated actions.

Cooperative target convergence using multiple agents

International Nuclear Information System (INIS)

Kwok, K.S.; Driessen, B.J.

1997-01-01

This work considers the problem of causing multiple (100''s) autonomous mobile robots to converge to a target and provides a follow-the-leader approach to the problem. Each robot has only a limited-range sensor for sending the target and also larger but also limited-range robot-to-robot communication capability. Because of the small amount of information available to the robots, a practical approach to improve convergence to the target is to have a robot follow the robot with the best quality of information. Specifically, each robot emits a signal that informs in-range robots what its status is. A robot has a status value of 0 if it is itself in range of the target. A robot has a status of 1 if it is not in range of the target but is in communication range of a robot that is in range of the target. A robot has a status of 2 if it is not in range of the target but is within range of another robot that has status 1, and so on. Of all the mobile robots that any given robot is in range of, it follows the one with the best status. The emergent behavior is the ant-like trails of robots following each other toward the target. If the robot is not in range of another robot that is either in range of the target or following another robot, the robot will assign-1 to its quality-of-information, and will execute an exhaustive search. The exhaustive search will continue until it encounters either the target or another robot with a nonnegative quality-of-information. The quality of information approach was extended to the case where each robot only has two-bit signals informing it of distance to in-range robots

Cooperative target convergence using multiple agents

Energy Technology Data Exchange (ETDEWEB)

Kwok, K.S.; Driessen, B.J.

1997-10-01

This work considers the problem of causing multiple (100`s) autonomous mobile robots to converge to a target and provides a follow-the-leader approach to the problem. Each robot has only a limited-range sensor for sending the target and also larger but also limited-range robot-to-robot communication capability. Because of the small amount of information available to the robots, a practical approach to improve convergence to the target is to have a robot follow the robot with the best quality of information. Specifically, each robot emits a signal that informs in-range robots what its status is. A robot has a status value of 0 if it is itself in range of the target. A robot has a status of 1 if it is not in range of the target but is in communication range of a robot that is in range of the target. A robot has a status of 2 if it is not in range of the target but is within range of another robot that has status 1, and so on. Of all the mobile robots that any given robot is in range of, it follows the one with the best status. The emergent behavior is the ant-like trails of robots following each other toward the target. If the robot is not in range of another robot that is either in range of the target or following another robot, the robot will assign-1 to its quality-of-information, and will execute an exhaustive search. The exhaustive search will continue until it encounters either the target or another robot with a nonnegative quality-of-information. The quality of information approach was extended to the case where each robot only has two-bit signals informing it of distance to in-range robots.

A compound chimeric antigen receptor strategy for targeting multiple myeloma.

Science.gov (United States)

Chen, K H; Wada, M; Pinz, K G; Liu, H; Shuai, X; Chen, X; Yan, L E; Petrov, J C; Salman, H; Senzel, L; Leung, E L H; Jiang, X; Ma, Y

2018-02-01

Current clinical outcomes using chimeric-antigen receptors (CARs) against multiple myeloma show promise in the eradication of bulk disease. However, these anti-BCMA (CD269) CARs observe relapse as a common phenomenon after treatment due to the reemergence of either antigen-positive or -negative cells. Hence, the development of improvements in CAR design to target antigen loss and increase effector cell persistency represents a critical need. Here, we report on the anti-tumor activity of a CAR T-cell possessing two complete and independent CAR receptors against the multiple myeloma antigens BCMA and CS1. We determined that the resulting compound CAR (cCAR) T-cell possesses consistent, potent and directed cytotoxicity against each target antigen population. Using multiple mouse models of myeloma and mixed cell populations, we are further able to show superior in vivo survival by directed cytotoxicity against multiple populations compared to a single-expressing CAR T-cell. These findings indicate that compound targeting of BCMA and CS1 on myeloma cells can potentially be an effective strategy for augmenting the response against myeloma bulk disease and for initiation of broader coverage CAR therapy.

Exploring the potential of a structural alphabet-based tool for mining multiple target conformations and target flexibility insight.

Science.gov (United States)

Regad, Leslie; Chéron, Jean-Baptiste; Triki, Dhoha; Senac, Caroline; Flatters, Delphine; Camproux, Anne-Claude

2017-01-01

Protein flexibility is often implied in binding with different partners and is essential for protein function. The growing number of macromolecular structures in the Protein Data Bank entries and their redundancy has become a major source of structural knowledge of the protein universe. The analysis of structural variability through available redundant structures of a target, called multiple target conformations (MTC), obtained using experimental or modeling methods and under different biological conditions or different sources is one way to explore protein flexibility. This analysis is essential to improve the understanding of various mechanisms associated with protein target function and flexibility. In this study, we explored structural variability of three biological targets by analyzing different MTC sets associated with these targets. To facilitate the study of these MTC sets, we have developed an efficient tool, SA-conf, dedicated to capturing and linking the amino acid and local structure variability and analyzing the target structural variability space. The advantage of SA-conf is that it could be applied to divers sets composed of MTCs available in the PDB obtained using NMR and crystallography or homology models. This tool could also be applied to analyze MTC sets obtained by dynamics approaches. Our results showed that SA-conf tool is effective to quantify the structural variability of a MTC set and to localize the structural variable positions and regions of the target. By selecting adapted MTC subsets and comparing their variability detected by SA-conf, we highlighted different sources of target flexibility such as induced by binding partner, by mutation and intrinsic flexibility. Our results support the interest to mine available structures associated with a target using to offer valuable insight into target flexibility and interaction mechanisms. The SA-conf executable script, with a set of pre-compiled binaries are available at http://www.mti.univ-paris-diderot.fr/recherche/plateformes/logiciels.

Exploring the potential of a structural alphabet-based tool for mining multiple target conformations and target flexibility insight.

Directory of Open Access Journals (Sweden)

Leslie Regad

Full Text Available Protein flexibility is often implied in binding with different partners and is essential for protein function. The growing number of macromolecular structures in the Protein Data Bank entries and their redundancy has become a major source of structural knowledge of the protein universe. The analysis of structural variability through available redundant structures of a target, called multiple target conformations (MTC, obtained using experimental or modeling methods and under different biological conditions or different sources is one way to explore protein flexibility. This analysis is essential to improve the understanding of various mechanisms associated with protein target function and flexibility. In this study, we explored structural variability of three biological targets by analyzing different MTC sets associated with these targets. To facilitate the study of these MTC sets, we have developed an efficient tool, SA-conf, dedicated to capturing and linking the amino acid and local structure variability and analyzing the target structural variability space. The advantage of SA-conf is that it could be applied to divers sets composed of MTCs available in the PDB obtained using NMR and crystallography or homology models. This tool could also be applied to analyze MTC sets obtained by dynamics approaches. Our results showed that SA-conf tool is effective to quantify the structural variability of a MTC set and to localize the structural variable positions and regions of the target. By selecting adapted MTC subsets and comparing their variability detected by SA-conf, we highlighted different sources of target flexibility such as induced by binding partner, by mutation and intrinsic flexibility. Our results support the interest to mine available structures associated with a target using to offer valuable insight into target flexibility and interaction mechanisms. The SA-conf executable script, with a set of pre-compiled binaries are available at

Immunogenic Targets for Specific Immunotherapy in Multiple Myeloma

Directory of Open Access Journals (Sweden)

Lu Zhang

2012-01-01

Full Text Available Multiple myeloma remains an incurable disease although the prognosis has been improved by novel therapeutics and agents recently. Relapse occurs in the majority of patients and becomes fatal finally. Immunotherapy might be a powerful intervention to maintain a long-lasting control of minimal residual disease or to even eradicate disseminated tumor cells. Several tumor-associated antigens have been identified in patients with multiple myeloma. These antigens are expressed in a tumor-specific or tumor-restricted pattern, are able to elicit immune response, and thus could serve as targets for immunotherapy. This review discusses immunogenic antigens with therapeutic potential for multiple myeloma.

TargetCompare: A web interface to compare simultaneous miRNAs targets.

Science.gov (United States)

Moreira, Fabiano Cordeiro; Dustan, Bruno; Hamoy, Igor G; Ribeiro-Dos-Santos, André M; Dos Santos, Andrea Ribeiro

2014-01-01

MicroRNAs (miRNAs) are small non-coding nucleotide sequences between 17 and 25 nucleotides in length that primarily function in the regulation of gene expression. A since miRNA has thousand of predict targets in a complex, regulatory cell signaling network. Therefore, it is of interest to study multiple target genes simultaneously. Hence, we describe a web tool (developed using Java programming language and MySQL database server) to analyse multiple targets of pre-selected miRNAs. We cross validated the tool in eight most highly expressed miRNAs in the antrum region of stomach. This helped to identify 43 potential genes that are target of at least six of the referred miRNAs. The developed tool aims to reduce the randomness and increase the chance of selecting strong candidate target genes and miRNAs responsible for playing important roles in the studied tissue. http://lghm.ufpa.br/targetcompare.

THINK OUTSIDE THE COLOR BOX: PROBABILISTIC TARGET SELECTION AND THE SDSS-XDQSO QUASAR TARGETING CATALOG

International Nuclear Information System (INIS)

Bovy, Jo; Hogg, David W.; Weaver, Benjamin A.; Hennawi, Joseph F.; Myers, Adam D.; Kirkpatrick, Jessica A.; Schlegel, David J.; Ross, Nicholas P.; Sheldon, Erin S.; McGreer, Ian D.; Schneider, Donald P.

2011-01-01

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 ∼ 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 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.

Think Outside The Color Box: Probabilistic Target Selection And The SDSS-XDQSO Quasar Targeting Catalog

International Nuclear Information System (INIS)

Bovy, J.; Sheldon, E.; Hennawi, J.F.; Hogg, D.W.; Myers, A.D.

2011-01-01

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 ∼ 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 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.

Quantum partial search for uneven distribution of multiple target items

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Zhang, Kun; Korepin, Vladimir

2018-06-01

Quantum partial search algorithm is an approximate search. It aims to find a target block (which has the target items). It runs a little faster than full Grover search. In this paper, we consider quantum partial search algorithm for multiple target items unevenly distributed in a database (target blocks have different number of target items). The algorithm we describe can locate one of the target blocks. Efficiency of the algorithm is measured by number of queries to the oracle. We optimize the algorithm in order to improve efficiency. By perturbation method, we find that the algorithm runs the fastest when target items are evenly distributed in database.

Irradiation uniformity of spherical targets by multiple uv beams from OMEGA

International Nuclear Information System (INIS)

Beich, W.; Dunn, M.; Hutchison, R.

1984-01-01

Direct-drive laser fusion demands extremely high levels of irradiation uniformity to ensure uniform compression of spherical targets. The assessment of illumination uniformity of targets irradiated by multiple beams from the OMEGA facility is made with the aid of multiple beams spherical superposition codes, which take into account ray tracing and absorption and a detailed knowledge of the intensity distribution of each beam in the target plane. In this report, recent estimates of the irradiation uniformity achieved with 6 and 12 uv beams of OMEGA will be compared with previous measurements in the IR, and predictions will be made for the uv illumination uniformity achievable with 24 beams of OMEGA

Cooperative multi-robot observation of multiple moving targets

International Nuclear Information System (INIS)

Parker, L.E.; Emmons, B.A.

1997-01-01

An important issue that arises in the automation of many security, surveillance, and reconnaissance tasks is that of monitoring, or observing, the movements of targets navigating in a bounded area of interest. A key research issue in these problems is that of sensor placement--determining where sensors should be located to maintain the targets in view. In complex applications of this type, the use of multiple sensors dynamically moving over time is required. In this paper, the authors investigate the sue of a cooperative team of autonomous sensor-based robots for multi-robot observation of multiple moving targets. They focus primarily on developing the distributed control strategies that allow the robot team to attempt to maximize the collective tie during which each object is being observed by at least one robot in the area of interest. The initial efforts in this problem address the aspects of distributed control in homogeneous robot teams with equivalent sensing and movement capabilities working in an uncluttered, bounded area. This paper first formalizes the problem, discusses related work, and then shows that this problem is NP-hard. They then present a distributed approximate approach to solving this problem that combines low-level multi-robot control with higher-level control

Targeting of phage particles towards endothelial cells by antibodies selected through a multi-parameter selection strategy.

Science.gov (United States)

Mandrup, Ole A; Lykkemark, Simon; Kristensen, Peter

2017-02-10

One of the hallmarks of cancer is sustained angiogenesis. Here, normal endothelial cells are activated, and their formation of new blood vessels leads to continued tumour growth. An improved patient condition is often observed when angiogenesis is prevented or normalized through targeting of these genomically stable endothelial cells. However, intracellular targets constitute a challenge in therapy, as the agents modulating these targets have to be delivered and internalized specifically to the endothelial cells. Selection of antibodies binding specifically to certain cell types is well established. It is nonetheless a challenge to ensure that the binding of antibodies to the target cell will mediate internalization. Previously selection of such antibodies has been performed targeting cancer cell lines; most often using either monovalent display or polyvalent display. In this article, we describe selections that isolate internalizing antibodies by sequential combining monovalent and polyvalent display using two types of helper phages, one which increases display valence and one which reduces background. One of the selected antibodies was found to mediate internalization into human endothelial cells, although our results confirms that the single stranded nature of the DNA packaged into phage particles may limit applications aimed at targeting nucleic acids in mammalian cells.

PLS-based and regularization-based methods for the selection of relevant variables in non-targeted metabolomics data

Directory of Open Access Journals (Sweden)

Renata Bujak

2016-07-01

Full Text Available Non-targeted metabolomics constitutes a part of systems biology and aims to determine many metabolites in complex biological samples. Datasets obtained in non-targeted metabolomics studies are multivariate and high-dimensional due to the sensitivity of mass spectrometry-based detection methods as well as complexity of biological matrices. Proper selection of variables which contribute into group classification is a crucial step, especially in metabolomics studies which are focused on searching for disease biomarker candidates. In the present study, three different statistical approaches were tested using two metabolomics datasets (RH and PH study. Orthogonal projections to latent structures-discriminant analysis (OPLS-DA without and with multiple testing correction as well as least absolute shrinkage and selection operator (LASSO were tested and compared. For the RH study, OPLS-DA model built without multiple testing correction, selected 46 and 218 variables based on VIP criteria using Pareto and UV scaling, respectively. In the case of the PH study, 217 and 320 variables were selected based on VIP criteria using Pareto and UV scaling, respectively. In the RH study, OPLS-DA model built with multiple testing correction, selected 4 and 19 variables as statistically significant in terms of Pareto and UV scaling, respectively. For PH study, 14 and 18 variables were selected based on VIP criteria in terms of Pareto and UV scaling, respectively. Additionally, the concept and fundaments of the least absolute shrinkage and selection operator (LASSO with bootstrap procedure evaluating reproducibility of results, was demonstrated. In the RH and PH study, the LASSO selected 14 and 4 variables with reproducibility between 99.3% and 100%. However, apart from the popularity of PLS-DA and OPLS-DA methods in metabolomics, it should be highlighted that they do not control type I or type II error, but only arbitrarily establish a cut-off value for PLS-DA loadings

An algorithm for preferential selection of spectroscopic targets in LEGUE

International Nuclear Information System (INIS)

Carlin, Jeffrey L.; Newberg, Heidi Jo; Lépine, Sébastien; Deng Licai; Chen Yuqin; Fu Xiaoting; Gao Shuang; Li Jing; Liu Chao; Beers, Timothy C.; Christlieb, Norbert; Grillmair, Carl J.; Guhathakurta, Puragra; Han Zhanwen; Hou Jinliang; Lee, Hsu-Tai; Liu Xiaowei; Pan Kaike; Sellwood, J. A.; Wang Hongchi

2012-01-01

We describe a general target selection algorithm that is applicable to any survey in which the number of available candidates is much larger than the number of objects to be observed. This routine aims to achieve a balance between a smoothly-varying, well-understood selection function and the desire to preferentially select certain types of targets. Some target-selection examples are shown that illustrate different possibilities of emphasis functions. Although it is generally applicable, the algorithm was developed specifically for the LAMOST Experiment for Galactic Understanding and Exploration (LEGUE) survey that will be carried out using the Chinese Guo Shou Jing Telescope. In particular, this algorithm was designed for the portion of LEGUE targeting the Galactic halo, in which we attempt to balance a variety of science goals that require stars at fainter magnitudes than can be completely sampled by LAMOST. This algorithm has been implemented for the halo portion of the LAMOST pilot survey, which began in October 2011.

Multiple operating system rotation environment moving target defense

Science.gov (United States)

Evans, Nathaniel; Thompson, Michael

2016-03-22

Systems and methods for providing a multiple operating system rotation environment ("MORE") moving target defense ("MTD") computing system are described. The MORE-MTD system provides enhanced computer system security through a rotation of multiple operating systems. The MORE-MTD system increases attacker uncertainty, increases the cost of attacking the system, reduces the likelihood of an attacker locating a vulnerability, and reduces the exposure time of any located vulnerability. The MORE-MTD environment is effectuated by rotation of the operating systems at a given interval. The rotating operating systems create a consistently changing attack surface for remote attackers.

Target Selection for the SDSS-III MARVELS Survey

Science.gov (United States)

Paegert, Martin; Stassun, Keivan G.; De Lee, Nathan; Pepper, Joshua; Fleming, Scott W.; Sivarani, Thirupathi; Mahadevan, Suvrath; Mack, Claude E., III; Dhital, Saurav; Hebb, Leslie; Ge, Jian

2015-06-01

We present the target selection process for the Multi-object APO Radial Velocity Exoplanets Large-area Survey (MARVELS), which is part of the Sloan Digital Sky Survey (SDSS) III. MARVELS is a medium-resolution (R ∼ 11,000) multi-fiber spectrograph capable of obtaining radial velocities for 60 objects at a time in order to find brown dwarfs and giant planets. The survey was configured to target dwarf stars with effective temperatures approximately between 4500 and 6250 K. For the first 2 years MARVELS relied on low-resolution spectroscopic pre-observations to estimate the effective temperature and log (g) for candidate stars and then selected suitable dwarf stars from this pool. Ultimately, the pre-observation spectra proved ineffective at filtering out giant stars; many giants were incorrectly classified as dwarfs, resulting in a giant contamination rate of ∼30% for the first phase of the MARVELS survey. Thereafter, the survey instead applied a reduced proper motion cut to eliminate giants and used the Infrared Flux Method to estimate effective temperatures, using only extant photmetric and proper-motion catalog information. The target selection method introduced here may be useful for other surveys that need to rely on extant catalog data for selection of specific stellar populations.

Structural Implications for Selective Targeting of PARPs.

Science.gov (United States)

Steffen, Jamin D; Brody, Jonathan R; Armen, Roger S; Pascal, John M

2013-12-20

Poly(ADP-ribose) polymerases (PARPs) are a family of enzymes that use NAD(+) as a substrate to synthesize polymers of ADP-ribose (PAR) as post-translational modifications of proteins. PARPs have important cellular roles that include preserving genomic integrity, telomere maintenance, transcriptional regulation, and cell fate determination. The diverse biological roles of PARPs have made them attractive therapeutic targets, which have fueled the pursuit of small molecule PARP inhibitors. The design of PARP inhibitors has matured over the past several years resulting in several lead candidates in clinical trials. PARP inhibitors are mainly used in clinical trials to treat cancer, particularly as sensitizing agents in combination with traditional chemotherapy to reduce side effects. An exciting aspect of PARP inhibitors is that they are also used to selectivity kill tumors with deficiencies in DNA repair proteins (e.g., BRCA1/2) through an approach termed "synthetic lethality." In the midst of the tremendous efforts that have brought PARP inhibitors to the forefront of modern chemotherapy, most clinically used PARP inhibitors bind to conserved regions that permits cross-selectivity with other PARPs containing homologous catalytic domains. Thus, the differences between therapeutic effects and adverse effects stemming from pan-PARP inhibition compared to selective inhibition are not well understood. In this review, we discuss current literature that has found ways to gain selectivity for one PARP over another. We furthermore provide insights into targeting other domains that make up PARPs, and how new classes of drugs that target these domains could provide a high degree of selectivity by affecting specific cellular functions. A clear understanding of the inhibition profiles of PARP inhibitors will not only enhance our understanding of the biology of individual PARPs, but may provide improved therapeutic options for patients.

An individual differences approach to multiple-target visual search errors: How search errors relate to different characteristics of attention.

Science.gov (United States)

Adamo, Stephen H; Cain, Matthew S; Mitroff, Stephen R

2017-12-01

A persistent problem in visual search is that searchers are more likely to miss a target if they have already found another in the same display. This phenomenon, the Subsequent Search Miss (SSM) effect, has remained despite being a known issue for decades. Increasingly, evidence supports a resource depletion account of SSM errors-a previously detected target consumes attentional resources leaving fewer resources available for the processing of a second target. However, "attention" is broadly defined and is composed of many different characteristics, leaving considerable uncertainty about how attention affects second-target detection. The goal of the current study was to identify which attentional characteristics (i.e., selection, limited capacity, modulation, and vigilance) related to second-target misses. The current study compared second-target misses to an attentional blink task and a vigilance task, which both have established measures that were used to operationally define each of four attentional characteristics. Second-target misses in the multiple-target search were correlated with (1) a measure of the time it took for the second target to recovery from the blink in the attentional blink task (i.e., modulation), and (2) target sensitivity (d') in the vigilance task (i.e., vigilance). Participants with longer recovery and poorer vigilance had more second-target misses in the multiple-target visual search task. The results add further support to a resource depletion account of SSM errors and highlight that worse modulation and poor vigilance reflect a deficit in attentional resources that can account for SSM errors. Copyright © 2016 Elsevier Ltd. All rights reserved.

Multi-target detection and positioning in crowds using multiple camera surveillance

Science.gov (United States)

Huang, Jiahu; Zhu, Qiuyu; Xing, Yufeng

2018-04-01

In this study, we propose a pixel correspondence algorithm for positioning in crowds based on constraints on the distance between lines of sight, grayscale differences, and height in a world coordinates system. First, a Gaussian mixture model is used to obtain the background and foreground from multi-camera videos. Second, the hair and skin regions are extracted as regions of interest. Finally, the correspondences between each pixel in the region of interest are found under multiple constraints and the targets are positioned by pixel clustering. The algorithm can provide appropriate redundancy information for each target, which decreases the risk of losing targets due to a large viewing angle and wide baseline. To address the correspondence problem for multiple pixels, we construct a pixel-based correspondence model based on a similar permutation matrix, which converts the correspondence problem into a linear programming problem where a similar permutation matrix is found by minimizing an objective function. The correct pixel correspondences can be obtained by determining the optimal solution of this linear programming problem and the three-dimensional position of the targets can also be obtained by pixel clustering. Finally, we verified the algorithm with multiple cameras in experiments, which showed that the algorithm has high accuracy and robustness.

The role of natural selection in shaping genetic variation in a promising Chagas disease drug target: Trypanosoma cruzi trans-sialidase.

Science.gov (United States)

Gallant, Joseph P; Lima-Cordón, Raquel Asunción; Justi, Silvia A; Monroy, Maria Carlota; Viola, Toni; Stevens, Lori

2018-04-21

Rational drug design creates innovative therapeutics based on knowledge of the biological target to provide more effective and responsible therapeutics. Chagas disease, endemic throughout Latin America, is caused by Trypanosoma cruzi, a protozoan parasite. Current therapeutics are problematic with widespread calls for new approaches. Researchers are using rational drug design for Chagas disease and one target receiving considerable attention is the T. cruzi trans-sialidase protein (TcTS). In T. cruzi, trans-sialidase catalyzes the transfer of sialic acid from a mammalian host to coat the parasite surface membrane and avoid immuno-detection. However, the role of TcTS in pathology variance among and within genetic variants of the parasite is not well understood despite numerous studies. Previous studies reported the crystalline structure of TcTS and the TS protein structure in other trypanosomes where the enzyme is often inactive. However, no study has examined the role of natural selection in genetic variation in TcTS. To understand the role of natural selection in TcTS DNA sequence and protein variation, we examined a 471 bp portion of the TcTS gene from 48 T. cruzi samples isolated from insect vectors. Because there may be multiple parasite genotypes infecting one insect and there are multiple copies of TcTS per parasite genome, all 48 sequences had multiple polymorphic bases. To resolve these polymorphisms, we examined cloned sequences from two insect vectors. The data are analyzed to understand the role of natural selection in shaping genetic variation in TcTS and interpreted in light of the possible role of TcTS as a drug target. The analysis highlights negative or purifying selection on three amino acids previously shown to be important in TcTS transfer activity. One amino acid in particular, Tyr342, is a strong candidate for a drug target because it is under negative selection and amino acid substitutions inactivate TcTS transfer activity. Chagas disease

Target-selected mutagenesis of the rat

NARCIS (Netherlands)

Smits, B.M.; Mudde, J.B.; Plasterk, R.; Cuppen, E.

2004-01-01

The rat is one of the most extensively studied model organisms, and with its genome being sequenced, tools to manipulate gene function in vivo have become increasingly important. We here report proof of principle for target-selected mutagenesis as a reverse genetic or knockout approach for the rat.

Purification-Free, Target-Selective Immobilization of a Protein from Cell Lysates.

Science.gov (United States)

Cha, Jaehyun; Kwon, Inchan

2018-02-27

Protein immobilization has been widely used for laboratory experiments and industrial processes. Preparation of a recombinant protein for immobilization usually requires laborious and expensive purification steps. Here, a novel purification-free, target-selective immobilization technique of a protein from cell lysates is reported. Purification steps are skipped by immobilizing a target protein containing a clickable non-natural amino acid (p-azidophenylalanine) in cell lysates onto alkyne-functionalized solid supports via bioorthogonal azide-alkyne cycloaddition. In order to achieve a target protein-selective immobilization, p-azidophenylalanine was introduced into an exogenous target protein, but not into endogenous non-target proteins using host cells with amber codon-free genomic DNAs. Immobilization of superfolder fluorescent protein (sfGFP) from cell lysates is as efficient as that of the purified sfGFP. Using two fluorescent proteins (sfGFP and mCherry), the authors also demonstrated that the target proteins are immobilized with a minimal immobilization of non-target proteins (target-selective immobilization). © 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Estimating Accurate Target Coordinates with Magnetic Resonance Images by Using Multiple Phase-Encoding Directions during Acquisition.

Science.gov (United States)

Kim, Minsoo; Jung, Na Young; Park, Chang Kyu; Chang, Won Seok; Jung, Hyun Ho; Chang, Jin Woo

2018-06-01

Stereotactic procedures are image guided, often using magnetic resonance (MR) images limited by image distortion, which may influence targets for stereotactic procedures. The aim of this work was to assess methods of identifying target coordinates for stereotactic procedures with MR in multiple phase-encoding directions. In 30 patients undergoing deep brain stimulation, we acquired 5 image sets: stereotactic brain computed tomography (CT), T2-weighted images (T2WI), and T1WI in both right-to-left (RL) and anterior-to-posterior (AP) phase-encoding directions. Using CT coordinates as a reference, we analyzed anterior commissure and posterior commissure coordinates to identify any distortion relating to phase-encoding direction. Compared with CT coordinates, RL-directed images had more positive x-axis values (0.51 mm in T1WI, 0.58 mm in T2WI). AP-directed images had more negative y-axis values (0.44 mm in T1WI, 0.59 mm in T2WI). We adopted 2 methods to predict CT coordinates with MR image sets: parallel translation and selective choice of axes according to phase-encoding direction. Both were equally effective at predicting CT coordinates using only MR; however, the latter may be easier to use in clinical settings. Acquiring MR in multiple phase-encoding directions and selecting axes according to the phase-encoding direction allows identification of more accurate coordinates for stereotactic procedures. © 2018 S. Karger AG, Basel.

Novel target configurations for selective ionization state studies in molybdenum

International Nuclear Information System (INIS)

Ilcisin, K.J.; Feldman, U.; Schwob, J.L.; Wouters, A.; Suckewer, S.; Princeton Univ., NJ

1990-03-01

Details of experiments aimed at achieving low ionization state selectivity in molybdenum are presented. Targets are excited with a 10 J CO 2 laser and the resultant VUV spectrum (300--700 Angstrom) has been studied. Combinations of focal spot size, target depth, and target geometries are compared. Simple attenuation of energy is shown not to vary ionization stage composition significantly. Experiments conducted with grazing incidence targets result only in a hot plasma. Modular targets with cooling cylinders of various radii demonstrated good selectivity of the ionization states, but with low absolute signals. Finally, results from combinations of focal spot adjustment and radiative cooling illustrate increased control over desired plasma temperature and density for spectroscopic studies of molybdenum. 7 refs., 14 figs

Selection of phage-displayed accessible recombinant targeted antibodies (SPARTA): methodology and applications.

Science.gov (United States)

D'Angelo, Sara; Staquicini, Fernanda I; Ferrara, Fortunato; Staquicini, Daniela I; Sharma, Geetanjali; Tarleton, Christy A; Nguyen, Huynh; Naranjo, Leslie A; Sidman, Richard L; Arap, Wadih; Bradbury, Andrew Rm; Pasqualini, Renata

2018-05-03

We developed a potentially novel and robust antibody discovery methodology, termed selection of phage-displayed accessible recombinant targeted antibodies (SPARTA). This combines an in vitro screening step of a naive human antibody library against known tumor targets, with in vivo selections based on tumor-homing capabilities of a preenriched antibody pool. This unique approach overcomes several rate-limiting challenges to generate human antibodies amenable to rapid translation into medical applications. As a proof of concept, we evaluated SPARTA on 2 well-established tumor cell surface targets, EphA5 and GRP78. We evaluated antibodies that showed tumor-targeting selectivity as a representative panel of antibody-drug conjugates (ADCs) and were highly efficacious. Our results validate a discovery platform to identify and validate monoclonal antibodies with favorable tumor-targeting attributes. This approach may also extend to other diseases with known cell surface targets and affected tissues easily isolated for in vivo selection.

A comparative study of fuzzy target selection methods in direct marketing

NARCIS (Netherlands)

Costa Sousa, da J.M.; Kaymak, U.; Madeira, S.

2002-01-01

Target selection in direct marketing is an important data mining problem for which fuzzy modeling can be used. The paper compares several fuzzy modeling techniques applied to target selection based on recency, frequency and monetary value measures. The comparison uses cross validation applied to

Multiple-Trait Genomic Selection Methods Increase Genetic Value Prediction Accuracy

Science.gov (United States)

Jia, Yi; Jannink, Jean-Luc

2012-01-01

Genetic correlations between quantitative traits measured in many breeding programs are pervasive. These correlations indicate that measurements of one trait carry information on other traits. Current single-trait (univariate) genomic selection does not take advantage of this information. Multivariate genomic selection on multiple traits could accomplish this but has been little explored and tested in practical breeding programs. In this study, three multivariate linear models (i.e., GBLUP, BayesA, and BayesCπ) were presented and compared to univariate models using simulated and real quantitative traits controlled by different genetic architectures. We also extended BayesA with fixed hyperparameters to a full hierarchical model that estimated hyperparameters and BayesCπ to impute missing phenotypes. We found that optimal marker-effect variance priors depended on the genetic architecture of the trait so that estimating them was beneficial. We showed that the prediction accuracy for a low-heritability trait could be significantly increased by multivariate genomic selection when a correlated high-heritability trait was available. Further, multiple-trait genomic selection had higher prediction accuracy than single-trait genomic selection when phenotypes are not available on all individuals and traits. Additional factors affecting the performance of multiple-trait genomic selection were explored. PMID:23086217

Improved targeted immunization strategies based on two rounds of selection

Science.gov (United States)

Xia, Ling-Ling; Song, Yu-Rong; Li, Chan-Chan; Jiang, Guo-Ping

2018-04-01

In the case of high degree targeted immunization where the number of vaccine is limited, when more than one node associated with the same degree meets the requirement of high degree centrality, how can we choose a certain number of nodes from those nodes, so that the number of immunized nodes will not exceed the limit? In this paper, we introduce a new idea derived from the selection process of second-round exam to solve this problem and then propose three improved targeted immunization strategies. In these proposed strategies, the immunized nodes are selected through two rounds of selection, where we increase the quotas of first-round selection according the evaluation criterion of degree centrality and then consider another characteristic parameter of node, such as node's clustering coefficient, betweenness and closeness, to help choose targeted nodes in the second-round selection. To validate the effectiveness of the proposed strategies, we compare them with the degree immunizations including the high degree targeted and the high degree adaptive immunizations using two metrics: the size of the largest connected component of immunized network and the number of infected nodes. Simulation results demonstrate that the proposed strategies based on two rounds of sorting are effective for heterogeneous networks and their immunization effects are better than that of the degree immunizations.

The Calibration Target for the Mars 2020 SHERLOC Instrument: Multiple Science Roles for Future Manned and Unmanned Mars Exploration

Science.gov (United States)

Fries, M.; Bhartia, R.; Beegle, L.; Burton, A.; Ross, A.; Shahar, A.

2014-01-01

The Scanning Habitable Environments with Raman & Luminescence for Organics & Chemicals (SHERLOC) instrument is a deep ultraviolet (UV) Raman/fluorescence instrument selected as part of the Mars 2020 rover instrument suite. SHERLOC will be mounted on the rover arm and its primary role is to identify carbonaceous species in martian samples, which may be selected for inclusion into a returnable sample cache. The SHERLOC instrument will require the use of a calibration target, and by design, multiple science roles will be addressed in the design of the target. Samples of materials used in NASA Extravehicular Mobility unit (EMU, or "space suit") manufacture have been included in the target to serve as both solid polymer calibration targets for SHERLOC instrument function, as well as for testing the resiliency of those materials under martian ambient conditions. A martian meteorite will also be included in the target to serve as a well-characterized example of a martian rock that contains trace carbonaceous material. This rock will be the first rock that we know of that has completed a round trip between planets and will therefore serve an EPO role to attract public attention to science and planetary exploration. The SHERLOC calibration target will address a wide range of NASA goals to include basic science of interest to both the Science Mission Directorate (SMD) and Human Exploration and Operations Mission Directorate (HEOMD).

Burglar Target Selection: A Cross-National Comparison

NARCIS (Netherlands)

Townsley, M.; Birks, D.; Bernasco, W.; Johnson, S.D.; Ruiter, S.; White, G.

2015-01-01

Objectives: This study builds on research undertaken by Bernasco and Nieuwbeerta and explores the generalizability of a theoretically derived offender target selection model in three cross-national study regions. Methods: Taking a discrete spatial choice approach, we estimate the impact of both

Burglar Target Selection : A Cross-national Comparison

NARCIS (Netherlands)

Townsley, Michael; Birks, Daniel; Bernasco, Wim; Ruiter, Stijn; Johnson, Shane D.; White, Gentry; Baum, Scott

Objectives: This study builds on research undertaken by Bernasco and Nieuwbeerta and explores the generalizability of a theoretically derived offender target selection model in three cross-national study regions. Methods: Taking a discrete spatial choice approach, we estimate the impact of both

Multiple-target method for sputtering amorphous films for bubble-domain devices

International Nuclear Information System (INIS)

Burilla, C.T.; Bekebrede, W.R.; Smith, A.B.

1976-01-01

Previously, sputtered amorphous metal alloys for bubble applications have ordinarily been prepared by standard sputtering techniques using a single target electrode. The deposition of these alloys is reported using a multiple target rf technique in which a separate target is used for each element contained in the alloy. One of the main advantages of this multiple-target approach is that the film composition can be easily changed by simply varying the voltages applied to the elemental targets. In the apparatus, the centers of the targets are positioned on a 15 cm-radius circle. The platform holding the film substrate is on a 15 cm-long arm which can rotate about the center, thus bringing the sample successively under each target. The platform rotation rate is adjustable from 0 to 190 rpm. That this latter speed is sufficient to homogenize the alloys produced is demonstrated by measurements made of the uniaxial anisotropy constant in Gd 0 . 12 Co 0 . 59 Cu 0 . 29 films. The anisotropy is 6.0 x 10 5 ergs/cm 3 and independent of rotation rate above approximately 25 rpm, but it drops rapidly for slower rotation rates, reaching 1.8 x 10 5 ergs/cm 3 for 7 rpm. The film quality is equal to that of films made by conventional methods. Coercivities of a few oersteds in samples with stripe widths of 1 to 2 μm and magnetizations of 800 to 2800 G were observed

Multiple Maneuvering Target Tracking by Improved Particle Filter Based on Multiscan JPDA

Directory of Open Access Journals (Sweden)

Jing Liu

2012-01-01

Full Text Available The multiple maneuvering target tracking algorithm based on a particle filter is addressed. The equivalent-noise approach is adopted, which uses a simple dynamic model consisting of target state and equivalent noise which accounts for the combined effects of the process noise and maneuvers. The equivalent-noise approach converts the problem of maneuvering target tracking to that of state estimation in the presence of nonstationary process noise with unknown statistics. A novel method for identifying the nonstationary process noise is proposed in the particle filter framework. Furthermore, a particle filter based multiscan Joint Probability Data Association (JPDA filter is proposed to deal with the data association problem in a multiple maneuvering target tracking. In the proposed multiscan JPDA algorithm, the distributions of interest are the marginal filtering distributions for each of the targets, and these distributions are approximated with particles. The multiscan JPDA algorithm examines the joint association events in a multiscan sliding window and calculates the marginal posterior probability based on the multiscan joint association events. The proposed algorithm is illustrated via an example involving the tracking of two highly maneuvering, at times closely spaced and crossed, targets, based on resolved measurements.

Feature Extraction and Selection Strategies for Automated Target Recognition

Science.gov (United States)

Greene, W. Nicholas; Zhang, Yuhan; Lu, Thomas T.; Chao, Tien-Hsin

2010-01-01

Several feature extraction and selection methods for an existing automatic target recognition (ATR) system using JPLs Grayscale Optical Correlator (GOC) and Optimal Trade-Off Maximum Average Correlation Height (OT-MACH) filter were tested using MATLAB. The ATR system is composed of three stages: a cursory region of-interest (ROI) search using the GOC and OT-MACH filter, a feature extraction and selection stage, and a final classification stage. Feature extraction and selection concerns transforming potential target data into more useful forms as well as selecting important subsets of that data which may aide in detection and classification. The strategies tested were built around two popular extraction methods: Principal Component Analysis (PCA) and Independent Component Analysis (ICA). Performance was measured based on the classification accuracy and free-response receiver operating characteristic (FROC) output of a support vector machine(SVM) and a neural net (NN) classifier.

Effects of Mode of Target Task Selection on Learning about Plants in a Mobile Learning Environment: Effortful Manual Selection versus Effortless QR-Code Selection

Science.gov (United States)

Gao, Yuan; Liu, Tzu-Chien; Paas, Fred

2016-01-01

This study compared the effects of effortless selection of target plants using quick respond (QR) code technology to effortful manual search and selection of target plants on learning about plants in a mobile device supported learning environment. In addition, it was investigated whether the effectiveness of the 2 selection methods was…

'Multi-epitope-targeted' immune-specific therapy for a multiple sclerosis-like disease via engineered multi-epitope protein is superior to peptides.

Directory of Open Access Journals (Sweden)

Nathali Kaushansky

Full Text Available Antigen-induced peripheral tolerance is potentially one of the most efficient and specific therapeutic approaches for autoimmune diseases. Although highly effective in animal models, antigen-based strategies have not yet been translated into practicable human therapy, and several clinical trials using a single antigen or peptidic-epitope in multiple sclerosis (MS yielded disappointing results. In these clinical trials, however, the apparent complexity and dynamics of the pathogenic autoimmunity associated with MS, which result from the multiplicity of potential target antigens and "epitope spread", have not been sufficiently considered. Thus, targeting pathogenic T-cells reactive against a single antigen/epitope is unlikely to be sufficient; to be effective, immunospecific therapy to MS should logically neutralize concomitantly T-cells reactive against as many major target antigens/epitopes as possible. We investigated such "multi-epitope-targeting" approach in murine experimental autoimmune encephalomyelitis (EAE associated with a single ("classical" or multiple ("complex" anti-myelin autoreactivities, using cocktail of different encephalitogenic peptides vis-a-vis artificial multi-epitope-protein (designated Y-MSPc encompassing rationally selected MS-relevant epitopes of five major myelin antigens, as "multi-epitope-targeting" agents. Y-MSPc was superior to peptide(s in concomitantly downregulating pathogenic T-cells reactive against multiple myelin antigens/epitopes, via inducing more effective, longer lasting peripheral regulatory mechanisms (cytokine shift, anergy, and Foxp3+ CTLA4+ regulatory T-cells. Y-MSPc was also consistently more effective than the disease-inducing single peptide or peptide cocktail, not only in suppressing the development of "classical" or "complex EAE" or ameliorating ongoing disease, but most importantly, in reversing chronic EAE. Overall, our data emphasize that a "multi-epitope-targeting" strategy is required for

Identification of genomic variants putatively targeted by selection during dog domestication.

Science.gov (United States)

Cagan, Alex; Blass, Torsten

2016-01-12

Dogs [Canis lupus familiaris] were the first animal species to be domesticated and continue to occupy an important place in human societies. Recent studies have begun to reveal when and where dog domestication occurred. While much progress has been made in identifying the genetic basis of phenotypic differences between dog breeds we still know relatively little about the genetic changes underlying the phenotypes that differentiate all dogs from their wild progenitors, wolves [Canis lupus]. In particular, dogs generally show reduced aggression and fear towards humans compared to wolves. Therefore, selection for tameness was likely a necessary prerequisite for dog domestication. With the increasing availability of whole-genome sequence data it is possible to try and directly identify the genetic variants contributing to the phenotypic differences between dogs and wolves. We analyse the largest available database of genome-wide polymorphism data in a global sample of dogs 69 and wolves 7. We perform a scan to identify regions of the genome that are highly differentiated between dogs and wolves. We identify putatively functional genomic variants that are segregating or at high frequency [> = 0.75 Fst] for alternative alleles between dogs and wolves. A biological pathways analysis of the genes containing these variants suggests that there has been selection on the 'adrenaline and noradrenaline biosynthesis pathway', well known for its involvement in the fight-or-flight response. We identify 11 genes with putatively functional variants fixed for alternative alleles between dogs and wolves. The segregating variants in these genes are strong candidates for having been targets of selection during early dog domestication. We present the first genome-wide analysis of the different categories of putatively functional variants that are fixed or segregating at high frequency between a global sampling of dogs and wolves. We find evidence that selection has been strongest

Targeting multiple pathogenic mechanisms with polyphenols for the treatment of Alzheimer’s disease: Experimental approach and therapeutic implications

Directory of Open Access Journals (Sweden)

Jun eWang

2014-03-01

Full Text Available Alzheimer’s disease (AD is the most prevalent neurodegenerative disease of aging and currently has no cure. Its onset and progression are influenced by multiple factors. There is growing consensus that successful treatment will rely on simultaneously targeting multiple pathological features of AD. Polyphenol compounds have many proven health benefits. In this study, we tested the hypothesis that combining three polyphenolic preparations (grape seed extract, resveratrol and Concord grape juice extract, with different polyphenolic compositions and partially redundant bioactivities, may simultaneously and synergistically mitigate amyloid-β (Aβ mediated neuropathology and cognitive impairments in a mouse model of AD. We found that administration of the polyphenols in combination did not alter the profile of bioactive polyphenol metabolites in the brain. We also found that combination treatment resulted in better protection against cognitive impairments compared to individual treatments, in J20 AD mice. Electrophysiological examination showed that acute treatment with select brain penetrating polyphenol metabolites, derived from these polyphenols, improved oligomeric Aβ (oAβ-induced long term potentiation (LTP deficits in hippocampal slices. Moreover, we found greatly reduced total amyloid content in the brain following combination treatment. Our studies provided experimental evidence that application of polyphenols targeting multiple disease-mechanisms may yield a greater likelihood of therapeutic efficacy.

A Convenient Cas9-based Conditional Knockout Strategy for Simultaneously Targeting Multiple Genes in Mouse.

Science.gov (United States)

Chen, Jiang; Du, Yinan; He, Xueyan; Huang, Xingxu; Shi, Yun S

2017-03-31

The most powerful way to probe protein function is to characterize the consequence of its deletion. Compared to conventional gene knockout (KO), conditional knockout (cKO) provides an advanced gene targeting strategy with which gene deletion can be performed in a spatially and temporally restricted manner. However, for most species that are amphiploid, the widely used Cre-flox conditional KO (cKO) system would need targeting loci in both alleles to be loxP flanked, which in practice, requires time and labor consuming breeding. This is considerably significant when one is dealing with multiple genes. CRISPR/Cas9 genome modulation system is advantaged in its capability in targeting multiple sites simultaneously. Here we propose a strategy that could achieve conditional KO of multiple genes in mouse with Cre recombinase dependent Cas9 expression. By transgenic construction of loxP-stop-loxP (LSL) controlled Cas9 (LSL-Cas9) together with sgRNAs targeting EGFP, we showed that the fluorescence molecule could be eliminated in a Cre-dependent manner. We further verified the efficacy of this novel strategy to target multiple sites by deleting c-Maf and MafB simultaneously in macrophages specifically. Compared to the traditional Cre-flox cKO strategy, this sgRNAs-LSL-Cas9 cKO system is simpler and faster, and would make conditional manipulation of multiple genes feasible.

Multiple scattering in electron fluid and energy loss in multi-ionic targets

Energy Technology Data Exchange (ETDEWEB)

Deutsch, C., E-mail: claude.deutsch@u-psud.fr [LPGP, UParis-Sud, 91405-Orsay (France); Tahir, N.A. [GSI, 1Planck Str., 64291-Darmstadt (Germany); Barriga-Carrasco, M. [ETSII, UCastilla-la-Mancha, 13071 Ciudad-Real (Spain); Ceban, V. [LPGP, UParis-Sud, 91405-Orsay (France); Fromy, P. [CRI, UParis-Sud, 91405-Orsay (France); Gilles, D. [CEA/Saclay/DSM/IRFU/SAP, 91191-Gif-s-Yvette (France); Leger, D. [Laboratoire Monthouy, UValenciennes-Hainaut Cambresis (France); Maynard, G. [LPGP, UParis-Sud, 91405-Orsay (France); Tashev, B. [Department of Physics, KazNu, Tole Bi82, Almaty (Kazakhstan); Volpe, L. [Department of Physics, UMilano-Bicocca, Milano 20126 (Italy)

2014-01-01

Extensions of the standard stopping model (SSM) for ion projectiles interacting with dense targets of timely concern for ICF and WDM are reviewed. They include multiple scattering on partially degenerate electrons, low velocity ion slowing down in demixing H–He mixtures within Jovian planets core or multiionic target such as Kapton.

Multiple scattering in electron fluid and energy loss in multi-ionic targets

International Nuclear Information System (INIS)

Deutsch, C.; Tahir, N.A.; Barriga-Carrasco, M.; Ceban, V.; Fromy, P.; Gilles, D.; Leger, D.; Maynard, G.; Tashev, B.; Volpe, L.

2014-01-01

Extensions of the standard stopping model (SSM) for ion projectiles interacting with dense targets of timely concern for ICF and WDM are reviewed. They include multiple scattering on partially degenerate electrons, low velocity ion slowing down in demixing H–He mixtures within Jovian planets core or multiionic target such as Kapton

Dissecting patterns of preparatory activity in the frontal eye fields during pursuit target selection.

Science.gov (United States)

Raghavan, Ramanujan T; Joshua, Mati

2017-10-01

We investigated the composition of preparatory activity of frontal eye field (FEF) neurons in monkeys performing a pursuit target selection task. In response to the orthogonal motion of a large and a small reward target, monkeys initiated pursuit biased toward the direction of large reward target motion. FEF neurons exhibited robust preparatory activity preceding movement initiation in this task. Preparatory activity consisted of two components, ramping activity that was constant across target selection conditions, and a flat offset in firing rates that signaled the target selection condition. Ramping activity accounted for 50% of the variance in the preparatory activity and was linked most strongly, on a trial-by-trial basis, to pursuit eye movement latency rather than to its direction or gain. The offset in firing rates that discriminated target selection conditions accounted for 25% of the variance in the preparatory activity and was commensurate with a winner-take-all representation, signaling the direction of large reward target motion rather than a representation that matched the parameters of the upcoming movement. These offer new insights into the role that the frontal eye fields play in target selection and pursuit control. They show that preparatory activity in the FEF signals more strongly when to move rather than where or how to move and suggest that structures outside the FEF augment its contributions to the target selection process. NEW & NOTEWORTHY We used the smooth eye movement pursuit system to link between patterns of preparatory activity in the frontal eye fields and movement during a target selection task. The dominant pattern was a ramping signal that did not discriminate between selection conditions and was linked, on trial-by-trial basis, to movement latency. A weaker pattern was composed of a constant signal that discriminated between selection conditions but was only weakly linked to the movement parameters. Copyright © 2017 the American

Integrative analysis to select cancer candidate biomarkers to targeted validation

Science.gov (United States)

Heberle, Henry; Domingues, Romênia R.; Granato, Daniela C.; Yokoo, Sami; Canevarolo, Rafael R.; Winck, Flavia V.; Ribeiro, Ana Carolina P.; Brandão, Thaís Bianca; Filgueiras, Paulo R.; Cruz, Karen S. P.; Barbuto, José Alexandre; Poppi, Ronei J.; Minghim, Rosane; Telles, Guilherme P.; Fonseca, Felipe Paiva; Fox, Jay W.; Santos-Silva, Alan R.; Coletta, Ricardo D.; Sherman, Nicholas E.; Paes Leme, Adriana F.

2015-01-01

Targeted proteomics has flourished as the method of choice for prospecting for and validating potential candidate biomarkers in many diseases. However, challenges still remain due to the lack of standardized routines that can prioritize a limited number of proteins to be further validated in human samples. To help researchers identify candidate biomarkers that best characterize their samples under study, a well-designed integrative analysis pipeline, comprising MS-based discovery, feature selection methods, clustering techniques, bioinformatic analyses and targeted approaches was performed using discovery-based proteomic data from the secretomes of three classes of human cell lines (carcinoma, melanoma and non-cancerous). Three feature selection algorithms, namely, Beta-binomial, Nearest Shrunken Centroids (NSC), and Support Vector Machine-Recursive Features Elimination (SVM-RFE), indicated a panel of 137 candidate biomarkers for carcinoma and 271 for melanoma, which were differentially abundant between the tumor classes. We further tested the strength of the pipeline in selecting candidate biomarkers by immunoblotting, human tissue microarrays, label-free targeted MS and functional experiments. In conclusion, the proposed integrative analysis was able to pre-qualify and prioritize candidate biomarkers from discovery-based proteomics to targeted MS. PMID:26540631

Forward-backward multiplicity correlations of target fragments in nucleus-emulsion collisions at a few hundred MeV/u

International Nuclear Information System (INIS)

Zhang Donghai; Chen Yanling; Wang Guorong; Li Wangdong; Wang Qing; Yao Jijie; Zhou Jianguo; Li Rong; Li Junsheng; Li Huiling

2015-01-01

The forward-backward multiplicity and correlations of a target evaporated fragment (black track particle) and target recoiled proton (grey track particle) emitted from 150 A MeV "4He, 290 A MeV "1"2C, 400 A MeV "1"2C, 400 A MeV "2"0Ne and 500 A MeV "5"6Fe induced different types of nuclear emulsion target interactions are investigated. It is found that the forward and backward averaged multiplicity of a grey, black and heavily ionized track particle increases with the increase of the target size. The averaged multiplicity of a forward black track particle, backward black track particle, and backward grey track particle do not depend on the projectile size and energy, but the averaged multiplicity of a forward grey track particle increases with an increase of projectile size and energy. The backward grey track particle multiplicity distribution follows an exponential decay law and the decay constant decreases with an increase of target size. The backward-forward multiplicity correlations follow linear law which is independent of the projectile size and energy, and the saturation effect is observed in some heavy target data sets. (authors)

Target Selection Models with Preference Variation Between Offenders

NARCIS (Netherlands)

Townsley, Michael; Birks, Daniel; Ruiter, Stijn; Bernasco, Wim; White, Gentry

2016-01-01

Objectives: This study explores preference variation in location choice strategies of residential burglars. Applying a model of offender target selection that is grounded in assertions of the routine activity approach, rational choice perspective, crime pattern and social disorganization theories,

Sequence-selective targeting of duplex DNA by peptide nucleic acids

DEFF Research Database (Denmark)

Nielsen, Peter E

2010-01-01

Sequence-selective gene targeting constitutes an attractive drug-discovery approach for genetic therapy, with the aim of reducing or enhancing the activity of specific genes at the transcriptional level, or as part of a methodology for targeted gene repair. The pseudopeptide DNA mimic peptide...

Selective association of multiple sclerosis with infectious mononucleosis

NARCIS (Netherlands)

Zaadstra, B.M.; Chorus, A.M.J.; Buuren, S. van; Kalsbeek, H.; Noort, J.M. van

2008-01-01

Previous studies have suggested an association between multiple sclerosis (MS) and infectious mononucleosis (IM) but data on the exact strength of this association or its selectivity have been conflicting. In this study we have evaluated the association between MS and a variety of common childhood

Efficient Selection of Multiple Objects on a Large Scale

DEFF Research Database (Denmark)

Stenholt, Rasmus

2012-01-01

The task of multiple object selection (MOS) in immersive virtual environments is important and still largely unexplored. The diffi- culty of efficient MOS increases with the number of objects to be selected. E.g. in small-scale MOS, only a few objects need to be simultaneously selected. This may...... consuming. Instead, we have implemented and tested two of the existing approaches to 3-D MOS, a brush and a lasso, as well as a new technique, a magic wand, which automati- cally selects objects based on local proximity to other objects. In a formal user evaluation, we have studied how the performance...

Targeting the Pim kinases in multiple myeloma.

LENUS (Irish Health Repository)

Keane, N A

2015-07-17

Multiple myeloma (MM) is a plasma cell malignancy that remains incurable. Novel treatment strategies to improve survival are urgently required. The Pims are a small family of serine\\/threonine kinases with increased expression across the hematological malignancies. Pim-2 shows highest expression in MM and constitutes a promising therapeutic target. It is upregulated by the bone marrow microenvironment to mediate proliferation and promote MM survival. Pim-2 also has a key role in the bone destruction typically seen in MM. Additional putative roles of the Pim kinases in MM include trafficking of malignant cells, promoting oncogenic signaling in the hypoxic bone marrow microenvironment and mediating resistance to therapy. A number of Pim inhibitors are now under development with lead compounds entering the clinic. The ATP-competitive Pim inhibitor LGH447 has recently been reported to have single agent activity in MM. It is anticipated that Pim inhibition will be of clinical benefit in combination with standard treatments and\\/or with novel drugs targeting other survival pathways in MM.

A placebo-controlled trial of oral cladribine for relapsing multiple sclerosis

DEFF Research Database (Denmark)

Giovannoni, Gavin; Comi, Giancarlo; Cook, Stuart

2010-01-01

Cladribine provides immunomodulation through selective targeting of lymphocyte subtypes. We report the results of a 96-week phase 3 trial of a short-course oral tablet therapy in patients with relapsing-remitting multiple sclerosis.......Cladribine provides immunomodulation through selective targeting of lymphocyte subtypes. We report the results of a 96-week phase 3 trial of a short-course oral tablet therapy in patients with relapsing-remitting multiple sclerosis....

Method for Multiple Targets Tracking in Cognitive Radar Based on Compressed Sensing

Directory of Open Access Journals (Sweden)

Yang Jun

2016-02-01

Full Text Available A multiple targets cognitive radar tracking method based on Compressed Sensing (CS is proposed. In this method, the theory of CS is introduced to the case of cognitive radar tracking process in multiple targets scenario. The echo signal is sparsely expressed. The designs of sparse matrix and measurement matrix are accomplished by expressing the echo signal sparsely, and subsequently, the restruction of measurement signal under the down-sampling condition is realized. On the receiving end, after considering that the problems that traditional particle filter suffers from degeneracy, and require a large number of particles, the particle swarm optimization particle filter is used to track the targets. On the transmitting end, the Posterior Cramér-Rao Bounds (PCRB of the tracking accuracy is deduced, and the radar waveform parameters are further cognitively designed using PCRB. Simulation results show that the proposed method can not only reduce the data quantity, but also provide a better tracking performance compared with traditional method.

Targeting p110gamma in gastrointestinal cancers: attack on multiple fronts

Directory of Open Access Journals (Sweden)

Marco eFalasca

2014-10-01

Full Text Available Phosphoinositide 3-kinases (PI3Ks regulate several cellular functions that are critical for cancer progression and development, including cell survival, proliferation and migration. Three classes of PI3Ks exist with the class I PI3K encompassing four isoforms of the catalytic subunit known as p110α, p110β, p110γ and p110δ. Although for many years attention has been mainly focused on p110α recent evidence supports the conclusion that p110β, p110γ and p110δ can also have a role in cancer. Amongst these, accumulating evidence now supports the conclusion that p110γ is involved in several cellular processes associated with cancer development and progression and indeed this specific isoform has emerged as a novel important player in cancer progression. Studies from our laboratory have identified a specific overexpression of p110γ in human pancreatic ductal adenocarcinoma (PDAC and in hepatocellular carcinoma (HCC tissues compared to their normal counterparts. Our data have further established that selective inhibition of this PI3K isoform is able to block PDAC and HCC cell proliferation, strongly suggesting that pharmacological inhibition of this enzyme can directly affect these tumors growth. Furthermore increasing evidence suggests that p110γ plays also a key role in the interactions between cancer cells and tumor microenvironment and in particular in tumor-associated immune response. It has also been reported that p110γ can regulate invasion of myeloid cells into tumors and tumor angiogenesis. Finally p110γ has also been directly involved in regulation of cancer cell migration. Taken together these data indicate that p110γ plays multiple roles in regulation of several processes that are critical for tumor progression and metastasis. This review will discuss the role of p110γ in gastrointestinal tumor development and progression and how targeting this enzyme might represent a way to target very aggressive tumors such as pancreatic and

First passage times for multiple particles with reversible target-binding kinetics

Science.gov (United States)

Grebenkov, Denis S.

2017-10-01

We investigate the first passage problem for multiple particles that diffuse towards a target, partially adsorb there, and then desorb after a finite exponentially distributed residence time. We search for the first time when m particles undergoing such reversible target-binding kinetics are found simultaneously on the target that may trigger an irreversible chemical reaction or a biophysical event. Even if the particles are independent, the finite residence time on the target yields an intricate temporal coupling between particles. We compute analytically the mean first passage time (MFPT) for two independent particles by mapping the original problem to higher-dimensional surface-mediated diffusion and solving the coupled partial differential equations. The respective effects of the adsorption and desorption rates on the MFPT are revealed and discussed.

Neural Networks for Target Selection in Direct Marketing

NARCIS (Netherlands)

R. Potharst (Rob); U. Kaymak (Uzay); W.H.L.M. Pijls (Wim)

2001-01-01

textabstractPartly due to a growing interest in direct marketing, it has become an important application field for data mining. Many techniques have been applied to select the targets in commercial applications, such as statistical regression, regression trees, neural computing, fuzzy clustering

Effector stage CC chemokine receptor-1 selective antagonism reduces multiple sclerosis-like rat disease.

Science.gov (United States)

Eltayeb, Sana; Sunnemark, Dan; Berg, Anna-Lena; Nordvall, Gunnar; Malmberg, Asa; Lassmann, Hans; Wallström, Erik; Olsson, Tomas; Ericsson-Dahlstrand, Anders

2003-09-01

We have studied the role of the chemokine receptor CCR1 during the effector stage of myelin oligodendrocyte glycoprotein-induced experimental autoimmune encephalomyelitis in DA rats. In situ hybridization histochemistry revealed local production of the CCR1 ligands CCL3 (MIP-1 alpha) and CCL5 (RANTES), as well as large numbers of CCR1 and CCR5 expressing cells within inflammatory brain lesions. A low-molecular weight CCR1 selective antagonist potently abrogated both clinical and histopathological disease signs during a 5-day treatment period, without signs of peripheral immune compromise. Thus, we demonstrate therapeutic targeting of CCR1-dependent leukocyte recruitment to the central nervous system in a multiple sclerosis (MS)-like rat model.

Exploiting off-targeting in guide-RNAs for CRISPR systems for simultaneous editing of multiple genes

DEFF Research Database (Denmark)

Ferreira, Raphael; Gatto, Francesco; Nielsen, Jens

2017-01-01

Bioinformatics tools to design guide-RNAs (gRNAs) in Clustered Regularly Interspaced Short Palindromic Repeats systems mostly focused on minimizing off-targeting to enhance efficacy of genome editing. However, there are circumstances in which off-targeting might be desirable to target multiple ge...

Hybrid value foraging: How the value of targets shapes human foraging behavior.

Science.gov (United States)

Wolfe, Jeremy M; Cain, Matthew S; Alaoui-Soce, Abla

2018-04-01

In hybrid foraging, observers search visual displays for multiple instances of multiple target types. In previous hybrid foraging experiments, although there were multiple types of target, all instances of all targets had the same value. Under such conditions, behavior was well described by the marginal value theorem (MVT). Foragers left the current "patch" for the next patch when the instantaneous rate of collection dropped below their average rate of collection. An observer's specific target selections were shaped by previous target selections. Observers were biased toward picking another instance of the same target. In the present work, observers forage for instances of four target types whose value and prevalence can vary. If value is kept constant and prevalence manipulated, participants consistently show a preference for the most common targets. Patch-leaving behavior follows MVT. When value is manipulated, observers favor more valuable targets, though individual foraging strategies become more diverse, with some observers favoring the most valuable target types very strongly, sometimes moving to the next patch without collecting any of the less valuable targets.

Contextual control over selective attention: evidence from a two-target method.

Science.gov (United States)

MacLellan, Ellen; Shore, David I; Milliken, Bruce

2015-07-01

Selective attention is generally studied with conflict tasks, using response time as the dependent measure. Here, we study the impact of selective attention to a first target, T1, presented simultaneously with a distractor, on the accuracy of subsequent encoding of a second target item, T2. This procedure produces an "attentional blink" (AB) effect much like that reported in other studies, and allowed us to study the influence of context on cognitive control with a novel method. In particular, we examined whether preparation to attend selectively to T1 had an impact on the selective encoding of T1 that would translate to report of T2. Preparation to attend selectively was manipulated by varying whether difficult selective attention T1 trials were presented in the context of other difficult selective attention T1 trials. The results revealed strong context effects of this nature, with smaller AB effects when difficult selective attention T1 trials were embedded in a context with many, rather than few, other difficult selective attention T1 trials. Further, the results suggest that both the trial-to-trial local context and the block-wide global context modulate performance in this task.

Targeted Diazotransfer Reagents Enable Selective Modification of Proteins with Azides.

Science.gov (United States)

Lohse, Jonas; Swier, Lotteke J Y M; Oudshoorn, Ruben C; Médard, Guillaume; Kuster, Bernhard; Slotboom, Dirk-Jan; Witte, Martin D

2017-04-19

In chemical biology, azides are used to chemically manipulate target structures in a bioorthogonal manner for a plethora of applications ranging from target identification to the synthesis of homogeneously modified protein conjugates. While a variety of methods have been established to introduce the azido group into recombinant proteins, a method that directly converts specific amino groups in endogenous proteins is lacking. Here, we report the first biotin-tethered diazotransfer reagent DtBio and demonstrate that it selectively modifies the model proteins streptavidin and avidin and the membrane protein BioY on cell surface. The reagent converts amines in the proximity of the binding pocket to azides and leaves the remaining amino groups in streptavidin untouched. Reagents of this novel class will find use in target identification as well as the selective functionalization and bioorthogonal protection of proteins.

Myth 6: Cosmetic Use of Multiple Selection Criteria

Science.gov (United States)

Friedman-Nimz, Reva

2009-01-01

Twenty-five years ago, armed with the courage of her convictions and a respectable collection of empirical evidence, the author articulated what she considered to be a compelling argument against the cosmetic use of multiple selection criteria as a guiding principle for identifying children and youth with high potential. To assess the current…

Selection of IFE target materials from a safety and environmental perspective

Science.gov (United States)

Latkowski, J. F.; Sanz, J.; Reyes, S.; Gomez del Rio, J.

2001-05-01

Target materials for inertial fusion energy (IFE) power plant designs might be selected for a wide variety of reasons including wall absorption of driver energy, material opacity, cost and ease of fabrication. While each of these issues are of great importance, target materials should also be selected based upon their safety and environmental (S&E) characteristics. The present work focuses on the recycling, waste management and accident dose characteristics of potential target materials. If target materials are recycled so that the quantity is small, isotopic separation may be economically viable. Therefore, calculations have been completed for all stable isotopes for all elements from lithium to polonium. The results of these calculations are used to identify specific isotopes and elements that are most likely to be offensive as well as those most likely to be acceptable in terms of their S&E characteristics.

Nanostructured materials for selective recognition and targeted drug delivery

International Nuclear Information System (INIS)

Kotrotsiou, O; Kotti, K; Dini, E; Kammona, O; Kiparissides, C

2005-01-01

Selective recognition requires the introduction of a molecular memory into a polymer matrix in order to make it capable of rebinding an analyte with a very high specificity. In addition, targeted drug delivery requires drug-loaded vesicles which preferentially localize to the sites of injury and avoid uptake into uninvolved tissues. The rapid evolution of nanotechnology is aiming to fulfill the goal of selective recognition and optimal drug delivery through the development of molecularly imprinted polymeric (MIP) nanoparticles, tailor-made for a diverse range of analytes (e.g., pharmaceuticals, pesticides, amino acids, etc.) and of nanostructured targeted drug carriers (e.g., liposomes and micelles) with increased circulation lifetimes. In the present study, PLGA microparticles containing multilamellar vesicles (MLVs), and MIP nanoparticles were synthesized to be employed as drug carriers and synthetic receptors respectively

Social exclusion impairs distractor suppression but not target enhancement in selective attention.

Science.gov (United States)

Xu, Mengsi; Li, Zhiai; Diao, Liuting; Fan, Lingxia; Zhang, Lijie; Yuan, Shuge; Yang, Dong

2017-11-01

Social exclusion has been thought to weaken one's ability to exert inhibitory control. Existing studies have primarily focused on the relationship between exclusion and behavioral inhibition, and have reported that exclusion impairs behavioral inhibition. However, whether exclusion also affects selective attention, another important aspect of inhibitory control, remains unknown. Therefore, the current study aimed to explore whether social exclusion impairs selective attention, and to specifically examine its effect on two hypothesized mechanisms of selective attention: target enhancement and distractor suppression. The Cyberball game was used to manipulate social exclusion. Participants then performed a visual search task while event-related potentials were recorded. In the visual search task, target and salient distractor were either both presented laterally or one was presented on the vertical midline and the other laterally. Results showed that social exclusion differentially affected target and distractor processing. While exclusion impaired distractor suppression, reflected as smaller distractor-positivity (Pd) amplitudes for the exclusion group compared to the inclusion group, it did not affect target enhancement, reflected as similar target-negativity (Nt) amplitudes for both the exclusion and inclusion groups. Together, these results extend our understanding of the relationship between exclusion and inhibitory control, and suggest that social exclusion affects selective attention in a more complex manner than previously thought. Copyright © 2017. Published by Elsevier B.V.

Getting satisfied with "satisfaction of search": How to measure errors during multiple-target visual search.

Science.gov (United States)

Biggs, Adam T

2017-07-01

Visual search studies are common in cognitive psychology, and the results generally focus upon accuracy, response times, or both. Most research has focused upon search scenarios where no more than 1 target will be present for any single trial. However, if multiple targets can be present on a single trial, it introduces an additional source of error because the found target can interfere with subsequent search performance. These errors have been studied thoroughly in radiology for decades, although their emphasis in cognitive psychology studies has been more recent. One particular issue with multiple-target search is that these subsequent search errors (i.e., specific errors which occur following a found target) are measured differently by different studies. There is currently no guidance as to which measurement method is best or what impact different measurement methods could have upon various results and conclusions. The current investigation provides two efforts to address these issues. First, the existing literature is reviewed to clarify the appropriate scenarios where subsequent search errors could be observed. Second, several different measurement methods are used with several existing datasets to contrast and compare how each method would have affected the results and conclusions of those studies. The evidence is then used to provide appropriate guidelines for measuring multiple-target search errors in future studies.

SAR Target Recognition Based on Multi-feature Multiple Representation Classifier Fusion

Directory of Open Access Journals (Sweden)

Zhang Xinzheng

2017-10-01

Full Text Available In this paper, we present a Synthetic Aperture Radar (SAR image target recognition algorithm based on multi-feature multiple representation learning classifier fusion. First, it extracts three features from the SAR images, namely principal component analysis, wavelet transform, and Two-Dimensional Slice Zernike Moments (2DSZM features. Second, we harness the sparse representation classifier and the cooperative representation classifier with the above-mentioned features to get six predictive labels. Finally, we adopt classifier fusion to obtain the final recognition decision. We researched three different classifier fusion algorithms in our experiments, and the results demonstrate thatusing Bayesian decision fusion gives thebest recognition performance. The method based on multi-feature multiple representation learning classifier fusion integrates the discrimination of multi-features and combines the sparse and cooperative representation classification performance to gain complementary advantages and to improve recognition accuracy. The experiments are based on the Moving and Stationary Target Acquisition and Recognition (MSTAR database,and they demonstrate the effectiveness of the proposed approach.

A multiple sampling ionization chamber for the External Target Facility

International Nuclear Information System (INIS)

Zhang, X.H.; Tang, S.W.; Ma, P.; Lu, C.G.; Yang, H.R.; Wang, S.T.; Yu, Y.H.; Yue, K.; Fang, F.; Yan, D.; Zhou, Y.; Wang, Z.M.; Sun, Y.; Sun, Z.Y.; Duan, L.M.; Sun, B.H.

2015-01-01

A multiple sampling ionization chamber used as a particle identification device for high energy heavy ions has been developed for the External Target Facility. The performance of this detector was tested with a 239 Pu α source and RI beams. A Z resolution (FWHM) of 0.4–0.6 was achieved for nuclear fragments of 18 O at 400 AMeV

In Vitro Selection and Characterization of DNA Aptamers to a Small Molecule Target.

Science.gov (United States)

Ruscito, Annamaria; McConnell, Erin M; Koudrina, Anna; Velu, Ranganathan; Mattice, Christopher; Hunt, Vernon; McKeague, Maureen; DeRosa, Maria C

2017-12-14

Aptamers, synthetic oligonucleotide-based molecular recognition probes, have found use in a wide array of biosensing technologies based on their tight and highly selective binding to a variety of molecular targets. However, the inherent challenges associated with the selection and characterization of aptamers for small molecule targets have resulted in their underrepresentation, despite the need for small molecule detection in fields such as medicine, the environment, and agriculture. This protocol describes the steps in the selection, sequencing, affinity characterization, and truncation of DNA aptamers that are specific for small molecule targets. © 2017 by John Wiley & Sons, Inc. Copyright © 2017 John Wiley & Sons, Inc.

Selection of IFE target materials from a safety and environmental perspective

Energy Technology Data Exchange (ETDEWEB)

Latkowski, J.F. E-mail: latkowski1@llnl.gov; Sanz, J.; Reyes, S.; Gomez del Rio, J

2001-05-21

Target materials for inertial fusion energy (IFE) power plant designs might be selected for a wide variety of reasons including wall absorption of driver energy, material opacity, cost and ease of fabrication. While each of these issues are of great importance, target materials should also be selected based upon their safety and environmental (S and E) characteristics. The present work focuses on the recycling, waste management and accident dose characteristics of potential target materials. If target materials are recycled so that the quantity is small, isotopic separation may be economically viable. Therefore, calculations have been completed for all stable isotopes for all elements from lithium to polonium. The results of these calculations are used to identify specific isotopes and elements that are most likely to be offensive as well as those most likely to be acceptable in terms of their S and E characteristics.

Modulation of orientation-selective neurons by motion: when additive, when multiplicative?

Directory of Open Access Journals (Sweden)

Torsten eLüdge

2014-06-01

Full Text Available The recurrent interaction among orientation-selective neurons in the primary visual cortex (V1 is suited to enhance contours in a noisy visual scene. Motion is known to have a strong pop-up effect in perceiving contours, but how motion-sensitive neurons in V1 support contour detection remains vastly elusive. Here we suggest how the various types of motion-sensitive neurons observed in V1 should be wired together in a micro-circuitry to optimally extract contours in the visual scene. Motion-sensitive neurons can be selective about the direction of motion occurring at some spot or respond equally to all directions (pandirectional. We show that, in the light of figure-ground segregation, direction-selective motion neurons should additively modulate the corresponding orientation-selective neurons with preferred orientation orthogonal to the motion direction. In turn, to maximally enhance contours, pandirectional motion neurons should multiplicatively modulate all orientation-selective neurons with co-localized receptive fields. This multiplicative modulation amplifies the local V1-circuitry among co-aligned orientation-selective neurons for detecting elongated contours. We suggest that the additive modulation by direction- specific motion neurons is achieved through synaptic projections to the somatic region, and the multiplicative modulation by pandirectional motion neurons through projections to the apical region of orientation-specific pyramidal neurons. For the purpose of contour detection, the V1- intrinsic integration of motion information is advantageous over a downstream integration as it exploits the recurrent V1-circuitry designed for that task.

In vitro Selection and Interaction Studies of a DNA Aptamer Targeting Protein A

OpenAIRE

Stoltenburg, Regina; Schubert, Thomas; Strehlitz, Beate

2015-01-01

A new DNA aptamer targeting Protein A is presented. The aptamer was selected by use of the FluMag-SELEX procedure. The SELEX technology (Systematic Evolution of Ligands by EXponential enrichment) is widely applied as an in vitro selection and amplification method to generate target-specific aptamers and exists in various modified variants. FluMag-SELEX is one of them and is characterized by the use of magnetic beads for target immobilization and fluorescently labeled oligonucleotides for moni...

Altering spatial priority maps via statistical learning of target selection and distractor filtering.

Science.gov (United States)

Ferrante, Oscar; Patacca, Alessia; Di Caro, Valeria; Della Libera, Chiara; Santandrea, Elisa; Chelazzi, Leonardo

2018-05-01

The cognitive system has the capacity to learn and make use of environmental regularities - known as statistical learning (SL), including for the implicit guidance of attention. For instance, it is known that attentional selection is biased according to the spatial probability of targets; similarly, changes in distractor filtering can be triggered by the unequal spatial distribution of distractors. Open questions remain regarding the cognitive/neuronal mechanisms underlying SL of target selection and distractor filtering. Crucially, it is unclear whether the two processes rely on shared neuronal machinery, with unavoidable cross-talk, or they are fully independent, an issue that we directly addressed here. In a series of visual search experiments, participants had to discriminate a target stimulus, while ignoring a task-irrelevant salient distractor (when present). We systematically manipulated spatial probabilities of either one or the other stimulus, or both. We then measured performance to evaluate the direct effects of the applied contingent probability distribution (e.g., effects on target selection of the spatial imbalance in target occurrence across locations) as well as its indirect or "transfer" effects (e.g., effects of the same spatial imbalance on distractor filtering across locations). By this approach, we confirmed that SL of both target and distractor location implicitly bias attention. Most importantly, we described substantial indirect effects, with the unequal spatial probability of the target affecting filtering efficiency and, vice versa, the unequal spatial probability of the distractor affecting target selection efficiency across locations. The observed cross-talk demonstrates that SL of target selection and distractor filtering are instantiated via (at least partly) shared neuronal machinery, as further corroborated by strong correlations between direct and indirect effects at the level of individual participants. Our findings are compatible

NEWTONIAN IMPERIALIST COMPETITVE APPROACH TO OPTIMIZING OBSERVATION OF MULTIPLE TARGET POINTS IN MULTISENSOR SURVEILLANCE SYSTEMS

Directory of Open Access Journals (Sweden)

A. Afghan-Toloee

2013-09-01

Full Text Available The problem of specifying the minimum number of sensors to deploy in a certain area to face multiple targets has been generally studied in the literatures. In this paper, we are arguing the multi-sensors deployment problem (MDP. The Multi-sensor placement problem can be clarified as minimizing the cost required to cover the multi target points in the area. We propose a more feasible method for the multi-sensor placement problem. Our method makes provision the high coverage of grid based placements while minimizing the cost as discovered in perimeter placement techniques. The NICA algorithm as improved ICA (Imperialist Competitive Algorithm is used to decrease the performance time to explore an enough solution compared to other meta-heuristic schemes such as GA, PSO and ICA. A three dimensional area is used for clarify the multiple target and placement points, making provision x, y, and z computations in the observation algorithm. A structure of model for the multi-sensor placement problem is proposed: The problem is constructed as an optimization problem with the objective to minimize the cost while covering all multiple target points upon a given probability of observation tolerance.

A color hierarchy for automatic target selection.

Directory of Open Access Journals (Sweden)

Illia Tchernikov

Full Text Available Visual processing of color starts at the cones in the retina and continues through ventral stream visual areas, called the parvocellular pathway. Motion processing also starts in the retina but continues through dorsal stream visual areas, called the magnocellular system. Color and motion processing are functionally and anatomically discrete. Previously, motion processing areas MT and MST have been shown to have no color selectivity to a moving stimulus; the neurons were colorblind whenever color was presented along with motion. This occurs when the stimuli are luminance-defined versus the background and is considered achromatic motion processing. Is motion processing independent of color processing? We find that motion processing is intrinsically modulated by color. Color modulated smooth pursuit eye movements produced upon saccading to an aperture containing a surface of coherently moving dots upon a black background. Furthermore, when two surfaces that differed in color were present, one surface was automatically selected based upon a color hierarchy. The strength of that selection depended upon the distance between the two colors in color space. A quantifiable color hierarchy for automatic target selection has wide-ranging implications from sports to advertising to human-computer interfaces.

Detection and localization of multiple short range targets using FMCW radar signal

KAUST Repository

Jardak, Seifallah

2016-07-26

In this paper, a 24 GHz frequency-modulated continuous wave radar is used to detect and localize both stationary and moving targets. Depending on the application, the implemented software offers different modes of operation. For example, it can simply output raw data samples for advanced offline processing or directly carry out a two dimensional fast Fourier transform to estimate the location and velocity of multiple targets. To suppress clutter and detect only moving targets, two methods based on the background reduction and the slow time processing techniques are implemented. A trade-off between the two methods is presented based on their performance and the required processing time. © 2016 IEEE.

The folate receptor as a molecular target for tumor-selective radionuclide delivery

International Nuclear Information System (INIS)

Ke, C.-Y.; Mathias, Carla J.; Green, Mark A.

2003-01-01

The cell-membrane folate receptor is a potential molecular target for tumor-selective drug delivery, including radiolabeled folate-chelate conjugates for diagnostic imaging. We review here some background on the folate receptor as tumor-associated molecular target for drug delivery, and briefly survey the literature on tumor-targeting with radiolabeled folate-chelate conjugates

Target Selection for the SDSS-IV APOGEE-2 Survey

International Nuclear Information System (INIS)

Zasowski, G.; Cohen, R. E.; Carlberg, J. K.; Fleming, Scott W.; Chojnowski, S. D.; Holtzman, J.; Santana, F.; Oelkers, R. J.; Bird, J. C.; Andrews, B.; Beaton, R. L.; Bender, C.; Cunha, K.; Bovy, J.; Covey, K.; Dell’Agli, F.; García-Hernández, D. A.; Frinchaboy, P. M.; Harding, P.; Johnson, J. A.

2017-01-01

APOGEE-2 is a high-resolution, near-infrared spectroscopic survey observing ∼3 × 10 5 stars across the entire sky. It is the successor to APOGEE and is part of the Sloan Digital Sky Survey IV (SDSS-IV). APOGEE-2 is expanding on APOGEE’s goals of addressing critical questions of stellar astrophysics, stellar populations, and Galactic chemodynamical evolution using (1) an enhanced set of target types and (2) a second spectrograph at Las Campanas Observatory in Chile. APOGEE-2 is targeting red giant branch and red clump stars, RR Lyrae, low-mass dwarf stars, young stellar objects, and numerous other Milky Way and Local Group sources across the entire sky from both hemispheres. In this paper, we describe the APOGEE-2 observational design, target selection catalogs and algorithms, and the targeting-related documentation included in the SDSS data releases.

The control of attentional target selection in a colour/colour conjunction task

OpenAIRE

Berggren, Nick; Eimer, Martin

2016-01-01

To investigate the time course of attentional object selection processes in visual search tasks where targets are defined by a combination of features from the same dimension, we measured the N2pc component as an electrophysiological marker of attentional object selection during colour/colour conjunction search. In Experiment 1, participants searched for targets defined by a combination of two colours, while ignoring distractor objects that matched only one of these colours. Reliable N2pc com...

Multi-Target Angle Tracking Algorithm for Bistatic Multiple-Input Multiple-Output (MIMO Radar Based on the Elements of the Covariance Matrix

Directory of Open Access Journals (Sweden)

Zhengyan Zhang

2018-03-01

Full Text Available In this paper, we consider the problem of tracking the direction of arrivals (DOA and the direction of departure (DOD of multiple targets for bistatic multiple-input multiple-output (MIMO radar. A high-precision tracking algorithm for target angle is proposed. First, the linear relationship between the covariance matrix difference and the angle difference of the adjacent moment was obtained through three approximate relations. Then, the proposed algorithm obtained the relationship between the elements in the covariance matrix difference. On this basis, the performance of the algorithm was improved by averaging the covariance matrix element. Finally, the least square method was used to estimate the DOD and DOA. The algorithm realized the automatic correlation of the angle and provided better performance when compared with the adaptive asymmetric joint diagonalization (AAJD algorithm. The simulation results demonstrated the effectiveness of the proposed algorithm. The algorithm provides the technical support for the practical application of MIMO radar.

Multi-Target Angle Tracking Algorithm for Bistatic Multiple-Input Multiple-Output (MIMO) Radar Based on the Elements of the Covariance Matrix.

Science.gov (United States)

Zhang, Zhengyan; Zhang, Jianyun; Zhou, Qingsong; Li, Xiaobo

2018-03-07

In this paper, we consider the problem of tracking the direction of arrivals (DOA) and the direction of departure (DOD) of multiple targets for bistatic multiple-input multiple-output (MIMO) radar. A high-precision tracking algorithm for target angle is proposed. First, the linear relationship between the covariance matrix difference and the angle difference of the adjacent moment was obtained through three approximate relations. Then, the proposed algorithm obtained the relationship between the elements in the covariance matrix difference. On this basis, the performance of the algorithm was improved by averaging the covariance matrix element. Finally, the least square method was used to estimate the DOD and DOA. The algorithm realized the automatic correlation of the angle and provided better performance when compared with the adaptive asymmetric joint diagonalization (AAJD) algorithm. The simulation results demonstrated the effectiveness of the proposed algorithm. The algorithm provides the technical support for the practical application of MIMO radar.

Selective reminding of prospective memory in Multiple Sclerosis.

Science.gov (United States)

McKeever, Joshua D; Schultheis, Maria T; Sim, Tiffanie; Goykhman, Jessica; Patrick, Kristina; Ehde, Dawn M; Woods, Steven Paul

2017-04-19

Multiple sclerosis (MS) is associated with prospective memory (PM) deficits, which may increase the risk of poor functional/health outcomes such as medication non-adherence. This study examined the potential benefits of selective reminding to enhance PM functioning in persons with MS. Twenty-one participants with MS and 22 healthy adults (HA) underwent a neuropsychological battery including a Selective Reminding PM (SRPM) experimental procedure. Participants were randomly assigned to either: (1) a selective reminding condition in which participants learn (to criterion) eight prospective memory tasks in a Selective Reminding format; or (2) a single trial encoding condition (1T). A significant interaction was demonstrated, with MS participants receiving greater benefit than HAs from the SR procedure in terms of PM performance. Across diagnostic groups, participants in the SR conditions (vs. 1T conditions) demonstrated significantly better PM performance. Individuals with MS were impaired relative to HAs in the 1T condition, but performance was statistically comparable in the SR condition. This preliminary study suggests that selective reminding can be used to enhance PM cue detection and retrieval in MS. The extent to which selective reminding of PM is effective in naturalistic settings and for health-related behaviours in MS remains to be determined.

Target Selection for the SDSS-IV APOGEE-2 Survey

Energy Technology Data Exchange (ETDEWEB)

Zasowski, G. [Department of Physics and Astronomy, University of Utah, Salt Lake City, UT 84112 (United States); Cohen, R. E.; Carlberg, J. K.; Fleming, Scott W. [Space Telescope Science Institute, Baltimore, MD 21218 (United States); Chojnowski, S. D.; Holtzman, J. [Department of Astronomy, New Mexico State University, Las Cruces, NM 88001 (United States); Santana, F. [Departamento de Astronomía, Universidad de Chile, Santiago (Chile); Oelkers, R. J.; Bird, J. C. [Department of Physics and Astronomy, Vanderbilt University, Nashville, TN 37235 (United States); Andrews, B. [PITT PACC, Department of Physics and Astronomy, University of Pittsburgh, Pittsburgh, PA 15260 (United States); Beaton, R. L. [The Observatories of the Carnegie Institution for Science, Pasadena, CA 91101 (United States); Bender, C.; Cunha, K. [Steward Observatory, The University of Arizona, Tucson, AZ 85719 (United States); Bovy, J. [Department of Astronomy and Astrophysics and Dunlap Institute for Astronomy and Astrophysics, University of Toronto, Toronto, ON M5S 3H4 (Canada); Covey, K. [Department of Physics and Astronomy, Western Washington University, Bellingham, WA 98225 (United States); Dell’Agli, F.; García-Hernández, D. A. [Departamento de Astrofísica, Universidad de La Laguna, and Instituto de Astrofísica de Canarias, La Laguna, Tenerife (Spain); Frinchaboy, P. M. [Department of Physics and Astronomy, Texas Christian University, Fort Worth, TX 76129 (United States); Harding, P. [Department of Astronomy, Case Western Reserve University, Cleveland, OH 44106 (United States); Johnson, J. A., E-mail: gail.zasowski@gmail.com [Department of Astronomy, The Ohio State University, Columbus, OH 43210 (United States); and others

2017-11-01

APOGEE-2 is a high-resolution, near-infrared spectroscopic survey observing ∼3 × 10{sup 5} stars across the entire sky. It is the successor to APOGEE and is part of the Sloan Digital Sky Survey IV (SDSS-IV). APOGEE-2 is expanding on APOGEE’s goals of addressing critical questions of stellar astrophysics, stellar populations, and Galactic chemodynamical evolution using (1) an enhanced set of target types and (2) a second spectrograph at Las Campanas Observatory in Chile. APOGEE-2 is targeting red giant branch and red clump stars, RR Lyrae, low-mass dwarf stars, young stellar objects, and numerous other Milky Way and Local Group sources across the entire sky from both hemispheres. In this paper, we describe the APOGEE-2 observational design, target selection catalogs and algorithms, and the targeting-related documentation included in the SDSS data releases.

Classification and Target Group Selection Based Upon Frequent Patterns

NARCIS (Netherlands)

W.H.L.M. Pijls (Wim); R. Potharst (Rob)

2000-01-01

textabstractIn this technical report , two new algorithms based upon frequent patterns are proposed. One algorithm is a classification method. The other one is an algorithm for target group selection. In both algorithms, first of all, the collection of frequent patterns in the training set is

Efficient and Adaptive Node Selection for Target Tracking in Wireless Sensor Network

Directory of Open Access Journals (Sweden)

Juan Feng

2016-01-01

Full Text Available In target tracking wireless sensor network, choosing the proper working nodes can not only minimize the number of active nodes, but also satisfy the tracking reliability requirement. However, most existing works focus on selecting sensor nodes which are the nearest to the target for tracking missions and they did not consider the correlation of the location of the sensor nodes so that these approaches can not meet all the goals of the network. This work proposes an efficient and adaptive node selection approach for tracking a target in a distributed wireless sensor network. The proposed approach combines the distance-based node selection strategy and particle filter prediction considering the spatial correlation of the different sensing nodes. Moreover, a joint distance weighted measurement is proposed to estimate the information utility of sensing nodes. Experimental results show that EANS outperformed the state-of-the-art approaches by reducing the energy cost and computational complexity as well as guaranteeing the tracking accuracy.

Two-dimensional multiplicity fluctuation analysis of target residues in nuclear collisions

International Nuclear Information System (INIS)

Dong-Hai, Zhang; Yao-Jie, Niu; Li-Chun, Wang; Wen-Jun, Yan; Li-Juan, Gao; Ming-Xing, Li; Li-Ping, Wu; Hui-Ling, Li; Jun-Sheng, Li

2010-01-01

Multiplicity fluctuation of the target residues emitted in the interactions in a wide range of projectile energies from 500 A MeV to 60 A GeV is investigated in the framework of two-dimensional scaled factorial moment methodology. The evidence of non-statistical multiplicity fluctuation is found in 16 O–AgBr collisions at 60 A GeV, but not in 56 Fe–AgBr collisions at 500 A MeV, 84 Kr–AgBr collisions at 1.7 A GeV, 16 O–AgBr collisions at 3.7 A GeV and 197 Au–AgBr collisions at 10.7 A GeV. (nuclear physics)

Positive-negative-selection-mediated gene targeting in rice

Directory of Open Access Journals (Sweden)

Zenpei eShimatani

2015-01-01

Full Text Available Gene targeting (GT refers to the designed modification of genomic sequence(s through homologous recombination (HR. GT is a powerful tool both for the study of gene function and for molecular breeding. However, in transformation of higher plants, non-homologous end joining (NHEJ occurs overwhelmingly in somatic cells, masking HR-mediated GT. Positive-negative selection (PNS is an approach for finding HR-mediated GT events because it can eliminate NHEJ effectively by expression of a negative-selection marker gene. In rice—a major crop worldwide—reproducible PNS-mediated GT of endogenous genes has now been successfully achieved. The procedure is based on strong PNS using diphtheria toxin A-fragment as a negative marker, and has succeeded in the directed modification of several endogenous rice genes in various ways. In addition to gene knock-outs and knock-ins, a nucleotide substitution in a target gene was also achieved recently. This review presents a summary of the development of the rice PNS system, highlighting its advantages. Different types of gene modification and gene editing aimed at developing new plant breeding technology (NPBT based on PNS are discussed.

Target Selection and Deselection at the Berkeley StructuralGenomics Center

Energy Technology Data Exchange (ETDEWEB)

Chandonia, John-Marc; Kim, Sung-Hou; Brenner, Steven E.

2005-03-22

At the Berkeley Structural Genomics Center (BSGC), our goalis to obtain a near-complete structural complement of proteins in theminimal organisms Mycoplasma genitalium and M. pneumoniae, two closelyrelated pathogens. Current targets for structure determination have beenselected in six major stages, starting with those predicted to be mosttractable to high throughput study and likely to yield new structuralinformation. We report on the process used to select these proteins, aswell as our target deselection procedure. Target deselection reducesexperimental effort by eliminating targets similar to those recentlysolved by the structural biology community or other centers. We measurethe impact of the 69 structures solved at the BSGC as of July 2004 onstructure prediction coverage of the M. pneumoniae and M. genitaliumproteomes. The number of Mycoplasma proteins for which thefold couldfirst be reliably assigned based on structures solved at the BSGC (24 M.pneumoniae and 21 M. genitalium) is approximately 25 percent of the totalresulting from work at all structural genomics centers and the worldwidestructural biology community (94 M. pneumoniae and 86M. genitalium)during the same period. As the number of structures contributed by theBSGC during that period is less than 1 percent of the total worldwideoutput, the benefits of a focused target selection strategy are apparent.If the structures of all current targets were solved, the percentage ofM. pneumoniae proteins for which folds could be reliably assigned wouldincrease from approximately 57 percent (391 of 687) at present to around80 percent (550 of 687), and the percentage of the proteome that could beaccurately modeled would increase from around 37 percent (254 of 687) toabout 64 percent (438 of 687). In M. genitalium, the percentage of theproteome that could be structurally annotated based on structures of ourremaining targets would rise from 72 percent (348 of 486) to around 76percent (371 of 486), with the

Tumor-targeted nanomedicines for cancer theranostics

Science.gov (United States)

Lammers, Twan; Shi, Yang

2017-01-01

Chemotherapeutic drugs have multiple drawbacks, including severe side effects and suboptimal therapeutic efficacy. Nanomedicines assist in improving the biodistribution and the target accumulation of chemotherapeutic drugs, and are therefore able to enhance the balance between efficacy and toxicity. Multiple different types of nanomedicines have been evaluated over the years, including liposomes, polymer-drug conjugates and polymeric micelles, which rely on strategies such as passive targeting, active targeting and triggered release for improved tumor-directed drug delivery. Based on the notion that tumors and metastases are highly heterogeneous, it is important to integrate imaging properties in nanomedicine formulations in order to enable non-invasive and quantitative assessment of targeting efficiency. By allowing for patient pre-selection, such next generation nanotheranostics are useful for facilitating clinical translation and personalizing nanomedicine treatments. PMID:27865762

Identification of Multiple Cryptococcal Fungicidal Drug Targets by Combined Gene Dosing and Drug Affinity Responsive Target Stability Screening

Directory of Open Access Journals (Sweden)

Yoon-Dong Park

2016-08-01

Full Text Available Cryptococcus neoformans is a pathogenic fungus that is responsible for up to half a million cases of meningitis globally, especially in immunocompromised individuals. Common fungistatic drugs, such as fluconazole, are less toxic for patients but have low efficacy for initial therapy of the disease. Effective therapy against the disease is provided by the fungicidal drug amphotericin B; however, due to its high toxicity and the difficulty in administering its intravenous formulation, it is imperative to find new therapies targeting the fungus. The antiparasitic drug bithionol has been recently identified as having potent fungicidal activity. In this study, we used a combined gene dosing and drug affinity responsive target stability (GD-DARTS screen as well as protein modeling to identify a common drug binding site of bithionol within multiple NAD-dependent dehydrogenase drug targets. This combination genetic and proteomic method thus provides a powerful method for identifying novel fungicidal drug targets for further development.

Selectivity on-target of bromodomain chemical probes by structure-guided medicinal chemistry and chemical biology.

Science.gov (United States)

Galdeano, Carles; Ciulli, Alessio

2016-09-01

Targeting epigenetic proteins is a rapidly growing area for medicinal chemistry and drug discovery. Recent years have seen an explosion of interest in developing small molecules binding to bromodomains, the readers of acetyl-lysine modifications. A plethora of co-crystal structures has motivated focused fragment-based design and optimization programs within both industry and academia. These efforts have yielded several compounds entering the clinic, and many more are increasingly being used as chemical probes to interrogate bromodomain biology. High selectivity of chemical probes is necessary to ensure biological activity is due to an on-target effect. Here, we review the state-of-the-art of bromodomain-targeting compounds, focusing on the structural basis for their on-target selectivity or lack thereof. We also highlight chemical biology approaches to enhance on-target selectivity.

Directional enhancement of selected high-order-harmonics from intense laser irradiated blazed grating targets.

Science.gov (United States)

Zhang, Guobo; Chen, Min; Liu, Feng; Yuan, Xiaohui; Weng, Suming; Zheng, Jun; Ma, Yanyun; Shao, Fuqiu; Sheng, Zhengming; Zhang, Jie

2017-10-02

Relativistically intense laser solid target interaction has been proved to be a promising way to generate high-order harmonics, which can be used to diagnose ultrafast phenomena. However, their emission direction and spectra still lack tunability. Based upon two-dimensional particle-in-cell simulations, we show that directional enhancement of selected high-order-harmonics can be realized using blazed grating targets. Such targets can select harmonics with frequencies being integer times of the grating frequency. Meanwhile, the radiation intensity and emission area of the harmonics are increased. The emission direction is controlled by tailoring the local blazed structure. Theoretical and electron dynamics analysis for harmonics generation, selection and directional enhancement from the interaction between multi-cycle laser and grating target are carried out. These studies will benefit the generation and application of laser plasma-based high order harmonics.

A Hybrid Multiple Criteria Decision Making Model for Supplier Selection

Directory of Open Access Journals (Sweden)

Chung-Min Wu

2013-01-01

Full Text Available The sustainable supplier selection would be the vital part in the management of a sustainable supply chain. In this study, a hybrid multiple criteria decision making (MCDM model is applied to select optimal supplier. The fuzzy Delphi method, which can lead to better criteria selection, is used to modify criteria. Considering the interdependence among the selection criteria, analytic network process (ANP is then used to obtain their weights. To avoid calculation and additional pairwise comparisons of ANP, a technique for order preference by similarity to ideal solution (TOPSIS is used to rank the alternatives. The use of a combination of the fuzzy Delphi method, ANP, and TOPSIS, proposing an MCDM model for supplier selection, and applying these to a real case are the unique features of this study.

Signatures of DNA target selectivity by ETS transcription factors.

Science.gov (United States)

Poon, Gregory M K; Kim, Hye Mi

2017-05-27

The ETS family of transcription factors is a functionally heterogeneous group of gene regulators that share a structurally conserved, eponymous DNA-binding domain. DNA target specificity derives from combinatorial interactions with other proteins as well as intrinsic heterogeneity among ETS domains. Emerging evidence suggests molecular hydration as a fundamental feature that defines the intrinsic heterogeneity in DNA target selection and susceptibility to epigenetic DNA modification. This perspective invokes novel hypotheses in the regulation of ETS proteins in physiologic osmotic stress, their pioneering potential in heterochromatin, and the effects of passive and pharmacologic DNA demethylation on ETS regulation.

Detection-Discrimination Method for Multiple Repeater False Targets Based on Radar Polarization Echoes

Directory of Open Access Journals (Sweden)

Z. W. ZONG

2014-04-01

Full Text Available Multiple repeat false targets (RFTs, created by the digital radio frequency memory (DRFM system of jammer, are widely used in practical to effectively exhaust the limited tracking and discrimination resource of defence radar. In this paper, common characteristic of radar polarization echoes of multiple RFTs is used for target recognition. Based on the echoes from two receiving polarization channels, the instantaneous polarization radio (IPR is defined and its variance is derived by employing Taylor series expansion. A detection-discrimination method is designed based on probability grids. By using the data from microwave anechoic chamber, the detection threshold of the method is confirmed. Theoretical analysis and simulations indicate that the method is valid and feasible. Furthermore, the estimation performance of IPRs of RFTs due to the influence of signal noise ratio (SNR is also covered.

Analyzing the multiple-target-multiple-agent scenario using optimal assignment algorithms

Science.gov (United States)

Kwok, Kwan S.; Driessen, Brian J.; Phillips, Cynthia A.; Tovey, Craig A.

1997-09-01

This work considers the problem of maximum utilization of a set of mobile robots with limited sensor-range capabilities and limited travel distances. The robots are initially in random positions. A set of robots properly guards or covers a region if every point within the region is within the effective sensor range of at least one vehicle. We wish to move the vehicles into surveillance positions so as to guard or cover a region, while minimizing the maximum distance traveled by any vehicle. This problem can be formulated as an assignment problem, in which we must optimally decide which robot to assign to which slot of a desired matrix of grid points. The cost function is the maximum distance traveled by any robot. Assignment problems can be solved very efficiently. Solution times for one hundred robots took only seconds on a silicon graphics crimson workstation. The initial positions of all the robots can be sampled by a central base station and their newly assigned positions communicated back to the robots. Alternatively, the robots can establish their own coordinate system with the origin fixed at one of the robots and orientation determined by the compass bearing of another robot relative to this robot. This paper presents example solutions to the multiple-target-multiple-agent scenario using a matching algorithm. Two separate cases with one hundred agents in each were analyzed using this method. We have found these mobile robot problems to be a very interesting application of network optimization methods, and we expect this to be a fruitful area for future research.

Analyzing the multiple-target-multiple-agent scenario using optimal assignment algorithms

International Nuclear Information System (INIS)

Kwok, K.S.; Driessen, B.J.; Phillips, C.A.; Tovey, C.A.

1997-01-01

This work considers the problem of maximum utilization of a set of mobile robots with limited sensor-range capabilities and limited travel distances. The robots are initially in random positions. A set of robots properly guards or covers a region if every point within the region is within the effective sensor range of at least one vehicle. The authors wish to move the vehicles into surveillance positions so as to guard or cover a region, while minimizing the maximum distance traveled by any vehicle. This problem can be formulated as an assignment problem, in which they must optimally decide which robot to assign to which slot of a desired matrix of grid points. The cost function is the maximum distance traveled by any robot. Assignment problems can be solved very efficiently. Solutions times for one hundred robots took only seconds on a Silicon Graphics Crimson workstation. The initial positions of all the robots can be sampled by a central base station and their newly assigned positions communicated back to the robots. Alternatively, the robots can establish their own coordinate system with the origin fixed at one of the robots and orientation determined by the compass bearing of another robot relative to this robot. This paper presents example solutions to the multiple-target-multiple-agent scenario using a matching algorithm. Two separate cases with one hundred agents in each were analyzed using this method. They have found these mobile robot problems to be a very interesting application of network optimization methods, and they expect this to be a fruitful area for future research

Targeting CD38 with Daratumumab Monotherapy in Multiple Myeloma

DEFF Research Database (Denmark)

Lokhorst, Henk M; Plesner, Torben; Laubach, Jacob P

2015-01-01

BACKGROUND: Multiple myeloma cells uniformly overexpress CD38. We studied daratumumab, a CD38-targeting, human IgG1κ monoclonal antibody, in a phase 1-2 trial involving patients with relapsed myeloma or relapsed myeloma that was refractory to two or more prior lines of therapy. METHODS: In part 1...... interval [CI], 4.2 to 8.1), and 65% (95% CI, 28 to 86) of the patients who had a response did not have progression at 12 months. CONCLUSIONS: Daratumumab monotherapy had a favorable safety profile and encouraging efficacy in patients with heavily pretreated and refractory myeloma. (Funded by Janssen...

Dynamic interactions between visual working memory and saccade target selection

Science.gov (United States)

Schneegans, Sebastian; Spencer, John P.; Schöner, Gregor; Hwang, Seongmin; Hollingworth, Andrew

2014-01-01

Recent psychophysical experiments have shown that working memory for visual surface features interacts with saccadic motor planning, even in tasks where the saccade target is unambiguously specified by spatial cues. Specifically, a match between a memorized color and the color of either the designated target or a distractor stimulus influences saccade target selection, saccade amplitudes, and latencies in a systematic fashion. To elucidate these effects, we present a dynamic neural field model in combination with new experimental data. The model captures the neural processes underlying visual perception, working memory, and saccade planning relevant to the psychophysical experiment. It consists of a low-level visual sensory representation that interacts with two separate pathways: a spatial pathway implementing spatial attention and saccade generation, and a surface feature pathway implementing color working memory and feature attention. Due to bidirectional coupling between visual working memory and feature attention in the model, the working memory content can indirectly exert an effect on perceptual processing in the low-level sensory representation. This in turn biases saccadic movement planning in the spatial pathway, allowing the model to quantitatively reproduce the observed interaction effects. The continuous coupling between representations in the model also implies that modulation should be bidirectional, and model simulations provide specific predictions for complementary effects of saccade target selection on visual working memory. These predictions were empirically confirmed in a new experiment: Memory for a sample color was biased toward the color of a task-irrelevant saccade target object, demonstrating the bidirectional coupling between visual working memory and perceptual processing. PMID:25228628

Dynamic interactions between visual working memory and saccade target selection.

Science.gov (United States)

Schneegans, Sebastian; Spencer, John P; Schöner, Gregor; Hwang, Seongmin; Hollingworth, Andrew

2014-09-16

Recent psychophysical experiments have shown that working memory for visual surface features interacts with saccadic motor planning, even in tasks where the saccade target is unambiguously specified by spatial cues. Specifically, a match between a memorized color and the color of either the designated target or a distractor stimulus influences saccade target selection, saccade amplitudes, and latencies in a systematic fashion. To elucidate these effects, we present a dynamic neural field model in combination with new experimental data. The model captures the neural processes underlying visual perception, working memory, and saccade planning relevant to the psychophysical experiment. It consists of a low-level visual sensory representation that interacts with two separate pathways: a spatial pathway implementing spatial attention and saccade generation, and a surface feature pathway implementing color working memory and feature attention. Due to bidirectional coupling between visual working memory and feature attention in the model, the working memory content can indirectly exert an effect on perceptual processing in the low-level sensory representation. This in turn biases saccadic movement planning in the spatial pathway, allowing the model to quantitatively reproduce the observed interaction effects. The continuous coupling between representations in the model also implies that modulation should be bidirectional, and model simulations provide specific predictions for complementary effects of saccade target selection on visual working memory. These predictions were empirically confirmed in a new experiment: Memory for a sample color was biased toward the color of a task-irrelevant saccade target object, demonstrating the bidirectional coupling between visual working memory and perceptual processing. © 2014 ARVO.

Exploitation of Microdoppler and Multiple Scattering Phenomena for Radar Target Recognition

Science.gov (United States)

2006-08-24

progress on the reserach grant "Exploitation of MicroDoppler and Multiple Scattering Phenomena for Radar Target Recognition" during the period 1...paper describes a methodology of modeling A number of ray-based EM techniques have been interferometric synthetic aperture radar (IFSAR) images...modes including the single present an IFSAR simulation methodology to simulate the antenna transmit mode, the ping-pong mode or the repeat interferogram

Development of targeted radiotherapy systems

International Nuclear Information System (INIS)

Ferro, Guillermina; Villarreal, Jose E.; Garcia, Laura; Tendilla, Jose I.; Paredes, Lydia; Murphy, Consuelo A.; Pedraza, Martha

2001-01-01

Conventional or external beam radiotherapy, has been a viable alternative for cancer treatment. Although this technique is effective, its use is limited if the patient has multiple malignant lesions (metastases). An alternative approach is based on the design of radiopharmaceuticals that, to be administered in the patient, are directed specifically toward the target cell producing a selective radiation delivery. This treatment is known as targeted radiotherapy. We have summarized and discussed some results related to our investigations on the development of targeted radiotherapy systems, including aspects of internal dosimetry

Analysis of multiple-foil XRL targets using x-ray spectroscopy

International Nuclear Information System (INIS)

Wang, J.; Boehly, T.; Yaakobi, B.; Epstein, R.; Meyerhofer, D.; Richardson, M.C.; Russotto, M.; Soures, J.M.

1989-01-01

The multiple-foil collisional excitation x-ray laser targets proposed by LLE have been studied spectroscopically. Using spatially resolved 3d-2p x-ray spectra, the authors compare the temperatures and densities obtained in single- and double-foil geometries. They use the ratio of the dipole transitions to the electric quadrupole transitions in the Neon-like species as a density diagnostic. A non-LTE average-ion atomic physics model is used to describe the ionization process and a relativistic atomic physics code is used for calculation of the level energies, populations, and gain calculations. They support their claims that the double-vfoils provide higher densities and in some cases concave density profiles. The XUV spectra in the range of 20-300 A show the effect of target geometry and incident laser intensity on the lasing lines and the ionization balance

THE SDSS-IV EXTENDED BARYON OSCILLATION SPECTROSCOPIC SURVEY: LUMINOUS RED GALAXY TARGET SELECTION

Energy Technology Data Exchange (ETDEWEB)

Prakash, Abhishek; Licquia, Timothy C.; Newman, Jeffrey A.; Rao, Sandhya M. [PITT PACC, Department of Physics and Astronomy, University of Pittsburgh, Pittsburgh, PA 15260 (United States); Ross, Ashley J. [Center for Cosmology and Astro-Particle Physics, Ohio State University, Columbus, OH 43210 (United States); Myers, Adam D. [Department of Physics and Astronomy, University of Wyoming, Laramie, WY 82071 (United States); Dawson, Kyle S.; Bautista, Julian E.; Brownstein, Joel R. [Department of Physics and Astronomy, University of Utah, Salt Lake City, UT 84112 (United States); Kneib, Jean-Paul [Laboratoire d’Astrophysique, Ecole Polytechnique Fédérale de Lausanne Observatoire de Sauverny, 1290 Versoix (Switzerland); Percival, Will J. [Institute of Cosmology and Gravitation, Dennis Sciama Building, University of Portsmouth, Portsmouth, PO1 3FX (United Kingdom); Comparat, Johan [Instituto de Física Teórica, (UAM/CSIC), Universidad Autónoma de Madrid, Cantoblanco, E-28049 Madrid (Spain); Tinker, Jeremy L. [Center for Cosmology and Particle Physics, Department of Physics, New York University, 4 Washington Place, New York, NY 10003 (United States); Schlegel, David J. [Lawrence Berkeley National Laboratory, One Cyclotron Road, Berkeley, CA 94720 (United States); Tojeiro, Rita [School of Physics and Astronomy, St Andrews, KY16 9SS (United Kingdom); Ho, Shirley; Lang, Dustin [Bruce and Astrid McWilliams Center for Cosmology, Department of Physics, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, PA 15213 (United States); McBride, Cameron K. [Harvard-Smithsonian Center for Astrophysics, Harvard University, 60 Garden Street, Cambridge, MA 02138 (United States); Zhu, Guangtun Ben, E-mail: abp15@pitt.edu [Department of Physics and Astronomy, Johns Hopkins University, Baltimore, MD 21218 (United States); and others

2016-06-01

We describe the algorithm used to select the luminous red galaxy (LRG) sample for the extended Baryon Oscillation Spectroscopic Survey (eBOSS) of the Sloan Digital Sky Survey IV (SDSS-IV) using photometric data from both the SDSS and the Wide-field Infrared Survey Explorer . LRG targets are required to meet a set of color selection criteria and have z -band and i -band MODEL magnitudes z < 19.95 and 19.9 < i < 21.8, respectively. Our algorithm selects roughly 50 LRG targets per square degree, the great majority of which lie in the redshift range 0.6 < z < 1.0 (median redshift 0.71). We demonstrate that our methods are highly effective at eliminating stellar contamination and lower-redshift galaxies. We perform a number of tests using spectroscopic data from SDSS-III/BOSS ancillary programs to determine the redshift reliability of our target selection and its ability to meet the science requirements of eBOSS. The SDSS spectra are of high enough signal-to-noise ratio that at least ∼89% of the target sample yields secure redshift measurements. We also present tests of the uniformity and homogeneity of the sample, demonstrating that it should be clean enough for studies of the large-scale structure of the universe at higher redshifts than SDSS-III/BOSS LRGs reached.

Design, construction, and characterization of high-performance membrane fusion devices with target-selectivity.

Science.gov (United States)

Kashiwada, Ayumi; Yamane, Iori; Tsuboi, Mana; Ando, Shun; Matsuda, Kiyomi

2012-01-31

Membrane fusion proteins such as the hemagglutinin glycoprotein have target recognition and fusion accelerative domains, where some synergistically working elements are essential for target-selective and highly effective native membrane fusion systems. In this work, novel membrane fusion devices bearing such domains were designed and constructed. We selected a phenylboronic acid derivative as a recognition domain for a sugar-like target and a transmembrane-peptide (Leu-Ala sequence) domain interacting with the target membrane, forming a stable hydrophobic α-helix and accelerating the fusion process. Artificial membrane fusion behavior between the synthetic devices in which pilot and target liposomes were incorporated was characterized by lipid-mixing and inner-leaflet lipid-mixing assays. Consequently, the devices bearing both the recognition and transmembrane domains brought about a remarkable increase in the initial rate for the membrane fusion compared with the devices containing the recognition domain alone. In addition, a weakly acidic pH-responsive device was also constructed by replacing three Leu residues in the transmembrane-peptide domain by Glu residues. The presence of Glu residues made the acidic pH-dependent hydrophobic α-helix formation possible as expected. The target-selective liposome-liposome fusion was accelerated in a weakly acidic pH range when the Glu-substituted device was incorporated in pilot liposomes. The use of this pH-responsive device seems to be a potential strategy for novel applications in a liposome-based delivery system. © 2011 American Chemical Society

The optimal hormonal replacement modality selection for multiple organ procurement from brain-dead organ donors

Directory of Open Access Journals (Sweden)

Mi Z

2014-12-01

Full Text Available Zhibao Mi,1 Dimitri Novitzky,2 Joseph F Collins,1 David KC Cooper3 1Cooperative Studies Program Coordinating Center, VA Maryland Health Care Systems, Perry Point, MD, USA; 2Department of Cardiothoracic Surgery, University of South Florida, Tampa, FL, USA; 3Thomas E Starzl Transplantation Institute, University of Pittsburgh, Pittsburgh, PA, USA Abstract: The management of brain-dead organ donors is complex. The use of inotropic agents and replacement of depleted hormones (hormonal replacement therapy is crucial for successful multiple organ procurement, yet the optimal hormonal replacement has not been identified, and the statistical adjustment to determine the best selection is not trivial. Traditional pair-wise comparisons between every pair of treatments, and multiple comparisons to all (MCA, are statistically conservative. Hsu’s multiple comparisons with the best (MCB – adapted from the Dunnett’s multiple comparisons with control (MCC – has been used for selecting the best treatment based on continuous variables. We selected the best hormonal replacement modality for successful multiple organ procurement using a two-step approach. First, we estimated the predicted margins by constructing generalized linear models (GLM or generalized linear mixed models (GLMM, and then we applied the multiple comparison methods to identify the best hormonal replacement modality given that the testing of hormonal replacement modalities is independent. Based on 10-year data from the United Network for Organ Sharing (UNOS, among 16 hormonal replacement modalities, and using the 95% simultaneous confidence intervals, we found that the combination of thyroid hormone, a corticosteroid, antidiuretic hormone, and insulin was the best modality for multiple organ procurement for transplantation. Keywords: best treatment selection, brain-dead organ donors, hormonal replacement, multiple binary endpoints, organ procurement, multiple comparisons

A multicolor panel of TALE-KRAB based transcriptional repressor vectors enabling knockdown of multiple gene targets.

Science.gov (United States)

Zhang, Zhonghui; Wu, Elise; Qian, Zhijian; Wu, Wen-Shu

2014-12-05

Stable and efficient knockdown of multiple gene targets is highly desirable for dissection of molecular pathways. Because it allows sequence-specific DNA binding, transcription activator-like effector (TALE) offers a new genetic perturbation technique that allows for gene-specific repression. Here, we constructed a multicolor lentiviral TALE-Kruppel-associated box (KRAB) expression vector platform that enables knockdown of multiple gene targets. This platform is fully compatible with the Golden Gate TALEN and TAL Effector Kit 2.0, a widely used and efficient method for TALE assembly. We showed that this multicolor TALE-KRAB vector system when combined together with bone marrow transplantation could quickly knock down c-kit and PU.1 genes in hematopoietic stem and progenitor cells of recipient mice. Furthermore, our data demonstrated that this platform simultaneously knocked down both c-Kit and PU.1 genes in the same primary cell populations. Together, our results suggest that this multicolor TALE-KRAB vector platform is a promising and versatile tool for knockdown of multiple gene targets and could greatly facilitate dissection of molecular pathways.

The optimal hormonal replacement modality selection for multiple organ procurement from brain-dead organ donors.

Science.gov (United States)

Mi, Zhibao; Novitzky, Dimitri; Collins, Joseph F; Cooper, David Kc

2015-01-01

The management of brain-dead organ donors is complex. The use of inotropic agents and replacement of depleted hormones (hormonal replacement therapy) is crucial for successful multiple organ procurement, yet the optimal hormonal replacement has not been identified, and the statistical adjustment to determine the best selection is not trivial. Traditional pair-wise comparisons between every pair of treatments, and multiple comparisons to all (MCA), are statistically conservative. Hsu's multiple comparisons with the best (MCB) - adapted from the Dunnett's multiple comparisons with control (MCC) - has been used for selecting the best treatment based on continuous variables. We selected the best hormonal replacement modality for successful multiple organ procurement using a two-step approach. First, we estimated the predicted margins by constructing generalized linear models (GLM) or generalized linear mixed models (GLMM), and then we applied the multiple comparison methods to identify the best hormonal replacement modality given that the testing of hormonal replacement modalities is independent. Based on 10-year data from the United Network for Organ Sharing (UNOS), among 16 hormonal replacement modalities, and using the 95% simultaneous confidence intervals, we found that the combination of thyroid hormone, a corticosteroid, antidiuretic hormone, and insulin was the best modality for multiple organ procurement for transplantation.

Targeting accuracy of single-isocenter intensity-modulated radiosurgery for multiple lesions

Energy Technology Data Exchange (ETDEWEB)

Calvo-Ortega, J.F., E-mail: jfcdrr@yahoo.es; Pozo, M.; Moragues, S.; Casals, J.

2017-07-01

To investigate the targeting accuracy of intensity-modulated SRS (IMRS) plans designed to simultaneously treat multiple brain metastases with a single isocenter. A home-made acrylic phantom able to support a film (EBT3) in its coronal plane was used. The phantom was CT scanned and three coplanar small targets (a central and two peripheral) were outlined in the Eclipse system. Peripheral targets were 6 cm apart from the central one. A reference IMRS plan was designed to simultaneously treat the three targets, but only a single isocenter located at the center of the central target was used. After positioning the phantom on the linac using the room lasers, a CBCT scan was acquired and the reference plan were mapped on it, by placing the planned isocenter at the intersection of the landmarks used in the film showing the linac isocenter. The mapped plan was then recalculated and delivered. The film dose distribution was derived using a cloud computing application ( (www.radiochromic.com)) that uses a triple-channel dosimetry algorithm. Comparison of dose distributions using the gamma index (5%/1 mm) were performed over a 5 × 5 cm{sup 2} region centered over each target. 2D shifts required to get the best gamma passing rates on the peripheral target regions were compared with the reported ones for the central target. The experiment was repeated ten times in different sessions. Average 2D shifts required to achieve optimal gamma passing rates (99%, 97%, 99%) were 0.7 mm (SD: 0.3 mm), 0.8 mm (SD: 0.4 mm) and 0.8 mm (SD: 0.3 mm), for the central and the two peripheral targets, respectively. No statistical differences (p > 0.05) were found for targeting accuracy between the central and the two peripheral targets. The study revealed a targeting accuracy within 1 mm for off-isocenter targets within 6 cm of the linac isocenter, when a single-isocenter IMRS plan is designed.

THE SDSS-III BARYON OSCILLATION SPECTROSCOPIC SURVEY: QUASAR TARGET SELECTION FOR DATA RELEASE NINE

Energy Technology Data Exchange (ETDEWEB)

Ross, Nicholas P.; Kirkpatrick, Jessica A.; Carithers, William C.; Ho, Shirley [Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA 94720 (United States); Myers, Adam D. [Department of Astronomy, MC-221, University of Illinois, 1002 West Green Street, Urbana, IL 61801 (United States); Sheldon, Erin S. [Brookhaven National Laboratory, Blgd 510, Upton, NY 11375 (United States); Yeche, Christophe; Aubourg, Eric [CEA, Centre de Saclay, IRFU, 91191 Gif-sur-Yvette (France); Strauss, Michael A.; Lee, Khee-Gan [Department of Astrophysical Sciences, Princeton University, Princeton, NJ 08544 (United States); Bovy, Jo; Blanton, Michael R.; Hogg, David W. [Center for Cosmology and Particle Physics, New York University, 4 Washington Place, New York, NY 10003 (United States); Richards, Gordon T. [Department of Physics, Drexel University, 3141 Chestnut Street, Philadelphia, PA 19104 (United States); Brandt, W. N. [Department of Astronomy and Astrophysics, The Pennsylvania State University, 525 Davey Laboratory, University Park, PA 16802 (United States); Croft, Rupert A. C. [Bruce and Astrid McWilliams Center for Cosmology, Carnegie Mellon University, Pittsburgh, PA 15213 (United States); Da Silva, Robert [Department of Astronomy and Astrophysics, University of California, Santa Cruz, Santa Cruz, CA 95064 (United States); Dawson, Kyle [Department of Physics and Astronomy, University of Utah, UT (United States); Eisenstein, Daniel J. [Steward Observatory, 933 North Cherry Avenue, Tucson, AZ 85721 (United States); Hennawi, Joseph F., E-mail: npross@lbl.gov [Max-Planck-Institut fuer Astronomie, Konigstuhl 17, 69117 Heidelberg (Germany); and others

2012-03-01

The SDSS-III Baryon Oscillation Spectroscopic Survey (BOSS), a five-year spectroscopic survey of 10,000 deg{sup 2}, achieved first light in late 2009. One of the key goals of BOSS is to measure the signature of baryon acoustic oscillations (BAOs) in the distribution of Ly{alpha} absorption from the spectra of a sample of {approx}150,000 z > 2.2 quasars. Along with measuring the angular diameter distance at z Almost-Equal-To 2.5, BOSS will provide the first direct measurement of the expansion rate of the universe at z > 2. One of the biggest challenges in achieving this goal is an efficient target selection algorithm for quasars in the redshift range 2.2 < z < 3.5, where their colors tend to overlap those of the far more numerous stars. During the first year of the BOSS survey, quasar target selection (QTS) methods were developed and tested to meet the requirement of delivering at least 15 quasars deg{sup -2} in this redshift range, with a goal of 20 out of 40 targets deg{sup -2} allocated to the quasar survey. To achieve these surface densities, the magnitude limit of the quasar targets was set at g {<=} 22.0 or r {<=} 21.85. While detection of the BAO signature in the distribution of Ly{alpha} absorption in quasar spectra does not require a uniform target selection algorithm, many other astrophysical studies do. We have therefore defined a uniformly selected subsample of 20 targets deg{sup -2}, for which the selection efficiency is just over 50% ({approx}10 z > 2.20 quasars deg{sup -2}). This 'CORE' subsample will be fixed for Years Two through Five of the survey. For the remaining 20 targets deg{sup -2}, we will continue to develop improved selection techniques, including the use of additional data sets beyond the Sloan Digital Sky Survey (SDSS) imaging data. In this paper, we describe the evolution and implementation of the BOSS QTS algorithms during the first two years of BOSS operations (through 2011 July), in support of the science investigations

Predictive distractor context facilitates attentional selection of high, but not intermediate and low, salience targets.

Science.gov (United States)

Töllner, Thomas; Conci, Markus; Müller, Hermann J

2015-03-01

It is well established that we can focally attend to a specific region in visual space without shifting our eyes, so as to extract action-relevant sensory information from covertly attended locations. The underlying mechanisms that determine how fast we engage our attentional spotlight in visual-search scenarios, however, remain controversial. One dominant view advocated by perceptual decision-making models holds that the times taken for focal-attentional selection are mediated by an internal template that biases perceptual coding and selection decisions exclusively through target-defining feature coding. This notion directly predicts that search times remain unaffected whether or not participants can anticipate the upcoming distractor context. Here we tested this hypothesis by employing an illusory-figure localization task that required participants to search for an invariant target amongst a variable distractor context, which gradually changed--either randomly or predictably--as a function of distractor-target similarity. We observed a graded decrease in internal focal-attentional selection times--correlated with external behavioral latencies--for distractor contexts of higher relative to lower similarity to the target. Critically, for low but not intermediate and high distractor-target similarity, these context-driven effects were cortically and behaviorally amplified when participants could reliably predict the type of distractors. This interactive pattern demonstrates that search guidance signals can integrate information about distractor, in addition to target, identities to optimize distractor-target competition for focal-attentional selection. © 2014 Wiley Periodicals, Inc.

Model selection with multiple regression on distance matrices leads to incorrect inferences.

Directory of Open Access Journals (Sweden)

Ryan P Franckowiak

Full Text Available In landscape genetics, model selection procedures based on Information Theoretic and Bayesian principles have been used with multiple regression on distance matrices (MRM to test the relationship between multiple vectors of pairwise genetic, geographic, and environmental distance. Using Monte Carlo simulations, we examined the ability of model selection criteria based on Akaike's information criterion (AIC, its small-sample correction (AICc, and the Bayesian information criterion (BIC to reliably rank candidate models when applied with MRM while varying the sample size. The results showed a serious problem: all three criteria exhibit a systematic bias toward selecting unnecessarily complex models containing spurious random variables and erroneously suggest a high level of support for the incorrectly ranked best model. These problems effectively increased with increasing sample size. The failure of AIC, AICc, and BIC was likely driven by the inflated sample size and different sum-of-squares partitioned by MRM, and the resulting effect on delta values. Based on these findings, we strongly discourage the continued application of AIC, AICc, and BIC for model selection with MRM.

Discovery of a selective catalytic p300/CBP inhibitor that targets lineage-specific tumours

Energy Technology Data Exchange (ETDEWEB)

Lasko, Loren M.; Jakob, Clarissa G.; Edalji, Rohinton P.; Qiu, Wei; Montgomery, Debra; Digiammarino, Enrico L.; Hansen, T. Matt; Risi, Roberto M.; Frey, Robin; Manaves, Vlasios; Shaw, Bailin; Algire, Mikkel; Hessler, Paul; Lam, Lloyd T.; Uziel, Tamar; Faivre, Emily; Ferguson, Debra; Buchanan, Fritz G.; Martin, Ruth L.; Torrent, Maricel; Chiang, Gary G.; Karukurichi, Kannan; Langston, J. William; Weinert, Brian T.; Choudhary, Chunaram; de Vries, Peter; Van Drie, John H.; McElligott, David; Kesicki, Ed; Marmorstein, Ronen; Sun, Chaohong; Cole, Philip A.; Rosenberg, Saul H.; Michaelides, Michael R.; Lai, Albert; Bromberg, Kenneth D. (AbbVie); (UCopenhagen); (Petra Pharma); (UPENN); (JHU); (Van Drie); (Faraday)

2017-09-27

The dynamic and reversible acetylation of proteins, catalysed by histone acetyltransferases (HATs) and histone deacetylases (HDACs), is a major epigenetic regulatory mechanism of gene transcription1 and is associated with multiple diseases. Histone deacetylase inhibitors are currently approved to treat certain cancers, but progress on the development of drug-like histone actyltransferase inhibitors has lagged behind2. The histone acetyltransferase paralogues p300 and CREB-binding protein (CBP) are key transcriptional co-activators that are essential for a multitude of cellular processes, and have also been implicated in human pathological conditions (including cancer3). Current inhibitors of the p300 and CBP histone acetyltransferase domains, including natural products4, bi-substrate analogues5 and the widely used small molecule C6466,7, lack potency or selectivity. Here, we describe A-485, a potent, selective and drug-like catalytic inhibitor of p300 and CBP. We present a high resolution (1.95 Å) co-crystal structure of a small molecule bound to the catalytic active site of p300 and demonstrate that A-485 competes with acetyl coenzyme A (acetyl-CoA). A-485 selectively inhibited proliferation in lineage-specific tumour types, including several haematological malignancies and androgen receptor-positive prostate cancer. A-485 inhibited the androgen receptor transcriptional program in both androgen-sensitive and castration-resistant prostate cancer and inhibited tumour growth in a castration-resistant xenograft model. These results demonstrate the feasibility of using small molecule inhibitors to selectively target the catalytic activity of histone acetyltransferases, which may provide effective treatments for transcriptional activator-driven malignancies and diseases.

Targets of balancing selection in the human genome

DEFF Research Database (Denmark)

Andrés, Aida M; Hubisz, Melissa J; Indap, Amit

2009-01-01

Balancing selection is potentially an important biological force for maintaining advantageous genetic diversity in populations, including variation that is responsible for long-term adaptation to the environment. By serving as a means to maintain genetic variation, it may be particularly relevant...... to maintaining phenotypic variation in natural populations. Nevertheless, its prevalence and specific targets in the human genome remain largely unknown. We have analyzed the patterns of diversity and divergence of 13,400 genes in two human populations using an unbiased single-nucleotide polymorphism data set......, a genome-wide approach, and a method that incorporates demography in neutrality tests. We identified an unbiased catalog of genes with signatures of long-term balancing selection, which includes immunity genes as well as genes encoding keratins and membrane channels; the catalog also shows enrichment...

Auditory Stream Segregation Improves Infants' Selective Attention to Target Tones Amid Distracters

Science.gov (United States)

Smith, Nicholas A.; Trainor, Laurel J.

2011-01-01

This study examined the role of auditory stream segregation in the selective attention to target tones in infancy. Using a task adapted from Bregman and Rudnicky's 1975 study and implemented in a conditioned head-turn procedure, infant and adult listeners had to discriminate the temporal order of 2,200 and 2,400 Hz target tones presented alone,…

Occurrence Prospect of HDR and Target Site Selection Study in Southeastern of China

Science.gov (United States)

Lin, W.; Gan, H.

2017-12-01

Hot dry rock (HDR) geothermal resource is one of the most important clean energy in future. Site selection a HDR resource is a fundamental work to explore the HDR resources. This paper compiled all the HDR development projects domestic and abroad, and summarized the location of HDR geothermal geological index. After comparing the geological background of HDR in the southeast coastal area of China, Yangjiang Xinzhou in Guangdong province, Leizhou Peninsula area, Lingshui in Hainan province and Huangshadong in Guangzhou were selected from some key potential target area along the southeast coast of China. Deep geothermal field model of the study area is established based on the comprehensive analysis of the target area of deep geothermal geological background and deep thermal anomalies. This paper also compared the hot dry rock resources target locations, and proposed suggestions for the priority exploration target area and exploration scheme.

The effects of interventions targeting multiple health behaviors on smoking cessation outcomes: a rapid realist review protocol.

Science.gov (United States)

Minian, Nadia; deRuiter, Wayne K; Lingam, Mathangee; Corrin, Tricia; Dragonetti, Rosa; Manson, Heather; Taylor, Valerie H; Zawertailo, Laurie; Ebnahmady, Arezoo; Melamed, Osnat C; Rodak, Terri; Hahn, Margaret; Selby, Peter

2018-03-01

Health behaviors directly impact the health of individuals, and populations. Since individuals tend to engage in multiple unhealthy behaviors such as smoking, excessive alcohol use, physical inactivity, and eating an unhealthy diet simultaneously, many large community-based interventions have been implemented to reduce the burden of disease through the modification of multiple health behaviors. Smoking cessation can be particularly challenging as the odds of becoming dependent on nicotine increase with every unhealthy behavior a smoker exhibits. This paper presents a protocol for a rapid realist review which aims to identify factors associated with effectively changing tobacco use and target two or more additional unhealthy behaviors. An electronic literature search will be conducted using the following bibliographic databases: MEDLINE, Embase, PsycINFO, Cumulative Index to Nursing and Allied Health Literature (CINAHL), The Cochrane Library, Social Science Abstracts, Social Work Abstracts, and Web of Science. Two reviewers will screen titles and abstracts for relevant research, and the selected full papers will be used to extract data and assess the quality of evidence. Throughout this process, the rapid realist approach proposed by Saul et al., 2013 will be used to refine our initial program theory and identify contextual factors and mechanisms that are associated with successful multiple health behavior change. This review will provide evidence-based research on the context and mechanisms that may drive the success or failure of interventions designed to support multiple health behavior change. This information will be used to guide curriculum and program development for a government funded project on improving smoking cessation by addressing multiple health behaviors in people in Canada. PROSPERO CRD42017064430.

The spatially global control of attentional target selection in visual search

OpenAIRE

Berggren, Nick; Jenkins, M.; McCants, C.W.; Eimer, Martin

2017-01-01

Glyn Humphreys and his co-workers have made numerous important theoretical and empirical contributions to research on visual search. They have introduced the concept of attentional target templates and investigated the nature of these templates and how they are involved in the control of search performance. In the experiments reported here, we investigated whether feature-specific search template for particular colours can guide target selection independently for different regions of visual s...

Competition between color and luminance for target selection in smooth pursuit and saccadic eye movements.

Science.gov (United States)

Spering, Miriam; Montagnini, Anna; Gegenfurtner, Karl R

2008-11-24

Visual processing of color and luminance for smooth pursuit and saccadic eye movements was investigated using a target selection paradigm. In two experiments, stimuli were varied along the dimensions color and luminance, and selection of the more salient target was compared in pursuit and saccades. Initial pursuit was biased in the direction of the luminance component whereas saccades showed a relative preference for color. An early pursuit response toward luminance was often reversed to color by a later saccade. Observers' perceptual judgments of stimulus salience, obtained in two control experiments, were clearly biased toward luminance. This choice bias in perceptual data implies that the initial short-latency pursuit response agrees with perceptual judgments. In contrast, saccades, which have a longer latency than pursuit, do not seem to follow the perceptual judgment of salience but instead show a stronger relative preference for color. These substantial differences in target selection imply that target selection processes for pursuit and saccadic eye movements use distinctly different weights for color and luminance stimuli.

Interacting Multiple Model (IMM Fifth-Degree Spherical Simplex-Radial Cubature Kalman Filter for Maneuvering Target Tracking

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Hua Liu

2017-06-01

Full Text Available For improving the tracking accuracy and model switching speed of maneuvering target tracking in nonlinear systems, a new algorithm named the interacting multiple model fifth-degree spherical simplex-radial cubature Kalman filter (IMM5thSSRCKF is proposed in this paper. The new algorithm is a combination of the interacting multiple model (IMM filter and the fifth-degree spherical simplex-radial cubature Kalman filter (5thSSRCKF. The proposed algorithm makes use of Markov process to describe the switching probability among the models, and uses 5thSSRCKF to deal with the state estimation of each model. The 5thSSRCKF is an improved filter algorithm, which utilizes the fifth-degree spherical simplex-radial rule to improve the filtering accuracy. Finally, the tracking performance of the IMM5thSSRCKF is evaluated by simulation in a typical maneuvering target tracking scenario. Simulation results show that the proposed algorithm has better tracking performance and quicker model switching speed when disposing maneuver models compared with the interacting multiple model unscented Kalman filter (IMMUKF, the interacting multiple model cubature Kalman filter (IMMCKF and the interacting multiple model fifth-degree cubature Kalman filter (IMM5thCKF.

Interacting Multiple Model (IMM) Fifth-Degree Spherical Simplex-Radial Cubature Kalman Filter for Maneuvering Target Tracking.

Science.gov (United States)

Liu, Hua; Wu, Wen

2017-06-13

For improving the tracking accuracy and model switching speed of maneuvering target tracking in nonlinear systems, a new algorithm named the interacting multiple model fifth-degree spherical simplex-radial cubature Kalman filter (IMM5thSSRCKF) is proposed in this paper. The new algorithm is a combination of the interacting multiple model (IMM) filter and the fifth-degree spherical simplex-radial cubature Kalman filter (5thSSRCKF). The proposed algorithm makes use of Markov process to describe the switching probability among the models, and uses 5thSSRCKF to deal with the state estimation of each model. The 5thSSRCKF is an improved filter algorithm, which utilizes the fifth-degree spherical simplex-radial rule to improve the filtering accuracy. Finally, the tracking performance of the IMM5thSSRCKF is evaluated by simulation in a typical maneuvering target tracking scenario. Simulation results show that the proposed algorithm has better tracking performance and quicker model switching speed when disposing maneuver models compared with the interacting multiple model unscented Kalman filter (IMMUKF), the interacting multiple model cubature Kalman filter (IMMCKF) and the interacting multiple model fifth-degree cubature Kalman filter (IMM5thCKF).

The mathematics of random mutation and natural selection for multiple simultaneous selection pressures and the evolution of antimicrobial drug resistance.

Science.gov (United States)

Kleinman, Alan

2016-12-20

The random mutation and natural selection phenomenon act in a mathematically predictable behavior, which when understood leads to approaches to reduce and prevent the failure of the use of these selection pressures when treating infections and cancers. The underlying principle to impair the random mutation and natural selection phenomenon is to use combination therapy, which forces the population to evolve to multiple selection pressures simultaneously that invoke the multiplication rule of probabilities simultaneously as well. Recently, it has been seen that combination therapy for the treatment of malaria has failed to prevent the emergence of drug-resistant variants. Using this empirical example and the principles of probability theory, the derivation of the equations describing this treatment failure is carried out. These equations give guidance as to how to use combination therapy for the treatment of cancers and infectious diseases and prevent the emergence of drug resistance. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

Locations of serial reach targets are coded in multiple reference frames.

Science.gov (United States)

Thompson, Aidan A; Henriques, Denise Y P

2010-12-01

an egocentric frame anchored to the eye. However, the amount of change in this distance was smaller than predicted by a pure eye-fixed representation, suggesting that relative positions of the targets or allocentric coding was also used in sequential reach planning. The spatial coding and updating of sequential reach target locations seems to rely on a combined weighting of multiple reference frames, with one of them centered on the eye. Copyright © 2010 Elsevier Ltd. All rights reserved.

Impact of high-risk conjunctions on Active Debris Removal target selection

OpenAIRE

Lidtke, Aleksander A.; Lewis, Hugh G.; Armellin, Roberto

2015-01-01

All rights reserved.Space debris simulations show that if current space launches continue unchanged, spacecraft operations might become difficult in the congested space environment. It has been suggested that Active Debris Removal (ADR) might be necessary in order to prevent such a situation. Selection of objects to be targeted by ADR is considered important because removal of non-relevant objects will unnecessarily increase the cost of ADR. One of the factors to be used in this ADR target se...

M402, a novel heparan sulfate mimetic, targets multiple pathways implicated in tumor progression and metastasis.

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He Zhou

Full Text Available Heparan sulfate proteoglycans (HSPGs play a key role in shaping the tumor microenvironment by presenting growth factors, cytokines, and other soluble factors that are critical for host cell recruitment and activation, as well as promoting tumor progression, metastasis, and survival. M402 is a rationally engineered, non-cytotoxic heparan sulfate (HS mimetic, designed to inhibit multiple factors implicated in tumor-host cell interactions, including VEGF, FGF2, SDF-1α, P-selectin, and heparanase. A single s.c. dose of M402 effectively inhibited seeding of B16F10 murine melanoma cells to the lung in an experimental metastasis model. Fluorescent-labeled M402 demonstrated selective accumulation in the primary tumor. Immunohistological analyses of the primary tumor revealed a decrease in microvessel density in M402 treated animals, suggesting anti-angiogenesis to be one of the mechanisms involved in-vivo. M402 treatment also normalized circulating levels of myeloid derived suppressor cells in tumor bearing mice. Chronic administration of M402, alone or in combination with cisplatin or docetaxel, inhibited spontaneous metastasis and prolonged survival in an orthotopic 4T1 murine mammary carcinoma model. These data demonstrate that modulating HSPG biology represents a novel approach to target multiple factors involved in tumor progression and metastasis.

Molecular evolution of pentatricopeptide repeat genes reveals truncation in species lacking an editing target and structural domains under distinct selective pressures

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Hayes Michael L

2012-05-01

Full Text Available Abstract Background Pentatricopeptide repeat (PPR proteins are required for numerous RNA processing events in plant organelles including C-to-U editing, splicing, stabilization, and cleavage. Fifteen PPR proteins are known to be required for RNA editing at 21 sites in Arabidopsis chloroplasts, and belong to the PLS class of PPR proteins. In this study, we investigate the co-evolution of four PPR genes (CRR4, CRR21, CLB19, and OTP82 and their six editing targets in Brassicaceae species. PPR genes are composed of approximately 10 to 20 tandem repeats and each repeat has two α-helical regions, helix A and helix B, that are separated by short coil regions. Each repeat and structural feature was examined to determine the selective pressures on these regions. Results All of the PPR genes examined are under strong negative selection. Multiple independent losses of editing site targets are observed for both CRR21 and OTP82. In several species lacking the known editing target for CRR21, PPR genes are truncated near the 17th PPR repeat. The coding sequences of the truncated CRR21 genes are maintained under strong negative selection; however, the 3’ UTR sequences beyond the truncation site have substantially diverged. Phylogenetic analyses of four PPR genes show that sequences corresponding to helix A are high compared to helix B sequences. Differential evolutionary selection of helix A versus helix B is observed in both plant and mammalian PPR genes. Conclusion PPR genes and their cognate editing sites are mutually constrained in evolution. Editing sites are frequently lost by replacement of an edited C with a genomic T. After the loss of an editing site, the PPR genes are observed with three outcomes: first, few changes are detected in some cases; second, the PPR gene is present as a pseudogene; and third, the PPR gene is present but truncated in the C-terminal region. The retention of truncated forms of CRR21 that are maintained under strong negative

Molecular evolution of pentatricopeptide repeat genes reveals truncation in species lacking an editing target and structural domains under distinct selective pressures.

Science.gov (United States)

Hayes, Michael L; Giang, Karolyn; Mulligan, R Michael

2012-05-14

Pentatricopeptide repeat (PPR) proteins are required for numerous RNA processing events in plant organelles including C-to-U editing, splicing, stabilization, and cleavage. Fifteen PPR proteins are known to be required for RNA editing at 21 sites in Arabidopsis chloroplasts, and belong to the PLS class of PPR proteins. In this study, we investigate the co-evolution of four PPR genes (CRR4, CRR21, CLB19, and OTP82) and their six editing targets in Brassicaceae species. PPR genes are composed of approximately 10 to 20 tandem repeats and each repeat has two α-helical regions, helix A and helix B, that are separated by short coil regions. Each repeat and structural feature was examined to determine the selective pressures on these regions. All of the PPR genes examined are under strong negative selection. Multiple independent losses of editing site targets are observed for both CRR21 and OTP82. In several species lacking the known editing target for CRR21, PPR genes are truncated near the 17th PPR repeat. The coding sequences of the truncated CRR21 genes are maintained under strong negative selection; however, the 3' UTR sequences beyond the truncation site have substantially diverged. Phylogenetic analyses of four PPR genes show that sequences corresponding to helix A are high compared to helix B sequences. Differential evolutionary selection of helix A versus helix B is observed in both plant and mammalian PPR genes. PPR genes and their cognate editing sites are mutually constrained in evolution. Editing sites are frequently lost by replacement of an edited C with a genomic T. After the loss of an editing site, the PPR genes are observed with three outcomes: first, few changes are detected in some cases; second, the PPR gene is present as a pseudogene; and third, the PPR gene is present but truncated in the C-terminal region. The retention of truncated forms of CRR21 that are maintained under strong negative selection even in the absence of an editing site target

TargetMine, an integrated data warehouse for candidate gene prioritisation and target discovery.

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Yi-An Chen

Full Text Available Prioritising candidate genes for further experimental characterisation is a non-trivial challenge in drug discovery and biomedical research in general. An integrated approach that combines results from multiple data types is best suited for optimal target selection. We developed TargetMine, a data warehouse for efficient target prioritisation. TargetMine utilises the InterMine framework, with new data models such as protein-DNA interactions integrated in a novel way. It enables complicated searches that are difficult to perform with existing tools and it also offers integration of custom annotations and in-house experimental data. We proposed an objective protocol for target prioritisation using TargetMine and set up a benchmarking procedure to evaluate its performance. The results show that the protocol can identify known disease-associated genes with high precision and coverage. A demonstration version of TargetMine is available at http://targetmine.nibio.go.jp/.

In vitro Selection and Interaction Studies of a DNA Aptamer Targeting Protein A.

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Regina Stoltenburg

Full Text Available A new DNA aptamer targeting Protein A is presented. The aptamer was selected by use of the FluMag-SELEX procedure. The SELEX technology (Systematic Evolution of Ligands by EXponential enrichment is widely applied as an in vitro selection and amplification method to generate target-specific aptamers and exists in various modified variants. FluMag-SELEX is one of them and is characterized by the use of magnetic beads for target immobilization and fluorescently labeled oligonucleotides for monitoring the aptamer selection progress. Structural investigations and sequence truncation experiments of the selected aptamer for Protein A led to the conclusion, that a stem-loop structure at its 5'-end including the 5'-primer binding site is essential for aptamer-target binding. Extensive interaction analyses between aptamer and Protein A were performed by methods like surface plasmon resonance, MicroScale Thermophoresis and bead-based binding assays using fluorescence measurements. The binding of the aptamer to its target was thus investigated in assays with immobilization of one of the binding partners each, and with both binding partners in solution. Affinity constants were determined in the low micromolar to submicromolar range, increasing to the nanomolar range under the assumption of avidity. Protein A provides more than one binding site for the aptamer, which may overlap with the known binding sites for immunoglobulins. The aptamer binds specifically to both native and recombinant Protein A, but not to other immunoglobulin-binding proteins like Protein G and L. Cross specificity to other proteins was not found. The application of the aptamer is directed to Protein A detection or affinity purification. Moreover, whole cells of Staphylococcus aureus, presenting Protein A on the cell surface, could also be bound by the aptamer.

In vitro Selection and Interaction Studies of a DNA Aptamer Targeting Protein A.

Science.gov (United States)

Stoltenburg, Regina; Schubert, Thomas; Strehlitz, Beate

2015-01-01

A new DNA aptamer targeting Protein A is presented. The aptamer was selected by use of the FluMag-SELEX procedure. The SELEX technology (Systematic Evolution of Ligands by EXponential enrichment) is widely applied as an in vitro selection and amplification method to generate target-specific aptamers and exists in various modified variants. FluMag-SELEX is one of them and is characterized by the use of magnetic beads for target immobilization and fluorescently labeled oligonucleotides for monitoring the aptamer selection progress. Structural investigations and sequence truncation experiments of the selected aptamer for Protein A led to the conclusion, that a stem-loop structure at its 5'-end including the 5'-primer binding site is essential for aptamer-target binding. Extensive interaction analyses between aptamer and Protein A were performed by methods like surface plasmon resonance, MicroScale Thermophoresis and bead-based binding assays using fluorescence measurements. The binding of the aptamer to its target was thus investigated in assays with immobilization of one of the binding partners each, and with both binding partners in solution. Affinity constants were determined in the low micromolar to submicromolar range, increasing to the nanomolar range under the assumption of avidity. Protein A provides more than one binding site for the aptamer, which may overlap with the known binding sites for immunoglobulins. The aptamer binds specifically to both native and recombinant Protein A, but not to other immunoglobulin-binding proteins like Protein G and L. Cross specificity to other proteins was not found. The application of the aptamer is directed to Protein A detection or affinity purification. Moreover, whole cells of Staphylococcus aureus, presenting Protein A on the cell surface, could also be bound by the aptamer.

Multiple Target Laser Designator (MTLD)

Science.gov (United States)

2007-03-01

Optimized Liquid Crystal Scanning Element Optimize the Nonimaging Predictive Algorithm for Target Ranging, Tracking, and Position Estimation...commercial potential. 3.0 PROGRESS THIS QUARTER 3.1 Optimization of Nonimaging Holographic Antenna for Target Tracking and Position Estimation (Task 6) In

Retroviral DNA integration: viral and cellular determinants of target-site selection.

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Mary K Lewinski

2006-06-01

Full Text Available Retroviruses differ in their preferences for sites for viral DNA integration in the chromosomes of infected cells. Human immunodeficiency virus (HIV integrates preferentially within active transcription units, whereas murine leukemia virus (MLV integrates preferentially near transcription start sites and CpG islands. We investigated the viral determinants of integration-site selection using HIV chimeras with MLV genes substituted for their HIV counterparts. We found that transferring the MLV integrase (IN coding region into HIV (to make HIVmIN caused the hybrid to integrate with a specificity close to that of MLV. Addition of MLV gag (to make HIVmGagmIN further increased the similarity of target-site selection to that of MLV. A chimeric virus with MLV Gag only (HIVmGag displayed targeting preferences different from that of both HIV and MLV, further implicating Gag proteins in targeting as well as IN. We also report a genome-wide analysis indicating that MLV, but not HIV, favors integration near DNase I-hypersensitive sites (i.e., +/- 1 kb, and that HIVmIN and HIVmGagmIN also favored integration near these features. These findings reveal that IN is the principal viral determinant of integration specificity; they also reveal a new role for Gag-derived proteins, and strengthen models for integration targeting based on tethering of viral IN proteins to host proteins.

Robust Ground Target Detection by SAR and IR Sensor Fusion Using Adaboost-Based Feature Selection

Science.gov (United States)

Kim, Sungho; Song, Woo-Jin; Kim, So-Hyun

2016-01-01

Long-range ground targets are difficult to detect in a noisy cluttered environment using either synthetic aperture radar (SAR) images or infrared (IR) images. SAR-based detectors can provide a high detection rate with a high false alarm rate to background scatter noise. IR-based approaches can detect hot targets but are affected strongly by the weather conditions. This paper proposes a novel target detection method by decision-level SAR and IR fusion using an Adaboost-based machine learning scheme to achieve a high detection rate and low false alarm rate. The proposed method consists of individual detection, registration, and fusion architecture. This paper presents a single framework of a SAR and IR target detection method using modified Boolean map visual theory (modBMVT) and feature-selection based fusion. Previous methods applied different algorithms to detect SAR and IR targets because of the different physical image characteristics. One method that is optimized for IR target detection produces unsuccessful results in SAR target detection. This study examined the image characteristics and proposed a unified SAR and IR target detection method by inserting a median local average filter (MLAF, pre-filter) and an asymmetric morphological closing filter (AMCF, post-filter) into the BMVT. The original BMVT was optimized to detect small infrared targets. The proposed modBMVT can remove the thermal and scatter noise by the MLAF and detect extended targets by attaching the AMCF after the BMVT. Heterogeneous SAR and IR images were registered automatically using the proposed RANdom SAmple Region Consensus (RANSARC)-based homography optimization after a brute-force correspondence search using the detected target centers and regions. The final targets were detected by feature-selection based sensor fusion using Adaboost. The proposed method showed good SAR and IR target detection performance through feature selection-based decision fusion on a synthetic database generated

Robust Ground Target Detection by SAR and IR Sensor Fusion Using Adaboost-Based Feature Selection

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Sungho Kim

2016-07-01

Full Text Available Long-range ground targets are difficult to detect in a noisy cluttered environment using either synthetic aperture radar (SAR images or infrared (IR images. SAR-based detectors can provide a high detection rate with a high false alarm rate to background scatter noise. IR-based approaches can detect hot targets but are affected strongly by the weather conditions. This paper proposes a novel target detection method by decision-level SAR and IR fusion using an Adaboost-based machine learning scheme to achieve a high detection rate and low false alarm rate. The proposed method consists of individual detection, registration, and fusion architecture. This paper presents a single framework of a SAR and IR target detection method using modified Boolean map visual theory (modBMVT and feature-selection based fusion. Previous methods applied different algorithms to detect SAR and IR targets because of the different physical image characteristics. One method that is optimized for IR target detection produces unsuccessful results in SAR target detection. This study examined the image characteristics and proposed a unified SAR and IR target detection method by inserting a median local average filter (MLAF, pre-filter and an asymmetric morphological closing filter (AMCF, post-filter into the BMVT. The original BMVT was optimized to detect small infrared targets. The proposed modBMVT can remove the thermal and scatter noise by the MLAF and detect extended targets by attaching the AMCF after the BMVT. Heterogeneous SAR and IR images were registered automatically using the proposed RANdom SAmple Region Consensus (RANSARC-based homography optimization after a brute-force correspondence search using the detected target centers and regions. The final targets were detected by feature-selection based sensor fusion using Adaboost. The proposed method showed good SAR and IR target detection performance through feature selection-based decision fusion on a synthetic

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

Science.gov (United States)

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.

In silico tools used for compound selection during target-based drug discovery and development.

Science.gov (United States)

Caldwell, Gary W

2015-01-01

The target-based drug discovery process, including target selection, screening, hit-to-lead (H2L) and lead optimization stage gates, is the most common approach used in drug development. The full integration of in vitro and/or in vivo data with in silico tools across the entire process would be beneficial to R&D productivity by developing effective selection criteria and drug-design optimization strategies. This review focuses on understanding the impact and extent in the past 5 years of in silico tools on the various stage gates of the target-based drug discovery approach. There are a large number of in silico tools available for establishing selection criteria and drug-design optimization strategies in the target-based approach. However, the inconsistent use of in vitro and/or in vivo data integrated with predictive in silico multiparameter models throughout the process is contributing to R&D productivity issues. In particular, the lack of reliable in silico tools at the H2L stage gate is contributing to the suboptimal selection of viable lead compounds. It is suggested that further development of in silico multiparameter models and organizing biologists, medicinal and computational chemists into one team with a single accountable objective to expand the utilization of in silico tools in all phases of drug discovery would improve R&D productivity.

The selective Aurora B kinase inhibitor AZD1152 is a potential new treatment for multiple myeloma.

Science.gov (United States)

Evans, Robert P; Naber, Claudia; Steffler, Tara; Checkland, Tamara; Maxwell, Christopher A; Keats, Jonathan J; Belch, Andrew R; Pilarski, Linda M; Lai, Raymond; Reiman, Tony

2008-02-01

Aurora kinases are potential targets for cancer therapy. Previous studies have validated Aurora kinase A as a therapeutic target in multiple myeloma (MM), and have demonstrated in vitro anti-myeloma effects of small molecule Aurora kinase inhibitors that inhibit both Aurora A and B. This study demonstrated that Aurora B kinase was strongly expressed in myeloma cell lines and primary plasma cells. The selective Aurora B inhibitor AZD1152-induced apoptotic death in myeloma cell lines at nanomolar concentrations, with a cell cycle phenotype consistent with that reported previously for Aurora B inhibition. In some cases, AZD1152 in combination with dexamethasone showed increased anti-myeloma activity compared with the use of either agent alone. AZD1152 was active against sorted CD138(+) BM plasma cells from myeloma patients but also, as expected, was toxic to CD138(-) marrow cells from the same patients. In a murine myeloma xenograft model, AZD1152-inhibited tumour growth at well-tolerated doses and induced cell death in established tumours, with associated mild, transient leucopenia. AZD1152 shows promise in these preclinical studies as a novel treatment for MM.

Low power multiple shell fusion targets for use with electron and ion beams

International Nuclear Information System (INIS)

Lindl, J.D.; Bangerter, R.O.

1975-01-01

Use of double shell targets with a separate low Z, low density ablator at large radius for the outer shell, reduces the focusing and power requirements while maintaining reasonable aspect ratios. A high Z, high density pusher shell is placed at a much smaller radius in order to obtain an aspect ratio small enough to protect against fluid instability. Velocity multiplication between these shells further lowers the power requirements. Careful tuning of the power profile and intershell density results in a low entropy implosion which allows breakeven at low powers. Ion beams appear to be a promising power source and breakeven at 10-20 Terrawatts with 10 MeV alpha particles appears feasible. Predicted performance of targets with various energy sources is shown and comparison is made with single shell targets

Target assignment for security officers to K targets (TASK)

International Nuclear Information System (INIS)

Rowland, J.R.; Shelton, K.W.; Stunkel, C.B.

1983-02-01

A probabilistic algorithm is developed to provide an optimal Target Assignment for Security officers to K targets (TASK) using a maximin criterion. Under the assumption of only a limited number (N) of security officers, the TASK computer model determines deployment assignments which maximize the system protection against sabotage by an adversary who may select any link in the system, including the weakest, for the point of attack. Applying the TASK model to a hypothetical nuclear facility containing a nine-level building reveals that aggregate targets covering multiple vital areas should be utilized to reduce the number of possible target assignments to a value equal to or only slightly larger than N. The increased probability that a given aggregate target is covered by one or more security officers offsets the slight decrease in interruption probability due to its occurring earlier in the adversary's path. In brief, the TASK model determines the optimal maximin deployment strategy for limited numbers of security officers and calculates a quantitative measure of the resulting system protection

Selection of multiple cued items is possible during visual short-term memory maintenance.

Science.gov (United States)

Matsukura, Michi; Vecera, Shaun P

2015-07-01

Recent neuroimaging studies suggest that maintenance of a selected object feature held in visual short-term/working memory (VSTM/VWM) is supported by the same neural mechanisms that encode the sensory information. If VSTM operates by retaining "reasonable copies" of scenes constructed during sensory processing (Serences, Ester, Vogel, & Awh, 2009, p. 207, the sensory recruitment hypothesis), then attention should be able to select multiple items represented in VSTM as long as the number of these attended items does not exceed the typical VSTM capacity. It is well known that attention can select at least two noncontiguous locations at the same time during sensory processing. However, empirical reports from the studies that examined this possibility are inconsistent. In the present study, we demonstrate that (1) attention can indeed select more than a single item during VSTM maintenance when observers are asked to recognize a set of items in the manner that these items were originally attended, and (2) attention can select multiple cued items regardless of whether these items are perceptually organized into a single group (contiguous locations) or not (noncontiguous locations). The results also replicate and extend the recent finding that selective attention that operates during VSTM maintenance is sensitive to the observers' goal and motivation to use the cueing information.

Group Targets Tracking Using Multiple Models GGIW-CPHD Based on Best-Fitting Gaussian Approximation and Strong Tracking Filter

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Yun Wang

2016-01-01

Full Text Available Gamma Gaussian inverse Wishart cardinalized probability hypothesis density (GGIW-CPHD algorithm was always used to track group targets in the presence of cluttered measurements and missing detections. A multiple models GGIW-CPHD algorithm based on best-fitting Gaussian approximation method (BFG and strong tracking filter (STF is proposed aiming at the defect that the tracking error of GGIW-CPHD algorithm will increase when the group targets are maneuvering. The best-fitting Gaussian approximation method is proposed to implement the fusion of multiple models using the strong tracking filter to correct the predicted covariance matrix of the GGIW component. The corresponding likelihood functions are deduced to update the probability of multiple tracking models. From the simulation results we can see that the proposed tracking algorithm MM-GGIW-CPHD can effectively deal with the combination/spawning of groups and the tracking error of group targets in the maneuvering stage is decreased.

Construction and applications of exon-trapping gene-targeting vectors with a novel strategy for negative selection.

Science.gov (United States)

Saito, Shinta; Ura, Kiyoe; Kodama, Miho; Adachi, Noritaka

2015-06-30

Targeted gene modification by homologous recombination provides a powerful tool for studying gene function in cells and animals. In higher eukaryotes, non-homologous integration of targeting vectors occurs several orders of magnitude more frequently than does targeted integration, making the gene-targeting technology highly inefficient. For this reason, negative-selection strategies have been employed to reduce the number of drug-resistant clones associated with non-homologous vector integration, particularly when artificial nucleases to introduce a DNA break at the target site are unavailable or undesirable. As such, an exon-trap strategy using a promoterless drug-resistance marker gene provides an effective way to counterselect non-homologous integrants. However, constructing exon-trapping targeting vectors has been a time-consuming and complicated process. By virtue of highly efficient att-mediated recombination, we successfully developed a simple and rapid method to construct plasmid-based vectors that allow for exon-trapping gene targeting. These exon-trap vectors were useful in obtaining correctly targeted clones in mouse embryonic stem cells and human HT1080 cells. Most importantly, with the use of a conditionally cytotoxic gene, we further developed a novel strategy for negative selection, thereby enhancing the efficiency of counterselection for non-homologous integration of exon-trap vectors. Our methods will greatly facilitate exon-trapping gene-targeting technologies in mammalian cells, particularly when combined with the novel negative selection strategy.

Stimulus selection and tracking during urination: autoshaping directed behavior with toilet targets.

Science.gov (United States)

Siegel, R K

1977-01-01

A simple procedure is described for investigating stimuli selected as targets during urination in the commode. Ten normal males preferred a floating target that could be tracked to a series of stationary targets. This technique was used to bring misdirected urinations in a severely retarded male under rapid stimulus control of a floating target in the commode. The float stimulus was also evaluated with nine institionalized, moderately retarded males and results indicated rapid autoshaping of directed urination without the use of verbal instructions or conventional toilet training. The technique can be applied in training children to control misdirected urinations in institution for the retarded, in psychiatric wards with regressed populations, and in certain male school dormitories. PMID:885828

Reallocating attention during multiple object tracking.

Science.gov (United States)

Ericson, Justin M; Christensen, James C

2012-07-01

Wolfe, Place, and Horowitz (Psychonomic Bulletin & Review 14:344-349, 2007) found that participants were relatively unaffected by selecting and deselecting targets while performing a multiple object tracking task, such that maintaining tracking was possible for longer durations than the few seconds typically studied. Though this result was generally consistent with other findings on tracking duration (Franconeri, Jonathon, & Scimeca Psychological Science 21:920-925, 2010), it was inconsistent with research involving cuing paradigms, specifically precues (Pylyshyn & Annan Spatial Vision 19:485-504, 2006). In the present research, we broke down the addition and removal of targets into separate conditions and incorporated a simple performance model to evaluate the costs associated with the selection and deselection of moving targets. Across three experiments, we demonstrated evidence against a cost being associated with any shift in attention, but rather that varying the type of cue used for target deselection produces no additional cost to performance and that hysteresis effects are not induced by a reduction in tracking load.

Yersinia pestis targets neutrophils via complement receptor 3

Science.gov (United States)

Merritt, Peter M.; Nero, Thomas; Bohman, Lesley; Felek, Suleyman; Krukonis, Eric S.; Marketon, Melanie M.

2015-01-01

Yersinia species display a tropism for lymphoid tissues during infection, and the bacteria select innate immune cells for delivery of cytotoxic effectors by the type III secretion system. Yet the mechanism for target cell selection remains a mystery. Here we investigate the interaction of Yersinia pestis with murine splenocytes to identify factors that participate in the targeting process. We find that interactions with primary immune cells rely on multiple factors. First, the bacterial adhesin Ail is required for efficient targeting of neutrophils in vivo. However, Ail does not appear to directly mediate binding to a specific cell type. Instead, we find that host serum factors direct Y. pestis to specific innate immune cells, particularly neutrophils. Importantly, specificity towards neutrophils was increased in the absence of bacterial adhesins due to reduced targeting of other cell types, but this phenotype was only visible in the presence of mouse serum. Addition of antibodies against complement receptor 3 and CD14 blocked target cell selection, suggesting that a combination of host factors participate in steering bacteria toward neutrophils during plague infection. PMID:25359083

One For All? Hitting multiple Alzheimer’s Disease targets with one drug

Directory of Open Access Journals (Sweden)

Rebecca Ellen Hughes

2016-04-01

Full Text Available Alzheimer’s disease is a complex and multifactorial disease for which the mechanism is still not fully understood. As new insights into disease progression are discovered, new drugs must be designed to target those aspects of the disease that cause neuronal damage rather than just the symptoms currently addressed by single target drugs. It is becoming possible to target several aspects of the disease pathology at once using multi-target drugs. Intended as a introduction for non-experts, this review describes the key multi-target drug design approaches, namely structure-based, in silico, and data-mining, to evaluate what is preventing compounds progressing through the clinic to the market. Repurposing current drugs using their off-target effects reduces the cost of development, time to launch and also the uncertainty associated with safety and pharmacokinetics. The most promising drugs currently being investigated for repurposing to Alzheimer’s Disease are rasagiline, originally developed for the treatment of Parkinson’s Disease, and liraglutide, an antidiabetic. Rational drug design can combine pharmacophores of multiple drugs, systematically change functional groups, and rank them by virtual screening. Hits confirmed experimentally are rationally modified to generate an effective multi-potent lead compound. Examples from this approach are ASS234 with properties similar to rasagiline, and donecopride, a hybrid of an acetylcholinesterase inhibitor and a 5-HT4 receptor agonist with pro-cognitive effects. Exploiting these interdisciplinary approaches, public-private collaborative lead factories promise faster delivery of new drugs to the clinic.

Simultaneous detection of multiple DNA targets by integrating dual-color graphene quantum dot nanoprobes and carbon nanotubes.

Science.gov (United States)

Qian, Zhaosheng; Shan, Xiaoyue; Chai, Lujing; Chen, Jianrong; Feng, Hui

2014-12-01

Simultaneous detection of multiple DNA targets was achieved based on a biocompatible graphene quantum dots (GQDs) and carbon nanotubes (CNTs) platform through spontaneous assembly between dual-color GQD-based probes and CNTs and subsequently self-recognition between DNA probes and targets. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A triple axes multiple target holder assembly

International Nuclear Information System (INIS)

Tribedi, L.C.; Narvekar, S.D.; Pillay, R.G.; Tandon, P.N.

1993-01-01

We have designed and fabricated a rotatable target holder assembly capable of accommodating 27 targets. The target foils are mounted along two concentric circles on a ss wheel. On the outer circle 18 targets can be mounted each 20deg apart, and on the inner circle the remaining targets are positioned each 40deg apart. The self supporting or carbon backed targets are mounted on thin frames and are placed concentrically at the targets are mounted on thin frames and are placed concentrically at the target position on the wheel. Three degrees of freedom are provided to the target holder assembly. (author). 1 fig

EBF factors drive expression of multiple classes of target genes governing neuronal development.

Science.gov (United States)

Green, Yangsook S; Vetter, Monica L

2011-04-30

Early B cell factor (EBF) family members are transcription factors known to have important roles in several aspects of vertebrate neurogenesis, including commitment, migration and differentiation. Knowledge of how EBF family members contribute to neurogenesis is limited by a lack of detailed understanding of genes that are transcriptionally regulated by these factors. We performed a microarray screen in Xenopus animal caps to search for targets of EBF transcriptional activity, and identified candidate targets with multiple roles, including transcription factors of several classes. We determined that, among the most upregulated candidate genes with expected neuronal functions, most require EBF activity for some or all of their expression, and most have overlapping expression with ebf genes. We also found that the candidate target genes that had the most strongly overlapping expression patterns with ebf genes were predicted to be direct transcriptional targets of EBF transcriptional activity. The identification of candidate targets that are transcription factor genes, including nscl-1, emx1 and aml1, improves our understanding of how EBF proteins participate in the hierarchy of transcription control during neuronal development, and suggests novel mechanisms by which EBF activity promotes migration and differentiation. Other candidate targets, including pcdh8 and kcnk5, expand our knowledge of the types of terminal differentiated neuronal functions that EBF proteins regulate.

A genetic algorithm for multiple relay selection in two-way relaying cognitive radio networks

KAUST Repository

Alsharoa, Ahmad M.

2013-09-01

In this paper, we investigate a multiple relay selection scheme for two-way relaying cognitive radio networks where primary users and secondary users operate on the same frequency band. More specifically, cooperative relays using Amplifyand- Forward (AF) protocol are optimally selected to maximize the sum rate of the secondary users without degrading the Quality of Service (QoS) of the primary users by respecting a tolerated interference threshold. A strong optimization tool based on genetic algorithm is employed to solve our formulated optimization problem where discrete relay power levels are considered. Our simulation results show that the practical heuristic approach achieves almost the same performance of the optimal multiple relay selection scheme either with discrete or continuous power distributions. Copyright © 2013 by the Institute of Electrical and Electronic Engineers, Inc.

Algal bioremediation of waste waters from land-based aquaculture using ulva: selecting target species and strains.

Directory of Open Access Journals (Sweden)

Rebecca J Lawton

Full Text Available The optimised reduction of dissolved nutrient loads in aquaculture effluents through bioremediation requires selection of appropriate algal species and strains. The objective of the current study was to identify target species and strains from the macroalgal genus Ulva for bioremediation of land-based aquaculture facilities in Eastern Australia. We surveyed land-based aquaculture facilities and natural coastal environments across three geographic locations in Eastern Australia to determine which species of Ulva occur naturally in this region and conducted growth trials at three temperature treatments on a subset of samples from each location to determine whether local strains had superior performance under local environmental conditions. DNA barcoding using the markers ITS and tufA identified six species of Ulva, with U. ohnoi being the most common blade species and U. sp. 3 the most common filamentous species. Both species occurred at multiple land-based aquaculture facilities in Townsville and Brisbane and multiple strains of each species grew well in culture. Specific growth rates of U. ohnoi and U. sp. 3 were high (over 9% and 15% day(-1 respectively across temperature treatments. Within species, strains of U. ohnoi had higher growth in temperatures corresponding to local conditions, suggesting that strains may be locally adapted. However, across all temperature treatments Townsville strains had the highest growth rates (11.2-20.4% day(-1 and Sydney strains had the lowest growth rates (2.5-8.3% day(-1. We also found significant differences in growth between strains of U. ohnoi collected from the same geographic location, highlighting the potential to isolate and cultivate fast growing strains. In contrast, there was no clearly identifiable competitive strain of filamentous Ulva, with multiple species and strains having variable performance. The fast growth rates and broad geographical distribution of U. ohnoi make this an ideal species to

Out with the old? The role of selective attention in retaining targets in partial report.

Science.gov (United States)

Lindsey, Dakota R B; Bundesen, Claus; Kyllingsbæk, Søren; Petersen, Anders; Logan, Gordon D

2017-01-01

In the partial-report task, subjects are asked to report only a portion of the items presented. Selective attention chooses which objects to represent in short-term memory (STM) on the basis of their relevance. Because STM is limited in capacity, one must sometimes choose which objects are removed from memory in light of new relevant information. We tested the hypothesis that the choices among newly presented information and old information in STM involve the same process-that both are acts of selective attention. We tested this hypothesis using a two-display partial-report procedure. In this procedure, subjects had to select and retain relevant letters (targets) from two sequentially presented displays. If selection in perception and retention in STM are the same process, then irrelevant letters (distractors) in the second display, which demanded attention because of their similarity to the targets, should have decreased target report from the first display. This effect was not obtained in any of four experiments. Thus, choosing objects to keep in STM is not the same process as choosing new objects to bring into STM.

Selective high-affinity polydentate ligands and methods of making such

Energy Technology Data Exchange (ETDEWEB)

Denardo, Sally J.; Denardo, Gerald L.; Balhorn, Rodney L.

2018-02-06

This invention provides novel polydentate selective high affinity ligands (SHALs) that can be used in a variety of applications in a manner analogous to the use of antibodies. SHALs typically comprise a multiplicity of ligands that each bind different region son the target molecule. The ligands are joined directly or through a linker thereby forming a polydentate moiety that typically binds the target molecule with high selectivity and avidity.

Selection of targets and ion sources for RIB generation at the Holifield Radioactive Ion Beam Facility

International Nuclear Information System (INIS)

Alton, G.D.

1995-01-01

In this report, the authors describe the performance characteristics for a selected number of target ion sources that will be employed for initial use at the Holifield Radioactive Ion Beam Facility (HRIBF) as well as prototype ion sources that show promise for future use for RIB applications. A brief review of present efforts to select target materials and to design composite target matrix/heat-sink systems that simultaneously incorporate the short diffusion lengths, high permeabilities, and controllable temperatures required to effect fast and efficient diffusion release of the short-lived species is also given

Engineering Multi-Walled Carbon Nanotube Therapeutic Bionanofluids to Selectively Target Papillary Thyroid Cancer Cells.

Directory of Open Access Journals (Sweden)

Idit Dotan

Full Text Available The incidence of papillary thyroid carcinoma (PTC has risen steadily over the past few decades as well as the recurrence rates. It has been proposed that targeted ablative physical therapy could be a therapeutic modality in thyroid cancer. Targeted bio-affinity functionalized multi-walled carbon nanotubes (BioNanofluid act locally, to efficiently convert external light energy to heat thereby specifically killing cancer cells. This may represent a promising new cancer therapeutic modality, advancing beyond conventional laser ablation and other nanoparticle approaches.Thyroid Stimulating Hormone Receptor (TSHR was selected as a target for PTC cells, due to its wide expression. Either TSHR antibodies or Thyrogen or purified TSH (Thyrotropin were chemically conjugated to our functionalized Bionanofluid. A diode laser system (532 nm was used to illuminate a PTC cell line for set exposure times. Cell death was assessed using Trypan Blue staining.TSHR-targeted BioNanofluids were capable of selectively ablating BCPAP, a TSHR-positive PTC cell line, while not TSHR-null NSC-34 cells. We determined that a 2:1 BCPAP cell:α-TSHR-BioNanofluid conjugate ratio and a 30 second laser exposure killed approximately 60% of the BCPAP cells, while 65% and >70% of cells were ablated using Thyrotropin- and Thyrogen-BioNanofluid conjugates, respectively. Furthermore, minimal non-targeted killing was observed using selective controls.A BioNanofluid platform offering a potential therapeutic path for papillary thyroid cancer has been investigated, with our in vitro results suggesting the development of a potent and rapid method of selective cancer cell killing. Therefore, BioNanofluid treatment emphasizes the need for new technology to treat patients with local recurrence and metastatic disease who are currently undergoing either re-operative neck explorations, repeated administration of radioactive iodine and as a last resort external beam radiation or chemotherapy, with

Dynamic studies of multiple configurations of CERN's Antiproton Decelerator Target core under proton beam impact

CERN Document Server

AUTHOR|(CDS)2248381

Antiprotons, like many other exotic particles, are produced by impacting high energy proton beams onto fixed targets. At the European Organization for Nuclear Research (CERN), this is done in the Antiproton Decelerator (AD) Facility. The engineering challenges related to the design of an optimal configuration of the AD-Target system derive from the extremely high energy depositions reached in the very thin target core as a consequence of each proton beam impact. A new target design is foreseen for operation after 2021, triggering multiple R&D activities since 2013 for this purpose. The goal of the present Master Thesis is to complement these activities with analytical and numerical calculations, delving into the phenomena associated to the dynamic response of the target core. In this context, two main studies have been carried out. First, the experimental data observed in targets subjected to low intensity proton pulses was cross-checked with analytical and computational methods for modal analysis, applie...

Selective whole genome amplification for resequencing target microbial species from complex natural samples.

Science.gov (United States)

Leichty, Aaron R; Brisson, Dustin

2014-10-01

Population genomic analyses have demonstrated power to address major questions in evolutionary and molecular microbiology. Collecting populations of genomes is hindered in many microbial species by the absence of a cost effective and practical method to collect ample quantities of sufficiently pure genomic DNA for next-generation sequencing. Here we present a simple method to amplify genomes of a target microbial species present in a complex, natural sample. The selective whole genome amplification (SWGA) technique amplifies target genomes using nucleotide sequence motifs that are common in the target microbe genome, but rare in the background genomes, to prime the highly processive phi29 polymerase. SWGA thus selectively amplifies the target genome from samples in which it originally represented a minor fraction of the total DNA. The post-SWGA samples are enriched in target genomic DNA, which are ideal for population resequencing. We demonstrate the efficacy of SWGA using both laboratory-prepared mixtures of cultured microbes as well as a natural host-microbe association. Targeted amplification of Borrelia burgdorferi mixed with Escherichia coli at genome ratios of 1:2000 resulted in >10(5)-fold amplification of the target genomes with genomic extracts from Wolbachia pipientis-infected Drosophila melanogaster resulted in up to 70% of high-throughput resequencing reads mapping to the W. pipientis genome. By contrast, 2-9% of sequencing reads were derived from W. pipientis without prior amplification. The SWGA technique results in high sequencing coverage at a fraction of the sequencing effort, thus allowing population genomic studies at affordable costs. Copyright © 2014 by the Genetics Society of America.

CD133, Selectively Targeting the Root of Cancer

Directory of Open Access Journals (Sweden)

Jörg U. Schmohl

2016-05-01

Full Text Available Cancer stem cells (CSC are capable of promoting tumor initiation and self-renewal, two important hallmarks of carcinoma formation. This population comprises a small percentage of the tumor mass and is highly resistant to chemotherapy, causing the most difficult problem in the field of cancer research, drug refractory relapse. Many CSC markers have been reported. One of the most promising and perhaps least ubiquitous is CD133, a membrane-bound pentaspan glycoprotein that is frequently expressed on CSC. There is evidence that directly targeting CD133 with biological drugs might be the most effective way to eliminate CSC. We have investigated two entirely unrelated, but highly effective approaches for selectively targeting CD133. The first involves using a special anti-CD133 single chain variable fragment (scFv to deliver a catalytic toxin. The second utilizes this same scFv to deliver components of the immune system. In this review, we discuss the development and current status of these CD133 associated biological agents. Together, they show exceptional promise by specific and efficient CSC elimination.

TARGET MARKET SELECTION IN FRESH FRUIT-VEGETABLE SECTOR USING FUZZY VIKOR METHOD

OpenAIRE

Tosun, Nedret

2017-01-01

Purpose- Companieshave to open up to new markets in order to develop and increase theircompetitiveness in the face of globalization and technological revolution.Target market selection is an important issue that needs to be addressed withpriority in terms of efficient use of resources. Methodology- The problemof market selection is a multi-criteria decision-making problem due to itsnature which requires the evaluation of different and sometimes conflictingcriteria in the decision-making proce...

Target objects defined by a conjunction of colour and shape can be selected independently and in parallel.

Science.gov (United States)

Jenkins, Michael; Grubert, Anna; Eimer, Martin

2017-11-01

It is generally assumed that during search for targets defined by a feature conjunction, attention is allocated sequentially to individual objects. We tested this hypothesis by tracking the time course of attentional processing biases with the N2pc component in tasks where observers searched for two targets defined by a colour/shape conjunction. In Experiment 1, two displays presented in rapid succession (100 ms or 10 ms SOA) each contained a target and a colour-matching or shape-matching distractor on opposite sides. Target objects in both displays elicited N2pc components of similar size that overlapped in time when the SOA was 10 ms, suggesting that attention was allocated in parallel to both targets. Analogous results were found in Experiment 2, where targets and partially matching distractors were both accompanied by an object without target-matching features. Colour-matching and shape-matching distractors also elicited N2pc components, and the target N2pc was initially identical to the sum of the two distractor N2pcs, suggesting that the initial phase of attentional object selection was guided independently by feature templates for target colour and shape. Beyond 230 ms after display onset, the target N2pc became superadditive, indicating that attentional selection processes now started to be sensitive to the presence of feature conjunctions. Results show that independent attentional selection processes can be activated in parallel by two target objects in situations where these objects are defined by a feature conjunction.

Selective Attention Enhances Beta-Band Cortical Oscillation to Speech under "Cocktail-Party" Listening Conditions.

Science.gov (United States)

Gao, Yayue; Wang, Qian; Ding, Yu; Wang, Changming; Li, Haifeng; Wu, Xihong; Qu, Tianshu; Li, Liang

2017-01-01

Human listeners are able to selectively attend to target speech in a noisy environment with multiple-people talking. Using recordings of scalp electroencephalogram (EEG), this study investigated how selective attention facilitates the cortical representation of target speech under a simulated "cocktail-party" listening condition with speech-on-speech masking. The result shows that the cortical representation of target-speech signals under the multiple-people talking condition was specifically improved by selective attention relative to the non-selective-attention listening condition, and the beta-band activity was most strongly modulated by selective attention. Moreover, measured with the Granger Causality value, selective attention to the single target speech in the mixed-speech complex enhanced the following four causal connectivities for the beta-band oscillation: the ones (1) from site FT7 to the right motor area, (2) from the left frontal area to the right motor area, (3) from the central frontal area to the right motor area, and (4) from the central frontal area to the right frontal area. However, the selective-attention-induced change in beta-band causal connectivity from the central frontal area to the right motor area, but not other beta-band causal connectivities, was significantly correlated with the selective-attention-induced change in the cortical beta-band representation of target speech. These findings suggest that under the "cocktail-party" listening condition, the beta-band oscillation in EEGs to target speech is specifically facilitated by selective attention to the target speech that is embedded in the mixed-speech complex. The selective attention-induced unmasking of target speech may be associated with the improved beta-band functional connectivity from the central frontal area to the right motor area, suggesting a top-down attentional modulation of the speech-motor process.

MULTIPLE CRITERIA DECISION MAKING APPROACH FOR INDUSTRIAL ENGINEER SELECTION USING FUZZY AHP-FUZZY TOPSIS

OpenAIRE

Deliktaş, Derya; ÜSTÜN, Özden

2018-01-01

In this study, a fuzzy multiple criteria decision-making approach is proposed to select an industrial engineer among ten candidates in a manufacturing environment. The industrial engineer selection problem is a special case of the personal selection problem. This problem, which has hierarchical structure of criteria and many decision makers, contains many criteria. The evaluation process of decision makers also includes ambiguous parameters. The fuzzy AHP is used to determin...

Advances in ranking and selection, multiple comparisons, and reliability methodology and applications

CERN Document Server

Balakrishnan, N; Nagaraja, HN

2007-01-01

S. Panchapakesan has made significant contributions to ranking and selection and has published in many other areas of statistics, including order statistics, reliability theory, stochastic inequalities, and inference. Written in his honor, the twenty invited articles in this volume reflect recent advances in these areas and form a tribute to Panchapakesan's influence and impact on these areas. Thematically organized, the chapters cover a broad range of topics from: Inference; Ranking and Selection; Multiple Comparisons and Tests; Agreement Assessment; Reliability; and Biostatistics. Featuring

Charged particles multiplicity in interactions of 3.7 A GeV 28Si with light and heavy target nuclei in nuclear emulsions

International Nuclear Information System (INIS)

Singh, B.K.; Tuli, S.K.

1998-01-01

Results from measurement of multiplicity of different charged particles emitted from the interactions of 3.7 A GeV 28 Si with different target groups in nuclear emulsion and correlations among them are presented. The nature of the dependence of multiplicities of charged particles on the impact parameter is examined. Analysis of data in terms of specific multiplicity for different target groups is performed and the results are discussed in the light of superposition model. (author)

Optical code-division multiple-access protocol with selective retransmission

Science.gov (United States)

Mohamed, Mohamed A. A.; Shalaby, Hossam M. H.; El-Badawy, El-Sayed A.

2006-05-01

An optical code-division multiple-access (OCDMA) protocol based on selective retransmission technique is proposed. The protocol is modeled using a detailed state diagram and is analyzed using equilibrium point analysis (EPA). Both traditional throughput and average delay are used to examine its performance for several network parameters. In addition, the performance of the proposed protocol is compared to that of the R3T protocol, which is based on a go-back-n technique. Our results show that a higher performance is achieved by the proposed protocol at the expense of system complexity.

Detection and Identification of Multiple Stationary Human Targets Via Bio-Radar Based on the Cross-Correlation Method

Directory of Open Access Journals (Sweden)

Yang Zhang

2016-10-01

Full Text Available Ultra-wideband (UWB radar has been widely used for detecting human physiological signals (respiration, movement, etc. in the fields of rescue, security, and medicine owing to its high penetrability and range resolution. In these applications, especially in rescue after disaster (earthquake, collapse, mine accident, etc., the presence, number, and location of the trapped victims to be detected and rescued are the key issues of concern. Ample research has been done on the first issue, whereas the identification and localization of multi-targets remains a challenge. False positive and negative identification results are two common problems associated with the detection of multiple stationary human targets. This is mainly because the energy of the signal reflected from the target close to the receiving antenna is considerably stronger than those of the targets at further range, often leading to missing or false recognition if the identification method is based on the energy of the respiratory signal. Therefore, a novel method based on cross-correlation is proposed in this paper that is based on the relativity and periodicity of the signals, rather than on the energy. The validity of this method is confirmed through experiments using different scenarios; the results indicate a discernible improvement in the detection precision and identification of the multiple stationary targets.

Detection and Identification of Multiple Stationary Human Targets Via Bio-Radar Based on the Cross-Correlation Method.

Science.gov (United States)

Zhang, Yang; Chen, Fuming; Xue, Huijun; Li, Zhao; An, Qiang; Wang, Jianqi; Zhang, Yang

2016-10-27

Ultra-wideband (UWB) radar has been widely used for detecting human physiological signals (respiration, movement, etc.) in the fields of rescue, security, and medicine owing to its high penetrability and range resolution. In these applications, especially in rescue after disaster (earthquake, collapse, mine accident, etc.), the presence, number, and location of the trapped victims to be detected and rescued are the key issues of concern. Ample research has been done on the first issue, whereas the identification and localization of multi-targets remains a challenge. False positive and negative identification results are two common problems associated with the detection of multiple stationary human targets. This is mainly because the energy of the signal reflected from the target close to the receiving antenna is considerably stronger than those of the targets at further range, often leading to missing or false recognition if the identification method is based on the energy of the respiratory signal. Therefore, a novel method based on cross-correlation is proposed in this paper that is based on the relativity and periodicity of the signals, rather than on the energy. The validity of this method is confirmed through experiments using different scenarios; the results indicate a discernible improvement in the detection precision and identification of the multiple stationary targets.

miR-137 inhibits the invasion of melanoma cells through downregulation of multiple oncogenic target genes.

Science.gov (United States)

Luo, Chonglin; Tetteh, Paul W; Merz, Patrick R; Dickes, Elke; Abukiwan, Alia; Hotz-Wagenblatt, Agnes; Holland-Cunz, Stefan; Sinnberg, Tobias; Schittek, Birgit; Schadendorf, Dirk; Diederichs, Sven; Eichmüller, Stefan B

2013-03-01

MicroRNAs are small noncoding RNAs that regulate gene expression and have important roles in various types of cancer. Previously, miR-137 was reported to act as a tumor suppressor in different cancers, including malignant melanoma. In this study, we show that low miR-137 expression is correlated with poor survival in stage IV melanoma patients. We identified and validated two genes (c-Met and YB1) as direct targets of miR-137 and confirmed two previously known targets, namely enhancer of zeste homolog 2 (EZH2) and microphthalmia-associated transcription factor (MITF). Functional studies showed that miR-137 suppressed melanoma cell invasion through the downregulation of multiple target genes. The decreased invasion caused by miR-137 overexpression could be phenocopied by small interfering RNA knockdown of EZH2, c-Met, or Y box-binding protein 1 (YB1). Furthermore, miR-137 inhibited melanoma cell migration and proliferation. Finally, miR-137 induced apoptosis in melanoma cell lines and decreased BCL2 levels. In summary, our study confirms that miR-137 acts as a tumor suppressor in malignant melanoma and reveals that miR-137 regulates multiple targets including c-Met, YB1, EZH2, and MITF.

Rationally engineered nanoparticles target multiple myeloma cells, overcome cell-adhesion-mediated drug resistance, and show enhanced efficacy in vivo

International Nuclear Information System (INIS)

Kiziltepe, T; Ashley, J D; Stefanick, J F; Qi, Y M; Alves, N J; Handlogten, M W; Suckow, M A; Navari, R M; Bilgicer, B

2012-01-01

In the continuing search for effective cancer treatments, we report the rational engineering of a multifunctional nanoparticle that combines traditional chemotherapy with cell targeting and anti-adhesion functionalities. Very late antigen-4 (VLA-4) mediated adhesion of multiple myeloma (MM) cells to bone marrow stroma confers MM cells with cell-adhesion-mediated drug resistance (CAM-DR). In our design, we used micellar nanoparticles as dynamic self-assembling scaffolds to present VLA-4-antagonist peptides and doxorubicin (Dox) conjugates, simultaneously, to selectively target MM cells and to overcome CAM-DR. Dox was conjugated to the nanoparticles through an acid-sensitive hydrazone bond. VLA-4-antagonist peptides were conjugated via a multifaceted synthetic procedure for generating precisely controlled number of targeting functionalities. The nanoparticles were efficiently internalized by MM cells and induced cytotoxicity. Mechanistic studies revealed that nanoparticles induced DNA double-strand breaks and apoptosis in MM cells. Importantly, multifunctional nanoparticles overcame CAM-DR, and were more efficacious than Dox when MM cells were cultured on fibronectin-coated plates. Finally, in a MM xenograft model, nanoparticles preferentially homed to MM tumors with ∼10 fold more drug accumulation and demonstrated dramatic tumor growth inhibition with a reduced overall systemic toxicity. Altogether, we demonstrate the disease driven engineering of a nanoparticle-based drug delivery system, enabling the model of an integrative approach in the treatment of MM

EBF factors drive expression of multiple classes of target genes governing neuronal development

Directory of Open Access Journals (Sweden)

Vetter Monica L

2011-04-01

Full Text Available Abstract Background Early B cell factor (EBF family members are transcription factors known to have important roles in several aspects of vertebrate neurogenesis, including commitment, migration and differentiation. Knowledge of how EBF family members contribute to neurogenesis is limited by a lack of detailed understanding of genes that are transcriptionally regulated by these factors. Results We performed a microarray screen in Xenopus animal caps to search for targets of EBF transcriptional activity, and identified candidate targets with multiple roles, including transcription factors of several classes. We determined that, among the most upregulated candidate genes with expected neuronal functions, most require EBF activity for some or all of their expression, and most have overlapping expression with ebf genes. We also found that the candidate target genes that had the most strongly overlapping expression patterns with ebf genes were predicted to be direct transcriptional targets of EBF transcriptional activity. Conclusions The identification of candidate targets that are transcription factor genes, including nscl-1, emx1 and aml1, improves our understanding of how EBF proteins participate in the hierarchy of transcription control during neuronal development, and suggests novel mechanisms by which EBF activity promotes migration and differentiation. Other candidate targets, including pcdh8 and kcnk5, expand our knowledge of the types of terminal differentiated neuronal functions that EBF proteins regulate.

Active target trigger for charm search in NA32

International Nuclear Information System (INIS)

Boehringer, T.

1984-01-01

An active target, made of 17 fine-grained silicon microstrip detector planes has been built. It will be used for an online trigger to select charm events through a change of charged multiplicity for the NA32 experiment at the CERN SPS

A low complexity algorithm for multiple relay selection in two-way relaying Cognitive Radio networks

KAUST Repository

Alsharoa, Ahmad M.

2013-06-01

In this paper, a multiple relay selection scheme for two-way relaying cognitive radio network is investigated. We consider a cooperative Cognitive Radio (CR) system with spectrum sharing scenario using Amplify-and-Forward (AF) protocol, where licensed users and unlicensed users operate on the same frequency band. The main objective is to maximize the sum rate of the unlicensed users allowed to share the spectrum with the licensed users by respecting a tolerated interference threshold. A practical low complexity heuristic approach is proposed to solve our formulated optimization problem. Selected numerical results show that the proposed algorithm reaches a performance close to the performance of the optimal multiple relay selection scheme either with discrete or continuous power distributions while providing a considerable saving in terms of computational complexity. In addition, these results show that our proposed scheme significantly outperforms the single relay selection scheme. © 2013 IEEE.

[Targeted pharmacist-led medication order review in hospital: Assessment of a selection method for drug prescriptions].

Science.gov (United States)

Jarre, C; Bouchet, J; Hellot-Guersing, M; Leromain, A-S; Derharoutunian, C; Gadot, A; Roubille, R

2017-11-01

The aim of this study was to assess a selection method for drug prescriptions developed at the hospital level that allows to target pharmacist-led medication order review for at-risk patients and drugs. A one-month study has been conducted on all targeted medication orders in 19 care units. Selection criteria have been identified: biological criteria, alert medications and drug interactions. Pharmacists' interventions proposed during medication order review were listed and the possible links to the selection criteria were determined. A total of 1612 prescriptions were analysed and 236 pharmacists' interventions were performed (14.6 interventions per 100 prescriptions). Physicians' acceptance rate was 60.6%. The percentage of pharmacists' interventions linked to the selection criteria was 35.6%. The relevance of the biological criteria was identified, particularly the one identifying patients with creatinine clearance below 30ml/min. Six alert medications were also relevant selection criteria: dabigatran, morphine, gentamicin, methotrexate, potassium chloride and trimethoprim sulfamethoxazole. Drug interactions criteria was irrelevant. This study allowed a first assessment of the selection criteria used. A largest study seems necessary to continue the analysis of this selection method for prescriptions, especially the assessment of the alert medications list, in order to refine the prescriptions targeting. Copyright © 2017 Académie Nationale de Pharmacie. Published by Elsevier Masson SAS. All rights reserved.

A placebo-controlled trial of oral cladribine for relapsing multiple sclerosis

DEFF Research Database (Denmark)

Giovannoni, Gavin; Comi, Giancarlo; Cook, Stuart

2010-01-01

Cladribine provides immunomodulation through selective targeting of lymphocyte subtypes. We report the results of a 96-week phase 3 trial of a short-course oral tablet therapy in patients with relapsing-remitting multiple sclerosis....

Selective Attention Enhances Beta-Band Cortical Oscillation to Speech under “Cocktail-Party” Listening Conditions

Science.gov (United States)

Gao, Yayue; Wang, Qian; Ding, Yu; Wang, Changming; Li, Haifeng; Wu, Xihong; Qu, Tianshu; Li, Liang

2017-01-01

Human listeners are able to selectively attend to target speech in a noisy environment with multiple-people talking. Using recordings of scalp electroencephalogram (EEG), this study investigated how selective attention facilitates the cortical representation of target speech under a simulated “cocktail-party” listening condition with speech-on-speech masking. The result shows that the cortical representation of target-speech signals under the multiple-people talking condition was specifically improved by selective attention relative to the non-selective-attention listening condition, and the beta-band activity was most strongly modulated by selective attention. Moreover, measured with the Granger Causality value, selective attention to the single target speech in the mixed-speech complex enhanced the following four causal connectivities for the beta-band oscillation: the ones (1) from site FT7 to the right motor area, (2) from the left frontal area to the right motor area, (3) from the central frontal area to the right motor area, and (4) from the central frontal area to the right frontal area. However, the selective-attention-induced change in beta-band causal connectivity from the central frontal area to the right motor area, but not other beta-band causal connectivities, was significantly correlated with the selective-attention-induced change in the cortical beta-band representation of target speech. These findings suggest that under the “cocktail-party” listening condition, the beta-band oscillation in EEGs to target speech is specifically facilitated by selective attention to the target speech that is embedded in the mixed-speech complex. The selective attention-induced unmasking of target speech may be associated with the improved beta-band functional connectivity from the central frontal area to the right motor area, suggesting a top-down attentional modulation of the speech-motor process. PMID:28239344

Multiplicities of charged kaons from deep-inelastic muon scattering off an isoscalar target

CERN Document Server

Adolph, C.

2017-04-10

Precise measurements of charged-kaon multiplicities in deep inelastic scattering were performed. The results are presented in three-dimensional bins of the Bjorken scaling variable x, the relative virtual-photon energy y, and the fraction z of the virtual-photon energy carried by the produced hadron. The data were obtained by the COMPASS Collaboration by scattering 160 GeV muons off an isoscalar 6 LiD target. They cover the kinematic domain 1 (GeV/c)2 5 GeV/c^2 in the invariant mass of the hadronic system. The results from the sum of the z-integrated K+ and K- multiplicities at high x point to a value of the non-strange quark fragmentation function larger than obtained by the earlier DSS fit.

Implications of structural genomics target selection strategies: Pfam5000, whole genome, and random approaches

Energy Technology Data Exchange (ETDEWEB)

Chandonia, John-Marc; Brenner, Steven E.

2004-07-14

The structural genomics project is an international effort to determine the three-dimensional shapes of all important biological macromolecules, with a primary focus on proteins. Target proteins should be selected according to a strategy which is medically and biologically relevant, of good value, and tractable. As an option to consider, we present the Pfam5000 strategy, which involves selecting the 5000 most important families from the Pfam database as sources for targets. We compare the Pfam5000 strategy to several other proposed strategies that would require similar numbers of targets. These include including complete solution of several small to moderately sized bacterial proteomes, partial coverage of the human proteome, and random selection of approximately 5000 targets from sequenced genomes. We measure the impact that successful implementation of these strategies would have upon structural interpretation of the proteins in Swiss-Prot, TrEMBL, and 131 complete proteomes (including 10 of eukaryotes) from the Proteome Analysis database at EBI. Solving the structures of proteins from the 5000 largest Pfam families would allow accurate fold assignment for approximately 68 percent of all prokaryotic proteins (covering 59 percent of residues) and 61 percent of eukaryotic proteins (40 percent of residues). More fine-grained coverage which would allow accurate modeling of these proteins would require an order of magnitude more targets. The Pfam5000 strategy may be modified in several ways, for example to focus on larger families, bacterial sequences, or eukaryotic sequences; as long as secondary consideration is given to large families within Pfam, coverage results vary only slightly. In contrast, focusing structural genomics on a single tractable genome would have only a limited impact in structural knowledge of other proteomes: a significant fraction (about 30-40 percent of the proteins, and 40-60 percent of the residues) of each proteome is classified in small

Interval MULTIMOORA method with target values of attributes based on interval distance and preference degree: biomaterials selection

Science.gov (United States)

Hafezalkotob, Arian; Hafezalkotob, Ashkan

2017-06-01

A target-based MADM method covers beneficial and non-beneficial attributes besides target values for some attributes. Such techniques are considered as the comprehensive forms of MADM approaches. Target-based MADM methods can also be used in traditional decision-making problems in which beneficial and non-beneficial attributes only exist. In many practical selection problems, some attributes have given target values. The values of decision matrix and target-based attributes can be provided as intervals in some of such problems. Some target-based decision-making methods have recently been developed; however, a research gap exists in the area of MADM techniques with target-based attributes under uncertainty of information. We extend the MULTIMOORA method for solving practical material selection problems in which material properties and their target values are given as interval numbers. We employ various concepts of interval computations to reduce degeneration of uncertain data. In this regard, we use interval arithmetic and introduce innovative formula for interval distance of interval numbers to create interval target-based normalization technique. Furthermore, we use a pairwise preference matrix based on the concept of degree of preference of interval numbers to calculate the maximum, minimum, and ranking of these numbers. Two decision-making problems regarding biomaterials selection of hip and knee prostheses are discussed. Preference degree-based ranking lists for subordinate parts of the extended MULTIMOORA method are generated by calculating the relative degrees of preference for the arranged assessment values of the biomaterials. The resultant rankings for the problem are compared with the outcomes of other target-based models in the literature.

Clinical efficacy and management of monoclonal antibodies targeting CD38 and SLAMF7 in multiple myeloma

DEFF Research Database (Denmark)

van de Donk, Niels W C J; Moreau, Philippe; Plesner, Torben

2016-01-01

Immunotherapeutic strategies are emerging as promising therapeutic approaches in multiple myeloma (MM), with several monoclonal antibodies in advanced stages of clinical development. Of these agents, CD38-targeting antibodies have marked single agent activity in extensively pretreated MM...... of therapeutic antibodies with immunofixation and serum protein electrophoresis assays may lead to underestimation of complete response. Strategies to mitigate interference, based on shifting the therapeutic antibody band, are in development. Furthermore, daratumumab, and probably also other CD38-targeting...

Selective control of multiple ferroelectric switching pathways using a trailing flexoelectric field

Science.gov (United States)

Park, Sung Min; Wang, Bo; Das, Saikat; Chae, Seung Chul; Chung, Jin-Seok; Yoon, Jong-Gul; Chen, Long-Qing; Yang, Sang Mo; Noh, Tae Won

2018-05-01

Flexoelectricity is an electromechanical coupling between electrical polarization and a strain gradient1 that enables mechanical manipulation of polarization without applying an electrical bias2,3. Recently, flexoelectricity was directly demonstrated by mechanically switching the out-of-plane polarization of a uniaxial system with a scanning probe microscope tip3,4. However, the successful application of flexoelectricity in low-symmetry multiaxial ferroelectrics and therefore active manipulation of multiple domains via flexoelectricity have not yet been achieved. Here, we demonstrate that the symmetry-breaking flexoelectricity offers a powerful route for the selective control of multiple domain switching pathways in multiaxial ferroelectric materials. Specifically, we use a trailing flexoelectric field that is created by the motion of a mechanically loaded scanning probe microscope tip. By controlling the SPM scan direction, we can deterministically select either stable 71° ferroelastic switching or 180° ferroelectric switching in a multiferroic magnetoelectric BiFeO3 thin film. Phase-field simulations reveal that the amplified in-plane trailing flexoelectric field is essential for this domain engineering. Moreover, we show that mechanically switched domains have a good retention property. This work opens a new avenue for the deterministic selection of nanoscale ferroelectric domains in low-symmetry materials for non-volatile magnetoelectric devices and multilevel data storage.

Aliskiren targets multiple systems to alleviate cancer cachexia.

Science.gov (United States)

Wang, Chaoyi; Guo, Dunwei; Wang, Qiang; You, Song; Qiao, Zhongpeng; Liu, Yong; Dai, Hang; Tang, Hua

2016-11-01

To examine the effects of aliskiren, a small-molecule renin inhibitor, on cancer cachexia and to explore the underlying mechanisms. A cancer cachexia model was established by subcutaneously injecting C26 mouse colon carcinoma cells into isogenic BALB/c mice. Aliskiren was administered intragastrically [10 mg/kg body weight (BW)] on day 5 (as a preventive strategy, AP group) or on day 12 (as a therapeutic strategy, AT group) after C26 injection. Mice that received no C26 injection (healthy controls, HC group) or only C26 injection but not aliskiren (cancer, CA group) were used as controls. BW, tumor growth, whole body functions, and survival were monitored daily in half of the mice in each group, whereas serum, tumors, and gastrocnemius muscles were harvested from the other mice after sacrifice on day 20 for further analysis. Aliskiren significantly alleviated multiple cachexia‑associated symptoms, including BW loss, tumor burden, muscle wasting, muscular dysfunction, and shortened survival. On the molecular level, aliskiren antagonized cachexia‑induced activation of the renin‑angiotensin system (RAS), systematic and muscular inflammation, oxidative stress, and autophagy‑lysosome as well as ubiquitin‑proteasome stimulation. In addition, early administration of aliskiren before cachexia development (AP group) resulted in more robust effects in alleviating cachexia or targeting underlying mechanisms than administration after cachexia development (AT group). Aliskiren exhibited potent anti‑cachexia activities. These activities were achieved through the targeting of at least four mechanisms underlying cachexia development: RAS activation, increase in systematic inflammation, upregulation of oxidative stress, and stimulation of autophagy-lysosome pathway (ALP) and ubiquitin-proteasome pathway (UPP).

Time-resolved x-ray line emission studies of thermal transport in multiple beam uv-irradiated targets

International Nuclear Information System (INIS)

Jaanimagi, P.A.; Henke, B.L.; Delettrez, J.; Richardson, M.C.

1984-01-01

Thermal transport in spherical targets irradiated with multiple, nanosecond duration laser beams, has been a topic of much discussion recently. Different inferences on the level of thermal flux inhibition have been drawn from plasma velocity and x-ray spectroscopic diagnostics. We present new measurements of thermal transport on spherical targets made through time-resolved x-ray spectroscopic measurements of the progress of the ablation surface through thin layers of material on the surface of the target. These measurements, made with 6 and 12 uv (351 nm) nanosecond beams from OMEGA, will be compared to previous thermal transport measurements. Transparencies of the conference presentation are given

Priming of pop-out modulates attentional target selection in visual search: Behavioural and electrophysiological evidence

OpenAIRE

Eimer, Martin; Kiss, Monika; Cheung, Theodore

2009-01-01

Previous behavioural studies have shown that the repetition of target or distractor features across trials speeds pop-out visual search. We obtained behavioural and event-related brain potential (ERP) measures in two experiments where participants searched for a colour singleton target among homogeneously coloured distractors. An ERP marker of spatially selective attention (N2pc component) was delayed when either target or distractor colours were swapped across successive trials, demonstratin...

Literature-based discovery of diabetes- and ROS-related targets

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Pande Manjusha

2010-10-01

Full Text Available Abstract Background Reactive oxygen species (ROS are known mediators of cellular damage in multiple diseases including diabetic complications. Despite its importance, no comprehensive database is currently available for the genes associated with ROS. Methods We present ROS- and diabetes-related targets (genes/proteins collected from the biomedical literature through a text mining technology. A web-based literature mining tool, SciMiner, was applied to 1,154 biomedical papers indexed with diabetes and ROS by PubMed to identify relevant targets. Over-represented targets in the ROS-diabetes literature were obtained through comparisons against randomly selected literature. The expression levels of nine genes, selected from the top ranked ROS-diabetes set, were measured in the dorsal root ganglia (DRG of diabetic and non-diabetic DBA/2J mice in order to evaluate the biological relevance of literature-derived targets in the pathogenesis of diabetic neuropathy. Results SciMiner identified 1,026 ROS- and diabetes-related targets from the 1,154 biomedical papers (http://jdrf.neurology.med.umich.edu/ROSDiabetes/. Fifty-three targets were significantly over-represented in the ROS-diabetes literature compared to randomly selected literature. These over-represented targets included well-known members of the oxidative stress response including catalase, the NADPH oxidase family, and the superoxide dismutase family of proteins. Eight of the nine selected genes exhibited significant differential expression between diabetic and non-diabetic mice. For six genes, the direction of expression change in diabetes paralleled enhanced oxidative stress in the DRG. Conclusions Literature mining compiled ROS-diabetes related targets from the biomedical literature and led us to evaluate the biological relevance of selected targets in the pathogenesis of diabetic neuropathy.

A threshold-based multiple optical signal selection scheme for WDM FSO systems

KAUST Repository

Nam, Sung Sik

2017-07-20

In this paper, we propose a threshold-based-multiple optical signal selection scheme (TMOS) for free-space optical systems based on wavelength division multiplexing. With the proposed TMOS, we can obtain higher spectral efficiency while reducing the potential increase in complexity of implementation caused by applying a selection-based beam selection scheme without a considerable performance loss. Here, to accurately characterize the performance of the proposed TMOS, we statistically analyze the characteristics with heterodyne detection technique over independent and identically distributed Log-normal turbulence conditions taking into considerations the impact of pointing error. Specifically, we derive exact closed-form expressions for the average bit error rate, and the average spectral efficiency by adopting an adaptive modulation. Some selected results shows that the average spectral efficiency can be increased with TMOS while the system requirement is satisfied.

A threshold-based multiple optical signal selection scheme for WDM FSO systems

KAUST Repository

Nam, Sung Sik; Alouini, Mohamed-Slim; Ko, Young-Chai; Cho, Sung Ho

2017-01-01

In this paper, we propose a threshold-based-multiple optical signal selection scheme (TMOS) for free-space optical systems based on wavelength division multiplexing. With the proposed TMOS, we can obtain higher spectral efficiency while reducing the potential increase in complexity of implementation caused by applying a selection-based beam selection scheme without a considerable performance loss. Here, to accurately characterize the performance of the proposed TMOS, we statistically analyze the characteristics with heterodyne detection technique over independent and identically distributed Log-normal turbulence conditions taking into considerations the impact of pointing error. Specifically, we derive exact closed-form expressions for the average bit error rate, and the average spectral efficiency by adopting an adaptive modulation. Some selected results shows that the average spectral efficiency can be increased with TMOS while the system requirement is satisfied.

Optimal design of compact and connected nature reserves for multiple species.

Science.gov (United States)

Wang, Yicheng; Önal, Hayri

2016-04-01

When designing a conservation reserve system for multiple species, spatial attributes of the reserves must be taken into account at species level. The existing optimal reserve design literature considers either one spatial attribute or when multiple attributes are considered the analysis is restricted only to one species. We built a linear integer programing model that incorporates compactness and connectivity of the landscape reserved for multiple species. The model identifies multiple reserves that each serve a subset of target species with a specified coverage probability threshold to ensure the species' long-term survival in the reserve, and each target species is covered (protected) with another probability threshold at the reserve system level. We modeled compactness by minimizing the total distance between selected sites and central sites, and we modeled connectivity of a selected site to its designated central site by selecting at least one of its adjacent sites that has a nearer distance to the central site. We considered structural distance and functional distances that incorporated site quality between sites. We tested the model using randomly generated data on 2 species, one ground species that required structural connectivity and the other an avian species that required functional connectivity. We applied the model to 10 bird species listed as endangered by the state of Illinois (U.S.A.). Spatial coherence and selection cost of the reserves differed substantially depending on the weights assigned to these 2 criteria. The model can be used to design a reserve system for multiple species, especially species whose habitats are far apart in which case multiple disjunct but compact and connected reserves are advantageous. The model can be modified to increase or decrease the distance between reserves to reduce or promote population connectivity. © 2015 Society for Conservation Biology.

The multiple mini-interview for emergency medicine resident selection.

Science.gov (United States)

Hopson, Laura R; Burkhardt, John C; Stansfield, R Brent; Vohra, Taher; Turner-Lawrence, Danielle; Losman, Eve D

2014-04-01

The Multiple Mini-Interview (MMI) uses multiple, short-structured contacts to evaluate communication and professionalism. It predicts medical school success better than the traditional interview and application. Its acceptability and utility in emergency medicine (EM) residency selection are unknown. We theorized that participants would judge the MMI equal to a traditional unstructured interview and it would provide new information for candidate assessment. Seventy-one interns from 3 programs in the first month of training completed an eight-station MMI focused on EM topics. Pre- and post-surveys assessed reactions. MMI scores were compared with application data. EM grades correlated with MMI performance (F[1, 66] = 4.18; p interview (mean difference = 1.36; p interview and MMI) was preferred over a MMI alone (mean difference = 1.1; p interview, participants were receptive to a mixed-methods interview. The MMI does correlate with performance on the EM clerkship and therefore can measure important abilities for EM success. Future work will determine whether MMI performance predicts residency performance. Copyright © 2014 Elsevier Inc. All rights reserved.

Channel selection for simultaneous and proportional myoelectric prosthesis control of multiple degrees-of-freedom

Science.gov (United States)

Hwang, Han-Jeong; Hahne, Janne Mathias; Müller, Klaus-Robert

2014-10-01

Objective. Recent studies have shown the possibility of simultaneous and proportional control of electrically powered upper-limb prostheses, but there has been little investigation on optimal channel selection. The objective of this study is to find a robust channel selection method and the channel subsets most suitable for simultaneous and proportional myoelectric prosthesis control of multiple degrees-of-freedom (DoFs). Approach. Ten able-bodied subjects and one person with congenital upper-limb deficiency took part in this study, and performed wrist movements with various combinations of two DoFs (flexion/extension and radial/ulnar deviation). During the experiment, high density electromyographic (EMG) signals and the actual wrist angles were recorded with an 8 × 24 electrode array and a motion tracking system, respectively. The wrist angles were estimated from EMG features with ridge regression using the subsets of channels chosen by three different channel selection methods: (1) least absolute shrinkage and selection operator (LASSO), (2) sequential feature selection (SFS), and (3) uniform selection (UNI). Main results. SFS generally showed higher estimation accuracy than LASSO and UNI, but LASSO always outperformed SFS in terms of robustness, such as noise addition, channel shift and training data reduction. It was also confirmed that about 95% of the original performance obtained using all channels can be retained with only 12 bipolar channels individually selected by LASSO and SFS. Significance. From the analysis results, it can be concluded that LASSO is a promising channel selection method for accurate simultaneous and proportional prosthesis control. We expect that our results will provide a useful guideline to select optimal channel subsets when developing clinical myoelectric prosthesis control systems based on continuous movements with multiple DoFs.

Multiplicities of charged kaons from deep-inelastic muon scattering off an isoscalar target

Directory of Open Access Journals (Sweden)

C. Adolph

2017-04-01

Full Text Available Precise measurements of charged-kaon multiplicities in deep inelastic scattering were performed. The results are presented in three-dimensional bins of the Bjorken scaling variable x, the relative virtual-photon energy y, and the fraction z of the virtual-photon energy carried by the produced hadron. The data were obtained by the COMPASS Collaboration by scattering 160 GeV muons off an isoscalar 6LiD target. They cover the kinematic domain 1(GeV/c25 GeV/c2 in the invariant mass of the hadronic system. The results from the sum of the z-integrated K+ and K− multiplicities at high x point to a value of the non-strange quark fragmentation function larger than obtained by the earlier DSS fit.

In Silico Design and Experimental Validation of siRNAs Targeting Conserved Regions of Multiple Hepatitis C Virus Genotypes.

Directory of Open Access Journals (Sweden)

Mahmoud ElHefnawi

Full Text Available RNA interference (RNAi is a post-transcriptional gene silencing mechanism that mediates the sequence-specific degradation of targeted RNA and thus provides a tremendous opportunity for development of oligonucleotide-based drugs. Here, we report on the design and validation of small interfering RNAs (siRNAs targeting highly conserved regions of the hepatitis C virus (HCV genome. To aim for therapeutic applications by optimizing the RNAi efficacy and reducing potential side effects, we considered different factors such as target RNA variations, thermodynamics and accessibility of the siRNA and target RNA, and off-target effects. This aim was achieved using an in silico design and selection protocol complemented by an automated MysiRNA-Designer pipeline. The protocol included the design and filtration of siRNAs targeting highly conserved and accessible regions within the HCV internal ribosome entry site, and adjacent core sequences of the viral genome with high-ranking efficacy scores. Off-target analysis excluded siRNAs with potential binding to human mRNAs. Under this strict selection process, two siRNAs (HCV353 and HCV258 were selected based on their predicted high specificity and potency. These siRNAs were tested for antiviral efficacy in HCV genotype 1 and 2 replicon cell lines. Both in silico-designed siRNAs efficiently inhibited HCV RNA replication, even at low concentrations and for short exposure times (24h; they also exceeded the antiviral potencies of reference siRNAs targeting HCV. Furthermore, HCV353 and HCV258 siRNAs also inhibited replication of patient-derived HCV genotype 4 isolates in infected Huh-7 cells. Prolonged treatment of HCV replicon cells with HCV353 did not result in the appearance of escape mutant viruses. Taken together, these results reveal the accuracy and strength of our integrated siRNA design and selection protocols. These protocols could be used to design highly potent and specific RNAi-based therapeutic

Chlorin e6 Conjugated Interleukin-6 Receptor Aptamers Selectively Kill Target Cells Upon Irradiation

Directory of Open Access Journals (Sweden)

Sven Kruspe

2014-01-01

Full Text Available Photodynamic therapy (PDT uses the therapeutic properties of light in combination with certain chemicals, called photosensitizers, to successfully treat brain, breast, prostate, and skin cancers. To improve PDT, current research focuses on the development of photosensitizers to specifically target cancer cells. In the past few years, aptamers have been developed to directly deliver cargo molecules into target cells. We conjugated the photosensitizer chlorin e6 (ce6 with a human interleukin-6 receptor (IL-6R binding RNA aptamer, AIR-3A yielding AIR-3A-ce6 for application in high efficient PDT. AIR-3A-ce6 was rapidly and specifically internalized by IL-6R presenting (IL-6R+ cells. Upon light irradiation, targeted cells were selectively killed, while free ce6 did not show any toxic effect. Cells lacking the IL-6R were also not affected by AIR-3A-ce6. With this approach, we improved the target specificity of ce6-mediated PDT. In the future, other tumor-specific aptamers might be used to selectively localize photosensitizers into cells of interest and improve the efficacy and specificity of PDT in cancer and other diseases.

Tyrosine kinase inhibitors: Multi-targeted or single-targeted?

Science.gov (United States)

Broekman, Fleur; Giovannetti, Elisa; Peters, Godefridus J

2011-02-10

Since in most tumors multiple signaling pathways are involved, many of the inhibitors in clinical development are designed to affect a wide range of targeted kinases. The most important tyrosine kinase families in the development of tyrosine kinase inhibitors are the ABL, SCR, platelet derived growth factor, vascular endothelial growth factor receptor and epidermal growth factor receptor families. Both multi-kinase inhibitors and single-kinase inhibitors have advantages and disadvantages, which are related to potential resistance mechanisms, pharmacokinetics, selectivity and tumor environment. In different malignancies various tyrosine kinases are mutated or overexpressed and several resistance mechanisms exist. Pharmacokinetics is influenced by interindividual differences and differs for two single targeted inhibitors or between patients treated by the same tyrosine kinase inhibitor. Different tyrosine kinase inhibitors have various mechanisms to achieve selectivity, while differences in gene expression exist between tumor and stromal cells. Considering these aspects, one type of inhibitor can generally not be preferred above the other, but will depend on the specific genetic constitution of the patient and the tumor, allowing personalized therapy. The most effective way of cancer treatment by using tyrosine kinase inhibitors is to consider each patient/tumor individually and to determine the strategy that specifically targets the consequences of altered (epi)genetics of the tumor. This strategy might result in treatment by a single multi kinase inhibitor for one patient, but in treatment by a couple of single kinase inhibitors for other patients.

Preliminary analysis of a target factory for laser fusion

International Nuclear Information System (INIS)

Sherohman, J.W.; Hendricks, C.D.

1980-01-01

An analysis of a target factory leading to the determination of production expressions has provided for the basis of a parametric study. Parameters involving the input and output rate of a process system, processing yield factors, and multiple processing steps and production lines have been used to develop an understanding of their dependence on the rate of target injection for laser fusion. Preliminary results have indicated that a parametric study of this type will be important in the selection of processing methods to be used in the final production scheme of a target factory

Trial-to-trial dynamics of selective long-term-memory retrieval with continuously changing retrieval targets.

Science.gov (United States)

Kizilirmak, Jasmin M; Rösler, Frank; Khader, Patrick H

2014-10-01

How do we control the successive retrieval of behaviorally relevant information from long-term memory (LTM) without being distracted by other potential retrieval targets associated to the same retrieval cues? Here, we approach this question by investigating the nature of trial-by-trial dynamics of selective LTM retrieval, i.e., in how far retrieval in one trial has detrimental or facilitatory effects on selective retrieval in the following trial. Participants first learned associations between retrieval cues and targets, with one cue always being linked to three targets, forming small associative networks. In successive trials, participants had to access either the same or a different target belonging to either the same or a different cue. We found that retrieval times were faster for targets that had already been relevant in the previous trial, with this facilitatory effect being substantially weaker when the associative network changed in which the targets were embedded. Moreover, staying within the same network still had a facilitatory effect even if the target changed, which became evident in a relatively higher memory performance in comparison to a network change. Furthermore, event-related brain potentials (ERPs) showed topographically and temporally dissociable correlates of these effects, suggesting that they result from combined influences of distinct processes that aid memory retrieval when relevant and irrelevant targets change their status from trial to trial. Taken together, the present study provides insight into the different processing stages of memory retrieval when fast switches between retrieval targets are required. Copyright © 2014 Elsevier Inc. All rights reserved.

Selective autophagy of non-ubiquitylated targets in plants: looking for cognate receptor/adaptor proteins

Directory of Open Access Journals (Sweden)

Vasko eVeljanovski

2014-06-01

Full Text Available Cellular homeostasis is essential for the physiology of eukaryotic cells. Eukaryotic cells, including plant cells, utilize two main pathways to adjust the level of cytoplasmic components, namely the proteasomal and the lysosomal/vacuolar pathways. Macroautophagy is a lysosomal/vacuolar pathway which, until recently, was thought to be non-specific and a bulk degradation process. However, selective autophagy which can be activated in the cell under various physiological conditions, involves the specific degradation of defined macromolecules or organelles by a conserved molecular mechanism. For this process to be efficient, the mechanisms underlying the recognition and selection of the cargo to be engulfed by the double-membrane autophagosome are critical, and not yet well understood. Ubiquitin (poly-ubiquitin conjugation to the target appears to be a conserved ligand mechanism in many types of selective autophagy, and defined receptors/adaptors recognizing and regulating the autophagosomal capture of the ubiquitylated target have been characterized. However, non-proteinaceous and non-ubiquitylated cargoes are also selectively degraded by this pathway. This ubiquitin-independent selective autophagic pathway also involves receptor and/or adaptor proteins linking the cargo to the autophagic machinery. Some of these receptor/adaptor proteins including accessory autophagy-related (Atg and non-Atg proteins have been described in yeast and animal cells but not yet in plants. In this review we discuss the ubiquitin-independent cargo selection mechanisms in selective autophagy degradation of organelles and macromolecules and speculate on potential plant receptor/adaptor proteins.

A note on “An alternative multiple attribute decision making methodology for solving optimal facility layout design selection problems”

OpenAIRE

R. Venkata Rao

2012-01-01

A paper published by Maniya and Bhatt (2011) (An alternative multiple attribute decision making methodology for solving optimal facility layout design selection problems, Computers & Industrial Engineering, 61, 542-549) proposed an alternative multiple attribute decision making method named as “Preference Selection Index (PSI) method” for selection of an optimal facility layout design. The authors had claimed that the method was logical and more appropriate and the method gives directly the o...

Foraging through multiple target categories reveals the flexibility of visual working memory.

Science.gov (United States)

Kristjánsson, Tómas; Kristjánsson, Árni

2018-02-01

A key assumption in the literature on visual attention is that templates, actively maintained in visual working memory (VWM), guide visual attention. An important question therefore involves the nature and capacity of VWM. According to load theories, more than one search template can be active at the same time and capacity is determined by the total load rather than a precise number of templates. By an alternative account only one search template can be active within visual working memory at any given time, while other templates are in an accessory state - but do not affect visual selection. We addressed this question by varying the number of targets and distractors in a visual foraging task for 40 targets among 40 distractors in two ways: 1) Fixed-distractor-number, involving two distractor types while target categories varied from one to four. 2) Fixed-color-number (7), so that if the target types were two, distractors types were five, while if target number increased to three, distractor types were four (etc.). The two accounts make differing predictions. Under the single-template account, we should expect large switch costs as target types increase to two, but switch-costs should not increase much as target types increase beyond two. Load accounts predict an approximately linear increase in switch costs with increased target type number. The results were that switch costs increased roughly linearly in both conditions, in line with load accounts. The results are discussed in light of recent proposals that working memory reflects lingering neural activity at various sites that operate on the stimuli in each case and findings showing neurally silent working memory representations. Copyright © 2017 Elsevier B.V. All rights reserved.

P2-21: Searching for Multiple Targets Using the iPad

Directory of Open Access Journals (Sweden)

Ian Thornton

2012-10-01

Full Text Available Search for multiple targets is constrained by both retrospective (i.e., where you've been and prospective (i.e., where you're planning to go components of performance. Previous studies using the Multi-Item Localisation (MILO task have demonstrated that participants accurately remember and discount locations they have already visited and that they plan future actions up to 2 or 3 items ahead (Thornton & Horowitz, 2004 Perception & Psychophysics 66 38–50. A prominent feature of the MILO serial-reaction time (SRT function is a highly elevated, that is slowed, response, to T1 compared to T2 and all the other items. This “prospective gap” is typically between 600 ms and 1000 ms. Here we present three experiments that use the MILO iPad app to explore this “prospective gap”. In Experiment 1, we “shuffled” the position of future targets each time a response was made. This blocks planning and thus slows all responses to the level of first target, effectively eliminating the gap. In Experiment 2, participants responded to eight identical targets, removing the need to plan a specific sequence of actions. In this situation, absolute response time is greatly reduced and the T1–T2 gap shrinks to around 350 ms. In Experiment 3, participants repeated their search through the same array 10 times. Under these circumstances, the gap systematically reduced from 1300 ms on trial 1 to 300 ms on trial 10. Together, these results suggest that the previously observed prospective gap is a combination of set-up time for registering a new visual layout, response preparation, and sequence planning.

Realization of quantum gates with multiple control qubits or multiple target qubits in a cavity

Science.gov (United States)

Waseem, Muhammad; Irfan, Muhammad; Qamar, Shahid

2015-06-01

We propose a scheme to realize a three-qubit controlled phase gate and a multi-qubit controlled NOT gate of one qubit simultaneously controlling n-target qubits with a four-level quantum system in a cavity. The implementation time for multi-qubit controlled NOT gate is independent of the number of qubit. Three-qubit phase gate is generalized to n-qubit phase gate with multiple control qubits. The number of steps reduces linearly as compared to conventional gate decomposition method. Our scheme can be applied to various types of physical systems such as superconducting qubits coupled to a resonator and trapped atoms in a cavity. Our scheme does not require adjustment of level spacing during the gate implementation. We also show the implementation of Deutsch-Joza algorithm. Finally, we discuss the imperfections due to cavity decay and the possibility of physical implementation of our scheme.

Systematic approach to optimize a pretreatment method for ultrasensitive liquid chromatography with tandem mass spectrometry analysis of multiple target compounds in biological samples.

Science.gov (United States)

Togashi, Kazutaka; Mutaguchi, Kuninori; Komuro, Setsuko; Kataoka, Makoto; Yamazaki, Hiroshi; Yamashita, Shinji

2016-08-01

In current approaches for new drug development, highly sensitive and robust analytical methods for the determination of test compounds in biological samples are essential. These analytical methods should be optimized for every target compound. However, for biological samples that contain multiple compounds as new drug candidates obtained by cassette dosing tests, it would be preferable to develop a single method that allows the determination of all compounds at once. This study aims to establish a systematic approach that enables a selection of the most appropriate pretreatment method for multiple target compounds without the use of their chemical information. We investigated the retention times of 27 known compounds under different mobile phase conditions and determined the required pretreatment of human plasma samples using several solid-phase and liquid-liquid extractions. From the relationship between retention time and recovery in a principal component analysis, appropriate pretreatments were categorized into several types. Based on the category, we have optimized a pretreatment method for the identification of three calcium channel blockers in human plasma. Plasma concentrations of these drugs in a cassette-dose clinical study at microdose level were successfully determined with a lower limit of quantitation of 0.2 pg/mL for diltiazem, 1 pg/mL for nicardipine, and 2 pg/mL for nifedipine. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Band selection method based on spectrum difference in targets of interest in hyperspectral imagery

Science.gov (United States)

Zhang, Xiaohan; Yang, Guang; Yang, Yongbo; Huang, Junhua

2016-10-01

While hyperspectral data shares rich spectrum information, it has numbers of bands with high correlation coefficients, causing great data redundancy. A reasonable band selection is important for subsequent processing. Bands with large amount of information and low correlation should be selected. On this basis, according to the needs of target detection applications, the spectral characteristics of the objects of interest are taken into consideration in this paper, and a new method based on spectrum difference is proposed. Firstly, according to the spectrum differences of targets of interest, a difference matrix which represents the different spectral reflectance of different targets in different bands is structured. By setting a threshold, the bands satisfying the conditions would be left, constituting a subset of bands. Then, the correlation coefficients between bands are calculated and correlation matrix is given. According to the size of the correlation coefficient, the bands can be set into several groups. At last, the conception of normalized variance is used on behalf of the information content of each band. The bands are sorted by the value of its normalized variance. Set needing number of bands, and the optimum band combination solution can be get by these three steps. This method retains the greatest degree of difference between the target of interest and is easy to achieve by computer automatically. Besides, false color image synthesis experiment is carried out using the bands selected by this method as well as other 3 methods to show the performance of method in this paper.

Targeting multiple heterogeneous hardware platforms with OpenCL

Science.gov (United States)

Fox, Paul A.; Kozacik, Stephen T.; Humphrey, John R.; Paolini, Aaron; Kuller, Aryeh; Kelmelis, Eric J.

2014-06-01

The OpenCL API allows for the abstract expression of parallel, heterogeneous computing, but hardware implementations have substantial implementation differences. The abstractions provided by the OpenCL API are often insufficiently high-level to conceal differences in hardware architecture. Additionally, implementations often do not take advantage of potential performance gains from certain features due to hardware limitations and other factors. These factors make it challenging to produce code that is portable in practice, resulting in much OpenCL code being duplicated for each hardware platform being targeted. This duplication of effort offsets the principal advantage of OpenCL: portability. The use of certain coding practices can mitigate this problem, allowing a common code base to be adapted to perform well across a wide range of hardware platforms. To this end, we explore some general practices for producing performant code that are effective across platforms. Additionally, we explore some ways of modularizing code to enable optional optimizations that take advantage of hardware-specific characteristics. The minimum requirement for portability implies avoiding the use of OpenCL features that are optional, not widely implemented, poorly implemented, or missing in major implementations. Exposing multiple levels of parallelism allows hardware to take advantage of the types of parallelism it supports, from the task level down to explicit vector operations. Static optimizations and branch elimination in device code help the platform compiler to effectively optimize programs. Modularization of some code is important to allow operations to be chosen for performance on target hardware. Optional subroutines exploiting explicit memory locality allow for different memory hierarchies to be exploited for maximum performance. The C preprocessor and JIT compilation using the OpenCL runtime can be used to enable some of these techniques, as well as to factor in hardware

Detecting and Georegistering Moving Ground Targets in Airborne QuickSAR via Keystoning and Multiple-Phase Center Interferometry

Directory of Open Access Journals (Sweden)

R. P. Perry

2008-03-01

Full Text Available SAR images experience significant range walk and, without some form of motion compensation, can be quite blurred. The MITRE-developed Keystone formatting simultaneously and automatically compensates for range walk due to the radial velocity component of each moving target, independent of the number of targets or the value of each target's radial velocity with respect to the ground. Target radial motion also causes moving targets in synthetic aperture radar images to appear at locations offset from their true instantaneous locations on the ground. In a multichannel radar, the interferometric phase values associated with all nonmoving points on the ground appear as a continuum of phase differences while the moving targets appear as interferometric phase discontinuities. By multiple threshold comparisons and grouping of pixels within the intensity and the phase images, we show that it is possible to reliably detect and accurately georegister moving targets within short-duration SAR (QuickSAR images.

ERP markers of target selection discriminate children with high vs. low working memory capacity

Directory of Open Access Journals (Sweden)

Andria eShimi

2015-11-01

Full Text Available Selective attention enables enhancing a subset out of multiple competing items to maximize the capacity of our limited visual working memory (VWM system. Multiple behavioral and electrophysiological studies have revealed the cognitive and neural mechanisms supporting adults’ selective attention of visual percepts for encoding in VWM. However, research on children is more limited. What are the neural mechanisms involved in children’s selection of incoming percepts in service of VWM? Do these differ from the ones subserving adults’ selection? Ten-year-olds and adults used a spatial arrow cue to select a colored item for later recognition from an array of four colored items. The temporal dynamics of selection were investigated through EEG signals locked to the onset of the memory array. Both children and adults elicited significantly more negative activity over posterior scalp locations contralateral to the item to-be-selected for encoding (N2pc. However, this activity was elicited later and for longer in children compared to adults. Furthermore, although children as a group did not elicit a significant N2pc during the time-window in which N2pc was elicited in adults, the magnitude of N2pc during the adult time-window related to their behavioral performance during the later recognition phase of the task. This in turn highlights how children’s neural activity subserving attention during encoding relates to better subsequent VWM performance. Significant differences were observed when children were divided into groups of high vs. low VWM capacity as a function of cueing benefit. Children with large cue benefits in VWM capacity elicited an adult-like contralateral negativity following attentional selection of the to-be-encoded item, whereas children with low VWM capacity did not. These results corroborate the close coupling between selective attention and VWM from childhood and elucidate further the attentional mechanisms constraining VWM

ERP markers of target selection discriminate children with high vs. low working memory capacity.

Science.gov (United States)

Shimi, Andria; Nobre, Anna Christina; Scerif, Gaia

2015-01-01

Selective attention enables enhancing a subset out of multiple competing items to maximize the capacity of our limited visual working memory (VWM) system. Multiple behavioral and electrophysiological studies have revealed the cognitive and neural mechanisms supporting adults' selective attention of visual percepts for encoding in VWM. However, research on children is more limited. What are the neural mechanisms involved in children's selection of incoming percepts in service of VWM? Do these differ from the ones subserving adults' selection? Ten-year-olds and adults used a spatial arrow cue to select a colored item for later recognition from an array of four colored items. The temporal dynamics of selection were investigated through EEG signals locked to the onset of the memory array. Both children and adults elicited significantly more negative activity over posterior scalp locations contralateral to the item to-be-selected for encoding (N2pc). However, this activity was elicited later and for longer in children compared to adults. Furthermore, although children as a group did not elicit a significant N2pc during the time-window in which N2pc was elicited in adults, the magnitude of N2pc during the "adult time-window" related to their behavioral performance during the later recognition phase of the task. This in turn highlights how children's neural activity subserving attention during encoding relates to better subsequent VWM performance. Significant differences were observed when children were divided into groups of high vs. low VWM capacity as a function of cueing benefit. Children with large cue benefits in VWM capacity elicited an adult-like contralateral negativity following attentional selection of the to-be-encoded item, whereas children with low VWM capacity did not. These results corroborate the close coupling between selective attention and VWM from childhood and elucidate further the attentional mechanisms constraining VWM performance in children.

Monoclonal IgG in MGUS and multiple myeloma targets infectious pathogens

Science.gov (United States)

Bosseboeuf, Adrien; Feron, Delphine; Tallet, Anne; Rossi, Cédric; Charlier, Cathy; Garderet, Laurent; Caillot, Denis; Moreau, Philippe; Cardó-Vila, Marina; Pasqualini, Renata; Nelson, Alfreda Destea; Wilson, Bridget S.; Perreault, Hélène; Piver, Eric; Weigel, Pierre; Harb, Jean; Bigot-Corbel, Edith; Hermouet, Sylvie

2017-01-01

Subsets of mature B cell neoplasms are linked to infection with intracellular pathogens such as Epstein-Barr virus (EBV), hepatitis C virus (HCV), or Helicobacter pylori. However, the association between infection and the immunoglobulin-secreting (Ig-secreting) B proliferative disorders remains largely unresolved. We investigated whether the monoclonal IgG (mc IgG) produced by patients diagnosed with monoclonal gammopathy of undetermined significance (MGUS) or multiple myeloma (MM) targets infectious pathogens. Antigen specificity of purified mc IgG from a large patient cohort (n = 244) was determined using a multiplex infectious-antigen array (MIAA), which screens for reactivity to purified antigens or lysates from 9 pathogens. Purified mc IgG from 23.4% of patients (57 of 244) specifically recognized 1 pathogen in the MIAA. EBV was the most frequent target (15.6%), with 36 of 38 mc IgGs recognizing EBV nuclear antigen-1 (EBNA-1). MM patients with EBNA-1–specific mc IgG (14.0%) showed substantially greater bone marrow plasma cell infiltration and higher β2-microglobulin and inflammation/infection–linked cytokine levels compared with other smoldering myeloma/MM patients. Five other pathogens were the targets of mc IgG: herpes virus simplex-1 (2.9%), varicella zoster virus (1.6%), cytomegalovirus (0.8%), hepatitis C virus (1.2%), and H. pylori (1.2%). We conclude that a dysregulated immune response to infection may underlie disease onset and/or progression of MGUS and MM for subsets of patients. PMID:28978808

Residue-based Coordinated Selection and Parameter Design of Multiple Power System Stabilizers (PSSs)

DEFF Research Database (Denmark)

Su, Chi; Hu, Weihao; Fang, Jiakun

2013-01-01

data from time domain simulations. Then a coordinated approach for multiple PSS selection and parameter design based on residue method is proposed and realized in MATLAB m-files. Particle swarm optimization (PSO) is adopted in the coordination process. The IEEE 39-bus New England system model...

Novel Chemokine-Based Immunotoxins for Potent and Selective Targeting of Cytomegalovirus Infected Cells

DEFF Research Database (Denmark)

Spiess, Katja; Jeppesen, Mads G.; Malmgaard-Clausen, Mikkel

2017-01-01

Immunotoxins as antiviral therapeutics are largely unexplored but have promising prospective due to their high selectivity potential and their unparalleled efficiency. One recent example targeted the virus-encoded G protein-coupled receptor US28 as a strategy for specific and efficient treatment ...

A genetic algorithm for multiple relay selection in two-way relaying cognitive radio networks

KAUST Repository

Alsharoa, Ahmad M.; Ghazzai, Hakim; Alouini, Mohamed-Slim

2013-01-01

In this paper, we investigate a multiple relay selection scheme for two-way relaying cognitive radio networks where primary users and secondary users operate on the same frequency band. More specifically, cooperative relays using Amplifyand- Forward

Selective dentate gyrus disruption causes memory impairment at the early stage of experimental multiple sclerosis.

Science.gov (United States)

Planche, Vincent; Panatier, Aude; Hiba, Bassem; Ducourneau, Eva-Gunnel; Raffard, Gerard; Dubourdieu, Nadège; Maitre, Marlène; Lesté-Lasserre, Thierry; Brochet, Bruno; Dousset, Vincent; Desmedt, Aline; Oliet, Stéphane H; Tourdias, Thomas

2017-02-01

Memory impairment is an early and disabling manifestation of multiple sclerosis whose anatomical and biological substrates are still poorly understood. We thus investigated whether memory impairment encountered at the early stage of the disease could be explained by a differential vulnerability of particular hippocampal subfields. By using experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis, we identified that early memory impairment was associated with selective alteration of the dentate gyrus as pinpointed in vivo with diffusion-tensor-imaging (DTI). Neuromorphometric analyses and electrophysiological recordings confirmed dendritic degeneration, alteration in glutamatergic synaptic transmission and impaired long-term synaptic potentiation selectively in the dentate gyrus, but not in CA1, together with a more severe pattern of microglial activation in this subfield. Systemic injections of the microglial inhibitor minocycline prevented DTI, morphological, electrophysiological and behavioral impairments in EAE-mice. Furthermore, daily infusions of minocycline specifically within the dentate gyrus were sufficient to prevent memory impairment in EAE-mice while infusions of minocycline within CA1 were inefficient. We conclude that early memory impairment in EAE is due to a selective disruption of the dentate gyrus associated with microglia activation. These results open new pathophysiological, imaging, and therapeutic perspectives for memory impairment in multiple sclerosis. Copyright © 2016 Elsevier Inc. All rights reserved.

State-selective electron capture into He-like U90+ ions in collisions with gaseous targets

International Nuclear Information System (INIS)

Ma, X.; Stoehlker, T.; Brinzanescu, O.; Fritzsche, S.; Ludziejewski, T.; Stachura, Z.; Warczak, A.

2000-11-01

For He-like uranium, a state-selective electron capture study was carried out for relativistic collisions with gaseous targets. In the experiment, the projectile X-ray emission produced by electron capture in collisions of 223 MeV/u U 90+ ions on N 2 , Ar, Kr, and Xe targets was measured in coincidence with down-charged U 89+ projectiles. Due to the large fine structure splitting in heavy ions, the well resolved Balmer transitions observed were used to deduce subshell sensitive cross-sections for electron capture. For this purpose a theoretical spectrum analysis and simulation was performed by taking into account electron cascades from states up to n = 40. The state-selective data are compared with theoretical calculations as a function of target atomic number. An overall agreement is found between the experimental data and the theoretical approaches applied except for the j-sensitive part. (orig.)

Nucleotide excision repair is a potential therapeutic target in multiple myeloma

Science.gov (United States)

Szalat, R; Samur, M K; Fulciniti, M; Lopez, M; Nanjappa, P; Cleynen, A; Wen, K; Kumar, S; Perini, T; Calkins, A S; Reznichenko, E; Chauhan, D; Tai, Y-T; Shammas, M A; Anderson, K C; Fermand, J-P; Arnulf, B; Avet-Loiseau, H; Lazaro, J-B; Munshi, N C

2018-01-01

Despite the development of novel drugs, alkylating agents remain an important component of therapy in multiple myeloma (MM). DNA repair processes contribute towards sensitivity to alkylating agents and therefore we here evaluate the role of nucleotide excision repair (NER), which is involved in the removal of bulky adducts and DNA crosslinks in MM. We first evaluated NER activity using a novel functional assay and observed a heterogeneous NER efficiency in MM cell lines and patient samples. Using next-generation sequencing data, we identified that expression of the canonical NER gene, excision repair cross-complementation group 3 (ERCC3), significantly impacted the outcome in newly diagnosed MM patients treated with alkylating agents. Next, using small RNA interference, stable knockdown and overexpression, and small-molecule inhibitors targeting xeroderma pigmentosum complementation group B (XPB), the DNA helicase encoded by ERCC3, we demonstrate that NER inhibition significantly increases sensitivity and overcomes resistance to alkylating agents in MM. Moreover, inhibiting XPB leads to the dual inhibition of NER and transcription and is particularly efficient in myeloma cells. Altogether, we show that NER impacts alkylating agents sensitivity in myeloma cells and identify ERCC3 as a potential therapeutic target in MM. PMID:28588253

An evolvable oestrogen receptor activity sensor: development of a modular system for integrating multiple genes into the yeast genome

NARCIS (Netherlands)

Fox, J.E.; Bridgham, J.T.; Bovee, T.F.H.; Thornton, J.W.

2007-01-01

To study a gene interaction network, we developed a gene-targeting strategy that allows efficient and stable genomic integration of multiple genetic constructs at distinct target loci in the yeast genome. This gene-targeting strategy uses a modular plasmid with a recyclable selectable marker and a

Breeding approaches in simultaneous selection for multiple stress tolerance of maize in tropical environments

Directory of Open Access Journals (Sweden)

Denić M.

2007-01-01

Full Text Available Maize is the principal crop and major staple food in the most countries of Sub-Saharan Africa. However, due to the influence of abiotic and biotic stress factors, maize production faces serious constraints. Among the agro-ecological conditions, the main constraints are: lack and poor distribution of rainfall; low soil fertility; diseases (maize streak virus, downy mildew, leaf blights, rusts, gray leaf spot, stem/cob rots and pests (borers and storage pests. Among the socio-economic production constraints are: poor economy, serious shortage of trained manpower; insufficient management expertise, lack of use of improved varieties and poor cultivation practices. To develop desirable varieties, and thus consequently alleviate some of these constraints, appropriate breeding approaches and field-based methodologies in selection for multiple stress tolerance, were implemented. These approaches are mainly based on: a Crossing selected genotypes with more desirable stress tolerant and other agronomic traits; b Using the disease/pest spreader row method, combined with testing and selection of created progenies under strong to intermediate pressure of drought and low soil fertility in nurseries; and c Evaluation of the varieties developed in multi-location trials under low and "normal" inputs. These approaches provide testing and selection of large number of progenies, which is required for simultaneous selection for multiple stress tolerance. Data obtained revealed that remarkable improvement of the traits under selection was achieved. Biggest progress was obtained in selection for maize streak virus and downy mildew resistance, flintiness and earliness. In the case of drought stress, statistical analyses revealed significant negative correlation between yield and anthesis-silking interval, and between yield and days to silk, but positive correlation between yield and grain weight per ear.

SPIDERS: selection of spectroscopic targets using AGN candidates detected in all-sky X-ray surveys

Science.gov (United States)

Dwelly, T.; Salvato, M.; Merloni, A.; Brusa, M.; Buchner, J.; Anderson, S. F.; Boller, Th.; Brandt, W. N.; Budavári, T.; Clerc, N.; Coffey, D.; Del Moro, A.; Georgakakis, A.; Green, P. J.; Jin, C.; Menzel, M.-L.; Myers, A. D.; Nandra, K.; Nichol, R. C.; Ridl, J.; Schwope, A. D.; Simm, T.

2017-07-01

SPIDERS (SPectroscopic IDentification of eROSITA Sources) is a Sloan Digital Sky Survey IV (SDSS-IV) survey running in parallel to the Extended Baryon Oscillation Spectroscopic Survey (eBOSS) cosmology project. SPIDERS will obtain optical spectroscopy for large numbers of X-ray-selected active galactic nuclei (AGN) and galaxy cluster members detected in wide-area eROSITA, XMM-Newton and ROSAT surveys. We describe the methods used to choose spectroscopic targets for two sub-programmes of SPIDERS X-ray selected AGN candidates detected in the ROSAT All Sky and the XMM-Newton Slew surveys. We have exploited a Bayesian cross-matching algorithm, guided by priors based on mid-IR colour-magnitude information from the Wide-field Infrared Survey Explorer survey, to select the most probable optical counterpart to each X-ray detection. We empirically demonstrate the high fidelity of our counterpart selection method using a reference sample of bright well-localized X-ray sources collated from XMM-Newton, Chandra and Swift-XRT serendipitous catalogues, and also by examining blank-sky locations. We describe the down-selection steps which resulted in the final set of SPIDERS-AGN targets put forward for spectroscopy within the eBOSS/TDSS/SPIDERS survey, and present catalogues of these targets. We also present catalogues of ˜12 000 ROSAT and ˜1500 XMM-Newton Slew survey sources that have existing optical spectroscopy from SDSS-DR12, including the results of our visual inspections. On completion of the SPIDERS programme, we expect to have collected homogeneous spectroscopic redshift information over a footprint of ˜7500 deg2 for >85 per cent of the ROSAT and XMM-Newton Slew survey sources having optical counterparts in the magnitude range 17 < r < 22.5, producing a large and highly complete sample of bright X-ray-selected AGN suitable for statistical studies of AGN evolution and clustering.

One Novel Multiple-Target Plasmid Reference Molecule Targeting Eight Genetically Modified Canola Events for Genetically Modified Canola Detection.

Science.gov (United States)

Li, Zhuqing; Li, Xiang; Wang, Canhua; Song, Guiwen; Pi, Liqun; Zheng, Lan; Zhang, Dabing; Yang, Litao

2017-09-27

Multiple-target plasmid DNA reference materials have been generated and utilized as good substitutes of matrix-based reference materials in the analysis of genetically modified organisms (GMOs). Herein, we report the construction of one multiple-target plasmid reference molecule, pCAN, which harbors eight GM canola event-specific sequences (RF1, RF2, MS1, MS8, Topas 19/2, Oxy235, RT73, and T45) and a partial sequence of the canola endogenous reference gene PEP. The applicability of this plasmid reference material in qualitative and quantitative PCR assays of the eight GM canola events was evaluated, including the analysis of specificity, limit of detection (LOD), limit of quantification (LOQ), and performance of pCAN in the analysis of various canola samples, etc. The LODs are 15 copies for RF2, MS1, and RT73 assays using pCAN as the calibrator and 10 genome copies for the other events. The LOQ in each event-specific real-time PCR assay is 20 copies. In quantitative real-time PCR analysis, the PCR efficiencies of all event-specific and PEP assays are between 91% and 97%, and the squared regression coefficients (R 2 ) are all higher than 0.99. The quantification bias values varied from 0.47% to 20.68% with relative standard deviation (RSD) from 1.06% to 24.61% in the quantification of simulated samples. Furthermore, 10 practical canola samples sampled from imported shipments in the port of Shanghai, China, were analyzed employing pCAN as the calibrator, and the results were comparable with those assays using commercial certified materials as the calibrator. Concluding from these results, we believe that this newly developed pCAN plasmid is one good candidate for being a plasmid DNA reference material in the detection and quantification of the eight GM canola events in routine analysis.

Candidate Targets for New Anti-Virulence Drugs: Selected Cases of Bacterial Adhesion and Biofilm Formation

DEFF Research Database (Denmark)

Klemm, Per; Hancock, Viktoria; Kvist, Malin

2007-01-01

is particularly problematic in medical contexts because biofilm-associated bacteria are particularly hard to eradicate. Several promising candidate drugs that target bacterial adhesion and biofilm formation are being developed. Some of these might be valuable weapons for fighting infectious diseases in the future...... formation are highly attractive targets for new drugs. Specific adhesion provides bacteria with target selection and prevents removal by hydrodynamic flow forces. Bacterial adhesion is of paramount importance for bacterial pathogenesis. Adhesion is also the first step in biofilm formation. Biofilm formation...

The control of single-colour and multiple-colour visual search by attentional templates in working memory and in long-term memory

OpenAIRE

Grubert, Anna; Carlisle, N.; Eimer, Martin

2016-01-01

The question whether target selection in visual search can be effectively controlled by simultaneous attentional templates for multiple features is still under dispute. We investigated whether multiple-colour attentional guidance is possible when target colours remain constant and can thus be represented in long-term memory but not when they change frequently and have to be held in working memory. Participants searched for one, two, or three possible target colours that were specified by cue ...

The TESS Input Catalog and Selection of Targets for the TESS Transit Search

Science.gov (United States)

Pepper, Joshua; Stassun, Keivan G.; Paegert, Martin; Oelkers, Ryan; De Lee, Nathan Michael; Torres, Guillermo; TESS Target Selection Working Group

2018-01-01

The TESS mission will photometrically survey millions of the brightest stars over almost the entire the sky to detect transiting exoplanets. A key step to enable that search is the creation of the TESS Input Catalog (TIC), a compiled catalog of 700 million stars and galaxies with observed and calculated parameters. From the TIC we derive the Candidate Target List (CTL) to identify target stars for the 2-minute TESS postage stamps. The CTL is designed to identify the best stars for the detection of small planets, which includes all bright cool dwarf stars in the sky. I will describe the target selection strategy, the distribution of stars in the current CTL, and how both the TIC and CTL will expand and improve going forward.

Targeting TMPRSS2 ERG in Prostate Cancer

Science.gov (United States)

2016-09-01

kinome library, using physiologic cell based assays of ERG activity. We made lentivirus expressing multiple shRNAs targeting each candidate 9...MDV3100 reverses the effect of R1881 (compare columns 2 and 3). Interestingly, PKCi inhibited a subset of androgen induced genes ( column 4...expenditures Nothing to report. Significant changes in use or care of human subjects, vertebrate animals, biohazards, and/or select agents Nothing to

Visual Search for Motion-Form Conjunctions: Selective Attention to Movement Direction.

Science.gov (United States)

Von Mühlenen, Adrian; Müller, Hermann J

1999-07-01

In 2 experiments requiring visual search for conjunctions of motion and form, the authors reinvestigated whether motion-based filtering (e.g., P. McLeod, J. Driver, Z. Dienes, & J. Crisp, 1991) is direction selective and whether cuing of the target direction promotes efficient search performance. In both experiments, the authors varied the number of movement directions in the display and the predictability of the target direction. Search was less efficient when items moved in multiple (2, 3, and 4) directions as compared with just 1 direction. Furthermore, precuing of the target direction facilitated the search, even with "wrap-around" displays, relatively more when items moved in multiple directions. The authors proposed 2 principles to explain that pattern of effects: (a) interference on direction computation between items moving in different directions (e.g., N. Qian & R. A. Andersen, 1994) and (b) selective direction tuning of motion detectors involving a receptive-field contraction (cf. J. Moran & R. Desimone, 1985; S. Treue & J. H. R. Maunsell, 1996).

Multiple targets of salicylic acid and its derivatives in plants and animals

Directory of Open Access Journals (Sweden)

Daniel F. Klessig

2016-05-01

Full Text Available Salicylic acid (SA is a critical plant hormone that is involved in many processes, including seed germination, root initiation, stomatal closure, floral induction, thermogenesis, and response to abiotic and biotic stresses. Its central role in plant immunity, although extensively studied, is still only partially understood. Classical biochemical approaches and, more recently, genome-wide high-throughput screens have identified more than two dozen plant SA-binding proteins (SABPs, as well as multiple candidates that have yet to be characterized. Some of these proteins bind SA with high affinity, while the affinity others exhibit is low. Given that SA levels vary greatly even within a particular plant species depending on subcellular location, tissue type, developmental stage, and with respect to both time and location after an environmental stimulus such as infection, the presence of SABPs exhibiting a wide range of affinities for SA may provide great flexibility and multiple mechanisms through which SA can act. SA and its derivatives, both natural and synthetic, also have multiple targets in animals/humans. Interestingly, many of these proteins, like their plant counterparts, are associated with immunity or disease development. Two recently identified SABPs, High Mobility Group Box protein (HMGB and Glyceraldehyde 3-Phosphate Dehydrogenase (GAPDH, are critical proteins that not only serve key structural or metabolic functions, but also play prominent roles in disease responses in both kingdoms.

Promysalin Elicits Species-Selective Inhibition of Pseudomonas aeruginosa by Targeting Succinate Dehydrogenase.

Science.gov (United States)

Keohane, Colleen E; Steele, Andrew D; Fetzer, Christian; Khowsathit, Jittasak; Van Tyne, Daria; Moynié, Lucile; Gilmore, Michael S; Karanicolas, John; Sieber, Stephan A; Wuest, William M

2018-02-07

Natural products have served as an inspiration to scientists both for their complex three-dimensional architecture and exquisite biological activity. Promysalin is one such Pseudomonad secondary metabolite that exhibits narrow-spectrum antibacterial activity, originally isolated from the rhizosphere. We herein utilize affinity-based protein profiling (AfBPP) to identify succinate dehydrogenase (Sdh) as the biological target of the natural product. The target was further validated in silico, in vitro, in vivo, and through the selection, and sequencing, of a resistant mutant. Succinate dehydrogenase plays an essential role in primary metabolism of Pseudomonas aeruginosa as the only enzyme that is involved both in the tricarboxylic acid cycle (TCA) and in respiration via the electron transport chain. These findings add credence to other studies that suggest that the TCA cycle is an understudied target in the development of novel therapeutics to combat P. aeruginosa, a significant pathogen in clinical settings.

The diffusion properties of ion implanted species in selected target materials

International Nuclear Information System (INIS)

Alton, G.D.; Dellwo, J.; Carter, H.K.; Kormicki, J.; Bartolo, G. di; Batchelder, J.C.; Breitenbach, J.; Chediak, J.A.; Jentoff-Nilsen, K.; Ichikawa, S.

1995-01-01

Experiments important to the future success of the Holifield Radioactive Ion Beam Facility (HRIBF) are in progress at the Oak Ridge National Laboratory which are designed to select the most appropriate target material for generating a particular radioactive ion beam (RIB). The 25-MV HHIRF tandem accelerator is used to implant stable complements of interesting radioactive elements into refractory targets mounted in a high-temperature FEBIAD ion source which is open-quotes on-lineclose quotes at the UNISOR facility. The intensity versus time of implanted species, which diffuse from the high-temperature target material (∼1700 degrees C) and are ionized in the FEBIAD ion source, is used to determine release times for a particular projectile/target material combination. From such release data, diffusion coefficients can be derived by fitting the theoretical results obtained by computational solution of Fick's second equation to experimental data. The diffusion coefficient can be used subsequently to predict the release properties of the particular element from the same material in other target geometries and at other temperatures, provided that the activation energy is also known. Diffusion coefficients for Cl implanted into and diffused from CeS and Zr 5 Si 3 and As, Br, and Se implanted into and diffused from Zr 5 Ge 3 have been derived from the resulting intensity versus time profiles. Brief descriptions of the experimental apparatus and procedures utilized in the present experiments and plans for future related experiments are presented

Merger and Acquisition Target Selection Based on Interval Neutrosophic Multigranulation Rough Sets over Two Universes

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Chao Zhang

2017-07-01

Full Text Available As a significant business activity, merger and acquisition (M&A generally means transactions in which the ownership of companies, other business organizations or their operating units are transferred or combined. In a typical M&A procedure, M&A target selection is an important issue that tends to exert an increasingly significant impact on different business areas. Although some research works based on fuzzy methods have been explored on this issue, they can only deal with incomplete and uncertain information, but not inconsistent and indeterminate information that exists universally in the decision making process. Additionally, it is advantageous to solve M&A problems under the group decision making context. In order to handle these difficulties in M&A target selection background, we introduce a novel rough set model by combining interval neutrosophic sets (INSs with multigranulation rough sets over two universes, called an interval neutrosophic (IN multigranulation rough set over two universes. Then, we discuss the definition and some fundamental properties of the proposed model. Finally, we establish decision making rules and computing approaches for the proposed model in M&A target selection background, and the effectiveness of the decision making approach is demonstrated by an illustrative case analysis.

Temporal brain dynamics of multiple object processing: the flexibility of individuation.

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Veronica Mazza

Full Text Available The ability to process concurrently multiple visual objects is fundamental for a coherent perception of the world. A core component of this ability is the simultaneous individuation of multiple objects. Many studies have addressed the mechanism of object individuation but it remains unknown whether the visual system mandatorily individuates all relevant elements in the visual field, or whether object indexing depends on task demands. We used a neural measure of visual selection, the N2pc component, to evaluate the flexibility of multiple object individuation. In three ERP experiments, participants saw a variable number of target elements among homogenous distracters and performed either an enumeration task (Experiment 1 or a detection task, reporting whether at least one (Experiment 2 or a specified number of target elements (Experiment 3 was present. While in the enumeration task the N2pc response increased as a function of the number of targets, no such modulation was found in Experiment 2, indicating that individuation of multiple targets is not mandatory. However, a modulation of the N2pc similar to the enumeration task was visible in Experiment 3, further highlighting that object individuation is a flexible mechanism that binds indexes to object properties and locations as needed for further object processing.

Aberrant Time to Most Recent Common Ancestor as a Signature of Natural Selection.

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Hunter-Zinck, Haley; Clark, Andrew G

2015-10-01

Natural selection inference methods often target one mode of selection of a particular age and strength. However, detecting multiple modes simultaneously, or with atypical representations, would be advantageous for understanding a population's evolutionary history. We have developed an anomaly detection algorithm using distributions of pairwise time to most recent common ancestor (TMRCA) to simultaneously detect multiple modes of natural selection in whole-genome sequences. As natural selection distorts local genealogies in distinct ways, the method uses pairwise TMRCA distributions, which approximate genealogies at a nonrecombining locus, to detect distortions without targeting a specific mode of selection. We evaluate the performance of our method, TSel, for both positive and balancing selection over different time-scales and selection strengths and compare TSel's performance with that of other methods. We then apply TSel to the Complete Genomics diversity panel, a set of human whole-genome sequences, and recover loci previously inferred to be under positive or balancing selection. © The Author 2015. Published by Oxford University Press on behalf of the Society for Molecular Biology and Evolution. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

D- production by multiple charge-transfer collisions in metal-vapor targets. [1 to 50 keV D/sup +/

Energy Technology Data Exchange (ETDEWEB)

Schlachter, A.S.

1977-09-01

A beam of D/sup -/ions can be produced by multiple charge-transfer collisions of a D/sup +/ beam in a thick metal-vapor target. Cross sections and equilibrium charge-state fractions are presented and discussed.

Perceptions of similarity and response to selected comparison targets in type 2 diabetes.

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Arigo, Danielle; Smyth, Joshua M; Suls, Jerry M

2015-01-01

Social comparisons (i.e. self-evaluations relative to others) may affect motivation for diabetes self-care behaviours. Comparisons can have either positive or negative effects, but it is not clear what differentiates these responses. This study tested the effect of a patient's perceived similarity to a comparison target on motivation for self-care. Individuals with type 2 diabetes (n = 180, MA1c = 7.59%) selected to read one of four brief descriptions of a patient with diabetes. Participants rated their motivation for self-care behaviours prior and subsequent to reading and reported the extent to which they focused on similarities between the self and the selected patient while reading. Perceived similarity moderated the effect of selection on motivation for self-care (p = .01, η2 = .06). Increased motivation was observed if participants focused on similarities with patients 'doing better' (i.e. high coping effectiveness/low symptom severity) and decreased motivation if they focused on similarities with patients 'doing worse' (low coping effectiveness/high symptom severity). Providing social comparison information in diabetes management (and perhaps other chronic diseases) may improve motivation for self-care among some patients. A subset of patients, however, may benefit from guidance to focus on similarities with certain targets.

Global Calibration of Multiple Cameras Based on Sphere Targets

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Junhua Sun

2016-01-01

Full Text Available Global calibration methods for multi-camera system are critical to the accuracy of vision measurement. Proposed in this paper is such a method based on several groups of sphere targets and a precision auxiliary camera. Each camera to be calibrated observes a group of spheres (at least three, while the auxiliary camera observes all the spheres. The global calibration can be achieved after each camera reconstructs the sphere centers in its field of view. In the process of reconstructing a sphere center, a parameter equation is used to describe the sphere projection model. Theoretical analysis and computer simulation are carried out to analyze the factors that affect the calibration accuracy. Simulation results show that the parameter equation can largely improve the reconstruction accuracy. In the experiments, a two-camera system calibrated by our method is used to measure a distance about 578 mm, and the root mean squared error is within 0.14 mm. Furthermore, the experiments indicate that the method has simple operation and good flexibility, especially for the onsite multiple cameras without common field of view.

Selection of RIB targets using ion implantation at the Holifield radioactive ion beam facility

International Nuclear Information System (INIS)

Alton, G.D.; Dellwo, J.

1995-01-01

Among several major challenges posed by generating and accelerating adequate intensities of RIBs, selection of the most appropriate target material is perhaps the most difficult because of the requisite fast and selective thermal release of minute amounts of the short-lived product atoms from the ISOL target in the presence of bulk amounts of target material. Experimental studies are under way at the Oak Ridge National Laboratory (ORNL) which are designed to measure the time evolution of implanted elements diffused from refractory target materials which are candidates for forming radioactive ion beams (RIBs) at the Holifield Radioactive Ion Beam Facility (HRIBF). The diffusion coefficients are derived by comparing experimental data with numerical solutions to a one-dimensional form of Fick's second law for ion implanted distributions. In this report, we describe the experimental arrangement, experimental procedures, and provide time release data and diffusion coefficients for releasing ion implanted 37 Cl from Zr 5 Si 3 and 75 As, 79 Br, and 78 Se from Zr 5 Ge 3 and estimates of the diffusion coefficients for 35 Cl, 63 Cu, 65 Cu, 69 Ga and 71 Ga diffused from BN; 35 Cl, 63 Cu, 65 Cu, 69 Ga, 75 As, and 78 Se diffused from C; 35 Cl, 68 Cu, 69 Ga, 75 As, and 78 Se diffused from Ta

Deep brain stimulation in uncommon tremor disorders: indications, targets, and programming.

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Artusi, Carlo Alberto; Farooqi, Ashar; Romagnolo, Alberto; Marsili, Luca; Balestrino, Roberta; Sokol, Leonard L; Wang, Lily L; Zibetti, Maurizio; Duker, Andrew P; Mandybur, George T; Lopiano, Leonardo; Merola, Aristide

2018-03-06

In uncommon tremor disorders, clinical efficacy and optimal anatomical targets for deep brain stimulation (DBS) remain inadequately studied and insufficiently quantified. We performed a systematic review of PubMed.gov and ClinicalTrials.gov. Relevant articles were identified using the following keywords: "tremor", "Holmes tremor", "orthostatic tremor", "multiple sclerosis", "multiple sclerosis tremor", "neuropathy", "neuropathic tremor", "fragile X-associated tremor/ataxia syndrome", and "fragile X." We identified a total of 263 cases treated with DBS for uncommon tremor disorders. Of these, 44 had Holmes tremor (HT), 18 orthostatic tremor (OT), 177 multiple sclerosis (MS)-associated tremor, 14 neuropathy-associated tremor, and 10 fragile X-associated tremor/ataxia syndrome (FXTAS). DBS resulted in favorable, albeit partial, clinical improvements in HT cases receiving Vim-DBS alone or in combination with additional targets. A sustained improvement was reported in OT cases treated with bilateral Vim-DBS, while the two cases treated with unilateral Vim-DBS demonstrated only a transient effect. MS-associated tremor responded to dual-target Vim-/VO-DBS, but the inability to account for the progression of MS-associated disability impeded the assessment of its long-term clinical efficacy. Neuropathy-associated tremor substantially improved with Vim-DBS. In FXTAS patients, while Vim-DBS was effective in improving tremor, equivocal results were observed in those with ataxia. DBS of select targets may represent an effective therapeutic strategy for uncommon tremor disorders, although the level of evidence is currently in its incipient form and based on single cases or limited case series. An international registry is, therefore, warranted to clarify selection criteria, long-term results, and optimal surgical targets.

Threshold-Based Multiple Optical Signal Selection Scheme for Free-Space Optical Wavelength Division Multiplexing Systems

KAUST Repository

Nam, Sung Sik; Alouini, Mohamed-Slim; Zhang, Lin; Ko, Young-Chai

2017-01-01

We propose a threshold-based multiple optical signal selection scheme (TMOS) for free-space optical wavelength division multiplexing systems. With this scheme, we can obtain higher spectral efficiency while reducing the possible complexity

Considering Interactions among Multiple Criteria for the Server Selection

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Vesna Čančer

2010-06-01

Full Text Available Decision-making about server selection is one of the multi-criteria decision-making (MCDM processes where interactions among criteria should be considered. The paper introduces and develops some solutions for considering interactions among criteria in the MCDM problems. In the frame procedure for MCDM by using the group of methods, based on assigning weights, special attention is given to the synthesis of the local alternatives’ values into the aggregate values where the mutual preferential independence between two criteria is not assumed. Firstly, we delineate how to complete the additive model into the multiplicative one with synergic and redundancy elements in the case that criteria are structured in one level and in two levels. Furthermore, we adapted the concept of the fuzzy Choquet integral to the multi-attribute value theory. Studying and comparing the results of the example case of the server selection obtained by both aggregation approaches, the paper highlights the advantages of the first one since it does not require from decision makers to determine the weights of all possible combinations of the criteria and it enables the further use of the most preferred MCDM methods.

Selective interferometric imaging of internal multiples

KAUST Repository

Zuberi, M. A H

2013-01-01

Internal multiples deteriorate the image when the imaging procedure assumes only single scattering, especially if the velocity model does not reproduce such scattering in the Green’s function. If properly imaged, internal multiples (and internally-scattered energy) can enhance the seismic image and illuminate areas otherwise neglected or poorly imaged by conventional single-scattering approaches. Conventionally, in order to image internal multiples, accurate, sharp contrasts in the velocity model are required to construct a Green’s function with all the scattered energy. As an alternative, we develop a three-step procedure, which images the first-order internal scattering using the background Green’s function (from the surface to each image point), constructed from a smooth velocity model: We first back-propagate the recorded surface data using the background Green’s function, then cross-correlate the back-propagated data with the recorded data and finally cross-correlate the result with the original background Green’s function. This procedure images the contribution of the recorded first-order internal multiples and is almost free of the single-scattering recorded energy. This image can be added to the conventional single-scattering image, obtained e.g. from Kirchhoff migration, to enhance the image. Application to synthetic data with reflectors illuminated by multiple scattering only demonstrates the effectiveness of the approach.

Modified random hinge transport mechanics and multiple scattering step-size selection in EGS5

International Nuclear Information System (INIS)

Wilderman, S.J.; Bielajew, A.F.

2005-01-01

The new transport mechanics in EGS5 allows for significantly longer electron transport step sizes and hence shorter computation times than required for identical problems in EGS4. But as with all Monte Carlo electron transport algorithms, certain classes of problems exhibit step-size dependencies even when operating within recommended ranges, sometimes making selection of step-sizes a daunting task for novice users. Further contributing to this problem, because of the decoupling of multiple scattering and continuous energy loss in the dual random hinge transport mechanics of EGS5, there are two independent step sizes in EGS5, one for multiple scattering and one for continuous energy loss, each of which influences speed and accuracy in a different manner. Further, whereas EGS4 used a single value of fractional energy loss (ESTEPE) to determine step sizes at all energies, to increase performance by decreasing the amount of effort expended simulating lower energy particles, EGS5 permits the fractional energy loss values which are used to determine both the multiple scattering and continuous energy loss step sizes to vary with energy. This results in requiring the user to specify four fractional energy loss values when optimizing computations for speed. Thus, in order to simplify step-size selection and to mitigate step-size dependencies, a method has been devised to automatically optimize step-size selection based on a single material dependent input related to the size of problem tally region. In this paper we discuss the new transport mechanics in EGS5 and describe the automatic step-size optimization algorithm. (author)

Identifying Patient-Specific Epstein-Barr Nuclear Antigen-1 Genetic Variation and Potential Autoreactive Targets Relevant to Multiple Sclerosis Pathogenesis.

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Monika Tschochner

Full Text Available Epstein-Barr virus (EBV infection represents a major environmental risk factor for multiple sclerosis (MS, with evidence of selective expansion of Epstein-Barr Nuclear Antigen-1 (EBNA1-specific CD4+ T cells that cross-recognize MS-associated myelin antigens in MS patients. HLA-DRB1*15-restricted antigen presentation also appears to determine susceptibility given its role as a dominant risk allele. In this study, we have utilised standard and next-generation sequencing techniques to investigate EBNA-1 sequence variation and its relationship to HLA-DR15 binding affinity, as well as examining potential cross-reactive immune targets within the central nervous system proteome.Sanger sequencing was performed on DNA isolated from peripheral blood samples from 73 Western Australian MS cases, without requirement for primary culture, with additional FLX 454 Roche sequencing in 23 samples to identify low-frequency variants. Patient-derived viral sequences were used to predict HLA-DRB1*1501 epitopes (NetMHCII, NetMHCIIpan and candidates were evaluated for cross recognition with human brain proteins.EBNA-1 sequence variation was limited, with no evidence of multiple viral strains and only low levels of variation identified by FLX technology (8.3% nucleotide positions at a 1% cut-off. In silico epitope mapping revealed two known HLA-DRB1*1501-restricted epitopes ('AEG': aa 481-496 and 'MVF': aa 562-577, and two putative epitopes between positions 502-543. We identified potential cross-reactive targets involving a number of major myelin antigens including experimentally confirmed HLA-DRB1*15-restricted epitopes as well as novel candidate antigens within myelin and paranodal assembly proteins that may be relevant to MS pathogenesis.This study demonstrates the feasibility of obtaining autologous EBNA-1 sequences directly from buffy coat samples, and confirms divergence of these sequences from standard laboratory strains. This approach has identified a number of

The Control of Single-color and Multiple-color Visual Search by Attentional Templates in Working Memory and in Long-term Memory.

Science.gov (United States)

Grubert, Anna; Carlisle, Nancy B; Eimer, Martin

2016-12-01

The question whether target selection in visual search can be effectively controlled by simultaneous attentional templates for multiple features is still under dispute. We investigated whether multiple-color attentional guidance is possible when target colors remain constant and can thus be represented in long-term memory but not when they change frequently and have to be held in working memory. Participants searched for one, two, or three possible target colors that were specified by cue displays at the start of each trial. In constant-color blocks, the same colors remained task-relevant throughout. In variable-color blocks, target colors changed between trials. The contralateral delay activity (CDA) to cue displays increased in amplitude as a function of color memory load in variable-color blocks, which indicates that cued target colors were held in working memory. In constant-color blocks, the CDA was much smaller, suggesting that color representations were primarily stored in long-term memory. N2pc components to targets were measured as a marker of attentional target selection. Target N2pcs were attenuated and delayed during multiple-color search, demonstrating less efficient attentional deployment to color-defined target objects relative to single-color search. Importantly, these costs were the same in constant-color and variable-color blocks. These results demonstrate that attentional guidance by multiple-feature as compared with single-feature templates is less efficient both when target features remain constant and can be represented in long-term memory and when they change across trials and therefore have to be maintained in working memory.

Interpolating between random walks and optimal transportation routes: Flow with multiple sources and targets

Science.gov (United States)

Guex, Guillaume

2016-05-01

In recent articles about graphs, different models proposed a formalism to find a type of path between two nodes, the source and the target, at crossroads between the shortest-path and the random-walk path. These models include a freely adjustable parameter, allowing to tune the behavior of the path toward randomized movements or direct routes. This article presents a natural generalization of these models, namely a model with multiple sources and targets. In this context, source nodes can be viewed as locations with a supply of a certain good (e.g. people, money, information) and target nodes as locations with a demand of the same good. An algorithm is constructed to display the flow of goods in the network between sources and targets. With again a freely adjustable parameter, this flow can be tuned to follow routes of minimum cost, thus displaying the flow in the context of the optimal transportation problem or, by contrast, a random flow, known to be similar to the electrical current flow if the random-walk is reversible. Moreover, a source-targetcoupling can be retrieved from this flow, offering an optimal assignment to the transportation problem. This algorithm is described in the first part of this article and then illustrated with case studies.

Does Angling Technique Selectively Target Fishes Based on Their Behavioural Type?

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Alexander D M Wilson

Full Text Available Recently, there has been growing recognition that fish harvesting practices can have important impacts on the phenotypic distributions and diversity of natural populations through a phenomenon known as fisheries-induced evolution. Here we experimentally show that two common recreational angling techniques (active crank baits versus passive soft plastics differentially target wild largemouth bass (Micropterus salmoides and rock bass (Ambloplites rupestris based on variation in their behavioural tendencies. Fish were first angled in the wild using both techniques and then brought back to the laboratory and tested for individual-level differences in common estimates of personality (refuge emergence, flight-initiation-distance, latency-to-recapture and with a net, and general activity in an in-lake experimental arena. We found that different angling techniques appear to selectively target these species based on their boldness (as characterized by refuge emergence, a standard measure of boldness in fishes but not other assays of personality. We also observed that body size was independently a significant predictor of personality in both species, though this varied between traits and species. Our results suggest a context-dependency for vulnerability to capture relative to behaviour in these fish species. Ascertaining the selective pressures angling practices exert on natural populations is an important area of fisheries research with significant implications for ecology, evolution, and resource management.

Sejong Open Cluster Survey (SOS). 0. Target Selection and Data Analysis

Science.gov (United States)

Sung, Hwankyung; Lim, Beomdu; Bessell, Michael S.; Kim, Jinyoung S.; Hur, Hyeonoh; Chun, Moo-Young; Park, Byeong-Gon

2013-06-01

Star clusters are superb astrophysical laboratories containing cospatial and coeval samples of stars with similar chemical composition. We initiate the Sejong Open cluster Survey (SOS) - a project dedicated to providing homogeneous photometry of a large number of open clusters in the SAAO Johnson-Cousins' UBVI system. To achieve our main goal, we pay much attention to the observation of standard stars in order to reproduce the SAAO standard system. Many of our targets are relatively small sparse clusters that escaped previous observations. As clusters are considered building blocks of the Galactic disk, their physical properties such as the initial mass function, the pattern of mass segregation, etc. give valuable information on the formation and evolution of the Galactic disk. The spatial distribution of young open clusters will be used to revise the local spiral arm structure of the Galaxy. In addition, the homogeneous data can also be used to test stellar evolutionary theory, especially concerning rare massive stars. In this paper we present the target selection criteria, the observational strategy for accurate photometry, and the adopted calibrations for data analysis such as color-color relations, zero-age main sequence relations, Sp - M_V relations, Sp - T_{eff} relations, Sp - color relations, and T_{eff} - BC relations. Finally we provide some data analysis such as the determination of the reddening law, the membership selection criteria, and distance determination.

The pituitary tumor transforming gene 1 (PTTG-1: An immunological target for multiple myeloma

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Gagliano Nicoletta

2008-04-01

Full Text Available Abstract Background Multiple Myeloma is a cancer of B plasma cells, which produce non-specific antibodies and proliferate uncontrolled. Due to the potential relapse and non-specificity of current treatments, immunotherapy promises to be more specific and may induce long-term immunity in patients. The pituitary tumor transforming gene 1 (PTTG-1 has been shown to be a novel oncogene, expressed in the testis, thymus, colon, lung and placenta (undetectable in most other tissues. Furthermore, it is over expressed in many tumors such as the pituitary adenoma, breast, gastrointestinal cancers, leukemia, lymphoma, and lung cancer and it seems to be associated with tumorigenesis, angiogenesis and cancer progression. The purpose was to investigate the presence/rate of expression of PTTG-1 in multiple myeloma patients. Methods We analyzed the PTTG-1 expression at the transcriptional and the protein level, by PCR, immunocytochemical methods, Dot-blot and ELISA performed on patient's sera in 19 multiple myeloma patients, 6 different multiple myeloma cell lines and in normal human tissue. Results We did not find PTTG-1 presence in the normal human tissue panel, but PTTG-1 mRNA was detectable in 12 of the 19 patients, giving evidence of a 63% rate of expression (data confirmed by ELISA. Four of the 6 investigated cell lines (66.6% were positive for PTTG-1. Investigations of protein expression gave evidence of 26.3% cytoplasmic expression and 16% surface expression in the plasma cells of multiple myeloma patients. Protein presence was also confirmed by Dot-blot in both cell lines and patients. Conclusion We established PTTG-1's presence at both the transcriptional and protein levels. These data suggest that PTTG-1 is aberrantly expressed in multiple myeloma plasma cells, is highly immunogenic and is a suitable target for immunotherapy of multiple myeloma.

A Signal Detection Approach in a Multiple Cohort Study: Different Admission Tools Uniquely Select Different Successful Students

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Linda van Ooijen-van der Linden

2018-05-01

Full Text Available Using multiple admission tools in university admission procedures is common practice. This is particularly useful if different admission tools uniquely select different subgroups of students who will be successful in university programs. A signal-detection approach was used to investigate the accuracy of Secondary School grade point average (SSGPA, an admission test score (ACS, and a non-cognitive score (NCS in uniquely selecting successful students. This was done for three consecutive first year cohorts of a broad psychology program. Each applicant's score on SSGPA, ACS, or NCS alone—and on seven combinations of these scores, all considered separate “admission tools”—was compared at two different (medium and high cut-off scores (criterion levels. Each of the tools selected successful students who were not selected by any of the other tools. Both sensitivity and specificity were enhanced by implementing multiple tools. The signal-detection approach distinctively provided useful information for decisions on admission instruments and cut-off scores.

To Make Good Decision: A Group DSS for Multiple Criteria Alternative Rank and Selection

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Chen-Shu Wang

2015-01-01

Full Text Available Decision making is a recursive process and usually involves multiple decision criteria. However, such multiple criteria decision making may have a problem in which partial decision criteria may conflict with each other. An information technology, such as the decision support system (DSS and group DSS (GDSS, emerges to assist decision maker for decision-making process. Both the DSS and GDSS should integrate with a symmetrical approach to assist decision maker to take all decision criteria into consideration simultaneously. This study proposes a GDSS architecture named hybrid decision-making support model (HDMSM and integrated four decision approaches (Delphi, DEMATEL, ANP, and MDS to help decision maker to rank and select appropriate alternatives. The HDMSM consists of five steps, namely, criteria identification, criteria correlation calculation, criteria evaluation, critical criteria selection, and alternative rank and comparison. Finally, to validate the proposed feasibility of the proposed model, this study also conducts a case study to find out the important indexes of corporate social responsibility (CSR from multiple perspectives. As the case study demonstrates the proposed HDMSM enables a group of decision makers to implement the MCDM effectively and help them to analyze the relation and degree of mutual influence among different evaluation factors.

Social comparisons in adults with type 2 diabetes: Patients' reasons for target selection.

Science.gov (United States)

Arigo, Danielle; Cornell, Max; Smyth, Joshua M

2018-07-01

To examine reasons for selecting a social comparison target (i.e. a specific other for relative self-evaluation), and their influence on affect and motivation for self-care, in type 2 diabetes (T2DM). Adults with T2DM (n = 180, M A1c  = 7.6%) chose to read about one of four targets. Participants rated five reasons for their choice (strongly disagree - strongly agree), and rated affect and self-care motivation before and after reading. To boost confidence in my ability to manage diabetes was rated highest overall (ps motivation (p motivation only among those who chose better-off targets (p = 0.01). Patients' reasons for a particular comparison are associated with short-term changes in affect and self-care motivation, and warrant greater empirical and clinical attention.

DOA Estimation of Low Altitude Target Based on Adaptive Step Glowworm Swarm Optimization-multiple Signal Classification Algorithm

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Zhou Hao

2015-06-01

Full Text Available The traditional MUltiple SIgnal Classification (MUSIC algorithm requires significant computational effort and can not be employed for the Direction Of Arrival (DOA estimation of targets in a low-altitude multipath environment. As such, a novel MUSIC approach is proposed on the basis of the algorithm of Adaptive Step Glowworm Swarm Optimization (ASGSO. The virtual spatial smoothing of the matrix formed by each snapshot is used to realize the decorrelation of the multipath signal and the establishment of a fullorder correlation matrix. ASGSO optimizes the function and estimates the elevation of the target. The simulation results suggest that the proposed method can overcome the low altitude multipath effect and estimate the DOA of target readily and precisely without radar effective aperture loss.

Active colloids as mobile microelectrodes for unified label-free selective cargo transport.

Science.gov (United States)

Boymelgreen, Alicia M; Balli, Tov; Miloh, Touvia; Yossifon, Gilad

2018-02-22

Utilization of active colloids to transport both biological and inorganic cargo has been widely examined in the context of applications ranging from targeted drug delivery to sample analysis. In general, carriers are customized to load one specific target via a mechanism distinct from that driving the transport. Here we unify these tasks and extend loading capabilities to include on-demand selection of multiple nano/micro-sized targets without the need for pre-labelling or surface functionalization. An externally applied electric field is singularly used to drive the active cargo carrier and transform it into a mobile floating electrode that can attract (trap) or repel specific targets from its surface by dielectrophoresis, enabling dynamic control of target selection, loading and rate of transport via the electric field parameters. In the future, dynamic selectivity could be combined with directed motion to develop building blocks for bottom-up fabrication in applications such as additive manufacturing and soft robotics.

A Dynamic and Adaptive Selection Radar Tracking Method Based on Information Entropy

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Ge Jianjun

2017-12-01

Full Text Available Nowadays, the battlefield environment has become much more complex and variable. This paper presents a quantitative method and lower bound for the amount of target information acquired from multiple radar observations to adaptively and dynamically organize the detection of battlefield resources based on the principle of information entropy. Furthermore, for minimizing the given information entropy’s lower bound for target measurement at every moment, a method to dynamically and adaptively select radars with a high amount of information for target tracking is proposed. The simulation results indicate that the proposed method has higher tracking accuracy than that of tracking without adaptive radar selection based on entropy.

Wavelength-selectable and steady single-mode erbium-doped fiber multiple ring laser

Science.gov (United States)

Yeh, Chien-Hung; Yang, Zi-Qing; Huang, Tzu-Jung; Chow, Chi-Wai; Chen, Jing-Heng; Chen, Kun-Huang

2017-11-01

To achieve a stable and selectable C-band erbium-doped fiber (EDF) laser with single-longitudinal-mode output, a multiple ring architecture is proposed and demonstrated experimentally. In this work, we design a passively quadruple-ring structure in the cavity of an EDF laser to produce a Vernier effect with a mode filter for suppressing the multimode spikes significantly. In addition, the output performance and stability of the proposed EDF ring laser are discussed.

Targeting MUC1-C suppresses polycomb repressive complex 1 in multiple myeloma.

Science.gov (United States)

Tagde, Ashujit; Markert, Tahireh; Rajabi, Hasan; Hiraki, Masayuki; Alam, Maroof; Bouillez, Audrey; Avigan, David; Anderson, Kenneth; Kufe, Donald

2017-09-19

The polycomb repressive complex 1 (PRC1) includes the BMI1, RING1 and RING2 proteins. BMI1 is required for survival of multiple myeloma (MM) cells. The MUC1-C oncoprotein is aberrantly expressed by MM cells, activates MYC and is also necessary for MM cell survival. The present studies show that targeting MUC1-C with (i) stable and inducible silencing and CRISPR/Cas9 editing and (ii) the pharmacologic inhibitor GO-203, which blocks MUC1-C function, downregulates BMI1, RING1 and RING2 expression. The results demonstrate that MUC1-C drives BMI1 transcription by a MYC-dependent mechanism. MUC1-C thus promotes MYC occupancy on the BMI1 promoter and thereby activates BMI1 expression. We also show that the MUC1-C→MYC pathway induces RING2 expression. Moreover, in contrast to BMI1 and RING2, we found that MUC1-C drives RING1 by an NF-κB p65-dependent mechanism. Targeting MUC1-C and thereby the suppression of these key PRC1 proteins was associated with downregulation of the PRC1 E3 ligase activity as evidenced by decreases in ubiquitylation of histone H2A. Targeting MUC1-C also resulted in activation of the PRC1-repressed tumor suppressor genes, PTEN, CDNK2A and BIM . These findings identify a heretofore unrecognized role for MUC1-C in the epigenetic regulation of MM cells.

Performance Analysis of a Threshold-Based Parallel Multiple Beam Selection Scheme for WDM FSO Systems

KAUST Repository

Nam, Sung Sik; Alouini, Mohamed-Slim; Ko, Young-Chai

2018-01-01

In this paper, we statistically analyze the performance of a threshold-based parallel multiple beam selection scheme for a free-space optical (FSO) based system with wavelength division multiplexing (WDM) in cases where a pointing error has occurred

Technical Note: Using k-means clustering to determine the number and position of isocenters in MLC-based multiple target intracranial radiosurgery.

Science.gov (United States)

Yock, Adam D; Kim, Gwe-Ya

2017-09-01

To present the k-means clustering algorithm as a tool to address treatment planning considerations characteristic of stereotactic radiosurgery using a single isocenter for multiple targets. For 30 patients treated with stereotactic radiosurgery for multiple brain metastases, the geometric centroids and radii of each met were determined from the treatment planning system. In-house software used this as well as weighted and unweighted versions of the k-means clustering algorithm to group the targets to be treated with a single isocenter, and to position each isocenter. The algorithm results were evaluated using within-cluster sum of squares as well as a minimum target coverage metric that considered the effect of target size. Both versions of the algorithm were applied to an example patient to demonstrate the prospective determination of the appropriate number and location of isocenters. Both weighted and unweighted versions of the k-means algorithm were applied successfully to determine the number and position of isocenters. Comparing the two, both the within-cluster sum of squares metric and the minimum target coverage metric resulting from the unweighted version were less than those from the weighted version. The average magnitudes of the differences were small (-0.2 cm 2 and 0.1% for the within cluster sum of squares and minimum target coverage, respectively) but statistically significant (Wilcoxon signed-rank test, P k-means clustering algorithm represented an advantage of the unweighted version for the within-cluster sum of squares metric, and an advantage of the weighted version for the minimum target coverage metric. While additional treatment planning considerations have a large influence on the final treatment plan quality, both versions of the k-means algorithm provide automatic, consistent, quantitative, and objective solutions to the tasks associated with SRS treatment planning using a single isocenter for multiple targets. © 2017 The Authors. Journal

PSP: rapid identification of orthologous coding genes under positive selection across multiple closely related prokaryotic genomes.

Science.gov (United States)

Su, Fei; Ou, Hong-Yu; Tao, Fei; Tang, Hongzhi; Xu, Ping

2013-12-27

With genomic sequences of many closely related bacterial strains made available by deep sequencing, it is now possible to investigate trends in prokaryotic microevolution. Positive selection is a sub-process of microevolution, in which a particular mutation is favored, causing the allele frequency to continuously shift in one direction. Wide scanning of prokaryotic genomes has shown that positive selection at the molecular level is much more frequent than expected. Genes with significant positive selection may play key roles in bacterial adaption to different environmental pressures. However, selection pressure analyses are computationally intensive and awkward to configure. Here we describe an open access web server, which is designated as PSP (Positive Selection analysis for Prokaryotic genomes) for performing evolutionary analysis on orthologous coding genes, specially designed for rapid comparison of dozens of closely related prokaryotic genomes. Remarkably, PSP facilitates functional exploration at the multiple levels by assignments and enrichments of KO, GO or COG terms. To illustrate this user-friendly tool, we analyzed Escherichia coli and Bacillus cereus genomes and found that several genes, which play key roles in human infection and antibiotic resistance, show significant evidence of positive selection. PSP is freely available to all users without any login requirement at: http://db-mml.sjtu.edu.cn/PSP/. PSP ultimately allows researchers to do genome-scale analysis for evolutionary selection across multiple prokaryotic genomes rapidly and easily, and identify the genes undergoing positive selection, which may play key roles in the interactions of host-pathogen and/or environmental adaptation.

Rank-based model selection for multiple ions quantum tomography

International Nuclear Information System (INIS)

Guţă, Mădălin; Kypraios, Theodore; Dryden, Ian

2012-01-01

The statistical analysis of measurement data has become a key component of many quantum engineering experiments. As standard full state tomography becomes unfeasible for large dimensional quantum systems, one needs to exploit prior information and the ‘sparsity’ properties of the experimental state in order to reduce the dimensionality of the estimation problem. In this paper we propose model selection as a general principle for finding the simplest, or most parsimonious explanation of the data, by fitting different models and choosing the estimator with the best trade-off between likelihood fit and model complexity. We apply two well established model selection methods—the Akaike information criterion (AIC) and the Bayesian information criterion (BIC)—two models consisting of states of fixed rank and datasets such as are currently produced in multiple ions experiments. We test the performance of AIC and BIC on randomly chosen low rank states of four ions, and study the dependence of the selected rank with the number of measurement repetitions for one ion states. We then apply the methods to real data from a four ions experiment aimed at creating a Smolin state of rank 4. By applying the two methods together with the Pearson χ 2 test we conclude that the data can be suitably described with a model whose rank is between 7 and 9. Additionally we find that the mean square error of the maximum likelihood estimator for pure states is close to that of the optimal over all possible measurements. (paper)

Methodology for Selecting Best Management Practices Integrating Multiple Stakeholders and Criteria. Part 1: Methodology

Directory of Open Access Journals (Sweden)

Mauricio Carvallo Aceves

2016-02-01

Full Text Available The implementation of stormwater Best Management Practices (BMPs could help re-establish the natural hydrological cycle of watersheds after urbanization, with each BMP presenting a different performance across a range of criteria (flood prevention, pollutant removal, etc.. Additionally, conflicting views from the relevant stakeholders may arise, resulting in a complex selection process. This paper proposes a methodology for BMP selection based on the application of multi-criteria decision aid (MCDA methods, integrating multiple stakeholder priorities and BMP combinations. First, in the problem definition, the MCDA methods, relevant criteria and design guidelines are selected. Next, information from the preliminary analysis of the watershed is used to obtain a list of relevant BMPs. The third step comprises the watershed modeling and analysis of the BMP alternatives to obtain performance values across purely objective criteria. Afterwards, a stakeholder analysis based on survey applications is carried out to obtain social performance values and criteria priorities. Then, the MCDA methods are applied to obtain the final BMP rankings. The last step considers the sensitivity analysis and rank comparisons in order to draw the final conclusions and recommendations. Future improvements to the methodology could explore inclusion of multiple objective analysis, and alternative means for obtaining social performance values.

Systematic Analysis of the Multiple Bioactivities of Green Tea through a Network Pharmacology Approach

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Shoude Zhang

2014-01-01

Full Text Available During the past decades, a number of studies have demonstrated multiple beneficial health effects of green tea. Polyphenolics are the most biologically active components of green tea. Many targets can be targeted or affected by polyphenolics. In this study, we excavated all of the targets of green tea polyphenolics (GTPs though literature mining and target calculation and analyzed the multiple pharmacology actions of green tea comprehensively through a network pharmacology approach. In the end, a total of 200 Homo sapiens targets were identified for fifteen GTPs. These targets were classified into six groups according to their related disease, which included cancer, diabetes, neurodegenerative disease, cardiovascular disease, muscular disease, and inflammation. Moreover, these targets mapped into 143 KEGG pathways, 26 of which were more enriched, as determined though pathway enrichment analysis and target-pathway network analysis. Among the identified pathways, 20 pathways were selected for analyzing the mechanisms of green tea in these diseases. Overall, this study systematically illustrated the mechanisms of the pleiotropic activity of green tea by analyzing the corresponding “drug-target-pathway-disease” interaction network.

Importance of Neutralizing Monoclonal Antibodies Targeting Multiple Antigenic Sites on the Middle East Respiratory Syndrome Coronavirus Spike Glycoprotein To Avoid Neutralization Escape

Energy Technology Data Exchange (ETDEWEB)

Wang, Lingshu; Shi, Wei; Chappell, James D.; Joyce, M. Gordon; Zhang, Yi; Kanekiyo, Masaru; Becker, Michelle M.; van Doremalen, Neeltje; Fischer, Robert; Wang, Nianshuang; Corbett, Kizzmekia S.; Choe, Misook; Mason, Rosemarie D.; Van Galen, Joseph G.; Zhou, Tongqing; Saunders, Kevin O.; Tatti, Kathleen M.; Haynes, Lia M.; Kwong, Peter D.; Modjarrad, Kayvon; Kong, Wing-Pui; McLellan, Jason S.; Denison, Mark R.; Munster, Vincent J.; Mascola, John R.; Graham, Barney S.; Gallagher, Tom

2018-03-07

Middle East respiratory syndrome coronavirus (MERS-CoV) causes a highly lethal pulmonary infection with ~35% mortality. The potential for a future pandemic originating from animal reservoirs or health care-associated events is a major public health concern. There are no vaccines or therapeutic agents currently available for MERS-CoV. Using a probe-based single B cell cloning strategy, we have identified and characterized multiple neutralizing monoclonal antibodies (MAbs) specifically binding to the receptor-binding domain (RBD) or S1 (non-RBD) regions from a convalescent MERS-CoV-infected patient and from immunized rhesus macaques. RBD-specific MAbs tended to have greater neutralizing potency than non-RBD S1-specific MAbs. Six RBD-specific and five S1-specific MAbs could be sorted into four RBD and three non-RBD distinct binding patterns, based on competition assays, mapping neutralization escape variants, and structural analysis. We determined cocrystal structures for two MAbs targeting the RBD from different angles and show they can bind the RBD only in the “out” position. We then showed that selected RBD-specific, non-RBD S1-specific, and S2-specific MAbs given prophylactically prevented MERS-CoV replication in lungs and protected mice from lethal challenge. Importantly, combining RBD- and non-RBD MAbs delayed the emergence of escape mutations in a cell-based virus escape assay. These studies identify MAbs targeting different antigenic sites on S that will be useful for defining mechanisms of MERS-CoV neutralization and for developing more effective interventions to prevent or treat MERS-CoV infections.

IMPORTANCEMERS-CoV causes a highly lethal respiratory infection for which no vaccines or antiviral therapeutic options are currently available. Based on continuing exposure from established reservoirs in dromedary camels and bats, transmission of MERS-CoV into humans and future outbreaks are expected. Using

Selective Detection of Target Volatile Organic Compounds in Contaminated Humid Air Using a Sensor Array with Principal Component Analysis

Science.gov (United States)

Itoh, Toshio; Akamatsu, Takafumi; Tsuruta, Akihiro; Shin, Woosuck

2017-01-01

We investigated selective detection of the target volatile organic compounds (VOCs) nonanal, n-decane, and acetoin for lung cancer-related VOCs, and acetone and methyl i-butyl ketone for diabetes-related VOCs, in humid air with simulated VOC contamination (total concentration: 300 μg/m3). We used six “grain boundary-response type” sensors, including four commercially available sensors (TGS 2600, 2610, 2610, and 2620) and two Pt, Pd, and Au-loaded SnO2 sensors (Pt, Pd, Au/SnO2), and two “bulk-response type” sensors, including Zr-doped CeO2 (CeZr10), i.e., eight sensors in total. We then analyzed their sensor signals using principal component analysis (PCA). Although the six “grain boundary-response type” sensors were found to be insufficient for selective detection of the target gases in humid air, the addition of two “bulk-response type” sensors improved the selectivity, even with simulated VOC contamination. To further improve the discrimination, we selected appropriate sensors from the eight sensors based on the PCA results. The selectivity to each target gas was maintained and was not affected by contamination. PMID:28753948

Assisting People with Multiple Disabilities by Improving Their Computer Pointing Efficiency with an Automatic Target Acquisition Program

Science.gov (United States)

Shih, Ching-Hsiang; Shih, Ching-Tien; Peng, Chin-Ling

2011-01-01

This study evaluated whether two people with multiple disabilities would be able to improve their pointing performance through an Automatic Target Acquisition Program (ATAP) and a newly developed mouse driver (i.e. a new mouse driver replaces standard mouse driver, and is able to monitor mouse movement and intercept click action). Initially, both…

Coping with Atmospheric Turbulence in the Selection of Laser Hardening Technology for FCS Targeting Systems

National Research Council Canada - National Science Library

Pritchett, Timothy M

2004-01-01

... by frequency-agile battlefield lasers at both long and short range. Evidently, the selection of sensor protection technologies for incorporation into the final targeting system will be based on their optical limiting performance under field conditions...

Alemtuzumab in the treatment of multiple sclerosis: patient selection and special considerations

Directory of Open Access Journals (Sweden)

Dörr J

2016-10-01

the other are not yet available. Thus, the overall success of alemtuzumab treatment critically depends on the patient selection. The aim of this article is therefore, to characterize the significance of alemtuzumab in the treatment of MS with a focus on the selection of the optimal patient. Keywords: multiple sclerosis, treatment, safety, efficacy, selection, benefit risk relation

"Killer" Microcapsules That Can Selectively Destroy Target Microparticles in Their Vicinity.

Science.gov (United States)

Arya, Chandamany; Oh, Hyuntaek; Raghavan, Srinivasa R

2016-11-02

We have developed microscale polymer capsules that are able to chemically degrade a certain type of polymeric microbead in their immediate vicinity. The inspiration here is from the body's immune system, where killer T cells selectively destroy cancerous cells or cells infected by pathogens while leaving healthy cells alone. The "killer" capsules are made from the cationic biopolymer chitosan by a combination of ionic cross-linking (using multivalent tripolyposphate anions) and subsequent covalent cross-linking (using glutaraldehyde). During capsule formation, the enzyme glucose oxidase (GOx) is encapsulated in these capsules. The target beads are made by ionic cross-linking of the biopolymer alginate using copper (Cu 2+ ) cations. The killer capsules harvest glucose from their surroundings, which is then enzymatically converted by GOx into gluconate ions. These ions are known for their ability to chelate Cu 2+ cations. Thus, when a killer capsule is next to a target alginate bead, the gluconate ions diffuse into the bead and extract the Cu 2+ cross-links, causing the disintegration of the target bead. Such destruction is visualized in real-time using optical microscopy. The destruction is specific, i.e., other microparticles that do not contain Cu 2+ are left undisturbed. Moreover, the destruction is localized, i.e., the targets destroyed in the short term are the ones right next to the killer beads. The time scale for destruction depends on the concentration of encapsulated enzyme in the capsules.

Characterizing lentic freshwater fish assemblages using multiple sampling methods

Science.gov (United States)

Fischer, Jesse R.; Quist, Michael C.

2014-01-01

Characterizing fish assemblages in lentic ecosystems is difficult, and multiple sampling methods are almost always necessary to gain reliable estimates of indices such as species richness. However, most research focused on lentic fish sampling methodology has targeted recreationally important species, and little to no information is available regarding the influence of multiple methods and timing (i.e., temporal variation) on characterizing entire fish assemblages. Therefore, six lakes and impoundments (48–1,557 ha surface area) were sampled seasonally with seven gear types to evaluate the combined influence of sampling methods and timing on the number of species and individuals sampled. Probabilities of detection for species indicated strong selectivities and seasonal trends that provide guidance on optimal seasons to use gears when targeting multiple species. The evaluation of species richness and number of individuals sampled using multiple gear combinations demonstrated that appreciable benefits over relatively few gears (e.g., to four) used in optimal seasons were not present. Specifically, over 90 % of the species encountered with all gear types and season combinations (N = 19) from six lakes and reservoirs were sampled with nighttime boat electrofishing in the fall and benthic trawling, modified-fyke, and mini-fyke netting during the summer. Our results indicated that the characterization of lentic fish assemblages was highly influenced by the selection of sampling gears and seasons, but did not appear to be influenced by waterbody type (i.e., natural lake, impoundment). The standardization of data collected with multiple methods and seasons to account for bias is imperative to monitoring of lentic ecosystems and will provide researchers with increased reliability in their interpretations and decisions made using information on lentic fish assemblages.

Multiple independent identification decisions: a method of calibrating eyewitness identifications.

Science.gov (United States)

Pryke, Sean; Lindsay, R C L; Dysart, Jennifer E; Dupuis, Paul

2004-02-01

Two experiments (N = 147 and N = 90) explored the use of multiple independent lineups to identify a target seen live. In Experiment 1, simultaneous face, body, and sequential voice lineups were used. In Experiment 2, sequential face, body, voice, and clothing lineups were used. Both studies demonstrated that multiple identifications (by the same witness) from independent lineups of different features are highly diagnostic of suspect guilt (G. L. Wells & R. C. L. Lindsay, 1980). The number of suspect and foil selections from multiple independent lineups provides a powerful method of calibrating the accuracy of eyewitness identification. Implications for use of current methods are discussed. ((c) 2004 APA, all rights reserved)

HisB as novel selection marker for gene targeting approaches in Aspergillus niger.

Science.gov (United States)

Fiedler, Markus R M; Gensheimer, Tarek; Kubisch, Christin; Meyer, Vera

2017-03-08

For Aspergillus niger, a broad set of auxotrophic and dominant resistance markers is available. However, only few offer targeted modification of a gene of interest into or at a genomic locus of choice, which hampers functional genomics studies. We thus aimed to extend the available set by generating a histidine auxotrophic strain with a characterized hisB locus for targeted gene integration and deletion in A. niger. A histidine-auxotrophic strain was established via disruption of the A. niger hisB gene by using the counterselectable pyrG marker. After curing, a hisB - , pyrG - strain was obtained, which served as recipient strain for further studies. We show here that both hisB orthologs from A. nidulans and A. niger can be used to reestablish histidine prototrophy in this recipient strain. Whereas the hisB gene from A. nidulans was suitable for efficient gene targeting at different loci in A. niger, the hisB gene from A. niger allowed efficient integration of a Tet-on driven luciferase reporter construct at the endogenous non-functional hisB locus. Subsequent analysis of the luciferase activity revealed that the hisB locus is tight under non-inducing conditions and allows even higher luciferase expression levels compared to the pyrG integration locus. Taken together, we provide here an alternative selection marker for A. niger, hisB, which allows efficient homologous integration rates as well as high expression levels which compare favorably to the well-established pyrG selection marker.

Targeting the Thioredoxin System for Cancer Therapy.

Science.gov (United States)

Zhang, Junmin; Li, Xinming; Han, Xiao; Liu, Ruijuan; Fang, Jianguo

2017-09-01

Thioredoxin (Trx) and thioredoxin reductase (TrxR) are essential components of the Trx system which plays pivotal roles in regulating multiple cellular redox signaling pathways. In recent years TrxR/Trx have been increasingly recognized as an important modulator of tumor development, and hence targeting TrxR/Trx is a promising strategy for cancer treatment. In this review we first discuss the structural details of TrxR, the functions of the Trx system, and the rational of targeting TrxR/Trx for cancer treatment. We also highlight small-molecule TrxR/Trx inhibitors that have potential anticancer activity and review their mechanisms of action. Finally, we examine the challenges of developing TrxR/Trx inhibitors as anticancer agents and perspectives for selectively targeting TrxR/Trx. Copyright © 2017 Elsevier Ltd. All rights reserved.

Analysis of the residential location choice and household energy consumption behavior by incorporating multiple self-selection effects

International Nuclear Information System (INIS)

Yu Biying; Junyi Zhang; Fujiwara, Akimasa

2012-01-01

It is expected that the residential location choice and household energy consumption behavior might correlate with each other. Besides, due to the existence of self-selection effects, the observed inter-relationship between them might be the spurious result of the fact that some unobserved variables are causing both. These concerns motivate us to (1) consider residential location choice and household energy consumption behavior (for both in-home appliances and out-of-home cars) simultaneously and, (2) explicitly control self-selection effects so as to capture a relatively true effect of land-use policy on household energy consumption behavior. An integrated model termed as joint mixed Multinomial Logit-Multiple Discrete-Continuous Extreme Value model is presented here to identify the sensitivity of household energy consumption to land use policy by considering multiple self-selection effects. The model results indicate that land-use policy do play a great role in changing Beijing residents’ energy consumption pattern, while the self-selection effects cannot be ignored when evaluating the effect of land-use policy. Based on the policy scenario design, it is found that increasing recreational facilities and bus lines in the neighborhood can greatly promote household's energy-saving behavior. Additionally, the importance of “soft policy” and package policy is also emphasized in the context of Beijing. - Highlights: ► Representing residential choice and household energy consumption behavior jointly. ► Land use policy is found effective to control the household energy use in Beijing. ► Multiple self-selection effects are posed to get the true effect of land use policy. ► Significant self-selection effects call an attention to the soft policy in Beijing. ► The necessity of package policy on saving Beijing residents’ energy use is confirmed.

Poster: Brush, Lasso, or Magic Wand? Picking the Right Tool for Large-Scale Multiple Object Selection Tasks

DEFF Research Database (Denmark)

Stenholt, Rasmus; Madsen, Claus B.

2012-01-01

are presented with a range of different geometric layouts of selection targets, to investigate the pros and cons of each of the MOS techniques. The evaluation shows that the magic wand is significantly faster to use than the other techniques, however the quality of the magic wand's selections is highly...

Comparing strategies to assess multiple behavior change in behavioral intervention studies.

Science.gov (United States)

Drake, Bettina F; Quintiliani, Lisa M; Sapp, Amy L; Li, Yi; Harley, Amy E; Emmons, Karen M; Sorensen, Glorian

2013-03-01

Alternatives to individual behavior change methods have been proposed, however, little has been done to investigate how these methods compare. To explore four methods that quantify change in multiple risk behaviors targeting four common behaviors. We utilized data from two cluster-randomized, multiple behavior change trials conducted in two settings: small businesses and health centers. Methods used were: (1) summative; (2) z-score; (3) optimal linear combination; and (4) impact score. In the Small Business study, methods 2 and 3 revealed similar outcomes. However, physical activity did not contribute to method 3. In the Health Centers study, similar results were found with each of the methods. Multivitamin intake contributed significantly more to each of the summary measures than other behaviors. Selection of methods to assess multiple behavior change in intervention trials must consider study design, and the targeted population when determining the appropriate method/s to use.

Specific and selective target detection of supra-genome 21 Mers Salmonella via silicon nanowires biosensor

Science.gov (United States)

Mustafa, Mohammad Razif Bin; Dhahi, Th S.; Ehfaed, Nuri. A. K. H.; Adam, Tijjani; Hashim, U.; Azizah, N.; Mohammed, Mohammed; Noriman, N. Z.

2017-09-01

The nano structure based on silicon can be surface modified to be used as label-free biosensors that allow real-time measurements. The silicon nanowire surface was functionalized using 3-aminopropyltrimethoxysilane (APTES), which functions as a facilitator to immobilize biomolecules on the silicon nanowire surface. The process is simple, economical; this will pave the way for point-of-care applications. However, the surface modification and subsequent detection mechanism still not clear. Thus, study proposed step by step process of silicon nano surface modification and its possible in specific and selective target detection of Supra-genome 21 Mers Salmonella. The device captured the molecule with precisely; the approach took the advantages of strong binding chemistry created between APTES and biomolecule. The results indicated how modifications of the nanowires provide sensing capability with strong surface chemistries that can lead to specific and selective target detection.

Designing the nanobiointerface of fluorescent nanodiamonds: highly selective targeting of glioma cancer cells.

Science.gov (United States)

Slegerova, Jitka; Hajek, Miroslav; Rehor, Ivan; Sedlak, Frantisek; Stursa, Jan; Hruby, Martin; Cigler, Petr

2015-01-14

Core-shell nanoparticles based on fluorescent nanodiamonds coated with a biocompatible N-(2-hydroxypropyl)methacrylamide copolymer shell were developed for background-free near-infrared imaging of cancer cells. The particles showed excellent colloidal stability in buffers and culture media. After conjugation with a cyclic RGD peptide they selectively targeted integrin αvβ3 receptors on glioblastoma cells with high internalization efficacy.

Targeting p53 via JNK pathway: a novel role of RITA for apoptotic signaling in multiple myeloma.

Science.gov (United States)

Saha, Manujendra N; Jiang, Hua; Yang, Yijun; Zhu, Xiaoyun; Wang, Xiaoming; Schimmer, Aaron D; Qiu, Lugui; Chang, Hong

2012-01-01

The low frequency of p53 alterations e.g., mutations/deletions (∼10%) in multiple myeloma (MM) makes this tumor type an ideal candidate for p53-targeted therapies. RITA is a small molecule which can induce apoptosis in tumor cells by activating the p53 pathway. We previously showed that RITA strongly activates p53 while selectively inhibiting growth of MM cells without inducing genotoxicity, indicating its potential as a drug lead for p53-targeted therapy in MM. However, the molecular mechanisms underlying the pro-apoptotic effect of RITA are largely undefined. Gene expression analysis by microarray identified a significant number of differentially expressed genes associated with stress response including c-Jun N-terminal kinase (JNK) signaling pathway. By Western blot analysis we further confirmed that RITA induced activation of p53 in conjunction with up-regulation of phosphorylated ASK-1, MKK-4 and c-Jun. These results suggest that RITA induced the activation of JNK signaling. Chromatin immunoprecipitation (ChIP) analysis showed that activated c-Jun binds to the activator protein-1 (AP-1) binding site of the p53 promoter region. Disruption of the JNK signal pathway by small interfering RNA (siRNA) against JNK or JNK specific inhibitor, SP-600125 inhibited the activation of p53 and attenuated apoptosis induced by RITA in myeloma cells carrying wild type p53. On the other hand, p53 transcriptional inhibitor, PFT-α or p53 siRNA not only inhibited the activation of p53 transcriptional targets but also blocked the activation of c-Jun suggesting the presence of a positive feedback loop between p53 and JNK. In addition, RITA in combination with dexamethasone, known as a JNK activator, displays synergistic cytotoxic responses in MM cell lines and patient samples. Our study unveils a previously undescribed mechanism of RITA-induced p53-mediated apoptosis through JNK signaling pathway and provides the rationale for combination of p53 activating drugs with JNK

Targeting p53 via JNK pathway: a novel role of RITA for apoptotic signaling in multiple myeloma.

Directory of Open Access Journals (Sweden)

Manujendra N Saha

Full Text Available The low frequency of p53 alterations e.g., mutations/deletions (∼10% in multiple myeloma (MM makes this tumor type an ideal candidate for p53-targeted therapies. RITA is a small molecule which can induce apoptosis in tumor cells by activating the p53 pathway. We previously showed that RITA strongly activates p53 while selectively inhibiting growth of MM cells without inducing genotoxicity, indicating its potential as a drug lead for p53-targeted therapy in MM. However, the molecular mechanisms underlying the pro-apoptotic effect of RITA are largely undefined. Gene expression analysis by microarray identified a significant number of differentially expressed genes associated with stress response including c-Jun N-terminal kinase (JNK signaling pathway. By Western blot analysis we further confirmed that RITA induced activation of p53 in conjunction with up-regulation of phosphorylated ASK-1, MKK-4 and c-Jun. These results suggest that RITA induced the activation of JNK signaling. Chromatin immunoprecipitation (ChIP analysis showed that activated c-Jun binds to the activator protein-1 (AP-1 binding site of the p53 promoter region. Disruption of the JNK signal pathway by small interfering RNA (siRNA against JNK or JNK specific inhibitor, SP-600125 inhibited the activation of p53 and attenuated apoptosis induced by RITA in myeloma cells carrying wild type p53. On the other hand, p53 transcriptional inhibitor, PFT-α or p53 siRNA not only inhibited the activation of p53 transcriptional targets but also blocked the activation of c-Jun suggesting the presence of a positive feedback loop between p53 and JNK. In addition, RITA in combination with dexamethasone, known as a JNK activator, displays synergistic cytotoxic responses in MM cell lines and patient samples. Our study unveils a previously undescribed mechanism of RITA-induced p53-mediated apoptosis through JNK signaling pathway and provides the rationale for combination of p53 activating drugs with

Selective Vitamin D Receptor Activation as Anti-Inflammatory Target in Chronic Kidney Disease

Directory of Open Access Journals (Sweden)

J. Donate-Correa

2014-01-01

Full Text Available Paricalcitol, a selective vitamin D receptor (VDR activator used for treatment of secondary hyperparathyroidism in chronic kidney disease (CKD, has been associated with survival advantages, suggesting that this drug, beyond its ability to suppress parathyroid hormone, may have additional beneficial actions. In this prospective, nonrandomised, open-label, proof-of-concept study, we evaluated the hypothesis that selective vitamin D receptor activation with paricalcitol is an effective target to modulate inflammation in CKD patients. Eight patients with an estimated glomerular filtration rate between 15 and 44 mL/min/1.73 m2 and an intact parathyroid hormone (PTH level higher than 110 pg/mL received oral paricalcitol (1 μg/48 hours as therapy for secondary hyperparathyroidism. Nine patients matched by age, sex, and stage of CKD, but a PTH level <110 pg/mL, were enrolled as a control group. Our results show that five months of paricalcitol administration were associated with a reduction in serum concentrations of hs-CRP (13.9%, P<0.01, TNF-α (11.9%, P=0.01, and IL-6 (7%, P<0.05, with a nonsignificant increase of IL-10 by 16%. In addition, mRNA expression levels of the TNFα and IL-6 genes in peripheral blood mononuclear cells decreased significantly by 30.8% (P=0.01 and 35.4% (P=0.01, respectively. In conclusion, selective VDR activation is an effective target to modulate inflammation in CKD.

Anticancer efficacy of the metabolic blocker 3-bromopyruvate: specific molecular targeting.

Science.gov (United States)

Ganapathy-Kanniappan, Shanmugasundaram; Kunjithapatham, Rani; Geschwind, Jean-Francois

2013-01-01

The anticancer efficacy of the pyruvate analog 3-bromopyruvate has been demonstrated in multiple tumor models. The chief principle underlying the antitumor effects of 3-bromopyruvate is its ability to effectively target the energy metabolism of cancer cells. Biochemically, the glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase (GAPDH) has been identified as the primary target of 3-bromopyruvate. Its inhibition results in the depletion of intracellular ATP, causing cell death. Several reports have also demonstrated that in addition to GAPDH inhibition, the induction of cellular stress also contributes to 3-bromopyruvate treatment-dependent apoptosis. Furthermore, recent evidence shows that 3-bromopyruvate is taken up selectively by tumor cells via the monocarboxylate transporters (MCTs) that are frequently overexpressed in cancer cells (for the export of lactate produced during aerobic glycolysis). The preferential uptake of 3-bromopyruvate via MCTs facilitates selective targeting of tumor cells while leaving healthy and non-malignant tissue untouched. Taken together, the specificity of molecular (GAPDH) targeting and selective uptake by tumor cells, underscore the potential of 3-bromopyruvate as a potent and promising anticancer agent. In this review, we highlight the mechanistic characteristics of 3-bromopyruvate and discuss its potential for translation into the clinic.

Molecular diagnostics of a single drug-resistant multiple myeloma case using targeted next-generation sequencing

Directory of Open Access Journals (Sweden)

Ikeda H

2015-10-01

Full Text Available Hiroshi Ikeda,1 Kazuya Ishiguro,1 Tetsuyuki Igarashi,1 Yuka Aoki,1 Toshiaki Hayashi,1 Tadao Ishida,1 Yasushi Sasaki,1,2 Takashi Tokino,2 Yasuhisa Shinomura1 1Department of Gastroenterology, Rheumatology and Clinical Immunology, 2Medical Genome Sciences, Research Institute for Frontier Medicine, Sapporo Medical University, Sapporo, Japan Abstract: A 69-year-old man was diagnosed with IgG λ-type multiple myeloma (MM, Stage II in October 2010. He was treated with one cycle of high-dose dexamethasone. After three cycles of bortezomib, the patient exhibited slow elevations in the free light-chain levels and developed a significant new increase of serum M protein. Bone marrow cytogenetic analysis revealed a complex karyotype characteristic of malignant plasma cells. To better understand the molecular pathogenesis of this patient, we sequenced for mutations in the entire coding regions of 409 cancer-related genes using a semiconductor-based sequencing platform. Sequencing analysis revealed eight nonsynonymous somatic mutations in addition to several copy number variants, including CCND1 and RB1. These alterations may play roles in the pathobiology of this disease. This targeted next-generation sequencing can allow for the prediction of drug resistance and facilitate improvements in the treatment of MM patients. Keywords: multiple myeloma, drug resistance, genome-wide sequencing, semiconductor sequencer, target therapy

A Peptidomimetic Antibiotic Targets Outer Membrane Proteins and Disrupts Selectively the Outer Membrane in Escherichia coli.

Science.gov (United States)

Urfer, Matthias; Bogdanovic, Jasmina; Lo Monte, Fabio; Moehle, Kerstin; Zerbe, Katja; Omasits, Ulrich; Ahrens, Christian H; Pessi, Gabriella; Eberl, Leo; Robinson, John A

2016-01-22

Increasing antibacterial resistance presents a major challenge in antibiotic discovery. One attractive target in Gram-negative bacteria is the unique asymmetric outer membrane (OM), which acts as a permeability barrier that protects the cell from external stresses, such as the presence of antibiotics. We describe a novel β-hairpin macrocyclic peptide JB-95 with potent antimicrobial activity against Escherichia coli. This peptide exhibits no cellular lytic activity, but electron microscopy and fluorescence studies reveal an ability to selectively disrupt the OM but not the inner membrane of E. coli. The selective targeting of the OM probably occurs through interactions of JB-95 with selected β-barrel OM proteins, including BamA and LptD as shown by photolabeling experiments. Membrane proteomic studies reveal rapid depletion of many β-barrel OM proteins from JB-95-treated E. coli, consistent with induction of a membrane stress response and/or direct inhibition of the Bam folding machine. The results suggest that lethal disruption of the OM by JB-95 occurs through a novel mechanism of action at key interaction sites within clusters of β-barrel proteins in the OM. These findings open new avenues for developing antibiotics that specifically target β-barrel proteins and the integrity of the Gram-negative OM. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Natalizumab treatment for multiple sclerosis: updated recommendations for patient selection and monitoring

DEFF Research Database (Denmark)

Kappos, Ludwig; Bates, David; Edan, Gilles

2011-01-01

Natalizumab, a highly specific α4-integrin antagonist, is approved for treatment of patients with active relapsing-remitting multiple sclerosis (RRMS). It is generally recommended for individuals who have not responded to a currently available first-line disease-modifying therapy or who have very......, based on additional long-term follow-up of clinical studies and post-marketing observations, including appropriate patient selection and management recommendations.......Natalizumab, a highly specific α4-integrin antagonist, is approved for treatment of patients with active relapsing-remitting multiple sclerosis (RRMS). It is generally recommended for individuals who have not responded to a currently available first-line disease-modifying therapy or who have very...... active disease. The expected benefits of natalizumab treatment have to be weighed against risks, especially the rare but serious adverse event of progressive multifocal leukoencephalopathy. In this Review, we revisit and update previous recommendations on natalizumab for treatment of patients with RRMS...

Multiple Attribute Decision Making Based Relay Vehicle Selection for Electric Vehicle Communication

Directory of Open Access Journals (Sweden)

Zhao Qiang

2015-01-01

Full Text Available Large-scale electric vehicle integration into power grid and charging randomly will cause serious impacts on the normal operation of power grid. Therefore, it is necessary to control the charging behavior of electric vehicle, while information transmission for electric vehicle is significant. Due to the highly mobile characteristics of vehicle, transferring information to power grid directly might be inaccessible. Relay vehicle (RV can be used for supporting multi-hop connection between SV and power grid. This paper proposes a multiple attribute decision making (MADM-based RV selection algorithm, which considers multiple attribute, including data transfer rate, delay, route duration. It takes the characteristics of electric vehicle communication into account, which can provide protection for the communication services of electric vehicle charging and discharging. Numerical results demonstrate that compared to previous algorithm, the proposed algorithm offer better performance in terms of throughput, transmission delay.

Sensitivity studies of the neutron multiplicity spectrum in the spallation of Pb targets

International Nuclear Information System (INIS)

Sinha, A.; Garg, S.B.; Srinivasan, M.

1986-01-01

The number of neutrons produced per incident proton in the spallation of Pb targets is of direct relevance to the design of accelerator breeders. The nuclear cascade initiated by high-energy protons in spallation targets is usually described by an intranuclear cascade evaporation (INCE) model. Even though this model describes various average nuclear properties of spallation targets fairly well, differential quantities such as energy spectra, angular spectra etc., are not reproduced within the limits of experimental uncertainty. One of the reasons for this is the uncertainty in the magnitude of the parameters involved in the model, notably the level density parameter Bsub(O) whose magnitude is quoted by different workers to be in the range of 8-20 MeV. The accuracy of Bsub(O) could be improved if we could experimentally determine a quantity which is much more sensitive to Bsub(O) than the average neutron yield. In this paper we discuss one such quantity, namely the neutron multiplicity spectrum (MS). We compute the MS due to the spallation of Pb targets of different sizes at proton energies of 1.5, 1.0 and 0.59 GeV using the Monte Carlo code HETC. It is noticed that for the 1.5 GeV proton case the probability P(ν) for leakage of ν neutrons for ν in the range of 60-65, changes by about 70% when Bsub(O) is varied from 8 to 20 MeV. The corresponding change in the average neutron yield is <20%. It is therefore suggested that an accurate measurement of the MS can serve as a useful tool to narrow down the range of uncertainty in the Bsub(O) parameter. (author)

A dual selection based, targeted gene replacement tool for Magnaporthe grisea and Fusarium oxysporum.

Science.gov (United States)

Khang, Chang Hyun; Park, Sook-Young; Lee, Yong-Hwan; Kang, Seogchan

2005-06-01

Rapid progress in fungal genome sequencing presents many new opportunities for functional genomic analysis of fungal biology through the systematic mutagenesis of the genes identified through sequencing. However, the lack of efficient tools for targeted gene replacement is a limiting factor for fungal functional genomics, as it often necessitates the screening of a large number of transformants to identify the desired mutant. We developed an efficient method of gene replacement and evaluated factors affecting the efficiency of this method using two plant pathogenic fungi, Magnaporthe grisea and Fusarium oxysporum. This method is based on Agrobacterium tumefaciens-mediated transformation with a mutant allele of the target gene flanked by the herpes simplex virus thymidine kinase (HSVtk) gene as a conditional negative selection marker against ectopic transformants. The HSVtk gene product converts 5-fluoro-2'-deoxyuridine to a compound toxic to diverse fungi. Because ectopic transformants express HSVtk, while gene replacement mutants lack HSVtk, growing transformants on a medium amended with 5-fluoro-2'-deoxyuridine facilitates the identification of targeted mutants by counter-selecting against ectopic transformants. In addition to M. grisea and F. oxysporum, the method and associated vectors are likely to be applicable to manipulating genes in a broad spectrum of fungi, thus potentially serving as an efficient, universal functional genomic tool for harnessing the growing body of fungal genome sequence data to study fungal biology.

The meninges: new therapeutic targets for multiple sclerosis.

Science.gov (United States)

Russi, Abigail E; Brown, Melissa A

2015-02-01

The central nervous system (CNS) largely comprises nonregenerating cells, including neurons and myelin-producing oligodendrocytes, which are particularly vulnerable to immune cell-mediated damage. To protect the CNS, mechanisms exist that normally restrict the transit of peripheral immune cells into the brain and spinal cord, conferring an "immune-specialized" status. Thus, there has been a long-standing debate as to how these restrictions are overcome in several inflammatory diseases of the CNS, including multiple sclerosis (MS). In this review, we highlight the role of the meninges, tissues that surround and protect the CNS and enclose the cerebral spinal fluid, in promoting chronic inflammation that leads to neuronal damage. Although the meninges have traditionally been considered structures that provide physical protection for the brain and spinal cord, new data have established these tissues as sites of active immunity. It has been hypothesized that the meninges are important players in normal immunosurveillance of the CNS but also serve as initial sites of anti-myelin immune responses. The resulting robust meningeal inflammation elicits loss of localized blood-brain barrier (BBB) integrity and facilitates a large-scale influx of immune cells into the CNS parenchyma. We propose that targeting the cells and molecules mediating these inflammatory responses within the meninges offers promising therapies for MS that are free from the constraints imposed by the BBB. Importantly, such therapies may avoid the systemic immunosuppression often associated with the existing treatments. Copyright © 2015 Elsevier Inc. All rights reserved.

Enhancing Auditory Selective Attention Using a Visually Guided Hearing Aid

Science.gov (United States)

Kidd, Gerald, Jr.

2017-01-01

Purpose: Listeners with hearing loss, as well as many listeners with clinically normal hearing, often experience great difficulty segregating talkers in a multiple-talker sound field and selectively attending to the desired "target" talker while ignoring the speech from unwanted "masker" talkers and other sources of sound. This…

Conformational Flexibility Determines Selectivity and Antibacterial, Antiplasmodial, and Anticancer Potency of Cationic α-Helical Peptides*

OpenAIRE

Vermeer, Louic S.; Lan, Yun; Abbate, Vincenzo; Ruh, Emrah; Bui, Tam T.; Wilkinson, Louise J.; Kanno, Tokuwa; Jumagulova, Elmira; Kozlowska, Justyna; Patel, Jayneil; McIntyre, Caitlin A.; Yam, W. C.; Siu, Gilman; Atkinson, R. Andrew; Lam, Jenny K. W.

2012-01-01

Background: Antimicrobial peptides (AMPs) have the potential to act against multiple pathogenic targets. Results: AMPs that maintain conformational flexibility are more potent against multiple pathogens and less hemolytic. Conclusion: Antimicrobial action and hemolysis proceed via differing mechanisms. Significance: The potency, selectivity, and ability of AMPs to reach intracellular pathogens can be modulated using general principles.

Multiple Model Particle Filtering For Multi-Target Tracking

National Research Council Canada - National Science Library

Hero, Alfred; Kreucher, Chris; Kastella, Keith

2004-01-01

.... The details of this method have been presented elsewhere 1. One feature of real targets is that they are poorly described by a single kinematic model Target behavior may change dramatically i.e...

Multiple-view, multiple-selection visualization of simulation geometry in CMS

CERN Document Server

Mrak Tadel, Alja

2012-01-01

Fireworks, the event-display program of CMS, was extended with an advanced geometry visualization package. ROOT's TGeo geometry is used as internal representation, shared among several geometry views. Each view is represented by a GUI list-tree widget, implemented as a flat vector to allow for fast searching, selection, and filtering by material type, node name, and shape type. Display of logical and physical volumes is supported. Color, transparency, and visibility flags can be modified for each node or for a selection of nodes. Further operations, like opening of a new view or changing of the root node, can be performed via a context menu. Node selection and graphical properties determined by the list-tree view can be visualized in any 3D graphics view of Fireworks. As each 3D view can display any number of geometry views, a user is free to combine different geometry-view selections within the same 3D view. Node-selection by proximity to a given point is possible. A visual clipping box can be set for each g...

How consumers pick a hotel strategic segmentation and target marketing

CERN Document Server

Winston, William

2013-01-01

Venture through the pages of How Consumers Pick a Hotel to learn the steps of selecting a target and using consumer behavior applications to segment the market to reach your target. Much as a consumer goes through the process of selecting a satisfying hotel, you can choose to use the information provided to make your hospitality career relaxing and satisfying. When you finish this fantastic reading journey, you'll be prepared to offer services that meet the public's demands, and you'll possess the prerequisite knowledge and skills for developing your own strategic approach to a target market. As the many methods of segmentation are discussed in detail, you will also learn effective strategies for communicating with multiple segments. Ideal as a supplementary text for marketing and hospitality marketing courses, How Consumers Pick a Hotel provides a concise overview of consumer behavior and intertwines marketing theory with sound ways in which to implement the theory. This will both orient you and give you a s...

Mass hierarchy sensitivity of medium baseline reactor neutrino experiments with multiple detectors

Energy Technology Data Exchange (ETDEWEB)

Wang, Hong-Xin, E-mail: hxwang@iphy.me [Department of Physics, Nanjing University, Nanjing 210093 (China); Zhan, Liang; Li, Yu-Feng; Cao, Guo-Fu [Institute of High Energy Physics, Chinese Academy of Sciences, Beijing 100049 (China); Chen, Shen-Jian [Department of Physics, Nanjing University, Nanjing 210093 (China)

2017-05-15

We report the neutrino mass hierarchy (MH) determination of medium baseline reactor neutrino experiments with multiple detectors, where the sensitivity of measuring the MH can be significantly improved by adding a near detector. Then the impact of the baseline and target mass of the near detector on the combined MH sensitivity has been studied thoroughly. The optimal selections of the baseline and target mass of the near detector are ∼12.5 km and ∼4 kton respectively for a far detector with the target mass of 20 kton and the baseline of 52.5 km. As typical examples of future medium baseline reactor neutrino experiments, the optimal location and target mass of the near detector are selected for the specific configurations of JUNO and RENO-50. Finally, we discuss distinct effects of the reactor antineutrino energy spectrum uncertainty for setups of a single detector and double detectors, which indicate that the spectrum uncertainty can be well constrained in the presence of the near detector.

New and emerging immune-targeted drugs for the treatment of multiple sclerosis.

Science.gov (United States)

Palmer, Alan M

2014-07-01

Multiple sclerosis (MS) is a neurodegenerative disease with a major inflammatory component that constitutes the most common progressive and disabling neurological condition in young adults. Injectable immunomodulatory medicines such as interferon drugs and glatiramer acetate have dominated the MS market for over the past two decades but this situation is set to change. This is because of: (i) patent expirations, (ii) the introduction of natalizumab, which targets the interaction between leukocytes and the blood-CNS barrier, (iii) the launch of three oral immunomodulatory drugs (fingolimod, dimethyl fumarate and teriflunomide), with another (laquinimod) under regulatory review and (iv) a number of immunomodulatory monoclonal antibodies (alemtuzumab, daclizumab and ocrelizumab) about to enter the market. Current and emerging medicines are reviewed and their impact on people with MS considered. © 2013 The British Pharmacological Society.

Highly stable aptamers selected from a 2'-fully modified fGmH RNA library for targeting biomaterials.

Science.gov (United States)

Friedman, Adam D; Kim, Dongwook; Liu, Rihe

2015-01-01

When developed as targeting ligands for the in vivo delivery of biomaterials to biological systems, RNA aptamers immediately face numerous obstacles, in particular nuclease degradation and post-selection 2' modification. This study aims to develop a novel class of highly stable, 2'-fully modified RNA aptamers that are ideal for the targeted delivery of biomaterials. We demonstrated the facile transcription of a fGmH (2'-F-dG, 2'-OMe-dA/dC/dU) RNA library with unexpected hydrophobicity, the direct selection of aptamers from a fGmH RNA library that bind Staphylococcus aureus Protein A (SpA) as a model target, and the superior nuclease and serum stability of these aptamers compared to 2'-partially modified RNA variants. Characterizations of fGmH RNA aptamers binding to purified SpA and to endogenous SpA present on the surface of S. aureus cells demonstrate fGmH RNA aptamer selectivity and stability. Significantly, fGmH RNA aptamers were able to functionalize, stabilize, and specifically deliver aggregation-prone silver nanoparticles (AgNPs) to S. aureus with SpA-dependent antimicrobial effects. This study describes a novel aptamer class with considerable potential to improve the in vivo applicability of nucleic acid-based affinity molecules to biomaterials.

Dual-target cost in visual search for multiple unfamiliar faces.

Science.gov (United States)

Mestry, Natalie; Menneer, Tamaryn; Cave, Kyle R; Godwin, Hayward J; Donnelly, Nick

2017-08-01

The efficiency of visual search for one (single-target) and either of two (dual-target) unfamiliar faces was explored to understand the manifestations of capacity and guidance limitations in face search. The visual similarity of distractor faces to target faces was manipulated using morphing (Experiments 1 and 2) and multidimensional scaling (Experiment 3). A dual-target cost was found in all experiments, evidenced by slower and less accurate search in dual- than single-target conditions. The dual-target cost was unequal across the targets, with performance being maintained on one target and reduced on the other, which we label "preferred" and "non-preferred" respectively. We calculated the capacity for each target face and show reduced capacity for representing the non-preferred target face. However, results show that the capacity for the non-preferred target can be increased when the dual-target condition is conducted after participants complete the single-target conditions. Analyses of eye movements revealed evidence for weak guidance of fixations in single-target search, and when searching for the preferred target in dual-target search. Overall, the experiments show dual-target search for faces is capacity- and guidance-limited, leading to superior search for 1 face over the other in dual-target search. However, learning faces individually may improve capacity with the second face. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Designed multiple ligands in metabolic disease research: from concept to platform.

Science.gov (United States)

Gattrell, W; Johnstone, C; Patel, S; Smith, C Sambrook; Scheel, A; Schindler, M

2013-08-01

Type 2 diabetes mellitus (T2DM) is a multifactorial disease, and drug monotherapy typically results in unsatisfactory treatment outcomes for patients. Even when used in combination, existing therapies lack efficacy in the long term. Designed multiple ligands (DMLs) are compounds developed to modulate multiple targets relevant to a disease. DMLs offer the potential to yield greater efficacy over monotherapies, either by modulating different biological pathways, or by boosting a single one. However, examples of DMLs progressing into clinical trials, or onto the market are rare; DML drug discovery is challenging, and perceived by some to be almost impossible. Nevertheless, with the judicious selection of biological targets, both from a biological and chemical perspective, it is possible to develop drug-like DMLs. Copyright © 2013 Elsevier Ltd. All rights reserved.

Coronary artery analysis: Computer-assisted selection of best-quality segments in multiple-phase coronary CT angiography

Energy Technology Data Exchange (ETDEWEB)

Zhou, Chuan, E-mail: chuan@umich.edu; Chan, Heang-Ping; Hadjiyski, Lubomir M.; Chughtai, Aamer; Wei, Jun; Kazerooni, Ella A. [Department of Radiology, The University of Michigan, Ann Arbor, Michigan 48109-0904 (United States)

2016-10-15

Purpose: The authors are developing an automated method to identify the best-quality coronary arterial segment from multiple-phase coronary CT angiography (cCTA) acquisitions, which may be used by either interpreting physicians or computer-aided detection systems to optimally and efficiently utilize the diagnostic information available in multiple-phase cCTA for the detection of coronary artery disease. Methods: After initialization with a manually identified seed point, each coronary artery tree is automatically extracted from multiple cCTA phases using our multiscale coronary artery response enhancement and 3D rolling balloon region growing vessel segmentation and tracking method. The coronary artery trees from multiple phases are then aligned by a global registration using an affine transformation with quadratic terms and nonlinear simplex optimization, followed by a local registration using a cubic B-spline method with fast localized optimization. The corresponding coronary arteries among the available phases are identified using a recursive coronary segment matching method. Each of the identified vessel segments is transformed by the curved planar reformation (CPR) method. Four features are extracted from each corresponding segment as quality indicators in the original computed tomography volume and the straightened CPR volume, and each quality indicator is used as a voting classifier for the arterial segment. A weighted voting ensemble (WVE) classifier is designed to combine the votes of the four voting classifiers for each corresponding segment. The segment with the highest WVE vote is then selected as the best-quality segment. In this study, the training and test sets consisted of 6 and 20 cCTA cases, respectively, each with 6 phases, containing a total of 156 cCTA volumes and 312 coronary artery trees. An observer preference study was also conducted with one expert cardiothoracic radiologist and four nonradiologist readers to visually rank vessel segment

Coronary artery analysis: Computer-assisted selection of best-quality segments in multiple-phase coronary CT angiography

International Nuclear Information System (INIS)

Zhou, Chuan; Chan, Heang-Ping; Hadjiyski, Lubomir M.; Chughtai, Aamer; Wei, Jun; Kazerooni, Ella A.

2016-01-01

Purpose: The authors are developing an automated method to identify the best-quality coronary arterial segment from multiple-phase coronary CT angiography (cCTA) acquisitions, which may be used by either interpreting physicians or computer-aided detection systems to optimally and efficiently utilize the diagnostic information available in multiple-phase cCTA for the detection of coronary artery disease. Methods: After initialization with a manually identified seed point, each coronary artery tree is automatically extracted from multiple cCTA phases using our multiscale coronary artery response enhancement and 3D rolling balloon region growing vessel segmentation and tracking method. The coronary artery trees from multiple phases are then aligned by a global registration using an affine transformation with quadratic terms and nonlinear simplex optimization, followed by a local registration using a cubic B-spline method with fast localized optimization. The corresponding coronary arteries among the available phases are identified using a recursive coronary segment matching method. Each of the identified vessel segments is transformed by the curved planar reformation (CPR) method. Four features are extracted from each corresponding segment as quality indicators in the original computed tomography volume and the straightened CPR volume, and each quality indicator is used as a voting classifier for the arterial segment. A weighted voting ensemble (WVE) classifier is designed to combine the votes of the four voting classifiers for each corresponding segment. The segment with the highest WVE vote is then selected as the best-quality segment. In this study, the training and test sets consisted of 6 and 20 cCTA cases, respectively, each with 6 phases, containing a total of 156 cCTA volumes and 312 coronary artery trees. An observer preference study was also conducted with one expert cardiothoracic radiologist and four nonradiologist readers to visually rank vessel segment

Chemical biology based on target-selective degradation of proteins and carbohydrates using light-activatable organic molecules.

Science.gov (United States)

Toshima, Kazunobu

2013-05-01

Proteins and carbohydrates play crucial roles in a wide range of biological processes, including serious diseases. The development of novel and innovative methods for selective control of specific proteins and carbohydrates functions has attracted much attention in the field of chemical biology. In this account article, the development of novel chemical tools, which can degrade target proteins and carbohydrates by irradiation with a specific wavelength of light under mild conditions without any additives, is introduced. This novel class of photochemical agents promise bright prospects for finding not only molecular-targeted bioprobes for understanding of the structure-activity relationships of proteins and carbohydrates but also novel therapeutic drugs targeting proteins and carbohydrates.

Multiplicities of charged pions and charged hadrons from deep-inelastic scattering of muons off an isoscalar target

Directory of Open Access Journals (Sweden)

C. Adolph

2017-01-01

Full Text Available Multiplicities of charged pions and charged hadrons produced in deep-inelastic scattering were measured in three-dimensional bins of the Bjorken scaling variable x, the relative virtual-photon energy y and the relative hadron energy z. Data were obtained by the COMPASS Collaboration using a 160GeV muon beam and an isoscalar target (6LiD. They cover the kinematic domain in the photon virtuality Q2>1(GeV/c2, 0.004multiplicity results to extract quark fragmentation functions.

A low-complexity interacting multiple model filter for maneuvering target tracking

KAUST Repository

Khalid, Syed Safwan; Abrar, Shafayat

2017-01-01

In this work, we address the target tracking problem for a coordinate-decoupled Markovian jump-mean-acceleration based maneuvering mobility model. A novel low-complexity alternative to the conventional interacting multiple model (IMM) filter is proposed for this class of mobility models. The proposed tracking algorithm utilizes a bank of interacting filters where the interactions are limited to the mixing of the mean estimates, and it exploits a fixed off-line computed Kalman gain matrix for the entire filter bank. Consequently, the proposed filter does not require matrix inversions during on-line operation which significantly reduces its complexity. Simulation results show that the performance of the low-complexity proposed scheme remains comparable to that of the traditional (highly-complex) IMM filter. Furthermore, we derive analytical expressions that iteratively evaluate the transient and steady-state performance of the proposed scheme, and establish the conditions that ensure the stability of the proposed filter. The analytical findings are in close accordance with the simulated results.

A low-complexity interacting multiple model filter for maneuvering target tracking

KAUST Repository

Khalid, Syed Safwan

2017-01-22

In this work, we address the target tracking problem for a coordinate-decoupled Markovian jump-mean-acceleration based maneuvering mobility model. A novel low-complexity alternative to the conventional interacting multiple model (IMM) filter is proposed for this class of mobility models. The proposed tracking algorithm utilizes a bank of interacting filters where the interactions are limited to the mixing of the mean estimates, and it exploits a fixed off-line computed Kalman gain matrix for the entire filter bank. Consequently, the proposed filter does not require matrix inversions during on-line operation which significantly reduces its complexity. Simulation results show that the performance of the low-complexity proposed scheme remains comparable to that of the traditional (highly-complex) IMM filter. Furthermore, we derive analytical expressions that iteratively evaluate the transient and steady-state performance of the proposed scheme, and establish the conditions that ensure the stability of the proposed filter. The analytical findings are in close accordance with the simulated results.

Antibody-Based Therapies in Multiple Myeloma

Directory of Open Access Journals (Sweden)

Yu-Tzu Tai

2011-01-01

Full Text Available The unmet need for improved multiple myeloma (MM therapy has stimulated clinical development of monoclonal antibodies (mAbs targeting either MM cells or cells of the bone marrow (BM microenvironment. In contrast to small-molecule inhibitors, therapeutic mAbs present the potential to specifically target tumor cells and directly induce an immune response to lyse tumor cells. Unique immune-effector mechanisms are only triggered by therapeutic mAbs but not by small molecule targeting agents. Although therapeutic murine mAbs or chimeric mAbs can cause immunogenicity, the advancement of genetic recombination for humanizing rodent mAbs has allowed large-scale production and designation of mAbs with better affinities, efficient selection, decreasing immunogenicity, and improved effector functions. These advancements of antibody engineering technologies have largely overcome the critical obstacle of antibody immunogenicity and enabled the development and subsequent Food and Drug Administration (FDA approval of therapeutic Abs for cancer and other diseases.

Novel Chemokine-Based Immunotoxins for Potent and Selective Targeting of Cytomegalovirus Infected Cells

DEFF Research Database (Denmark)

Spiess, Katja; Jeppesen, Mads G.; Malmgaard-Clausen, Mikkel

2017-01-01

of human cytomegalovirus (HCMV) infections. US28 is expressed on virus-infected cells and scavenge chemokines by rapid internalization. The chemokine-based fusion-toxin protein (FTP) consisted of a variant (F49A) of CX3CL1 specifically targeting US28 linked to the catalytic domain of Pseudomonas exotoxin...... A (PE). Here, we systematically seek to improve F49A-FTP by modifications in its three structural domains; we generated variants with (1) altered chemokine sequence (K14A, F49L, and F49E), (2) shortened and elongated linker region, and (3) modified toxin domain. Only F49L-FTP displayed higher...... selectivity in its binding to US28 versus CX3CR1, the endogenous receptor for CX3CL1, but this was not matched by a more selective killing of US28-expressing cells. A longer linker and different toxin variants decreased US28 affinity and selective killing. Thereby, F49A-FTP represents the best candidate...

Natural selection of mitochondria during somatic lifetime promotes healthy aging

DEFF Research Database (Denmark)

Rodell, Anders; Rasmussen, Lene J; Bergersen, Linda H

2013-01-01

Stimulation of mitochondrial biogenesis during life-time challenges both eliminates disadvantageous properties and drives adaptive selection of advantageous phenotypic variations. Intermittent fission and fusion of mitochondria provide specific targets for health promotion by brief temporal...... stressors, interspersed with periods of recovery and biogenesis. For mitochondria, the mechanisms of selection, variability, and heritability, are complicated by interaction of two independent genomes, including the multiple copies of DNA in each mitochondrion, as well as the shared nuclear genome of each...

Management Model for Evaluation and Selection of Engineering Equipment Suppliers for Construction Projects in Iraq

Directory of Open Access Journals (Sweden)

Kadhim Raheem Erzaij

2016-06-01

Full Text Available Engineering equipment is essential part in the construction project and usually manufactured with long lead times, large costs and special engineering requirements. Construction manager targets that equipment to be delivered in the site need date with the right quantity, appropriate cost and required quality, and this entails an efficient supplier can satisfy these targets. Selection of engineering equipment supplier is a crucial managerial process .it requires evaluation of multiple suppliers according to multiple criteria. This process is usually performed manually and based on just limited evaluation criteria, so better alternatives may be neglected. Three stages of survey comprised number of public and private companies in Iraqi construction sector were employed to identify main criteria and sub criteria for supplier selection and their priorities.The main criteria identified were quality of product, commercial aspect, delivery, reputation and position, and system quality . An effective technique in multiple criteria decision making (MCDM as analytical hierarchy process (AHP have been used to get importance weights of criteria based on experts judgment. Thereafter, a management software system for Evaluation and Selection of Engineering Equipment Suppliers (ESEES has been developed based on the results obtained from AHP. This model was validated in a case study at municipality of Baghdad involved actual cases of selection pumps suppliers for infrastructure projects .According to experts, this model can improve the current process followed in the supplier selection and aid decision makers to adopt better choices in the domain of selection engineering equipment suppliers.

Selection of flowing liquid lead target structural materials for accelerator driven transmutation applications

International Nuclear Information System (INIS)

Park, J.J.; Buksa, J.J.

1994-01-01

The beam entry window and container for a liquid lead spallation target will be exposed to high fluxes of protons and neutrons that are both higher in magnitude and energy than have been experienced in proton accelerators and fission reactors, as well as in a corrosive environment. The structural material of the target should have a good compatibility with liquid lead, a sufficient mechanical strength at elevated temperatures, a good performance under an intense irradiation environment, and a low neutron absorption cross section; these factors have been used to rank the applicability of a wide range of materials for structural containment Nb-1Zr has been selected for use as the structural container for the LANL ABC/ATW molten lead target. Corrosion and mass transfer behavior for various candidate structural materials in liquid lead are reviewed, together with the beneficial effects of inhibitors and various coatings to protect substrate against liquid lead corrosion. Mechanical properties of some candidate materials at elevated temperatures and the property changes resulting from 800 MeV proton irradiation are also reviewed

Estimating Single and Multiple Target Locations Using K-Means Clustering with Radio Tomographic Imaging in Wireless Sensor Networks

Science.gov (United States)

2015-03-26

clustering is an algorithm that has been used in data mining applications such as machine learning applications , pattern recognition, hyper-spectral imagery...42 3.7.2 Application of K-means Clustering . . . . . . . . . . . . . . . . . 42 3.8 Experiment Design...Tomographic Imaging WLAN Wireless Local Area Networks WSN Wireless Sensor Network xx ESTIMATING SINGLE AND MULTIPLE TARGET LOCATIONS USING K-MEANS CLUSTERING

Selection of Novel Peptides Homing the 4T1 CELL Line: Exploring Alternative Targets for Triple Negative Breast Cancer.

Directory of Open Access Journals (Sweden)

Vera L Silva

Full Text Available The use of bacteriophages to select novel ligands has been widely explored for cancer therapy. Their application is most warranted in cancer subtypes lacking knowledge on how to target the cancer cells in question, such as the triple negative breast cancer, eventually leading to the development of alternative nanomedicines for cancer therapeutics. Therefore, the following study aimed to select and characterize novel peptides for a triple negative breast cancer murine mammary carcinoma cell line- 4T1. Using phage display, 7 and 12 amino acid random peptide libraries were screened against the 4T1 cell line. A total of four rounds, plus a counter-selection round using the 3T3 murine fibroblast cell line, was performed. The enriched selective peptides were characterized and their binding capacity towards 4T1 tissue samples was confirmed by immunofluorescence and flow cytometry analysis. The selected peptides (4T1pep1 -CPTASNTSC and 4T1pep2-EVQSSKFPAHVS were enriched over few rounds of selection and exhibited specific binding to the 4T1 cell line. Interestingly, affinity to the human MDA-MB-231 cell line was also observed for both peptides, promoting the translational application of these novel ligands between species. Additionally, bioinformatics analysis suggested that both peptides target human Mucin-16. This protein has been implicated in different types of cancer, as it is involved in many important cellular functions. This study strongly supports the need of finding alternative targeting systems for TNBC and the peptides herein selected exhibit promising future application as novel homing peptides for breast cancer therapy.

Material Selection for Dye Sensitized Solar Cells Using Multiple Attribute Decision Making Approach

Directory of Open Access Journals (Sweden)

Sarita Baghel

2014-01-01

Full Text Available Dye sensitized solar cells (DSCs provide a potential alternative to conventional p-n junction photovoltaic devices. The semiconductor thin film plays a crucial role in the working of DSC. This paper aims at formulating a process for the selection of optimum semiconductor material for nanostructured thin film using multiple attribute decision making (MADM approach. Various possible available semiconducting materials and their properties like band gap, cost, mobility, rate of electron injection, and static dielectric constant are considered and MADM technique is applied to select the best suited material. It was found that, out of all possible candidates, titanium dioxide (TiO2 is the best semiconductor material for application in DSC. It was observed that the proposed results are in good agreement with the experimental findings.

Object-based target templates guide attention during visual search.

Science.gov (United States)

Berggren, Nick; Eimer, Martin

2018-05-03

During visual search, attention is believed to be controlled in a strictly feature-based fashion, without any guidance by object-based target representations. To challenge this received view, we measured electrophysiological markers of attentional selection (N2pc component) and working memory (sustained posterior contralateral negativity; SPCN) in search tasks where two possible targets were defined by feature conjunctions (e.g., blue circles and green squares). Critically, some search displays also contained nontargets with two target features (incorrect conjunction objects, e.g., blue squares). Because feature-based guidance cannot distinguish these objects from targets, any selective bias for targets will reflect object-based attentional control. In Experiment 1, where search displays always contained only one object with target-matching features, targets and incorrect conjunction objects elicited identical N2pc and SPCN components, demonstrating that attentional guidance was entirely feature-based. In Experiment 2, where targets and incorrect conjunction objects could appear in the same display, clear evidence for object-based attentional control was found. The target N2pc became larger than the N2pc to incorrect conjunction objects from 250 ms poststimulus, and only targets elicited SPCN components. This demonstrates that after an initial feature-based guidance phase, object-based templates are activated when they are required to distinguish target and nontarget objects. These templates modulate visual processing and control access to working memory, and their activation may coincide with the start of feature integration processes. Results also suggest that while multiple feature templates can be activated concurrently, only a single object-based target template can guide attention at any given time. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Mature Epitope Density - A strategy for target selection based on immunoinformatics and exported prokaryotic proteins

DEFF Research Database (Denmark)

Santos, Anderson R; Pereira, Vanessa Bastos; Barbosa, Eudes

2013-01-01

. However, currently available tools do not account for the concentration of epitope products in the mature protein product and its relation to the reliability of target selection. RESULTS: We developed a computational strategy based on measuring the epitope's concentration in the mature protein, called...... Mature Epitope Density (MED). Our method, though simple, is capable of identifying promising vaccine targets. Our online software implementation provides a computationally light and reliable analysis of bacterial exoproteins and their potential for vaccines or diagnosis projects against pathogenic...... proteins were confirmed as related. There was no experimental evidence of antigenic or pathogenic contributions for three of the highest MED-scored Mtb proteins. Hence, these three proteins could represent novel putative vaccine and drug targets for Mtb. A web version of MED is publicly available online...

Multiplicities of charged pions and unidentified charged hadrons from deep-inelastic scattering of muons off an isoscalar target

CERN Document Server

Adolph, C.; Aghasyan, M.; Akhunzyanov, R.; Alexeev, M.G.; Alexeev, G.D.; Amoroso, A.; Andrieux, V.; Anfimov, N.V.; Anosov, V.; Augustyniak, W.; Austregesilo, A.; Azevedo, C.D.R.; Badelek, B.; Balestra, F.; Barth, J.; Beck, R.; Bedfer, Y.; Bernhard, J.; Bicker, K.; Bielert, E.R.; Birsa, R.; Bisplinghoff, J.; Bodlak, M.; Boer, M.; Bordalo, P.; Bradamante, F.; Braun, C.; Bressan, A.; Buechele, M.; Capozza, L.; Chang, W. -C.; Chatterjee, C.; Chiosso, M.; Choi, I.; Chung, S. -U.; Cicuttin, A.; Crespo, M.L.; Curiel, Q.; Dalla Torre, S.; Dasgupta, S.S.; Dasgupta, S.; Denisov, O. Yu.; Dhara, L.; Donskov, S.V.; Doshita, N.; Duic, V.; Duennweber, W.; Dziewiecki, M.; Efremov, A.; Eversheim, P.D.; Eyrich, W.; Faessler, M.; Ferrero, A.; Finger, M.; Fischer, H.; Franco, C.; von Hohenesche, N. du Fresne; Friedrich, J.M.; Frolov, V.; Fuchey, E.; Gautheron, F.; Gavrichtchouk, O.P.; Gerassimov, S.; Giordano, F.; Gnesi, I.; Gorzellik, M.; Grabmueller, S.; Grasso, A.; Grosse Perdekamp, M.; Grube, B.; Grussenmeyer, T.; Guskov, A.; Haas, F.; Hahne, D.; von Harrach, D.; Hashimoto, R.; Heinsius, F.H.; Heitz, R.; Herrmann, F.; Hinterberger, F.; Horikawa, N.; dHose, N.; Hsieh, C. -Y.; Huber, S.; Ishimoto, S.; Ivanov, A.; Ivanshin, Yu.; Iwata, T.; Jahn, R.; Jary, V.; Joosten, R.; Joerg, P.; Kabuss, E.; Ketzer, B.; Khaustov, G.V.; Khokhlov, Yu. A.; Kisselev, Yu.; Klein, F.; Klimaszewski, K.; Koivuniemi, J.H.; Kolosov, V.N.; Kondo, K.; Koenigsmann, K.; Konorov, I.; Konstantinov, V.F.; Kotzinian, A.M.; Kouznetsov, O.M.; Kuhn, R.; Kraemer, M.; Kremser, P.; Krinner, F.; Kroumchtein, Z.V.; Kulinich, Y.; Kunne, F.; Kurek, K.; Kurjata, R.P.; Lednev, A.A.; Lehmann, A.; Levillain, M.; Levorato, S.; Lichtenstadt, J.; Longo, R.; Maggiora, A.; Magnon, A.; Makins, N.; Makke, N.; Mallot, G.K.; Marchand, C.; Marianski, B.; Martin, A.; Marzec, J.; Matousek, J.; Matsuda, H.; Matsuda, T.; Meshcheryakov, G.V.; Meyer, W.; Michigami, T.; Mikhailov, Yu. V.; Mikhasenko, M.; Mitrofanov, E.; Mitrofanov, N.; Miyachi, Y.; Montuenga, P.; Nagaytsev, A.; Nerling, F.; Neyret, D.; Nikolaenko, V.I.; Novy, J.; Nowak, W.-D.; Nukazuka, G.; Nunes, A.S.; Olshevsky, A.G.; Orlov, I.; Ostrick, M.; Panzieri, D.; Parsamyan, B.; Paul, S.; Peng, J. -C.; Pereira, F.; Pesek, M.; Peshekhonov, D.V.; Pierre, N.; Platchkov, S.; Pochodzalla, J.; Polyakov, V.A.; Pretz, J.; Quaresma, M.; Quintans, C.; Ramos, S.; Regali, C.; Reicherz, G.; Riedl, C.; Roskot, M.; Ryabchikov, D.I.; Rybnikov, A.; Rychter, A.; Salac, R.; Samoylenko, V.D.; Sandacz, A.; Santos, C.; Sarkar, S.; Savin, I.A.; Sawada, T.; Sbrizzai, G.; Schiavon, P.; Schmidt, K.; Schmieden, H.; Schoenning, K.; Schopferer, S.; Seder, E.; Selyunin, A.; Shevchenko, O. Yu.; Steffen, D.; Silva, L.; Sinha, L.; Sirtl, S.; Slunecka, M.; Smolik, J.; Sozzi, F.; Srnka, A.; Stolarski, M.; Sulc, M.; Suzuki, H.; Szabelski, A.; Szameitat, T.; Sznajder, P.; Takekawa, S.; Tasevsky, M.; Tessaro, S.; Tessarotto, F.; Thibaud, F.; Tosello, F.; Tskhay, V.; Uhl, S.; Veloso, J.; Virius, M.; Vondra, J.; Weisrock, T.; Wilfert, M.; Windmolders, R.; ter Wolbeek, J.; Zaremba, K.; Zavada, P.; Zavertyaev, M.; Zemlyanichkina, E.; Ziembicki, M.; Zink, A.

2017-01-10

Multiplicities of charged pions and unidentified hadrons produced in deep-inelastic scattering were measured in bins of the Bjorken scaling variable $x$, the relative virtual-photon energy $y$ and the relative hadron energy $z$. Data were obtained by the COMPASS Collaboration using a 160 GeV muon beam and an isoscalar target ($^6$LiD). They cover the kinematic domain in the photon virtuality $Q^2$ > 1(GeV/c$)^2$, $0.004 < x < 0.4$, $0.2 < z < 0.85$ and $0.1 < y < 0.7$. In addition, a leading-order pQCD analysis was performed using the pion multiplicity results to extract quark fragmentation functions.

Addressing the targeting range of the ABILHAND-56 in relapsing-remitting multiple sclerosis: A mixed methods psychometric study.

Science.gov (United States)

Cleanthous, Sophie; Strzok, Sara; Pompilus, Farrah; Cano, Stefan; Marquis, Patrick; Cohan, Stanley; Goldman, Myla D; Kresa-Reahl, Kiren; Petrillo, Jennifer; Castrillo-Viguera, Carmen; Cadavid, Diego; Chen, Shih-Yin

2018-01-01

ABILHAND, a manual ability patient-reported outcome instrument originally developed for stroke patients, has been used in multiple sclerosis clinical trials; however, psychometric analyses indicated the measure's limited measurement range and precision in higher-functioning multiple sclerosis patients. The purpose of this study was to identify candidate items to expand the measurement range of the ABILHAND-56, thus improving its ability to detect differences in manual ability in higher-functioning multiple sclerosis patients. A step-wise mixed methods design strategy was used, comprising two waves of patient interviews, a combination of qualitative (concept elicitation and cognitive debriefing) and quantitative (Rasch measurement theory) analytic techniques, and consultation interviews with three clinical neurologists specializing in multiple sclerosis. Original ABILHAND was well understood in this context of use. Eighty-two new manual ability concepts were identified. Draft supplementary items were generated and refined with patient and neurologist input. Rasch measurement theory psychometric analysis indicated supplementary items improved targeting to higher-functioning multiple sclerosis patients and measurement precision. The final pool of Early Multiple Sclerosis Manual Ability items comprises 20 items. The synthesis of qualitative and quantitative methods used in this study improves the ABILHAND content validity to more effectively identify manual ability changes in early multiple sclerosis and potentially help determine treatment effect in higher-functioning patients in clinical trials.

Target selection for direct marketing.

NARCIS (Netherlands)

Bult, Jan Roelf

1993-01-01

In this thesis we concentrated on the use ol direct mail for targeting potential buyers. The major characteristics that influences the success of a plomotional direct mail campaign are the of-fbr,the communication elements, the timing or sequence of these communication elements, and the list of

Hindsight regulates photoreceptor axon targeting through transcriptional control of jitterbug/Filamin and multiple genes involved in axon guidance in Drosophila.

Science.gov (United States)

Oliva, Carlos; Molina-Fernandez, Claudia; Maureira, Miguel; Candia, Noemi; López, Estefanía; Hassan, Bassem; Aerts, Stein; Cánovas, José; Olguín, Patricio; Sierralta, Jimena

2015-09-01

During axon targeting, a stereotyped pattern of connectivity is achieved by the integration of intrinsic genetic programs and the response to extrinsic long and short-range directional cues. How this coordination occurs is the subject of intense study. Transcription factors play a central role due to their ability to regulate the expression of multiple genes required to sense and respond to these cues during development. Here we show that the transcription factor HNT regulates layer-specific photoreceptor axon targeting in Drosophila through transcriptional control of jbug/Filamin and multiple genes involved in axon guidance and cytoskeleton organization.Using a microarray analysis we identified 235 genes whose expression levels were changed by HNT overexpression in the eye primordia. We analyzed nine candidate genes involved in cytoskeleton regulation and axon guidance, six of which displayed significantly altered gene expression levels in hnt mutant retinas. Functional analysis confirmed the role of OTK/PTK7 in photoreceptor axon targeting and uncovered Tiggrin, an integrin ligand, and Jbug/Filamin, a conserved actin- binding protein, as new factors that participate of photoreceptor axon targeting. Moreover, we provided in silico and molecular evidence that supports jbug/Filamin as a direct transcriptional target of HNT and that HNT acts partially through Jbug/Filamin in vivo to regulate axon guidance. Our work broadens the understanding of how HNT regulates the coordinated expression of a group of genes to achieve the correct connectivity pattern in the Drosophila visual system. © 2015 Wiley Periodicals, Inc. Develop Neurobiol 75: 1018-1032, 2015. © 2015 Wiley Periodicals, Inc.

Target-matched insertion gain derived from three different hearing aid selection procedures.

Science.gov (United States)

Punch, J L; Shovels, A H; Dickinson, W W; Calder, J H; Snead, C

1995-11-01

Three hearing aid selection procedures were compared to determine if any one was superior in producing prescribed real-ear insertion gain. For each of three subject groups, 12 in-the-ear style hearing aids with Class D circuitry and similar dispenser controls were ordered from one of three manufacturers. Subject groups were classified based on the type of information included on the hearing aid order form: (1) the subject's audiogram, (2) a three-part matrix specifying the desired maximum output, full-on gain, and frequency response slope of the hearing aid, or (3) the desired 2-cc coupler full-in grain of the hearing aid, based on real-ear coupler difference (RECD) measurements. Following electroacoustic adjustments aimed at approximating a commonly used target insertion gain formula, results revealed no significant differences among any of the three selection procedures with respect to obtaining acceptable insertion gain values.

Endocytosis of Cytotoxic Granules Is Essential for Multiple Killing of Target Cells by T Lymphocytes.

Science.gov (United States)

Chang, Hsin-Fang; Bzeih, Hawraa; Schirra, Claudia; Chitirala, Praneeth; Halimani, Mahantappa; Cordat, Emmanuelle; Krause, Elmar; Rettig, Jens; Pattu, Varsha

2016-09-15

CTLs are serial killers that kill multiple target cells via exocytosis of cytotoxic granules (CGs). CG exocytosis is tightly regulated and has been investigated in great detail; however, whether CG proteins are endocytosed following exocytosis and contribute to serial killing remains unknown. By using primary CTLs derived from a knock-in mouse of the CG membrane protein Synaptobrevin2, we show that CGs are endocytosed in a clathrin- and dynamin-dependent manner. Following acidification, endocytosed CGs are recycled through early and late, but not recycling endosomes. CGs are refilled with granzyme B at the late endosome stage and polarize to subsequent synapses formed between the CTL and new target cells. Importantly, inhibiting CG endocytosis in CTLs results in a significant reduction of their cytotoxic activity. Thus, our data demonstrate that continuous endocytosis of CG membrane proteins is a prerequisite for efficient serial killing of CTLs and identify key events in this process. Copyright © 2016 by The American Association of Immunologists, Inc.

Mimotopes selected with neutralizing antibodies against multiple subtypes of influenza A

Directory of Open Access Journals (Sweden)

Zhong Yanwei

2011-12-01

Full Text Available Abstract Background The mimotopes of viruses are considered as the good targets for vaccine design. We prepared mimotopes against multiple subtypes of influenza A and evaluate their immune responses in flu virus challenged Balb/c mice. Methods The mimotopes of influenza A including pandemic H1N1, H3N2, H2N2 and H1N1 swine-origin influenza virus were screened by peptide phage display libraries, respectively. These mimotopes were engineered in one protein as multi- epitopes in Escherichia coli (E. coli and purified. Balb/c mice were immunized using the multi-mimotopes protein and specific antibody responses were analyzed using hemagglutination inhibition (HI assay and enzyme-linked immunosorbent assay (ELISA. The lung inflammation level was evaluated by hematoxylin and eosin (HE. Results Linear heptopeptide and dodecapeptide mimotopes were obtained for these influenza virus. The recombinant multi-mimotopes protein was a 73 kDa fusion protein. Comparing immunized infected groups with unimmunized infected subsets, significant differences were observed in the body weight loss and survival rate. The antiserum contained higher HI Ab titer against H1N1 virus and the lung inflammation level were significantly decreased in immunized infected groups. Conclusions Phage-displayed mimotopes against multiple subtypes of influenza A were accessible to the mouse immune system and triggered a humoral response to above virus.

Multiple-view, Multiple-selection Visualization of Simulation Geometry in CMS

International Nuclear Information System (INIS)

Bauerdick, L A T; Eulisse, G; Jones, C; McCauley, T; Osborne, I; Kovalskyi, D; Mrak Tadel, A; Tadel, M; Yagil, A

2012-01-01

Fireworks, the event-display program of CMS, was extended with an advanced geometry visualization package. ROOT's TGeo geometry is used as internal representation, shared among several geometry views. Each view is represented by a GUI list-tree widget, implemented as a flat vector to allow for fast searching, selection, and filtering by material type, node name, and shape type. Display of logical and physical volumes is supported. Color, transparency, and visibility flags can be modified for each node or for a selection of nodes. Further operations, like opening of a new view or changing of the root node, can be performed via a context menu. Node selection and graphical properties determined by the list-tree view can be visualized in any 3D graphics view of Fireworks. As each 3D view can display any number of geometry views, a user is free to combine different geometry-view selections within the same 3D view. Node-selection by proximity to a given point is possible. A visual clipping box can be set for each geometry view to limit geometry drawing into a specified region. Visualization of geometric overlaps, as detected by TGeo, is also supported. The geometry visualization package is used for detailed inspection and display of simulation geometry with or without the event data. It also serves as a tool for geometry debugging and inspection, facilitating development of geometries for CMS detector upgrades and for SLHC.

Threshold-Based Multiple Optical Signal Selection Scheme for Free-Space Optical Wavelength Division Multiplexing Systems

KAUST Repository

Nam, Sung Sik

2017-11-13

We propose a threshold-based multiple optical signal selection scheme (TMOS) for free-space optical wavelength division multiplexing systems. With this scheme, we can obtain higher spectral efficiency while reducing the possible complexity of implementation caused by the beam-selection scheme and without a considerable performance loss. To characterize the performance of our scheme, we statistically analyze the operation characteristics under conventional detection conditions (i.e., heterodyne detection and intensity modulation/direct detection techniques) with log-normal turbulence while taking into consideration the impact of pointing error. More specifically, we derive exact closed-form expressions for the outage probability, the average bit error rate, and the average spectral efficiency while adopting an adaptive modulation. Some selected results show that TMOS increases the average spectral efficiency while maintaining a minimum average bit error rate requirement.

Selective Inhibition of Histone Deacetylation in Melanoma Increases Targeted Gene Delivery by a Bacteriophage Viral Vector

Directory of Open Access Journals (Sweden)

Samuel Campbell

2018-04-01

Full Text Available The previously developed adeno-associated virus/phage (AAVP vector, a hybrid between M13 bacteriophage (phage viruses that infect bacteria only and human Adeno-Associated Virus (AAV, is a promising tool in targeted gene therapy against cancer. AAVP can be administered systemically and made tissue specific through the use of ligand-directed targeting. Cancer cells and tumor-associated blood vessels overexpress the αν integrin receptors, which are involved in tumor angiogenesis and tumor invasion. AAVP is targeted to these integrins via a double cyclic RGD4C ligand displayed on the phage capsid. Nevertheless, there remain significant host-defense hurdles to the use of AAVP in targeted gene delivery and subsequently in gene therapy. We previously reported that histone deacetylation in cancer constitutes a barrier to AAVP. Herein, to improve AAVP-mediated gene delivery to cancer cells, we combined the vector with selective adjuvant chemicals that inhibit specific histone deacetylases (HDAC. We examined the effects of the HDAC inhibitor C1A that mainly targets HDAC6 and compared this to sodium butyrate, a pan-HDAC inhibitor with broad spectrum HDAC inhibition. We tested the effects on melanoma, known for HDAC6 up-regulation, and compared this side by side with a normal human kidney HEK293 cell line. Varying concentrations were tested to determine cytotoxic levels as well as effects on AAVP gene delivery. We report that the HDAC inhibitor C1A increased AAVP-mediated transgene expression by up to ~9-fold. These findings indicate that selective HDAC inhibition is a promising adjuvant treatment for increasing the therapeutic value of AAVP.

Rapid and targeted introgression of genes into popular wheat cultivars using marker-assisted background selection.

Directory of Open Access Journals (Sweden)

Harpinder S Randhawa

Full Text Available A marker-assisted background selection (MABS-based gene introgression approach in wheat (Triticum aestivum L. was optimized, where 97% or more of a recurrent parent genome (RPG can be recovered in just two backcross (BC generations. A four-step MABS method was developed based on 'Plabsim' computer simulations and wheat genome structure information. During empirical optimization of this method, double recombinants around the target gene were selected in a step-wise fashion during the two BC cycles followed by selection for recurrent parent genotype on non-carrier chromosomes. The average spacing between carrier chromosome markers was <4 cM. For non-carrier chromosome markers that flanked each of the 48 wheat gene-rich regions, this distance was approximately 12 cM. Employed to introgress seedling stripe rust (Puccinia striiformis f. sp. tritici resistance gene Yr15 into the spring wheat cultivar 'Zak', marker analysis of 2,187 backcross-derived progeny resulted in the recovery of a BC(2F(2ratio3 plant with 97% of the recurrent parent genome. In contrast, only 82% of the recurrent parent genome was recovered in phenotypically selected BC(4F(7 plants developed without MABS. Field evaluation results from 17 locations indicated that the MABS-derived line was either equal or superior to the recurrent parent for the tested agronomic characteristics. Based on these results, MABS is recommended as a strategy for rapidly introgressing a targeted gene into a wheat genotype in just two backcross generations while recovering 97% or more of the recurrent parent genotype.

Evodiamine selectively targets cancer stem-like cells through the p53-p21-Rb pathway

International Nuclear Information System (INIS)

Han, Seula; Woo, Jong Kyu; Jung, Yuchae; Jeong, Dawoon; Kang, Minsook; Yoo, Young-Ji; Lee, Hani; Oh, Seung Hyun; Ryu, Jae-Ha; Kim, Woo-Young

2016-01-01

In spite of the recent improvements, the resistance to chemotherapy/radiotherapy followed by relapse is the main hurdle for the successful treatment of breast cancer, a leading cause of death in women. A small population of breast cancer cells that have stem-like characteristics (cancer stem-like cells; CSLC) may contribute to this resistance and relapse. Here, we report on a component of a traditional Chinese medicine, evodiamine, which selectively targets CSLC of breast cancer cell lines MCF7 and MDAMB 231 at a concentration that does show a little or no cytotoxic effect on bulk cancer cells. While evodiamine caused the accumulation of bulk cancer cells at the G2/M phase, it did not hold CSLC in a specific cell cycle phase but instead, selectively killed CSLC. This was not due to the culture of CSLC in suspension or without FBS. A proteomic analysis and western blotting revealed that evodiamine changed the expression of cell cycle regulating molecules more efficiently in CSLC cells than in bulk cancer cells. Surprisingly, evodiamine selectively activated p53 and p21 and decreased inactive Rb, the master molecules in G1/S checkpoint. These data collectively suggest a novel mechanism involving CSLC-specific targeting by evodiamine and its possible use to the therapy of breast cancer. - Highlights: • Evodiamine selectively kills breast cancer stem like cells at G1 phase. • Evodiamine utilizes different mechanism of cell cycle modulation in CSLC and in bulk cancer cells. • Evodiamine activate the p53, p21 and Rb pathway.

Evodiamine selectively targets cancer stem-like cells through the p53-p21-Rb pathway

Energy Technology Data Exchange (ETDEWEB)

Han, Seula [The Research Center for Cell Fate Control, College of Pharmacy, Sookmyung Women' s University, Seoul (Korea, Republic of); Woo, Jong Kyu [College of Pharmacy, Gachon University, Incheon (Korea, Republic of); Jung, Yuchae; Jeong, Dawoon; Kang, Minsook; Yoo, Young-Ji; Lee, Hani [The Research Center for Cell Fate Control, College of Pharmacy, Sookmyung Women' s University, Seoul (Korea, Republic of); Oh, Seung Hyun [College of Pharmacy, Gachon University, Incheon (Korea, Republic of); Ryu, Jae-Ha [The Research Center for Cell Fate Control, College of Pharmacy, Sookmyung Women' s University, Seoul (Korea, Republic of); Kim, Woo-Young, E-mail: wykim@sookmyung.ac.kr [The Research Center for Cell Fate Control, College of Pharmacy, Sookmyung Women' s University, Seoul (Korea, Republic of)

2016-01-22

In spite of the recent improvements, the resistance to chemotherapy/radiotherapy followed by relapse is the main hurdle for the successful treatment of breast cancer, a leading cause of death in women. A small population of breast cancer cells that have stem-like characteristics (cancer stem-like cells; CSLC) may contribute to this resistance and relapse. Here, we report on a component of a traditional Chinese medicine, evodiamine, which selectively targets CSLC of breast cancer cell lines MCF7 and MDAMB 231 at a concentration that does show a little or no cytotoxic effect on bulk cancer cells. While evodiamine caused the accumulation of bulk cancer cells at the G2/M phase, it did not hold CSLC in a specific cell cycle phase but instead, selectively killed CSLC. This was not due to the culture of CSLC in suspension or without FBS. A proteomic analysis and western blotting revealed that evodiamine changed the expression of cell cycle regulating molecules more efficiently in CSLC cells than in bulk cancer cells. Surprisingly, evodiamine selectively activated p53 and p21 and decreased inactive Rb, the master molecules in G1/S checkpoint. These data collectively suggest a novel mechanism involving CSLC-specific targeting by evodiamine and its possible use to the therapy of breast cancer. - Highlights: • Evodiamine selectively kills breast cancer stem like cells at G1 phase. • Evodiamine utilizes different mechanism of cell cycle modulation in CSLC and in bulk cancer cells. • Evodiamine activate the p53, p21 and Rb pathway.

Companion diagnostics for the targeted therapy of gastric cancer.

Science.gov (United States)

Yoo, Changhoon; Park, Young Soo

2015-10-21

Gastric cancer is the fourth most common type of cancer and represents a major cause of cancer-related deaths worldwide. With recent biomedical advances in our understanding of the molecular characteristics of gastric cancer, many genetic alterations have been identified as potential targets for its treatment. Multiple novel agents are currently under development as the demand for active agents that improve the survival of gastric cancer patients constantly increases. Based on lessons from previous trials of targeted agents, it is now widely accepted that the establishment of an optimal diagnostic test to select molecularly defined patients is of equal importance to the development of active agents against targetable genetic alterations. Herein, we highlight the current status and future perspectives of companion diagnostics in the treatment of gastric cancer.

Aspirin acetylates multiple cellular proteins in HCT-116 colon cancer cells: Identification of novel targets.

Science.gov (United States)

Marimuthu, Srinivasan; Chivukula, Raghavender S V; Alfonso, Lloyd F; Moridani, Majid; Hagen, Fred K; Bhat, G Jayarama

2011-11-01

Epidemiological and clinical observations provide consistent evidence that regular intake of aspirin may effectively inhibit the occurrence of epithelial tumors; however, the molecular mechanisms are not completely understood. In the present study, we determined the ability of aspirin to acetylate and post-translationally modify cellular proteins in HCT-116 human colon cancer cells to understand the potential mechanisms by which it may exerts anti-cancer effects. Using anti-acetyl lysine antibodies, here we demonstrate that aspirin causes the acetylation of multiple proteins whose molecular weight ranged from 20 to 200 kDa. The identity of these proteins was determined, using immuno-affinity purification, mass spectrometry and immuno-blotting. A total of 33 cellular proteins were potential targets of aspirin-mediated acetylation, while 16 were identified as common to both the control and aspirin-treated samples. These include enzymes of glycolytic pathway, cytoskeleton proteins, histones, ribosomal and mitochondrial proteins. The glycolytic enzymes which were identified include aldolase, glyceraldehyde-3-phosphate dehydrogenase, enolase, pyruvate kinase M2, and lactate dehydrogenase A and B chains. Immunoblotting experiment showed that aspirin also acetylated glucose-6-phosphate dehydrogenase and transketolase, both enzymes of pentose phosphate pathway involved in ribonucleotide biosynthesis. In vitro assays of these enzymes revealed that aspirin did not affect pyruvate kinase and lactate dehydrogenase activity; however, it decreased glucose 6 phosphate dehydrogenase activity. Similar results were also observed in HT-29 human colon cancer cells. Selective inhibition of glucose-6-phosphate dehydrogenase may represent an important mechanism by which aspirin may exert its anti-cancer effects through inhibition of ribonucleotide synthesis.

Damage to Preheated Tungsten Targets after Multiple Plasma Impacts Simulating ITER ELMs

Energy Technology Data Exchange (ETDEWEB)

Garkusha, I.E.; Bandura, A.N.; Byrka, O.V.; Chebotarev, V.V.; Makhlay, V.A.; Tereshin, V.I. [Kharkov Inst. of Physics and Technology, Inst. of Plasma Physics of National Science Center, Akademicheskaya street, 1, 61108 Kharkov (Ukraine); Landman, I.; Pestchanyi, S. [FZK-Forschungszentrum Karlsruhe, Association Euratom-FZK, Technik und Umwelt, Postfach 3640, D-7602 1 Karlsruhe (Germany)

2007-07-01

Full text of publication follows: The energy loads onto ITER divertor surfaces associated with the Type I ELMs are expected to be up to 1 MJ/m{sup 2} during 0.1-0.5 ms, with the number of pulses about 103 per discharge. Tungsten is a candidate material for major part of the surface, but its brittleness can result in substantial macroscopic erosion after the repetitive heat loads. To minimize the brittle destruction, tungsten may be preheated above the ductile-to-brittle transition temperature. In this work the behavior of preheated tungsten targets under repetitive ELM-like plasma pulses is studied in simulation experiments with the quasi-stationary plasma accelerator QSPA Kh-50. The targets have been exposed up to 450 pulses of the duration 0.25 ms and the heat loads either 0.45 MJ/m{sup 2} or 0.75 MJ/m{sup 2}, which is respectively below and above the melting threshold. During the exposures the targets were permanently kept preheated at 650 deg. C by a heater at target backside. In the course of exposures the irradiated surfaces were examined after regular numbers of pulses using the SEM and the optical microscopy. The profilometry, XRD, microhardness and weight loss measurements have been performed, as well as comparisons of surface damages after the heat loads both below and above the melting threshold. It is obtained that macro-cracks do not develop on the preheated surface. After the impacts with surface melting, a fine mesh of intergranular microcracks has appeared. The width of fine intergranular cracks grows with pulse number, achieving 1-1.5 microns after 100 pulses, and after 210 pulses the crack width increases up to 20 microns, which is comparable with grain sizes. Threshold changes in surface morphology resulting in corrugation structures and pits on the surface as well as importance of surface tension in resulted 'micro-brush' structures are discussed. Further evolution of the surface pattern is caused by loss of separated grains on exposed

Factor Analysis of Therapist-Identified Treatment Targets in Community-Based Children's Mental Health.

Science.gov (United States)

Love, Allison R; Okado, Izumi; Orimoto, Trina E; Mueller, Charles W

2018-01-01

The present study used exploratory and confirmatory factor analyses to identify underlying latent factors affecting variation in community therapists' endorsement of treatment targets. As part of a statewide practice management program, therapist completed monthly reports of treatment targets (up to 10 per month) for a sample of youth (n = 790) receiving intensive in-home therapy. Nearly 75 % of youth were diagnosed with multiple co-occurring disorders. Five factors emerged: Disinhibition, Societal Rules Evasion, Social Engagement Deficits, Emotional Distress, and Management of Biodevelopmental Outcomes. Using logistic regression, primary diagnosis predicted therapist selection of Disinhibition and Emotional Distress targets. Client age predicted endorsement of Societal Rules Evasion targets. Practice-to-research implications are discussed.

Post-Coma Persons with Extensive Multiple Disabilities Use Microswitch Technology to Access Selected Stimulus Events or Operate a Radio Device

Science.gov (United States)

Lancioni, Giulio E.; Singh, Nirbhay N.; O'Reilly, Mark F.; Sigafoos, Jeff; Alberti, Gloria; Oliva, Doretta; Megna, Gianfranco; Iliceto, Carla; Damiani, Sabino; Ricci, Irene; Spica, Antonella

2011-01-01

The present two studies extended research evidence on the use of microswitch technology by post-coma persons with multiple disabilities. Specifically, Study I examined whether three adults with a diagnosis of minimally conscious state and multiple disabilities could use microswitches as tools to access brief, selected stimulus events. Study II…

The selective processing of emotional visual stimuli while detecting auditory targets: an ERP analysis.

Science.gov (United States)

Schupp, Harald T; Stockburger, Jessica; Bublatzky, Florian; Junghöfer, Markus; Weike, Almut I; Hamm, Alfons O

2008-09-16

Event-related potential studies revealed an early posterior negativity (EPN) for emotional compared to neutral pictures. Exploring the emotion-attention relationship, a previous study observed that a primary visual discrimination task interfered with the emotional modulation of the EPN component. To specify the locus of interference, the present study assessed the fate of selective visual emotion processing while attention is directed towards the auditory modality. While simply viewing a rapid and continuous stream of pleasant, neutral, and unpleasant pictures in one experimental condition, processing demands of a concurrent auditory target discrimination task were systematically varied in three further experimental conditions. Participants successfully performed the auditory task as revealed by behavioral performance and selected event-related potential components. Replicating previous results, emotional pictures were associated with a larger posterior negativity compared to neutral pictures. Of main interest, increasing demands of the auditory task did not modulate the selective processing of emotional visual stimuli. With regard to the locus of interference, selective emotion processing as indexed by the EPN does not seem to reflect shared processing resources of visual and auditory modality.

Are multiple-trial experiments appropriate for eyewitness identification studies? Accuracy, choosing, and confidence across trials.

Science.gov (United States)

Mansour, J K; Beaudry, J L; Lindsay, R C L

2017-12-01

Eyewitness identification experiments typically involve a single trial: A participant views an event and subsequently makes a lineup decision. As compared to this single-trial paradigm, multiple-trial designs are more efficient, but significantly reduce ecological validity and may affect the strategies that participants use to make lineup decisions. We examined the effects of a number of forensically relevant variables (i.e., memory strength, type of disguise, degree of disguise, and lineup type) on eyewitness accuracy, choosing, and confidence across 12 target-present and 12 target-absent lineup trials (N = 349; 8,376 lineup decisions). The rates of correct rejections and choosing (across both target-present and target-absent lineups) did not vary across the 24 trials, as reflected by main effects or interactions with trial number. Trial number had a significant but trivial quadratic effect on correct identifications (OR = 0.99) and interacted significantly, but again trivially, with disguise type (OR = 1.00). Trial number did not significantly influence participants' confidence in correct identifications, confidence in correct rejections, or confidence in target-absent selections. Thus, multiple-trial designs appear to have minimal effects on eyewitness accuracy, choosing, and confidence. Researchers should thus consider using multiple-trial designs for conducting eyewitness identification experiments.

Energy, target, projectile and multiplicity dependences of intermittency behaviour in high energy O(Si,S) induced interactions

International Nuclear Information System (INIS)

Adamovich, M.I.; Alexandrov, Y.A.; Chernyavski, M.M.; Gerassimov, S.G.; Kharlamov, S.P.; Larionova, V.G.; Maslennikova, N.V.; Orlova, G.I.; Peresadko, N.G.; Salmanova, N.A.; Tretyakova, M.I.; Ameeva, Z.U.; Andreeva, N.P.; Anzon, Z.V.; Bubnov, V.I.; Chasnikov, I.Y.; Eligbaeva, G.Z.; Eremenko, G.Z.; Gaitinov, A.S.; Kalyachkina, G.S.; Kanygina, E.K.; Skakhova, C.I.; Bhalla, K.B.; Kumar, V.; Lal, P.; Lokanathan, S.; Mookerjee, S.; Raniwala, R.; Raniwala, S.; Burnett, T.H.; Grote, J.; Koss, T.; Lord, J.; Skelding, D.; Strausz, S.C.; Wilkes, R.J.; Cai, X.; Huang, H.; Liu, L.S.; Qian, W.Y.; Wang, H.Q.; Zhou, D.C.; Zhou, J.C.; Chernova, L.P.; Gadzhieva, S.I.; Gulamov, K.G.; Kadyrov, F.G.; Lukicheva, N.S.; Navotny, V.S.; Svechnikova, L.N.; Friedlander, E.M.; Heckman, H.H.; Lindstrom, P.J.; Garpman, S.; Jakobsson, B.; Otterlund, I.; Persson, S.; Soederstroem, K.; Stenlund, E.; Judek, B.; Nasyrov, S.H.; Petrov, N.V.; Xu, G.F.; Zheng, P.Y.

1991-01-01

Fluctuations of charged particles in high energy oxygen, silicon and sulphur induced interactions are investigated with the method of scaled factorial moments. It is found that for decreasing bin size down to δη∝0.1 the EMU01 data exhibits intermittent behaviour. The intermittency indexes are found to decrease with increasing incident energy and multiplicity and to increase with increasing target mass. It seems also to increase as the projectile mass increases. (orig.)

The reactive metabolite target protein database (TPDB)--a web-accessible resource.

Science.gov (United States)

Hanzlik, Robert P; Koen, Yakov M; Theertham, Bhargav; Dong, Yinghua; Fang, Jianwen

2007-03-16

The toxic effects of many simple organic compounds stem from their biotransformation to chemically reactive metabolites which bind covalently to cellular proteins. To understand the mechanisms of cytotoxic responses it may be important to know which proteins become adducted and whether some may be common targets of multiple toxins. The literature of this field is widely scattered but expanding rapidly, suggesting the need for a comprehensive, searchable database of reactive metabolite target proteins. The Reactive Metabolite Target Protein Database (TPDB) is a comprehensive, curated, searchable, documented compilation of publicly available information on the protein targets of reactive metabolites of 18 well-studied chemicals and drugs of known toxicity. TPDB software enables i) string searches for author names and proteins names/synonyms, ii) more complex searches by selecting chemical compound, animal species, target tissue and protein names/synonyms from pull-down menus, and iii) commonality searches over multiple chemicals. Tabulated search results provide information, references and links to other databases. The TPDB is a unique on-line compilation of information on the covalent modification of cellular proteins by reactive metabolites of chemicals and drugs. Its comprehensiveness and searchability should facilitate the elucidation of mechanisms of reactive metabolite toxicity. The database is freely available at http://tpdb.medchem.ku.edu/tpdb.html.

Automatic detection of multiple UXO-like targets using magnetic anomaly inversion and self-adaptive fuzzy c-means clustering

Science.gov (United States)

Yin, Gang; Zhang, Yingtang; Fan, Hongbo; Ren, Guoquan; Li, Zhining

2017-12-01

We have developed a method for automatically detecting UXO-like targets based on magnetic anomaly inversion and self-adaptive fuzzy c-means clustering. Magnetic anomaly inversion methods are used to estimate the initial locations of multiple UXO-like sources. Although these initial locations have some errors with respect to the real positions, they form dense clouds around the actual positions of the magnetic sources. Then we use the self-adaptive fuzzy c-means clustering algorithm to cluster these initial locations. The estimated number of cluster centroids represents the number of targets and the cluster centroids are regarded as the locations of magnetic targets. Effectiveness of the method has been demonstrated using synthetic datasets. Computational results show that the proposed method can be applied to the case of several UXO-like targets that are randomly scattered within in a confined, shallow subsurface, volume. A field test was carried out to test the validity of the proposed method and the experimental results show that the prearranged magnets can be detected unambiguously and located precisely.

Multi-data integration of exploration criteria and selection of prospecting targets

International Nuclear Information System (INIS)

Dechang, L.; Jingke, Z.; Maorong, S.; Guojuan, W.

1991-01-01

In this paper based on the analysis of the exploration criteria for Shengyuan Basin-a uranium ore field, the multi-data integration and information extraction of exploration criteria are carried out on computer and image processing system so that the areas with best combinations of exploration criteria are directly displayed on the screen. Six prospecting targets are selected through the field examination. Shengyuan basin in Jiangxi province is a uranium-producing, Jurassic Cretaceous volcanic-sedimentary basin with an area of about 400 sq km. Its basement consists of Sinian-Cambrian rocks with Caledonian granites intruded. Several uranium deposits, occurrences and anomalies were discovered over the basin region which, therefore, becomes a very important uranium ore field in China

Enhanced Algorithms for EO/IR Electronic Stabilization, Clutter Suppression, and Track-Before-Detect for Multiple Low Observable Targets

Science.gov (United States)

Tartakovsky, A.; Brown, A.; Brown, J.

The paper describes the development and evaluation of a suite of advanced algorithms which provide significantly-improved capabilities for finding, fixing, and tracking multiple ballistic and flying low observable objects in highly stressing cluttered environments. The algorithms have been developed for use in satellite-based staring and scanning optical surveillance suites for applications including theatre and intercontinental ballistic missile early warning, trajectory prediction, and multi-sensor track handoff for midcourse discrimination and intercept. The functions performed by the algorithms include electronic sensor motion compensation providing sub-pixel stabilization (to 1/100 of a pixel), as well as advanced temporal-spatial clutter estimation and suppression to below sensor noise levels, followed by statistical background modeling and Bayesian multiple-target track-before-detect filtering. The multiple-target tracking is performed in physical world coordinates to allow for multi-sensor fusion, trajectory prediction, and intercept. Output of detected object cues and data visualization are also provided. The algorithms are designed to handle a wide variety of real-world challenges. Imaged scenes may be highly complex and infinitely varied -- the scene background may contain significant celestial, earth limb, or terrestrial clutter. For example, when viewing combined earth limb and terrestrial scenes, a combination of stationary and non-stationary clutter may be present, including cloud formations, varying atmospheric transmittance and reflectance of sunlight and other celestial light sources, aurora, glint off sea surfaces, and varied natural and man-made terrain features. The targets of interest may also appear to be dim, relative to the scene background, rendering much of the existing deployed software useless for optical target detection and tracking. Additionally, it may be necessary to detect and track a large number of objects in the threat cloud

Mass hierarchy sensitivity of medium baseline reactor neutrino experiments with multiple detectors

Directory of Open Access Journals (Sweden)

Hong-Xin Wang

2017-05-01

Full Text Available We report the neutrino mass hierarchy (MH determination of medium baseline reactor neutrino experiments with multiple detectors, where the sensitivity of measuring the MH can be significantly improved by adding a near detector. Then the impact of the baseline and target mass of the near detector on the combined MH sensitivity has been studied thoroughly. The optimal selections of the baseline and target mass of the near detector are ∼12.5 km and ∼4 kton respectively for a far detector with the target mass of 20 kton and the baseline of 52.5 km. As typical examples of future medium baseline reactor neutrino experiments, the optimal location and target mass of the near detector are selected for the specific configurations of JUNO and RENO-50. Finally, we discuss distinct effects of the reactor antineutrino energy spectrum uncertainty for setups of a single detector and double detectors, which indicate that the spectrum uncertainty can be well constrained in the presence of the near detector.

The effect of spatial organization of targets and distractors on the capacity to selectively memorize objects in visual short-term memory.

Science.gov (United States)

Abbes, Aymen Ben; Gavault, Emmanuelle; Ripoll, Thierry

2014-01-01

We conducted a series of experiments to explore how the spatial configuration of objects influences the selection and the processing of these objects in a visual short-term memory task. We designed a new experiment in which participants had to memorize 4 targets presented among 4 distractors. Targets were cued during the presentation of distractor objects. Their locations varied according to 4 spatial configurations. From the first to the last configuration, the distance between targets' locations was progressively increased. The results revealed a high capacity to select and memorize targets embedded among distractors even when targets were extremely distant from each other. This capacity is discussed in relation to the unitary conception of attention, models of split attention, and the competitive interaction model. Finally, we propose that the spatial dispersion of objects has different effects on attentional allocation and processing stages. Thus, when targets are extremely distant from each other, attentional allocation becomes more difficult while processing becomes easier. This finding implicates that these 2 aspects of attention need to be more clearly distinguished in future research.

Comparing the Selection and Placement of Best Management Practices in Improving Water Quality Using a Multiobjective Optimization and Targeting Method

Directory of Open Access Journals (Sweden)

Li-Chi Chiang

2014-03-01

Full Text Available Suites of Best Management Practices (BMPs are usually selected to be economically and environmentally efficient in reducing nonpoint source (NPS pollutants from agricultural areas in a watershed. The objective of this research was to compare the selection and placement of BMPs in a pasture-dominated watershed using multiobjective optimization and targeting methods. Two objective functions were used in the optimization process, which minimize pollutant losses and the BMP placement areas. The optimization tool was an integration of a multi-objective genetic algorithm (GA and a watershed model (Soil and Water Assessment Tool—SWAT. For the targeting method, an optimum BMP option was implemented in critical areas in the watershed that contribute the greatest pollutant losses. A total of 171 BMP combinations, which consist of grazing management, vegetated filter strips (VFS, and poultry litter applications were considered. The results showed that the optimization is less effective when vegetated filter strips (VFS are not considered, and it requires much longer computation times than the targeting method to search for optimum BMPs. Although the targeting method is effective in selecting and placing an optimum BMP, larger areas are needed for BMP implementation to achieve the same pollutant reductions as the optimization method.

Design and selection of load control strategies using a multiple objective model and evolutionary algorithms

International Nuclear Information System (INIS)

Gomes, Alvaro; Antunes, Carlos Henggeler; Martins, Antonio Gomes

2005-01-01

This paper aims at presenting a multiple objective model to evaluate the attractiveness of the use of demand resources (through load management control actions) by different stakeholders and in diverse structure scenarios in electricity systems. For the sake of model flexibility, the multiple (and conflicting) objective functions of technical, economical and quality of service nature are able to capture distinct market scenarios and operating entities that may be interested in promoting load management activities. The computation of compromise solutions is made by resorting to evolutionary algorithms, which are well suited to tackle multiobjective problems of combinatorial nature herein involving the identification and selection of control actions to be applied to groups of loads. (Author)

Variable selection for confounder control, flexible modeling and Collaborative Targeted Minimum Loss-based Estimation in causal inference

Science.gov (United States)

Schnitzer, Mireille E.; Lok, Judith J.; Gruber, Susan

2015-01-01

This paper investigates the appropriateness of the integration of flexible propensity score modeling (nonparametric or machine learning approaches) in semiparametric models for the estimation of a causal quantity, such as the mean outcome under treatment. We begin with an overview of some of the issues involved in knowledge-based and statistical variable selection in causal inference and the potential pitfalls of automated selection based on the fit of the propensity score. Using a simple example, we directly show the consequences of adjusting for pure causes of the exposure when using inverse probability of treatment weighting (IPTW). Such variables are likely to be selected when using a naive approach to model selection for the propensity score. We describe how the method of Collaborative Targeted minimum loss-based estimation (C-TMLE; van der Laan and Gruber, 2010) capitalizes on the collaborative double robustness property of semiparametric efficient estimators to select covariates for the propensity score based on the error in the conditional outcome model. Finally, we compare several approaches to automated variable selection in low-and high-dimensional settings through a simulation study. From this simulation study, we conclude that using IPTW with flexible prediction for the propensity score can result in inferior estimation, while Targeted minimum loss-based estimation and C-TMLE may benefit from flexible prediction and remain robust to the presence of variables that are highly correlated with treatment. However, in our study, standard influence function-based methods for the variance underestimated the standard errors, resulting in poor coverage under certain data-generating scenarios. PMID:26226129

Analysis of Myc-induced histone modifications on target chromatin.

Directory of Open Access Journals (Sweden)

Francesca Martinato

Full Text Available The c-myc proto-oncogene is induced by mitogens and is a central regulator of cell growth and differentiation. The c-myc product, Myc, is a transcription factor that binds a multitude of genomic sites, estimated to be over 10-15% of all promoter regions. Target promoters generally pre-exist in an active or poised chromatin state that is further modified by Myc, contributing to fine transcriptional regulation (activation or repression of the afferent gene. Among other mechanisms, Myc recruits histone acetyl-transferases to target chromatin and locally promotes hyper-acetylation of multiple lysines on histones H3 and H4, although the identity and combination of the modified lysines is unknown. Whether Myc dynamically regulates other histone modifications (or marks at its binding sites also remains to be addressed. Here, we used quantitative chromatin immunoprecipitation (qChIP to profile a total of 24 lysine-acetylation and -methylation marks modulated by Myc at target promoters in a human B-cell line with a regulatable c-myc transgene. Myc binding promoted acetylation of multiple lysines, primarily of H3K9, H3K14, H3K18, H4K5 and H4K12, but significantly also of H4K8, H4K91 and H2AK5. Dimethylation of H3K79 was also selectively induced at target promoters. A majority of target promoters showed co-induction of multiple marks - in various combinations - correlating with recruitment of the two HATs tested (Tip60 and HBO1, incorporation of the histone variant H2A.Z and transcriptional activation. Based on this and previous findings, we surmise that Myc recruits the Tip60/p400 complex to achieve a coordinated histone acetylation/exchange reaction at activated promoters. Our data are also consistent with the additive and redundant role of multiple acetylation events in transcriptional activation.

Fine tuning of RFX/DAF-19-regulated target gene expression through binding to multiple sites in Caenorhabditis elegans

OpenAIRE

Chu, Jeffery S. C.; Tarailo-Graovac, Maja; Zhang, Di; Wang, Jun; Uyar, Bora; Tu, Domena; Trinh, Joanne; Baillie, David L.; Chen, Nansheng

2011-01-01

In humans, mutations of a growing list of regulatory factor X (RFX) target genes have been associated with devastating genetics disease conditions including ciliopathies. However, mechanisms underlying RFX transcription factors (TFs)-mediated gene expression regulation, especially differential gene expression regulation, are largely unknown. In this study, we explore the functional significance of the co-existence of multiple X-box motifs in regulating differential gene expression in Caenorha...

Fusion strategies for selecting multiple tuning parameters for multivariate calibration and other penalty based processes: A model updating application for pharmaceutical analysis

Energy Technology Data Exchange (ETDEWEB)

Tencate, Alister J. [Department of Chemistry, Idaho State University, Pocatello, ID 83209 (United States); Kalivas, John H., E-mail: kalijohn@isu.edu [Department of Chemistry, Idaho State University, Pocatello, ID 83209 (United States); White, Alexander J. [Department of Physics and Optical Engineering, Rose-Hulman Institute of Technology, Terre Huate, IN 47803 (United States)

2016-05-19

New multivariate calibration methods and other processes are being developed that require selection of multiple tuning parameter (penalty) values to form the final model. With one or more tuning parameters, using only one measure of model quality to select final tuning parameter values is not sufficient. Optimization of several model quality measures is challenging. Thus, three fusion ranking methods are investigated for simultaneous assessment of multiple measures of model quality for selecting tuning parameter values. One is a supervised learning fusion rule named sum of ranking differences (SRD). The other two are non-supervised learning processes based on the sum and median operations. The effect of the number of models evaluated on the three fusion rules are also evaluated using three procedures. One procedure uses all models from all possible combinations of the tuning parameters. To reduce the number of models evaluated, an iterative process (only applicable to SRD) is applied and thresholding a model quality measure before applying the fusion rules is also used. A near infrared pharmaceutical data set requiring model updating is used to evaluate the three fusion rules. In this case, calibration of the primary conditions is for the active pharmaceutical ingredient (API) of tablets produced in a laboratory. The secondary conditions for calibration updating is for tablets produced in the full batch setting. Two model updating processes requiring selection of two unique tuning parameter values are studied. One is based on Tikhonov regularization (TR) and the other is a variation of partial least squares (PLS). The three fusion methods are shown to provide equivalent and acceptable results allowing automatic selection of the tuning parameter values. Best tuning parameter values are selected when model quality measures used with the fusion rules are for the small secondary sample set used to form the updated models. In this model updating situation, evaluation of

Fusion strategies for selecting multiple tuning parameters for multivariate calibration and other penalty based processes: A model updating application for pharmaceutical analysis

International Nuclear Information System (INIS)

Tencate, Alister J.; Kalivas, John H.; White, Alexander J.

2016-01-01

New multivariate calibration methods and other processes are being developed that require selection of multiple tuning parameter (penalty) values to form the final model. With one or more tuning parameters, using only one measure of model quality to select final tuning parameter values is not sufficient. Optimization of several model quality measures is challenging. Thus, three fusion ranking methods are investigated for simultaneous assessment of multiple measures of model quality for selecting tuning parameter values. One is a supervised learning fusion rule named sum of ranking differences (SRD). The other two are non-supervised learning processes based on the sum and median operations. The effect of the number of models evaluated on the three fusion rules are also evaluated using three procedures. One procedure uses all models from all possible combinations of the tuning parameters. To reduce the number of models evaluated, an iterative process (only applicable to SRD) is applied and thresholding a model quality measure before applying the fusion rules is also used. A near infrared pharmaceutical data set requiring model updating is used to evaluate the three fusion rules. In this case, calibration of the primary conditions is for the active pharmaceutical ingredient (API) of tablets produced in a laboratory. The secondary conditions for calibration updating is for tablets produced in the full batch setting. Two model updating processes requiring selection of two unique tuning parameter values are studied. One is based on Tikhonov regularization (TR) and the other is a variation of partial least squares (PLS). The three fusion methods are shown to provide equivalent and acceptable results allowing automatic selection of the tuning parameter values. Best tuning parameter values are selected when model quality measures used with the fusion rules are for the small secondary sample set used to form the updated models. In this model updating situation, evaluation of

Identifying Drug-Target Interactions with Decision Templates.

Science.gov (United States)

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

Construction of multiple linear regression models using blood biomarkers for selecting against abdominal fat traits in broilers.

Science.gov (United States)

Dong, J Q; Zhang, X Y; Wang, S Z; Jiang, X F; Zhang, K; Ma, G W; Wu, M Q; Li, H; Zhang, H

2018-01-01

Plasma very low-density lipoprotein (VLDL) can be used to select for low body fat or abdominal fat (AF) in broilers, but its correlation with AF is limited. We investigated whether any other biochemical indicator can be used in combination with VLDL for a better selective effect. Nineteen plasma biochemical indicators were measured in male chickens from the Northeast Agricultural University broiler lines divergently selected for AF content (NEAUHLF) in the fed state at 46 and 48 d of age. The average concentration of every parameter for the 2 d was used for statistical analysis. Levels of these 19 plasma biochemical parameters were compared between the lean and fat lines. The phenotypic correlations between these plasma biochemical indicators and AF traits were analyzed. Then, multiple linear regression models were constructed to select the best model used for selecting against AF content. and the heritabilities of plasma indicators contained in the best models were estimated. The results showed that 11 plasma biochemical indicators (triglycerides, total bile acid, total protein, globulin, albumin/globulin, aspartate transaminase, alanine transaminase, gamma-glutamyl transpeptidase, uric acid, creatinine, and VLDL) differed significantly between the lean and fat lines (P linear regression models based on albumin/globulin, VLDL, triglycerides, globulin, total bile acid, and uric acid, had higher R2 (0.73) than the model based only on VLDL (0.21). The plasma parameters included in the best models had moderate heritability estimates (0.21 ≤ h2 ≤ 0.43). These results indicate that these multiple linear regression models can be used to select for lean broiler chickens. © 2017 Poultry Science Association Inc.

Selection and Characterization of Single Chain Antibody Fragments Specific for Hsp90 as a Potential Cancer Targeting Molecule

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Edyta Petters

2015-08-01

Full Text Available Heat shock proteins play an essential role in facilitating malignant transformation and they have been recognized as important factors in human cancers. One of the key elements of the molecular chaperones machinery is Hsp90 and it has recently become a target for anticancer therapeutic approaches. The potential and importance of Hsp90-directed agents becomes apparent when one realizes that disruption of Hsp90 function may influence over 200 oncogenic client proteins. Here, we described the selection and characterization of Hsp90-specific antibody fragments from commercially available Tomlinson I and J phage display libraries. The affinities of Hsp90-binding scFv variants were measured using SPR method. Then, based on the best clone selected, we performed the affinity maturation procedure and obtained valuable Hsp90-specific clones. The selected binders were expressed and applied for immunostaining, ELISA and SPR analysis using model cancer cell lines. All performed experiments confirmed the ability of selected antibodies to interact with the Hsp90. Therefore, the presented Hsp90-specific scFv, might be a starting point for the development of a novel antibody-based strategy targeting cancer.

Discovery and optimization of potent and selective imidazopyridine and imidazopyridazine mTOR inhibitors.

Science.gov (United States)

Peterson, Emily A; Boezio, Alessandro A; Andrews, Paul S; Boezio, Christiane M; Bush, Tammy L; Cheng, Alan C; Choquette, Deborah; Coats, James R; Colletti, Adria E; Copeland, Katrina W; DuPont, Michelle; Graceffa, Russell; Grubinska, Barbara; Kim, Joseph L; Lewis, Richard T; Liu, Jingzhou; Mullady, Erin L; Potashman, Michele H; Romero, Karina; Shaffer, Paul L; Stanton, Mary K; Stellwagen, John C; Teffera, Yohannes; Yi, Shuyan; Cai, Ti; La, Daniel S

2012-08-01

mTOR is a critical regulator of cellular signaling downstream of multiple growth factors. The mTOR/PI3K/AKT pathway is frequently mutated in human cancers and is thus an important oncology target. Herein we report the evolution of our program to discover ATP-competitive mTOR inhibitors that demonstrate improved pharmacokinetic properties and selectivity compared to our previous leads. Through targeted SAR and structure-guided design, new imidazopyridine and imidazopyridazine scaffolds were identified that demonstrated superior inhibition of mTOR in cellular assays, selectivity over the closely related PIKK family and improved in vivo clearance over our previously reported benzimidazole series. Copyright © 2012. Published by Elsevier Ltd.

Analysis of LFM-waveform Libraries for Cognitive Tracking Maneuvering Targets

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Wang Hongyan

2016-01-01

Full Text Available Based on the idea of the waveform agility in cognitive radars，the waveform libraries for maneuvering target tracking are discussed. LFM-waveform libraries are designed according to different combinations of chirp parameters and FrFT rotation angles. By applying the interact multiple model (IMM algorithm in tracking maneuvering targets, transmitted waveform is called real time from the LFM-waveform libraries. The waveforms are selected from the library according to the criterion of maximum mutual information between the current state of knowledge of the model and the measurement. Simulation results show that waveform library containing certain amount LFM-waveforms can improve the performance of cognitive tracking radar.

High-efficiency target-ion sources for RIB generation

International Nuclear Information System (INIS)

Alton, G.D.

1993-01-01

A brief review is given of high-efficiency ion sources which have been developed or are under development at ISOL facilities which show particular promise for use at existing, future, or radioactive ion beam (RIB) facilities now under construction. Emphasis will be placed on those sources which have demonstrated high ionization efficiency, species versatility, and operational reliability and which have been carefully designed for safe handling in the high level radioactivity radiation fields incumbent at such facilities. Brief discussions will also be made of the fundamental processes which affect the realizable beam intensities in target-ion sources. Among the sources which will be reviewed will be selected examples of state-of-the-art electron-beam plasma-type ion sources, thermal-ionization, surface-ionization, ECR, and selectively chosen ion source concepts which show promise for radioactive ion beam generation. A few advanced, chemically selective target-ion sources will be described, such as sources based on the use of laser-resonance ionization, which, in principle, offer a more satisfactory solution to isobaric contamination problems than conventional electromagnetic techniques. Particular attention will be given to the sources which have been selected for initial or future use at the Holifield Radioactive Ion Beam Facility now under construction at the Oak Ridge National Laboratory

Non-targeted detection of chemical contamination in carbonated soft drinks using NMR spectroscopy, variable selection and chemometrics

Energy Technology Data Exchange (ETDEWEB)

Charlton, Adrian J. [Department for Environment, Food and Rural Affairs, Central Science Laboratory, Sand Hutton, York YO41 1LZ (United Kingdom)], E-mail: adrian.charlton@csl.gov.uk; Robb, Paul; Donarski, James A.; Godward, John [Department for Environment, Food and Rural Affairs, Central Science Laboratory, Sand Hutton, York YO41 1LZ (United Kingdom)

2008-06-23

An efficient method for detecting malicious and accidental contamination of foods has been developed using a combined {sup 1}H nuclear magnetic resonance (NMR) and chemometrics approach. The method has been demonstrated using a commercially available carbonated soft drink, as being capable of identifying atypical products and to identify contaminant resonances. Soft-independent modelling of class analogy (SIMCA) was used to compare {sup 1}H NMR profiles of genuine products (obtained from the manufacturer) against retail products spiked in the laboratory with impurities. The benefits of using feature selection for extracting contaminant NMR frequencies were also assessed. Using example impurities (paraquat, p-cresol and glyphosate) NMR spectra were analysed using multivariate methods resulting in detection limits of approximately 0.075, 0.2, and 0.06 mM for p-cresol, paraquat and glyphosate, respectively. These detection limits are shown to be approximately 100-fold lower than the minimum lethal dose for paraquat. The methodology presented here is used to assess the composition of complex matrices for the presence of contaminating molecules without a priori knowledge of the nature of potential contaminants. The ability to detect if a sample does not fit into the expected profile without recourse to multiple targeted analyses is a valuable tool for incident detection and forensic applications.

Non-targeted detection of chemical contamination in carbonated soft drinks using NMR spectroscopy, variable selection and chemometrics

International Nuclear Information System (INIS)

Charlton, Adrian J.; Robb, Paul; Donarski, James A.; Godward, John

2008-01-01

An efficient method for detecting malicious and accidental contamination of foods has been developed using a combined 1 H nuclear magnetic resonance (NMR) and chemometrics approach. The method has been demonstrated using a commercially available carbonated soft drink, as being capable of identifying atypical products and to identify contaminant resonances. Soft-independent modelling of class analogy (SIMCA) was used to compare 1 H NMR profiles of genuine products (obtained from the manufacturer) against retail products spiked in the laboratory with impurities. The benefits of using feature selection for extracting contaminant NMR frequencies were also assessed. Using example impurities (paraquat, p-cresol and glyphosate) NMR spectra were analysed using multivariate methods resulting in detection limits of approximately 0.075, 0.2, and 0.06 mM for p-cresol, paraquat and glyphosate, respectively. These detection limits are shown to be approximately 100-fold lower than the minimum lethal dose for paraquat. The methodology presented here is used to assess the composition of complex matrices for the presence of contaminating molecules without a priori knowledge of the nature of potential contaminants. The ability to detect if a sample does not fit into the expected profile without recourse to multiple targeted analyses is a valuable tool for incident detection and forensic applications

Tracking a convoy of multiple targets using acoustic sensor data

Science.gov (United States)

Damarla, T. R.

2003-08-01

In this paper we present an algorithm to track a convoy of several targets in a scene using acoustic sensor array data. The tracking algorithm is based on template of the direction of arrival (DOA) angles for the leading target. Often the first target is the closest target to the sensor array and hence the loudest with good signal to noise ratio. Several steps were used to generate a template of the DOA angle for the leading target, namely, (a) the angle at the present instant should be close to the angle at the previous instant and (b) the angle at the present instant should be within error bounds of the predicted value based on the previous values. Once the template of the DOA angles of the leading target is developed, it is used to predict the DOA angle tracks of the remaining targets. In order to generate the tracks for the remaining targets, a track is established if the angles correspond to the initial track values of the first target. Second the time delay between the first track and the remaining tracks are estimated at the highest correlation points between the first track and the remaining tracks. As the vehicles move at different speeds the tracks either compress or expand depending on whether a target is moving fast or slow compared to the first target. The expansion and compression ratios are estimated and used to estimate the predicted DOA angle values of the remaining targets. Based on these predicted DOA angles of the remaining targets the DOA angles obtained from the MVDR or Incoherent MUSIC will be appropriately assigned to proper tracks. Several other rules were developed to avoid mixing the tracks. The algorithm is tested on data collected at Aberdeen Proving Ground with a convoy of 3, 4 and 5 vehicles. Some of the vehicles are tracked and some are wheeled vehicles. The tracking algorithm results are found to be good. The results will be presented at the conference and in the paper.

Sociodemographic and social contextual predictors of multiple health behavior change: data from the Healthy Directions-Small Business study.

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Harley, Amy E; Sapp, Amy L; Li, Yi; Marino, Miguel; Quintiliani, Lisa M; Sorensen, Glorian

2013-03-01

Multiple modifiable health behaviors contribute to the chronic diseases that are the leading causes of death in the USA. Disparities for meeting recommended health behavior guidelines exist across occupational classes and socioeconomic levels. The purpose of this paper was to investigate sociodemographic and social contextual predictors of multiple health behavior change in a worksite intervention. We analyzed data on four diet and exercise variables from an intervention trial with worksite-level randomization. Eight hundred forty-one employees had complete data from baseline (response rate = 84 %) and follow-up surveys (response rate = 77 %). Multilevel logistic regression estimated associations between least absolute shrinkage and selection operator-selected sociodemographic and social contextual predictor variables and the multiple health behavior change outcome (changing 2+ versus 0 behaviors). Gender, being married/partnered, and perceived discrimination were significantly associated with multiple health behavior change. Sociodemographic and social contextual factors predict multiple health behavior change and could inform the design and delivery of worksite interventions targeting multiple health behaviors.

Highly Stable Aptamers Selected from a 2′-Fully Modified fGmH RNA Library for Targeting Biomaterials

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Friedman, Adam D.; Kim, Dongwook; Liu, Rihe

2014-01-01

When developed as targeting ligands for the in vivo delivery of biomaterials to biological systems, RNA aptamers immediately face numerous obstacles, in particular nuclease degradation and post-selection 2′ modification. This study aims to develop a novel class of highly stable, 2′-fully modified RNA aptamers that are ideal for the targeted delivery of biomaterials. We demonstrated the facile transcription of a fGmH (2′-F-dG, 2′-OMe-dA/dC/dU) RNA library with unexpected hydrophobicity, the direct selection of aptamers from a fGmH RNA library that bind Staphylococcus aureus Protein A (SpA) as a model target, and the superior nuclease and serum stability of these aptamers compared to 2′-partially modified RNA variants. Characterizations of fGmH RNA aptamers binding to purified SpA and to endogenous SpA present on the surface of S. aureus cells demonstrate fGmH RNA aptamer selectivity and stability. Significantly, fGmH RNA aptamers were able to functionalize, stabilize, and further deliver aggregation-prone silver nanoparticles (AgNPs) to S. aureus with SpA-dependent antimicrobial effects. This study describes a novel aptamer class with considerable potential to improve the in vivo applicability of nucleic acid-based affinity molecules to biomaterials. PMID:25443790

Exploring the Trypanosoma brucei Hsp83 potential as a target for structure guided drug design.

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Juan Carlos Pizarro

Full Text Available Human African trypanosomiasis is a neglected parasitic disease that is fatal if untreated. The current drugs available to eliminate the causative agent Trypanosoma brucei have multiple liabilities, including toxicity, increasing problems due to treatment failure and limited efficacy. There are two approaches to discover novel antimicrobial drugs--whole-cell screening and target-based discovery. In the latter case, there is a need to identify and validate novel drug targets in Trypanosoma parasites. The heat shock proteins (Hsp, while best known as cancer targets with a number of drug candidates in clinical development, are a family of emerging targets for infectious diseases. In this paper, we report the exploration of T. brucei Hsp83--a homolog of human Hsp90--as a drug target using multiple biophysical and biochemical techniques. Our approach included the characterization of the chemical sensitivity of the parasitic chaperone against a library of known Hsp90 inhibitors by means of differential scanning fluorimetry (DSF. Several compounds identified by this screening procedure were further studied using isothermal titration calorimetry (ITC and X-ray crystallography, as well as tested in parasite growth inhibitions assays. These experiments led us to the identification of a benzamide derivative compound capable of interacting with TbHsp83 more strongly than with its human homologs and structural rationalization of this selectivity. The results highlight the opportunities created by subtle structural differences to develop new series of compounds to selectively target the Trypanosoma brucei chaperone and effectively kill the sleeping sickness parasite.

QSRR modeling for the chromatographic retention behavior of some β-lactam antibiotics using forward and firefly variable selection algorithms coupled with multiple linear regression.

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Fouad, Marwa A; Tolba, Enas H; El-Shal, Manal A; El Kerdawy, Ahmed M

2018-05-11

The justified continuous emerging of new β-lactam antibiotics provokes the need for developing suitable analytical methods that accelerate and facilitate their analysis. A face central composite experimental design was adopted using different levels of phosphate buffer pH, acetonitrile percentage at zero time and after 15 min in a gradient program to obtain the optimum chromatographic conditions for the elution of 31 β-lactam antibiotics. Retention factors were used as the target property to build two QSRR models utilizing the conventional forward selection and the advanced nature-inspired firefly algorithm for descriptor selection, coupled with multiple linear regression. The obtained models showed high performance in both internal and external validation indicating their robustness and predictive ability. Williams-Hotelling test and student's t-test showed that there is no statistical significant difference between the models' results. Y-randomization validation showed that the obtained models are due to significant correlation between the selected molecular descriptors and the analytes' chromatographic retention. These results indicate that the generated FS-MLR and FFA-MLR models are showing comparable quality on both the training and validation levels. They also gave comparable information about the molecular features that influence the retention behavior of β-lactams under the current chromatographic conditions. We can conclude that in some cases simple conventional feature selection algorithm can be used to generate robust and predictive models comparable to that are generated using advanced ones. Copyright © 2018 Elsevier B.V. All rights reserved.

Multiple-output support vector machine regression with feature selection for arousal/valence space emotion assessment.

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Torres-Valencia, Cristian A; Álvarez, Mauricio A; Orozco-Gutiérrez, Alvaro A

2014-01-01

Human emotion recognition (HER) allows the assessment of an affective state of a subject. Until recently, such emotional states were described in terms of discrete emotions, like happiness or contempt. In order to cover a high range of emotions, researchers in the field have introduced different dimensional spaces for emotion description that allow the characterization of affective states in terms of several variables or dimensions that measure distinct aspects of the emotion. One of the most common of such dimensional spaces is the bidimensional Arousal/Valence space. To the best of our knowledge, all HER systems so far have modelled independently, the dimensions in these dimensional spaces. In this paper, we study the effect of modelling the output dimensions simultaneously and show experimentally the advantages in modeling them in this way. We consider a multimodal approach by including features from the Electroencephalogram and a few physiological signals. For modelling the multiple outputs, we employ a multiple output regressor based on support vector machines. We also include an stage of feature selection that is developed within an embedded approach known as Recursive Feature Elimination (RFE), proposed initially for SVM. The results show that several features can be eliminated using the multiple output support vector regressor with RFE without affecting the performance of the regressor. From the analysis of the features selected in smaller subsets via RFE, it can be observed that the signals that are more informative into the arousal and valence space discrimination are the EEG, Electrooculogram/Electromiogram (EOG/EMG) and the Galvanic Skin Response (GSR).

Molecular Targets for Targeted Radionuclide Therapy

International Nuclear Information System (INIS)

Mather, S.J.

2009-01-01

Molecular targeted radionuclide cancer therapy is becoming of increasing importance, especially for disseminated diseases. Systemic chemotherapies often lack selectivity while targeted radionuclide therapy has important advantages as the radioactive cytotoxic unit of the targeting vector is specifically directed to the cancer, sparing normal tissues. The principle strategy to improve cancer selectivity is to couple therapeutic agents to tumour-targeting vectors. In targeted radionuclide therapy (TRT), the cytotoxic portion of the conjugates normally contains a therapeutic radiometal immobilised by a bifunctional chelator. The aim is therefore to use as ligand-targeted therapeutics vectors coupled to Auger-, alpha- and/or beta-emitting radionuclides. An advantage of using radiation instead of chemotherapeutics as the cytotoxic agent is the so called 'crossfire effect'. This allows sterilisation of tumour cells that are not directly targeted due to heterogeneity in target molecule expression or inhomogeneous vector delivery. However, before the targeting ligands can be selected, the target molecule on the tumour has to be selected. It should be uniquely expressed, or at least highly overexpressed, on or in the target cells relative to normal tissues. The target should be easily accessible for ligand delivery and should not be shed or down- regulated after ligand binding. An important property of a receptor (or antigen) is its potential to be internalized upon binding of the ligand. This provides an active uptake mechanism and allows the therapeutic agent to be trapped within the tumour cells. Molecular targets of current interest include: Receptors: G-protein coupled receptors are overexpressed on many major human tumours. The prototype of these receptors are somatostatin receptors which show very high density in neuroendocrine tumours, but there are many other most interesting receptors to be applied for TRT. The targeting ligands for these receptors are

Visual encoding and fixation target selection in free viewing: presaccadic brain potentials

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Andrey R Nikolaev

2013-06-01

Full Text Available In scrutinizing a scene, the eyes alternate between fixations and saccades. During a fixation, two component processes can be distinguished: visual encoding and selection of the next fixation target. We aimed to distinguish the neural correlates of these processes in the electrical brain activity prior to a saccade onset. Participants viewed color photographs of natural scenes, in preparation for a change detection task. Then, for each participant and each scene we computed an image heat map, with temperature representing the duration and density of fixations. The temperature difference between the start and end points of saccades was taken as a measure of the expected task-relevance of the information concentrated in specific regions of a scene. Visual encoding was evaluated according to whether subsequent change was correctly detected. Saccades with larger temperature difference were more likely to be followed by correct detection than ones with smaller temperature differences. The amplitude of presaccadic activity over anterior brain areas was larger for correct detection than for detection failure. This difference was observed for short scrutinizing but not for long explorative saccades, suggesting that presaccadic activity reflects top-down saccade guidance. Thus, successful encoding requires local scanning of scene regions which are expected to be task-relevant. Next, we evaluated fixation target selection. Saccades moving up in temperature were preceded by presaccadic activity of higher amplitude than those moving down. This finding suggests that presaccadic activity reflects attention deployed to the following fixation location. Our findings illustrate how presaccadic activity can elucidate concurrent brain processes related to the immediate goal of planning the next saccade and the larger-scale goal of constructing a robust representation of the visual scene.

Optimal management of radial artery grafts in CABG: Patient and target vessel selection and anti-spasm therapy.

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Schwann, Thomas A; Gaudino, Mario; Baldawi, Mustafa; Tranbaugh, Robert; Schwann, Alexandra N; Habib, Robert H

2018-05-01

The current literature on radial artery grafting is reviewed focusing on the optimal deployment of radial artery grafts in coronary artery bypass surgery with specific attention to the selection of patients and target vessels for radial artery grafting. © 2018 Wiley Periodicals, Inc.

Target-specific NMR detection of protein–ligand interactions with antibody-relayed {sup 15}N-group selective STD

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Hetényi, Anasztázia [University of Szeged, Department of Medical Chemistry (Hungary); Hegedűs, Zsófia [University of Szeged, SZTE-MTA Lendület Foldamer Research Group, Institute of Pharmaceutical Analysis Department (Hungary); Fajka-Boja, Roberta; Monostori, Éva [Biological Research Center of the Hungarian Academy of Sciences, Lymphocyte Signal Transduction Laboratory, Institute of Genetics (Hungary); Kövér, Katalin E. [University of Debrecen, Department of Inorganic and Analytical Chemistry (Hungary); Martinek, Tamás A., E-mail: martinek@pharm.u-szeged.hu [University of Szeged, SZTE-MTA Lendület Foldamer Research Group, Institute of Pharmaceutical Analysis Department (Hungary)

2016-12-15

Fragment-based drug design has been successfully applied to challenging targets where the detection of the weak protein–ligand interactions is a key element. {sup 1}H saturation transfer difference (STD) NMR spectroscopy is a powerful technique for this work but it requires pure homogeneous proteins as targets. Monoclonal antibody (mAb)-relayed {sup 15}N-GS STD spectroscopy has been developed to resolve the problem of protein mixtures and impure proteins. A {sup 15}N-labelled target-specific mAb is selectively irradiated and the saturation is relayed through the target to the ligand. Tests on the anti-Gal-1 mAb/Gal-1/lactose system showed that the approach is experimentally feasible in a reasonable time frame. This method allows detection and identification of binding molecules directly from a protein mixture in a multicomponent system.

A BAND SELECTION METHOD FOR SUB-PIXEL TARGET DETECTION IN HYPERSPECTRAL IMAGES BASED ON LABORATORY AND FIELD REFLECTANCE SPECTRAL COMPARISON

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S. Sharifi hashjin

2016-06-01

Full Text Available In recent years, developing target detection algorithms has received growing interest in hyperspectral images. In comparison to the classification field, few studies have been done on dimension reduction or band selection for target detection in hyperspectral images. This study presents a simple method to remove bad bands from the images in a supervised manner for sub-pixel target detection. The proposed method is based on comparing field and laboratory spectra of the target of interest for detecting bad bands. For evaluation, the target detection blind test dataset is used in this study. Experimental results show that the proposed method can improve efficiency of the two well-known target detection methods, ACE and CEM.

Using the Dual-Target Cost to Explore the Nature of Search Target Representations

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Stroud, Michael J.; Menneer, Tamaryn; Cave, Kyle R.; Donnelly, Nick

2012-01-01

Eye movements were monitored to examine search efficiency and infer how color is mentally represented to guide search for multiple targets. Observers located a single color target very efficiently by fixating colors similar to the target. However, simultaneous search for 2 colors produced a dual-target cost. In addition, as the similarity between…

The Vasa Homolog RDE-12 engages target mRNA and multiple argonaute proteins to promote RNAi in C. elegans.

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Shirayama, Masaki; Stanney, William; Gu, Weifeng; Seth, Meetu; Mello, Craig C

2014-04-14

Argonaute (AGO) proteins are key nuclease effectors of RNAi. Although purified AGOs can mediate a single round of target RNA cleavage in vitro, accessory factors are required for small interfering RNA (siRNA) loading and to achieve multiple-target turnover. To identify AGO cofactors, we immunoprecipitated the C. elegans AGO WAGO-1, which engages amplified small RNAs during RNAi. These studies identified a robust association between WAGO-1 and a conserved Vasa ATPase-related protein RDE-12. rde-12 mutants are deficient in RNAi, including viral suppression, and fail to produce amplified secondary siRNAs and certain endogenous siRNAs (endo-siRNAs). RDE-12 colocalizes with WAGO-1 in germline P granules and in cytoplasmic and perinuclear foci in somatic cells. These findings and our genetic studies suggest that RDE-12 is first recruited to target mRNA by upstream AGOs (RDE-1 and ERGO-1), where it promotes small RNA amplification and/or WAGO-1 loading. Downstream of these events, RDE-12 forms an RNase-resistant (target mRNA-independent) complex with WAGO-1 and may thus have additional functions in target mRNA surveillance and silencing. Copyright © 2014 Elsevier Ltd. All rights reserved.

Short, multiple-stranded β-hairpin peptides have antimicrobial potency with high selectivity and salt resistance.

Science.gov (United States)

Chou, Shuli; Shao, Changxuan; Wang, Jiajun; Shan, Anshan; Xu, Lin; Dong, Na; Li, Zhongyu

2016-01-01

The β-hairpin structure has been proposed to exhibit potent antimicrobial properties with low cytotoxicity, thus, multiple β-hairpin structures have been proved to be highly stable in structures containing tightly packed hydrophobic cores. The aim of this study was to develop peptide-based synthetic strategies for generating short, but effective AMPs as inexpensive antimicrobial agents. Multiple-stranded β-hairpin peptides with the same β-hairpin unit, (WRXxRW)n where n=1, 2, 3, or 4 and Xx represent the turn sequence, were synthesized, and their potential as antimicrobial agents was evaluated. Owning to the tightly packed hydrophobic core and paired Trp of this multiple-stranded β-hairpin structure, all the 12-residues peptides exhibited high cell selectivity towards bacterial cells over human red blood cells (hRBCs), and the peptide W2 exhibited stronger antimicrobial activities with the MIC values of 2-8μM against various tested bacteria. Not only that, but W2 also showed obvious synergy with streptomycin and chloramphenicol against Escherichia coli, and displayed synergy with ciprofloxacin against Staphylococcus aureus with the FICI values ⩽0.5. Fluorescence spectroscopy and electron microscopy analyses indicated that W2 kills microbial cells by permeabilizing the cell membrane and damaging membrane integrity. Collectively, based on the multiple β-hairpin peptides, the ability to develop libraries of short and effective peptides will be a powerful approach to the discovery of novel antimicrobial agents. We successfully screened a peptide W2 ((WRPGRW)2) from a series of multiple-stranded β-hairpin antimicrobial peptides based on the "S-shaped" motif that induced the formation of a globular structure, and Trp zipper was used to replace the disulfide bonds to reduce the cost of production. This novel structure applied to AMPs improved cell selectivity and salt stability. The findings of this study will promote the development of peptide

Genome-wide identification of the regulatory targets of a transcription factor using biochemical characterization and computational genomic analysis

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Jolly Emmitt R

2005-11-01

Full Text Available Abstract Background A major challenge in computational genomics is the development of methodologies that allow accurate genome-wide prediction of the regulatory targets of a transcription factor. We present a method for target identification that combines experimental characterization of binding requirements with computational genomic analysis. Results Our method identified potential target genes of the transcription factor Ndt80, a key transcriptional regulator involved in yeast sporulation, using the combined information of binding affinity, positional distribution, and conservation of the binding sites across multiple species. We have also developed a mathematical approach to compute the false positive rate and the total number of targets in the genome based on the multiple selection criteria. Conclusion We have shown that combining biochemical characterization and computational genomic analysis leads to accurate identification of the genome-wide targets of a transcription factor. The method can be extended to other transcription factors and can complement other genomic approaches to transcriptional regulation.

Scientific objectives and selection of targets for the SMART-1 Infrared Spectrometer (SIR)

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Basilevsky, A. T.; Keller, H. U.; Nathues, A.; Mall, U.; Hiesinger, H.; Rosiek, M.

2004-12-01

The European SMART-1 mission to the Moon, primarily a testbed for innovative technologies, was launched in September 2003 and will reach the Moon in 2005. On board are several scientific instruments, including the point-spectrometer SMART-1 Infrared Spectrometer (SIR). Taking into account the capabilities of the SMART-1 mission and the SIR instrument in particular, as well as the open questions in lunar science, a selection of targets for SIR observations has been compiled. SIR can address at least five topics: (1) Surface/regolith processes; (2) Lunar volcanism; (3) Lunar crust structure; (4) Search for spectral signatures of ices at the lunar poles; and (5) Ground truth and study of geometric effects on the spectral shape. For each topic we will discuss specific observation modes, necessary to achieve our scientific goals. The majority of SIR targets will be observed in the nadir-tracking mode. More than 100 targets, which require off-nadir pointing and off-nadir tracking, are planned. It is expected that results of SIR observations will significantly increase our understanding of the Moon. Since the exact arrival date and the orbital parameters of the SMART-1 spacecraft are not known yet, a more detailed planning of the scientific observations will follow in the near future.

Right hemisphere dominance during spatial selective attention and target detection occurs outside the dorsal fronto-parietal network

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Shulman, Gordon L.; Pope, Daniel L. W.; Astafiev, Serguei V.; McAvoy, Mark P.; Snyder, Abraham Z.; Corbetta, Maurizio

2010-01-01

Spatial selective attention is widely considered to be right hemisphere dominant. Previous functional magnetic resonance imaging (fMRI) studies, however, have reported bilateral blood-oxygenation-level-dependent (BOLD) responses in dorsal fronto-parietal regions during anticipatory shifts of attention to a location (Kastner et al., 1999; Corbetta et al., 2000; Hopfinger et al., 2000). Right-lateralized activity has mainly been reported in ventral fronto-parietal regions for shifts of attention to an unattended target stimulus (Arrington et al., 2000; Corbetta et al., 2000). However, clear conclusions cannot be drawn from these studies because hemispheric asymmetries were not assessed using direct voxel-wise comparisons of activity in left and right hemispheres. Here, we used this technique to measure hemispheric asymmetries during shifts of spatial attention evoked by a peripheral cue stimulus and during target detection at the cued location. Stimulus-driven shifts of spatial attention in both visual fields evoked right-hemisphere dominant activity in temporo-parietal junction (TPJ). Target detection at the attended location produced a more widespread right hemisphere dominance in frontal, parietal, and temporal cortex, including the TPJ region asymmetrically activated during shifts of spatial attention. However, hemispheric asymmetries were not observed during either shifts of attention or target detection in the dorsal fronto-parietal regions (anterior precuneus, medial intraparietal sulcus, frontal eye fields) that showed the most robust activations for shifts of attention. Therefore, right hemisphere dominance during stimulus-driven shifts of spatial attention and target detection reflects asymmetries in cortical regions that are largely distinct from the dorsal fronto-parietal network involved in the control of selective attention. PMID:20219998

Developing a multi-pollutant conceptual framework for the selection and targeting of interventions in water industry catchment management schemes.

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Bloodworth, J W; Holman, I P; Burgess, P J; Gillman, S; Frogbrook, Z; Brown, P

2015-09-15

In recent years water companies have started to adopt catchment management to reduce diffuse pollution in drinking water supply areas. The heterogeneity of catchments and the range of pollutants that must be removed to meet the EU Drinking Water Directive (98/83/EC) limits make it difficult to prioritise areas of a catchment for intervention. Thus conceptual frameworks are required that can disaggregate the components of pollutant risk and help water companies make decisions about where to target interventions in their catchments to maximum effect. This paper demonstrates the concept of generalising pollutants in the same framework by reviewing key pollutant processes within a source-mobilisation-delivery context. From this, criteria are developed (with input from water industry professionals involved in catchment management) which highlights the need for a new water industry specific conceptual framework. The new CaRPoW (Catchment Risk to Potable Water) framework uses the Source-Mobilisation-Delivery concept as modular components of risk that work at two scales, source and mobilisation at the field scale and delivery at the catchment scale. Disaggregating pollutant processes permits the main components of risk to be ascertained so that appropriate interventions can be selected. The generic structure also allows for the outputs from different pollutants to be compared so that potential multiple benefits can be identified. CaRPow provides a transferable framework that can be used by water companies to cost-effectively target interventions under current conditions or under scenarios of land use or climate change. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

Paired hormone response elements predict caveolin-1 as a glucocorticoid target gene.